Theoretical studies of oxygen diffusion in face-centered cubic matrices of xenon, argon, and krypton

Analytical Chemistr

Whole Animal Automated Platform for Drug Discovery against Multi-Drug Resistant Staphylococcus aureus

Staphylococcus aureus, the leading cause of hospital-acquired infections in the United States, is also pathogenic to the model nematode Caenorhabditis elegans. The C. elegans-S. aureus infection model was previously carried out on solid agar plates where the bacteriovorous C. elegans feeds on a lawn of S. aureus. However, agar-based assays are not amenable to large scale screens for antibacterial compounds. We have developed a high throughput liquid screening assay that uses robotic instrumentation to dispense a precise amount of methicillin resistant S. aureus (MRSA) and worms in 384-well assay plates, followed by automated microscopy and image analysis. In validation of the liquid assay, an MRSA cell wall defective mutant, MW2ΔtarO, which is attenuated for killing in the agar-based assay, was found to be less virulent in the liquid assay. This robust assay with a Z’-factor consistently greater than 0.5 was utilized to screen the Biomol 4 compound library consisting of 640 small molecules with well characterized bioactivities. As proof of principle, 27 of the 30 clinically used antibiotics present in the library conferred increased C. elegans survival and were identified as hits in the screen. Surprisingly, the antihelminthic drug closantel was also identified as a hit in the screen. In further studies, we confirmed the anti-staphylococcal activity of closantel against vancomycin-resistant S. aureus isolates and other Gram-positive bacteria. The liquid C. elegans – S. aureus assay described here allows screening for anti-staphylococcal compounds that are not toxic to the host

Third Bose Fugacity Coefficient in One Dimension, as a Function of Asymptotic Quantities

In one of the very few exact quantum mechanical calculations of fugacity coefficients, Dodd and Gibbs (\textit{J. Math.Phys}.,\textbf{15}, 41 (1974)) obtained $b_{2}$ and $b_{3}$ for a one dimensional Bose gas, subject to repulsive delta-function interactions, by direct integration of the wave functions. For $b_{2}$, we have shown (\textit{Mol. Phys}.,\textbf{103}, 1301 (2005)) that Dodd and Gibbs' result can be obtained from a phase shift formalism, if one also includes the contribution of oscillating terms, usually contributing only in 1 dimension. Now, we develop an exact expression for $b_{3}-b_{3}^{0}$ (where $b_{3}^{0}$ is the free particle fugacity coefficient) in terms of sums and differences of 3-body eigenphase shifts. Further, we show that if we obtain these eigenphase shifts in a distorted-Born approximation, then, to first order, we reproduce the leading low temperature behaviour, obtained from an expansion of the two-fold integral of Dodd and Gibbs. The contributions of the oscillating terms cancel. The formalism that we propose is not limited to one dimension, but seeks to provide a general method to obtain virial coefficients, fugacity coefficients, in terms of asymptotic quantities. The exact one dimensional results allow us to confirm the validity of our approach in this domain.Comment: 29 page

Effects of Vitamin D Supplementation on a Deep Learning-Based Mammographic Evaluation in SWOG S0812

Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20 000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was not statistically significantly different between vitamin D and placebo groups at 12 months (0.005 vs 0.002, P = .875) or at 24 months (0.020 vs 0.001, P = .563). The findings are consistent with the primary analysis of S0812, which did not demonstrate statistically significant changes in mammographic density with vitamin D supplementation compared with placebo. There is an ongoing need to evaluate biomarkers of response to novel breast cancer chemopreventive agents

Challenges to adaptation: a fundamental concept for the shared socio-economic pathways and beyond

The framework for the new scenarios being developed for climate research calls for the development of a set of Shared Socioeconomic Pathways (SSPs), which are meant to differ in terms of their challenges to mitigation and challenges to adaptation. In order for the scenario process to fulfill its goals, the research and policy communities need to develop a shared understanding of these concepts. This paper focuses on challenges to adaptation. We begin by situating this new concept in the context of the rich literatures related to inter alia adaptation, vulnerability, and resilience. We argue that a proper characterization of challenges to adaptation requires a rich, exploration of the concept, which goes beyond mere description. This has a number of implications for the operationalization of the concept in the basic and extended versions of the SSPs. First, the elements comprising challenges to adaptation must include a wide range of socioeconomic and even some (non-climatic) biophysical factors. Second, careful consideration must be given to differences in these factors across scales, as well as cross-scale interactions. Third, any representation of the concept will require both quantitative and qualitative elements. The scenario framework offers the opportunity for the SSPs and full scenarios to be of greater value than has been the case in past exercises to both Integrated Assessment Modeling (IAM) and Impacts,Adaptation, and Vulnerability (IAV) researchers, but this will require a renegotiation of the traditional, primarily unidirectional relationship between the two communities

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Ecosystem Processes and Human Influences Regulate Streamflow Response to Climate Change at Long-Term Ecological Research Sites

Analyses of long-term records at 35 headwater basins in the United States and Canada indicate that climate change effects on streamflow are not as clear as might be expected, perhaps because of ecosystem processes and human influences. Evapotranspiration was higher than was predicted by temperature in water-surplus ecosystems and lower than was predicted in water-deficit ecosystems. Streamflow was correlated with climate variability indices (e.g., the El Nino Southern Oscillation, the Pacific Decadal Oscillation, the North Atlantic Oscillation), especially in seasons when vegetation influences are limited. Air temperature increased significantly at 17 of the 19 sites with 20- to 60-year records, but streamflow trends were directly related to climate trends (through changes in ice and snow) at only 7 sites. Past and present human and natural disturbance, vegetation succession, and human water use can mimic, exacerbate, counteract, or mask the effects of climate change on streamflow, even in reference basins. Long-term ecological research sites are ideal places to disentangle these processes

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly