http://www.mdpi.com/ Latest open access articles published at http://www.mdpi.com/ http://www.mdpi.com/2076-0817/2/2/383 Burkholderia mallei, the etiologic agent of glanders, are Category B select agents with biothreat potential, and yet effective therapeutic treatments are lacking. In this study, we showed that CpG administration increased survival, demonstrating protection in the murine glanders model. Bacterial recovery from infected lungs, liver and spleen was significantly reduced in CpG-treated animals as compared with non-treated mice. Reciprocally, lungs of CpG-treated infected animals were infiltrated with higher levels of neutrophils and inflammatory monocytes, as compared to control animals. Employing the B. mallei bioluminescent strain CSM001 and the Neutrophil-Specific Fluorescent Imaging Agent, bacterial dissemination and neutrophil trafficking were monitored in real-time using multimodal in vivo whole body imaging techniques. CpG-treatment increased recruitment of neutrophils to the lungs and reduced bioluminescent bacteria, correlating with decreased bacterial burden and increased protection against acute murine glanders. Our results indicate that protection of CpG-treated animals was associated with recruitment of neutrophils prior to infection and demonstrated, for the first time, simultaneous real time in vivo imaging of neutrophils and bacteria. This study provides experimental evidence supporting the importance of incorporating optimized in vivo imaging methods to monitor disease progression and to evaluate the efficacy of therapeutic treatment during bacterial infections. Pathogens 2013-05-23 2 2 Article 10.3390/pathogens2020383 383 401 2076-0817 2013-05-23 doi: 10.3390/pathogens2020383 Tiffany Mott R. Johnston Sudhamathi Vijayakumar D. Estes Massoud Motamedi Elena Sbrana Janice Endsley Alfredo Torres http://www.mdpi.com/1422-8599/2013/2/M802 A new spiro[indole-3,3'-pyrrolizine] derivative is regioselectively synthesized by the straightforward multicomponent reaction of 1-(4-fluorophenyl)-3-phenylprop-2-en-1-one, isatin and L-proline without any catalyst. The structure of the newly synthesized compound is characterized by IR, NMR, UV-visible and mass spectral data. The compound is also screened for its reducing power assay. Molbank 2013-05-23 2013 2 Short Note 10.3390/M802 M802 1422-8599 2013-05-23 doi: 10.3390/M802 Majal Sapnakumari Badiadka Narayana Seranthimata Samshuddin Balladka Sarojini http://www.mdpi.com/2075-1680/2/2/224 We introduce and study Clarkson, Dol’nikov-Pichugov, Jacobi and mutual diameter constants reflecting the geometry of a Banach space and Clarkson, Jacobi and Pichugov classes of Banach spaces and their relations with James, self-Jung, Kottman and Sch¨affer constants in order to establish quantitative versions of Hahn-Banach separability theorem and to characterise the isometric extendability of H¨older-Lipschitz mappings. Abstract results are further applied to the spaces and pairs from the wide classes IG and IG+ and non-commutative Lp-spaces. The intimate relation between the subspaces and quotients of the IG-spaces on one side and various types of anisotropic Besov, Lizorkin-Triebel and Sobolev spaces of functions on open subsets of an Euclidean space defined in terms of differences, local polynomial approximations, wavelet decompositions and other means (as well as the duals and the lp-sums of all these spaces) on the other side, allows us to present the algorithm of extending the main results of the article to the latter spaces and pairs. Special attention is paid to the matter of sharpness. Our approach is quasi-Euclidean in its nature because it relies on the extrapolation of properties of Hilbert spaces and the study of 1-complemented subspaces of the spaces under consideration. Axioms 2013-05-23 2 2 Article 10.3390/axioms2020224 224 270 2075-1680 2013-05-23 doi: 10.3390/axioms2020224 Sergey Ajiev http://www.mdpi.com/2073-4468/2/2/353 The DOCK-AND-LOCKTM (DNLTM) method provides a modular approach to develop multivalent, multifunctional complexes of defined structures, of which bispecific hexavalent antibodies (bsHexAbs) are prominent examples with potential applications in targeted therapy for malignant, autoimmune, and infectious diseases. Currently, bsHexAbs are constructed by derivatizing a divalent IgG, at the carboxyl termini of either the heavy chain (the CH3-format) or the light chain (the Ck-format), to contain two stabilized dimers of Fab having a different specificity from the IgG. In this review, we briefly outline the features of the DNLTM method and describe key aspects of bsHexAbs examined with diverse preclinical studies, which include binding affinity to target cells, induction of signaling pathways, effector functions, serum stability, pharmacokinetics, and antitumor activity in human tumor xenograft models. Our findings favor the selection of the CK- over the CH3-format for further exploration of bsHexAbs in clinical trials. Antibodies 2013-05-23 2 2 Review 10.3390/antib2020353 353 370 2073-4468 2013-05-23 doi: 10.3390/antib2020353 Chien-Hsing Chang Edmund Rossi Yang Wang Thomas Cardillo David Goldenberg http://www.mdpi.com/1424-8247/6/6/689 Dihydropyridine Ca2+ channel blockers (CCBs) are widely accepted in the treatment of premature labour. Their mechanism of action in tocolysis involves the blockade of L-type Ca2+ channels, influenced by the Ca2+-activated K+ channels, beta-adrenergic receptors (β-ARs) and sexual hormones. In clinical practice, most experience has been gained with the use of nifedipine, whose efficacy is superior or comparable to those of β-agonists and oxytocin antagonists. Additionally, it has a favourable adverse effect profile as compared with the majority of other tocolytics. The most frequent and well-tolerated side-effects of CCBs are tachycardia, headache and hypotension. In tocolytic therapy efforts are currently being made to find combinations of tocolytic agents that yield better therapeutic action. The available human and animal studies suggest that the combination of CCBs with β-AR agonists is beneficial, although such combinations can pose risk of pulmonary oedema in multiple pregnancies and maternal cardiovascular diseases. Preclinical data indicate the potential benefit of combinations of CCBs and oxytocin antagonists. However, the combinations of CCBs with progesterone or cyclooxygenase inhibitors may decrease their efficacy. The CCBs are likely to remain one of the most important groups of drugs for the rapid inhibition of premature uterine contractions. Their significance may be magnified by further clinical studies on their combined use for tocolysis. Pharmaceuticals 2013-05-23 6 6 Review 10.3390/ph6060689 689 699 1424-8247 2013-05-23 doi: 10.3390/ph6060689 Róbert Gáspár Judit Hajagos-Tóth http://www.mdpi.com/2072-4292/5/6/2590 Earthquake is one of the dominant triggering factors of landslides. Given the wide areas covered by mega earthquake-triggered landslides, their inventory requires development of automatic or semi-automatic methods applied to satellite imagery. A detection method is here proposed for this purpose, to fit with simple datasets; SPOT5 panchromatic images of 5 m resolution coupled with a freely and globally available DEM. The method takes advantage of multi-temporal images to detect changes based on radiometric variations after precise coregistration/orthorectification. Removal of false alarms is then undertaken using shape, orientation and radiometric properties of connected pixels defining objects. 80% of the landslides and 93% of the landslide area are detected indicating small omission errors but 50% of false alarms remain. They are removed using expert based analysis of the inventory. The method is applied to realize the first comprehensive inventory of landslides triggered by the Pisco earthquake (Peru, 15/08/2007, Mw 8.0) over an area of 27,000 km2. 866 landslides larger than 100 m2 are detected covering a total area of 1.29 km2. The area/number distribution follows a power-law with an exponent of 1.63, showing a very particular regime of triggering in this arid environment compared to other areas in the world. This specific triggering can be explained by the little soil cover in the coastal and forearc regions of Peru. Analysis of this database finally shows a major control of the topography (both orientation and inclination) on the repartition of the Pisco-triggered landslides. Remote Sensing 2013-05-23 5 6 Article 10.3390/rs5062590 2590 2616 2072-4292 2013-05-23 doi: 10.3390/rs5062590 Pascal Lacroix Bilberto Zavala Etienne Berthier Laurence Audin http://www.mdpi.com/2072-4292/5/6/2571 Rainfall intensity plays an important role in landslide prediction especially in mountain areas. However, the rainfall intensity of a location is usually interpolated from rainfall recorded at nearby gauges without considering any possible effects of topographic slopes. In order to obtain reliable rainfall intensity for disaster mitigation, this study proposes a rainfall-vector projection method for topographic-corrected rainfall. The topographic-corrected rainfall is derived from wind speed, terminal velocity of raindrops, and topographical factors from digital terrain model. In addition, scatter plot was used to present landslide distribution with two triggering factors and kernel density analysis is adopted to enhance the perception of the distribution. Numerical analysis is conducted for a historic event, typhoon Mindulle, which occurred in 2004, in a location in central Taiwan. The largest correction reaches 11%, which indicates that topographic correction is significant. The corrected rainfall distribution is then applied to the analysis of landslide triggering factors. The result with corrected rainfall distribution provides better agreement with the actual landslide occurrence than the result without correction. Remote Sensing 2013-05-23 5 6 Article 10.3390/rs5062571 2571 2589 2072-4292 2013-05-23 doi: 10.3390/rs5062571 Jin-King Liu Peter Shih http://www.mdpi.com/1420-3049/18/6/6153 A new 8,4¢-oxyneolignane glucoside 1 has been isolated from the stems of Dendrobium aurantiacum var. denneanum together with six known phenolic glucosides 2-7. The structure of the new compound, including its absolute configuration, was determined by spectroscopic and chemical methods as (–)-(7S,8R,7¢E)-4-hydroxy-3,3¢,5,5¢-tetramethoxy-8,4¢-oxyneolign-7¢-ene-7,9,9¢-triol 7,9¢-bis-O-β-D-glucopyranoside (1). In the in vitro assays, compound 1 and (-)-syringaresinol-4,4¢-bis-O-β-D-glucopyranoside (2) showed evident activity against glutamate-induced neurotoxicity in PC12 cells. Shashenoside I (4) showed a selective cytotoxic activity with the IC50 value of 4.17 μM against the acute myeloid leukemia cell line MV4-11, while it was inactive against 10 other human tumor cell lines. Molecules 2013-05-23 18 6 Article 10.3390/molecules18066153 6153 6160 1420-3049 2013-05-23 doi: 10.3390/molecules18066153 Liang Xiong Zhi-Xing Cao Cheng Peng Xiao-Hong Li Xiao-Fang Xie Ting-Mo Zhang Qin-Mei Zhou Lian Yang Li Guo http://www.mdpi.com/1420-3049/18/6/6142 An efficient one-pot synthesis of novel β-amino acid derivatives containing a thiadiazole moiety was developed using a chiral squaramide cinchona alkaloid as organocatalyst. The reactions afforded chiral β-amino acid derivatives in moderate yields and with moderate to excellent enantioselectivities. The present study demonstrated for the first time the use of a Mannich reaction catalyzed by a chiral bifunctional organocatalyst for the one-pot synthesis of novel β-amino acid derivatives bearing a 1,3,4-thiadiazole moiety on nitrogen. Molecules 2013-05-23 18 6 Article 10.3390/molecules18066142 6142 6152 1420-3049 2013-05-23 doi: 10.3390/molecules18066142 Kankan Zhang Xueping Liang Ming He Jian Wu Yuping Zhang Wei Xue Linhong Jin Song Yang Deyu Hu http://www.mdpi.com/1420-3049/18/6/6128 Novel antioxidants have been synthesized and characterized by their chemical properties as antioxidants with high superoxide scavenging activity. (2R,3R)-diphenylethylenediamine is a spacer in antioxidants, and we synthesized targets 11a and 11b by conjugation with o-hydroquinone and p-hydroquinone at the two N-termini, respectively. Superoxide scavenging activities of the plant flavonoid-like 11a and 11b were compared with those of known antioxidants, and shown to increase in the following order: curcumin << ascorbic acid < Trolox < (+)-epicatechin < 11a < quercetin £ 11b. Compound 11a also formed a solvated 11a–metal complex with metal ions. The 11a–Cu2+ complex was shown to have higher superoxide scavenging activity than that of 11a, 11b, Cu2+, and the 11a–Al3+ and 11a–La3+ complexes, whereas the 11a–Al3+ complex increased rather than decreased superoxide levels. The 11a–Al3+ complex did not abstract one electron from the SOMO of O2−. since the HOMO and LUMO phases of Al3+ do not exist in the center of the 11a–Al3+ complex. However, the SOMO of the 11a–Cu2+ complex distributed in the center of Cu2+ may abstract one electron from the SOMO of O2−.. These results suggest that 11a and 11b are powerful antioxidants. Molecules 2013-05-23 18 6 Article 10.3390/molecules18066128 6128 6141 1420-3049 2013-05-23 doi: 10.3390/molecules18066128 Shigeki Kobayashi Sachi Kanai http://www.mdpi.com/1099-4300/15/6/2012 The paper addresses informational interactions in a community and considers the dynamics of concepts that represent distribution of knowledge among the individuals. The evolution of a set of concepts maintained by a community is derived by the use of the concepts’ significance in the communication between “cognoscenti” and “dilettanti” and of birth-death processes. The dynamics of concepts depend on the allocation of communication resources and can be governed by an informational principle that requires minimum self-information of the set of concepts over a time horizon. With respect to that principle, the introduction of a new concept into a community’s disposal is shown to lead to a steady-state self-information, which is smaller than that before the introduction of the new concept. Entropy 2013-05-23 15 6 Article 10.3390/e15062012 2012 2022 1099-4300 2013-05-23 doi: 10.3390/e15062012 Eugene Khmelnitsky Eugene Kagan http://www.mdpi.com/1099-4300/15/6/1999 Zhang in 2012 introduced a nonparametric estimator of Shannon’s entropy, whose bias decays exponentially fast when the alphabet is finite. We propose a methodology to estimate the bias of this estimator. We then use it to construct a new estimator of entropy. Simulation results suggest that this bias adjusted estimator has a significantly lower bias than many other commonly used estimators. We consider both the case when the alphabet is finite and when it is countably infinite. Entropy 2013-05-23 15 6 Article 10.3390/e15061999 1999 2011 1099-4300 2013-05-23 doi: 10.3390/e15061999 Zhiyi Zhang Michael Grabchak http://www.mdpi.com/1099-4300/15/6/1985 We propose a model for Lorenz curves. It provides two-parameter fits to data on incomes, electric consumption, life expectation and rate of survival after cancer. Graphs result from the condition of maximum entropy and from the symmetry of statistical distributions. Differences in populations composing a binary system (poor and rich, young and old, etc.) bring about chance inequality. Symmetrical distributions insure equality of chances, generate Gini coefficients Gi £ ⅓, and imply that nobody gets more than twice the per capita benefit. Graphs generated by different symmetric distributions, but having the same Gini coefficient, intersect an even number of times. The change toward asymmetric distributions follows the pattern set by second-order phase transitions in physics, in particular universality: Lorenz plots reduce to a single universal curve after normalisation and scaling. The order parameter is the difference between cumulated benefit fractions for equal and unequal chances. The model also introduces new parameters: a cohesion range describing the extent of apparent equality in an unequal society, a poor-rich asymmetry parameter, and a new Gini-like indicator that measures unequal-chance inequality and admits a theoretical expression in closed form. Entropy 