Latest Articles

Open AccessArticle
A Systematic Grey-Box Modeling Methodology via Data Reconciliation and SOS Constrained Regression
Processes 2019, 7(3), 170; https://doi.org/10.3390/pr7030170 (registering DOI) -
Abstract
Developing the so-called grey box or hybrid models of limited complexity for process systems is the cornerstone in advanced control and real-time optimization routines. These models must be based on fundamental principles and customized with sub-models obtained from process experimental data. This allows [...] Read more.
Developing the so-called grey box or hybrid models of limited complexity for process systems is the cornerstone in advanced control and real-time optimization routines. These models must be based on fundamental principles and customized with sub-models obtained from process experimental data. This allows the engineer to transfer the available process knowledge into a model. However, there is still a lack of a flexible but systematic methodology for grey-box modeling which ensures certain coherence of the experimental sub-models with the process physics. This paper proposes such a methodology based in data reconciliation (DR) and polynomial constrained regression. A nonlinear optimization of limited complexity is to be solved in the DR stage, whereas the proposed constrained regression is based in sum-of-squares (SOS) convex programming. It is shown how several desirable features on the polynomial regressors can be naturally enforced in this optimization framework. The goodnesses of the proposed methodology are illustrated through: (1) an academic example and (2) an industrial evaporation plant with real experimental data. Full article
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Open AccessArticle
Electrostatics of Tau Protein by Molecular Dynamics
Biomolecules 2019, 9(3), 116; https://doi.org/10.3390/biom9030116 (registering DOI) -
Abstract
Tau is a microtubule-associated protein that promotes microtubule assembly and stability. This protein is implicated in several neurodegenerative diseases, including Alzheimer’s. To date, the three-dimensional (3D) structure of tau has not been fully solved, experimentally. Even the most recent information is sometimes controversial [...] Read more.
Tau is a microtubule-associated protein that promotes microtubule assembly and stability. This protein is implicated in several neurodegenerative diseases, including Alzheimer’s. To date, the three-dimensional (3D) structure of tau has not been fully solved, experimentally. Even the most recent information is sometimes controversial in regard to how this protein folds, interacts, and behaves. Predicting the tau structure and its profile sheds light on the knowledge about its properties and biological function, such as the binding to microtubules (MT) and, for instance, the effect on ionic conductivity. Our findings on the tau structure suggest a disordered protein, with discrete portions of well-defined secondary structure, mostly at the microtubule binding region. In addition, the first molecular dynamics simulation of full-length tau along with an MT section was performed, unveiling tau structure when associated with MT and interaction sites. Electrostatics and conductivity were also examined to understand how tau affects the ions in the intracellular fluid environment. Our results bring a new insight into tau and tubulin MT proteins, their characteristics, and the structure–function relationship. Full article
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Open AccessFeature PaperArticle
The Evolving Value of Photovoltaic Module Efficiency
Appl. Sci. 2019, 9(6), 1227; https://doi.org/10.3390/app9061227 (registering DOI) -
Abstract
PV research is making efforts to create new cell and module efficiency records, while the manufacturing industry and the downstream project developers want to choose the optimal efficiency point where the best economics can be achieved at the system level. In this paper, [...] Read more.
PV research is making efforts to create new cell and module efficiency records, while the manufacturing industry and the downstream project developers want to choose the optimal efficiency point where the best economics can be achieved at the system level. In this paper, we define representative system cost structurers for various applications in 2018 and quantify the value of greater module efficiency in lowering the levelized cost of electricity (LCOE). With the transparent methodology, we also extended the analysis into the future until 2025. As the value of module efficiency resides in non-module costs and the non-module costs will account for a higher percentage for a PV system in the future, industry will develop stronger motivation to adopt more efficient modules. Specifically, we examined the economics of bifacial modules and forecast that its market share would grow from 3% in 2018 to 40% in 2025. Full article
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Open AccessArticle
Simulation Approach for Cathodic Protection Prediction of Aluminum Fin-Tube Heat Exchanger Using Boundary Element Method
Metals 2019, 9(3), 376; https://doi.org/10.3390/met9030376 (registering DOI) -
Abstract
The multi-galvanic effect of an Al fin-tube heat exchanger was evaluated using polarization tests, numerical simulation, and the seawater acetic acid test (SWAAT). Determination of the polarization state using polarization curves was well correlated with numerical simulations using a high-conductivity electrolyte. However, the [...] Read more.
