cssi/SciSciGPT-SciSciNet huggingface dataset:
Activation of JAZ by Small Molecules in Human Leukemia Cells.

By screening a murine interleukin-3 (IL-3)-dependent myeloid cell cDNA library, we previously identified JAZ (Just Another Zinc Finger Protein), a novel zinc finger protein. JAZ belongs to a new class of evolutionarily conserved C2H2-type ZFPs that feature an unusually long linker sequence and preferentially bind to double-stranded RNA. JAZ localizes in the nucleus and its human gene is localized to the chromosome 5q35-qter, a specific chromosomal region at which deletions and translocations occur in leukemia and lymphoma. We have recently discovered JAZ as a novel direct, positive regulator of p53 transcriptional activity. The mechanism involves direct binding to p53’s C-terminal (negative) regulatory domain to activate “latent” p53 in response to non-genotoxic stress signals (such as interleukin-3 growth factor withdrawal). Thus, we have explored JAZ as a potentially novel molecular target in human leukemia by identifying small molecules to activate JAZ-mediated leukemic cell killing. A structure-based drug design approach was employed to screen small molecules that potentially bind and activate JAZ. Cytotoxicity assays were then carried out with a set of candidate compounds in a dose- and time-dependent manner in various human leukemia cell lines including REH, HL-60, U937, HEL and K562 cells. Several JAZ “activating” compounds were selected, which display differential abilities to induce leukemic cell killing (IC50 = < 1 to 100 μM). Interestingly, biochemical analysis shows that the J-compound(s) can mediate cell death in p53 expressing leukemia cells in association with upregulation of expression of JAZ, p53 and the proapoptotic p53 target gene BAX, indicating activation of p53. Furthermore, the J-compound(s) synergizes induction of leukemic cell death when combined with other known p53 activating agents including cisplatin and nutlin-3, a recently developed small molecule MDM2 antagonist that disrupts the p53-MDM2 interaction. Therefore, the J-compound(s) may mediate leukemic cell death in a mechanism involving activation of “latent”, wild-type p53 by targeting JAZ. However, the J-compound-mediated cell death was also observed in some p53-deficient leukemia cell lines. This suggests that depending on the cell type the J-compounds may also act by a p53-independent mechanism. Since JAZ was recently reported to be a cargo protein for exportin-5, the nuclear export receptor for pre-microRNAs, this dsRNA-binding ZFP may also have an unknown p53-independent function via which the J-compound(s) may possibly act. While these possible mechanisms remain to be further investigated, the J-compound(s) points the way to develop a potentially novel therapeutic strategy targeting JAZ to treat human leukemia.
God’s Creativity

God-or-Substance-or Nature is the totality of the real, infinite in the sense of absolutely complete, self-contained, self-caused and self-maintaining. Its eternal essences is expressed in infinite attributes each inexhaustible and illimitable in its own kind, but limited wholly to its own kind. Under each of these attributes there follow from the infinite power (or essence) of God interminable series of modes, some infinite in themselves and the rest infinite, singular things. The infinite modes are the immediate consequences of God’s essences as expressed in his attributes; they follow from his nature, Spinoza insists, in the same way as the properties of a triangle follow from its definition; that is, they are logical consequences of God’s eternal essence. But his essence is the same as his power, so they are consequences, likewise, or effects, of God’s casual efficacy. This two-fold character of God’s creative potency involves some obscurity and needs explanation, to provide which will be the main object of the present chapter.
Trends and clinico-sociodemographic determinants of stereotactic body radiotherapy use for localized prostate cancer: A National Cancer Database study.

e545Background: Stereotactic body radiotherapy (SBRT) represents an emerging and cautiously guideline-approved definitive therapy option for prostate cancer, though long-term data on efficacy and t...
Chemotherapy for Hepatocellular Carcinoma: Current Evidence and Future Perspectives.