2013-05-23 15 6 Article 10.3390/e15061985 1985 1998 1099-4300 2013-05-23 doi: 10.3390/e15061985 Jorge Rosenblatt http://www.mdpi.com/1099-4300/15/6/1963 We derive expressions for the invariant length element and measure for the simple compact Lie group SU(4) in a coordinate system particularly suitable for treating entanglement in quantum information processing. Using this metric, we compute the invariant volume of the space of two-qubit perfect entanglers. We find that this volume corresponds to more than 84% of the total invariant volume of the space of two-qubit gates. This same metric is also used to determine the effective target sizes that selected gates will present in any quantum-control procedure designed to implement them. Entropy 2013-05-23 15 6 Article 10.3390/e15061963 1963 1984 1099-4300 2013-05-23 doi: 10.3390/e15061963 Paul Watts Maurice O'Connor Jiří Vala http://www.mdpi.com/2076-0787/2/2/253 This layered account of an inquiry into ‘red’ emerged out of a collective biography workshop. In the middle of the Wiltshire countryside, an international and interdisciplinary group of scholars gathered together to write and make other things and marks on paper that asked questions of, and into, the spaces between words, people, things and their environments. We did not set out to workshop or write into or paint ‘red’ but, rather, it was red that slipped in, uninvited, and painted and wrote us. Red arose as a blush or a stain seeping amongst us that became referenced obliquely by material objects, metaphors and fairytales. The stain spread, became noticeable through our weekend together and beyond it, creating another (bright red artery) vein of connection to write with. Humanities 2013-05-23 2 2 Article 10.3390/h2020253 253 277 2076-0787 2013-05-23 doi: 10.3390/h2020253 Ken Gale Mike Gallant Susanne Gannon Davina Kirkpatrick Marina Malthouse McClain Percy Maud Perrier Sue Porter Ann Rippin Artemi Sakellariadis Jane Speedy Jonathan Wyatt Tess Wyatt http://www.mdpi.com/1660-4601/10/6/2109 The purpose of this study was to investigate the oxidative damage induced by dietary nickel chloride (NiCl2) in the intestinal mucosa of different parts of the intestine of broilers, including duodenum, jejunum and ileum. A total of 240 one-day-old broilers were divided into four groups and fed on a corn-soybean basal diet as control diet or the same basal diet supplemented with 300, 600 or 900 mg/kg NiCl2 during a 42-day experimental period. The results showed that the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and the ability to inhibit hydroxy radical and glutathione (GSH) content were significantly (p < 0.05 or p < 0.01) decreased in the 300, 600 and 900 mg/kg groups in comparison with those of the control group. In contrast, malondialdehyde (MDA) content was significantly (p < 0.05 or p < 0.01) higher in the 300, 600 and 900 mg/kg groups than that in the control group. It was concluded that dietary NiCl2 in excess of 300 mg/kg could cause oxidative damage in the intestinal mucosa in broilers, which finally impaired the intestinal functions including absorptive function and mucosal immune function. The oxidative damage might be a main mechanism on the effects of NiCl2 on the intestinal health of broilers. International Journal of Environmental Research and Public Health 2013-05-23 10 6 Article 10.3390/ijerph10062109 2109 2119 1660-4601 2013-05-23 doi: 10.3390/ijerph10062109 Bangyuan Wu Hengmin Cui Xi Peng Jing Fang Zhicai Zuo Junliang Deng Jianying Huang http://www.mdpi.com/1422-0067/14/6/10819 In this Editorial, I comment on the exciting and original topic of plant neurobiology, focusing on natural products whose biosynthesis is shared by animal and plant organisms, i.e., indoleamines (melatonin and serotonin) and catecholamines (dopamine, norepinephrine and epinephrine). International Journal of Molecular Sciences 2013-05-23 14 6 Editorial 10.3390/ijms140610819 10819 10821 1422-0067 2013-05-23 doi: 10.3390/ijms140610819 Marcello Iriti http://www.mdpi.com/1422-0067/14/6/10809 The transmission of T-2 toxin and its metabolites into the edible tissues of poultry has potential effects on human health. We report that T-2 toxin significantly induces CYP1A4 and CYP1A5 expression in chicken embryonic hepatocyte cells. The enzyme activity assays of CYP1A4 and CYP1A5 heterologously expressed in HeLa cells indicate that only CYP1A5 metabolizes T-2 to 3'OH-T-2 by the 3'-hydroxylation of isovaleryl groups. In vitro enzyme assays of recombinant CYP1A5 expressed in DH5α further confirm that CYP1A5 can convert T-2 into TC-1 (3'OH-T-2). Therefore, CYP1A5 is critical for the metabolism of trichothecene mycotoxin in chickens. International Journal of Molecular Sciences 2013-05-23 14 6 Article 10.3390/ijms140610809 10809 10818 1422-0067 2013-05-23 doi: 10.3390/ijms140610809 Shufeng Shang Jun Jiang Yiqun Deng http://www.mdpi.com/1422-0067/14/6/10791 Penile carcinoma (PeCa) represents an important public health problem in poor and developing countries. Despite its unpredictable behavior and aggressive treatment, there have only been a few reports regarding its molecular data, especially epigenetic mechanisms. The functional diversity in different cell types is acquired by chromatin modifications, which are established by epigenetic regulatory mechanisms involving DNA methylation, histone acetylation, and miRNAs. Recent evidence indicates that the dysregulation in these processes can result in the development of several diseases, including cancer. Epigenetic alterations, such as the methylation of CpGs islands, may reveal candidates for the development of specific markers for cancer detection, diagnosis and prognosis. There are a few reports on the epigenetic alterations in PeCa, and most of these studies have only focused on alterations in specific genes in a limited number of cases. This review aims to provide an overview of the current knowledge of the epigenetic alterations in PeCa and the promising results in this field. The identification of epigenetically altered genes in PeCa is an important step in understanding the mechanisms involved in this unexplored disease. International Journal of Molecular Sciences 2013-05-23 14 6 Review 10.3390/ijms140610791 10791 10808 1422-0067 2013-05-23 doi: 10.3390/ijms140610791 Hellen Kuasne Fabio Marchi Silvia Rogatto Ilce de Syllos Cólus http://www.mdpi.com/1422-0067/14/6/10761 The Src gene product (Src) and the epidermal growth factor receptor (EGFR) are prototypes of oncogene products and function primarily as a cytoplasmic non-receptor tyrosine kinase and a transmembrane receptor tyrosine kinase, respectively. The identification of Src and EGFR, and the subsequent extensive investigations of these proteins have long provided cutting edge research in cancer and other molecular and cellular biological studies. In 1995, we reported that the human epidermoid carcinoma cells, A431, contain a small fraction of Src and EGFR in which these two kinase were in physical association with each other, and that Src phosphorylates EGFR on tyrosine 845 (Y845) in the Src-EGFR complex. Y845 of EGFR is located in the activation segment of the kinase domain, where many protein kinases contain kinase-activating autophosphorylation sites (e.g., cAMP-dependent protein kinase, Src family kinases, transmembrane receptor type tyrosine kinases) or trans-phosphorylation sites (e.g., cyclin-dependent protein kinase, mitogen-activated protein kinase, Akt protein kinase). A number of studies have demonstrated that Y845 phosphorylation serves an important role in cancer as well as normal cells. Here we compile the experimental facts involving Src phosphorylation of EGFR on Y845, by which cell proliferation, cell cycle control, mitochondrial regulation of cell metabolism, gamete activation and other cellular functions are regulated. We also discuss the physiological relevance, as well as structural insights of the Y845 phosphorylation. International Journal of Molecular Sciences 2013-05-23 14 6 Review 10.3390/ijms140610761 10761 10790 1422-0067 2013-05-23 doi: 10.3390/ijms140610761 Ken-ichi Sato http://www.mdpi.com/1422-0067/14/6/10749 The deubiquitinating enzyme USP14 has been identified and biochemically studied, but its role in lung cancer remains to be elucidated. The aim of this study was to evaluate the prognostic significance of USP14 in patients with lung adenocarcinoma and to define its role in lung cancer cell proliferation. USP14 mRNA levels in different non-small cell lung cancer (NSCLC) cell lines were detected by real-time qPCR. USP14 protein levels in surgically resected samples from NSCLC patients, and in NSCLC cell lines, were detected by immunohistochemistry or Western blot. The correlation of USP14 expression with clinical characteristics and prognosis was determined by survival analysis. After silencing USP14, cell proliferation was assessed by MTT assay and the cell cycle was measured by FACS assay. It was found that USP14 expression was upregulated in NSCLC cells, especially in adenocarcinoma cells. Over-expression of USP14 was associated with shorter overall survival of patients. Downregulation of USP14 expression arrested the cell cycle, which may be related to β-catenin degradation. Over-expression of USP14 was associated with poor prognosis in NSCLC patients and promoted tumor cell proliferation, which suggests that USP14 is a tumor-promoting factor and a promising therapeutic target for NSCLC. International Journal of Molecular Sciences 2013-05-23 14 6 Article 10.3390/ijms140610749 10749 10760 1422-0067 2013-05-23 doi: 10.3390/ijms140610749 Ning Wu Cong Liu Chong Bai Yi-Ping Han William Cho Qiang Li http://www.mdpi.com/1422-0067/14/6/10727 Poly-(R)-3-hydroxybutyrate (PHB), a linear polymer of R-3-hydroxybutyrate (R-3HB), is a fundamental constituent of biological cells. Certain prokaryotes accumulate PHB of very high molecular weight (10,000 to >1,000,000 residues), which is segregated within granular deposits in the cytoplasm; however, all prokaryotes and all eukaryotes synthesize PHB of medium-chain length (~100–200 residues) which resides within lipid bilayers or lipid vesicles, and PHB of short-chain length (<12 residues) which is conjugated to proteins (cPHB), primarily proteins in membranes and organelles. The physical properties of cPHB indicate it plays important roles in the targeting and folding of cPHB-proteins. Here we review the occurrence, physical properties and molecular characteristics of cPHB, and discuss its influence on the folding and structure of outer membrane protein A (OmpA) of Escherichia coli. International Journal of Molecular Sciences 2013-05-23 14 6 Review 10.3390/ijms140610727 10727 10748 1422-0067 2013-05-23 doi: 10.3390/ijms140610727 Rosetta Reusch http://www.mdpi.com/1422-0067/14/6/10710 Bone marrow derived human mesenchymal stem cells (hMSCs) show promising potential in regeneration of defective tissue. Recently, gene silencing strategies using microRNAs (miR) emerged with the aim to expand the therapeutic potential of hMSCs. However, researchers are still searching for effective miR delivery methods for clinical applications. Therefore, we aimed to develop a technique to efficiently deliver miR into hMSCs with the help of a magnetic non-viral vector based on cationic polymer polyethylenimine (PEI) bound to iron oxide magnetic nanoparticles (MNP). We tested different magnetic complex compositions and determined uptake efficiency and cytotoxicity by flow cytometry. Additionally, we monitored the release, processing and functionality of delivered miR-335 with confocal laser scanning microscopy, real-time PCR and live cell imaging, respectively. On this basis, we established parameters for construction of magnetic non-viral vectors with optimized uptake efficiency (~75%) and moderate cytotoxicity in hMSCs. Furthermore, we observed a better transfection performance of magnetic complexes compared to PEI complexes 72 h after transfection. We conclude that MNP-mediated transfection provides a long term effect beneficial for successful genetic modification of stem cells. Hence, our findings may become of great importance for future in vivo applications. International Journal of Molecular Sciences 2013-05-23 14 6 Article 10.3390/ijms140610710 10710 10726 1422-0067 2013-05-23 doi: 10.3390/ijms140610710 Anna Schade Evgenya Delyagina Dorothee Scharfenberg Anna Skorska Cornelia Lux Robert David Gustav Steinhoff http://www.mdpi.com/1422-0067/14/6/10694 The aim of this work was to evaluate the ability of oxidative and glycative stressors to modify properties of human serum albumin (HSA) by analyzing markers of glycation (pentosidine) and oxidation (advanced oxidative protein products (AOPPs)) and assessing fluorescence and circular dichroism. HSA was incubated for up to 21 days with ribose, ascorbic acid (AA) and diethylenetriamine pentacetate (DTPA) in various combinations in order to evaluate influences of these substances on the structure of HSA. Ribose was included as a strong glycative molecule, AA as a modulator of oxidative stress, and DTPA as an inhibitor of metal-catalyzed oxidation. Ribose induced a significant increase in pentosidine levels. AA and DTPA prevented the accumulation of pentosidine, especially at later time points. Ribose induced a mild increase in AOPP formation, while AA was a strong inducer of AOPP formation. Ribose, in combination with AA, further increased the formation of AOPP. DTPA prevented the AA-induced generation of AOPP. Ribose was also a potent inducer of fluorescence at 335nm ex/385nm em, which is typical of pentosidine. AA and DTPA prevented this fluorescence. Circular dichroism showed complex results, in which AA and DTPA were strong modifiers of the percentages of the alpha-helical structure of HSA, while ribose affected the structure of HSA only at later time points. International Journal of Molecular Sciences 2013-05-23 14 6 Article 10.3390/ijms140610694 10694 10709 1422-0067 2013-05-23 doi: 10.3390/ijms140610694 Fiammetta Monacelli Daniela Storace Cristina D'Arrigo Roberta Sanguineti Roberta Borghi Davide Pacini Anna Furfaro Maria Pronzato Patrizio Odetti Nicola Traverso http://www.mdpi.com/1422-0067/14/6/10683 Patients with solid cancer frequently develop bone metastases (BM). Zoledronic acid (Zometa®, ZA), routinely used to treat patients with BM, acts on osteoclasts and also has antitumor properties. We aimed to assess the effect of ZA over time in novel bone turnover markers (RANK/receptor activator of nuclear factor-k B ligand (RANK-L)/ Osteoprotegerin (OPG)) and to correlate these with serum N-terminal telopeptide (NTX). The study prospectively evaluated levels of RANK, RANK-L and OPG transcripts by real-time PCR and NTX expression by ELISA in the peripheral blood of 49 consecutive patients with advanced breast, lung or prostate cancer. All patients received the standard ZA schedule and were monitored for 12 months. Median baseline values of RANK, RANK-L and OPG were 78.28 (range 7.34–620.64), 319.06 (21.42–1884.41) and 1.52 (0.10–58.02), respectively. At 12 months, the median RANK-L value had decreased by 22% with respect to the baseline, whereas median OPG levels had increased by about 96%. Consequently, the RANK-L/OPG ratio decreased by 56% from the baseline. Median serum NTX levels decreased over the 12-month period, reaching statistical significance (p < 0.0001). Our results would seem to indicate that ZA modulates RANK, RANK-L and OPG expression, thus decreasing osteoclast activity. International Journal of Molecular Sciences 2013-05-23 14 6 Article 10.3390/ijms140610683 10683 10693 1422-0067 2013-05-23 doi: 10.3390/ijms140610683 Laura Mercatali Marianna Ricci Emanuela Scarpi Patrizia Serra Francesca Fabbri Rossana Ricci Chiara Liverani Michele Zanoni Wainer Zoli Roberta Maltoni Erica Gunelli Dino Amadori Toni Ibrahim http://www.mdpi.com/1999-4915/5/5/1346 Kaposi’s sarcoma-associated herpesvirus is an oncogenic γ-herpesvirus that causes latent infection in humans. In cells, the viral genome adopts a highly organized chromatin structure, which is controlled by a wide variety of cellular and viral chromatin regulatory factors. In the past few years, interrogation of the chromatinized KSHV genome