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The spherical diffusion that occurs when using ultramicroelectrodes (i.e., electrodes with a characteristic size of 1–10 µm) contributes to a higher mass transfer rate. This leads to equalization of the depletion rates of the near-electrode layer due to the electrochemical reaction and to the supply of the product from the solution depth. This is the reason why, for ultramicroelectrodes, a limiting size of the spherical layer exists in which the concentration gradient is localized (diffusion layer). Thus, a stationary mass transfer mode is achieved, which is expressed in the sigmoidal CV curve’s shape. In ultramicroelectrode arrays, when the diffusion hemispheres are separated, a steady-state diffusion is realized. However, with a decrease in the interelectrode distance, which leads to the diffusion spheres intersection, a mixed regime arises, which is not fully time-independent. The resulting voltammogram’s shape change can serve as an analytical signal in the study of substances with differing diffusion coefficients, since the diffusion layer growth rate and, consequently, the area of intersection of neighboring spheres, depends on it. This work shows the applicability of voltammetry using ensembles of ultramicroelectrodes operating in the transient mode for the analysis of mixtures of electrochemically active compounds with close electrode reaction parameters, such as exchange currents and electrode potential. Ferrocenemethanol esters are used as an example. The applicability of cyclic voltammetry on the UME array for analysis of mixtures was illustrated by means of finite element modelling. The reliability of the modelling results was experimentally proved for ferrocenemethanol esters with glycine and triglycine.

Surface modification of polysulfone ultrafiltration membranes was performed via addition of an anionic polymer flocculant based on acrylamide and sodium acrylate (PASA) to the coagulation bath upon membrane preparation by non-solvent induced phase separation (NIPS). The effect of PASA concentration in the coagulant at different coagulation bath temperatures on membrane formation time, membrane structure, surface roughness, hydrophilic-hydrophobic balance of the skin layer, surface charge, as well as separation and antifouling performance was studied. Scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared (FTIR) spectroscopy, contact angle and zeta potential measurements were utilized for membrane characterization. Membrane barrier and antifouling properties were evaluated in ultrafiltration of model solutions containing human serum albumin and humic acids as well as with real surface water. PASA addition was found to affect the kinetics of phase separation leading to delayed demixing mechanism of phase separation due to the substantial increase of coagulant viscosity, which is proved by a large increase of membrane formation time. Denser and thicker skin layer is formed and formation of macrovoids in membrane matrix is suppressed. FTIR analysis confirms the immobilization of PASA macromolecules into the membrane skin layer, which yields improvement of hydrophilicity and change of zeta potential. Modified membrane demonstrated better separation and antifouling performance in the ultrafiltration of humic acid solution and surface water compared to the reference membrane.

The development of electrochemical multisensor systems is driven by the need for fast, miniature, inexpensive, analytical devices, and advanced interdisciplinary based on both chemometric and (nano)material approaches. A multicomponent analysis of complex mixtures in environmental and technological monitoring, biological samples, and cell culture requires chip-based multisensor systems with high-stability sensors. In this paper, we describe the development, characterization, and applications of chip-based nanoelectrochemical sensor arrays prepared by the directed electrochemical nanowire assembly (DENA) of noble metals and metal alloys to analyze aqueous solutions. A synergic action of the electrode transducer function and electrocatalytic activity of the nanostructured surface toward analytes is achieved in the assembled metal nanowire (NW) sensors. Various sensor nanomaterials (Pd, Ni, Au, and their multicomponent compositions) can be electrochemically assembled on a single chip without employing multiple cycles of photolithography process to realize multi-analyte sensing applications as well as spatial resolution of sensor analysis by this single-chip multisensor system. For multi-analyte electrochemical sensing, individual amperometric signals of two or more nanowires can be acquired, making use of the specific electrocatalytic surface properties of the individual nanowire sensors of the array toward analytes. To demonstrate the application of a new electrochemical multisensor platform, Pd-Au, Pd-Ni, Pd, and Au NW electrode arrays on a single chip were employed for the non-enzymatic analysis of hydrogen peroxide, glucose, and ethanol. The analytes are determined at low absolute values of the detection potentials with linear concentration ranges of 1.0 × 10−6 − 1.0 × 10−3 M (H2O2), 1.5 × 10−7 − 2.0 × 10−3 M (glucose), and 0.7 × 10−3 − 3.0 × 10−2 M (ethanol), detection limits of 2 × 10−7 M (H2O2), 4 × 10−8 M (glucose), and 5.2 × 10−4 M (ethanol), and sensitivities of 18 μA M−1 (H2O2), 178 μA M−1 (glucose), and 28 μA M−1 (ethanol), respectively. The sensors demonstrate a high level of stability due to the non-enzymatic detection mode. Based on the DENA-assembled nanowire electrodes of a compositional diversity, we propose a novel single-chip electrochemical multisensor platform, which is promising for acquiring complex analytical signals for advanced data processing with chemometric techniques aimed at the development of electronic tongue-type multisensor systems for flexible multi-analyte monitoring and healthcare applications.

