cssi/SciSciGPT-SciSciNet huggingface dataset:
Role of facilitated diffusion of calcium by calbindin in intestinal calcium absorption

Computer simulations of transcellular Ca2+ transport in enterocytes were carried out using the simulation program SPICE. The program incorporated a negative-feedback entry of Ca2+ at the brush-border membrane that was characterized by an inhibitor constant of 0.5 microM cytosolic Ca2+ concentration ([Ca2+]). The basolateral Ca(2+)-ATPase was simulated by a four-step mechanism that resulted in Michaelis-Menten kinetics with a Michaelis constant of 0.24 microM [Ca2+]. The cytosolic diffusion of Ca2+ was simulated by dividing the cytosol into 10 slabs of equal width. Ca2+ binding to calbindin-D9K was simulated in each slab, and diffusion of free Ca2+, free calbindin, and Ca(2+)-laden calbindin was simulated between each slab. The cytosolic [Ca2+] of the simulated cells was regulated within the physiological range. Calbindin-D9K reduced the cytosolic [Ca2+] gradient, increased Ca2+ entry into the cell by removing the negative-feedback inhibition of Ca2+ entry, increased cytosolic Ca2+ flow, and increased the efflux of Ca2+ across the basolateral membrane by increasing the free [Ca2+] immediately adjacent to the pump. The enhancement of transcellular Ca2+ transport was nearly linearly dependent on calbindin-D9K concentration. The values of the dissociation constant (Kd) for calbindin-D9K were previously obtained experimentally in the presence and absence of KCl. Calbindin with the Kd obtained in the presence of KCl enhanced the simulated Ca2+ transport more than with the Kd obtained in the absence of KCl. This result suggests that the physiological Kd of calbindin is optimal for the enhancement of transcellular Ca2+ transport. The simulated Ca2+ flow was less than that predicted from the "near-equilibrium" analytic solution of the reaction-diffusion problem.
Deployment of a retinal determination gene network drives directed cell migration in the sea urchin embryo

Gene regulatory networks (GRNs) provide a systems-level orchestration of an organism's genome encoded anatomy. As biological networks are revealed, they continue to answer many questions including knowledge of how GRNs control morphogenetic movements and how GRNs evolve. The migration of the small micromeres to the coelomic pouches in the sea urchin embryo provides an exceptional model for understanding the genomic regulatory control of morphogenesis. An assay using the robust homing potential of these cells reveals a 'coherent feed-forward' transcriptional subcircuit composed of Pax6, Six3, Six1/2, Eya, and Dach1 that is responsible for the directed homing mechanism of these multipotent progenitors. The linkages of that circuit are strikingly similar to a circuit involved in retinal specification in Drosophila suggesting that systems-level tasks can be highly conserved even though the tasks drive unrelated processes in different animals.
How to Keep our Youth away from IS: The Need for Narrative Analysis and Strategy

The German war theorist Carl von Clausewitz pointed out that in order to defeat an opponent one had to crush his point of gravitation (Schwerpunkt).[1] In the case of non-state opponents, like the Islamic State, which do occupy territory, but more or less in a nomadic way, moving like a snake among the rocks, it is difficult to target a physical point of gravitation. In fact their Schwerpunkt is their ideological narrative, which functions as a redoubtable pull-factor, responsible for attracting throngs of foreign fighters. So far the West has shown a poor record in targeting this narrative. This paper tries to map some of the elements in IS’s Schwerpunkt that look vulnerable and may be targeted in order to diminish the power of the Islamic State as much as possible without actually fighting the self-proclaimed Caliphate.
Climatic Change: the state of the journal

Just over two years ago, the death of our founding editor, Stephen Schneider, sent shockwaves around the global scientific community, and we keenly felt his loss in the Climatic Change office. At the time, the journal only recently had celebrated the publication of volume 100, and it is perhaps fitting that I return to that issue as a springboard to assess what has transpired in the interim, take stock of the current state of the journal, and contemplate its future. The title of Steve’s introductory essay is very revealing about the challenges then facing the journal: “be careful what you wish for!—what if you get it?” Truly, Climatic Change has been a victim of his own success. Steve had invested heavily in nurturing scholars, cultivating the field, and educating an audience. Over the years, the investment paid off handsomely. Starting with humble beginnings in 1975, taking two years to publish the first issue of four articles, the journal has grown to a world-class “journal of record for interdisciplinary analysis of climate change science and policy” (Schneider 2010) due to Steve’s determination and perseverance. A look at the rough numbers over the past decade is revealing. Between 2002 and 2007, the journal received around 200 submissions a year. That number jumped to nearly 300 in 2008 and again to 400 in 2009. We received 225 submissions in the first half of 2010 alone, before Steve passed away. Steve had taken some steps to address the increased numbers of submissions, as he mentioned in his volume 100 essay:
Carbide formation during activation of iron Fisher-Tropsch catalysts

