BINA

Calculation of temperature-dependent kinetic isotope effects (KIE) in enzymes presents a significant theoretical challenge. Additionally, it is not trivial to identify enzymes with available experimental accurate intrinsic KIEs in a range of temperatures. In the current work, we present a theoretical study of KIEs in the primitive R67 dihydrofolate reductase (DHFR) enzyme and compare with experimental work. The advantage of R67 DHFR is its significantly lower kinetic complexity compared to more evolved DHFR isoforms. We employ mass-perturbation-based path-integral simulations in conjunction with umbrella sampling and a hybrid quantum mechanics–molecular mechanics Hamiltonian. We obtain temperature-dependent KIEs in good agreement with experiments and ascribe the temperature-dependent KIEs primarily to zero-point energy effects. The active site in the primitive enzyme is found to be poorly …

The reversible and fast redox kinetics of bromine/bromide makes it a desirable couple as a catholyte in redox‐flow batteries (RFBs). In principle, the highest possible energy density is obtained with hydrogen‐bromine RFBs. Bromine sequestration agents, also called bromine complexing agents (BCAs), bind bromine in a non‐miscible phase and can, therefore, reduce the vapor pressure of bromine, mitigate its crossover, and result in higher practical range of electrolyte concentration. Therefore, BCAs can enhance the battery's safety and competitivity by significantly decreasing the cost of components. To date, BCAs are commonly used in membrane‐free bromine systems, which cannot provide the high current density demonstrated in hydrogen‐bromine RFBs. Herein, the drastic limitations encountered are shown while operating a hydrogen‐bromine RFB with a standard perfluorinated sulfonic acid membrane due …

The recent rise in the activity of platinum group metal–free oxygen reduction reaction catalysts for polymer electrolyte fuel cells, made them very interesting alternative for Pt-based catalysts. Currently, the application of this family of catalysts in fuel cells is impeded by their relatively low durability and stability. The lack of simple methods to follow the specific degradation of these catalysts in situ and in operando fuel cells inhibits durability and stability studies, where the key catalyst performance descriptor is the turnover frequency, for which the electrochemical site density needs to be accurately measured. Herein, the most commonly available techniques for measuring the active site density were surveyed, along with their advantages and disadvantages, leading to the conclusion that only electrochemical techniques such as square wave voltammetry and Fourier transform alternating current voltammetry can be used …

We designed a heterostructure of Fe3S4@ Ni3S2, as a potent oxygen evolution reaction (OER) electrocatalyst in an alkaline medium. Intriguingly, Fe3S4@ Ni3S2 exhibits low onset potential of290 mV and overpotential of 360 mV at a current density of 10 mA cm-2. We examined the OER kinetics of Fe3S4@ Ni3S2 using distribution function of relaxation times (DFRT), which are attained with the help of impedance spectroscopy genetic programming (ISGP). ISGP reveals the occurrences of three events of OER, manifested as peaks in the DFRT, such as active material or pores (P2), charge transfer (P1’), and production rate of intermediates (P1) in case of Fe3S4@ Ni3S2 at different faradic overpotentials. The effective resistance of each phenomenon can be easily calculated. It decreases with an increase in conductivity at high overpotentials for all the three, which suggests the high performance of the as-synthesized composite due to faster kinetics.

The recent rise in the activity of platinum group metal–free oxygen reduction reaction catalysts for polymer electrolyte fuel cells, made them very interesting alternative for Pt-based catalysts. Currently, the application of this family of catalysts in fuel cells is impeded by their relatively low durability and stability. The lack of simple methods to follow the specific degradation of these catalysts in situ and in operando fuel cells inhibits durability and stability studies, where the key catalyst performance descriptor is the turnover frequency, for which the electrochemical site density needs to be accurately measured. Herein, the most commonly available techniques for measuring the active site density were surveyed, along with their advantages and disadvantages, leading to the conclusion that only electrochemical techniques such as square wave voltammetry and Fourier transform alternating current voltammetry can be used …

Speckle pattern analysis has been found by many researchers to be applicable to remote sensing of various biomedical parameters. This paper shows how analysis of dynamic differential speckle patterns scattered from subjects’ sclera illuminated by a laser beam allows extraction of micro-saccades movement in the human eye. Analysis of micro-saccades movement using advanced machine learning techniques based on convolutional neural networks offers a novel approach for non-contact assessment of human blood oxygen saturation level (SpO2). Early stages of hypoxia can rapidly progress into pneumonia and death, and lives can be saved by advance remote detection of reduced blood oxygen saturation.

