Automated Estimation of Aquifer Parameters from Arbitrary-Rate Pumping Tests in Python and MATLAB.

Inspired by the analysis by Mishra et al. (2012) of variable pumping rate tests using piecewise-linear reconstructions of the pumping history, this article contains a derivation of the convolutional form of pumping tests in which the pumping history may take any possible form. The solution is very similar to the classical Theis (1935) equation but uses the Green's function for a pumped aquifer given by taking the time derivative of the well function W ( u ( t ) ) . This eliminates one integration inside another and renders the convolution including the pumping history about as computationally demanding as calculating the well function alone, so that the convolution can be completed using handy mathematical software. It also allows nonlinear well losses, and because an easily-computed deterministic model exists for all data points and pumping history, an objective function may include all data, so that errors are reduced in calculating any nonlinear-well losses. In addition, data from multiple observation wells may be used simultaneously in the inversion. We provide codes in MATLAB and Python to solve for drawdown resulting from an arbitrary pumping history and compute the optimal aquifer parameters to fit the data. We find that the subtleties in parameter dependencies and constructing an appropriate objective function have a substantial effect on the interpreted parameters. Furthermore, the optimization from step-drawdown tests is typically nonunique and strongly suggests that a Bayesian inversion should be used to fully estimate the joint probability density of the parameter vector.

The N-terminal intrinsically disordered region of Ncb5or docks with the cytochrome b5 core to form a helical motif that is of ancient origin.

NADH cytochrome b5 oxidoreductase (Ncb5or) is a cytosolic ferric reductase implicated in diabetes and neurological conditions. Ncb5or comprises cytochrome b5 (b5 ) and cytochrome b5 reductase (b5 R) domains separated by a CHORD-Sgt1 (CS) linker domain. Ncb5or redox activity depends on proper inter-domain interactions to mediate electron transfer from NADH or NADPH via FAD to heme. While full-length human Ncb5or has proven resistant to crystallization, we have succeeded in obtaining high-resolution atomic structures of the b5 domain and a construct containing the CS and b5 R domains (CS/b5 R). Ncb5or also contains an N-terminal intrinsically disordered region of 50 residues that has no homologs in other protein families in animals but features a distinctive, conserved L34 MDWIRL40 motif also present in reduced lateral root formation (RLF) protein in rice and increased recombination center 21 in baker's yeast, all attaching to a b5 domain. After unsuccessful attempts at crystallizing a human Ncb5or construct comprising the N-terminal region naturally fused to the b5 domain, we were able to obtain a high-resolution atomic structure of a recombinant rice RLF construct corresponding to residues 25-129 of human Ncb5or (52% sequence identity; 74% similarity). The structure reveals Trp120 (corresponding to invariant Trp37 in Ncb5or) to be part of an 11-residue α-helix (S116 QMDWLKLTRT126 ) packing against two of the four helices in the b5 domain that surround heme (α2 and α5). The Trp120 side chain forms a network of interactions with the side chains of four highly conserved residues corresponding to Tyr85 and Tyr88 (α2), Cys124 (α5), and Leu47 in Ncb5or. Circular dichroism measurements of human Ncb5or fragments further support a key role of Trp37 in nucleating the formation of the N-terminal helix, whose location in the N/b5 module suggests a role in regulating the function of this multi-domain redox enzyme. This study revealed for the first time an ancient origin of a helical motif in the N/b5 module as reflected by its existence in a class of cytochrome b5 proteins from three kingdoms among eukaryotes.

Role of global public sector research in discovering new drugs and vaccines.