The effect of amphiphilic block copolymer polyethylene glycol (PEG)-polypropylene glycol (PPG)-PEG concentration in the polyphenylsulfone (PPSU) casting solution and coagulation bath temperature (CBT) on the structure, separation, and antifouling performance of PPSU ultrafiltration membranes was studied for the first time. According to the phase diagram obtained, PPSU/PEG-PPG-PEG/N-methyl-2-pyrrolidone (NMP) systems are characterized by a narrow miscibility gap. It was found that 20 wt.% PPSU solutions in NMP with the addition of 5-15 wt.% of PEG-PPG-PEG block copolymer feature upper critical solution temperature, gel point, and lower critical solution temperature. Membrane composition and structure were studied by Fourier-transform infrared spectroscopy, scanning electron and atomic force microscopies, and water contact angle measurements. The addition of PEG-PPG-PPG to the PPSU casting solution was found to increase the hydrophilicity of the membrane surface (water contact angle decreased from 78° for the reference PPSU membrane down to 50° for 20 wt.%PPSU/15 wt.% PEG-PPG-PEG membrane). It was revealed that the pure water flux increased with the rise of CBT from 18-20 L·m -2 ·h -1 for the reference PPSU membrane up to 38-140 L·m -2 ·h -1 for 20 wt.% PPSU/10-15 wt.% PEG-PPG-PEG membranes. However, the opposite trend was observed for 20 wt.% PPSU/5-7 wt.% PEG-PPG-PEG membranes: pure water flux decreased with an increase in CBT. This is due to the differences in the mechanism of phase separation (non-solvent-induced phase separation (NIPS) or a combination of NIPS and temperature-induced phase separation (TIPS)). It was shown that 20 wt.% PPSU/10 wt.% PEG-PPG-PEG membranes were characterized by significantly higher antifouling performance (FRR-81-89%, DR r -26-32%, DR ir -10-20%, DT-33-45%) during the ultrafiltration of bovine serum albumin solutions compared to the reference PPSU membrane prepared at different CBTs (FRR-29-38%, DR r -6-14%, DR ir -74-89%, DT-88-94%).

Pervaporation is considered the most promising technology for dehydration of bioalcohols, attracting increasing attention as a renewable energy source. In this regard, the development of stable and effective membranes is required. In this study, highly efficient membranes for the enhanced pervaporation dehydration of ethanol were developed by modification of sodium alginate (SA) with a polyethylenimine (PEI) forming polyelectrolyte complex (PEC) and graphene oxide (GO). The effect of modifications with GO or/and PEI on the structure, physicochemical, and transport characteristics of dense membranes was studied. The formation of a PEC by ionic cross-linking and its interaction with GO led to changes in membrane structure, confirmed by spectroscopic and microscopic methods. The physicochemical properties of membranes were investigated by a thermogravimetric analysis, a differential scanning calorimetry, and measurements of contact angles. The theoretical consideration using computational methods showed favorable hydrogen bonding interactions between GO, PEI, and water, which caused improved membrane performance. To increase permeability, supported membranes without treatment and cross-linked were developed by the deposition of a thin dense layer from the optimal PEC/GO (2.5%) composite onto a developed porous substrate from polyacrylonitrile. The cross-linked supported membrane demonstrated more than two times increased permeation flux, higher selectivity (above 99.7 wt.% water in the permeate) and stability for separating diluted mixtures compared to the dense pristine SA membrane.

One of the solutions for the growing problem of water purification is photocatalytic degradation of the pollutants. Semiconductor nanoparticles are widely under study as a promising photocatalyst for this purpose. However, there is still lack of understanding of the relation between properties of nanoparticles, in their turn related with synthesis conditions, and photocatalytic efficiency, as well as of the other factors influencing the process. For the first time, a possibility to regulate photocatalytic activity of SnO 2 nanoparticles under UV light via regulation of structural parameters is shown. A method for obtaining spherical nanoparticles with different parameters was developed. Obtained nanoparticles were fully characterized. Special attention was paid to the study of oxygen vacancies. With the help of quantum computational methods, it was shown, that the concentration of vacancies is around 1 per 32 tin atoms. Obtained data on oxygen vacancies were further used for the evaluation of pollutant-nanoparticle surface interaction to get closer to the calculations of real systems. On the example of methylene blue, it was shown that the greater is the amount of oxygen vacancies and the lower the amount of defects, the higher photocatalytic activity. The obtained dependence is confirmed by the fact that the photoresponse increases with a decrease of amount of defects in the sample. Degradation kinetics of sulfonamides mixture was studied, and its dependence on active complex formation was shown based on the quantum chemical calculation data. Degradation of antibiotics in water from Neva River reached more than 95% in 35 min, which indicates that developed photocatalyst efficiency is not affected by pollutants contained in open water in the centre of the metropolis. It was shown, that the use of nanoparticles allows to speed up the process of bacteria destruction under UV light, which indicates the antibacterial activity of obtained nanoparticles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Presently, water pollution poses a serious threat to the environment; the removal of organic pollutants from resources, especially dyes, is very important. Nanofiltration (NF) is a promising membrane method to carry out this task. In the present work, advanced supported poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) membranes were developed for NF of anionic dyes using bulk (the introduction of graphene oxide (GO) into the polymer matrix) and surface (the deposition of polyelectrolyte (PEL) layers by layer-by-layer (LbL) technique) modifications. The effect of PEL combinations (polydiallyldimethylammonium chloride/polyacrylic acid (PAA), polyethyleneimine (PEI)/PAA, and polyallylamine hydrochloride/PAA) and the number of PEL bilayers deposited by LbL method on properties of PPO-based membranes were studied by scanning electron microscopy (SEM), atomic force microscopy (AFM), and contact angle measurements. Membranes were evaluated in NF of food dye solutions in ethanol (Sunset yellow (SY), Congo red (CR), and Alphazurine (AZ)). The supported PPO membrane, modified with 0.7 wt.% GO and three PEI/PAA bilayers, exhibited optimal transport characteristics: ethanol, SY, CR, and AZ solutions permeability of 0.58, 0.57, 0.50, and 0.44 kg/(m 2 h atm), respectively, with a high level of rejection coefficients-58% for SY, 63% for CR, and 58% for AZ. It was shown that the combined use of bulk and surface modifications significantly improved the characteristics of the PPO membrane in NF of dyes.