The morphological transformations during activation of a commercial, precipitated and spray-dried, Fe2O3-CuO-K2O Fischer-Tropsch Catal.yst are studied. The Catal.yst is activated in a flowing (H2/CO = 0.7/1.0) mixture at 523 K and 543 K and subsequent reaction is carried out at 523 K. The activation temperature causes these Catal.ysts to exhibit significant differences in their Catal.ytic activity for CO hydrogenation. The solid-state phase transformations from the oxide phase (hematite) to the iron carbide are studied by high resolution transmission electron microscopy (HRTEM), X-ray diffraction and elemental analysis. The differing extents of formation of the carbide phase correlate well with the Catal.ytic activity of iron. HRTEM shows that as magnetite transforms into carbide, the crystals of magnetite break down into smaller crystallites of the carbide phase. Deposition of carbon on the surface causes the carbide crystallites to further separate from each other. Morphological transformations such as these determine the attrition of the Catal.yst and help provide clues to understanding the deactivation of iron Fischer-Tropsch Catalysts.
Reflections on Home Concrete : Writing Tax Regulations and Interpreting Tax Statutes

Positive statutory law -- principally the Internal Revenue Code -- is the most important source of tax rules. Despite its volume, however, the Code contains many gaps. Tax regulations promulgated by the Department of the Treasury are the principal vehicles for filling the most important gaps.
A Method for Developing Preliminary Adaptive Optics Designs for Lasercom Applications

There is a need for fast and intuitive methods for developing preliminary adaptive optics designs so that free space lasercom channels through the atmosphere meet performance requirements. We describe one.
Milk matrix effects on antibody binding analyzed by enzyme-linked immunosorbent assay and biolayer interferometry.

Biolayer interferometry (BLI) was employed to study the impact of the milk matrix on the binding of ricin to asialofetuin (ASF) and to antibodies. This optical sensing platform used ligands immobilized covalently or via biotin–streptavidin linkage, and the results were compared to those obtained by enzyme-linked immunosorbent assay (ELISA). In sandwich ELISA, the binding of ricin to ASF was dramatically decreased when galactose was present during the analyte or detection antibody binding step. Low concentrations of milk (1%, v/v) produced a similar reduction in ricin binding to ASF but not to a high-affinity monoclonal antibody (mAb), increasing the dissociation rate of ASF–ricin complexes up to 100-fold. The effect of milk on the binding of ricin to ASF was ascribable to dialyzable factors, and milk sugar can account for these effects. The use of high-affinity mAbs in ELISA effectively limits the milk matrix effect on ricin analysis.
Potent and selective in vitro and in vivo inhibition of tumor proliferation by KXO1, a novel non-ATP competitive Src inhibitor

3245 Elevated protein and activation levels of Src, a non-receptor tyrosine kinase, are thought to play important roles in primary tumor growth and metastatic progression. Several multikinase Src inhibitors have entered clinical trials (AZD0530, SKI-606) and one has recently reached the market (dasatinib). These multikinase inhibitors target the ubiquitous ATP substrate binding site, as do the vast majority of kinase inhibitors currently under investigation. Kinex Pharmaceuticals has developed a novel platform technology, MimeticaTM, that facilitates the development of peptide substrate site targeted inhibitors of kinases or phosphatases. The peptide substrate site is envisioned to be a more unique binding cavity, leading to more selective inhibitors, due to differing peptide substrate selectivity’s among the kinases. Utilizing this technology, Kinex developed KXO1, a novel small molecule, non-ATP competitive Src kinase inhibitor. Targeting the Src peptide substrate binding site provided much higher selectivity than is obtained with the ATP competitive Src inhibitors, as demonstrated by phosphotyrosine protein level analyses of cell lysates. KXO1 inhibits Src kinase activity in whole cells with low nM potency, Lyn and BCR-Abl at sub-micromolar potencies, yet is >1,000-fold less active against other tyrosine kinases such as EGFR, PDGFR, JAK1, JAK2, ZAP70 and Lck. KXO1 also has low nM potency as an in vitro inhibitor of tumor cell proliferation for a broad range of human cancer types. KXO1 substantially reduces the growth of human HT29 colon tumors in SCID mouse xenografts (T/C=30%) when dosed orally at 5 mg/kg/dose bid, and with no observed toxicity. KXO1 is currently completing late preclinical development and, in 2007, will be the first non-ATP competitive Src inhibitor to enter Phase I clinical trials.
The Design of AC High Precision Constant Current Source

This paper presents the performance parameters first,then analyzes the working principle of the constant-current source,puts forward the design method of the high-precision power-frequency constant-current source,introduces the key point of the significant circuit,gives the method of thermal design,reliability design and software design,finally gives test data and conclusions.
Analysis of surveillance results of main vectors in Shenzhen Universiade venues from 2010 to 2011