The multi-galvanic effect of an Al fin-tube heat exchanger was evaluated using polarization tests, numerical simulation, and the seawater acetic acid test (SWAAT). Determination of the polarization state using polarization curves was well correlated with numerical simulations using a high-conductivity electrolyte. However, the polarization results did not match those of the low-conductivity electrolyte due to the lower galvanic effect. Although the polarization state is changed by electrolyte conductivity, the total net current of the tube is decreased in the case of the anodic joint. From SWAAT results, the leakage time of Al fin-tube heat exchanger assembled by anodic joint was longer than the case with cathodic joint. Full article
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Open AccessArticle
Preparation Method of Spherical and Monocrystalline Aluminum Powder
Metals 2019, 9(3), 375; https://doi.org/10.3390/met9030375 (registering DOI) -
Abstract
This paper presents a new production method for a spherical and monocrystalline aluminum powder. Aluminum powder of irregular particle shapes was mixed with silica nanoparticles and heated to a temperature above the melting point of aluminum. Due to its molten state, high surface [...] Read more.
This paper presents a new production method for a spherical and monocrystalline aluminum powder. Aluminum powder of irregular particle shapes was mixed with silica nanoparticles and heated to a temperature above the melting point of aluminum. Due to its molten state, high surface tension, and poor wettability, the aluminum particles were transformed into liquid and spherical droplets separated by silica nanoparticles. The spherical shape was then retained when the aluminum particles solidified. The influence of the processing temperature on the particle shape, phase composition, and microstructure was investigated. Moreover, calorimetric, X-ray diffraction, grain size, and scanning electron microscopy with electron backscatter diffraction (SEM-EBSD) measurements of the particles’ microstructure are presented. It is proven that, by this means, a spherical and monocrystalline aluminum powder can be efficiently created directly from an air-atomized irregular powder. The observed phenomenon of particles becoming round is of great importance, especially when considering powder preparation for powder-based additive manufacturing processes. Full article
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Open AccessReview
2,4 Dinitrophenol as Medicine
Cells 2019, 8(3), 280; https://doi.org/10.3390/cells8030280 (registering DOI) -
Abstract
In the sanctity of pure drug discovery, objective reasoning can become clouded when pursuing ideas that appear unorthodox, but are spot on physiologically. To put this into historical perspective, it was an unorthodox idea in the 1950’s to suggest that warfarin, a rat [...] Read more.
In the sanctity of pure drug discovery, objective reasoning can become clouded when pursuing ideas that appear unorthodox, but are spot on physiologically. To put this into historical perspective, it was an unorthodox idea in the 1950’s to suggest that warfarin, a rat poison, could be repositioned into a breakthrough drug in humans to protect against strokes as a blood thinner. Yet it was approved in 1954 as Coumadin® and has been prescribed to billions of patients as a standard of care. Similarly, no one can forget the horrific effects of thalidomide, prescribed or available without a prescription, as both a sleeping pill and “morning sickness” anti-nausea medication targeting pregnant women in the 1950’s. The “thalidomide babies” became the case-in-point for the need of strict guidelines by the U.S. Food & Drug Administration (FDA) or full multi-species teratogenicity testing before drug approval. More recently it was found that thalidomide is useful in graft versus host disease, leprosy and resistant tuberculosis treatment, and as an anti-angiogenesis agent as a breakthrough drug for multiple myeloma (except for pregnant female patients). Decades of diabetes drug discovery research has historically focused on every possible angle, except, the energy-out side of the equation, namely, raising mitochondrial energy expenditure with chemical uncouplers. The idea of “social responsibility” allowed energy-in agents to be explored and the portfolio is robust with medicines of insulin sensitizers, insulin analogues, secretagogues, SGLT2 inhibitors, etc., but not energy-out medicines. The primary reason? It appeared unorthodox, to return to exploring a drug platform used in the 1930s in over 100,000 obese patients used for weight loss. This is over 80-years ago and prior to Dr Peter Mitchell explaining the mechanism of how mitochondrial uncouplers, like 2,4-dinitrophenol (DNP) even worked by three decades later in 1961. Although there is a clear application for metabolic disease, it was not