Hepatocarcinogenesis is a multistep process, heralded by abnormalities in cell differentiation and proliferation and sustained by an aberrant neoangiogenesis. Understanding the underlying molecular pathogenesis leading to hepatocellular carcinoma is a prerequisite to develop new drugs that will hamper or block the steps of these pathways. As hepatocellular carcinoma has higher arterial vascularization than normal liver, this could be a good target for novel molecular therapies. Introduction of the antiangiogenic drug sorafenib into clinical practice since 2008 has led to new perspectives in the management of this tumor. The importance of this drug lies not only in the modest gain of patients’ survival, but in having opened a roadmap towards the development of new molecules and targets. Unfortunately, after the introduction of sorafenib, during the last years, a wide number of clinical trials on antiangiogenic therapies failed in achieving significant results. However, many of these trials are still ongoing and promise to improve overall survival and progression-free survival. A recent clinical trial has proven regorafenib effective in patients showing tumor progression under sorafenib, thus opening new interesting therapeutic perspectives. Many other expectations have been borne from the discovery of the immune checkpoint blockade, already known in other solid malignancies. Furthermore, a potential role in hepatocellular carcinoma therapy may derive from the use of branched-chain amino acids and of nutritional support. This review analyses the biomolecular pathways of hepatocellular carcinoma and the ongoing studies, the actual evidence and the future perspectives concerning drug therapy in this open field.
Explaining extreme ground motion in Osaka basin during the 2011 Tohoku earthquake

Despite being 770 km away from the epicenter, observed ground motions due to the Tohoku earthquake in the Osaka Basin were unexpectedly large, with an amplification of more than a factor of 20 compared to immediately outside the basin, and including 2.7 m peak-to-peak roof displacements at one high-rise building. The local ground motions exceeded expectations based on standard computations of site response by a factor of 3, predicted frequencies of peak acceleration were off by at least 50%, and such discrepancies have not yet been explained quantitatively. Here we show that utilizing semianalytic theory for surface-wave amplification, we are able to accurately predict both the amplitudes and frequencies of large ground amplification in the Osaka Basin using only knowledge of the local one-dimensional structure. Comparison between this simple prediction and observed amplification was not expected to be so favorable and suggests that simple one-dimensional surface-wave site amplification factors can be useful in the absence of full three-dimensional wave propagation simulations. Such surface-wave amplification factors can be included in addition to the standard measures of site-specific site amplification and should help explain strong ground motion variability in future large earthquakes that shake Osaka Basin and elsewhere in the world.
Thermal, Energy and Daylight Analysis of Different Types of Double Skin Facades in Various Climates

This article explores thermal, energy and daylighting performance of double skin facades (DSFs) in different climate types, specifically focusing on three typologies: box window, corridor and multi-story DSFs. These systems were investigated and analyzed to determine how different DSFs perform in comparison to each other, as well as a typical curtain wall (single skin glazed facade used as a baseline), in a multitude of climate applications. The utilized research methods included two-dimensional heat transfer analysis (Finite Element Method analysis), Computational Fluid Dynamics (CFD) analysis, energy modeling, and daylight simulations. Heat transfer analysis was used to determine heat transfer coefficients (U-values) of all analyzed facade types, as well as temperature gradients through the facades for four exterior environmental conditions. CFD analysis investigated three-dimensional heat flow, airflow and air velocity within air cavity of DSFs. Energy modeling and daylight simulations were conducted for an office space, which was enclosed by the analyzed facade types. Individual energy models were developed for each facade type and for fifteen different climates representing various climate zones and subzones, from very hot to arctic. For daylighting simulations, multiple models were developed to study investigated typologies of DSFs, depth of air cavity between the two skins, orientations and four climate types, as well as different sky conditions. Results indicate that there is not a lot of variation in thermal performance of the different DSF types, but that all DSF facades would have significantly improved thermal performance compared to the baseline single skin facade. Energy modeling results indicate significant differences in performance between the DSFs and single skin facade, but fewer variations between the different typologies of investigated DSFs. Moreover, the results show the effect of DSFs in different climate types on energy performance, heating, cooling and lighting loads. Daylighting results indicate that all types of DSFs would decrease daylight levels compared to a conventional curtain wall, however, the differences between lighting levels are also dependent on the orientation, air cavity depth, facade type and climate.
Value of Face-to-Face Interactions Between Clinician-Educators and Patients or Students to Improve Health Care Education