by whole genome-analyzing tools revealed that the complex chromatin landscape spanning the viral genome in infected cells has important regulatory roles during the viral life cycle. This review summarizes the most recent findings regarding the role of histone modifications, histone modifying enzymes, DNA methylation, microRNAs, non-coding RNAs and the nuclear organization of the KSHV epigenome in the regulation of latent and lytic viral gene expression programs as well as their connection to KSHV-associated pathogenesis. Viruses 2013-05-23 5 5 Review 10.3390/v5051346 1346 1373 1999-4915 2013-05-23 doi: 10.3390/v5051346 Zsolt Toth Kevin Brulois Jae Jung http://www.mdpi.com/1999-4915/5/5/1325 Cytomegalovirus (CMV) gene expression is repressed in latency due to heterochromatinization of viral genomes. In murine CMV (MCMV) latently infected mice, viral genomes are bound to histones with heterochromatic modifications, to enzymes that mediate these modifications, and to adaptor proteins that may recruit co-repressor complexes. Kinetic analyses of repressor binding show that these repressors are recruited at the earliest time of infection, suggesting that latency may be the default state. Kidney transplantation leads to epigenetic reprogramming of latent viral chromatin and reactivation of immediate early gene expression. Inflammatory signaling pathways, which activate transcription factors that regulate the major immediate early promoter (MIEP), likely mediate the switch in viral chromatin. Viruses 2013-05-23 5 5 Article 10.3390/v5051325 1325 1345 1999-4915 2013-05-23 doi: 10.3390/v5051325 Xue-feng Liu Xueqiong Wang Shixian Yan Zheng Zhang Michael Abecassis Mary Hummel http://www.mdpi.com/2075-4701/3/2/202 The purpose of this review was to investigate the correlation between magnetism and crystallographic structures as it relates to the martensite transformation of Ni2MnGa type alloys, which undergo martensite transformation below the Curie temperature. In particular, this paper focused on the physical properties in magnetic fields. Recent researches show that the martensite starting temperature (martensite transformation temperature) TM and the martensite to austenite transformation temperature (reverse martensite temperature) TR of Fe, Cu, or Co-doped Ni–Mn–Ga ferromagnetic shape memory alloys increase when compared to Ni2MnGa. These alloys show large field dependence of the martensite transformation temperature. The field dependence of the martensite transformation temperature, dTM/dB, is −4.2 K/T in Ni41Co9Mn32Ga18. The results of linear thermal strain and magnetization indicate that a magneto-structural transition occurred at TM and magnetic field influences the magnetism and also the crystal structures. Magnetocrystalline anisotropy was also determined and compared with other components of Ni2MnGa type shape memory alloys. In the last section, magnetic field-induced strain and magnetostriction was determined with some novel alloys. Metals 2013-05-23 3 2 Review 10.3390/met3020202 202 224 2075-4701 2013-05-23 doi: 10.3390/met3020202 Takuo Sakon Yoshiya Adachi Takeshi Kanomata http://www.mdpi.com/1999-4915/5/5/1292 Hepatitis C virus (HCV) is a leading cause of chronic liver disease, including chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatitis C infection associates with lipid and lipoprotein metabolism disorders such as hepatic steatosis, hypobetalipoproteinemia, and hypocholesterolemia. Furthermore, virus production is dependent on hepatic very-low-density lipoprotein (VLDL) assembly, and circulating virions are physically associated with lipoproteins in complexes termed lipoviral particles. Evidence has indicated several functional roles for the formation of these complexes, including co-opting of lipoprotein receptors for attachment and entry, concealing epitopes to facilitate immune escape, and hijacking host factors for HCV maturation and secretion. Here, we review the evidence surrounding pathogenesis of the hepatitis C infection regarding lipoprotein engagement, cholesterol and triglyceride regulation, and the molecular mechanisms underlying these effects. Viruses 2013-05-23 5 5 Review 10.3390/v5051292 1292 1324 1999-4915 2013-05-23 doi: 10.3390/v5051292 Daniel Felmlee Mohamed Hafirassou Mathieu Lefevre Thomas Baumert Catherine Schuster http://www.mdpi.com/2071-1050/5/5/2272 In recent years, air pollution has become a major worldwide concern. Air pollutants can affect metabolic activity, impede healthy development, and exhibit carcinogenic and toxic properties in humans. Over the past two decades, the use of microbes to remove pollutants from contaminated air streams has become a widely accepted and efficient alternative to the classical physical and chemical treatment technologies. Air Pollution Prevention and Control: Bioreactors and Bioenergy focusses on these biotechnological alternatives looking at both the optimization of bioreactors and the development of cleaner biofuels. Sustainability 2013-05-22 5 5 New Book Received 10.3390/su5052272 2272 2287 2071-1050 2013-05-22 doi: 10.3390/su5052272 Shu-Kun Lin http://www.mdpi.com/2072-4292/5/5/2554 An inventory of landslides with an indication of the state of activity is necessary in order to establish hazard maps. We combine interpretation of aerial photographs and information on surface displacement from satellite Synthetic Aperture Radar (SAR) interferometry for mapping landslides and intensity classification. Sketch maps of landslides distinguished by typology and depth, including geomorphological features, are compiled by stereoscopic photo-interpretation. Results achieved with differential SAR interferometry (InSAR) and Persistent Scatterer Interferometry (PSI) are used to estimate the state of activity of landslides around villages and in sparsely vegetated areas with numerous exposed rocks. For validation and possible extension of the inventory around vegetated areas, where InSAR and PSI failed to retrieve displacement information, traditional monitoring data such as topographic measurements and GPS are considered. Our results, covering extensive areas, are a valuable contribution towards the analysis of landslide hazards in areas where traditional monitoring techniques are sparse or unavailable. In this contribution we discuss our methodology for a study area around the deep-seated landslide in Osco in southern Switzerland. Remote Sensing 2013-05-22 5 5 Article 10.3390/rs5052554 2554 2570 2072-4292 2013-05-22 doi: 10.3390/rs5052554 Tazio Strozzi Christian Ambrosi Hugo Raetzo http://www.mdpi.com/2073-4360/5/2/576 Protein aggregation and protein self-assembly is an important occurrence in natural systems, and is in some form or other dictated by biopolymers. Very obvious influences of biopolymers on protein assemblies are, e.g., virus particles. Viruses are a multi-protein assembly of which the morphology is dictated by poly-nucleotides namely RNA or DNA. This “biopolymer” directs the proteins and imposes limitations on the structure like the length or diameter of the particle. Not only do these bionanoparticles use polymer-directed self-assembly, also processes like amyloid formation are in a way a result of directed protein assembly by partial unfolded/misfolded biopolymers namely, polypeptides. The combination of proteins and synthetic polymers, inspired by the natural processes, are therefore regarded as a highly promising area of research. Directed protein assembly is versatile with respect to the possible interactions which brings together the protein and polymer, e.g., electrostatic, v.d. Waals forces or covalent conjugation, and possible combinations are numerous due to the large amounts of different polymers and proteins available. The protein-polymer interacting behavior and overall morphology is envisioned to aid in clarifying protein-protein interactions and are thought to entail some interesting new functions and properties which will ultimately lead to novel bio-hybrid materials. Polymers 2013-05-22 5 2 Review 10.3390/polym5020576 576 599 2073-4360 2013-05-22 doi: 10.3390/polym5020576 Patrick van Rijn http://www.mdpi.com/1999-4923/5/2/318 Efforts to take advantage of the beneficial activities of thyrotropin-releasing hormone (TRH) in the brain are hampered by its poor metabolic stability and lack of adequate central nervous system bioavailability. We report here novel and metabolically stable analogs that we derived from TRH by replacing its amino-terminal pyroglutamyl (pGlu) residue with pyridinium-containing moieties. Exploratory studies have shown that the resultant compounds were successfully delivered into the mouse brain after systemic administration via their bioprecursor prodrugs, where they manifested neuropharmacological responses characteristic of the endogenous parent peptide. On the other hand, the loss of potency compared to TRH in a model testing antidepressant-like effect with a simultaneous preservation of analeptic activity has been observed, when pGlu was replaced with trigonelloyl residue. This finding may indicate an opportunity for designing TRH analogs with potential selectivity towards cholinergic effects. Pharmaceutics 2013-05-22 5 2 Communication 10.3390/pharmaceutics5020318 318 328 1999-4923 2013-05-22 doi: 10.3390/pharmaceutics5020318 Katalin Prokai-Tatrai Vien Nguyen Szabolcs Szarka Krisztina Konya Laszlo Prokai http://www.mdpi.com/1422-8599/2013/2/M801 In this paper (R)-7-(azepan-3-ylamino)-8-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydrochloride 1 was isolated and identified as the N-substituted regioisomer of besifloxacin, which has been synthesized from the reaction of 8-chloro-1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 3 with (R)-tert-butyl 3-aminoazepane-1-carboxylate 2 in acetonitrile as solvent in 37% yield. The chemical structure of compound 1 was established on the basis of 1H-NMR, 13C-NMR, mass spectrometry data and elemental analysis. Molbank 2013-05-22 2013 2 Short Note 10.3390/M801 M801 1422-8599 2013-05-22 doi: 10.3390/M801 Zhengjun Xia Zaixing Chen Shuitao Yu http://www.mdpi.com/1660-3397/11/5/1728 On a global scale, jellyfish populations in coastal marine ecosystems exhibit increasing trends of abundance. High-density outbreaks may directly or indirectly affect human economical and recreational activities, as well as public health. As the interest in biology of marine jellyfish grows, a number of jellyfish metabolites with healthy potential, such as anticancer or antioxidant activities, is increasingly reported. In this study, the Mediterranean “fried egg jellyfish” Cotylorhiza tuberculata (Macri, 1778) has been targeted in the search forputative valuable bioactive compounds. A medusa extract was obtained, fractionated, characterized by HPLC, GC-MS and SDS-PAGE and assayed for its biological activity on breast cancer cells (MCF-7) and human epidermal keratinocytes (HEKa). The composition of the jellyfish extract included photosynthetic pigments, valuable ω-3 and ω-6 fatty acids, and polypeptides derived either from jellyfish tissues and their algal symbionts. Extract fractions showed antioxidant activity and the ability to affect cell viability and intercellular communication mediated by gap junctions (GJIC) differentially in MCF-7and HEKa cells. A significantly higher cytotoxicity and GJIC enhancement in MCF-7 compared to HEKa cells was recorded. A putative action mechanism for the anticancer bioactivity through the modulation of GJIC has been hypothesized and its nutraceutical and pharmaceutical potential was discussed. Marine Drugs 2013-05-22 11 5 Article 10.3390/md11051728 1728 1762 1660-3397 2013-05-22 doi: 10.3390/md11051728 Antonella Leone Raffaella Lecci Miriana Durante Stefano Piraino http://www.mdpi.com/2075-1729/3/2/346 Although hypersaline environments pose challenges to life because of the low water content (water activity), many such habitats appear to support eukaryotic microbes. This contribution presents brief reviews of our current knowledge on eukaryotes of water-column haloclines and brines from Deep Hypersaline Anoxic Basins (DHABs) of the Eastern Mediterranean, as well as shallow-water hypersaline microbial mats in solar salterns of Guerrero Negro, Mexico and benthic microbialite communities from Hamelin Pool, Shark Bay, Western Australia. New data on eukaryotic diversity from Shark Bay microbialites indicates eukaryotes are more diverse than previously reported. Although this comparison shows that eukaryotic communities in hypersaline habitats with varying physicochemical characteristics are unique, several groups are commonly found, including diverse alveolates, strameonopiles, and fungi, as well as radiolaria. Many eukaryote sequences (SSU) in both regions also have no close homologues in public databases, suggesting that these environments host unique microbial eukaryote assemblages with the potential to enhance our understanding of the capacity of eukaryotes to adapt to hypersaline conditions. Life 2013-05-22 3 2 Article 10.3390/life3020346 346 362 2075-1729 2013-05-22 doi: 10.3390/life3020346 Virginia Edgcomb Joan Bernhard http://www.mdpi.com/2073-4336/4/2/200 Gladiatorial combat was in reality a lot less lethal than it is depicted in the cinema. This short paper highlights how cooperative strategies could have prevailed in the arenas, which is generally what happened during the Games. Cooperation in the arena corresponded to a situation of the professionalization of gladiators, who been trained in gladiatorial schools. This case provides an analogy of the conditions under which cooperation occurs in a context of competition between rival companies. Games 2013-05-22 4 2 Article 10.3390/g4020200 200 207 2073-4336 2013-05-22 doi: 10.3390/g4020200 Jérôme Ballet Damien Bazin Radu Vranceanu http://www.mdpi.com/1996-1073/6/5/2709 This paper presents a model-based cell-health-conscious thermal energy management method. An Arrhenius equation-based mathematical model is firstly identified to quantify the effect of temperature on the cell lifetime of a Nickel Metal Hydride (NiMH) battery pack. The cell aging datasets collected under multiple ambient temperatures are applied to extract the Arrhenius equation parameters. The model is then used as an assessment criterion and guidance for the thermal management design of battery packs. The feasibility and applicability of a pack structure with its cooling system, is then evaluated, and its design problems are studied by a computational fluid dynamics (CFD) analysis. The performance and eligibility of the design method is validated by both CFD simulations and experiments. Energies 2013-05-22 6 5 Article 10.3390/en6052709 2709 2725 1996-1073 2013-05-22 doi: 10.3390/en6052709 Yalian Yang Xiaosong Hu Datong Qing Fangyuan Chen http://www.mdpi.com/1999-4907/4/2/364 Partial harvesting has been proposed as a key aspect to implementing ecosystem management in the Canadian boreal forest. We report on a replicated experiment located in boreal mixedwoods of Northwestern Quebec. In the winter of 2000–2001, two partial harvesting treatments, one using a dispersed pattern, and a second, which created a (400 m2) gap pattern, were applied to a 90-year-old aspen-dominated mixed stand. The design also included a clear cut and a control. Over the course of the following eight years, live tree, coarse woody debris, regeneration and ground beetles were inventoried at variable intervals. Our results indicate that all harvesting treatments created conditions favorable to balsam fir (Abies balsamea) sapling growth and trembling aspen (Populus tremuloides) sapling recruitment. However, balsam fir and trembling aspen regeneration and ground beetles response to gap cuts were closer to patterns observed in clear cuts than in dispersed harvesting. The underlying reasons for these differing patterns can be linked to factors associated with the contrasting light regimes created by the two partial harvesting treatments. The study confirms that partially harvesting is an ecologically sound approach in boreal mixedwoods and could contribute to maintaining the distribution of stand ages at the landscape level. Forests 2013-05-22 4 2 Article 10.3390/f4020364 364 385 1999-4907 2013-05-22 doi: 10.3390/f4020364 