until recently that this platform was explored for its merit at very low, weight-neutral doses, for treating insidious human illnesses and completely unrelated to weight reduction. It is known that mitochondrial uncouplers specifically target the entire organelle’s physiology non-genomically. It has been known for years that many neuromuscular and neurodegenerative diseases are associated with overt production of reactive oxygen species (ROSs), a rise in isoprostanes (biomarker of mitochondrial ROSs in urine or blood) and poor calcium (Ca2+) handing. It has also been known that mitochondrial uncouplers lower ROS production and Ca2+ overload. There is evidence that elevation of isoprostanes precedes disease onset, in Alzheimer’s Disease (AD). It is also curious, why so many neurodegenerative diseases of known and unknown etiology start at mid-life or later, such as Multiple Sclerosis (MS), Huntington Disease (HD), AD, Parkinson Disease, and Amyotrophic Lateral Sclerosis (ALS). Is there a relationship to a buildup of mutations that are sequestered over time due to ROSs exceeding the rate of repair? If ROS production were managed, could disease onset due to aging be delayed or prevented? Is it possible that most, if not all neurodegenerative diseases are manifested through mitochondrial dysfunction? Although DNP, a historic mitochondrial uncoupler, was used in the 1930s at high doses for obesity in well over 100,000 humans, and so far, it has never been an FDA-approved drug. This review will focus on the application of using DNP, but now, repositioned as a potential disease-modifying drug for a legion of insidious diseases at much lower and paradoxically, weight neutral doses. DNP will be addressed as a treatment for “metabesity”, an emerging term related to the global comorbidities associated with the over-nutritional phenotype; obesity, diabetes, nonalcoholic steatohepatitis (NASH), metabolic syndrome, cardiovascular disease, but including neurodegenerative disorders and accelerated aging. Some unexpected drug findings will be discussed, such as DNP’s induction of neurotrophic growth factors involved in neuronal heath, learning and cognition. For the first time in 80’s years, the FDA has granted (to Mitochon Pharmaceutical, Inc., Blue Bell, PA, USA) an open Investigational New Drug (IND) approval to begin rigorous clinical testing of DNP for safety and tolerability, including for the first ever, pharmacokinetic profiling in humans. Successful completion of Phase I clinical trial will open the door to explore the merits of DNP as a possible treatment of people with many truly unmet medical needs, including those suffering from HD, MS, PD, AD, ALS, Duchenne Muscular Dystrophy (DMD), and Traumatic Brain Injury (TBI). Full article
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Open AccessReview
Recent Progress on the Localization of the Spindle Assembly Checkpoint Machinery to Kinetochores
Cells 2019, 8(3), 278; https://doi.org/10.3390/cells8030278 (registering DOI) -
Abstract
Faithful chromosome segregation during mitosis is crucial for maintaining genome stability. The spindle assembly checkpoint (SAC) is a surveillance mechanism that ensures accurate mitotic progression. Defective SAC signaling leads to premature sister chromatid separation and aneuploid daughter cells. Mechanistically, the SAC couples the [...] Read more.
Faithful chromosome segregation during mitosis is crucial for maintaining genome stability. The spindle assembly checkpoint (SAC) is a surveillance mechanism that ensures accurate mitotic progression. Defective SAC signaling leads to premature sister chromatid separation and aneuploid daughter cells. Mechanistically, the SAC couples the kinetochore microtubule attachment status to the cell cycle progression machinery. In the presence of abnormal kinetochore microtubule attachments, the SAC prevents the metaphase-to-anaphase transition through a complex kinase-phosphatase signaling cascade which results in the correct balance of SAC components recruited to the kinetochore. The correct kinetochore localization of SAC proteins is a prerequisite for robust SAC signaling and, hence, accurate chromosome segregation. Here, we review recent progresses on the kinetochore recruitment of core SAC factors. Full article
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Open AccessArticle
The Effect of Serum 25-Hydroxyvitamin D on Serum Ferritin Concentrations: A Longitudinal Study of Participants of a Preventive Health Program
Nutrients 2019, 11(3), 692; https://doi.org/10.3390/nu11030692 (registering DOI) -
Abstract
Various studies have suggested a role of vitamin D in inflammation. However, its effect on ferritin, a biomarker of inflammation, has received relatively little attention. Therefore, we aimed to assess the association of serum 25-hydroxyvitamin D (25(OH)D) with serum ferritin (SF) concentrations, and [...] Read more.