Membrane fouling is a serious issue in membrane technology which cannot be completely avoided but can be diminished. The perspective technique of membrane modification is the introduction of hydrophilic polymers or polyelectrolytes into the coagulation bath during membrane preparation via non-solvent-induced phase separation. The influence of polyacrylic acid (PAA) molecular weight (100,000, 250,000 and 450,000 g·mol -1 ) added to the aqueous coagulation bath (0.4-2.0 wt.%) on the polysulfone membrane structure, surface roughness, water contact angle and zeta potential of the selective layer, as well as the separation and antifouling performance, was systematically studied. It was found that membranes obtained via the addition of PAA with higher molecular weight feature smaller pore size and porosity, extremely high hydrophilicity and higher values of negative charge of membrane surface. It was shown that the increase in PAA concentration from 0.4 wt.% to 2.0 wt.% for all studied PAA molecular weights yielded a substantial decrease in water contact angle compared with the reference membrane (65 ± 2°) (from 27 ± 2° to 17 ± 2° for PAA with M n = 100,000 g·mol -1 ; from 25 ± 2° to 16 ± 2° for PAA with M n = 250,000 g·mol -1 ; and from 19 ± 2° to 10 ± 2° for PAA with M n = 450,000 g·mol -1 ). An increase in PAA molecular weight from 100,000 to 450,000 g·mol -1 led to a decrease in membrane permeability, an increase in rejection and tailoring excellent antifouling performance in the ultrafiltration of humic acid solutions. The fouling recovery ratio increased from 73% for the reference membrane up to 91%, 100% and 136% for membranes modified with the addition to the coagulation bath of 1.5 wt.% of PAA with molecular weights of 100,000 g·mol -1 , 250,000 g·mol -1 and 450,000 g·mol -1 , respectively. Overall, the addition of PAA of different molecular weights to the coagulation bath is an efficient tool to adjust membrane separation and antifouling properties for different separation tasks.

Nowadays, nanofiltration is actively used for water softening and disinfection, pre-treatment, nitrate, and color removal, in particular, for heavy metal ions removal from wastewater. In this regard, new, effective materials are required. In the present work, novel sustainable porous membranes from cellulose acetate (CA) and supported membranes consisting of CA porous substrate with a thin dense selective layer from carboxymethyl cellulose (CMC) modified with first-time synthesized Zn-based metal-organic frameworks (Zn(SEB), Zn(BDC)Si, Zn(BIM)) were developed to increase the efficiency of nanofiltration for the removal of heavy metal ions. Zn-based MOFs were characterized by sorption measurements, X-ray diffraction (XRD), and scanning electron microscopy (SEM). The obtained membranes were studied by the spectroscopic (FTIR), standard porosimetry and microscopic (SEM and AFM) methods, and contact angle measurement. The CA porous support was compared with other, prepared in the present work, porous substrates from poly(m-phenylene isophthalamide) and polyacrylonitrile. Membrane performance was tested in the nanofiltration of the model and real mixtures containing heavy metal ions. The improvement of the transport properties of the developed membranes was achieved through Zn-based MOF modification due to their porous structure, hydrophilic properties, and different particle shapes.

Thin-film composite membranes (TFC) obtained by the formation of a selective layer on a porous membrane-substrate via interfacial polymerization (IP) are indispensable for separation procedures in reverse osmosis, nanofiltration, pervaporation, and gas separation. Achieving high selectivity and permeability for TFC membranes is still one of the main challenges in membrane science and technology. This study focuses on the development of thin film nanocomposite (TFN) membranes with a hierarchically structured polyamide (PA)/chitosan succinate (ChS) selective layer embedded with a metal-organic framework of iron 1,3,5-benzenetricarboxylate (Fe-BTC) for the enhanced pervaporation dehydration of isopropanol. The aim of this work was to study the effect of Fe-BTC incorporation into the ChS interlayer and PA selective layer, obtained via IP, on the structure, properties, and performance of pervaporation TFN membranes. The structure and hydrophilicity of the developed TFN membranes were investigated using scanning electron microscopy (SEM) and atomic force microscopy (AFM), along with water contact angle measurements. The developed TFN membranes were studied in the pervaporation dehydration of isopropanol (12-30 wt % water). It was found that incorporation of Fe-BTC into the ChS interlayer yielded the formation of a smoother, more uniform, and defect-free PA ultrathin selective layer via IP, due to the amorpho-crystalline structure of particles serving as the amine storage reservoir and led to an increase in membrane selectivity toward water, and a slight decrease in permeation flux compared to the ChS interlayered TFC membranes. The best pervaporation performance was demonstrated by the TFN membrane with a ChS-Fe-BTC interlayer and the addition of 0.03 wt % Fe-BTC in the PA layer, yielding a permeation flux of 197-826 g·m -2 ·h -1 and 98.50-99.99 wt % water in the permeate, in the pervaporation separation of isopropanol/water mixtures (12-30 wt % water).

The application of environmentally friendly and energy-efficient membrane processes allows improvement the ecological safety and sustainability of industrial production. However, the effective application of membrane processes requires novel high-performance thin film composite (TFC) membranes based on biopolymers to solve environmental problems. In this work for the first time novel thin film nanocomposite (TFN) membranes based on biopolymer chitosan succinate (ChS) modified with the metal organic framework iron 1,3,5-benzenetricarboxylate (Fe-BTC) were developed for enhanced pervaporation dehydration. The formation of a selective layer of TFN membranes on the porous membrane-support was carried out by two methods-dynamic technique and physical adsorption. The effect of the membrane formation method and Fe-BTC content in ChS layer on the structure and physicochemical properties of TFN membranes was investigated. The developed TFN ChS-based membranes were evaluated in the pervaporation dehydration of isopropanol (12-30 wt.% water). It was found that TFN ChS-Fe-BTC membranes prepared by two methods demonstrated improved permeation flux compared to the reference TFC ChS membrane. The best transport properties in pervaporation dehydration of isopropanol (12-30 wt.% water) were possessed by TFN membranes with 40 wt.% Fe-BTC prepared by dynamic technique (permeation flux 99-499 g m -2 h -1 and 99.99% water in permeate) and TFN membranes with 5 wt.% Fe-BTC developed by physical adsorption (permeation flux 180-701 g m -2 h -1 and 99.99% water in permeate).