The power and outreach of the media is enormous and has restructured our society today; the author acknowledges the impact and appreciates the outreach. However, I question the relative lack of focus on physical human interactions and express concern over future training efforts. I have compared and attempted to highlight the components of two interaction scenarios: those of teacher-student, and those of physician-patient. The physician-educators need to generate a discussion regarding the value of each interaction. As a teacher, there is value in online classrooms, and a different value in face-to-face interactions. Similarly, a physician can have major outreach impact by online tele-medicine and tele-education efforts, but in some instances, may need to have the human, physical interaction with the patient. The value of these interactions depends on the roles in which these interactions are experienced. Medical education training must incorporate an understanding of the unique value of different interactions.
Using binaural beat sensitivity to explore mechanisms of bimodal temporal envelope beat sensitivity

Current cochlear implant (CI) fitting strategies aim to maximize speech perception through the CI by allocating all spectral information across the electrode array without regard to tonotopic placement of each electrode along the basilar membrane. For patients with considerable residual hearing in the non-implanted ear, this approach may not be optimal for binaural hearing. This study aims to explore fitting procedures in which CI maps better complement information from the acoustic ear by reducing the frequency mismatch between them. We investigate the mechanisms of binaural temporal-envelope beat sensitivity in normal-hearing listeners using bandpass filtered pulse trains with parameters including stimulus level, filter bandwidth, filter slope, and spectral overlap using bandpass filtered pulse trains. We find the minimum baseline interaural timing difference and spectral mismatch that normal-hearing listeners can tolerate while maintaining their ability to detect interaural timing differences. Initial results consistently demonstrate maximum sensitivity to binaural beats when place of stimulation is matched across ears. The outcomes of this study will provide new information on binaural interactions in normal-hearing listeners and guide methodology for incoming single-sided-deafness patients as we adjust their CI maps in an effort to reduce the frequency-mismatch. [Work supported by NIH grant F32DC016815-01.]Current cochlear implant (CI) fitting strategies aim to maximize speech perception through the CI by allocating all spectral information across the electrode array without regard to tonotopic placement of each electrode along the basilar membrane. For patients with considerable residual hearing in the non-implanted ear, this approach may not be optimal for binaural hearing. This study aims to explore fitting procedures in which CI maps better complement information from the acoustic ear by reducing the frequency mismatch between them. We investigate the mechanisms of binaural temporal-envelope beat sensitivity in normal-hearing listeners using bandpass filtered pulse trains with parameters including stimulus level, filter bandwidth, filter slope, and spectral overlap using bandpass filtered pulse trains. We find the minimum baseline interaural timing difference and spectral mismatch that normal-hearing listeners can tolerate while maintaining their ability to detect interaural timing differences. Initial ...
Karma: Cost-Effective Geo-Replicated Cloud Storage with Dynamic Enforcement of Causal Consistency

Causal consistency has emerged as an attractive middle-ground to architecting cloud storage systems, as it allows for high availability and low latency, while supporting semantics stronger than eventual consistency. However, causally-consistent cloud storage systems have seen limited deployment in practice. A key factor is these systems employ full replication of all the data in all the data centers ( DCs ), incurring high cost. A simple extension of current causal systems to support partial replication by clustering DCs into rings incurs availability and latency problems. We propose Karma , the first system to enable causal consistency for partitioned data stores while achieving the cost advantages of partial replication without the availability and latency problems of the simple extension. Our evaluation with 64 servers emulating 8 geo-distributed DCs shows that Karma (i) incurs much lower cost than a fully-replicated causal store (obviously due to the lower replication factor); and (ii) offers higher availability and better performance than the above partial-replication extension at similar costs.
Endovascular Retrieval of Migrated Coil within the Distal Middle Cerebral Artery Using Stentriever Device