Objective To surveil the population distribution and density fluctuation of the main vectors in Shenzhen Universiade venues from 2010 to 2011,and to provide a scientific basis for controlling vectors.Methods The CO2 light trap was used for the surveillance of adult mosquitoes,the mosq-ovitrap for Aedes albopictus,the cage for flies and rats,and sticky board for cockroaches.Results Culex pipiens pallens was the dominant species of mosquitoes caught in Shenzhen Universiade venues,accounting for 89.47%(476/532),and Ae.albopictus accounted for 9.96% of all caught mosquitoes.The dominant species of caught flies was Chrysomya megacephala(37.83%,2428/6419),followed by Lucilia cuprina(19.16%,1230/6419),and Boettcherisca peregrina(17.36%,1114/6419).Rattus norvegicus was the dominant species of caught rats,accounting for 88.37%(38/43).Blattella germanica was the dominant species of caught cockroaches,accounting for 97.15%(477/491).Compared with the data obtained in 2010,the densities of main vectors decreased significantly in 2011.During the Universiade held in Shenzhen,the densities of main vectors were kept at low levels.The density of adult mosquitoes decreased by 20.55%,and the mosquito and oviposition positive index of Ae.albopictus decreased by 77.70%,and the densities of flies,rats,and cockroaches decreased by 91.29%,44.38%,and 73.10%,respectively.Conclusion Surveillance and control significantly decreased the densities of the main vectors in Shenzhen Universiade venues and prevented the adverse effects of vectors during Universiade.
Scaffolding causal, diagnostic reasoning in a case-based learning environment in medicine

Medical diagnosis is a critical skill that is usually developed with experience in interacting with, diagnosing, and managing patients. Computerdelivered, case-based learning environments can be developed to provide students with valuable diagnostic experiences prior to dealing with real patients. Diagnostic skill requires physicians to understand and use causal reasoning in order to make predictions. That causal reasoning may be scaffolded in the design of those environments. This paper describes the scaffolding of causal reasoning in making initial diagnoses, determining etiology, and making differential diagnoses in plateletrelated problems.
Fetal MRI: incidental findings in the mother

Background Fetal magnetic resonance imaging (MRI) is a routinely used tool in prenatal diagnosis; however, there is a lack of studies evaluating incidental findings observed in the mother.
Greco-Roman Education

When one moves from the study of Alexandrian practitioners of truth to their rhetorical theory—and practice has always preceded theory—he is struck by similarities and differences in what he finds farther to the west. Similarities there were because since its foundation the city had been a Greek outpost of civilization and emersed itself in things Greek. But differences obtained simply due to ethnic variety and geographic distance from Athens and Greek culture.
‘We can’t do that here’: negotiating evidence in HIV prevention campaigns in southwest China

AbstractDisease prevention and health care delivery, areas traditionally governed by the nation state and local communities, are increasingly being inhabited by ‘mobile sovereigns’ who carry a global currency of prevention strategies and treatments grounded in the universal standards of scientific evidence. Drawing on ethnographic evidence from research conducted on HIV in southwest China, this paper examines the impact of evidence-based science on the effectiveness of global health programming. It interrogates the intentions of global health partnerships and how the balance of power waged between those with money, science, and technical expertise, and those seeking assistance and resources, influences global health programming. Ultimately, the paper demonstrates the disconnect between the demand for a system of universal standards developed on the basis of scientific evidence and an appreciation for the local context, which shapes the way these standards should be modified for effective implementation of...
Phylogenetics of Kingsnakes, Lampropeltis getula Complex (Serpentes: Colubridae), in Eastern North America

Kingsnakes of the Lampropeltis getula complex range throughout much of temperate and subtropical North America. Studies over the last century have used morphology and color pattern to describe numerous subspecies. More recently, DNA analyses have made invaluable contributions to our understanding of their evolution and taxonomy. We use genetic and ecological methods to test previous hypotheses of distinct evolutionary lineages by examining 66 total snakes and 1) analyzing phylogeographic structure using 2 mtDNA loci and 1 nuclear locus, 2) estimating divergence dates and historical demography among lineages in a Bayesian coalescent framework, and 3) applying ecological niche modeling (ENM). Our molecular data and ENMs illustrate that 3 previously recognized subspecies in the eastern United States comprise well-supported monophyletic lineages that diverged during the Pleistocene. The geographic boundaries of these 3 lineages correspond closely to known biogeographic barriers (Florida peninsula, Appalachian Mountains, and Apalachicola River) previously identified for other plants and animals, indicating shared geographic influences on evolutionary history. We conclude that genetic, ecological, and morphological data support recognition of these 3 lineages as distinct species (Lampropeltis floridana, Lampropeltis getula, and Lampropeltis meansi).
Signaling Microdomains: InsP3 Receptor Localization Takes on New Meaning

Abstract A fundamental question in cell biology is how different receptor-mediated signaling cascades, despite utilizing many of the same intracellular components, can generate specific cellular responses. Delmas and colleagues (in this issue of Neuron ) address this question in relation to the muscarinic acetylcholine receptor (M 1 AchR) and the B 2 bradykinin receptor (B 2 R). Using Trp channel isoforms as biosensors for PLC stimulation in response to agonist activation, they demonstrate a role for signaling microdomains in the induction of such selective responses.
Core Support for the New Economy