Various studies have suggested a role of vitamin D in inflammation. However, its effect on ferritin, a biomarker of inflammation, has received relatively little attention. Therefore, we aimed to assess the association of serum 25-hydroxyvitamin D (25(OH)D) with serum ferritin (SF) concentrations, and to examine whether temporal increases in serum 25(OH)D concentrations are paralleled by a reduction in SF concentrations. Data from a community sample of Canadian adults who participated in a preventive health program (n = 6812) were analyzed. During the follow-up, serum 25(OH)D concentrations increased from 80.7 to 115.0 nmol/L whereas SF concentrations decreased from 122.0 to 92.0 µg/L (median follow-up time was 11.67 months). Cross-sectional analyses revealed that compared to participants with 25(OH)D concentrations of <50 nmol/L, those with 25(OH)D concentrations of 75 to <100, 100 to <125, and ≥125 nmol/L had SF concentrations that were 13.00, 23.15, and 27.59 µg/L lower respectively (p < 0.001). Compared to those without temporal improvements in 25(OH)D concentrations between baseline and follow-up, participants who improved their 25(OH)D concentrations with ≥50 nmol/L decreased their SF concentrations with 5.71 µg/L. For participants for whom the increase in 25(OH)D concentrations was less than 50 nmol/L, decreases in SF concentrations were less pronounced and not statistically significant. These observations suggest that despite strong associations between 25(OH)D and SF concentrations, interventions aiming to lower SF concentrations through sun-exposure and vitamin D supplementation should target substantial increases in 25(OH)D concentrations. Full article
Open AccessArticle
Staple Food Item Availability among Small Retailers in Providence, RI
Int. J. Environ. Res. Public Health 2019, 16(6), 1052; https://doi.org/10.3390/ijerph16061052 (registering DOI) -
Abstract
Inventory requirements for authorized Supplemental Nutrition Assistance Program (SNAP) retailers have undergone several revisions to increase the availability of healthful foods. A proposed rule of 84 staple food items was not implemented due to concerns that stores would not withstand this expansion, resulting [...] Read more.
Inventory requirements for authorized Supplemental Nutrition Assistance Program (SNAP) retailers have undergone several revisions to increase the availability of healthful foods. A proposed rule of 84 staple food items was not implemented due to concerns that stores would not withstand this expansion, resulting in a final rule requiring 36 items. This study used the Food Access Research Atlas data to characterize food provisions in 30 small retailers in areas with high and low proportions of SNAP and racial minority residents in Providence, Rhode Island (RI). Stores were assessed with an audit instrument to tally variety, perishability, and depth of stock of four staple food categories. Descriptive, analysis of variance, and chi-square analyses were performed. Across stores, 80% were compliant with the final rule, but 66.7% would need to expand their offerings to meet the proposed rule. Mean dairy variety was lowest among all categories (p < 0.05). Most stores met the perishability (92.3%) and depth-of-stock requirements (96.1%) under both rules. No difference was detected between areas with high and low proportions of SNAP and racial minority residents. Future expansion of requirements may increase healthful food availability without imposing undue burdens on retailers in Providence, RI, excluding increased requirements for dairy variety. Full article
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Open AccessArticle
Rat Glioma Cell-Based Functional Characterization of Anti-Stress and Protein Deaggregation Activities in the Marine Carotenoids, Astaxanthin and Fucoxanthin
Mar. Drugs 2019, 17(3), 189; https://doi.org/10.3390/md17030189 (registering DOI) -
Abstract
Stress, protein aggregation, and loss of functional properties of cells have been shown to contribute to several deleterious pathologies including cancer and neurodegeneration. The incidence of these pathologies has also been shown to increase with age and are often presented as evidence to [...] Read more.
Stress, protein aggregation, and loss of functional properties of cells have been shown to contribute to several deleterious pathologies including cancer and neurodegeneration. The incidence of these pathologies has also been shown to increase with age and are often presented as evidence to the cumulative effect of stress and protein aggregation. Prevention or delay of onset of these diseases may prove to be unprecedentedly beneficial. In this study, we explored the anti-stress and differentiation-inducing potential of two marine bioactive carotenoids (astaxanthin and fucoxanthin) using rat glioma cells as a model. We found that the low (nontoxic) doses of both protected cells against UV-induced DNA damage, heavy metal, and heat-induced protein misfolding and aggregation of proteins. Their long-term treatment in glioma cells caused the induction of physiological differentiation into astrocytes. These phenotypes were supported by upregulation of proteins that regulate cell proliferation, DNA damage repair mechanism, and glial differentiation, suggesting their potential for prevention and treatment of stress, protein aggregation, and age-related pathologies. Full article
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Open AccessArticle
Synthesis of AMPSA Polymeric Derivatives Monitored by Electrical Conductivity and Evaluation of Thermosensitive Properties of Resulting Microspheres
Molecules 2019, 24(6), 1164; https://doi.org/10.3390/molecules24061164 (registering DOI) -
Abstract
Four stimuli-responsive polymers of N-isopropylacrylamide (NIPA) and 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPSA) and crosslinked derivatives by N,N′-methylene bisacrylamide (MBA) were synthesized: PNA, PAMPSA, PNAM, PAMPSAM. The effect of the cross-linker and methyl sulphonic acid (-CH3-SO3H) group on particle size, [...] Read more.