Suzanne Brais Timothy Work Émilie Robert Christopher O'Connor Manuella Strukelj Arun Bose Danielle Celentano Brian Harvey http://www.mdpi.com/2304-8158/2/2/213 Optical oxygen sensors were used to ascertain the level of oxygen consumed by individual salad leaves for optimised packaging of ready-to-eat (RTE) Italian salad mixes during refrigerated storage. Seven commonly found leaves in Italian salad mixes were individually assessed for oxygen utilisation in packs. Each leaf showed varying levels of respiration throughout storage. Using the information obtained, an experimental salad mix was formulated (termed Mix 3) which consisted of the four slowest respiring salad leaves—Escarole, Frisee, Red Batavia, Lollo Rosso. Mix 3 was then compared against two commercially available Italian salads; Mix 1 (Escarole, Frisee, Radicchio, Lollo Rosso) and Mix 2 (Cos, Frisee, Radicchio, Lollo Rosso). Optical sensors were used to non-destructively monitor oxygen usage in all mixes throughout storage. In addition to oxygen consumption, all three salad mixes were quality assessed in terms of microbial load and sensorial acceptability. In conclusion, Mix 3 was found to consume the least amount of oxygen over time, had the lowest microbial load and was most sensorially preferred (p < 0.05) in terms of overall appearance and acceptability. This study clearly shows the potential that oxygen sensors possess in terms of assisting in the optimised development of commercial RTE salad products. Foods 2013-05-22 2 2 Article 10.3390/foods2020213 213 224 2304-8158 2013-05-22 doi: 10.3390/foods2020213 Andreas Hempel Maurice O'Sullivan Dmitri Papkovsky Joseph Kerry http://www.mdpi.com/1099-4300/15/5/1929 Infectious agents, their hosts, and relevant abiotic components are directly involved in the complex dynamic process of maintaining infectious diseases in Nature. The current tendency to focus on host-pathogen interactions at the molecular and organismal levels does not advance our knowledge about infectious diseases, as much as it potentially could, by ignoring the ecological context pivotal for understanding the biology of the diseases. A new model of investigation requires a dynamic shift of perspectives in the “simplicity-complexity” dimension: from virulence factors to multi-sided descriptions of the pathogens; from particular microbes to wide microbial communities; from clinical manifestations to a variety of infectious patterns; from findings of infectious agents to defining a natural focus of the infection as a self-regulated system; from single factors affecting host-parasite relations to the complex ecological context. Various aspects of interactions between hosts, vectors, pathogens, and environmental niches should be integrated at multiple spatiotemporal scales and at different levels of biological organization (molecular, genomic, organismal, population, and ecosystem). Entropy 2013-05-22 15 5 Review 10.3390/e15051929 1929 1962 1099-4300 2013-05-22 doi: 10.3390/e15051929 Michael Kosoy http://www.mdpi.com/1999-4893/6/2/352 In biology, the notion of degenerate pattern plays a central role for describing various phenomena. For example, protein active site patterns, like those contained in the PROSITE database, e.g., [FY ]DPC[LIM][ASG]C[ASG], are, in general, represented by degenerate patterns with character classes. Researchers have developed several approaches over the years to discover degenerate patterns. Although these methods have been exhaustively and successfully tested on genomes and proteins, their outcomes often far exceed the size of the original input, making the output hard to be managed and to be interpreted by refined analysis requiring manual inspection. In this paper, we discuss a characterization of degenerate patterns with character classes, without gaps, and we introduce the concept of pattern priority for comparing and ranking different patterns. We define the class of underlying patterns for filtering any set of degenerate patterns into a new set that is linear in the size of the input sequence. We present some preliminary results on the detection of subtle signals in protein families. Results show that our approach drastically reduces the number of patterns in output for a tool for protein analysis, while retaining the representative patterns. Algorithms 2013-05-22 6 2 Article 10.3390/a6020352 352 370 1999-4893 2013-05-22 doi: 10.3390/a6020352 Matteo Comin Davide Verzotto http://www.mdpi.com/1996-1073/6/5/2686 In the first part of this work, combined heat and power (CHP) criteria pertaining to energy, exergy, environmental (pollutant emission) and economic aspects, have been investigated and compared. Although the constraints in legislation usually refer to energy efficiency, primary energy savings and greenhouse gas savings, other criteria should also be taken into account in order to obtain a better evaluation of a cogeneration plant. Here particular attention has been paid to saving indexes for both an individual CHP-unit and for a CHP-system, that is the complete system with all the cogeneration units and the auxiliary plants necessary to cover the users’ demand. Five indexes, named potential indexes, have been introduced to evaluate the cogeneration potential: one for energy saving, one for exergy, two for environmental aspects (global and local scale) and one for economic aspects. Finally, some indexes analysed in the paper have been applied to a case study concerning a district heating cogeneration system, and the different behaviour of the energy-exergy, environmental and economic aspects has been discussed. Energies 2013-05-22 6 5 Article 10.3390/en6052686 2686 2708 1996-1073 2013-05-22 doi: 10.3390/en6052686 Marco Torchio http://www.mdpi.com/2075-5309/3/2/422 Wind loading and windborne debris (missile) impact are the two primary mechanisms that result in window glazing damage during hurricanes. Wind-borne debris is categorized into two types: small hard missiles; such as roof gravel; and large soft missiles representing lumber from wood-framed buildings. Laminated architectural glazing (LAG) may be used in buildings where impact resistance is needed. The glass plies in LAG undergo internal damage before total failure. The bulk of the published work on this topic either deals with the stress and dynamic analyses of undamaged LAG or the total failure of LAG. The pre-failure damage response of LAG due to the combination of wind loading and windborne debris impact is studied. A continuum damage mechanics (CDM) based constitutive model is developed and implemented via an axisymmetric finite element code to study the failure and damage behavior of laminated architectural glazing subjected to combined loading of wind and windborne debris impact. The effect of geometric and material properties on the damage pattern is studied parametrically. Buildings 2013-05-22 3 2 Article 10.3390/buildings3020422 422 441 2075-5309 2013-05-22 doi: 10.3390/buildings3020422 Mahesh Shetty Jun Wei Lokeswarappa Dharani Daniel Stutts http://www.mdpi.com/2075-5309/3/2/399 The objective of this study is to investigate the accuracy of Computational Fluid Dynamics (CFD) for simultaneously predicting the outdoor and indoor airflows of single-cell and multi-storey buildings. Empirical models and two existing wind tunnel experimental data are used for validation. This study found that coupled CFD simulations provide sufficiently accurate airflow predictions and, in cases of buildings with complex façade treatments, accurately accounts for changes in ventilation performance, which may be impossible using empirical models. This study concludes that coupled CFD simulations can generally be used to predict ventilation performance in small and large buildings. Buildings 2013-05-22 3 2 Article 10.3390/buildings3020399 399 421 2075-5309 2013-05-22 doi: 10.3390/buildings3020399 Mohd Mohamed Steve King Masud Behnia Deo Prasad http://www.mdpi.com/1424-8220/13/5/6865 In this paper, a panel of single-stranded DNA aptamers with high affinity and specificity against Salmonella Paratyphi A was selected from an enriched oligonucleotide pool by a whole-cell-Systematic Evolution of Ligands by Exponential Enrichment (SELEX) procedure, during which four other Salmonella serovars were used as counter-selection targets. It was determined through a fluorescence assay that the selected aptamers had high binding ability and specificity to this pathogen. The dissociation constant of these aptamers were up to nanomolar range, and aptamer Apt22 with the lowest Kd (47 ± 3 nM) was used in cell imaging experiments. To detect this bacteria with high specificity and cost-efficiently, a novel useful detection method was also constructed based on the noncovalent self-assembly of single-walled carbon nanotubes (SWNTs) and DNAzyme-labeled aptamer detection probes. The amounts of target bacteria could be quantified by exploiting chemoluminescence intensity changes at 420 nm and the detection limit of the method was 103 cfu/mL. This study demonstrated the applicability of Salmonella specific aptamers and their potential for use in the detection of Salmonella in food, clinical and environmental samples. Sensors 2013-05-22 13 5 Article 10.3390/s130506865 6865 6881 1424-8220 2013-05-22 doi: 10.3390/s130506865 Ming Yang Zhihui Peng Yi Ning Yongzhe Chen Qin Zhou Le Deng http://www.mdpi.com/1424-8220/13/5/6832 In this paper, a human electrocardiogram (ECG) identification system based on ensemble empirical mode decomposition (EEMD) is designed. A robust preprocessing method comprising noise elimination, heartbeat normalization and quality measurement is proposed to eliminate the effects of noise and heart rate variability. The system is independent of the heart rate. The ECG signal is decomposed into a number of intrinsic mode functions (IMFs) and Welch spectral analysis is used to extract the significant heartbeat signal features. Principal component analysis is used reduce the dimensionality of the feature space, and the K-nearest neighbors (K-NN) method is applied as the classifier tool. The proposed human ECG identification system was tested on standard MIT-BIH ECG databases: the ST change database, the long-term ST database, and the PTB database. The system achieved an identification accuracy of 95% for 90 subjects, demonstrating the effectiveness of the proposed method in terms of accuracy and robustness. Sensors 2013-05-22 13 5 Article 10.3390/s130506832 6832 6864 1424-8220 2013-05-22 doi: 10.3390/s130506832 Zhidong Zhao Lei Yang Diandian Chen Yi Luo http://www.mdpi.com/1424-8220/13/5/6811 It is easy to measure energy consumption with a power meter. However, energy savings cannot be directly computed by the powers measured using existing power meter technologies, since the power consumption only reflects parts of the real energy flows. The International Performance Measurement and Verification Protocol (IPMVP) was proposed by the Efficiency Valuation Organization (EVO) to quantify energy savings using four different methodologies of A, B, C and D. Although energy savings can be estimated following the IPMVP, there are limitations on its practical implementation. Moreover, the data processing methods of the four IPMVP alternatives use multiple sensors (thermometer, hygrometer, Occupant information) and power meter readings to simulate all facilities, in order to determine an energy usage benchmark and the energy savings. This study proposes a simple sensor platform to measure energy savings. Using usually the Electronic Product Code (EPC) global standard, an architecture framework for an information system is constructed that integrates sensors data, power meter readings and occupancy conditions. The proposed sensor platform is used to monitor a building with a newly built vertical garden system (VGS). A VGS shields solar radiation and saves on energy that would be expended on air-conditioning. With this platform, the amount of energy saved in the whole facility is measured and reported in real-time. The data are compared with those obtained from detailed measurement and verification (M&V) processes. The discrepancy is less than 1.565%. Using measurements from the proposed sensor platform, the energy savings for the entire facility are quantified, with a resolution of ±1.2%. The VGS gives an 8.483% daily electricity saving for the building. Thus, the results show that the simple sensor platform proposed by this study is more widely applicable than the four complicated IPMVP alternatives and the VGS is an effective tool in reducing the carbon footprint of a building. Sensors 2013-05-22 13 5 Article 10.3390/s130506811 6811 6831 1424-8220 2013-05-22 doi: 10.3390/s130506811 Yen-Chieh Tseng Da-Sheng Lee Cheng-Fang Lin Ching-Yuan Chang http://www.mdpi.com/2073-4409/2/2/330 Resolution of acute inflammation is an active process that requires inhibition of further leukocyte recruitment and removal of leukocytes from inflamed sites. Emigrated neutrophils undergo apoptosis before being removed by scavenger macrophages. Recent studies using a variety of gene knockout, transgenic and pharmacological strategies in diverse models of inflammation established neutrophil apoptosis as a critical control point in resolving inflammation. Analysis of death mechanisms revealed distinct features in executing the death program in neutrophils, which can be exploited as targets for controlling the lifespan of neutrophils. Indeed, anti-inflammatory and pro-resolution lipid mediators derived from essential fatty acids, such as lipoxin A4 and resolvin E1, autacoids and proteins, such as annexin A1 and TRAIL, and cyclin-dependent kinase inhibitors, can enhance the resolution of inflammation through induction of neutrophil apoptosis and promoting their removal by efferocytosis. In this review, we discuss recent advances in understanding the molecular basis of these actions, highlighting the potential of therapeutic induction of neutrophil apoptosis for dampening neutrophil-mediated tissue injury and inflammation underlying a variety of diseases. Cells 2013-05-22 2 2 Review 10.3390/cells2020330 330 348 2073-4409 2013-05-22 doi: 10.3390/cells2020330 Driss El Kebir János Filep http://www.mdpi.com/2075-5309/3/2/380 This paper describes potential challenges and opportunities for using thermal simulation tools to optimize building performance. After reviewing current trends in thermal simulation, it outlines major criteria for the evaluation of building thermal simulation tools based on specifications and capabilities in interoperability. Details are discussed including workflow of data exchange of multiple thermal analyses such as the BIM-based application. The present analysis focuses on selected thermal simulation tools that provide functionalities to exchange data with other tools in order to obtain a picture of its basic work principles and to identify selection criteria for generic thermal tools in BIM. Significances and barriers to integration design with BIM and building thermal simulation tools are also discussed. Buildings 2013-05-22 3 2 Article 10.3390/buildings3020380 380 398 2075-5309 2013-05-22 doi: 10.3390/buildings3020380 Yudi Bahar Christian Pere Jérémie Landrieu Christophe Nicolle http://www.mdpi.com/2076-3425/3/2/800 In the early 1960s intrinsically generated widespread neuronal discharges were discovered to be the basis for the earliest motor behavior throughout the animal kingdom. The pattern generating system is in fact programmed into the developing nervous system, in a regionally specific manner, already at the early neural plate stage. Such rhythmically modulated phasic bursts were next discovered to be a general feature of developing neural networks and, largely on the basis of experimental interventions in cultured neural tissues, to contribute significantly to their morpho-physiological maturation. In particular, the level of spontaneous synchronized bursting is homeostatically regulated, and has the effect of constraining the development of excessive network excitability. After birth or hatching, this “slow-wave” activity pattern becomes sporadically suppressed in favor of sensory oriented “waking” behaviors better adapted to dealing with environmental