Analysis of international public-sector contributions to Food and Drug Administration (FDA)-approved drugs and vaccines allows for a more thorough examination of the global biomedical innovation ecosystem by institution of origin. Using new and existing methods, we have identified 364 FDA-approved drugs and vaccines approved from 1973 to 2016 discovered in whole or in part by Public Sector Research Institutions (PSRIs) worldwide. We identified product-specific intellectual property contributions to FDA-approved small molecule and biologic drugs and vaccines from the FDA Orange Book, our peer network, published studies, and three new sources: reports of medical product manufacturers' payments to physicians and teaching hospitals under The Sunshine Act of 2010, a paper by Kneller and 64 royalty monetization transactions by academic institutions and/or their faculty that one of us (AS) maintains. We include a total of 293 drugs discovered either wholly by a US PSRI or jointly by a U.S. and a non-U.S. PSRI. 119 FDA-approved drugs and vaccines were discovered by PSRIs outside the U.S. Of these, 71 were solely discovered outside the US, while 48 also involved intellectual property contributions by US PSRIs. In the context of the global public sector landscape, the US dominates drug discovery, accounting for two-thirds of these drugs and many of the important, innovative vaccines introduced over the past 30 years. Contributions by Canada, UK, Germany, Belgium, Japan, and others each amount to 5.4% or less of the total. Supplementary Information: The online version contains supplementary material available at 10.1007/s10961-023-10007-z.

A Review on Electric and Fuel Cell Vehicle Anatomy, Technology Evolution and Policy Drivers towards EVs and FCEVs Market Propagation.

The transportation sector is the largest consumer of fossil fuels; making it a major producer of greenhouse gases. Due to declining fossil fuel reserves and increasingly stringent vehicle emission regulations globally, it is essential to shift to alternative energy sources. Economic and eco-friendly fuel-efficient hybrid, electric, and fuel cell vehicles are regarded as one of the best alternative solutions to cope with the government policies and to reduce the rise in global temperature caused by the automotive sector. Technological advancements in fuel cells, batteries, and chargers have further supported the development of electric vehicles. The major challenges of range and charging time in electric vehicles can be countered by range extension technology and developing all-electric hybrid vehicles. In this review, a comprehensive study of different type of vehicles and their architectures are presented. Insights on energy storage devices and converters of electric vehicles currently in use were also provided. Furthermore, various fuel cell advancements and the technical challenges faced during the commercialization of fuel cell vehicles were highlighted.

Effect of actinorhizal root exudates on the proteomes of Frankia soli NRRL B-16219, a strain colonizing the root tissues of its actinorhizal host via intercellular pathway.

Frankia and actinorhizal plants exchange signals in the rhizosphere leading to specific mutual recognition of partners and nitrogen-fixing nodule organogenesis. Frankia soli strain NRRL B-16219, from the Elaeagnus specificity group, colonizes the root tissues of its actinorhizal host through direct intercellular penetration of root epidermis cells and cortex. Here, we studied the early proteogenomic response of strain NRRL B-16219 to treatment with root exudates from compatible Elaeagnus angustifolia, and incompatible Ceanothus thyrsiflorus and Coriaria myrtifolia, host plants grown in nitrogen depleted hydroponic medium. Next-generation proteomics was used to identify the main Frankia proteins differentially expressed in response to the root exudates. No products of the nod genes present in B-16219 were detected. Proteins specifically upregulated in presence of E. angustifolia root exudates include those connected to nitrogen fixation and assimilation (glutamate synthetase, hydrogenase and squalene synthesis), respiration (oxidative phosphorylation and citric acid cycle pathways), oxidative stress (catalase, superoxide dismutase, and peroxidase), proteolysis (proteasome, protease, and peptidase) and plant cell wall degrading proteins involved in the depolymerization of celluloses (endoglucanase, glycosyltransferase, beta-mannanases, glycoside hydrolase and glycosyl hydrolase). Proteomic data obtained in this study will help link signaling molecules/factors to their biosynthetic pathways once those factors have been fully characterized.

Emplacement of screen-printed graphene oxide coating for building thermal comfort discernment.

This study demonstrates the development of flexible graphene oxide coatings (GOCs) by the screen-printed technique and further its implementation as a thermal absorber for buildings' thermal comfort purpose. The basic concept consists the integration of the GOC as a flat absorber on the top of a low iron glass or aluminium-based substrate (5 × 5 cm2) connecting through a phase change material channel in contact with direct sun exposure. The function of GOC as an outdoor cover of the prototype chamber is to maintain the high indoor temperature while the outdoor temperature is low. Using the GOC, it has been observed that the indoor temperature (at the substrate) of the prototype chamber always remains higher as compared to the outdoor temperature (at the GOC) as measured under 1 SUN 1.5 AM condition. The temperature difference between outdoor and indoor exterior surface significantly increases during the light exposure time, whereas the difference drastically approaches to zero during the cooling period. The variation of different crucial environmental factors such as high temperature, moisture, flexibility and water resistivity has been investigated on the developed GOCs to understand the stability of the coating further.

