Graph theory in the last two decades penetrated sociology, molecular biology, genetics, chemistry, computer engineering, and numerous other fields of science. One of the more recent areas of its applications is the study of the connections of the human brain. By the development of diffusion magnetic resonance imaging (diffusion MRI), it is possible today to map the connections between the 1–1.5 cm${}^2$ regions of the gray matter of the human brain. These connections can be viewed as a graph. We have computed 1015-vertex graphs with thousands of edges for hundreds of human brains from one of the highest quality data sources: the Human Connectome Project. Here we analyze the male and female braingraphs graph-theoretically and show statistically significant differences in numerous parameters between the sexes: the female braingraphs are better expanders, have more edges, larger bipartition widths, and larger vertex cover than the braingraphs of the male subjects. These parameters are closely related to the quality measures of highly parallel computer interconnection networks: the better expanding property, the large bipartition width, and the large vertex cover characterize high-quality interconnection networks. We apply the data of 426 subjects and demonstrate the statistically significant (corrected) differences in 116 graph parameters between the sexes. Full article

The mountains of High Mountain Asia serve as an important source of water for roughly one billion people living downstream. This research uses 15 years of dynamically downscaled precipitation produced by the Weather Research and Forecasting (WRF) model to delineate contrasts in precipitation characteristics and events between regions dominated by the Indian Summer Monsoon (ISM) versus westerly disturbances during the cool season (Dec to Mar). Cluster analysis reveals a more complex spatial pattern than indicated by some previous studies and illustrates the increasing importance of westerly disturbances at higher elevations. Although prior research suggests that a small number of westerly disturbances dominate precipitation in the western Himalaya and Karakoram, the WRF-downscaled precipitation is less dominated by infrequent large events. Integrated vapor transport (IVT) and precipitation are tightly coupled in both regions during the cool season, with precipitation maximizing for IVT from the south-southwest over the Karakoram and southeast-southwest over the western Himalaya. During the ISM, Karakoram precipitation is not strongly related to IVT direction, whereas over the western Himalaya, primary and secondary precipitation maxima occur for flow from the west-southwest and northwest, respectively. These differences in the drivers and timing of precipitation have implications for hydrology, glacier mass balance, snow accumulation, and their sensitivity to climate variability and change. Full article

The quality of execution tracing impacts the time to a great extent to locate errors in software components; moreover, execution tracing is the most suitable tool, in the majority of the cases, for doing postmortem analysis of failures in the field. Nevertheless, software product quality models do not adequately consider execution tracing quality at present neither do they define the quality properties of this important entity in an acceptable manner. Defining these quality properties would be the first step towards creating a quality model for execution tracing. The current research fills this gap by identifying and defining the variables, i.e., the quality properties, on the basis of which the quality of execution tracing can be judged. The present study analyses the experiences of software professionals in focus groups at multinational companies, and also scrutinises the literature to elicit the mentioned quality properties. Moreover, the present study also contributes to knowledge with the combination of methods while computing the saturation point for determining the number of the necessary focus groups. Furthermore, to pay special attention to validity, in addition to the the indicators of qualitative research: credibility, transferability, dependability, and confirmability, the authors also considered content, construct, internal and external validity. Full article