This paper proposes an income guarantee called Core Support (CS), defined as compensation for household activities such as childcare, food preparation, care of elderly or ill persons in the home, and maintenance of the home and of household vehicles and appliances. The immediate goals of the proposal are to highlight, through compensation, the reality that the productive activities carried on in households are of essential importance for the whole economy and society, and to enable the people who carry out these essential activities to do so without having to short-change the care work because of the need to earn money through the market. The CS concept builds on literature on Basic Income Guarantees (BIG) and on feminist economics, which tends to be skeptical of BIG proposals. By addressing intra-household allocations, CS shows how a basic income system can promote a more caring democracy and a more partnership-oriented socioeconomic system that rewards the essential work of care. Appendix A surveys seven ways by which such a program could be financed.
Exposure to Surgery and Anesthesia After Concussion Due to Mild Traumatic Brain Injury

Abstract Objective To describe the epidemiology of surgical and anesthetic procedures in patients recently diagnosed as having a concussion due to mild traumatic brain injury. Patients and Methods Study patients presented to a tertiary care center after a concussion due to mild traumatic brain injury from July 1, 2005, through June 30, 2015, and underwent a surgical procedure and anesthesia support under the direct or indirect care of a physician anesthesiologist. Results During the study period, 1038 patients met all the study inclusion criteria and subsequently received 1820 anesthetics. In this population of anesthetized patients, rates of diagnosed concussions due to sports injuries, falls, and assaults, but not motor vehicle accidents, increased during 2010-2011. Concussions were diagnosed in 965 patients (93%) within 1 week after injury. In the 552 patients who had surgery within 1 week after concussive injury, 29 (5%) had anesthesia and surgical procedures unrelated to their concussion-producing traumatic injury. The highest use of surgery occurred early after injury and most frequently required general anesthesia. Orthopedic and general surgical procedures accounted for 57% of procedures. Nine patients received 29 anesthetics before a concussion diagnosis, and all of these patients had been involved in motor vehicle accidents and received at least 1 anesthetic within 1 week of injury. Conclusion Surgical and anesthesia use are common in patients after concussion. Clinicians should have increased awareness for concussion in patients who sustain a trauma and may need to take measures to avoid potentially injury-augmenting cerebral physiology in these patients.
Elimination of locus-specific inter-individual variation in quantitative PCR.

Robust dosage PCR (RD-PCR), a duplex and quantitative PCR, detects large heterozygous deletions and duplications in genomic DNA samples. RD-PCR amplifies an endogenous internal control and a target...
Reforming Management Accounting To Support Today's Technology

(1990). Reforming Management Accounting To Support Today's Technology. Research-Technology Management: Vol. 33, No. 2, pp. 30-34.
Deeply Confusing: Conflating Difficulty With Deep Revelation on Personality Assessment:

The factors that contribute to lay expectations of personality assessments are not well understood. Five studies demonstrate that people conflate difficulty of personality assessment items with rev...
Continuous monitoring of indoor environmental quality using an Arduino-based data acquisition system

Abstract Building performance monitoring could be limited due to the cost and inflexibility of hardware and software platforms for data acquisition. This paper describes a portable continuous measurement toolbox which provides a robust, easily extendable, and low-cost setup for indoor environmental quality (IEQ) monitoring and performance assessment. Various sensors—temperature, relative humidity, illuminance, CO2, VOC, PM2.5, and occupancy—for IEQ performance measurement are included in this toolbox. Arduino Uno boards were connected to the sensors for data acquisition. ZigBee communication protocol was established between an XBee device for each Arduino board and an XBee receiver connected to a computer. The toolbox utilized the open source, agent-based software platform VOLTTRON for data communication and analysis. The data collection system was calibrated against an accurate data acquisition card. Experiments have been conducted using the toolbox for assessing IEQ performance in an open computer lab within a commercial building. Thermal comfort, indoor air quality, and lighting performance have been analyzed based on collected data. The study demonstrated reliability and robustness of the toolbox for continuous monitoring of indoor environmental quality.
CSolve: verifying c with liquid types

We present CSolve, an automated verifier for C programs based on Liquid Type inference. We show how CSolve verifies memory safety through an example and describe its architecture and interface.
Efficacy Versus Hepatotoxicity of High-dose Rifampin, Pyrazinamide, and Moxifloxacin to Shorten Tuberculosis Therapy Duration: There Is Still Fight in the Old Warriors Yet!

Background One approach that could increase the efficacy and reduce the duration of antituberculosis therapy is pharmacokinetics/pharmacodynamics-based optimization of doses. However, this could increase toxicity. Methods We mimicked the concentration-time profiles achieved by human equivalent doses of moxifloxacin 800 mg/day, rifampin 1800 mg/day, and pyrazinamide 4000 mg/day (high-dose regimen) vs isoniazid 300 mg/day, rifampin 600 mg/day, and pyrazinamide 2000 mg/day (standard therapy) in bactericidal and sterilizing effect studies in the hollow fiber system model of tuberculosis (HFS-TB). In an intracellular Mycobacterium tuberculosis (Mtb) HFS-TB experiment, we added a 3-dimensional human organotypic liver to determine potential hepatotoxicity of the high-dose regimen, based on lactate dehydrogenase (LDH). Treatment lasted 28 days and Mtb bacterial burden was based on colony counts. We calculated the time to extinction (TTE) of the Mtb population in the HFS-TB and used morphism-based transformation and Latin hypercube sampling to identify the minimum therapy duration in patients. Results The kill rate of standard therapy in the bactericidal effect and sterilizing effect experiments were 0.97 (95% confidence interval [CI], .91-.99) log10 colony-forming units (CFU)/mL/day, and 0.56 (95% CI, .49-.59) log10 CFU/mL/day, respectively. The high-dose regimen's bactericidal and sterilizing effect kill rates were 0.99 (95% CI, .96-.99) log10 CFU/mL/day and 0.72 (95% CI, .56-.79) log10 CFU/mL/day, respectively. The upper confidence bound for TTE in patients was 4.5-5 months for standard therapy vs 3.7 months on the high-dose regimen. There were no differences in LDH concentrations between the 2 regimens at any time point (P > .05). Conclusions The high-dose regimen may moderately shorten therapy without increased hepatotoxicity compared to standard therapy.
Grazing-Induced Changes to Biological Soil Crust Cover Mediate Hillslope Erosion in Long-Term Exclosure Experiment

