cssi/SciSciGPT-SciSciNet huggingface dataset:
Occupational dermatoses among farmers.

Occupational dermatoses seen among farmers include fungous, viral and bacterial infections and infestations; dermatitis, including eczema; and tumors.Milker's eczema and ragweed and poison ivy dermatitis are probably the most common forms of contact dermatitis occurring in farmers. Sensitization also results from use of fertilizers, soaps, detergents, insecticides, weed killers, preparations used to treat skin infections in animals, and other materials used on the farm.Basal-cell epithelioma and squamous-cell carcinoma also may be classified as occupational diseases of farmers. The author recommends gentle but thorough curettage of such tumors, supplemented by irradiation with the gamma rays of radium.
Finite-Element-Alternating Method for Analysis of Cracked Three-Dimensional Solids

The finite-element-alternating method is used to analyze part-elliptic circumferential surface cracks in cylinders. The method showed excellent convergence characteristics and yielded accurate stress-intensity factors.
Formation of Teachers as Leaders: Response to the Articles in This Special Issue.

This article contains a response to three manuscripts that are part of the JRLE special issue entitled Developing and Empowering Teacher Leaders for Collective Leadership. Discussion of the articles, lessons learned, and implications for teacher leadership development are discussed.
Autophagy as a Therapeutic Target in Cancer

Autophagy is the process by which cellular material is delivered to the lysosome for degradation and recycling. Macroautophagy involves delivery of macromolecules and organelles to double membrane vesicles called autophagosomes that fuse with lysosomes leading to degradation of the contents of the autophagosomes. Chaperone-mediated autophagy involves direct recognition of specific proteins by chaperone complexes that then directly deliver the protein target to the lysosome. Microautophagy involves direct lysosomal capture of cytoplasmic material. Of these three types, macroautophagy is by far the most studied and is known to have multiple roles in cancer development, progression and response to therapy. This has led to autophagy being widely viewed as a potential therapeutic target in cancer. Important questions that must be answered include: Which tumors should or should not be treated by direct autophagy inhibition? And, what is the best way to target autophagy for cancer therapy? In this overview we summarize the background and some current ideas about the answers to such questions.
Reward vs. Retaliation-the Role of the Mesocorticolimbic Salience Network in Human Reactive Aggression.

The propensity for reactive aggression (RA) which occurs in response to provocation has been linked to hyperresponsivity of the mesocorticolimbic reward network in healthy adults. Here, we aim to elucidate the role of the mesocorticolimbic network in clinically significant RA for two competing motivated behaviors, reward-seeking versus retaliation. 18 male participants performed a variant of the Point-Subtraction Aggression Paradigm (PSAP) during functional magnetic resonance imaging (fMRI). We examined whether RA participants compared with non-aggressive controls would choose to obtain a monetary reward over the opportunity to retaliate against a fictitious opponent, who provoked the participant by randomly stealing money from his earnings. Across all fMRI-PSAP runs, RA individuals vs. controls chose to work harder to earn money but not to retaliate. When engaging in such reward-seeking behavior vs. retaliation in a single fMRI-PSAP run, RA individuals exhibited increased activation in the insular-striatal part of the mesocorticolimbic salience network, and decreased precuneus and ventromedial prefrontal cortex activation compared to controls. Enhanced overall reward-seeking behavior along with an up-regulation of the mesocorticolimbic salience network and a down-regulation of the default-mode network in RA individuals indicate that RA individuals are willing to work more for monetary reward than for retaliation when presented with a choice. Our findings may suggest that the use of positive reinforcement might represent an efficacious intervention approach for the potential reduction of retaliatory behavior in clinically significant RA.
Pore-body and -throat size distributions of The Geysers

Abstract A better understanding of the transport properties of geothermal reservoirs will enable us to improve their energy recovery. With this in mind, we determine pore-body and pore-throat size distributions of The Geysers, which is the largest operating geothermal resource. We determine the former by modeling water adsorption and desorption, and the latter by investigating capillary pressure measurements for The Geysers samples. Our study is based on the acyclic pore model, which is physically representative of the matrix porosity. The matrix of rock is the finer grained mass that acts as a framework for larger grains. An integrated analysis of the petrophysical measurements helps us characterize the connected pore system of the formation more accurately because such measurements are sensitive to different aspects of the pore topology.
The influence of orographic Rossby and gravity waves on rainfall