Oxyresveratrol (OxyR), a well-known polyphenolic phytoalexin, possesses a wide range of pharmacological and biological properties, comprising antioxidant, anti-inflammatory, free radical scavenging, anti-cancer, and neuroprotective activities. Autophagy is a cellular self-degradation system that removes aggregated or misfolded intracellular components via the autophagosome-lysosomal pathway. Astrocyte accumulation is one of the earliest neuropathological changes in Alzheimer’s disease (AD), and amyloid precursor protein (APP) is the hallmark of AD. OxyR could affect APP modulation via the autophagy pathway. Here, we have reported that OxyR promotes autophagy signaling and attenuates APP production in primary cortical astrocytes based on immunofluorescence and immunoblotting assay results. Co-treatment with the late-stage autophagy inhibitor chloroquine (CQ) and OxyR caused significantly higher microtubule-associated protein light chain 3 (LC3)-II protein levels and LC3 puncta counts, demonstrating that OxyR stimulated autophagic flux. We also found that OxyR significantly reduced the levels of the autophagy substrate p62/SQSTM1, and p62 levels were significantly augmented by co-treatment with OxyR and CQ, because of the impaired deficiency of p62 in autolysosome. Likewise, pretreatment with the autophagy inhibitor, 3-methyladenine (3-MA), resulted in significantly fewer OxyR-induced LC3 puncta and lower LC3-II expression, suggesting that OxyR-mediated autophagy was dependent on the class III PI3-kinase pathway. In contrast, OxyR caused significantly lower LC3-II protein expression when pretreated with compound C, an AMP-activated protein kinase (AMPK) inhibitor, indicating that AMPK signaling regulated the OxyR-induced autophagic pathway. Additionally, co-treatment with OxyR with rapamycin intended to inhibit the mammalian target of rapamycin (mTOR) caused significantly lower levels of phospho-S6 ribosomal protein (pS6) and higher LC3-II expression, implying that OxyR-mediated autophagy was dependent on the mTOR pathway. Conversely, OxyR treatment significantly upregulated unc-51-like autophagy activating kinase 1 (ULK1) expression, and ULK1 small interfering RNAs (siRNA) caused significantly lower OxyR-induced LC3 puncta counts and LC3-II expression, indicating that ULK1 was essential for initiating OxyR-induced autophagy. However, we found that OxyR treatment astrocytes significantly increased the expression of lysosome-associated membrane protein 1 (LAMP1). Finally, we established a stress-induced APP production model using corticosterone (CORT) in cortical astrocytes, which produced significantly more APP than the equivalent using dexamethasone (DEX). In our experiment we found that CORT-induced APP production was significantly attenuated by OxyR through the autophagy pathway. Therefore, our study reveals that OxyR regulates AMPK/ULK1/mTOR-dependent autophagy induction and APP reduction in mouse cortical astrocytes. Full article

Continuous-time linear systems with uncertain parameters are widely used for modeling real-life processes. The uncertain parameters, contained in the system and input matrices, can be constant or time-varying. In the latter case, they may represent state dependencies of these matrices. Assuming bounded uncertainties, interval methods become applicable for a verified reachability analysis, for feasibility analysis of feedback controllers, or for the design of robust set-valued state estimators. The evaluation of these system models becomes computationally efficient after a transformation into a cooperative state-space representation, where the dynamics satisfy certain monotonicity properties with respect to the initial conditions. To obtain such representations, similarity transformations are required which are not trivial to find for sufficiently wide a-priori bounds of the uncertain parameters. This paper deals with the derivation and algorithmic comparison of two different transformation techniques for which their applicability to processes with constant and time-varying parameters has to be distinguished. An interval-based reachability analysis of the states of a simple electric step-down converter concludes this paper. Full article

This research investigates the relationships between airborne and depositional industrial lead emission concentrations modeled using Environmental Protection Agency’s (EPA’s) American Meteorological Society/Environmental Protection Agency Regulatory Model (AERMOD) and childhood blood lead levels (BLL) in the Detroit Metropolitan Area (DMA) 2006–2013. Linear and mediation interaction regression models estimated the effects of older housing and airborne and depositional lead emission concentrations on black and white childhood BLLs, controlling for neighborhood levels of racial isolation and poverty—important social structures in the DMA. The results showed a direct relationship between airborne and depositional lead emissions and higher childhood BLL, after controlling for median housing age. Lead emissions also exacerbated the effect of older housing on black and white children’s BLLs (indirect relationship), after controlling for social structures. Findings from this research indicate that black and white children exposed to lead-based paint/pipes in older housing are further impacted by industrial lead pollution that may lead to permanent neurological damage. Full article

Background: Childhood obesity has negative impact on heart-rate variability (HRV) and, thereby, on the cardiovascular health of children and adolescents. Thus, physical-exercise interventions were proposed to increase HRV. The present systematic review aims to provide an up-to-date analysis of research on the effect of physical-exercise interventions on HRV in obese children and adolescents. Methods: An electronic search of the literature was performed, and 10 articles were included. PRISMA guideline methodology was employed. Results: Physical-exercise interventions predominantly involved aerobic training; however, alternative training programs, including judo or recreational soccer, were found. The duration of intervention ranged from 6 to 24 weeks, with a training frequency of between 2 and 7 times per week. The duration of sessions typically ranged from 40 to 60 min. Conclusions: Results of the included articles indicated that physical-exercise intervention increased the HRV and thereby the autonomic modulation of obese children and adolescents. This is significant, as HRV is associated with cardiovascular health. Such physical-exercise interventions are crucial to reduce weight and improve cardiovascular health in children and adolescents, thereby achieving a sustainable future. Full article