Abstract Dryland ecosystems are particularly vulnerable to erosion generated by livestock grazing. Quantifying this risk across a variety of landscape settings is essential for successful adaptive management, particularly in light of a changing climate. In the Upper Colorado River Basin, there are nearly 25 000 km2 of rangelands with underlying soils derived from Mancos Shale, an erodible and saline geologic parent material. Salinity is a major concern within the Colorado River watershed, much of which is attributed to runoff and leaching from Mancos Shale deposits. In a 60-yr paired-watershed experiment in western Colorado, we used silt fences to measure differences in saline hillslope erosion, including both total sediment yield and concentrations of primary saline constituents (Na and Se), in watersheds that were either exposed to grazing or where livestock was excluded. After accounting for the strong effects of soil type, slope, and antecedent precipitation, we found that grazing increased sediment loss by ≈50% across our 8-yr time series (0.1–1.5 tn ha−1), consistent with levels reported at the watershed scale in early published work from studies at the same location. Eroded sediment Se levels were low and unaffected by grazing history, but Na concentrations were significantly reduced on grazed hillslopes, likely due to depletion of surface Na in soils exposed to chronic soil disturbance by livestock. Variable selection and path analysis identified that biological soil crust (BSC) cover, more than any other variable, explained the differences in sediment yields between grazed and ungrazed watersheds, partially through the enhancement of soil aggregate stability. Our results suggest that BSC cover should be granted heightened consideration in rangeland decision support tools (e.g., state-and-transition models) and that measures to reduce surface disturbance from livestock such as altering the timing or intensity of grazing may be effective for reducing downstream impacts.
FSI-inspired solvent and “full fluorosulfonyl” electrolyte for 4 V class lithium-metal batteries

High-voltage rechargeable lithium-metal batteries (LMBs) require electrolytes that are compatible with both the Li metal anode (LMA) and the metal-oxide cathode. Herein, by imitating the fluorosulfonyl imide group from a well-known LMA-compatible salt, lithium bis(fluorosulfonyl) imide (LiFSI), we come up with an organic solvent dimethylsulfamoyl fluoride (FSO2NC2H6), a fluorosulfonamide (FSA) with two methyl substituents, to develop a new “full fluorosulfonyl” (FFS) electrolyte. Remarkably, it enables a highly reversible LMA with an excellent initial coulombic efficiency (CE) ∼91%, and rapidly approaching 99% within only 10 cycles, with average CE outperforming the well-known LMA-compatible fluoroethylene carbonate (FEC)-based electrolyte. Furthermore, benefitting from its high anodic stability against the oxidative LiNi0.6Mn0.2Co0.2O2 (NMC622) and LiMn2O4 (LMO) surfaces, the Li‖NMC622 cell retains 89% of its original capacity after 200 cycles using a limited Li excess anode. This electrolyte design strategy opens a new avenue for exploring new medium-concentration organic electrolytes for 4 V class lithium-metal batteries (LMBs).
Point-of-care ultrasound use in umbilical line placement: a review

Point-of-care ultrasound (POCUS) has become a novel tool for assessing umbilical catheter tip location in the neonate. This review analyzes the current evidence on the efficacy and utility of POCUS for identifying umbilical catheter positioning. Medline, EMBASE, and Cochrane searches were performed until October 2018. Eight studies were identified comparing POCUS to x-ray in assessing umbilical catheter tip location in the last 10 years. POCUS was shown to be feasible and appears to be a superior imagining modality to x-rays in assessing umbilical line tip location. POCUS is more accurate in determining umbilical catheter positioning, allows for more rapid line umbilical catheter placement, and reduces the time to treatment as well as radiation exposure to the neonate when compared with x-ray. The available studies support further education in training neonatal providers to become proficient in POCUS for assessing umbilical lines.
Does Hepatic Impairment Affect the Exposure of Monoclonal Antibodies