contingencies. It nevertheless reappears periodically as “sleep” at several species-specific points in the diurnal/nocturnal cycle. Although this “default” behavior pattern evolves with development, its essential features are preserved throughout the life cycle, and are based upon a few simple mechanisms which can be both experimentally demonstrated and simulated by computer modeling. In contrast, a late onto- and phylogenetic aspect of sleep, viz., the intermittent “paradoxical” activation of the forebrain so as to mimic waking activity, is much less well understood as regards its contribution to brain development. Some recent findings dealing with this question by means of cholinergically induced “aroused” firing patterns in developing neocortical cell cultures, followed by quantitative electrophysiological assays of immediate and longterm sequelae, will be discussed in connection with their putative implications for sleep ontogeny. Brain Sciences 2013-05-22 3 2 Review 10.3390/brainsci3020800 800 820 2076-3425 2013-05-22 doi: 10.3390/brainsci3020800 Michael Corner http://www.mdpi.com/2073-4395/3/2/462 Biochar application to agricultural soils is an interesting emerging technology with promising potential for long-term carbon storage, sustainable waste disposal, and soil fertility enhancement. Extensive information exists in the literature on the highly beneficial properties of biochar. Nevertheless, systematic application of biochar on European agricultural soils may have wide ranging policy implications as well as environmental and public health concerns. In this paper we critically review existing scientific evidence from a European policy perspective and identify research gaps for future comprehensive assessments of the policy, environmental, economic, and health implications of the systematic use of biochar in European agricultural soils. Agronomy 2013-05-22 3 2 Review 10.3390/agronomy3020462 462 473 2073-4395 2013-05-22 doi: 10.3390/agronomy3020462 Luca Montanarella Emanuele Lugato http://www.mdpi.com/2076-3387/3/2/6 The following paragraphs are reproduced from the website of the publisher [1]. Taking a unique approach to business ethics unlike the typical focus on conceptual/legal frameworks, this book features 25 case studies that cover a full range of business practices, controls, and ethics issues. The new edition is fully updated with new case studies from the recent financial crisis, comparing it with Enron's crossing of various ethical lines. Interpretive essays explore financial control systems and lessons learned from specific case studies and circumstances. Readers will find a practical toolkit they can use to identify ethics issues and tackle problems effectively within corporations. Administrative Sciences 2013-05-22 3 2 New Book Received 10.3390/admsci3020006 6 8 2076-3387 2013-05-22 doi: 10.3390/admsci3020006 Shu-Kun Lin http://www.mdpi.com/2072-6643/5/5/1823 The lens and retina of the human eye are exposed constantly to light and oxygen. In situ phototransduction and oxidative phosphorylation within photoreceptors produces a high level of phototoxic and oxidative related stress. Within the eye, the carotenoids lutein and zeaxanthin are present in high concentrations in contrast to other human tissues. We discuss the role of lutein and zeaxanthin in ameliorating light and oxygen damage, and preventing age-related cellular and tissue deterioration in the eye. Epidemiologic research shows an inverse association between levels of lutein and zeaxanthin in eye tissues and age related degenerative diseases such as macular degeneration (AMD) and cataracts. We examine the role of these carotenoids as blockers of blue-light damage and quenchers of oxygen free radicals. This article provides a review of possible mechanisms of lutein action at a cellular and molecular level. Our review offers insight into current clinical trials and experimental animal studies involving lutein, and possible role of nutritional intervention in common ocular diseases that cause blindness. Nutrients 2013-05-22 5 5 Review 10.3390/nu5051823 1823 1839 2072-6643 2013-05-22 doi: 10.3390/nu5051823 Keyvan Koushan Raluca Rusovici Wenhua Li Lee Ferguson Kakarla Chalam http://www.mdpi.com/1999-4915/5/5/1272 Successful infection of herpes simplex virus is dependent upon chromatin modulation by the cellular coactivator host cell factor-1 (HCF-1). This review focuses on the multiple chromatin modulation components associated with HCF-1 and the chromatin-related dynamics mediated by this coactivator that lead to the initiation of herpes simplex virus (HSV) immediate early gene expression. Viruses 2013-05-22 5 5 Review 10.3390/v5051272 1272 1291 1999-4915 2013-05-22 doi: 10.3390/v5051272 Jodi Vogel Thomas Kristie http://www.mdpi.com/1999-4915/5/5/1261 The role of hepatitis B virus (HBV) X protein (HBx) in the regulation of HBV replication remains controversial. In the present study, the role of HBx in regulating HBV replication was initially investigated in both HepG2 and Huh7 in vitro cell lines with a transient transfection system. Next, the regions of HBx responsible for transcriptional transactivation and promotion of HBV replication were mapped in an HBV replication mouse model by in vivo transfection of a series of HBx expression plasmids. In an in vitro setting, HBx deficiency had little effect on HBV replication in Huh7 cells, but impaired HBV replication in HepG2 cells. In an in vivo setting, HBx had a strong enhancing effect on HBV transcription and replication. For the C-terminal two-thirds of the protein (amino acids [aa] 51 to 154) was required for this function of HBx, and the regions spanning aa 52 to 72 and 88 to 154 were found to be important for the stimulatory function of HBx on HBV replication. In conclusion, the role of HBx in HBV replication regulation is affected by host cell type, and HBx has an important role in stimulating HBV transcription and replication in hepatocytes in vivo. Further, the transcriptional transactivation function of HBx may be crucial for its stimulatory effect on HBV transcription and replication. Viruses 2013-05-22 5 5 Article 10.3390/v5051261 1261 1271 1999-4915 2013-05-22 doi: 10.3390/v5051261 Dao-Yin Gong En-Qiang Chen Fei-Jun Huang Xiao-Hua Leng Xing Cheng Hong Tang http://www.mdpi.com/1999-4915/5/5/1250 Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS), feline infectious peritonitis (FIP), mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA), could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication. Viruses 2013-05-22 5 5 Review 10.3390/v5051250 1250 1260 1999-4915 2013-05-22 doi: 10.3390/v5051250 Yoshikazu Tanaka Yuka Sato Takashi Sasaki http://www.mdpi.com/2072-6643/5/5/1801 Functional innate and acquired immune responses are required to protect the host from pathogenic bacterial infections. Modulation of host immune functions may have beneficial or deleterious effects on disease outcome. Different types of dietary fatty acids have been shown to have variable effects on bacterial clearance and disease outcome through suppression or activation of immune responses. Therefore, we have chosen to review research across experimental models and food sources on the effects of commonly consumed fatty acids on the most common food-borne pathogens, including Salmonella sp., Campylobacter sp., Shiga toxin-producing Escherichia coli, Shigella sp., Listeria monocytogenes, and Staphylococcus aureus. Altogether, the compilation of literature suggests that no single fatty acid is an answer for protection from all food-borne pathogens, and further research is necessary to determine the best approach to improve disease outcomes. Nutrients 2013-05-22 5 5 Review 10.3390/nu5051801 1801 1822 2072-6643 2013-05-22 doi: 10.3390/nu5051801 Lisa Harrison Kannan Balan Uma Babu http://www.mdpi.com/2072-6643/5/5/1757 Diarrhoea is a common disease which causes pain and may be deadly, especially in developing countries. In Bangladesh, diarrhoeal diseases affect thousands of people every year, and children are especially vulnerable. Bacterial toxins or viral infections are the most common cause of the disease. The diarrhoea outbreaks are often associated with flood affected areas with contaminated drinking water and an increased risk of spreading the water-borne disease. Not surprisingly, plants found in the near surroundings have been taken into use by the local community as medicine to treat diarrhoeal symptoms. These plants are cheaper and more easily available than conventional medicine. Our question is: What is the level of documentation supporting the use of these plants against diarrhoea and is their consumption safe? Do any of these plants have potential for further exploration? In this review, we have choosen seven plant species that are used in the treatment of diarrhoea; Diospyros peregrina, Heritiera littoralis, Ixora coccinea, Pongamia pinnata, Rhizophora mucronata, Xylocarpus granatum, and Xylocarpus moluccensis. Appearance and geographical distribution, traditional uses, chemical composition, and biological studies related to antidiarrhoeal activity will be presented. This review reveals that there is limited scientific evidence supporting the traditional use of these plants. Most promising are the barks from D. peregrina, X. granatum and X. moluccensis which contain tannins and have shown promising results in antidiarrhoeal mice models. The leaves of P. pinnata also show potential. We suggest these plants should be exploited further as possible traditional herbal remedies against diarrhoea including studies on efficacy, optimal dosage and safety. Nutrients 2013-05-22 5 5 Review 10.3390/nu5051757 1757 1800 2072-6643 2013-05-22 doi: 10.3390/nu5051757 Helle Wangensteen Line Klarpås Mahiuddin Alamgir Anne Samuelsen Karl Malterud http://www.mdpi.com/1420-3049/18/5/6113 Sophoricoside exhibits numerous pharmacological effects, including anti- inflammatory and anti-cancer actions, yet the exact mechanism that accounts for the anti-allergic effects of sophoricoside is not completely understood. The aim of the present study was to elucidate whether and how sophoricoside modulates the mast cell-mediated allergic inflammation in vitro and in vivo. We investigated the pharmacological effects of sophoricoside on both compound 48/80 or histamine-induced scratching behaviors and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in mice. Additionally, to find a possible explanation for the anti-inflammatory effects of sophoricoside, we evaluated the effects of sophoricoside on the production of histamine and inflammatory cytokines and activation of nuclear factor-κB (NF-κB) and caspase-1 in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). The finding of this study demonstrated that sophoricoside reduced compound 48/80 or histamine-induced scratching behaviors and DNCB-induced atopic dermatitis in mice. Additionally, sophoricoside inhibited the production of inflammatory cytokines as well as the activation of NF-κB and caspase-1 in stimulated HMC-1. Collectively, the findings of this study provide us with novel insights into the pharmacological actions of sophoricoside as a potential molecule for use in the treatment of allergic inflammation diseases. Molecules 2013-05-22 18 5 Article 10.3390/molecules18056113 6113 6127 1420-3049 2013-05-22 doi: 10.3390/molecules18056113 Su-Jin Kim Gil-Yong Lee Ji-Wook Jung Sa-Rang Oh Eun-Mi Ahn Sung-Hoon Kim Seung-Heon Hong Jae-Young Um http://www.mdpi.com/1420-3049/18/5/6101 The two step synthesis of a new bolaamphiphile derived from alkenyl l-rhamnosides was described. The general synthetic strategy of bolaamphiphiles derived from l-rhamnose was based on a previous work describing the synthesis of bolaamphiphiles derived from d-xylose. The conformational properties of this new compound were investigated by FTIR spectroscopy in an aqueous film in order to obtain a reference for further studies about the membrane-interacting properties. Moreover, the surface activity of this new bolaamphiphile was analyzed by Langmuir balance technology and was compared with that of the analogous bolaamphiphile derived from alkenyl D-xylosides. The findings indicate that the rhamnoside-based bolaform has an increased surface activity and a better ability to form aggregates than xyloside-based one. Molecules 2013-05-22 18 5 Short Note 10.3390/molecules18056101 6101 6112 1420-3049 2013-05-22 doi: 10.3390/molecules18056101 Sylvain Gatard Mehmet Nasir Magali Deleu Nadia Klai Vincent Legrand Sandrine Bouquillon http://www.mdpi.com/1420-3049/18/5/6092 Six biflavonoids were isolated from G. madruno, one of which, 7''-O-(6''''-acetyl)-glucoside of morelloflavone, is a new compound identified on the basis of 1D, 2D NMR (HMQC and HMBC) spectroscopic methods and chemical evidence. The antioxidant activity of the biflavonoids against low-density lipoprotein (LDL) peroxidation induced with Cu2+, was studied by means of a TBARS assay. The antioxidant potential of a biflavonoid fraction (BF) was also evaluated and correlated with its biflavonoid content. The flavanone-(3→8'')-flavone biflavonoids displayed antioxidant activity, particularly morelloflavone, which was significantly more potent than quercetin, with a CE50 of 12.36 μg/mL. Lipid peroxidation, was also significantly reduced in the presence of the BF (EC50 = 11.85 μg/mL). These results suggest that the BF is an excellent antioxidant. Molecules 2013-05-22 18 5 Article 10.3390/molecules18056092 6092 6100 1420-3049 2013-05-22 doi: 10.3390/molecules18056092 Edison Osorio Julián Londoño Jaume Bastida http://www.mdpi.com/1996-1073/6/5/2663 The promotion of hybrid and electric vehicles (EVs) has been proposed as one promising solution for reducing transport energy consumption and mitigating vehicular emissions in China. In this study, the energy and environmental impacts of hybrid and EVs during 2010–2020 were evaluated through an energy conversion analysis and a life cycle assessment (LCA), and the per-kilometer energy consumptions of gasoline, coal, natural gas (NG), oil, biomass, garbage and electricity for EVs and HEVs were estimated. Results show that the EVs and HEVs can reduce the energy consumption of vehicles by national average ratios of 17%–19% and 30%–33%, respectively. The study also calculated the detailed emission factors of SO2, NOX, VOC, CO, NH3, PM10, PM2.5, OC, EC, CO2, N2O, CH4, Pb and Hg. It is indicated that the HEVs can bring significant reductions of NOX, VOC and CO emissions and lesser decreases of SO2 and CO2 for a single vehicle. The EVs could decrease many of the VOC, NH3, CO and CO2 emissions, but increase the SO2, NOX and particles by 10.8–13.0, 2.7–2.9 and 3.6–11.5 times, respectively. In addition, the electricity sources had significant influence on energy consumption (EC) and emissions. A high proportion of coal-fired energy resulted in large ECs and emission factors. The total energy consumption and pollutants emission changes in 2015 and 2020 were also calculated. Based on the energy use and emission analysis of HEVs and EVs, it is suggested that EVs should be promoted in the regions with higher proportions of hydropower, natural gas-fired power and clean energy power, while HEVs can be widely adopted in the regions with high coal-fired power ratios. This is to achieve a higher energy consumption reduction and pollutant emission mitigation. Moreover, the results can also provide scientific support for the total amount control of regional air pollutants in China. Energies 2013-05-22 6 5 Article 10.3390/en6052663 2663 2685 1996-1073 2013-05-22 doi: 10.3390/en6052663 Jianlei Lang Shuiyuan Cheng Ying Zhou Beibei Zhao Haiyan Wang Shujing Zhang http://www.mdpi.com/1996-1073/6/5/2644 This paper compares the greenhouse gas (GHG) emissions of natural gas (NG)- based fuels to the GHG emissions of electric vehicles (EVs) powered with NG-to-electricity in China. A life-cycle model is used to account for full fuel cycle and use-phase emissions, as well as vehicle cycle and battery manufacturing. The reduction of life-cycle GHG emissions of EVs charged by electricity generated from NG, without utilizing carbon dioxide capture and storage (CCS) technology can be 36%–47% when compared