Author(s): Cohen, NY; Boos, WR | Abstract: Orography is known to influence winter precipitation in Asia and the Indo-Pacific Ocean by mechanically forcing winds, but the dynamics involved in the precipitation response are incompletely understood. This study investigates how two types of orographically forced oscillatory motions alter time-mean winds and precipitation. The quasi-geostrophic omega equation is used together with previous ideas of ‘downward control’ to develop a simple theory of the spatial distribution and amplitude of the vertical motion response to orographically forced stationary Rossby waves and gravity wave drag in a precipitating atmosphere. This theory is then used to understand the response of the boreal winter atmosphere to realistic Asian orography in a global numerical model that includes representations of moist processes and unresolved gravity wave drag. We isolate the effects of the orographically forced stationary Rossby wave and the gravity wave drag by incremental addition of wave sources in this model. The peak precipitation response to the forced Rossby wave is about a factor of three larger than that of the gravity wave drag, but the wave drag response has a distinct spatial structure that dominates in some regions. Both the Rossby wave and the gravity wave drag perturb precipitation in areas distant from orography, producing shifts in the equatorial intertropical convergence zone, an increase in precipitation over southern Asia, and drying in much of northern Asia.
Out of the Cave of the Cyclops

ABSTRACTDespite the deep respect that readers continue to discover in the great twentieth-century texts of hermeneutics, the academic career and reputation of Gadamer's philosophical version has fallen into the shadows; it seems a long time since the heady days that it could claim universality as an intellectual koine. This decline is a genuine shame, because at the peak of its reputation it held out the promise of returning the power of humanistic judgement to greater recognition against the domination of method in an age of technique. Gadamer teased out the unreflective meta-logic of the Western traditions of prudence as an alternative paradigm and powerful antidote to our rationalist excesses. This paper offers one strategy for salvaging that effort and recuperating an important role for philosophical hermeneutics in the academy.
An Ultrahigh-Dimensional Mapping Model of High-order Epistatic Networks for Complex Traits.

Background Genetic interactions involving more than two loci have been thought to affect quantitatively inherited traits and diseases more pervasively than previously appreciated. However, the detection of such high-order interactions to chart a complete portrait of genetic architecture has not been well explored. Methods We present an ultrahigh-dimensional model to systematically characterize genetic main effects and interaction effects of various orders among all possible markers in a genetic mapping or association study. The model was built on the extension of a variable selection procedure, called iFORM, derived from forward selection. The model shows its unique power to estimate the magnitudes and signs of high-order epistatic effects, in addition to those of main effects and pairwise epistatic effects. Results The statistical properties of the model were tested and validated through simulation studies. By analyzing a real data for shoot growth in a mapping population of woody plant, mei (Prunus mume), we demonstrated the usefulness and utility of the model in practical genetic studies. The model has identified important high-order interactions that contribute to shoot growth for mei. Conclusion The model provides a tool to precisely construct genotype-phenotype maps for quantitative traits by identifying any possible high-order epistasis which is often ignored in the current genetic literature.
Fully Numerical Methods for Continuing Families of Quasi-Periodic Invariant Tori in Astrodynamics

Quasi-periodic invariant tori are of great interest in astrodynamics because of their capability to further expand the design space of satellite missions. However, there is no general consent on what is the best methodology for computing these dynamical structures. This paper compares the performance of four different approaches available in the literature. The first two methods compute invariant tori of flows by solving a system of partial differential equations via either central differences or Fourier techniques. In contrast, the other two strategies calculate invariant curves of maps via shooting algorithms: one using surfaces of section, and one using a stroboscopic map. All of the numerical procedures are tested in the co-rotating frame of the Earth as well as in the planar circular restricted three-body problem. The results of our numerical simulations show which of the reviewed procedures should be preferred for future studies of astrodynamics systems.
2D molybdenum disulfide (MoS 2 ) transistors driving RRAMs with 1T1R configuration

We demonstrate the first 1-transistor-1-resistor (1T1R) memory cell using the atomically thin molybdenum disulfide (MoS2) field-effect transistor (FET) and resistive random access memory (RRAM). This 1T1R demonstration realizes a key milestone for tight integration of memory with logic in a monolithic 3D integrated chip. The monolayer MoS2 is grown by chemical vapor deposition (CVD), suitable for wafer-scale fabrication. The MoS 2 FETs have ON-state current of 190 μA/μm at V d = 2.5 V, showing strong driving capability for RRAM. Metal-oxide RRAMs are fabricated at low process temperature, compatible with MoS 2 FET fabrication. 1T1R measurements show higher resistances, and less resistance and voltage variation compared with measurements using only the RRAM. The multiple resistance states obtained for pulsed reset measurements show promise for in-memory computing and neuromorphic computing applications.
A reconfigurable 28/37GHz hybrid-beamforming MIMO receiver with inter-band carrier aggregation and RF-domain LMS weight adaptation

This paper presents a hybrid beamforming mm-wave MIMO receiver with two key innovations. First, it can be configured into three modes: two single-band multistream modes at 28 or 37 GHz that can support single-or multi-user MIMO, and a concurrent 28 and 37GHz dual-band single-stream phased-array inter-band carrier-aggregation mode. In all modes, the receiver features full connectivity from each antenna element input to each output stream, thereby maximizing usage of the available aperture. Second, the digitally programmable RF beamforming weights can be controlled by an external serial interface, or by an on-chip “one-port” mixed-signal adaptation loop that implements a technique that we call double-sampling time-multiplexed LMS (DS-TM-LMS). Unlike conventional LMS-type adaptation algorithms that require access to the individual array inputs and the combined output, and are therefore not easily amenable to a hybrid beamformer, DS-TM-LMS updates the RF-domain weights by accessing only the combined downconverted array outputs. Such adaptation is valuable for adaptive main-lobe, side-lobe or null steering, but more importantly, it can assist/augment codebook-based beam acquisition/tracking algorithms, which may fail in the presence of multipath, on- or off-channel interferers.
Stress relaxation in quasi-two-dimensional self-assembled nanoparticle monolayers