In this work, a reversed-phase dispersive liquid-liquid microextraction procedure based on the decomposition of deep eutectic solvent was suggested for the first time. The procedure was utilized for fast and simple separation of lead and cadmium from vegetable oil samples. The procedure assumed mixing of oil sample and DES based on menthol, formic acid and water. Water as component of DES promoted its decomposition in sample matrix resulting menthol dissolution in the sample phase and dispersion of aqueous formic acid solution. In this procedure menthol acted as a dispersive solvent during DES decomposition for dispersion of aqueous formic acid solution. The metals were determined by the square-wave anodic stripping voltammetry. The limits of detection, were 0.01 µg kg -1 for lead and 0.006 µg kg -1 for cadmium. The RSD was less then 6% for both analytes. The enrichment factor was 36 and 39 for lead and cadmium, respectively., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Nowadays, nanofiltration is widely used for water treatment due to its advantages, such as energy-saving, sustainability, high efficiency, and compact equipment. In the present work, novel nanofiltration membranes based on the polymer of intrinsic microporosity PIM-1 modified by metal-organic frameworks (MOFs)-MIL-140A and MIL-125-were developed to increase nanofiltration efficiency for the removal of heavy metal ions and dyes. The structural and physicochemical properties of the developed PIM-1 and PIM-1/MOFs membranes were studied by the spectroscopic technique (FTIR), microscopic methods (SEM and AFM), and contact angle measurement. Transport properties of the developed PIM-1 and PIM-1/MOFs membranes were evaluated in the nanofiltration of the model and real mixtures containing food dyes and heavy metal ions. It was found that the introduction of MOFs (MIL-140A and MIL-125) led to an increase in membrane permeability. It was demonstrated that the membranes could be used to remove and concentrate the food dyes and heavy metal ions from model and real mixtures.

Cardiac and renal function are inextricably connected through both hemodynamic and neurohormonal mechanisms, and the interaction between these organ systems plays an important role in adaptive and pathophysiologic remodeling of the heart, as well as in the response to renally acting therapies. Insufficient understanding of the integrative function or dysfunction of these physiological systems has led to many examples of unexpected or incompletely understood clinical trial results. Mathematical models of heart and kidney physiology have long been used to better understand the function of these organs, but an integrated model of renal function and cardiac function and cardiac remodeling has not yet been published. Here we describe an integrated cardiorenal model that couples existing cardiac and renal models, and expands them to simulate cardiac remodeling in response to pressure and volume overload, as well as hypertrophy regression in response to angiotensin receptor blockers and beta-blockers. The model is able to reproduce different patterns of hypertrophy in response to pressure and volume overload. We show that increases in myocyte diameter are adaptive in pressure overload not only because it normalizes wall shear stress, as others have shown before, but also because it limits excess volume accumulation and further elevation of cardiac stresses by maintaining cardiac output and renal sodium and water balance. The model also reproduces the clinically observed larger LV mass reduction with angiotensin receptor blockers than with beta blockers. We further provide a mechanistic explanation for this difference by showing that heart rate lowering with beta blockers limits the reduction in peak systolic wall stress (a key signal for myocyte hypertrophy) relative to ARBs., Competing Interests: SE was an employee of Amgen, Inc. KH has received funding from AstraZeneca, Pfizer, Merck, and Takeda within the last 2 years. The authors declare that this study received funding from AstraZeneca, Pfizer, and Merck. The funder was not involved in the study design, collection, analysis, interpretation of data, writing of this article, or decision to submit it for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hallow, Van Brackle, Anjum and Ermakov.)

Membrane methods, especially pervaporation, are quickly growing up. In line with that, effective membrane materials based on biopolymers are required for the industrially significant mixtures separation. To essentially improve membrane transport characteristics, the application of the surface or/and bulk modifications can be carried out. In the present study, novel dense and supported membranes based on hydroxyethyl cellulose (HEC)/sodium alginate (SA) were developed for pervaporation dehydration of isopropanol using several approaches: (1) the selection of the optimal ratio of polymers, (2) the introduction of fullerenol in blend polymer matrix, (3) the selection of the optimal cross-linking agent for the membranes, (4) the application of layer-by-layer deposition of polyelectrolytes on supported membrane surface (poly(sodium 4-styrenesulfonate) (PSS)/poly(allylamine hydrochloride) (PAH) and PSS/SA). Structural and physicochemical characteristics of the membranes were analyzed by different methods. A cross-linked supported membrane based on HEC/SA/fullerenol (5%) composite possessed the following transport characteristics in pervaporation dehydration of isopropanol (12-50 wt.% water): 0.42-1.72 kg/(m 2 h) permeation flux, and 77.8-99.99 wt.% water content in the permeate. The surface modification of this membrane with 5 bilayers of PSS/PAH and PSS/SA resulted in the increase of permeation flux up to 0.47-3.0 and 0.46-1.9 kg/(m 2 h), respectively, with lower selectivity.