Cities defined mainly from the administrative aspect can create impact and problems especially in the case of China. However, only a few researchers from China have attempted to identify urban areas from the morphology dimension. In addition, previous studies have been mostly based on the national and regional scales or a single prefecture city and have completely ignored cross-boundary cities. Defining urban areas on the basis of a single data type also has limitations. To address these problems, this study integrates point of interest and nighttime light data, applies the breaking point analysis method to determine the physical geographic scope of the Guangzhou–Foshan cross-border city, and then compares this city with Beijing and Shanghai. Results show that Guangzhou–Foshan comprises one core urban area and six suburban counties, among which the core urban area extends across the administrative boundaries of Guangzhou and Foshan. The urban area and average urban radius of Guangzhou–Foshan are larger than those of Beijing and Shanghai, and this finding contradicts the city size measurements based on the administrative division system of China and those published on traditional official statistical yearbooks. In terms of urban density value, Shanghai has the steepest profile followed by Guangzhou–Foshan and Beijing, and the profile line of Guangzhou–Foshan has a bimodal shape. Full article

Nanopatterns can readily be formed by annealing block copolymers (BCPs) in organic solvents at moderate or high temperatures. However, this approach can be challenging from an environmental and industrial point of view. Herein, we describe a simple and environmentally friendly alternative to achieve periodically ordered nanoscale phase separated BCP structures. Asymmetric polystyrene-b-poly(ethylene oxide) (PS-b-PEO) thin film patterns of different molecular weight were achieved by annealing in supercritical carbon dioxide (sc-CO₂). Microphase separation of PS-b-PEO (16,000–5000) film patterns were achieved by annealing in scCO₂ at a relatively low temperature was previously reported by our group. The effects of annealing temperature, time and depressurisation rates for the polymer system were also discussed. In this article, we have expanded this study to create new knowledge on the structural and dimensional evolution of nanohole and line/space surface periodicity of four other different molecular weights PS-b-PEO systems. Periodic, well defined, hexagonally ordered films of line and hole patterns were obtained at low CO₂ temperatures (35–40 °C) and pressures (1200–1300 psi). Further, the changes in morphology, ordering and feature sizes for a new PS-b-PEO system (42,000–11,500) are discussed in detail upon changing the scCO₂ annealing parameters (temperature, film thickness, depressurization rates, etc.). In relation to our previous reports, the broad annealing temperature and depressurisation rate were explored together for different film thicknesses. In addition, the effects of SCF annealing for three other BCP systems (PEO-b-PS, PS-b-PDMS, PS-b-PLA) is also investigated with similar processing conditions. The patterns were also generated on a graphoepitaxial substrate for device application. Full article

Published data suggest that immunotherapy plays a role even in patients with very advanced tumours. We investigated the immune profile of end-stage cancer patients treated with immunotherapy to identify changes induced by treatment. Breast, colon, renal and prostate cancer patients were eligible. Treatment consisted of metronomic cyclophosphamide, low-dose interleukin-2 (IL-2) and a single radiation shot. A panel of 16 cytokines was assessed using automated ELISA before treatment (T0), after radiation (RT; T1), at cycle 2 (T2) and at disease progression (TPD). Receiving operating characteristic (ROC) analysis was used to identify cytokine cut-off related to overall survival (OS). Principal component analysis (PCA) was used to identify the immune profile correlating better with OS and progression-free survival. Twenty-three patients were enrolled. High IL-2, low IL-8 and CCL-2 correlated with OS. The PCA identified a cluster of patients, with high IL-2, IL-12 and IFN-γ levels at T0 having longer PFS and OS. In all cohorts, IL-2 and IL-5 increased from T0 to T2; a higher CCL-4 level compared to T2 and a higher IL-8 level compared to T0 were found at TPD. The progressive increase of the IL-10 level during treatment negatively correlated with OS. Our data suggested that baseline cytokine levels may predict patients’ outcome and that the treatment may affect their kinetic even in end-stage patients. Cytokine profiling of end-stage patients might offer a tool for medical decisions (EUDRACT: 2016-000578-39). Full article

The consumers’ interest towards beer consumption has been on the rise during the past decade: new approaches and ingredients get tested, expanding the traditional recipe for brewing beer. As a consequence, the field of “beeromics” has also been constantly growing, as well as the demand for quick and exhaustive analytical methods. In this study, we propose a combination of nuclear magnetic resonance (NMR) spectroscopy and chemometrics to characterize beer. ¹H-NMR spectra were collected and then analyzed using chemometric tools. An interval-based approach was applied to extract chemical features from the spectra to build a dataset of resolved relative concentrations. One aim of this work was to compare the results obtained using the full spectrum and the resolved approach: with a reasonable amount of time needed to obtain the resolved dataset, we show that the resolved information is comparable with the full spectrum information, but interpretability is greatly improved. Full article