We experimentally probed the stress relaxation of a monolayer of iron oxide nanoparticles at the water-air interface. Upon drop-casting onto a water surface, the nanoparticles self-assembled into islands of two-dimensional hexagonally close packed crystalline domains surrounded by large voids. When compressed laterally, the voids gradually disappeared as the surface pressure increased. After the compression was stopped, the surface pressure (as measured by a Wilhelmy plate) evolved as a function of the film aging time with three distinct timescales. These aging dynamics were intrinsic to the stressed state built up during the non-equilibrium compression of the film. Utilizing x-ray photon correlation spectroscopy, we measured the characteristic relaxation time (τ) of in-plane nanoparticle motion as a function of the aging time through both second-order and two-time autocorrelation analysis. Compressed and stretched exponential fitting of the intermediate scattering function yielded exponents (β) indicating different relaxation mechanisms of the films under different compression stresses. For a monolayer compressed to a lower surface pressure (between 20 mN/m and 30 mN/m), the relaxation time (τ) decreased continuously as a function of the aging time, as did the fitted exponent, which transitioned from being compressed (>1) to stretched (<1), indicating that the monolayer underwent a stress release through crystalline domain reorganization. However, for a monolayer compressed to a higher surface pressure (around 40 mN/m), the relaxation time increased continuously and the compressed exponent varied very little from a value of 1.6, suggesting that the system may have been highly stressed and jammed. Despite the interesting stress relaxation signatures seen in these samples, the structural ordering of the monolayer remained the same over the sample lifetime, as revealed by grazing incidence x-ray diffraction.
Importance of identification of prostatic adenocarcinoma in urine cytology.

Background Prostate carcinoma (PCa) occasionally involves the urethra and/or bladder. In these cases, PCa cells may be detected in urine. The purpose of this study was to describe the salient cytomorphologic, immunocytochemical, and epidemiologic features of PCa cells detected in urine cytology slides via a retrospective case series review. Materials and Methods We retrospectively identified 28 cases with urine cytology either suspicious or positive for PCa. Clinical and histopathologic data were reviewed. Results We identified 23 prostatic acinar adenocarcinomas (PAAs) and 5 prostatic adenocarcinomas with ductal features (PDAs). Urine cytology was the first evidence of disease in 6 (26%) patients with PAA and in 4 (80%) of the patients with PDA. In patients with PAA, 17 had a previous history of PAA, with positive urine cytology in the setting of disease recurrence or persistence within the bladder or urethra. The PAA in urine presented as single or small clusters of atypical cuboidal glandular cells with large, eccentric, round, or oval uniform nuclei containing conspicuous nucleoli, and scant to moderate delicate or granular cytoplasm, whereas the PDA presented as atypical columnar glandular cells in flat nests or 3-dimensional clusters, and with prominent nucleoli. Conclusions Using standard urine cytology, we were able to detect PCa cells in the urine. Although rare, PCa was first diagnosed by urine cytology in select cases, with a higher frequency in patients with PDA. Clinicians should be aware that PCa cells can be identified by urine cytology as this can lead to an earlier diagnosis and treatment.
Multiresolution analyses, tiles, and scaling functions

Several, hopefully useful, observations concerning the topic in he title are discussed: (i) It is noted that the axiom of intersection is not essential in the definition of a multiresolution analysis, (ii) Several conditions, which are often easily verifiable, are given for scaling sequences which imply that such sequences generate scaling functions whose supports give rise to non-overlapping tilings of ℜn.
Success and Backlash: The Remarkable (Continuing) Story of the Clean Water Act

The Clean Water Act has produced a tremendous amount of progress over the past forty years. Both municipal and industrial discharges have declined sharply, the loss of wetlands has been cut decisively, and water quality has broadly improved. Much more work, however, remains to be done. Not surprisingly, given the limits of human forethought and political capacity, the original statutory design was not perfect. Furthermore, the statute's implementation has not been perfect due, in large part, to often straitened budgets, instances of bureaucratic timidity and lethargy, and the hostility that some administrations and some Congresses have exhibited towards strong environmental protection. Although more robust administrative action can improve the effectiveness of the Act in a number of ways, it will take contressional action to fully address the jurisdictional, budgetary, and structural problems that are obstructing efforts to fully restore and maintain the chemical, physical, and biological integrity of the nation's waters. The prospects for such comprehensive congressional action are slight at the present time. In fact, we are enduring yet another backlash on Capitol Hill against regulation as well as against the protections provided by the Clean Water Act. It will take renewed and stronger efforts to inform and galvanize public opinion, not only to defeat the current backlash, but to build the level of support necessary to complete the task that the nation so boldly embarked upon in 1972. This article discusses both the Act's major successes as well as the problems that remain. In addition, the article explores the most recent congressional backlash against the Act's regulatory structure and proposes a number of steps aimed toward turning generalized public support for clean water into legislative action.
Vibration Effect in the Order-Disorder Transition Theory of RbAg4I5