We study a two state “jumping diffusivity” model for a Brownian process alternating between two different diffusion constants, D+> D−, with random waiting times in both states whose distribution is rather general. In the limit of long measurement times, Gaussian behavior with an effective diffusion coefficient is recovered. We show that, for equilibrium initial conditions and when the limit of the diffusion coefficient D−⟶ 0 is taken, the short time behavior leads to a cusp, namely a non-analytical behavior, in the distribution of the displacements P (x, t) for x⟶ 0. Visually this cusp, or tent-like shape, resembles similar behavior found in many experiments of diffusing particles in disordered environments, such as glassy systems and intracellular media. This general result depends only on the existence of finite mean values of the waiting times at the different states of the model. Gaussian statistics in the long time limit is achieved due to ergodicity and convergence of the distribution of the temporal occupation fraction in state D+ to a δ-function. The short time behavior of the same quantity converges to a uniform distribution, which leads to the non-analyticity in P (x, t). We demonstrate how super-statistical framework is a zeroth order short time expansion of P (x, t), in the number of transitions, that does not yield the cusp like shape. The latter, considered as the key feature of experiments in the field, is found with the first correction in perturbation theory.

Carbon dots (CDs) were obtained from medicinal turmeric leaves (Curcuma longa) by a facile one-step hydrothermal method and evaluated for their bactericidal activities against two gram-negative; Escherichia coli, Klebsiella pneumoniae, and two gram-positive counterparts; Staphylococcus aureus, S. epidermidis. The CDs exhibited spherical shapes with a mean size of 2.6 nm. The fluorescence spectra of CDs revealed intense fluorescence at λ ex/em= 362/429 nm with a bright blue color in an aqueous solution. The CDs showed strong photostability under various environmental conditions (pH, salt, and UV-radiation). The complete bactericidal potency of CDs was 0.25 mg/mL for E. coli and S. aureus after 8 h of exposure, while for K. pneumoniae, and S. epidermidis, the CDs at 0.5 mg/mL good antibacterial effect within 8 h and complete eradication after 24 h of exposure is observed. The release of reactive oxygen species played a crucial role in the death of the bacterial cell. The present study provides a strategy for the preparation of CDs from a medicinal plant and their potential antibacterial activities against four common contagious pathogens. View Full-Text

Prophages are bacteriophages in the lysogenic state, where the viral genome is inserted within the bacterial chromosome. They contribute to strain genetic variability and can influence bacterial phenotypes. Prophages are highly abundant among the strains of the opportunistic pathogen Pseudomonas aeruginosa and were shown to confer specific traits that can promote strain pathogenicity. The main difficulty of studying those regions is the lack of a simple prophage-curing method for P. aeruginosa strains. In this study, we developed a novel, targeted-curing approach for prophages in P. aeruginosa. In the first step, we tagged the prophage for curing with an ampicillin resistance cassette (ampR) and further used this strain for the sacB counter-selection marker’s temporal insertion into the prophage region. The sucrose counter-selection resulted in different variants when the prophage-cured mutant is the sole variant that lost the ampR cassette. Next, we validated the targeted-curing with local PCR amplification and Whole Genome Sequencing. The application of the strategy resulted in high efficiency both for curing the Pf4 prophage of the laboratory wild-type (WT) strain PAO1 and for PR2 prophage from the clinical, hard to genetically manipulate, 39016 strain. We believe this method can support the research and growing interest in prophage biology in P. aeruginosa as well as additional Gram-negative bacteria.

We solve for the statistics of the first detection of a quantum system in a particular desired state, when the system is subject to a projective measurement at independent identically distributed random time intervals. We present formulas for the probability of detection in the n th attempt. We calculate as well the mean and mean square, both of the number of the first successful detection attempt and the time until first detection. We present explicit results for a particle initially localized at a site on a ring of size L, probed at some arbitrary given site, in the case when the detection intervals are distributed exponentially. We prove that, for all interval distributions and finite-dimensional Hamiltonians, the mean detection time is equal to the mean attempt number times the mean time interval between attempts. We further prove that for the return problem when the initial and target state are identical, the total detection probability is …

We demonstrate a new approach to supercontinuum generation and carrier-envelope-offset detection in dispersion-engineered nanophotonic waveguides based on saturated second-harmonic generation of femtosecond pulses. In contrast with traditional approaches based on self-phase modulation, this technique simultaneously broadens both harmonics by generating rapid amplitude modulations of the field envelopes. The generated supercontinuum produces coherent carrier-envelope-offset beatnotes in the overlap region that remain in phase across 100's of nanometers of bandwidth while requiring 10 picojoules of pulse energy.