The aim of the study is to improve the performance of thin-film composite (TFC) membranes with a thin selective layer based on chitosan (CS) via different approaches by: (1) varying the concentration of the CS solution; (2) changing the porosity of substrates from polyacrylonitrile (PAN); (3) deposition of the additional ultrathin layers on the surface of the selective CS layer using interfacial polymerization and layer-by-layer assembly. The developed membranes were characterized by different methods of analyses (SEM and AFM, IR spectroscopy, measuring of water contact angles and porosity). The transport characteristics of the developed TFC membranes were studied in pervaporation separation of isopropanol/water mixtures. It was found that the application of the most porous PAN-4 substrate with combination of formation of an additional polyamide selective layer by interfacial polymerization on the surface of a dense selective CS layer with the subsequent layer-by-layer deposition of five bilayers of poly (sodium 4-styrenesulfonate)/CS polyelectrolyte pair led to the significant improvement of permeance and high selectivity for the entire concentration feed range. Thus, for TFC membrane on the PAN-4 substrate the optimal transport characteristics in pervaporation dehydration of isopropanol (12-90 wt.% water) were achieved: 0.22-1.30 kg/(m 2 h), 99.9 wt.% water in the permeate.

Novel mixed matrix dense and supported membranes based on biopolymer sodium alginate (SA) modified by fullerenol were developed. Two kinds of SA-fullerenol membranes were investigated: untreated and cross-linked by immersing the dry membranes in 1.25 wt % calcium chloride (CaCl 2 ) in water for 10 min. The structural and physicochemical characteristics features of the SA-fullerenol composite were investigated by Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopic methods, scanning electron (SEM) and atomic force (AFM) microscopies, thermogravimetric analysis (TGA), and swelling experiments. Transport properties were evaluated in pervaporation dehydration of isopropanol in a wide concentration range. It was found that the developed supported cross-linked SA-5/PAN CaCl2 membrane (modified by 5 wt % fullerenol) possessed the best transport properties (the highest permeation fluxes 0.64-2.9 kg/(m 2 h) and separation factors 26-73,326) for the pervaporation separation of the water-isopropanol mixture in the wide concentration range (12-90 wt % water) at 22 °C and is suitable for the promising application in industry.

In this work, dense and supported pervaporation polyvinyl alcohol (PVA)-based membranes modified with poly(allylamine hydrochloride) (PAH) and poly(sodium 4-styrenesulfonate)(PSS)/PAH top nanolayers were synthesized. Two main points were investigated: the role of the polyelectrolyte PAH on water selectivity of the selective polymer matrix and the impact of the porous substrate based on polyacrylonitrile (PAN) and aromatic polysulfone amide (UPM-20 ® ), used to get supported high-performance membranes. Various methods of analysis (fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), atomic force microscopy (AFM), small-angle X-ray scattering (SAXS), porosity, contact angles, ultrafiltration) were applied to study the developed membranes. Transport characteristics of the developed membranes were studied in isopropanol dehydration by pervaporation. Obtained results are discussed in the light of the structure and physicochemical characteristics of these PVA/PAH membranes and the types of porous substrate. It was shown that the PAN-supported membrane with the selective layer based on PVA/PAH modified by 10 polyelectrolyte PSS/PAH bilayers possessed ~4.5 times higher permeation flux with the same high selectivity level (99.9 wt % water in the permeate) for the dehydration of the isopropanol (20 wt % water) at 60 °C compared to the commercial analog PERVAP TM 1201., Competing Interests: The authors declare no conflicts of interest.

Quantitative systems pharmacology (QSP) is a rapidly emerging discipline with application across a spectrum of challenges facing the pharmaceutical industry, including mechanistically informed prioritization of target pathways and combinations in discovery, target population, and dose expansion decisions early in clinical development, and analyses for regulatory authorities late in clinical development. QSP's development has influences from physiologic modeling, systems biology, physiologically-based pharmacokinetic modeling, and pharmacometrics. Given a varied scientific heritage, a variety of tools to accomplish the demands of model development, application, and model-based analysis of available data have been developed. We report the outcome from a community survey and resulting analysis of how modelers view the impact and growth of QSP, how they utilize existing tools, and capabilities they need improved to further accelerate their impact on drug development. These results serve as a benchmark and roadmap for advancements to the QSP tool set., (© 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

An easily performed miniaturized, cheap, selective and sensitive procedure for the determination of H 2 S in fuel oil samples based on a headspace liquid-phase microextraction followed by a cyclic voltammetry detection using a paper-based analytical device (PAD) was developed. A modified wax dipping method was applied to fabricate the PAD. The PAD included hydrophobic zones of sample and supporting electrolyte connecting by hydrophilic channel. The zones of sample and supporting electrolyte were connected with nickel working, platinum auxiliary and Ag/AgCl reference electrodes. The analytical procedure included separation of H 2 S from fuel oil sample based on the headspace liquid-phase microextraction in alkaline solution. Then, sulfide ions solution obtained and supporting electrolyte were dropped on the zones followed by analyte detection at + 0.45 V. Under the optimized conditions, H 2 S concentration in the range from 2 to 20 mg kg -1 had a good linear relation with the peak current. The limit of detection (3σ) was 0.6 mg kg -1 . The procedure was successfully applied to the analysis of fuel oil samples., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In the present work, the novel dense and supported membranes based on polyvinyl alcohol (PVA) with improved transport properties were developed by bulk and surface modifications. Bulk modification included the blending of PVA with chitosan (CS) and the creation of a mixed-matrix membrane by introduction of fullerenol. This significantly altered the internal structure of PVA membrane, which led to an increase in permeability with high selectivity to water. Surface modification of the developed modified dense membranes, based on composites PVA-CS and PVA-fullerenol-CS, was performed through (i) making of a supported membrane with a thin selective composite layer and (ii) applying of the layer-by-layer assembly (LbL) method for coating of nano-sized polyelectrolyte (PEL) layers to increase the membrane productivity. The nature of polyelectrolyte type-(poly(allylamine hydrochloride) (PAH), poly(sodium 4-styrenesulfonate) (PSS), poly(acrylic acid) (PAA), CS), and number of PEL bilayers (2⁻10)-were studied. The structure of the composite membranes was investigated by FTIR, X-ray diffraction, and SEM. Transport properties were studied during the pervaporation separation of 80% isopropanol⁻20% water mixture. It was shown that supported membrane consisting of hybrid layer of PVA-fullerenol (5%)⁻chitosan (20%) with five polyelectrolyte bilayers (PSS, CS) deposited on it had the best transport properties.

