Electric Scooter Injuries and Hospital Admissions in the United States, 2014-2018.

This study investigates trends of injury and hospital admission associated with electric scooter use

Multi-elemental speciation analysis of barley genotypes diering in tolerance to cadmium toxicity using SEC-ICP-MS and ESI-TOF-MS

Plants respond to Cd exposure by synthesizing heavy-metal-binding oligopeptides, called phytochelatins (PCs). These peptides reduce the activity of Cd2+ ions in the plant tissues by forming Cd chelates. The main objective of the present work was to develop an analytical technique, which allowed identication of the most prominent Cd species in plant tissue by SEC-ICP-MS and ESI-TOF-MS. An integrated part of the method development was to test the hypothesis that dierential Cd tolerance between two barley genotypes was linked to dierences in Cd speciation. Only one fraction of Cd species, ranging from 7001800 Da, was detected in the shoots of both genotypes. In the roots, two additional fractions ranging from 29004600 and 670015 000 Da were found. The Cd-rich SEC fractions were heart-cut, de-salted and demetallized using reversed-phase chromatography (RPC), followed by ESI-MS-TOF to identify the ligands. Three dierent families of PCs, viz. (gGlu-Cys)n-Gly (PCn), (gGlu-Cys)n-Ser (iso-PCn) and Cys-(gGlu-Cys)n-Gly (des-gGlu-PCn), the last lacking the N-terminal amino acid, were identied. The PCs induced by Cd toxicity also bound several essential trace elements in plants, including Zn, Cu, and Ni, whereas no Mn species were detected. Zn, Cu and Ni-species were distributed between the 7001800 Da and 670015 000 Da fractions, whereas only Cd species were found in the 29004600 Da fraction dominated by PC3 ligands. Although the total tissue concentration of Cd was similar for the two species, the tolerant barley genotype synthesized signicantly more CdPC3 species with a high Cd specicity than the intolerant genotype, clearly indicating a correlation between Cd tolerance and the CdPC speciation

Impact of surface roughness on diffusion of confined fluids

Using event-driven molecular dynamics simulations, we quantify how the self diffusivity of confined hard-sphere fluids depends on the nature of the confining boundaries. We explore systems with featureless confining boundaries that treat particle-boundary collisions in different ways and also various types of physically (i.e., geometrically) rough boundaries. We show that, for moderately dense fluids, the ratio of the self diffusivity of a rough wall system to that of an appropriate smooth-wall reference system is a linear function of the reciprocal wall separation, with the slope depending on the nature of the roughness. We also discuss some simple practical ways to use this information to predict confined hard-sphere fluid behavior in different rough-wall systems

Cofinement, entropy, and single-particle dynamics of equilibrium hard-sphere mixtures

We use discontinuous molecular dynamics and grand-canonical transition-matrix Monte Carlo simulations to explore how confinement between parallel hard walls modifies the relationships between packing fraction, self-diffusivity, partial molar excess entropy, and total excess entropy for binary hard-sphere mixtures. To accomplish this, we introduce an efficient algorithm to calculate partial molar excess entropies from the transition-matrix Monte Carlo simulation data. We find that the species-dependent self-diffusivities of confined fluids are very similar to those of the bulk mixture if compared at the same, appropriately defined, packing fraction up to intermediate values, but then deviate negatively from the bulk behavior at higher packing fractions. On the other hand, the relationships between self-diffusivity and partial molar excess entropy (or total excess entropy) observed in the bulk fluid are preserved under confinement even at relatively high packing fractions and for different mixture compositions. This suggests that the partial molar excess entropy, calculable from classical density functional theories of inhomogeneous fluids, can be used to predict some of the nontrivial dynamical behaviors of fluid mixtures in confined environments.Comment: submitted to JC

A strategic model for the simulation of drug resistance in African animal trypanosomiasis

African Animal Trypanosomiasis (AAT) is a major constraint to the productivity of African agricultural systems, both where animals are used for dairy or meat production and where traction power is needed to cultivate the land. Tsetse flies of the genus Glossina act as vectors that transport the parasitic protozoan Trypanosoma spp. between hosts. The strategy most widely used to manage the disease is application of trypanocidal drugs, but the emergence of resistance has put into question the long-term viability of their use. In certain areas of West Africa, drug resistant and drug susceptible strains of trypanosomes co-exist. When in such an area the disease prevalence is successfully reduced by removal of the majority of the tsetse vectors, the remaining numbers of diseased animals is so small that it becomes difficult to measure the impact of vector control on the development of drug resistance. Moreover, little is known about how resistance is likely to evolve if vector control is subsequently discontinued. Dynamic system models can simulate the processes that drive the dynamics of vector, host and parasite populations. Such models can increase our understanding of the diseases dynamics even in situations where empirical measurement is problematic. We describe a model in which cattle hosts are represented as individuals. Cattle can be infected by a drug resistant or drug susceptible strain of the pathogen, or a mix of both. Tsetse flies, represented as cohorts, can spread disease between hosts. The model incorporates processes that potentially alter the ratio of drug resistant to drug susceptible trypanosomes, such as reaction to medication, and keeps track of the proportions of drug resistance and drug susceptible strains in the trypanosome population. The model is strategic in the sense that it doesn't attempt to represent a particular situation in a particular region, but more generally aims to improve our understanding of a situation in which empirical science is constrained

The Origin of Primordial Dwarf Stars and Baryonic Dark Matter

I present a scenario for the production of low mass, degenerate dwarfs of mass $>0.1 M_{\odot}$ via the mechanism of Lenzuni, Chernoff & Salpeter (1992). Such objects meet the mass limit requirements for halo dark matter from microlensing surveys while circumventing the chemical evolution constraints on normal white dwarf stars. I describe methods to observationally constrain this scenario and suggest that such objects may originate in small clusters formed from the thermal instability of shocked, heated gas in dark matter haloes, such as suggested by Fall & Rees (1985) for globular clusters.Comment: TeX, 4 pages plus 2 postscript figures. To appear in Astrophysical Journal Letter

Anticancer Therapy with HDAC Inhibitors: Mechanism-Based Combination Strategies and Future Perspectives

The increasing knowledge of molecular drivers of tumorigenesis has fueled targeted cancer therapies based on specific inhibitors. Beyond “classic” oncogene inhibitors, epigenetic therapy is an emerging field. Epigenetic alterations can occur at any time during cancer progression, altering the structure of the chromatin, the accessibility for transcription factors and thus the transcription of genes. They rely on post-translational histone modifications, particularly the acetylation of histone lysine residues, and are determined by the inverse action of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Importantly, HDACs are often aberrantly overexpressed, predominantly leading to the transcriptional repression of tumor suppressor genes. Thus, histone deacetylase inhibitors (HDACis) are powerful drugs, with some already approved for certain hematological cancers. Albeit HDACis show activity in solid tumors as well, further refinement and the development of novel drugs are needed. This review describes the capability of HDACis to influence various pathways and, based on this knowledge, gives a comprehensive overview of various preclinical and clinical studies on solid tumors. A particular focus is placed on strategies for achieving higher efficacy by combination therapies, including phosphoinositide 3-kinase (PI3K)-EGFR inhibitors and hormone- or immunotherapy. This also includes new bifunctional inhibitors as well as novel approaches for HDAC degradation via PROteolysis-TArgeting Chimeras (PROTACs)