Reactive particle-tracking solutions to a benchmark problem on heavy metal cycling in lake sediments.

Geochemical systems are known to exhibit highly variable spatiotemporal behavior. This may be observed both in non-smooth concentration curves in space for a single sampling time and also in variability between samples taken from the same location at different times. However, most models that are designed to simulate these systems provide only single-solution smooth curves and fail to capture the noise and variability seen in the data. We apply a recently developed reactive particle-tracking method to a system that displays highly complex geochemical behavior. When the method is made to most closely resemble a corresponding Eulerian method, in its unperturbed form, we see near-exact match between solutions of the two models. More importantly, we consider two approaches for perturbing the model and find that the spatially-perturbed condition is able to capture a greater degree of the variability present in the data. This method of perturbation is a task to which particle methods are uniquely suited and Eulerian models are not well-suited. Additionally, because of the nature of the algorithm, noisy spatial gradients can be highly resolved by a large number of mobile particles, and this incurs negligible computational cost, as compared to expensive chemistry calculations.

Fast-changing life-styles and ecotoxicity of hair dyes drive the emergence of hidden toxicants threatening environmental sustainability in Asia.

The practice of hair dyeing is a rapidly expanding industry on a global scale; however, it has become a major concern for Asian countries because they have been undergoing rapid transformations of their environment and lifestyles. While the socio-economic benefits and impacts of this globalization trend are widely understood, the environmental effects are largely unknown. In particular, commonly available oxidative dyes potentially pose specific environmental risks due to their use of a toxic aromatic amine p-Phenylenediamine (PPD). In investigating the environmental impacts of PPD chemicals, we first provide context to the study by setting out the socio-psychological drivers to industrial expansion in Asian countries along with an overview of research into its effects, to show that its environmental impacts are under-researched. We then investigate the environmental toxicity of PPD by focusing on the role of microbes in metabolizing waste products. Results show that Acinetobacter baumannii EB1 isolated from dye effluent prevents autoxidation of PPD under oxygen-enriched (shaking) or oxygen-deficient (static) conditions representing different environmental settings. Microbes transformed PPD into more toxic metabolites, which then significantly reduced plant growth, thereby having a direct bearing on ecosystem services. Based on the findings, we argue that stricter regulatory controls on hair dye wastewater are necessary, particularly in newly industrialising Asian countries where the expansion of commercial practice is most prevalent.

Crystal structures of the naturally fused CS and cytochrome b5 reductase (b5R) domains of Ncb5or reveal an expanded CS fold, extensive CS-b5R interactions and productive binding of the NAD(P)+ nicotinamide ring.

Ncb5or (NADH-cytochrome b5 oxidoreductase), a cytosolic ferric reductase implicated in diabetes and neurological diseases, comprises three distinct domains, cytochrome b5 (b5) and cytochrome b5 reductase (b5R) domains separated by a CHORD-Sgt1 (CS) domain, and a novel 50-residue N-terminal region. Understanding how interdomain interactions in Ncb5or facilitate the shuttling of electrons from NAD(P)H to heme, and how the process compares with the microsomal b5 (Cyb5A) and b5R (Cyb5R3) system, is of interest. A high-resolution structure of the b5 domain (PDB entry 3lf5) has previously been reported, which exhibits substantial differences in comparison to Cyb5A. The structural characterization of a construct comprising the naturally fused CS and b5R domains with bound FAD and NAD+ (PDB entry 6mv1) or NADP+ (PDB entry 6mv2) is now reported. The structures reveal that the linker between the CS and b5R cores is more ordered than predicted, with much of it extending the ß-sandwich motif of the CS domain. This limits the flexibility between the two domains, which recognize one another via a short ß-sheet motif and a network of conserved side-chain hydrogen bonds, salt bridges and cation-π interactions. Notable differences in FAD-protein interactions in Ncb5or and Cyb5R3 provide insight into the selectivity for docking of their respective b5 redox partners. The structures also afford a structural explanation for the unusual ability of Ncb5or to utilize both NADH and NADPH, and represent the first examples of native, fully oxidized b5R family members in which the nicotinamide ring of NAD(P)+ resides in the active site. Finally, the structures, together with sequence alignments, show that the b5R domain is more closely related to single-domain Cyb5R proteins from plants, fungi and some protists than to Cyb5R3 from animals.