A novel vapor permeation-stepwise injection (VP-SWI) method for the determination of methanol and ethanol in biodiesel samples is discussed. In the current study, stepwise injection analysis was successfully combined with voltammetric detection and vapor permeation. This method is based on the separation of methanol and ethanol from a sample using a vapor permeation module (VPM) with a selective polymer membrane based on poly(phenylene isophtalamide) (PA) containing high amounts of a residual solvent. After the evaporation into the headspace of the VPM, methanol and ethanol were transported, by gas bubbling, through a PA membrane to a mixing chamber equipped with a voltammetric detector. Ethanol was selectively detected at +0.19 V, and both compounds were detected at +1.20 V. Current subtractions (using a correction factor) were used for the selective determination of methanol. A linear range between 0.05 and 0.5% (m/m) was established for each analyte. The limits of detection were estimated at 0.02% (m/m) for ethanol and methanol. The sample throughput was 5 samples h(-1). The method was successfully applied to the analysis of biodiesel samples., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Multiple software programs are available for designing and running large scale system-level pharmacology models used in the drug development process. Depending on the problem, scientists may be forced to use several modeling tools that could increase model development time, IT costs and so on. Therefore, it is desirable to have a single platform that allows setting up and running large-scale simulations for the models that have been developed with different modeling tools. We developed a workflow and a software platform in which a model file is compiled into a self-contained executable that is no longer dependent on the software that was used to create the model. At the same time the full model specifics is preserved by presenting all model parameters as input parameters for the executable. This platform was implemented as a model agnostic, therapeutic area agnostic and web-based application with a database back-end that can be used to configure, manage and execute large-scale simulations for multiple models by multiple users. The user interface is designed to be easily configurable to reflect the specifics of the model and the user's particular needs and the back-end database has been implemented to store and manage all aspects of the systems, such as Models, Virtual Patients, User Interface Settings, and Results. The platform can be adapted and deployed on an existing cluster or cloud computing environment. Its use was demonstrated with a metabolic disease systems pharmacology model that simulates the effects of two antidiabetic drugs, metformin and fasiglifam, in type 2 diabetes mellitus patients.

Reproducibly differential responses to different classes of antihypertensive agents are observed among hypertensive patients and may be due to interindividual differences in hypertension pathology. Computational models provide a tool for investigating the impact of underlying disease mechanisms on the response to antihypertensive therapies with different mechanisms of action. We present the development, calibration, validation, and application of an extension of the Guyton/Karaaslan model of blood pressure regulation. The model incorporates a detailed submodel of the renin-angiotensin-aldosterone system (RAAS), allowing therapies that target different parts of this pathway to be distinguished. Literature data on RAAS biomarker and blood pressure responses to different classes of therapies were used to refine the physiological actions of ANG II and aldosterone on renin secretion, renal vascular resistance, and sodium reabsorption. The calibrated model was able to accurately reproduce the RAAS biomarker and blood pressure responses to combinations of dual-RAAS agents, as well as RAAS therapies in combination with diuretics or calcium channel blockers. The final model was used to explore the impact of underlying mechanisms of hypertension on the blood pressure response to different classes of antihypertensive agents. Simulations indicate that the underlying etiology of hypertension can impact the magnitude of response to a given class of therapy, making a patient more sensitive to one class and less sensitive others. Given that hypertension is usually the result of multiple mechanisms, rather than a single factor, these findings yield insight into why combination therapy is often required to adequately control blood pressure.

Objective: Bardet-Biedl syndrome (BBS) is a rare monogenic multi-systemic disorder manifesting with marked obesity. Fourteen BBS genes have been identified to date and additional loci are expected. Mutations of several BBS genes were shown to affect fat cell differentiation. The purpose was to Investigate the association between common polymorphisms in all 14 genes as a group and body weight., Design and Methods: We investigated association between tagging single nucleotide polymorphisms (tSNPs) located between 10 kb upstream and downstream from the transcribed sequences of each of 14 BBS genes, and body weight and fat in 2462 adult women from the UK Twins study. Significant results were further tested in a confirmation sample of 2003 women from the same cohort and additionally in the GIANT consortium population (n = 123,865)., Results: 105 SNPs in 14 BBS genes were selected and tested in the first cohort of women for association with the body weight and fat related phenotypes, i.e. weight, body mass index (BMI), total body fat (assessed by DEXA), total fat/height(2), and total fat/weight. We used principal component (PC) derived using the latter five traits as a primary phenotype for this study. Of the 105 SNPs, 3 variants in BBS9 and BBS11 showed evidence of nominally significant association with elevated body weight and fat. However, none of the associations survived multiple-testing correction., Conclusions: The results suggest that common variation in 14 BBS genes (within or adjacent to the genes) are unlikely to have a substantial effect on body weight and fat in the European population., (Copyright © 2013 The Obesity Society.)

Objective: Osteoarthritis (OA) and osteoporosis are often considered to lie at opposite ends of a spectrum of bone phenotypes. Lumbar degenerative disc disease (LDD) may be associated with low back pain (LBP) and is similar in many ways to OA. LDD is reported in small studies to be associated with increased spine bone mineral density (BMD). The present work aimed to confirm this association in a large population sample using MRI and explore the relationship further, in particular to determine whether it is mediated genetically., Methods: A population based sample (N = 908, age range 32-74 years) of UK female twins having MRI of the lumbar spine was used in this study. LDD traits and summary measures and their relationship with BMD at the lumbar spine and hip were examined using multivariate multiple regression and maximum likelihood based variance decomposition., Results: There was a significant positive correlation between LDD and BMD at the lumbar spine and hip, which remained significant after adjustment for confounders. Both traits were highly heritable and the associations between them were mediated genetically., Conclusions: A clear, significant and independent association of BMD at hip and lumbar spine with LDD was found which is, in part, genetically mediated. The association with the non-axial site, the hip, is of particular interest and suggests a systemic bone effect. This should encourage the search for pleiotropic genes to help in the understanding of the bone-cartilage relationship. Moreover, genetic variants identified could provide novel therapeutic targets in the management of LBP.