Vibrational frequencies are expected to be quite diferent at different sites of the carrier ion in a superionic conductor. For a simple model of RbAg4I5, we have studied the effect of vibrational frequency differences on the equilibrium distribution of Ag+ ions. It is found that one could introduce a considerable error by neglecting the above mentioned effect.
Sex differences in major depression and comorbidity of cardiometabolic disorders: impact of prenatal stress and immune exposures

Major depressive disorder topped ischemic heart disease as the number one cause of disability worldwide in 2012, and women have twice the risk of men. Further, the comorbidity of depression and cardiometabolic disorders will be one of the primary causes of disability worldwide by 2020, with women at twice the risk. Thus, understanding the sex-dependent comorbidities has public health consequences worldwide. We propose here that sex differences in MDD-cardiometabolic comorbidity originate, in part, from pathogenic processes initiated in fetal development that involve sex differences in shared pathophysiology between the brain, the vascular system, the CNS control of the heart and associated hormonal, immune, and metabolic physiology. Pathways implicate neurotrophic and angiogenic growth factors, gonadal hormone receptors, and neurotransmitters (such as GABA) on neuronal and vascular development of HPA axis regions, such as the PVN, in addition to blood pressure, in part through the renin–angiotensin system, and insulin and glucose metabolism. We show that the same prenatal exposures have consequences for sex differences across multiple organ systems that, in part, share common pathophysiology. Thus, we believe that applying a sex differences lens to understanding shared biologic substrates underlying these comorbidities will provide novel insights into the development of sex-dependent therapeutics. Further, taking a lifespan perspective beginning in fetal development provides the opportunity to target abnormalities early in the natural history of these disorders in a sex-dependent way.
Methods of Genetic Transformation: The Gene Gun

In the decade since its introduction, the gene gun has gone from being a scientific novelty to an established tool for introducing DNA and other molecules into plant cells. The unique ability of biolistic technology to deliver macromolecules into intact cells has been exploited in studies ranging from control of gene expression to organelle transformation. Further, biolistics is the critical technology allowing for the genetic transformation of the world’s most important crop species. Still, many of the factors that influence the efficiency of transformation using the gene gun are poorly understood. The purpose of this paper, then, is to review the current research addressing the physical and biological parameters that effect biolistic transformation.
Role of Lipids in Coxiella burnetii Infection

Lipids are essential components of both eukaryotic and prokaryotic cells, serving diverse functions including energy metabolism and membrane structure. Intracellular vacuolar pathogens such as Coxiella burnetii require lipids for both normal bacterial functions as well as formation of the acidic, phagolysosomal-like parasitophorous vacuole (PV) surrounding the bacteria. As an intracellular pathogen, C. burnetii can acquire lipid through both de novo bacterial synthesis and subversion of host cell pools. The C. burnetii genome encodes enzymes required for de novo synthesis of fatty acids and phospholipids. The high percentage of branched fatty acids suggests C. burnetii modifies these molecules to generate a bacterial cell envelope that can resist the harsh environment of the PV, such as the acidic pH. In addition to fatty acids and their derivatives, C. burnetii requires isoprenoids, particularly sterols as the PV membrane is cholesterol-rich. With the exception of two eukaryote-like sterol reductases, C. burnetii does not have the capability to generate cholesterol, suggesting sterols are actively diverted from the host cell. While C. burnetii utilizes host cell lipids for membrane biogenesis and possibly energy, bacterial manipulation of host cell lipid signaling pathways may support establishment of the intracellular niche. For example, effectors secreted by the C. burnetii Type IV secretion system may either directly or indirectly modify host cell lipids. Further understanding of the lipid biosynthetic capabilities of C. burnetii, along with C. burnetii’s manipulation of host cell lipids, will provide insight into the host-pathogen relationship.
Immuno-spin trapping of macromolecules free radicals in vitro and in vivo - One stop shopping for free radical detection.