19th International Meeting on Frankia and Actinorhizal Plants.

It has been 40 years since the first meeting dedicated to Frankia and actinorhizal plants, which was held at Petersham, Massachusetts (reported in Torrey and Tjepkema, 1979). Since then biennial meetings have been organised and held in different venues around the globe (Table 1). The most recent meeting, the "19th International Meeting on Frankia and Actinorhizal Plants", organised in Hammamet, Tunisia from 17th to 19th of March, 2018, gathered scientists from Algeria, Argentina, Belgium, China, Egypt, France, India, Portugal, Senegal, Sweden, UK, USA and Tunisia. The event was a stimulating opportunity for active researchers to share many advances since the previous meeting held in Montpellier, France (Franche et al. 2016) and to discuss new perspectives in this research field.

Protein oxidation involved in Cys-Tyr post-translational modification.

Some post-translationally modified tyrosines can perform reversible redox chemistry similar to metal cofactors. The most studied of these tyrosine modifications is the intramolecular thioether-crosslinked 3'-(S-cysteinyl)-tyrosine (Cys-Tyr) in galactose oxidase. This Cu-mediated tyrosine modification in galactose oxidase involves direct electron transfer (inner-sphere) to the coordinated tyrosine. Mammalian cysteine dioxygenase enzymes also contain a Cys-Tyr that is formed, presumably, through outer-sphere electron transfer from a non-heme iron center ~6Å away from the parent residues. An orphan protein (BF4112), amenable to UV spectroscopic characterization, has also been shown to form Cys-Tyr between Tyr 52 and Cys 98 by an adjacent Cu2+ ion-loaded, mononuclear metal ion binding site. Native Cys-Tyr fluorescence under denaturing conditions provides a more robust methodology for Cys-Tyr yield determination. Cys-Tyr specificity, relative to 3,3'-dityrosine, was provided in this fluorescence assay by guanidinium chloride. Replacing Tyr 52 with Phe or the Cu2+ ion with a Zn2+ ion abolished Cys-Tyr formation. The Cys-Tyr fluorescence-based yields were decreased but not completely removed by surface Tyr mutations to Phe (Y4F/Y109F, 50%) and Cys 98 to Ser (25%). The small absorbance and fluorescence emission intensities for C98S BF4112 were surprising until a significantly red-shifted emission was observed. The red-shifted emission spectrum and monomer to dimer shift seen by reducing, denaturing SDS-PAGE demonstrate a surface tyrosyl radical product (dityrosine) when Cys 98 is replaced with Ser. These results demonstrate surface tyrosine oxidation in BF4112 during Cys-Tyr formation and that protein oxidation can be a significant side reaction in forming protein derived cofactors.

Clinical and financial implications of emergency department visits for synthetic marijuana.

BACKGROUND: Many users believe that synthetic cannabinoids offer a safe and legal means of getting high. However, spikes in emergency department visits have been associated with use of synthetic cannabinoids. The purpose of the current study was to document emergency department visits from three large hospitals in one metropolitan area over a two month period. METHOD: This was a retrospective chart review examining 218 patients presenting to three inner city emergency departments between March and April 2014. Data collected included demographic information, information regarding ED diagnosis and treatment, signs and symptoms, ancillary testing, ED disposition, and cost of the medical treatment. RESULTS: The majority of patients (75.7%) were discharged after ED workup, but 12.4% were admitted for medical treatment and 11.5% were admitted for psychiatric treatment. Ten patients (4.6%) were admitted to the ICU. Symptoms experienced most frequently include: hypertension, tachycardia, agitation, drowsiness, nausea, and confusion. Cluster analysis revealed four symptom clusters of individuals presenting after using synthetic cannabinoids: 1) confusion, hostility, agitation, 2) nausea, vomiting, abdominal pain, 3) drowsiness, and 4) the absence of these symptoms. CONCLUSION: This study has three important findings. First, significant ED resources are being used to treat individuals presenting due to effects of synthetic cannabis. Second, synthetic cannabis is not a benign substance. Third, while the hostile and agitated user is generally presented in the media, this study finds significant heterogeneity in presentation. Further research is needed to fully understand the implications of synthetic cannabinoid use.