In an effort to develop durable, corrosion-resistant catalyst support materials for polymer electrolyte fuel cells, modified polymer-assisted deposition method was used to synthesize tungsten carbide (WC, WC1–x), which was later used as a support material for Pt-based oxygen reduction reaction catalyst, as an alternative for the corrosion-susceptible, carbon supports. The Pt-deposited tungsten carbide’s corrosion-resistance, oxygen reduction reaction electrocatalysis, and durability were studied and compared to that of Pt/C. Bulk free carbon was found to be absent from the ceramic matrix which had particle size in the range of 2–25 nm. Tungsten carbide support appears to enhance the oxygen reduction activity on Pt, showing an increase in mass activity (nearly 2-fold at 0.85 V vs RHE) and specific activity (more than 7 times higher), alongside decrease in overpotential, in comparison to Pt/C. A significant increase in …

The use of CuO nanoparticles (NPs) has increased greatly and their potential effects on human health need to be investigated. Differentiated Caco‐2 cells were treated from the apical (Ap) and the basolateral (Bl) compartment with different concentrations (0, 10, 50 and 100 μg/mL) of commercial or sonochemically synthesized (sono) CuO NPs. Sono NPs were prepared in ethanol (CuOe) or in water (CuOw), obtaining CuO NPs differing in size and shape. The effects on the Caco‐2 cell barrier were assessed via transepithelial electrical resistance (TEER) evaluation just before and after 1, 2 and 24 hours of exposure and through the analysis of cytokine release and biomarkers of oxidative damage to proteins after 24 hours. Sono CuOe and CuOw NPs induced a TEER decrease with a dose‐dependent pattern after Bl exposure. Conversely, TEER values were not affected by the Ap exposure to commercial CuO NPs …

A microporous carboxylate metal-organic framework MIL-100 Fe was prepared as submicron particles by microwave-assisted hydrothermal synthesis (Fe-MOF-MW). This product was explored, for the first time, for the preparation of polylactic acid (PLA) mixed matrix membranes. The produced MOF was characterised by powder X-ray diffraction (PXRD), environmental scanning electron microscopy (ESEM) as well as by thermogravimetric analysis (TGA) and nitrogen adsorption/desorption. The effect of different Fe-MOF-MW concentrations (0.1 and 0.5 wt%) on the membrane properties and performance were evaluated. These membranes were used in the pervaporation process for the separation of methanol/methyl tert-butyl-ether mixtures at the azeotropic point. The influence of the feed temperature and vacuum pressure on the membrane performance was evaluated and the results were compared with PLA pristine membranes. Moreover, the produced membranes have been characterised in terms of morphology, MOF dispersion in the polymeric membrane matrix, wettability, thickness, mechanical resistance and swelling propensity. The presence of Fe-MOF-MW was found to have a beneficial effect in improving the selectivity of mixed matrix membranes towards methanol at both concentrations. The highest selectivity was obtained for the PLA membranes embedded with 0.5 wt% of Fe-MOF-MW and tested at the temperature of 25 C and vacuum pressure of 0.09 mbar. View Full-Text

Electron paramagnetic resonance (EPR) spectroscopy has emerged as an ideal biophysical tool to study complex biological processes. EPR spectroscopy can follow minor conformational changes in various proteins as a function of ligand or protein binding or interactions with high resolution and sensitivity. Resolving cellular mechanisms, involving small ligand binding or metal ion transfer, is not trivial and cannot be studied using conventional biophysical tools. In recent years, our group has been using EPR spectroscopy to study the mechanism underlying copper ion transfer in eukaryotic and prokaryotic systems. This mini-review focuses on our achievements following copper metal coordination in the diamagnetic oxidation state, Cu(I), between biomolecules. We discuss the conformational changes induced in proteins upon Cu(I) binding, as well as the conformational changes induced in two proteins involved in Cu(I) transfer. We also consider how EPR spectroscopy, together with other biophysical and computational tools, can identify the Cu(I)-binding sites. This work describes the advantages of EPR spectroscopy for studying biological processes that involve small ligand binding and transfer between intracellular proteins.