Pyruvate kinase M2 (PKM2) mainly catalyzes glycolysis, but it also exerts non-glycolytic functions in several cancers. While it has been shown to interact with the human papillomavirus 16 (HPV16) E7 oncoprotein, the functional significance of PKM2 in HPV-associated cervical cancer has been elusive. Here, we show that HPV16 E7 increased the expression of PKM2 in cervical cancer cells. TCGA data analyses revealed a higher level of PKM2 in HPV⁺ than HPV⁻ cervical cancers and a worse prognosis for patients with high PKM2 expression. Functionally, we demonstrate that shRNA-mediated PKM2 knockdown decreased the proliferation of HPV⁺ SiHa cervical cancer cells. PKM2 knockdown also inhibited the E7-induced proliferation of cervical cancer cells. ML265 activating the pyruvate kinase function of PKM2 inhibited cell cycle progression and colony formation. ML265 treatments decreased phosphorylation of PKM2 at the Y105 position that has been associated with non-glycolytic functions. On the contrary, HPV16 E7 increased the PKM2 phosphorylation. Our results indicate that E7 increases PKM2 expression and activates a non-glycolytic function of PKM2 to promote cervical cancer cell proliferation. Full article

The construction industry is affected by the constant growth in the populations of urban areas. The demand for cement production has an increasing environmental impact, and there are urgent demands for alternative sustainable solutions. Volcanic ash (VA) is an abundant low-cost material that, because of its chemical composition and amorphous atomic structure, has been considered as a suitable material to replace Portland cement clinker for use as a binder in cement production. In the last decade, there has been interest in using alkali-activated VA material as an alternative material to replace ordinary Portland cement. In this way, a valuable product may be derived from a currently under-utilized material. Additionally, alkali-activated VA-based materials may be suitable for building applications because of their good densification behaviour, mechanical properties and low porosity. This article describes the most relevant findings from researchers around the world on the role of the chemical composition and mineral contents of VA on reactivity during the alkali-activation reaction; the effect of synthesis factors, which include the concentration of the alkaline activator, the solution-to-binder ratio and the curing conditions, on the properties of alkali-activated VA-based materials; and the mechanical performance and durability properties of these materials. Full article

Although animal health surveillance programmes are useful for gaining information to help improve global health and food security, these programmes can be challenging to establish in developing economies with a low-resource base. This study focused on establishing a national surveillance system initiated by the Lao PDR government using a passive surveillance system of abattoir samples as a pilot model, and to gain information on contagious zoonoses, particularly Q fever and brucellosis, in the large ruminant population. A total of 683 cattle and buffalo samples were collected from six selected provinces of Lao PDR between March–December 2019. Out of 271 samples tested, six samples (2.2%, 95% confidence interval (CI) of 1.0, 4.8) were positive in the Q fever antibody ELISA test. Only one sample (out of 683; 0.2%, 95% CI 0.0, 0.8) tested positive to the Brucella antibody ELISA test. Seroprevalence of these important zoonoses in Lao PDR were relatively low in cattle and buffaloes; however, extensive animal movement within the country was identified which could increase risks of spreading transboundary diseases. The study highlights the importance of ongoing animal health surveillance and the need to find cost-effective approaches for its long-term sustainability. Full article

The aim of this study was to explore the impact of bariatric surgery on fat and sweet taste perceptions and to determine the possible correlations with gut appetite-regulating peptides and subjective food sensations. Women suffering from severe obesity (BMI > 35 kg/m²) were studied 2 weeks before and 6 months after a vertical sleeve gastrectomy (VSG, n = 32) or a Roux-en-Y gastric bypass (RYGB, n = 12). Linoleic acid (LA) and sucrose perception thresholds were determined using the three-alternative forced-choice procedure, gut hormones were assayed before and after a test meal and subjective changes in oral food sensations were self-reported using a standardized questionnaire. Despite a global positive effect of both surgeries on the reported gustatory sensations, a change in the taste sensitivity was only found after RYGB for LA. However, the fat and sweet taste perceptions were not homogenous between patients who underwent the same surgery procedure, suggesting the existence of two subgroups: patients with and without taste improvement. These gustatory changes were not correlated to the surgery-mediated modifications of the main gut appetite-regulating hormones. Collectively these data highlight the complexity of relationships between bariatric surgery and taste sensitivity and suggest that VSG and RYGB might impact the fatty taste perception differently. Full article

A new PSMA ligand (PSMA-D4) containing the Glu-CO-Lys pharmacophore connected with a new linker system (L-Trp-4-Amc) and chelator DOTA was developed for radiolabeling with therapeutic radionuclides. Herein we describe the synthesis, radiolabeling, and preliminary biological evaluation of the novel PSMA-D4 ligand. Synthesized PSMA-D4 was characterized using TOF-ESI-MS, NMR, and HPLC methods. The novel compound was subject to molecular modeling with GCP-II to compare its binding mode to analogous reference compounds. The radiolabeling efficiency of PSMA-D4 with ¹⁷⁷Lu, ⁹⁰Y, ⁴⁷Sc, and ²²⁵Ac was chromatographically tested. In vitro studies were carried out in PSMA-positive LNCaP tumor cells membranes. The ex vivo tissue distribution profile of the radioligands and Cerenkov luminescence imaging (CLI) was studied in LNCaP tumor-bearing mice. PSMA-D4 was synthesized in 24% yield and purity >97%. The radio complexes were obtained with high yields (>97%) and molar activity ranging from 0.11 to 17.2 GBq mcmol⁻¹, depending on the radionuclide. In vitro assays confirmed high specific binding and affinity for all radiocomplexes. Biodistribution and imaging studies revealed high accumulation in LNCaP tumor xenografts and rapid clearance of radiocomplexes from blood and non-target tissues. These render PSMA-D4 a promising ligand for targeted therapy of prostate cancer (PCa) metastases. Full article

Enteroviruses (EVs) are highly prevalent viruses world-wide, causing a wide range of diseases in both children and adults. Insight in the global prevalence of EVs is important to define their clinical significance and total disease burden, and assists in making therapeutic decisions. While many studies have been conducted to describe epidemiology of EVs in specific (sub)populations and patient cohorts, little effort has been made to aggregate the available evidence. In the current study, we conducted a search in the PubMed and Embase (Ovid) databases to identify articles reporting EV prevalence and type distribution. We summarized the findings of 153 included studies. We found that EVs are highly prevalent viruses in all continents. Enterovirus B was the most detected species worldwide, while the other species showed continent-specific differences, with Enterovirus C more detected in Africa and Enterovirus A more detected in Asia. Echovirus 30 was by far the most detected type, especially in studies conducted in Europe. EV types in species Enterovirus B—including echovirus 30—were often detected in patient groups with neurological infections and in cerebrospinal fluid, while Enterovirus C types were often found in stool samples. Full article

Occupational Safety and Health (OSH) issues in the urban rail transport industry need to be given full attention due to the factors of the instability of declining occupational accident rate, increasing number of passengers each year, and the pressure of technological development; in addition, the day-to-day operations also involve the public and various interested communities. Organization is one of the factors that influence worker safety and health status. This study aimed to propose a factor model of the organizational safety climate towards a better safety and health status for Malaysian urban rail industry. This quantitative study used a questionnaire randomly distributed to Malaysian rail system workers. A total of 441 workers in the operation and maintenance division were involved in this study. Confirmatory factor analysis (CFA) using IBM SEM-AMOS was conducted to determine the reliability and validity of the observed variables and the latent variables. This study proved that all four dimensions identified as safety communication, safety training, safety support system, and safety value represents the organizational safety climate. Following the analysis, an organizational safety climate model is successfully developed. This factor model aims to be used in the context of rail management studies to measure the safety climate of their organization, thereby improving the safety level of the workers within the organization. Full article

Melanoleuca is one of the taxonomically most complicated genera of Agaricomycetes with several taxonomically lineages. The subgenus Urticocystis of the genus Melanoleuca contains species with either urticoid or absent cheilocystidia. In this paper, three new European species, Melanoleuca galbuserae, Melanoleuca fontenlae, and Melanoleuca acystidiata are described as new to science. Melanoleuca galbuserae, related to Melanoleuca stepposa and Melanoleuca tristis, was discovered in alpine grasslands in North Italy. The type specimens and recent collections of Melanoleuca angelesiana, Melanoleuca castaneofusca, Melanoleuca luteolosperma, Melanoleuca pseudopaedida, and Melanoleuca robertiana were sequenced and morphologically examined. Moreover, the related Melanoleuca microcephala and Melanoleuca paedida were included in morphological examination and DNA sequence analyses. All the species were delimited by macro- and micromorphological characters and the multigene phylogenetic analyses of a combined (ITS, rpb2, and tef1) dataset on the basis of the species tree estimation. In accordance with new molecular and morphological data, we suggest taxonomic reappraisal of M. pseudopaedida and M. robertiana, and M. fontenlae and M. acystidiata are proposed as new species. The differences between the type material of M. angelesiana from the USA and European M. angelesiana specimens are discussed. Full article