to gasoline vehicles. The large range change in emissions reduction potential is driven by the different generation technologies that could in the future be used to generate electricity in China. When CCS is employed in power plants, the GHG emission reductions increase to about 71%–73% compared to gasoline vehicles. It is found that compressed NG (CNG) and liquefied NG (LNG) fuels can save about 10% of carbon as compared to gasoline vehicles. However, gas-to-liquid (GTL) fuel made through the Fischer-Tropsch method will likely lead to a life-cycle GHG emissions increase, potentially 3%–15% higher than gasoline, but roughly equal to petroleum-based diesel. When CCS is utilized, the GTL fueled vehicles emit roughly equal GHG emissions to petroleum-based diesel fuel high-efficient hybrid electric vehicle from the life-cycle perspective. Energies 2013-05-22 6 5 Article 10.3390/en6052644 2644 2662 1996-1073 2013-05-22 doi: 10.3390/en6052644 Xunmin Ou Xiliang Zhang Xu Zhang Qian Zhang http://www.mdpi.com/1996-1073/6/5/2624 This paper proposes a new model for short-term forecasting of electric energy production in a photovoltaic (PV) plant. The model is called HIstorical SImilar MIning (HISIMI) model; its final structure is optimized by using a genetic algorithm, based on data mining techniques applied to historical cases composed by past forecasted values of weather variables, obtained from numerical tools for weather prediction, and by past production of electric power in a PV plant. The HISIMI model is able to supply spot values of power forecasts, and also the uncertainty, or probabilities, associated with those spot values, providing new useful information to users with respect to traditional forecasting models for PV plants. Such probabilities enable analysis and evaluation of risk associated with those spot forecasts, for example, in offers of energy sale for electricity markets. The results of spot forecasting of an illustrative example obtained with the HISIMI model for a real-life grid-connected PV plant, which shows high intra-hour variability of its actual power output, with forecasting horizons covering the following day, have improved those obtained with other two power spot forecasting models, which are a persistence model and an artificial neural network model. Energies 2013-05-22 6 5 Article 10.3390/en6052624 2624 2643 1996-1073 2013-05-22 doi: 10.3390/en6052624 Claudio Monteiro Tiago Santos L. Fernandez-Jimenez Ignacio Ramirez-Rosado M. Terreros-Olarte http://www.mdpi.com/1999-4893/6/2/319 The suffix tree is an extremely important data structure in bioinformatics. Classical implementations require much space, which renders them useless to handle large sequence collections. Recent research has obtained various compressed representations for suffix trees, with widely different space-time tradeoffs. In this paper we show how the use of range min-max trees yields novel representations achieving practical space/time tradeoffs. In addition, we show how those trees can be modified to index highly repetitive collections, obtaining the first compressed suffix tree representation that effectively adapts to that scenario. Algorithms 2013-05-21 6 2 Article 10.3390/a6020319 319 351 1999-4893 2013-05-21 doi: 10.3390/a6020319 Andrés Abeliuk Rodrigo Cánovas Gonzalo Navarro http://www.mdpi.com/2079-9284/1/1/1 It is my great pleasure to announce a newly launched open access journal, Cosmetics, published by MDPI, dedicated to this fascinating world. Do we need a new journal in this area? This was the question I had in mind before starting the project and I will try to answer in the following paragraphs. [...] Cosmetics 2013-05-21 1 1 Editorial 10.3390/cosmetics1010001 1 2 2079-9284 2013-05-21 doi: 10.3390/cosmetics1010001 Enzo Berardesca http://www.mdpi.com/2076-3263/3/2/216 The Upper Ordovician (Edenian) Lindsay Formation of the Ottawa Embayment represents the final stage of carbonate platform development in the Taconic foreland periphery inboard of the northern Appalachian orogen. The succession overlies a narrow (~60 km) axis of a Neoproterozoic Laurentian rift extending across the Grenville orogen. The Lindsay Formation consists of a lower heavily bioturbated skeletal limestone that represents a warm-water shoal facies following an underlying outer ramp stratigraphy, and an upper division of renewed deep-water deposition with organic-rich shale and fossiliferous lime mudstone. Pyritic deep-water black shale of the westerly advancing Taconic foreland basin disconformably overlies this platform succession. Stratigraphic correlation through the central embayment identifies likely synsedimentary faults and seaward-directed erosion bounding the Lindsay Formation in a region of older Ordovician faults and a change in the lithotectonic character of the crystalline basement. The Late Ordovician shallowing and localization of structural/erosional features are interpreted to record a structural hinge: a local accommodation to, first, foreland periphery uplift, then rapid subsidence related to westerly diachronous foreland subsidence through the platform interior. Spatial association of structures of differing ages suggests that reactivation of inherited weakened crust influenced Late Ordovician sedimentary patterns. Geosciences 2013-05-21 3 2 Article 10.3390/geosciences3020216 216 239 2076-3263 2013-05-21 doi: 10.3390/geosciences3020216 Ruth Gbadeyan George Dix http://www.mdpi.com/2218-1989/3/2/397 The Critical Assessment of Small Molecule Identification (CASMI) contest was developed to provide a systematic comparative evaluation of strategies applied for the annotation and identification of small molecules. The authors participated in eleven challenges in both category 1 (to deduce a molecular formula) and category 2 (to deduce a molecular structure) related to high resolution LC-MS data. For category 1 challenges, the PUTMEDID_LCMS workflows provided the correct molecular formula in nine challenges; the two incorrect submissions were related to a larger mass error in experimental data than expected or the absence of the correct molecular formula in a reference file applied in the PUTMEDID_LCMS workflows. For category 2 challenges, MetFrag was applied to construct in silico fragmentation data and compare with experimentally-derived MS/MS data. The submissions for three challenges were correct, and for eight challenges, the submissions were not correct; some submissions showed similarity to the correct structures, while others showed no similarity. The low number of correct submissions for category 2 was a result of applying the assumption that all chemicals were derived from biological samples and highlights the importance of knowing the origin of biological or chemical samples studied and the metabolites expected to be present to define the correct chemical space to search in annotation processes. Metabolites 2013-05-21 3 2 Article 10.3390/metabo3020397 397 411 2218-1989 2013-05-21 doi: 10.3390/metabo3020397 J. Allwood Ralf Weber Jiarui Zhou Shan He Mark Viant Warwick Dunn http://www.mdpi.com/2218-6581/2/2/66 In this paper, we introduce an adaptive type-2 fuzzy logic controller (FLC) for flexible-joint manipulators with structured and unstructured dynamical uncertainties. Simplified interval fuzzy sets are used for real-time efficiency, and internal stability is enhanced by adopting a trade-off strategy between the manipulator’s and the actuators’ velocities. Furthermore, the control scheme is independent of the computationally expensive noisy torque and acceleration signals. The controller is validated through a set of numerical simulations and by comparing it against its type-1 counterpart. The ability of the adaptive type-2 FLC in coping with large magnitudes of uncertainties yields an improved performance. The stability of the proposed control system is guaranteed using Lyapunov stability theory. Robotics 2013-05-21 2 2 Article 10.3390/robotics2020066 66 91 2218-6581 2013-05-21 doi: 10.3390/robotics2020066 Hicham Chaoui Wail Gueaieb Mohammad Biglarbegian Mustapha Yagoub http://www.mdpi.com/2079-9268/3/2/73 In this paper, we demonstrate how a network of dendrites can be used to build the state decoding block of a wordspotter similar to a Hidden Markov Model (HMM) classifier structure. We present simulation and experimental data for a single line dendrite and also experimental results for a dendrite-based classifier structure. This work builds on previously demonstrated building blocks of a neural network: the channel, synapses and dendrites using CMOS circuits. These structures can be used for speech and pattern recognition. The computational efficiency of such a system is >10 MMACs/μW as compared to Digital Systems which perform 10 MMACs/mW. Journal of Low Power Electronics and Applications 2013-05-21 3 2 Article 10.3390/jlpea3020073 73 98 2079-9268 2013-05-21 doi: 10.3390/jlpea3020073 Suma George Jennifer Hasler Scott Koziol Stephen Nease Shubha Ramakrishnan http://www.mdpi.com/2073-4360/5/2/527 4,4′-Dithiodipyridine (dtdp), also termed 4,4′-dipyridyldisulfide, is a bridging ligand of the 4,4′-bipyridine type. The introduction of the disulfide moiety inevitably leads to a relatively rigid angular structure, which exhibits axial chirality. More than 90 metal complexes containing the dtdp ligand have been crystallographically characterised until now. This review focuses on the preparation and structural diversity of discrete and polymeric metallosupramolecular assemblies constructed from dtdp as bridging ligands. These encompass metallamacrocycles with M2L2 topology and coordination polymers with periodicity in one or two dimensions. One-dimensional coordination polymers represent the vast majority of the metallosupramolecular structures obtained from dtdp. These include repeated rhomboids, zigzag, helical and arched chains among other types. In this contribution, we make an attempt to provide a comprehensive account of the structural data that are currently available for metallosupramolecular assemblies based on the bent bridging ligand dtdp. Polymers 2013-05-21 5 2 Review 10.3390/polym5020527 527 575 2073-4360 2013-05-21 doi: 10.3390/polym5020527 Rüdiger Seidel Richard Goddard Iris Oppel http://www.mdpi.com/2076-3905/2/2/131 While Illumina microarrays can be used successfully for detecting small gene expression changes due to their high degree of technical replicability, there is little information on how different normalization and differential expression analysis strategies affect outcomes. To evaluate this, we assessed concordance across gene lists generated by applying different combinations of normalization strategy and analytical approach to two Illumina datasets with modest expression changes. In addition to using traditional statistical approaches, we also tested an approach based on combinatorial optimization. We found that the choice of both normalization strategy and analytical approach considerably affected outcomes, in some cases leading to substantial differences in gene lists and subsequent pathway analysis results. Our findings suggest that important biological phenomena may be overlooked when there is a routine practice of using only one approach to investigate all microarray datasets. Analytical artefacts of this kind are likely to be especially relevant for datasets involving small fold changes, where inherent technical variation—if not adequately minimized by effective normalization—may overshadow true biological variation. This report provides some basic guidelines for optimizing outcomes when working with Illumina datasets involving small expression changes. Microarrays 2013-05-21 2 2 Article 10.3390/microarrays2020131 131 152 2076-3905 2013-05-21 doi: 10.3390/microarrays2020131 Daniel Johnstone Carlos Riveros Moones Heidari Ross Graham Debbie Trinder Regina Berretta John Olynyk Rodney Scott Pablo Moscato Elizabeth Milward http://www.mdpi.com/2076-0787/2/2/209 The hallmark of our species is our ability to hybridize symbolic thinking with behavioral output. We began with the symmetrical hand axe around 1.7 mya and have progressed, slowly at first, then with greater rapidity, to producing increasingly more complex hybridized products. We now live in the age where our drive to hybridize has pushed us to the brink of a neuroscientific revolution, where for the first time we are in a position to willfully alter the brain and hence, our behavior and evolution. Nootropics, transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), deep brain stimulation (DBS) and invasive brain mind interface (BMI) technology are allowing humans to treat previously inaccessible diseases as well as open up potential vistas for cognitive enhancement. In the future, the possibility exists for humans to hybridize with BMIs and mobile architectures. The notion of self is becoming increasingly extended. All of this to say: are we in control of our brains, or are they in control of us? Humanities 2013-05-21 2 2 Article 10.3390/h2020209 209 252 2076-0787 2013-05-21 doi: 10.3390/h2020209 Robert Dielenberg http://www.mdpi.com/2073-4360/5/2/431 This review summarizes the state of the art in the synthesis of well-defined glycopolymers by Reversible-Deactivation Radical Polymerization (RDRP) from its inception in 1998 until August 2012. Glycopolymers architectures have been successfully synthesized with four major RDRP techniques: Nitroxide-mediated radical polymerization (NMP), cyanoxyl-mediated radical polymerization (CMRP), atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. Over 140 publications were analyzed and their results summarized according to the technique used and the type of monomer(s) and carbohydrates involved. Particular emphasis was placed on the experimental conditions used, the structure obtained (comonomer distribution, topology), the degree of control achieved and the (potential) applications sought. A list of representative examples for each polymerization process can be found in tables placed at the beginning of each section covering a particular RDRP technique. Polymers 2013-05-21 5 2 Review 10.3390/polym5020431 431 526 2073-4360 2013-05-21 doi: 10.3390/polym5020431 Ali Ghadban Luca Albertin http://www.mdpi.com/2072-4292/5/5/2534 Accurate assessments of spatio-temporal variations in gross primary productivity (GPP), evapotranspiration (ET), and water use efficiency (WUE) play a crucial role in the evaluation of carbon and water balance as well as have considerable effects on climate change. In this study, Moderate Resolution Imaging Spectroradiometer (MODIS) products were used to quantify the mean annual GPP and ET at Korean regional flux network site. We found that the seasonal mean values of WUE were 2.86 to 2.92 g∙C∙g∙H2O−1 in the dormant season and 1.81 to 1.88 g∙C∙g∙H2O−1 in the growing season during 2007 and 2008. The WUE was relatively stable during the growing season and tended to vary in the dormant season. Remote sensing data obtained by the MODIS satellite were appeared to be effective to improve our understanding of the spatio-temporal variation of ecohydrological parameters which have not yet been investigated in a number of previous articles. Based on the results of this study, we summarize the interactions between carbon and water circulation in terrestrial ecosystems and how their ecological procedures generated by the photosynthesis of vegetation influence in climatological perspectives. Remote Sensing 2013-05-21 5 5 Article 10.3390/rs5052534 2534 2553 2072-4292 2013-05-21 doi: 10.3390/rs5052534 Chanyang Sur Minha Choi http://www.mdpi.com/2220-9964/2/2/432 The GeoMemories project aims at publishing on the Web and digitally preserving historical aerial photographs that are currently stored in physical form within the archives of the Aerofototeca Nazionale in Rome. We describe a system, available at http://www.geomemories.org, that lets users visualize the evolution of the Italian landscape throughout the last century. The Web portal allows comparison of recent satellite imagery with several layers of historical maps, obtained from the aerial photos through a complex workflow that merges them together. We present several case studies carried out in collaboration