Limited information is available regarding the effect of hepatic impairment (HI) on the pharmacokinetics of monoclonal antibodies (mAbs). The results of an earlier report based on therapeutic proteins, including mAbs, approved through the end of 2012 were inconclusive due to limited HI data available at that time. New HI data for mAbs or antibody-drug conjugates (ADCs; with a focus on the mAb component) available between 2013 and 2018 were evaluated. The investigation indicates there is almost no data for severe HI, limited data for moderate HI, and abundant data for mild HI. A significant exposure decrease was found for several mAbs or ADCs and a trend for decreasing area under the concentration-time curve (AUC) was observed for other mAbs. Multiple potential mechanisms may contribute to the exposure decrease. Dose may need to be adjusted for patients with HI, after taking into account the exposure-response relationships for both efficacy and safety.
Empathy in Medicine: What It Is, and How Much We Really Need It

It is acknowledged that empathy plays a critical role in the physician-patient relationship and has a positive impact on health outcomes. However, as the field of empathy expands, the lack of conceptual coherence challenges advances in medicine. In fact, in some medical settings, there is little added theoretical or clinical value in applying the all-encompassing term of empathy, which is by nature multidimensional, interpersonal, and modulated by context. Functional neuroimaging studies of health professionals, designed to examine patterns of brain activation in response to empathy-eliciting situations, bring theoretical clarity to the neurocognitive mechanisms that underlie interpersonal sensitivity, emotional empathy, cognitive empathy, and caring. These components are relatively independent but often interact and are deeply interwoven in the fabric of the brain. Nevertheless, it seems clear from this review that cultivating empathic concern or compassion in today's medicine is more important than other aspects of empathy, like vicariously experiencing and introspecting about patients' emotions. Specific neurobiological mechanisms explain the benefit to patients of their physicians' perceived empathy.
Relationship between soleus H-reflex asymmetry and postural control in multiple sclerosis.

Background: Impaired postural control is a common symptom in people with multiple sclerosis. Multiple sclerosis frequently presents with asymmetric motor involvement. One measurement yet to be eval...
Cardiac myosin binding protein-C phosphorylation accelerates β-cardiac myosin detachment rate in mouse myocardium

Length perturbation analysis was used to demonstrate that β-cardiac myosin characteristic rates of detachment and recruitment in the intact myofilament lattice are accelerated by Pi, phosphorylatio...
Methamphetamine facilitates HIV infection of primary human monocytes through inhibiting cellular viral restriction factors

Background Methamphetamine (METH), a potent addictive psychostimulant, is highly prevalent in HIV-infected individuals. Clinically, METH use is implicated in alteration of immune system and increase of HIV spread/replication. Therefore, it is of importance to examine whether METH has direct effect on HIV infection of monocytes, the major target and reservoir cells for the virus. Results METH-treated monocytes were more susceptible to HIV infection as evidenced by increased levels of viral proteins (p24 and Pr55Gag) and expression of viral GAG gene. In addition, using HIV Bal with luciferase reporter gene (HIV Bal-eLuc), we showed that METH-treated cells expressed higher luciferase activities than untreated monocytes. Mechanistically, METH inhibited the expression of IFN-λ1, IRF7, STAT1, and the antiviral IFN-stimulated genes (ISGs: OAS2, GBP5, ISG56, Viperin and ISG15). In addition, METH down-regulated the expression of the HIV restriction microRNAs (miR-28, miR-29a, miR-125b, miR-146a, miR-155, miR-223, and miR-382). Conclusions METH compromises the intracellular anti-HIV immunity and facilitates HIV replication in primary human monocytes. Supplementary Information The online version contains supplementary material available at 10.1186/s13578-021-00703-4.
Analysis of the development of the flame brush in turbulent premixed spherical flames

Abstract The thickness of the turbulent flame brush is central to the modeling of premixed turbulent combustion and the theory of turbulent diffusion is often applied to explain the growth of the brush with varying success. However, numerous studies have shown that the brush evolves differently from the dispersion of material points on the account of flame propagation, density changes across the front, and hydrodynamic instabilities. Modifications to turbulent diffusion theory to incorporate these effects are challenging since the theory is Lagrangian. In this article, we present an alternate Eulerian framework based on the surface density formalism. We employ the proposed framework to analyze a database of direct numerical simulations of spherical turbulent premixed flames in decaying isotropic turbulence and recover mechanisms for which scaling laws are proposed and assessed against data. We characterize quantitatively two mechanisms: one related to the mean velocity gradient induced by thermal expansion and the other due to flame propagation in the presence of curvature. We demonstrate that the net effect of these two processes is to hinder the growth of the turbulent flame brush in the present configuration. Our analysis supports the notion that the turbulent flame brush does not grow indefinitely, rather it attains a maximum thickness.
Abstract MP27: Adipose-derived Human Soluble (Pro)renin Receptor Causes Resistance To Losartan Treatment In High-Fat Diet Male And Female Mice

Obesity, affecting more that 37% of the US, contributes to hypertension. Despite the use of one or more anti-hypertensive treatments, 48% of the hypertensive population remains with resistant hyper...
Executive compensation and executive incentive problems: an empirical analysis

Abstract The question of whether the design of the corporate executive pay package reflects an attempt to reduce agency costs between shareholders and managers is addressed. The components of senior executive pay are found to vary systematically across firms in a manner that cannot easily be explained by tax effects, and which would indicate that individual elements of pay are aimed at controlling for limited horizon and risk exposure problems. Managerial decisions and the structure of managerial pay therefore appear to be interrelated.
An evaluation of ventilator reliability: a multivariate, failure time analysis of 5 common ventilator brands.