Background Displacement of endovascular coils during endovascular embolization of an intracranial aneurysm is a potentially life-threatening complication. Several methods for coil retrieval have been described, including the use of microsnares and microforceps retrieval devices. With the recent surge of stentriever implementation in the treatment of ischemic stroke, some operators are now using such devices in the retrieval of migrated coils. We present a case of a balloon-assisted coil embolization of a communicating segment internal carotid artery aneurysm, complicated by coil migration far distally into the middle cerebral artery, which was retrieved successfully with a stentriever. To the best of our knowledge, this is the furthest migration of a coil to be successfully retrieved with a stentriever. We review conservative and invasive management of displaced coils and the technical advantages of stentrievers over retrieval devices. Methods The patient's medical records were retrospectively reviewed, including clinical and radiographic information. This study received institutional review board approval. Results The patient was treated with balloon-assisted coil embolization of the internal carotid artery aneurysm. The migrated coil was retrieved successfully using a novel application of a stentriever. Conclusions In certain situations, a stentriever does not mandate complete ensnaring of the target to be retrieved and thus need not always be deployed distal to a migrated coil mass to be successful. Due to the mechanical advantage of strut-engagement, stentrievers can afford to be positioned in relatively suboptimal positions, and this is especially useful in cases involving tortuous and small distal vessels (
An Exploratory Analysis of Preliminary Blinded Applicant Scoring Data From the Baldrige National Quality Program

[This abstract is based on the author’s abstract.] Insights related to the Baldrige program and its scoring process are investigated using data released in 2009 by the National Institute of Standards and Technology. The focus is on applicant performance..
Odontogenic fibroma with calcification. Report of a case with a review of the literature.

Abstract The diagnostic problems associated with the discovery of a rare benign odontogenic tumor, the odontogenic fibroma, have been presented. A review of the literature reveals seven cases with similar clinical and radiographic evidence but with inconsistent microscopic features. Because of the inadequate number of cases reported, positive conclusions are not possible.
Singlet Molecular Oxygen: From a Scientific Curiosity to a Ubiquitous Chemical Species

Spectroscopists have recognized the existence of infrared electronic states of molecular oxygen through observations of an astrophysical nature. In the 40 years since careful spectroscopic observations on singlet molecular oxygen were made, no research on its terrestrial chemical and biological importance was carried out. Suddenly it was discovered about ten years ago that singlet molecular oxygen could be produced quantitatively in simple chemical reactions. The last ten years have seen a renascence of research in singlet molecular oxygen indicating its general importance as an organic reactant, as a chemical species occurring under widely different chemical reaction conditions, and, more recently, in extensive applications to biochemical systems, some of which are directly involved in human physiology. This lecture reviewed the study of singlet molecular oxygen and some interesting recent developments.
Porosity and electrical resistivity-based empirical calculation of the oxygen diffusion coefficient in concrete

Abstract Concrete carbonation induced by gas transport has an adverse effect on the service life of the steel-reinforced material. Gas tightness is crucial where concrete is used to contain radioactive materials and of utmost importance where acting as a radon barrier. Since as a rule gas travel inside concrete is governed either by diffusion or permeability, the material’s performance in that respect is assessed by analysing those two parameters. The gas diffusion coefficient in concrete is not readily found, however, due to the practical difficulties involved in preventing gas from leaking out of standard diffusion cells. An alternative approach is to measure permeability at high gas concentration and pressure. The existence of a relationship between the oxygen diffusion coefficient and permeability in OPC concrete was established by the authors in a previous paper. Diffusion has also been shown to be related to porosity and, in solutions, to electrical resistivity. Little is known, however, about the relationship between gas diffusion and resistivity where the pores may be filled not with a liquid, but with air. Inasmuch as resistivity is a non-destructive technique and porosity a property that can be readily measured, these two parameters could be used to directly assess concrete durability, its performance in nuclear facilities and its suitability as a radon barrier. This paper describes a study conducted to formulate equations from which to analytically determine the oxygen diffusion coefficient. These equations are derived from empirical measurements of oxygen diffusion coefficient, concrete porosity and electrical resistivity. The findings, which corroborate the existence of such relationships, were used to formulate an equation to calculate the diffusion coefficient directly from the experimental values of concrete porosity and resistivity. Since porosity depends primarily on concrete batching, curing and moisture content, two OPC concrete mixes were prepared using different water/cement ratios and two curing conditions. The combination resulted in four types of concrete. Pre-conditioning at three values of relative humidity was subsequently deployed.
Decreased milk yield is associated with delayed milk ejection.

ABSTRACT To determine whether individual cow milking vacuum (within the short milk tube and the liner mouthpiece) could be substituted for milk flow technology to identify delayed (bimodal) milk ejection, and the possible relationship between bimodal milk flow and milk yield, we recorded milking data from 663 Holstein cows on a 3,600-cow Michigan dairy that milked 3 times per day. Overall, delayed milk ejection occurred in 45.6% of the milkings, and 98% of the cows with delayed milk ejection also had bimodal flow. Multivariable analysis revealed that milk yield during each individual cow milking was positively associated with increasing lactation number but negatively associated with increasing days in milk and delayed milk ejection. As the time between unit attachment and the estimated milk letdown (the lag period) increased, milk yield decreased; relative to a lag of
Correspondence between lung function and symptom measures from the Cystic Fibrosis Respiratory Symptom Diary–Chronic Respiratory Infection Symptom Score (CFRSD-CRISS)

Abstract Background Pulmonary exacerbations (PEx) in cystic fibrosis (CF) patients reduce quality of life. Lung function, measured by the percent predicted forced expiratory volume in 1 s (ppFEV1), is widely used to evaluate PEx treatments. We analyzed the correspondence of ppFEV1 with 8 patient-reported symptom-based questions from the Cystic Fibrosis Respiratory Symptom Diary–Chronic Respiratory Infection Symptom Score (CFRSD-CRISS). Methods Data were derived from the observational Standardized Treatment of Pulmonary Exacerbations (STOP) study. CF patients who had CFRSD-CRISS and ppFEV1 measurements on ≥2 timepoints were included: 1) day of initial PEx, 2) 7 days later, and/or 3) end of PEx. We calculated age-stratified Spearman correlation coefficients and 95% confidence intervals (95% CIs) between the change in ppFEV1 and change in CFRSD-CRISS items from index to day 7 and from index to the end of PEx treatment. Results Lung function and symptom scores improved by the end of treatment; however, correlations between ppFEV1 and the specific CFRSD-CRISS measures were mostly weak to moderate. An exception was that among patients Conclusions As novel treatments are developed for PEx, it is important to ensure that improvement is measured meaningfully. The generally weak associations between patient-reported symptoms and ppFEV1 that we found suggest that these measures capture different aspects of the disease and both metrics are important when evaluating new treatments.
A Machine Learning Approach to Load Tracking and Usage Monitoring for Legacy Fleets

With changes to aircraft usage due to expanded roles, operators need to monitor the usage of the aircraft and component loads to ensure safe operation of the components within their fatigue lives. Accurate load monitoring of aircraft component loads during flight is a challenge that has inspired the implementation of computational intelligence and machine learning techniques to replace the need for costly sensor systems. Much research has been carried out to develop a methodology for load signal and fatigue life estimation using only data from standard flight state and control system parameters. The National Research Council’s approach to load and usage monitoring is centered on leveraging the data recorded by existing instrumentation using machine learning models and data mining techniques. This flexible approach has been demonstrated on several helicopter platforms manufactured by different original equipment manufacturers. Results from the Australian S-70A-9 Black Hawk and Canadian Forces CH-146 Griffon (Bell 412) are provided to demonstrate the analysis and outputs enabled by accurate load monitoring. These outputs include load signal estimates, fatigue damage accumulation, and load exceedance plots and comparisons.
Dynamic Plastic Deformation for Non-Proportional Loading Paths

Improved understanding of the plastic response of metals subjected to loading histories which include marked changes in direction of the stress trajectories (in a hyperspace of components of the stress tensor) is of fundamental importance in plasticity theory and its applications. In particular, the plastic response following abrupt changes in direction of the stress trajectory provides, for rate independent models of plastic response, a critical distinction between models incorporating smooth yield surfaces and those incorporating yield surfaces with vertices. Differences between predictions obtained using these two classes of models appear to be important in a number of applications including plastic buckling, stability of finite plastic deformations, strain localization, and plastic waves.
Women’s Risk and Needs Assessment (WRNA) in the Czech Republic

The focus of practitioners and academics alike has been shifting toward gender-responsive treatment of justice-involved women. One instrument that accounts for the realities of justice-involved wom...
Utility, Publicity, and Law : Essays on Bentham's Moral and Legal Philosophy