Enhanced Kinetics of Electrochemical Hydrogen Uptake and Release by Palladium Powders Modified by Electrochemical Atomic Layer Deposition.

Electrochemical atomic layer deposition (E-ALD) is a method for the formation of nanofilms of materials, one atomic layer at a time. It uses the galvanic exchange of a less noble metal, deposited using underpotential deposition (UPD), to produce an atomic layer of a more noble element by reduction of its ions. This process is referred to as surface limited redox replacement and can be repeated in a cycle to grow thicker deposits. It was previously performed on nanoparticles and planar substrates. In the present report, E-ALD is applied for coating a submicron-sized powder substrate, making use of a new flow cell design. E-ALD is used to coat a Pd powder substrate with different thicknesses of Rh by exchanging it for Cu UPD. Cyclic voltammetry and X-ray photoelectron spectroscopy indicate an increasing Rh coverage with increasing numbers of deposition cycles performed, in a manner consistent with the atomic layer deposition (ALD) mechanism. Cyclic voltammetry also indicated increased kinetics of H sorption and desorption in and out of the Pd powder with Rh present, relative to unmodified Pd.

Testing the limits of the spatial Markov model for upscaling transport: The role of nonmonotonic effective velocity autocorrelations.

The spatial Markov model is a Lagrangian random walk model, widely and successfully used for upscaling transport in heterogeneous flows across a broad range of problems. It is particularly useful at early or pre-asymptotic times when many other conventional upscaling approaches may not be valid. However, as with all upscaled models, it must have its limits. In particular, the question of what the smallest scale at which it can be legitimately applied, without violating implicit assumptions, remains. Here we address this issue by considering one of the most classical transport upscaling problems: Taylor dispersion in a bounded shear flow. We demonstrate that the smallest scale for the spatial Markov model depends on the transverse width of the domain, the variability of the flow field as quantified by a coefficient of variation, and the competition of longitudinal and transverse diffusion coefficients. We show that this scale is a factor of the Peclet number smaller than the classical Taylor dispersion scale, meaning that for advection-dominated systems where Peclet numbers are large, this model can be applied at much smaller scales than classical Taylor-Aris dispersion theories.

Multiple scales of shock waves in dissipative laminate materials.

The shock waves generated by a plate impact are numerically investigated in Al-W laminates with different mesostructures. The main characteristic time scales (and the corresponding spatial scales) related to the formation of the stationary shock are identified: the duration (width) of the leading front, the time (distance) from the impact required to establish a stationary profile, and the shock front width, identified as a time span (distance) from the initial state to the final quasiequilibrium state. It is demonstrated that the width of the leading front and the maximum strain rates are determined by the dispersive and the nonlinear parameters of the laminate and not by the dissipation, as is the case for uniform solids. The characteristic spatial scale of the leading front is related to the spatial scale observed on solitarylike waves, which are satisfactorily described by the Korteweg-de Vries (KdV) approximation, as well as the speed of the wave and the ratio of maximum to final strain. The dissipation affects the width of the transition distance (shock front width) where multiple loading-unloading cycles bring the laminate into the final quasiequilibrium state. This spatial scale is of the same order of magnitude as the distance to form stationary shock wave. The period of fast decaying oscillations is well described by the KdV approach and scales linearly with the cell size. The rate of the decay of the oscillations in the numerical calculations does not scale with the square of the cell size as expected from the dissipative KdV approach that assumes a constant viscosity. This is due to the different mechanisms of dissipation in high-amplitude compression pulses.

Visual H2 sensor for monitoring biodegradation of magnesium implants in vivo.