Abstract The only general technique that allows the unambiguous detection of free radicals is electron spin resonance (ESR). However, ESR spin trapping has severe limitations especially in biological systems. The greatest limitation of ESR is poor sensitivity relative to the low steady-state concentration of free radical adducts, which in cells and in vivo is much lower than the best sensitivity of ESR. Limitations of ESR have led to an almost desperate search for alternatives to investigate free radicals in biological systems. Here we explore the use of the immuno-spin trapping technique, which combine the specificity of the spin trapping to the high sensitivity and universal use of immunological techniques. All of the immunological techniques based on antibody binding have become available for free radical detection in a wide variety of biological systems.
An Apparatus for Tensile Characterization of Materials within the Upper Intermediate Strain Rate Regime

A new “Drop-Hopkinson bar” apparatus has been successfully developed for material tensile property characterization at intermediate strain rates. This new apparatus design combines a drop table, which generates a relatively long and stable low-speed impact to the specimen, with a Hopkinson bar, which provides the load history while accounting for inertia effect in the system. The inertia effect in the specimen was minimized through pulse shaping. The pulse shaping technique was also used to facilitate constant strain rate in the specimen. The newly developed apparatus for intermediate-strain-rate tests was experimentally verified by comparing the tensile stress-strain responses of two materials, 6061-T6 aluminum and 304L stainless steel, obtained from the new apparatus and the conventional Kolsky tension bar, respectively, at the same strain rate of ~600 s−1. The results showed that the new apparatus apparatus is reliable and repeatable for intermediate strain-rate testing as well as comparable to Kolsky bar measurements. The 6061-T6 aluminum and 304L stainless steel were also characterized at low, intermediate, and high strain rates with MTS, the new apparatus, and Kolsky tension bar, respectively, to determine the effect of strain rate on tensile stress-strain response for both materials.
Effect of strut length and orientation on elastic mechanical response of modified body-centered cubic lattice structures:

Lattice structures (LSs) have been exploited for wide range of applications including mechanical, thermal, and biomedical structures because of their unique attributes combining the light weight an...
Rule by Law: A Much Maligned Preposition

Commentators working in the law-and-development field distinguish between the rule of law and "rule by law," with the latter being treated as an authoritarian caricature of the former. Under "rule by law" a regime may use law and legal institutions to control its population, but it will not allow law to be used to control the regime. There are also a number of other understandings of "rule by law," most notably a conception that associates ideologically it with enacted law, as opposed to autonomous law. This paper re-examines the idea of rule by law and suggests that if it is taken at face value it involves the admirable willingness of a regime to submit itself to the discipline of legality. It should not be disparaged, and indeed (like the rule of law itself) it admits of a spectrum of applications, some of them quite demanding.
Intracytoplasmic crystalline inclusions in chronic lymphocytic leukemia

Neoplastic B cells may have cytoplasmic inclusions that are visible in routine peripheral blood smears by light microscopy.
Structure-activity-distribution relationship study of anti-cancer antimycin-type depsipeptides.

Small-molecule natural products have been an essential source of pharmaceuticals to treat human diseases, but very little is known about their behavior inside dynamic, live human cells. Here, we demonstrate the first structure–activity–distribution relationship (SADR) study of complex natural products, the anti-cancer antimycin-type depsipeptides, using the emerging bioorthogonal Stimulated Raman Scattering (SRS) Microscopy. Our results show that the intracellular enrichment and distribution of these compounds are driven by their potency and specific protein targets, as well as the lipophilic nature of compounds.
FLightNNs: Lightweight Quantized Deep Neural Networks for Fast and Accurate Inference

To improve the throughput and energy efficiency of Deep Neural Networks (DNNs) on customized hardware, lightweight neural networks constrain the weights of DNNs to be a limited combination (denoted as k $\in$ {1, 2}) of powers of 2. In such networks, the multiply-accumulate operation can be replaced with a single shift operation, or two shifts and an add operation. To provide even more design flexibility, the k for each convolutional filter can be optimally chosen instead of being fixed for every filter. In this paper, we formulate the selection of k to be differentiable, and describe model training for determining k-based weights on a per-filter basis. Over 46 FPGA-design experiments involvmg eight configurations and four data sets reveal that lightweight neural networks with a flexible k value (dubbed FLightNNs) fully utilize the hardware resources on Field Programmable Gate Arrays (FPGAs), our experimental results show that FLightNNs can achieve $2\times$ speedup when compared to lightweight NNs with k = 2, with only 0.1% accuracy degradation. Compared to a 4-bit fixed-point quantization, FLightNNs achieve higher accuracy and up to $2\times$ inference speedup, due to their lightweight shift operations. In adchtion, our experiments also demonstrate that FLightNNs can achieve higher computational energy efficiency for ASIC implementation.CCS CONCEPTS• Computing methodologies $\rightarrow$ Machine learning; • Hardware$\rightarrow$Electronic design automation.
Angela Marino. Populism and Performance in the Bolivarian Revolution of Venezuela.

Angela Marino’s Populism and Performance in the Bolivarian Revolution of Venezuela makes a seminal contribution to understanding the complex synergies between performance and populism as they inter...
Increasing Photosynthesis: Unlikely Solution For World Food Problem.