Background: Human craniofacial morphology is characterized by considerable diversity among individuals. The ENPP1 gene is essential for bone physiology. However, the potential effects of its genetic variants on head size phenotypes have not yet been studied., Aim: The aim of this research was to investigate the association of polymorphisms in the ENPP1 locus with normal variability of craniofacial phenotypes., Subjects and Methods: Fourteen SNPs and 13 haplotypes in the ENPP1 locus were tested for association with six head size traits in 1042 Western Eurasian individuals., Results: The most significant and consistent association was observed between upper facial height and the polymorphisms located near the promoter region and upstream from ENPP1 gene (p = 0.00009), which remained significant after adjustment for multiple testing. Additionally, association signals were detected between head breadths and lower face height, and markers residing in or close to the promoter and 3' untranslated regions of the ENPP1 gene (p < 0.05)., Conclusions: The findings obtained in this study suggest that the upstream, promoter and 3' untranslated regions in the ENPP1 locus harbor genetic variants affecting different aspects of craniofacial morphology. Further research is required to validate the relevancy of the potentially functional ENPP1 regions to normal and pathologic craniofacial growth.

Background: Tumor necrosis factor alpha (TNFalpha) is a cytokine involved in inflammatory, immune, and metabolic events. TNFalpha signals are mediated through activation of two receptors, one of which is tumor necrosis factor receptor TNF-RII., Objective: To examine the effects of genetic and environmental factors on TNF-RII plasma concentration and its association with polymorphisms in the TNF-RII gene locus., Methods: The levels of sTNF-RII were determined in 897 individuals. The association between sTNF-RII and polymorphisms in its structural gene locus was examined by pedigree-based association analyses (PDT) and transmission disequilibrium tests (TDTs)., Results: 49.57% of the adjusted sTNF-RII variability was attributable to genetic factors. sTNF-RII plasma levels were nominally associated with the genomic region spanning TNF-RII promoter and the first intron, represented by rs976881 (p=0.029). Although after correction for multiple testing this PDT signal formally did not reach statistical significance, it was reflected also in series of TDTs and further confirmed by association observed for haplotype of rs976881 with rs590368 (nominal p=0.006) and by ANOVA., Conclusions: sTNF-RII plasma concentration is determined by both genetic and environmental factors. Our results suggest association between sTNF-RII levels and polymorphisms in vicinity to TNF-RII promoter region. This finding requires further thorough validation in other populations., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Mineralization of the extracellular matrix of bone is an essential element of bone development, maintenance and repair. ALPL and ENPP1 genes and their products are known to be central in local regulation of bone mineralization. The present study investigates potential associations of ENPP1 and ALPL polymorphisms with several phenotypes reflecting bone size and hand BMD. The study sample included 310 Caucasian nuclear families. Forty SNPs in ALPL and 14 SNPs in ENPP1 genetic loci as well as pairwise haplotypes were tested for association with bone strength related traits. Our findings suggest that the region corresponding to exons 7 through 9 of the ALPL gene harbors functional polymorphism affecting both bone size at various skeletal sites (p-value ranged from 0.01 to 0.0001) and hand bone mineral density (p-value=0.0007). The other important finding of consistent association between bone size phenotypes and the 3' untranslated region of ENPP1 gene (p-value ranged from 0.01 to 0.001) imply functional significance of this region to bone growth. The considered anthropometric and radiographic bone phenotypes are closely related to bone fragility thus suggesting a role for both genes in osteoporosis. Further research is required to validate the relevancy of the potentially functional regions identified by our and other studies to normal and pathologic bone development as well as to determine the relevancy of the polymorphisms in ALPL and ENPP1 gene loci to clinical practice., (Copyright (c) 2009 Elsevier Inc. All rights reserved.)

Osteoarthritis (OA) is a complex, age dependent disease in which various factors, including metabolic changes, are all major contributors to its onset and progression. Anatomically, OA embraces the whole joint, i.e. articular cartilage, subchondral bone alterations and joint-lining synovial membrane. Correspondingly, OA development involves elaborate interactions of cartilaginous tissue metabolism and maintenance, osteogenesis, mineralization and inflammation of the synovial membrane. Identification of the molecular pathways and individual factors involved in OA etiology, understanding of mechanisms of their action and interaction are necessary conditions for developing the accurate diagnostic and prognostic tools and for providing OA patients effective treatment. There is a major progress in understanding of the molecular mechanisms of OA appearance and progression, which are pointing out to the network of biochemical factors important for normal functioning of the joints and changes leading to OA. The present review summarizes the data on the efficacy of the relevant biochemical factors affecting all the components of the joint and that could be therefore useful targets in treatment of OA. However, despite the dramatic growth of the knowledge concerning the biochemistry of OA and discovery of a number of useful biomarkers the real breakthrough in this area is still not achieved.