Introduction Mechanical ventilator failures expose patients to unacceptable risks and are expensive. By identifying factors that correlate with the amount of time between consecutive ventilator failures, we might reduce patient risk, save money, and shed light on a number of important questions concerning whether reliability changes as a function of time. Objective Investigate the correlation between several explanatory variables and the time between consecutive ventilator failures and address the following questions: (1) Are ventilators as safe and reliable following repairs as they were before failing? (2) Does reliability change significantly as a ventilator is used or ages? (3) Does a hospital's particular operating environment play a role in ventilator reliability? (4) Are ventilator service contracts worth the money? Methods A retrospective review was conducted using repair and maintenance records from 2 hospitals: a 570-bed teaching hospital and a 410-bed local community hospital. Records were examined from a total of 66 individual ventilators, of 5 different brands, used between July 1, 1991, and January 3, 2001. The ventilators included 13 Tyco-Mallinckrodt Infant Star, 10 Bird VIP, 11 Bird 6400ST, 16 Bird 8400STi, and 16 Tyco-Mallinckrodt 7200ae. The dependent variable was the operating time between or before unexpected mechanical failures; this was determined by the difference between hours logged on the ventilator hour meter at the time of failure and that recorded when the study began, or when the ventilator was new. Thereafter (when applicable), the time before failure was the difference in hours at consecutive failures. Seven independent explanatory covariates were selected and analyzed as potential correlates with time between failures. Another independent variable, the site of ventilator use (community or teaching hospital), was also tested for significance. Data were analyzed using the Cox proportional hazard model, the multiple-groups survival statistic, and the Cox-Mantel test. Results In 2,567,365 hours of ventilator operation, 290 observations were recorded (226 failures and 64 censored observations). Two of the 7 covariates were judged time-dependent, excluded from the Cox model, and evaluated using other techniques. Of the 5 remaining covariates, 2 were significantly related to reliability, both indirectly. There was no difference in reliability, regardless of how many times a ventilator had been previously repaired, but hospital environment did significantly affect reliability. Conclusions Ventilator reliability depends on a number of factors. This study indicates that, on average, ventilator reliability improves the more a ventilator is used and the longer the brand has been commercially available. The number of previous ventilator repairs did not affect reliability, but the hospital environment did. These data, if validated, should help to enhance our understanding of ventilator reliability and could eventually have profound economic and safety implications as well.
Social Policy & U.S. Poverty 1960-1999: An Economic History

Interrogates poverty debate (growth versus redistribution) reignited by underperforming poverty reductions during 1980s' social spending austerity compared to 1960s' "War on Poverty." Growth and inequality explain 75% 1959-1999 poverty variation; census measurement changes 17%. Significantly, census measurement changes plus overestimated inflation biased-up 1980s measured poverty (deflated 1960s) partly explaining eighties' underperformance. Growth's poverty effect remained constant; rising inequality required 1980's growth 50% higher (1960s) for equivalent poverty reductions. Counterfactual simulations 1959-1999: absent rising earnings inequality, growth drives poverty to 5.4%; increased workerless households offset two-thirds poverty reduction from cash transfers; had Carter and Reagan redistributed like predecessors, poverty reduced one-half.
Predictors of late-onset smoking and cessation over 10 years.

Abstract Purpose: To identify predictors of smoking onset and cessation between early (age 13 years) and late adolescence (age 18 years) and between late adolescence (age 18 years) and young adulthood (age 23 years). Methods: We employed logistic regression to predict smoking initiation and cessation for an ethnically diverse sample of 3056 adolescents recruited from 30 West Coast schools in 1985 and observed from age 13 to age 23 years. Fifty-six percent of the sample was female. Predictors tapping sociodemographic characteristics, environmental influences, attitudes and beliefs about smoking, bonds with school, and problem behavior were measured at age 13 years (older teenager models) and at age 18 years (young adult models). Results: Robust predictors of both initiation and cessation across the two developmental periods included doing poorly in middle/high school and prior smoking behavior. Predictors common to three of the four models included being young for one's grade cohort and intending to smoke in the next 6 months. Early deviant behavior and drinking fostered initiation among older teenagers, but problem behavior as an older teenager did not predict young adult initiation. Smokers who had few or no high school friends who smoked and felt able to resist prosmoking pressures at age 18 years were more likely to quit by age 23 years. Being female predicted initiation by age 18 years; being African-American, Hispanic, or Asian inhibited it. Conclusions: The strong association of prior smoking behavior and intentions with later smoking status among both adolescents and young adults underscores the importance of starting smoking prevention early and continuing it through high school. Such programs might also consider the greater vulnerability of females, youth who are young for their grade cohort, and those who are doing poorly in school.
Trace ideals and their applications