Increasing the photosynthesis rate of plants has been recently revitalized as an approach for increasing grain crop yields and solving world food crises. The idea that photosynthesis is the key to increasing grain crop yields is not new. Considerable research in the 1970s and 1980s showed that carbon input was not limiting for crop growth and yield. Instead, the availability and uptake of water and nutrients were found to be critical for increasing grain yield, and that conclusion still applies today. In this Opinion article, nitrogen limitation is given particular attention because of its quantitative linkage with vegetative and reproductive growth and its essential role as a quantitative component of seeds.
Identification of a critical horseshoe-shaped region in the nsp5 (Mpro, 3CLpro) protease interdomain loop (IDL) of coronavirus mouse hepatitis virus (MHV)

Abstract Human coronaviruses are enveloped, positive-strand RNA viruses which cause respiratory diseases ranging in severity from the seasonal common cold to SARS and COVID-19. Of the 7 human coronaviruses discovered to date, 3 emergent and severe human coronavirus strains (SARS-CoV, MERS-CoV, and SARS-CoV-2) have recently jumped to humans in the last 20 years. The COVID-19 pandemic spawned by the emergence of SARS-CoV-2 in late 2019 has highlighted the importance for development of effective therapeutics to target emerging coronaviruses. Upon entry, the replicase genes of coronaviruses are translated and subsequently proteolytically processed by virus-encoded proteases. Of these proteases, nonstructural protein 5 (nsp5, Mpro, or 3CLpro), mediates the majority of these cleavages and remains a key drug target for therapeutic inhibitors. Efforts to develop nsp5 active-site inhibitors for human coronaviruses have thus far been unsuccessful, establishing the need for identification of other critical and conserved non-active-site regions of the protease. In this study, we describe the identification of an essential, conserved horseshoe-shaped region in the nsp5 interdomain loop (IDL) of mouse hepatitis virus (MHV), a common coronavirus replication model. Using site-directed mutagenesis and replication studies, we show that several residues comprising this horseshoe-shaped region either fail to tolerate mutagenesis or were associated with viral temperature-sensitivity. Structural modeling and sequence analysis of these sites in other coronaviruses, including all 7 human coronaviruses, suggests that the identified structure and sequence of this horseshoe regions is highly conserved and may represent a new, non-active-site regulatory region of the nsp5 (3CLpro) protease to target with coronavirus inhibitors. Importance In December 2019, a novel coronavirus (SARS-CoV-2) emerged in humans and triggered a pandemic which has to date resulted in over 8 million confirmed cases of COVID-19 across more than 180 countries and territories (June 2020). SARS-CoV-2 represents the third emergent coronavirus in the past 20 years and the future emergence of new coronaviruses in humans remains certain. Critically, there remains no vaccine nor established therapeutics to treat cases of COVID-19. The coronavirus nsp5 protease is a conserved and indispensable virus-encoded enzyme which remains a key target for therapeutic design. However, past attempts to target the active site of nsp5 with inhibitors have failed stressing the need to identify new conserved non-active-site targets for therapeutic development. This study describes the discovery of a novel conserved structural region of the nsp5 protease of coronavirus mouse hepatitis virus (MHV) which may provide a new target for coronavirus drug development.
Oral Semaglutide: Balancing Promising Therapeutics with Adverse Effects and Access Barriers.

DISCLOSURES: No funding was received for this commentary. The author has nothing to disclose.
Simulation-based optimization framework for economic operations of autonomous electric taxicab considering battery aging

Abstract This paper proposes a simulation-based optimization framework for an autonomous electric taxi (AET) to achieve economic optimization by determining the optimal operations in the operating time horizon. The operating time horizon of the AET is equally divided into a set of consecutive time slots. For each time slot, there are four possible operations: driving, cruising, parking, and charging. To reduce the computational complexity, instead of solving the scheduling problem for the whole operating time horizon as a single problem, the whole problem is decomposed into a set of subproblems that are built for a one-day period. From an integrated electric vehicle simulation model, which simulates the AET operation based on the optimal schedule determined by the optimization problem, precise battery status parameters, such as the state of charge, capacity loss and battery temperature, are derived and used as the initial values for the optimization problem with rolling horizon implementation. A case study on NYC is presented, and the results show that the proposed framework can extend the battery life by 3%, and also increase the daily profit by 3% and 520%, compared to the 24hr rule-based strategy and 8hr rule-based strategy, respectively.
The Benefits and Costs of Tax Deferral: An Analysis of Section 1031 Exchanges

We examine the effects of Section 1031 of the Internal Revenue Code on commercial real estate (CRE) investors and markets, as well as on U.S. Treasury revenue. We first develop a partial equilibriu...
Comparison of the effect of cigarette smoke on mesenchymal stem cells and dental stem cells

The persistent prevalence of cigarette smoking continues to contribute to preventable disease and death in the United States. Although much is known about the deleterious systemic effects of cigarette smoke and nicotine, some clinically relevant areas, such as the impact of cigarette smoke and nicotine on stem cells and the subsequent implications in regenerative medicine, still remain unclear. This review focuses on recent studies on the effect of cigarette smoke and one of its deleterious components, nicotine, on mesenchymal stem cells, with an emphasis on dental stem cells.
Considering Uber Technologies Inc v Heller Under US Law