A visual sensor for H2 was used to transdermally monitor H2 that originated from biodegrading magnesium (Mg) alloys implanted subcutaneously in mice. The visual sensor consisted of a thin film of H2-sensitive material (MoO3 and Pd catalyst) coated on a flexible plastic sheet that was pressed against the mouse skin directly above the implant. Although the H2 levels permeating through the skin during the degradation process were very low, the sensor changed color to give a three dimensional (3D) visualization of H2 permeation. The correlation between the visual sensor response and measurements made with an electrochemical H2 microsensor on several magnesium alloys demonstrates that the visual sensor has the capability to monitor in real-time the dissolution rate of implants in vivo. This detection method is noninvasive, easy to implement, effective and potentially low cost compared to electrochemical detection. STATEMENT OF SIGNIFICANCE: Biodegradable Mg implants offer advantages over permanent implants such as stainless steel that are used for broken bone repair. Mg alloys gradually dissolve, avoiding the need for removal by a later surgery if complications arise. Here we report a visual H2 sensor that can be used in the research laboratory to monitor the corrosion process in vivo during animal testing of different Mg alloys. The sensor consists of a plastic sheet with a thin coating that changes color in the presence of H2 gas. The sensor is easily used by taping it on the skin over the Mg implant. The color change gives a map of the H2 level permeating from the degrading Mg through the skin above it. This low cost, simple method of monitoring the dissolution of biodegradable implants would greatly facilitate the development of the biodegradable materials, especially in animal studies where in vivo biodegradation is tested.

Single-Molecule FRET States, Conformational Interchange, and Conformational Selection by Dye Labels in Calmodulin.

We investigate the roles of measurement time scale and the nature of the fluorophores in the FRET states measured for calmodulin, a calcium signaling protein known to undergo pronounced conformational changes. The measured FRET distributions depend markedly on the measurement time scale (nanosecond or microsecond). Comparison of FRET distributions measured by donor fluorescence decay with FRET distributions recovered from single-molecule burst measurements binned over time scales of 90 µs to 1 ms reveals conformational averaging over the intervening time regimes. We find further that, particularly in the presence of saturating Ca(2+), the nature of the measured single-molecule FRET distribution depends markedly on the identity of the FRET pair. The results suggest interchange between conformational states on time scales of hundreds of microseconds or less. Interaction with a fluorophore such as the dye Texas Red alters both the nature of the measured FRET distributions and the dynamics of conformational interchange. The results further suggest that the fluorophore may not be merely a benign reporter of protein conformations in FRET studies, but may in fact alter the conformational landscape.

Nature of short, high-amplitude compressive stress pulses in a periodic dissipative laminate.

We study the evolution of high-amplitude stress pulses in periodic dissipative laminates taking into account the nonlinear constitutive equations of the components and their dissipative behavior. Aluminum-tungsten laminate was selected due to the large difference in acoustic impedances of components, the significant nonlinearity of the aluminum constitutive equation at the investigated range of stresses, and its possible practical applications. Laminates with different cell size, which controls the internal time scale, impacted by plates with different thicknesses that determine the incoming pulse duration, were investigated. It has been observed that the ratio of the duration of the incoming pulse to the internal characteristic time determines the nature of the high-amplitude dissipative propagating waves-a triangular oscillatory shock-like profile, a train of localized pulses, or a single localized pulse. These localized quasistationary waves resemble solitary waves even in the presence of dissipation: The similar pulses emerged from different initial conditions, indicating that they are inherent properties of the corresponding laminates; their characteristic length scale is determined by the scale of mesostructure, nonlinear properties of materials, and the stress amplitude; and a linear relationship exists between their speed and amplitude. They mostly recover their shapes after collision with phase shift. A theoretical description approximating the shape, length scale, and speed of these high-amplitude dissipative pulses was proposed based on the Korteweg-de Vries equation with a dispersive term determined by the mesostructure and a nonlinear term derived using Hugoniot curves of components.

Predicting the enhancement of mixing-driven reactions in nonuniform flows using measures of flow topology.

The ability for reactive constituents to mix is often the key limiting factor for the completion of reactions across a huge range of scales in a variety of media. In flowing systems, deformation and shear enhance mixing by bringing constituents into closer proximity, thus increasing reaction potential. Accurately quantifying this enhanced mixing is key to predicting reactions and typically is done by observing or simulating scalar transport. To eliminate this computationally expensive step, we use a Lagrangian stochastic framework to derive the enhancement to reaction potential by calculating the collocation probability of particle pairs in a heterogeneous flow field accounting for deformations. We relate the enhanced reaction potential to three well known flow topology metrics and demonstrate that it is best correlated to (and asymptotically linear with) one: the largest eigenvalue of the (right) Cauchy-Green tensor.