with geologists, historians and archaeologists, that illustrate the great potential of our system in different research fields. Experiments and advances in image processing technologies are envisaged as a key factor in solving the inherent issue of vast amounts of manual work, from georeferencing to mosaicking to analysis. ISPRS International Journal of Geo-Information 2013-05-21 2 2 Article 10.3390/ijgi2020432 432 455 2220-9964 2013-05-21 doi: 10.3390/ijgi2020432 Matteo Abrate Clara Bacciu Anders Hast Andrea Marchetti Salvatore Minutoli Maurizio Tesconi http://www.mdpi.com/1424-8220/13/5/6793 The objective of the current research was not only to provide a fast and automatic positioning platform for single cells, but also improved biomolecular manipulation techniques. In this study, an automatic platform for cell positioning using electroosmotic flow and image processing technology was designed. The platform was developed using a PCI image acquisition interface card for capturing images from a microscope and then transferring them to a computer using human-machine interface software. This software was designed by the Laboratory Virtual Instrument Engineering Workbench, a graphical language for finding cell positions and viewing the driving trace, and the fuzzy logic method for controlling the voltage or time of an electric field. After experiments on real human leukemic cells (U-937), the success of the cell positioning rate achieved by controlling the voltage factor reaches 100% within 5 s. A greater precision is obtained when controlling the time factor, whereby the success rate reaches 100% within 28 s. Advantages in both high speed and high precision are attained if these two voltage and time control methods are combined. The control speed with the combined method is about 5.18 times greater than that achieved by the time method, and the control precision with the combined method is more than five times greater than that achieved by the voltage method. Sensors 2013-05-21 13 5 Article 10.3390/s130506793 6793 6810 1424-8220 2013-05-21 doi: 10.3390/s130506793 Chyung Ay Chao-Wang Young Jhong-Yin Chen http://www.mdpi.com/1424-8220/13/5/6775 A single-chip sensor system-on-a-chip (SoC) that implements radio for 2.4 GHz, complete digital baseband physical layer (PHY), 10-bit sigma-delta analog-to-digital converter and dedicated sensor calibration hardware for industrial sensing systems has been proposed and integrated in a 0.18-μm CMOS technology. The transceiver’s building block includes a low-noise amplifier, mixer, channel filter, receiver signal-strength indicator, frequency synthesizer, voltage-controlled oscillator, and power amplifier. In addition, the digital building block consists of offset quadrature phase-shift keying (OQPSK) modulation, demodulation, carrier frequency offset compensation, auto-gain control, digital MAC function, sensor calibration hardware and embedded 8-bit microcontroller. The digital MAC function supports cyclic redundancy check (CRC), inter-symbol timing check, MAC frame control, and automatic retransmission. The embedded sensor signal processing block consists of calibration coefficient calculator, sensing data calibration mapper and sigma-delta analog-to-digital converter with digital decimation filter. The sensitivity of the overall receiver and the error vector magnitude (EVM) of the overall transmitter are −99 dBm and 18.14%, respectively. The proposed calibration scheme has a reduction of errors by about 45.4% compared with the improved progressive polynomial calibration (PPC) method and the maximum current consumption of the SoC is 16 mA. Sensors 2013-05-21 13 5 Article 10.3390/s130506775 6775 6792 1424-8220 2013-05-21 doi: 10.3390/s130506775 Dong-Sun Kim Sung-Joon Jang Tae-Ho Hwang http://www.mdpi.com/2220-9964/2/2/413 Urban economic modeling and effective spatial planning are critical tools towards achieving urban sustainability. However, in practice, many technical obstacles, such as information islands, poor documentation of data and lack of software platforms to facilitate virtual collaboration, are challenging the effectiveness of decision-making processes. In this paper, we report on our efforts to design and develop a geospatial cyberinfrastructure (GCI) for urban economic analysis and simulation. This GCI provides an operational graphic user interface, built upon a service-oriented architecture to allow (1) widespread sharing and seamless integration of distributed geospatial data; (2) an effective way to address the uncertainty and positional errors encountered in fusing data from diverse sources; (3) the decomposition of complex planning questions into atomic spatial analysis tasks and the generation of a web service chain to tackle such complex problems; and (4) capturing and representing provenance of geospatial data to trace its flow in the modeling task. The Greater Los Angeles Region serves as the test bed. We expect this work to contribute to effective spatial policy analysis and decision-making through the adoption of advanced GCI and to broaden the application coverage of GCI to include urban economic simulations. ISPRS International Journal of Geo-Information 2013-05-21 2 2 Article 10.3390/ijgi2020413 413 431 2220-9964 2013-05-21 doi: 10.3390/ijgi2020413 Wenwen Li Linna Li Michael Goodchild Luc Anselin http://www.mdpi.com/1099-4300/15/5/1916 In the present paper, several issues concerning the second law of thermodynamics, Maxwell’s demon and Landauer’s principle are dealt with. I argue that if the demon and the system on which it operates without dissipation of external energy are made of atoms and molecules (gas, liquid or solid) in thermal equilibrium (whose behaviour is described by a canonical distribution), then the unavoidable reason why the demon cannot successfully operate resides in the ubiquity of thermal fluctuations and friction. Landauer’s principle appears to be unnecessary. I also suggest that if the behaviour of the demon and the system on which it acts is not always describable by a canonical distribution, as would happen for instance with the ballistic motion of electrons at early stages of thermionic emission, then a successful working demon cannot be ruled out a priori. A critical review of two recent experiments on thermionic emission Maxwell’s demons is also given. Entropy 2013-05-21 15 5 Article 10.3390/e15051916 1916 1928 1099-4300 2013-05-21 doi: 10.3390/e15051916 Germano D'Abramo http://www.mdpi.com/1099-4300/15/5/1887 The field of embodied intelligence emphasises the importance of the morphology and environment with respect to the behaviour of a cognitive system. The contribution of the morphology to the behaviour, commonly known as morphological computation, is well-recognised in this community. We believe that the field would benefit from a formalisation of this concept as we would like to ask how much the morphology and the environment contribute to an embodied agent’s behaviour, or how an embodied agent can maximise the exploitation of its morphology within its environment. In this work we derive two concepts of measuring morphological computation, and we discuss their relation to the Information Bottleneck Method. The first concepts asks how much the world contributes to the overall behaviour and the second concept asks how much the agent’s action contributes to a behaviour. Various measures are derived from the concepts and validated in two experiments that highlight their strengths and weaknesses. Entropy 2013-05-21 15 5 Article 10.3390/e15051887 1887 1915 1099-4300 2013-05-21 doi: 10.3390/e15051887 Keyan Zahedi Nihat Ay http://www.mdpi.com/1424-8220/13/5/6759 Bio-composite coatings consisting of poly(3,4-ethylenedioxythiophene) (PEDOT) and tyrosinase (Ty) were successfully electrodeposited on conventional size gold (Au) disk electrodes and microelectrode arrays using sinusoidal voltages. Electrochemical polymerization of the corresponding monomer was carried out in the presence of various Ty amounts in aqueous buffered solutions. The bio-composite coatings prepared using sinusoidal voltages and potentiostatic electrodeposition methods were compared in terms of morphology, electrochemical properties, and biocatalytic activity towards various analytes. The amperometric biosensors were tested in dopamine (DA) and catechol (CT) electroanalysis in aqueous buffered solutions. The analytical performance of the developed biosensors was investigated in terms of linear response range, detection limit, sensitivity, and repeatability. A semi-quantitative multi-analyte procedure for simultaneous determination of DA and CT was developed. The amperometric biosensor prepared using sinusoidal voltages showed much better analytical performance. The Au disk biosensor obtained by 50 mV alternating voltage amplitude displayed a linear response for DA concentrations ranging from 10 to 300 μM, with a detection limit of 4.18 μM. Sensors 2013-05-21 13 5 Article 10.3390/s130506759 6759 6774 1424-8220 2013-05-21 doi: 10.3390/s130506759 Stelian Lupu Cecilia Lete Paul Balaure Dan Caval Constantin Mihailciuc Boris Lakard Jean-Yves Hihn Francisco Campo http://www.mdpi.com/1424-8220/13/5/6746 High-rise buildings subjected to lateral loads such as wind and earthquake loads must be checked not to exceed the limits on the maximum lateral displacement or the maximum inter-story drift ratios. In this paper, a sensing model for deformed shapes of a building structure in motion is presented. The deformed shape sensing model based on a 2D scanner consists of five modules: (1) module for acquiring coordinate information of a point in a building; (2) module for coordinate transformation and data arrangement for generation of time history of the point; (3) module for smoothing by adjacent averaging technique; (4) module for generation of the displacement history for each story and deformed shape of a building, and (5) module for evaluation of the serviceability of a building. The feasibility of the sensing model based on a 2D laser scanner is tested through free vibration tests of a three-story steel frame structure with a relatively high slenderness ratio of 5.0. Free vibration responses measured from both laser displacement sensors and a 2D laser scanner are compared. In the experimentation, the deformed shapes were obtained from three different methods: the model based on the 2D laser scanner, the direct measurement based on laser displacement sensors, and the numerical method using acceleration data and the displacements from GPS. As a result, it is confirmed that the deformed shape measurement model based on a 2D laser scanner can be a promising alternative for high-rise buildings where installation of laser displacement sensors is impossible. Sensors 2013-05-21 13 5 Article 10.3390/s130506746 6746 6758 1424-8220 2013-05-21 doi: 10.3390/s130506746 Se Choi Bub Kim Hong Lee Yousok Kim Hyo Park http://www.mdpi.com/1660-3397/11/5/1718 Eighteen polyketides (1–18) including six citrinin derivatives, two phenol derivatives, one cyclopentenone, two naphthol derivatives, and seven tetralone derivatives were isolated from the culture broth of a marine-derived fungal strain Xylariaceae sp. SCSGAF0086. Five of these compounds (1, 2, 8, 9, and 10) were new, and their structures were determined by spectroscopic methods. Compounds 4, 6, 7, and 17 showed enzyme-inhibitory activities towards several tested enzymes, and 6 and 7 showed strong antifouling activity against Bugula neritina larvae settlement. This is the first time that the antifouling and enzyme-inhibitory activities of these compounds has been reported. Marine Drugs 2013-05-21 11 5 Article 10.3390/md11051718 1718 1727 1660-3397 2013-05-21 doi: 10.3390/md11051718 Xu-Hua Nong Zhi-Hui Zheng Xiao-Yong Zhang Xin-Hua Lu Shu-Hua Qi http://www.mdpi.com/1424-8220/13/5/6730 The work presented here is part of a larger study to identify novel technologies and biomarkers for early Alzheimer disease (AD) detection and it focuses on evaluating the suitability of a new approach for early AD diagnosis by non-invasive methods. The purpose is to examine in a pilot study the potential of applying intelligent algorithms to speech features obtained from suspected patients in order to contribute to the improvement of diagnosis of AD and its degree of severity. In this sense, Artificial Neural Networks (ANN) have been used for the automatic classification of the two classes (AD and control subjects). Two human issues have been analyzed for feature selection: Spontaneous Speech and Emotional Response. Not only linear features but also non-linear ones, such as Fractal Dimension, have been explored. The approach is non invasive, low cost and without any side effects. Obtained experimental results were very satisfactory and promising for early diagnosis and classification of AD patients. Sensors 2013-05-21 13 5 Article 10.3390/s130506730 6730 6745 1424-8220 2013-05-21 doi: 10.3390/s130506730 Karmele López-de-Ipiña Jesus-Bernardino Alonso Carlos Travieso Jordi Solé-Casals Harkaitz Egiraun Marcos Faundez-Zanuy Aitzol Ezeiza Nora Barroso Miriam Ecay-Torres Pablo Martinez-Lage Unai Lizardui http://www.mdpi.com/1660-3397/11/5/1693 Since the late 1980s, a large number of depsipeptides that contain a new topography, referred to as “head-to-side-chain” cyclodepsipeptides, have been isolated and characterized. These peptides present a unique structural arrangement that comprises a macrocyclic region closed through an ester bond between the C-terminus and a β-hydroxyl group, and terminated with a polyketide moiety or a more simple branched aliphatic acid. This structural pattern, the presence of unique and complex residues, and relevant bioactivity are the main features shared by all the members of this new class of depsipeptides, which are reviewed herein. Marine Drugs 2013-05-21 11 5 Review 10.3390/md11051693 1693 1717 1660-3397 2013-05-21 doi: 10.3390/md11051693 Marta Pelay-Gimeno Judit Tulla-Puche Fernando Albericio http://www.mdpi.com/1424-8220/13/5/6713 In this paper, we present a new reset tree-based scheme to protect cryptographic hardware against optical fault injection attacks. As one of the most powerful invasive attacks on cryptographic hardware, optical fault attacks cause semiconductors to misbehave by injecting high-energy light into a decapped integrated circuit. The contaminated result from the affected chip is then used to reveal secret information, such as a key, from the cryptographic hardware. Since the advent of such attacks, various countermeasures have been proposed. Although most of these countermeasures are strong, there is still the possibility of attack. In this paper, we present a novel optical fault detection scheme that utilizes the buffers on a circuit’s reset signal tree as a fault detection sensor. To evaluate our proposal, we model radiation-induced currents into circuit components and perform a SPICE simulation. The proposed scheme is expected to be used as a supplemental security tool. Sensors 2013-05-21 13 5 Article 10.3390/s130506713 6713 6729 1424-8220 2013-05-21 doi: 10.3390/s130506713 Dong-Geon Lee Dooho Choi Jungtaek Seo Howon Kim http://www.mdpi.com/2072-6643/5/5/1734 Determining the speciation of selenium in vivo is crucial to understanding the biological activity of this essential element, which is a popular dietary supplement due to its anti-cancer properties. Hyphenated techniques that combine separation and detection methods are traditionally and effectively used in selenium speciation analysis, but require extensive sample preparation that may affect speciation. Synchrotron-based X-ray absorption and fluorescence techniques offer an alternative approach to selenium speciation analysis that requires minimal sample preparation. We present a brief summary of some key HPLC-ICP-MS and ESI-MS/MS studies of the speciation of selenium in cells and rat tissues. We review the results of a top-down approach to selenium speciation in human lung cancer cells that aims to link the speciation and distribution of selenium to its biological activity using a combination of X-ray absorption spectroscopy (XAS) and X-ray fluorescence microscopy (XFM). The results of this approach highlight