Recently, the Supreme Court of Canada in Uber Technologies Inc v Heller used the unconscionability doctrine to strike down a pre-dispute arbitration clause in an Uber driver agreement that required arbitration in the Netherlands. This has led some to ask: How would a court in the United States analyze this case? This comment will address this question, giving due weight to the US Supreme Court’s trend toward strengthening the Federal Arbitration Act (FAA) and enforcing pre-dispute arbitration agreements in employment and consumer contexts. Nonetheless, this comment diverges from critiques of unconscionability’s flexibility and lack of clear definition—which allegedly threaten efficiency in contract law. Instead, the comment urges that unconscionability remains steadfast in US law to protect core human values. Unconscionability is not a frivolous gloss on classical contract law. Instead, it provides a flexible safety net for catching contractual unfairness. Accordingly, one could argue that under US law, a court would find the arbitration clause in Heller unconscionable. However, a US court may have provided a different remedy.
Effect of footwear on arch rise and drop when walking: a preliminary analysis

Observational studies have found that habitually barefoot populations tend to have stronger feet, lower incidence of flat foot, and decreased lower extremity injury rates compared to traditionally ...
Religion, Insurrection, and Social Forgiveness

The riot at the Capitol summoned a familiar impulse to demonize. But the impulse sits uneasily alongside the scriptural admonition in Luke to forgive them "for they know not what they do." The essay ponders the meaning of this admonition by introducing the concept of social forgiveness, When society forgives, it extends an invitation to someone who has transgressed to rejoin the group as a full member. Because membership in a democracy in the norm, social forgiveness facilitates a return to normalcy by conditioning us to see that exclusion is an aberration. Moreover, membership in a democracy must never be withheld arbitrarily or gratuitously, and ostracism or exile based on impermissible grounds is wholly indefensible. Thus, by restoring full membership, social forgiveness also brings unjust exile to a merciful end. Finally, because membership is the norm, the goal of the justice system should be to restore membership as soon as reasonably possible.
Serotonin Release is Responsible for the Locomotor Hyperactivity in Rats Induced by Derivatives of Amphetamine Related to MDMA

A structural derivative of amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), is a potent serotonin (5-HT) releasing drug. When administered to humans, MDMA produces psychological effects that are distinct from the effects of classical psycho-stimulants and hallucinogens. In rats, MDMA produces locomotor hyperactivity, but the spatial pattern of locomotion and the suppression of investigatory behaviors in MDMA-treated rats differs qualitatively from the pattern of exploration produced by other psycho-stimulants. Previous experiments have indicated that the motor activating effects of MDMA in rats depend upon 5-HT release. Antagonism of MDMA-induced norepinephrine release by pretreatment with nisoxetine was less effective than serotonergic manipulations at reducing the behavioral effects of MDMA, suggesting a minor contribution of norepinephrine release to the behavioral effects of MDMA. A derivative of MDMA with greater selectivity for serotonergic systems over catecholaminergic systems, 5,6-(methylenedioxy)-2-aminoindan (MDAI), produced a biphasic effect in rats consisting of an early suppression of exploratory activity and a later motor activation. Only the motor activation by MDAI is antagonized by treatments designed to prevent drug-induced 5-HT release, consistent with the importance of 5-HT release for the activating effects of MDMA. Finally, the locomotor activation, suppression of investigatory responding and detailed spatial patterning of activity produced by MDMA was not diminished in a familiar environment. Similar effects produced by hallucinogens are attenuated in a familiar testing environment, suggesting that these effects of MDMA do not reflect hallucinogenic properties of this drug. These results demonstrate the potential utility of 5-HT releasing drugs in future studies of the influence of endogenous 5-HT on unconditioned exploratory activity.
Scanning probe microscope trajectory measurement by scanning a single feature

In this paper, a method for estimating scanning probe microscope (SPM) trajectories using only the probe-surface interaction signal is presented. The novelty of this approach is that the trajectory estimate can be made by scanning over one feature. SPMs are perhaps the most important devices for nanotechnology because of their unrivaled ability to measure, manipulate, and modify surfaces at extremely high resolution. Although widely used, SPM operating speed is limited. In order to increase operating speed, SPM trajectory measurement is useful to enable control and modeling, but the sensors required to make those measurements are not always available due to various sensor issues. The probe-surface interaction signal-based probe trajectory estimation technique in this paper overcomes issues associated with conventional sensors by using the existing probe-surface interaction measurement capabilities of SPM systems. The presented method analyzes probe-surface interactions from one feature on the sample's surface to determine a set of probe trajectory zero crossings. This set can be used to estimate the probe trajectory through a nonlinear least squares fit. In order to show the validity of this approach, proof-of-concept simulations are presented.
Outflow Driven Turbulence in Star Forming Clouds