Preliminaries Calkin's theory of operator ideals and symmetrically normed ideals convergence theorems for $\mathcal J_P$ Trace, determinant, and Lidskii's theorem $f(x)g(-i\nabla)$ Fredholm theory Scattering with a trace condition Bound state problems Lots of inequalities Regularized determinants and renormalization in quantum field theory An introduction to the theory on a Banach space Borel transforms, the Krein spectral shift, and all that Spectral theory of rank one perturbations Localization in the Anderson model following Aizenman-Molchanov The Xi function Addenda Bibliography Index.
Structure of the gene encoding the human leukocyte adhesion molecule-1 (TQ1, Leu-8) of lymphocytes and neutrophils

The leukocyte adhesion molecule-1 (LAM-1, TQ1, Leu-8), expressed by human lymphocytes, neutrophils, monocytes, and their precursors, is a member of the selectin family of cellular adhesion/homing receptors which play important roles in leukocyte-endothelial cell interactions. These cell surface molecules contain an amino-terminal lectin-like domain followed by an epidermal growth factor-like domain and a variable number of short consensus repeat sequences similar to those found in C3/C4 binding proteins. In this report, the structure of the lyam-1 gene that encodes the LAM-1 protein was determined by isolating overlapping genomic DNA clones that hybridized with a LAM-1 cDNA probe. The lyam-1 gene spans greater than 30 kilo base pairs of DNA and is composed of at least 10 exons. The 5' end of the LAM-1 mRNA was mapped by primer extension analysis revealing a single initiation region for transcription. Exons II through X contain translated sequences; exon II encodes the translation initiation codon; exon III, the leader peptide; IV, the lectin-like domain; V, the epidermal growth factor-like domain; VI and VII, the short consensus repeat units; exon VIII, the transmembrane region; exon IX encodes seven amino acids containing a potential phosphorylation site; and exon X encodes the five remaining amino acids of the cytoplasmic tail and the long 3' untranslated region. Sequencing of LAM-1 cDNA clones derived from neutrophils revealed that the protein expressed by neutrophils would be identical in sequence with the protein expressed by lymphocytes and cDNAs that would encode different isoforms of LAM-1 protein were not detected. In addition, the level of LAM-1 expression by lymphocytes and neutrophils from two patients with paroxysmal nocturnal hemoglobinuria, a disorder in which linkage of phosphatidylinositol anchors to proteins is defective, was similar to that of normal controls. Therefore, the usage of exons II through X results in the generation of a single major LAM-1 protein product expressed by lymphocytes and neutrophils.
Synaptic calcium-channel function in Drosophila: analysis and transformation rescue of temperature-sensitive paralytic and lethal mutations of cacophony.

Voltage-gated calcium channels play a key role in chemical synaptic transmission by providing the calcium trigger for regulated neurotransmitter release. Genes encoding the primary structural subunit, α1, as well as accessory subunits of presynaptic calcium channels have now been identified in a variety of organisms. Thecacophony (cac) gene in Drosophila, also known as nightblind A, encodes a voltage-gated calcium-channel α1 subunit homologous to vertebrate α1 subunits implicated in neurotransmitter release. A recent genetic screen in our laboratory isolated cacTS2, a conditional cac mutant exhibiting rapid paralysis at elevated temperatures. This mutant has allowed synaptic electrophysiology after acute perturbation of a specific calcium-channel gene product, demonstrating that cacencodes a primary calcium channel functioning in neurotransmitter release. Here we report the molecular lesion incacTS2, a missense mutation within a calcium-dependent regulatory domain of the α1 subunit, as well as phenotypic rescue of temperature-sensitive and lethalcac mutations by transgenic expression of a wild-typecac cDNA. Notably, rescue of rapid, calcium-triggered neurotransmitter release was achieved by neural expression of a single cDNA containing a subset of alternative exons and lacking any conserved synaptic-protein interaction sequence. Possible implications of these findings are discussed in the context of structure–function studies of synaptic calcium channels, as well as alternative splicing and mRNA editing of the cac transcript.
Effects of time of season and cottonseed meal and lasalocid supplementation on steers grazing rye pastures

A study was conducted to estimate changes in rye (Secale cereale L.) forage quality during the grazing season and to determine the effects of supplemental cottonseed meal (CSM) with and without the ionophore lasalocid on the growth rate of steers grazing rye pastures
Household pesticide usage in the United States.

A total of 10,000 U.S. households in 25 standard metropolitan statistical areas and 25 counties were included in the United States. More than 8,200 households granted an interview. Nine of every ten households in the United States used some types of pesticide in their house, garden, or yard. Households in the southeastern United States used the most pesticides. Although more than 500 different pesticide formulations were used by the sampled households, 15 pesticides accounted for 65.5% of all pesticides reported in this study. Thirteen of these 15 pesticides were insecticides, one was a herbicide, and one was a rodenticide.
Experiences in developing an automated factor-jump method of thermogravimetry

Abstract We have recently provided details of an apparatus and computer programs to implement the factor-jump method of thermogravimetry. This paper describes the refinement of the technique to the present status of quasi-automatic routine operation. The procedure was worked out using samples of polymethyl-methacrylate, polystyrene and polyurethane polymers. The activation energies obtained are measured to 0.2 kcal mole −1 in favorable cases. This is adequate for diagnosis of changes in mechanism but may sometimes be inadequate for scaling temperature accelerated tests to room temperature.