Recent advances in molecular simulations have allowed scientists to investigate slower biological processes than ever before. Together with these advances came an explosion of data that has ...transformed a traditionally computing-bound into a data-bound problem. Here, we present HTMD, a programmable, extensible platform written in Python that aims to solve the data generation and analysis problem as well as increase reproducibility by providing a complete workspace for simulation-based discovery. So far, HTMD includes system building for CHARMM and AMBER force fields, projection methods, clustering, molecular simulation production, adaptive sampling, an Amazon cloud interface, Markov state models, and visualization. As a result, a single, short HTMD script can lead from a PDB structure to useful quantities such as relaxation time scales, equilibrium populations, metastable conformations, and kinetic rates. In this paper, we focus on the adaptive sampling and Markov state modeling features.
Currently, US unemployment claims have skyrocketed to 30 million in the past six weeks, continuing in a stark upward trend, and labor economists estimate the unemployment rate at minimally 18.3%. ...These unemployment figures are a feature of the COVID-19 recession that is characterized by sharp gross domestic product (GDP) growth decline. Despite the greatly damaging impact of the opioid crisis over 2015 to 2017 resulting in a decrease in life expectancy over these three years, the long-term increases in average GDP per capita from 1999 to 2018 managed to save lives on average (i.e., age-adjusted mortality rates declined in the United States). For example, during 1999 to 2018, the average GDP per capita annually increased 1.2%, whereas the related age-adjusted mortality rate has shown an annual decrease of approximately 1% on average (0.99%). However, recessions erase some of this beneficial effect of GDP growth on mortality reduction.1The legislated relief measures have challenged the dichotomy between either combating the COVID-19 pandemic or concentrating on economic recovery. Similarly, an epidemic of chronic disease, mental illness, and mortality is a potential consequence of the COVID-19- related recession. This can be hypothesized considering both primary health care use decline and stress-induced illness likely to result from short- and long-term unemployment, including loss of income and employer-based health insurance as well as the destruction of wealth.These corollary effects of major economic distress need to be distinguished from the anxiety, fear, and depression that have arisen from the pandemic itself and its widespread mental health consequences. The supervening corollary public health outcomes are expected to be generated by unemployment, poverty, prevailing health disparities, and a decline in access to health care resulting from the COVID-19 economic breakdown. Public policy experts have already sounded the alarm, questioning whether the $2 trillion relief package as well as planned additional measures will be sufficient to stem the tide of economic shock, sharp GDP decline, and projected long-term damage to livelihoods. However, although the priority is to contain the spread of COVID-19, public health officials need to anticipate and plan for the potential health impact of the recession that results from the pandemic.
To determine whether unemployment and bankruptcy rates are related to increased excess deaths during the COVID-19 recession and to examine whether the current recession-based mortality rate not only ...is dependent on COVID-19 but also continues the pattern of recessions, especially the Great Recession, in relation to chronic disease mortality rates and mental health disturbances (e.g., including suicide) from 2000 to 2018.
This study used pooled cross-sectional time series analysis to determine the impact of unemployment and bankruptcy rates on excess deaths from February to November 2020 for US states. The study used a second pooled cross-sectional time series analysis to determine whether the COVID-19‒ era recessional mortality continues the impact of prepandemic recessions (2000-2018) on multiple causes of mortality.
Ten percent unemployment was associated with approximately 48thin space149 excess deaths, while, jointly with bankruptcies, their combined effect produced 35 700 and 144 483 excess deaths, for unemployment and bankruptcies, respectively. These health-damaging COVID-19‒recessional findings suggest a reiteration of the significantly increased major cause‒specific mortality during 2000 to 2018, mitigated by the size of the health care workforce.
Minimization of deaths attributable to the COVID-19 recession requires ample funding for the unemployed and underemployed, especially Black and Hispanic communities, along with significant investments in the health workforce. (
. 2021;111(11):1950-1959. https://doi.org/10.2105/AJPH.2021.306490).
More than a half century ago, the NMR spectra of diamagnetic products resulting from radical pair reactions were observed to have strongly enhanced absorptive and emissive resonances. At the same ...time, photogenerated radical pairs were discovered to exhibit unusual electron paramagnetic resonance spectra that also had such resonances. These non-Boltzmann, spin-polarized spectra were observed in both chemical systems as well as in photosynthetic reaction center proteins following photodriven charge separation. Subsequent studies of these phenomena led to a variety of chemical electron donor–acceptor model systems that provided a broad understanding of the spin dynamics responsible for these spectra. When the distance between the two radicals is restricted, these observations result from the formation of spin-correlated radical pairs (SCRPs) in which the spin–spin exchange and dipolar interactions between the two unpaired spins play an important role in the spin dynamics. Early on, it was recognized that SCRPs photogenerated by ultrafast electron transfer are entangled spin pairs created in a well-defined spin state. These SCRPs can serve as spin qubit pairs (SQPs), whose spin dynamics can be manipulated to study a wide variety of quantum phenomena intrinsic to the field of quantum information science. This Perspective highlights the role of SCRPs as SQPs, gives examples of possible quantum manipulations using SQPs, and provides some thoughts on future directions.