Setting young stellar object jets and outflows in their broadest context requires an understanding of outflows as “feedback” in the development of molecular cloud turbulence and the determination of star formation efficiencies. In this contribution I review our group’s recent studies exploring relationships between protostellar outflows and turbulence in molecular clouds. We first present studies of turbulence and fossil cavities driven by YSO outflows using numerical simulations which track the evolution of single transient jets driven into a turbulent medium. Our simulations show both the effect of turbulence on outflow structures and, conversely, the effect of outflows on the ambient turbulence. These studies demonstrate that individual transient outflows have the capacity to re-energize decaying turbulence. Next we present simulations of multiple interacting jets. We show that turbulence can readily be sustained by these interactions and show that it is possible to broadly characterize an effective driving scale of the outflows. Comparing the velocity spectrum obtained in our studies to that of an isotropically forced control we show that in outflow driven turbulence a power law of the form E(k) ∝ k − β is indeed achieved. However we find a steeper spectrum β ∼ 3 is obtained in outflow driven turbulence models than in isotropically forced simulations β ∼ 2. 0. Taken together both studies provide broad support for the conclusion that fossil cavities driven by decaying jets can provide a source of turbulence and feedback which mediate star formation processes in molecular clouds. Whether this does obtain in real clouds remains a point which must be demonstrated
Molecular structures of other galaxies compared to that of the galaxy

Of the eleven galaxies with detected CO emission, eight have bright nuclear CO sources: M82, NGC 253, M51, NGC 5236, NGC 1068, Maffei 2 (Rickard et al . 1977a,b), NGC 6946, and IC 342 (Morris and Lo 1978). Two have disk-population CO sources and no detectable nuclear source (M31 and M81, Combes et al . 1977a), and one has no obvious nucleus (LMC, Huggins, et al . 1975). Nuclear maxima thus appear to be the rule for galaxies with extensive molecular components, and such a peak is also seen in our Galaxy ( e.g. , Bania 1977). In Figure 1, I compare the CO data for the nuclei of M82 and M31 with spectra of the Galactic nucleus as it would be seen at their respective distances. (The Galactic spectra were synthesized from the date of Bania [1977], and assume a uniform z-distribution of 30 pc width.) The Galaxy is roughly intermediate, being about one-fifth the intensity of M82 and more than six times the intensity of M31.
Pixelated transmission-mode diamond X-ray detector.

Fabrication and testing of a prototype transmission-mode pixelated diamond X-ray detector (pitch size 60–100 µm), designed to simultaneously measure the flux, position and morphology of an X-ray beam in real time, are described. The pixel density is achieved by lithographically patterning vertical stripes on the front and horizontal stripes on the back of an electronic-grade chemical vapor deposition single-crystal diamond. The bias is rotated through the back horizontal stripes and the current is read out on the front vertical stripes at a rate of ∼1 kHz, which leads to an image sampling rate of ∼30 Hz. This novel signal readout scheme was tested at beamline X28C at the National Synchrotron Light Source (white beam, 5–15 keV) and at beamline G3 at the Cornell High Energy Synchrotron Source (monochromatic beam, 11.3 keV) with incident beam flux ranges from 1.8 × 10−2 to 90 W mm−2. Test results show that the novel detector provides precise beam position (positional noise within 1%) and morphology information (error within 2%), with an additional software-controlled single channel mode providing accurate flux measurement (fluctuation within 1%).
Distinct Nature of Directional Signals Among Parietal Cortical Areas During Visual Guidance

We examined neuronal signals in the monkey medial superior temporal area (MST), the medial intraparietal area (MIP), and the lateral intraparietal area (LIP) during visually guided hand movements. ...
Hierarchical scheduling approach in flexible assembly systems

The scheduling and dispatching problem for flexible assembly systems operating in a MRP environment is described. These flexible assembly systems (FAS) can perform the required operations on multiple product types which are assembled simultaneously. A non-exact procedure is presented as the basis for SCHEDULER and DISPATCHER functionality in a hierarchical scheduling system design.
Reproducibility of Serum Potassium Values in Serum From Blood Samples Stored for Increasing Times Prior to Centrifugation and Analysis.

Goals The goal of this work was to determine if immediate versus postponed centrifugation of samples affects the levels of serum potassium. Methods Twenty participants donated normal venous blood that was collected in four serum separator tubes per donor, each of which was analyzed at 0, 1, 2, or 4 hr on the Siemens Advia 1800 autoanalyzer. Results Coefficients of variation (CVs) for potassium levels ranged from 0% to 7.6% with a mean of 3 ± 2%. ANOVA testing of the means for all 20 samples showed a P-value of 0.72 (>0.05) indicating that there was no statistically significant difference between the means of the samples at the four time points. Sixteen samples were found to have CVs that were ≤5%. Two samples showed increases of potassium from the reference range to levels higher than the upper reference limit, one of which had a 4-hr value that was within the reference or normal range (3.5–5 mEq/l). Overall, most samples were found to have reproducible levels of serum potassium. Conclusions Serum potassium levels from stored whole blood collected in serum separator tubes are, for the most part, stable at room temperature for at least 4 hr prior to analysis. However, some samples can exhibit significant fluctuations of values.