the distinct fates of selenomethionine, methylselenocysteine and selenite in terms of their speciation and distribution within cells: organic selenium metabolites were widely distributed throughout the cells, whereas inorganic selenium metabolites were compartmentalized and associated with copper. New data from the XFM mapping of electrophoretically-separated cell lysates show the distribution of selenium in the proteins of selenomethionine-treated cells. Future applications of this top-down approach are discussed. Nutrients 2013-05-21 5 5 Review 10.3390/nu5051734 1734 1756 2072-6643 2013-05-21 doi: 10.3390/nu5051734 Claire Weekley Jade Aitken Lydia Finney Stefan Vogt Paul Witting Hugh Harris http://www.mdpi.com/1660-3397/11/5/1677 Plitidepsin is an antitumor drug of marine origin currently in Phase III clinical trials in multiple myeloma. In cultured cells, plitidepsin induces cell cycle arrest or an acute apoptotic process in which sustained activation of c-Jun N-terminal kinase (JNK) plays a crucial role. With a view to optimizing clinical use of plitidepsin, we have therefore evaluated the possibility of using JNK activation as an in vivo biomarker of response. In this study, we show that administration of a single plitidepsin dose to mice xenografted with human cancer cells does indeed lead to increased phosphorylation of JNK in tumors at 4 to 12 h. By contrast, no changes were found in other in vitro plitidepsin targets such as the levels of phosphorylated-ERK, -p38MAPK or the protein p27KIP1. Interestingly, plitidepsin also increased JNK phosphorylation in spleens from xenografted mice showing similar kinetics to those seen in tumors, thereby suggesting that normal tissues might be useful for predicting drug activity. Furthermore, plitidepsin administration to rats at plasma concentrations comparable to those achievable in patients also increased JNK phosphorylation in peripheral mononuclear blood cells. These findings suggest that changes in JNK activity provide a reliable biomarker for plitidepsin activity and this could be useful for designing clinical trials and maximizing the efficacy of plitidepsin. Marine Drugs 2013-05-21 11 5 Article 10.3390/md11051677 1677 1692 1660-3397 2013-05-21 doi: 10.3390/md11051677 María Muñoz-Alonso Enrique Álvarez María Guillén-Navarro Marina Pollán Pablo Avilés Carlos Galmarini Alberto Muñoz http://www.mdpi.com/2072-6643/5/5/1719 Dietary intake among other lifestyle factors influence blood pressure. We examined the associations of an ―a priori‖ diet score with incident high normal blood pressure (HNBP; systolic blood pressure (SBP) 120–139 mmHg, or diastolic blood pressure (DBP) 80–89 mmHg and no antihypertensive medications) and hypertension (SBP ≥ 140 mmHg, DBP ≥ 90 mmHg, or taking antihypertensive medication). We used proportional hazards regression to evaluate this score in quintiles (Q) and each food group making up the score relative to incident HNBP or hypertension over nine years in the Atherosclerosis Risk of Communities (ARIC) study of 9913 African-American and Caucasian adults aged 45–64 years and free of HNBP or hypertension at baseline. Incidence of HNBP varied from 42.5% in white women to 44.1% in black women; and incident hypertension from 26.1% in white women to 40.8% in black women. Adjusting for demographics and CVD risk factors, the ―a priori‖ food score was inversely associated with incident hypertension; but not HNBP. Compared to Q1, the relative hazards of hypertension for the food score Q2–Q5 were 0.97 (0.87–1.09), 0.91 (0.81–1.02), 0.91 (0.80–1.03), and 0.86 (0.75–0.98); ptrend = 0.01. This inverse relation was largely attributable to greater intake of dairy products and nuts, and less meat. These findings support the 2010 Dietary Guidelines to consume more dairy products and nuts, but suggest a reduction in meat intake. Nutrients 2013-05-21 5 5 Article 10.3390/nu5051719 1719 1733 2072-6643 2013-05-21 doi: 10.3390/nu5051719 Lu-Chen Weng Lyn Steffen Moyses Szklo Jennifer Nettleton Lloyd Chambless Aaron Folsom http://www.mdpi.com/1660-3397/11/5/1669 In 2011, a Diarrhetic Shellfish Poisoning (DSP) outbreak occurred in British Columbia (BC), Canada that was associated with cooked mussel consumption. This is the first reported DSP outbreak in BC. Investigation of ill individuals, traceback of product and laboratory testing for toxins were used in this investigation. Sixty-two illnesses were reported. Public health and food safety investigation identified a common food source and harvest area. Public health and regulatory agencies took actions to recall product and notify the public. Shellfish monitoring program changes were implemented after the outbreak. Improved response and understanding of toxin production will improve management of future DSP outbreaks. Marine Drugs 2013-05-21 11 5 Article 10.3390/md11051669 1669 1676 1660-3397 2013-05-21 doi: 10.3390/md11051669 Marsha Taylor Lorraine McIntyre Mark Ritson Jason Stone Roni Bronson Olga Bitzikos Wade Rourke Eleni Galanis Outbreak Team http://www.mdpi.com/2072-6643/5/5/1706 Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening and the Women’s Health Initiative (WHI). We tested association between 2,474,333 single nucleotide polymorphisms (SNPs) and serum selenium concentrations using linear regression models. In the first stage (PLCO) 41 SNPs clustered in 15 regions had p < 1 × 10−5. None of these 41 SNPs reached the significant threshold (p = 0.05/15 regions = 0.003) in the second stage (WHI). Three SNPs had p < 0.05 in the second stage (rs1395479 and rs1506807 in 4q34.3/AGA-NEIL3; and rs891684 in 17q24.3/SLC39A11) and had p between 2.62 × 10−7 and 4.04 × 10−7 in the combined analysis (PLCO + WHI). Additional studies are needed to replicate these findings. Identification of genetic variation that impacts selenium concentrations may contribute to a better understanding of which genes regulate circulating selenium concentrations. Nutrients 2013-05-21 5 5 Article 10.3390/nu5051706 1706 1718 2072-6643 2013-05-21 doi: 10.3390/nu5051706 Jian Gong Li Hsu Tabitha Harrison Irena King Stefan Stürup Xiaoling Song David Duggan Yan Liu Carolyn Hutter Stephen Chanock Charles Eaton James Marshall Ulrike Peters http://www.mdpi.com/1660-3397/11/5/1656 Protein phosphorylation is involved in the regulation of a wide variety of physiological processes and is the result of a balance between protein kinase and phosphatase activities. Biologically active marine derived compounds have been shown to represent an interesting source of novel compounds that could modify that balance. Among them, the marine toxin and tumor promoter, okadaic acid (OA), has been shown as an inhibitor of two of the main cytosolic, broad-specificity protein phosphatases, PP1 and PP2A, thus providing an excellent cell-permeable probe for examining the role of protein phosphorylation, and PP1 and PP2A in particular, in any physiological or pathological process. In the present work, we review the use of okadaic acid to identify specific phosphoepitopes mainly in proteins relevant for neurodegeneration. We will specifically highlight those cases of highly dynamic phosphorylation-dephosphorylation events and the ability of OA to block the high turnover phosphorylation, thus allowing the detection of modified residues that could be otherwise difficult to identify. Finally, its effect on tau hyperhosphorylation and its relevance in neurodegenerative pathologies such as Alzheimer’s disease and related dementia will be discussed. Marine Drugs 2013-05-21 11 5 Review 10.3390/md11051656 1656 1668 1660-3397 2013-05-21 doi: 10.3390/md11051656 Miguel Medina Jesús Avila Nieves Villanueva http://www.mdpi.com/2072-6643/5/5/1672 Obesity, a chronic low-grade inflammatory condition is associated with the development of many comorbidities including dyslipidemia. This review examines interactions between single nucleotide polymorphisms (SNP) in the inflammatory genes tumor necrosis alpha (TNFA) and interleukin-6 (IL-6) and dietary fatty acids, and their relationship with obesity and serum lipid levels. In summary, dietary fatty acids, in particular saturated fatty acids and the omega-3 and omega-6 polyunsaturated fatty acids, impact the expression of the cytokine genes TNFA and IL-6, and alter TNFα and IL-6 production. In addition, sequence variants in these genes have also been shown to alter their gene expression and plasma levels, and are associated with obesity, measures of adiposity and serum lipid concentrations. When interactions between dietary fatty acids and TNFA and IL-6 SNPs on obesity and serum lipid were analyzed, both the quantity and quality of dietary fatty acids modulated the relationship between TNFA and IL-6 SNPs on obesity and serum lipid profiles, thereby impacting the association between phenotype and genotype. Researching these diet–gene interactions more extensively, and understanding the role of ethnicity as a confounder in these relationships, may contribute to a better understanding of the inter-individual variability in the obese phenotype. Nutrients 2013-05-21 5 5 Review 10.3390/nu5051672 1672 1705 2072-6643 2013-05-21 doi: 10.3390/nu5051672 Yael Joffe Malcolm Collins Julia Goedecke http://www.mdpi.com/2072-6643/5/5/1660 Uncoupling protein 3 (UCP3) is a mitochondrial membrane transporter that is expressed mainly in skeletal muscle where it plays an important role in energy expenditure and fat oxidation. In this study, we investigated the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on UCP3 gene expression in C2C12 muscle cells. EPA and DHA up-regulated UCP3 mRNA level in a dose-dependent manner and similarly increased UCP3 promoter activity in C2C12 muscle cells. To determine whether AMP-activated protein kinase (AMPK) signaling may also directly regulate UCP3 expression, 5′-amino-4-imidazolecarboxamide-ribonucleoside (AICAR), an AMP analog that activates AMPK, was treated in C2C12 muscle cells. AICAR showed additive effects with EPA or DHA on the UCP3 promoter activation. These results indicate that EPA and DHA directly regulate the gene expression of UCP3, potentially through AMPK-mediated pathway in C2C12 muscle cells. Nutrients 2013-05-21 5 5 Article 10.3390/nu5051660 1660 1671 2072-6643 2013-05-21 doi: 10.3390/nu5051660 Mak-Soon Lee In-Hwan Kim Yangha Kim http://www.mdpi.com/1660-3397/11/5/1644 Astaxanthin is a novel carotenoid nutraceutical occurring in many crustaceans and red yeasts. It has exhibited various biological activities including prevention or amelioration of cardiovascular disease, gastric ulcer, hypertension, and diabetic nephropathy. In this study, ultrasound-assisted extraction was developed for the effective extraction of astaxanthin from Haematococcus pluvialis. Some parameters such as extraction solvent, liquid-to-solid ratio, extraction temperature, and extraction time were optimized by single-factor experiment and response surface methodology. The optimal extraction conditions were 48.0% ethanol in ethyl acetate, the liquid-to-solid ratio was 20:1 (mL/g), and extraction for 16.0 min at 41.1 °C under ultrasound irradiation of 200 W. Under optimal conditions, the yield of astaxanthin was 27.58 ± 0.40 mg/g. The results obtained are beneficial for the full utilization of Haematococcus pluvialis, which also indicated that ultrasound-assisted extraction is a very useful method for extracting astaxanthin from marine life. Marine Drugs 2013-05-21 11 5 Article 10.3390/md11051644 1644 1655 1660-3397 2013-05-21 doi: 10.3390/md11051644 Tang-Bin Zou Qing Jia Hua-Wen Li Chang-Xiu Wang Hong-Fu Wu http://www.mdpi.com/1422-0067/14/5/10674 The vasopressin-regulated urea transporter UT-A1, expressed in kidney inner medullary collecting duct (IMCD) epithelial cells, plays a critical role in the urinary concentrating mechanisms. As a membrane protein, the function of UT-A1 transport activity relies on its presence in the plasma membrane. Therefore, UT-A1 successfully trafficking to the apical membrane of the polarized epithelial cells is crucial for the regulation of urea transport. This review summarizes the research progress of UT-A1 regulation over the past few years, specifically on the regulation of UT-A1 membrane trafficking by lipid rafts, N-linked glycosylation and a group of accessory proteins. International Journal of Molecular Sciences 2013-05-21 14 5 Review 10.3390/ijms140510674 10674 10682 1422-0067 2013-05-21 doi: 10.3390/ijms140510674 Guangping Chen http://www.mdpi.com/1422-0067/14/5/10661 To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT) on the erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. SD rats (n = 75) were randomly divided into 5 groups (normal control, diabetic control, 3 different dose LESWT treated diabetic groups). Diabetic rats were induced by intra-peritoneal injection of STZ (60 mg/kg) and rats with fasting blood glucose ≥ 300 mg/dL were selected as diabetic models. Twelve weeks later, different doses of LESWT (100, 200 and 300 shocks each time) treatment on penises were used to treat ED (7.33 MPa, 2 shocks/s) three times a week for two weeks. The erectile function was evaluated by intracavernous pressure (ICP) after 1 week washout period. Then the penises were harvested for histological study. The results showed LESWT could significantly improve the erectile function of diabetic rats, increase smooth muscle and endothelial contents, up-regulate the expression of α-SMA, vWF, nNOS and VEGF, and down- regulate the expression of RAGE in corpus cavernosum. The therapeutic effect might relate to treatment dose positively, and the maximal therapeutic effect was noted in the LESWT300 group. Consequently, 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment. International Journal of Molecular Sciences 2013-05-21 14 5 Article 10.3390/ijms140510661 10661 10673 1422-0067 2013-05-21 doi: 10.3390/ijms140510661 Jing Liu Feng Zhou Guang-Yong Li Lin Wang Hui-Xi Li Guang-Yi Bai Rui-Li Guan Yong-De Xu Ze-Zhu Gao Wen-Jie Tian Zhong-Cheng Xin http://www.mdpi.com/1422-0067/14/5/10626 Porcine pleuropneumonia is a highly contagious respiratory disease that causes great economic losses worldwide. In this study, we aimed to explore the underlying relationship between infection and injury by investigation of the whole porcine genome expression profiles of swine lung tissues post-inoculated with experimentally Actinobacillus pleuropneumoniae. Expression profiling experiments of the control group and the treatment group were conducted using a commercially available Agilent Porcine Genechip including 43,603 probe sets. Microarray analysis was conducted on profiles of lung from challenged versus non-challenged swine. We found 11,929 transcripts, identified as differentially expressed at the p ≤0.01 level. There were 1188 genes annotated as swine genes in the GenBank Data Base. GO term analysis identified a total of 89 biological process categories, 82 cellular components and 182 molecular functions that were significantly affected, and at least 27 biological process categories that were related to the host immune response. Gene set enrichment analysis identified 13 pathways that were significantly associated with host response. Many proinflammatory-inflammatory cytokines were activated and involved in the regulation of the host defense response at the site of inflammation; while the cytokines involved in regulation of the host immune response were suppressed. All changes of genes and pathways of induced or repressed expression not only led to a decrease in antigenic peptides presented to T lymphocytes by APCs via the MHC and alleviated immune response injury induced by infection, but also stimulated stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocyte, and promote neutrophils and macrophages to phagocytose bacterial and foreign antigen at the site of inflammation. The defense function of swine infection with Actinobacillus pleuropneumoniae was improved, while its immune function was decreased. International Journal of Molecular Sciences 2013-05-21 14 5 Article 10.3390/ijms140510626 10626 10660 1422-0067 2013-05-21 doi: 10.3390/ijms140510626 Zhicai Zuo Hengmin Cui Mingzhou Li Xi Peng Ling Zhu Ming Zhang Jideng Ma Zhiwen Xu Meng Gan Junliang Deng Xuewei Li Jing Fang