The SARS-CoV-2 (COVID-19) pandemic has contributed to increasing levels of anxiety, depression and other symptoms of stress around the globe. Reasons for this increase are understandable in the ...context of individual level factors such as self-isolation, lockdown, grief, survivor guilt, and other factors but also broader social and economic factors such as unemployment, insecure employment and resulting poverty, especially as the impacts of 2008 recession are still being felt in many countries further accompanied by social isolation. For those who are actively employed a fear of job and income loss and those who have actually become ill and recovered or those who have lost family and friends to illness, it is not surprising that they are stressed and feeling the psychological impact. Furthermore, multiple uncertainties contribute to this sense of anxiety. These fears and losses are major immediate stresses and undoubtedly can have long-term implications on mental health. Economic uncertainty combined with a sense of feeling trapped and resulting lack of control can contribute to helplessness and hopelessness where people may see suicide as a way out. Taking a macro view, we present a statistical model of the impact of unemployment, and national income declines, on suicide, separately for males and females over the life cycle in developed countries. This impact may reflect a potent combination of social changes and economic factors resulting in anomie. The governments and policymakers have a moral and ethical obligation to ensure the physical health and well-being of their populations. While setting in place preventive measures to avoid infections and then subsequent mortality, the focus on economic and social recovery is crucial. A global pandemic requires a global response with a clear inter-linked strategy for health as well as economic solutions. The models we have constructed represent predictions of suicide rates among the 38 highly industrialized OECD countries over a period of 18 years (2000-2017). Unemployment has a major effect on increasing suicide, especially in middle-aged groups. However, the impact of economic decline through losses of national income (GDP per capita) are substantially greater than those of unemployment and influence suicide throughout the life course, especially at the oldest ages.
The high arithmetic performance and intrinsic parallelism of recent graphical processing units (GPUs) can offer a technological edge for molecular dynamics simulations. ACEMD is a production-class ...biomolecular dynamics (MD) engine supporting CHARMM and AMBER force fields. Designed specifically for GPUs it is able to achieve supercomputing scale performance of 40 ns/day for all-atom protein systems with over 23 000 atoms. We provide a validation and performance evaluation of the code and run a microsecond-long trajectory for an all-atom molecular system in explicit TIP3P water on a single workstation computer equipped with just 3 GPUs. We believe that microsecond time scale molecular dynamics on cost-effective hardware will have important methodological and scientific implications.
The smooth particle mesh Ewald summation method is widely used to efficiently compute long-range electrostatic force terms in molecular dynamics simulations, and there has been considerable work in ...developing optimized implementations for a variety of parallel computer architectures. We describe an implementation for Nvidia graphical processing units (GPUs) which are general purpose computing devices with a high degree of intrinsic parallelism and arithmetic performance. We find that, for typical biomolecular simulations (e.g., DHFR, 26K atoms), a single GPU equipped workstation is able to provide sufficient performance to permit simulation rates of ≈50 ns/day when used in conjunction with the ACEMD molecular dynamics package and exhibits an accuracy comparable to that of a reference double-precision CPU implementation.
Voluntary spatial attention concentrates neural resources at the attended location. Here, we examined the effects of spatial attention on spatial position selectivity in humans. We measured ...population receptive fields (pRFs) using high-field functional MRI (fMRI) (7T) while subjects performed an attention-demanding task at different locations. We show that spatial attention attracts pRF preferred positions across the entire visual field, not just at the attended location. This global change in pRF preferred positions systematically increases up the visual hierarchy. We model these pRF preferred position changes as an interaction between two components: an attention field and a pRF without the influence of attention. This computational model suggests that increasing effects of attention up the hierarchy result primarily from differences in pRF size and that the attention field is similar across the visual hierarchy. A similar attention field suggests that spatial attention transforms different neural response selectivities throughout the visual hierarchy in a similar manner.
Numerosity, the set size of a group of items, is processed by the association cortex, but certain aspects mirror the properties of primary senses. Sensory cortices contain topographic maps reflecting ...the structure of sensory organs. Are the cortical representation and processing of numerosity organized topographically, even though no sensory organ has a numerical structure? Using high-field functional magnetic resonance imaging (at a field strength of 7 teslas), we described neural populations tuned to small numerosities in the human parietal cortex. They are organized topographically, forming a numerosity map that is robust to changes in low-level stimulus features. The cortical surface area devoted to specific numerosities decreases with increasing numerosity, and the tuning width increases with preferred numerosity. These organizational properties extend topographic principles to the representation of higher-order abstract features in the association cortex.
Animals synchronize to the environmental day-night cycle by means of an internal circadian clock in the brain. In mammals, this timekeeping mechanism is housed in the suprachiasmatic nucleus (SCN) of ...the hypothalamus and is entrained by light input from the retina. The output of the SCN is a neural code for circadian time, which arises from the collective activity of neurons within the SCN circuit and is comprised of two fundamental components: 1) periodic alterations in the spontaneous excitability of individual neurons that result in higher firing rates during the day and lower firing rates at night, and 2) synchronization of these cellular oscillations throughout the SCN. In this review, we summarize current evidence for the identity of ion channels in SCN neurons and the mechanisms by which they set the rhythmic parameters of the time code. During the day, voltage-dependent and independent Na
and Ca
currents, as well as several K
currents, contribute to increased membrane excitability and therefore higher firing frequency. At night, an increase in different K
currents, including Ca
-activated BK currents, contribute to membrane hyperpolarization and decreased firing. Layered on top of these intrinsically-regulated changes in membrane excitability, more than a dozen neuromodulators influence action potential activity and rhythmicity in SCN neurons, facilitating both synchronization and plasticity of the neural code.
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