Four stimuli-responsive polymers of N-isopropylacrylamide (NIPA) and 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPSA) and crosslinked derivatives by N,N′-methylene bisacrylamide (MBA) were synthesized: PNA, PAMPSA, PNAM, PAMPSAM. The effect of the cross-linker and methyl sulphonic acid (-CH3-SO3H) group on particle size, aggregation and volume phase transition temperature (VPTT) was investigated. Polymeric particles were synthesized via the surfactant free precipitation polymerization (SFPP) at 70 °C in the presence of cationic initiator 2,2′-azobis[2-methylpropionamidine] dihydrochloride (AMP) system. Chemical composition and morphology of investigated samples were evaluated using ATR-FTIR spectroscopy, 1H-NMR spectrometry and SEM-EDS techniques. The hydrodynamic diameters (HD), zeta potential (ZP), and polydispersity index (PDI) in aqueous dispersions were assessed by dynamic light scattering (DLS) between 18–42 °C. HD values at 18 °C for PNA, PAMPSA, PNAM, PAMPSAM polymers were approx. 32, 730, 715, 665 nm, and ZP values were −1.36, −0.01, 8.90, −0.09 mV, respectively. The VPTT range was observed between 29 and 41 °C. PDI’s for PNA and PNAM were low and varied between 0.276 and 0.460, and between 0.119 and 0.056, respectively. PAMPSA and PAMPSAM were characterized by higher PDI in the range 0.728–0.959 and 0.658–0.836, respectively. The results confirmed the thermal sensitivity of the synthesized polymers and indicated a significant polydispersity and aggregation tendency of the resulting molecules. The conductivity results were applied for the interpretation of the polymerization process. Full article
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Open AccessArticle
Discovery of 2-Substituted 3-Arylquinoline Derivatives as Potential Anti-Inflammatory Agents Through Inhibition of LPS-Induced Inflammatory Responses in Macrophages
Molecules 2019, 24(6), 1162; https://doi.org/10.3390/molecules24061162 (registering DOI) -
Abstract
We describe herein the preparation of certain 2-substituted 3-arylquinoline derivatives and the evaluation of their anti-inflammatory effects in LPS-activated murine J774A.1 macrophage cells. Among these newly synthesized 2-substituted 3-arylquinoline derivatives, 2-(4-methoxy- benzoyl)-3-(3,4,5-trimethoxyphenyl)quinoline (18a) and 2-(4-fluorobenzoyl)-3-(3,4,5-trimethoxy- phenyl)quinoline (18b) are two [...] Read more.
We describe herein the preparation of certain 2-substituted 3-arylquinoline derivatives and the evaluation of their anti-inflammatory effects in LPS-activated murine J774A.1 macrophage cells. Among these newly synthesized 2-substituted 3-arylquinoline derivatives, 2-(4-methoxy- benzoyl)-3-(3,4,5-trimethoxyphenyl)quinoline (18a) and 2-(4-fluorobenzoyl)-3-(3,4,5-trimethoxy- phenyl)quinoline (18b) are two of the most active compounds which can inhibit the production of NO at non-cytotoxic concentrations. Our results have also indicated that compounds 18a and 18b significantly decrease the secretion of pro-inflammatory cytokines (TNF-á and IL-6), inhibit the expression of iNOS, suppress the phosphorylation of MAPKs, and attenuate the activity of NF-êB by LPS-activated macrophages. Through molecular docking analysis, we found that 18b could fit into the middle of the TNF-á dimer and form hydrophobic interactions with Leu55, Leu57 chain A and B, Tyr59, Val123 chain B and D, Ile 155. These results suggest that both 18a and 18b are potential lead compounds in inhibiting LPS-induced inflammatory responses. Further structural optimization to discover novel anti-inflammatory agents is ongoing. Full article
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