Narrow-bandwidth luminescent materials are already used in optoelectronic devices, superresolution, lasers, imaging, and sensing. The new-generation carbon fluorescence nanomaterials—carbon dots—have attracted considerable attention due to their advantages, such as simple operation, environmental friendliness, and good photoelectric performance. In this work, two narrower-bandwidth (21 and 30 nm) emission graphene quantum dots with long-wavelength fluorescence were successfully prepared by a one-step method, and their photoluminescence (PL) peaks were at 683 and 667 nm, respectively. These red-emitting graphene quantum dots were characterized by excitation wavelength dependence of the fluorescence lifetimes, and they were successfully applied to spectral and spatial superresolved sensing. Here, we proposed to develop an infrared spectroscopic sensing configuration based on two …

Bell’s theorem implies that any completion of quantum mechanics which uses hidden variables (that is, preexisting values of all observables) must be nonlocal in the Einstein sense. This customarily indicates that knowledge of the hidden variables would permit superluminal communication. Such superluminal signaling, akin to the existence of a preferred reference frame, is to be expected. However, here we provide a protocol that allows an observer with knowledge of the hidden variables to communicate with her own causal past, without superluminal signaling. That is, such knowledge would contradict causality, irrespectively of the validity of relativity theory. Among the ways we propose for bypassing the paradox there is the possibility of hidden variables that change their values even when the state does not, and that means that signaling backwards in time is prohibited in Bohmian mechanics. View Full-Text

The protozoan parasite Leishmania donovani causes fatal human visceral leishmaniasis in absence of treatment. Genome instability has been recognized as a driver in Leishmania fitness gain in response to environmental change or chemotherapy. How genome instability generates beneficial phenotypes despite potential deleterious gene dosage effects is unknown. Here we address this important open question applying experimental evolution and integrative systems approaches on parasites adapting to in vitro culture. Phenotypic analyses of parasites from early and late stages of culture adaptation revealed an important fitness tradeoff, with selection for accelerated growth (fitness gain) impairing infectivity (fitness costs). Comparative genomics, transcriptomics and proteomics analyses revealed a complex regulatory network driving parasite fitness, with genome instability causing highly reproducible, gene dosage-dependent changes in protein linked to post-transcriptional regulation. These in turn were associated with a gene dosage-independent reduction in flagellar transcripts and a coordinated increase in abundance of coding and non-coding RNAs known to regulate ribosomal biogenesis and protein translation. We correlated differential expression of small nucleolar RNAs (snoRNAs) with changes in rRNA modification, providing first evidence that Leishmania fitness gain may be controlled by post-transcriptional and epitranscriptomic regulation. Our findings propose a novel model for Leishmania fitness gain, where differential regulation of mRNA stability and the generation of fitness-adapted ribosomes may potentially filter deleterious …

In this work, we continued our systematic investigations on synthesis, structural studies, and electrochemical behavior of Ni-rich materials Li [Ni x Co y Mn z] O 2 (x+ y+ z= 1; x≥ 0.8) for advanced lithium-ion batteries (LIBs). We focused, herein, on LiNi 0.85 Co 0.10 Mn 0.05 O 2 (NCM85) and demonstrated that doping this material with high-charge cation Mo 6+(1 at.%, by a minor nickel substitution) results in substantially stable cycling performance, increased rate capability, lowering of the voltage hysteresis, and impedance in Li-cells with EC-EMC/LiPF 6 solutions. Incorporation of Mo-dopant into the NCM85 structure was carried out by in-situ approach, upon the synthesis using ammonium molybdate as the precursor. From X-ray diffraction studies and based on our previous investigation of Mo-doped NCM523 and Ni-rich NCM811 materials, it was revealed that Mo 6+ preferably substitutes Ni residing either in 3a or 3b sites. We correlated the improved behavior of the doped NCM85 electrode materials in Li-cells with a partial Mo segregation at the surface and at the grain boundaries, a tendency established previously in our lab for the other members of the Li [Ni x Co y Mn z] O 2 family. View Full-Text

Immunoglobulin loci are rich in germline polymorphisms and identification of novel polymorphic variants can be facilitated by germline inference of B cell receptor repertoires. Germline gene inference is complicated by somatic hypermutations, errors arising from PCR amplification, and DNA sequencing as well as from the varying length of reference alleles. Inference of light chain genes is even more challenging than inference of heavy chain genes due to large gene duplication events on the kappa locus as well as absence of D genes in the rearranged light chain transcripts. Here, we analyzed the light chain cDNA sequences from naïve BCR repertoires of a Norwegian cohort of 100 individuals. We optimized light chain allele inference by tweaking parameters within TIgGER functions, extending the germline reference sequences, and establishing mismatch frequency patterns at polymorphic positions to filter out false positive candidates. As a result, we identified 48 previously unreported variants of light chain variable genes. Altogether, we selected 14 candidates for novel light chain polymorphisms for validation and successfully validated 11 by Sanger sequencing. Additional clustering of light chain 5′UTR, L-PART1 and L-PART2 revealed partial intron retention in alternative splice variants in 11 kappa and 9 lambda V alleles. The alternatively spliced transcripts were only observed in genes with low expression levels, suggesting a possible role in expression regulation. Our results provide novel insight into germline variation in human light chain immunoglobulin loci.