Recent genome-wide (GW) scans have identified several independent loci affecting human stature, but their contribution through the different skeletal components of height is still poorly understood. We carried out a genome-wide scan in 12,611 participants, followed by replication in an additional 7,187 individuals, and identified 17 genomic regions with GW-significant association with height. Of these, two are entirely novel (rs11809207 in CATSPER4, combined P-value = 6.1x10(-8) and rs910316 in TMED10, P-value = 1.4x10(-7)) and two had previously been described with weak statistical support (rs10472828 in NPR3, P-value = 3x10(-7) and rs849141 in JAZF1, P-value = 3.2x10(-11)). One locus (rs1182188 at GNA12) identifies the first height eQTL. We also assessed the contribution of height loci to the upper- (trunk) and lower-body (hip axis and femur) skeletal components of height. We find evidence for several loci associated with trunk length (including rs6570507 in GPR126, P-value = 4x10(-5) and rs6817306 in LCORL, P-value = 4x10(-4)), hip axis length (including rs6830062 at LCORL, P-value = 4.8x10(-4) and rs4911494 at UQCC, P-value = 1.9x10(-4)), and femur length (including rs710841 at PRKG2, P-value = 2.4x10(-5) and rs10946808 at HIST1H1D, P-value = 6.4x10(-6)). Finally, we used conditional analyses to explore a possible differential contribution of the height loci to these different skeletal size measurements. In addition to validating four novel loci controlling adult stature, our study represents the first effort to assess the contribution of genetic loci to three skeletal components of height. Further statistical tests in larger numbers of individuals will be required to verify if the height loci affect height preferentially through these subcomponents of height., Competing Interests: The authors have declared that no competing interests exist.

Background: There is a wealth of publications establishing the involvement of genetic factors in the determination of inter-individual variability of head size traits. However, little is known about the mode of inheritance of craniofacial traits in the healthy population., Aim: The aims of this study were to investigate the mode of inheritance of horizontal (HOC) and vertical (VEC) components of head dimensions, and to test the hypothesis of a common major gene for these traits., Subjects and Methods: The study was conducted on 1406 individuals belonging to 357 pedigrees. Univariate and bivariate complex segregation analyses were conducted on two principal components, HOC and VEC, extracted from 10 original head traits., Results: The hypothesis of Mendelian transmission was accepted in both studied traits. The inferred major genes explained 54.0% and 45.6% of HOC and VEC variance, adjusted for covariates. For both traits an additive mode of major gene alleles interaction was suggested. No positive evidence for a common major gene for both HOC and VEC was obtained., Conclusion: We conclude that head size in horizontal and vertical dimensions is determined by two different major genes together with modest and minor effect genes, the latter being partly shared by HOV and VEC.

Loss of bone strength is the main determinant of bone fragility. Bone strength is directly dependent on bone size (BS). A substantial portion of BS variation is attributable to genetic effects. However, the list of genes and allelic variants involved in the determination of BS variation is far from being complete. Polymorphisms in the ANKH gene have been shown to be associated with radiographic hand BS-related phenotypes. The present study examined the possible association of the ANKH gene with skeletal size and shape in order to test the universality of the ANKH effect on BS traits. Our sample consisted of a total of 212 ethnically homogeneous nuclear families (743 individuals) of European origin. Each individual was measured for body height, weight, and several other anthropometrical measurements, and genotyped for nine polymorphic markers (the average heterozygosity level was 0.4). We observed significant associations with practically all the anthropometrical phenotypes studied. More specifically, we found associations with body weight and height, limb length (P

Introduction: Bone size is an important determinant of bone strength. Although it is well established that bone size traits are under the strong genetic control, genes involved in their determination are poorly characterized. The major objective of the present study was to test hypothesis of possible association between three RUNX2 SNP polymorphisms (rs2819858, rs1406846, rs2819854) and anthropometrical femoral length (FEML). In addition, the possibility of association between anthropometrical tibial length (TIBL) and stature and chosen RUNX2 polymorphisms was tested., Materials and Methods: The study was conducted on 265 nuclear families comprised of a total of 904 individuals. DNA samples were available for 705 individuals, belonging to 212 nuclear families. Three different transmission disequilibrium tests (TDTs), population-based and pedigree-based (PDT) association analyses were implemented in order to test the working hypothesis., Results: The results unambiguously and consistently demonstrated significant association for FEML regardless of the specific polymorphism tested and type of analysis implemented. The P values obtained by TDTs ranged between 0.0155 and 0.0007. The effect of RUNX2 polymorphisms was estimated to explain 1.9% of the total FEML variation after adjustment for sex and age. The data suggested that the strength of association between RUNX2 polymorphisms and FEML may be higher in females (P = 0.007) than in males (P = 0.046), according to PDT. Conversely, no reliable evidence of association between RUNX2 polymorphisms and either TIBL or stature was found., Conclusions: For the first time, the evidence of association between RUNX2 polymorphisms and FEML was provided. The results of the present research contribute to the deeper understanding of the genetic architecture of femoral size and introduce the issues of site and sex dependency of the extent of RUNX2 effect. Further studies are required to confirm our findings, specifically focused on clinically oriented sites of skeleton, like femoral neck.

Background: It is well established that genetic factors contribute significantly to the determination of head size and shape traits variability. However, the controversies in views and findings with respect to the more specific aspects of this issue have not yet been resolved., Aim: The primary objective of the study was to examine the patterns of the intergenerational familial transmission of 12 head size related traits in a large ethnically homogeneous sample of Chuvasha pedigrees., Subjects and Methods: The research was carried out on 1406 individuals belonging to 357 nuclear and more complex families. Univariate and bivariate family-based analyses were performed to establish the pattern of head traits inheritance., Results: Maximum heritability estimates ranged from 0.52 to 0.72 for traits adjusted for significant covariates. No significant sex differences were observed with respect to the genetic determination of the studied traits. Bivariate analysis of horizontal and vertical head size components suggested the existence of common genetic and environmental factors that explained 33.0% and 23.2% of the total variance of the adjusted traits, respectively., Conclusions: A significant genetic component is involved in inter-individual variation and covariation of various studied craniofacial traits.