The essays in this volume offer a reassessment of Jeremy Bentham’s strikingly original legal philosophy. Early on, Bentham discovered his “genius for legislation” — “legislation” included not only law making and code writing, but also political and social institution building and engineering of public spaces for effective control of the exercise of political power. In his general philosophical work, Bentham sought to articulate a public philosophy to guide and direct all of his “legislative” efforts. Part I explores the philosophical foundations of his public philosophy: his theory of meaning and framework for analysis and definition of key concepts, his theory of human affections and motivations, and his utilitarian theory of value. It is argued that, while concepts of pleasure and happiness play nominal roles in his theory of value, concepts of publicity, equality, and interests emerge as the dominant concepts of his public philosophy. Part II explores several dimensions of Bentham’s jurisprudence, including his radically revised command model of law, his early reflections on justice and law in adjudication, his theories of judicial evidence, constitutional rights, the rule of law, and international law. The concluding essay demonstrates the centrality of the notion of publicity in his moral, legal, and political thought. Emerging from this study is a positivist legal theory and a utilitarian moral-political philosophy that challenge in fundamental ways contemporary understandings of those doctrines.
Cognitive Science Is and Should Be Pluralistic

Nunez et al (2019) argue (1) that the field of Cognitive Science has failed, in that it has not arrived at a cohesive theory, and (2) that this is contrary to the intentions of the founders. Their survey of publication and citation patterns bears out the lack of a cohesive theory and also provides corroboration for (3) the concern that the field is becoming unbalanced, with psychology overweighted (Gentner, 2010). I will argue against points (1) and (2), but agree with point (3). My central claim is that cognitive science was never meant to have one unified theoretical framework, nor should it have.
Conclusions About Using TIMSS and TIMSS Advanced Data to Explore Student Misconceptions, Errors, and Misunderstandings in Physics and Mathematics

Assessment items from twenty years of TIMSS and TIMSS Advanced assessments enabled the identification of specific types of student misconceptions, errors, and misunderstandings related to two core concepts (gravity in physics and linear equations in mathematics). Results across grade levels, genders, and assessment years for five countries (Italy, Norway, the Russian Federation, Slovenia, and the United States) were compared. In physics, misconceptions and misunderstandings related to gravity were common across all five countries; for most misconceptions at each grade level, at least 25% of students demonstrated the misconception, and, in some countries, >50% of students demonstrated certain misconceptions. Errors and misunderstandings related to linear equations were extremely common across all five countries; on average >50% of students demonstrated errors at each grade level. Gender differences were found at all three grade levels, but to a greater extent in physics than in mathematics. Classroom teachers who are aware of the misconceptions or types of errors students may make will be able to plan for and provide additional support to their students when they are teaching these concepts. TIMSS resources can provide in-depth information about students’ level of understanding, and their misconceptions and errors, across a range of core mathematics and science concepts. Access to released assessment items, scoring rationales, and actual student responses may allow researchers to undertake even richer secondary data analysis.
Firearm Storage Practices and Risk Perceptions.

Introduction During the past 2 decades, gun owners have become more likely to store household firearms loaded and unlocked, and believe that guns make homes safer rather than more dangerous. Methods Self-reported household firearm storage practices were described among 2,001 gun owners in relation to whether they report that firearms make homes (1) safer, (2) more dangerous, or (3) it depends. Data were from a probability-based online survey administered in 2015 (completion rate, 55%) and analyzed in 2018. Results Nearly 60% of gun owners said that guns make homes safer (57.6%, 95% CI=55.1%, 60.1%), 39.9% (95% CI=37.4%, 42.5%) said that it depends (on other factors), and 2.5% (95% CI=1.8%, 3.4%) said that guns make homes more dangerous. A higher proportion of gun owners who reported that they believe guns increase household safety said that they store household firearms loaded and unlocked (39.2%, 95% CI=35.9%, 42.6%), compared with those who thought guns make the home either more dangerous (3.7%, 95% CI=1.3%, 10.1%) or those who thought the effect of guns on household safety depends on additional factors (17.5%, 95% CI=14.7%, 20.7%). Conclusions Gun owners who are most likely to assert categorically that firearms in the home make homes safer are, as a group, far more likely to store guns in their home loaded and unlocked.
Comparing Methods for Handling Missing Moderators in Meta-Analysis: A Robustness Study.

Meta-regression is used to estimate the true effect size and to assess heterogeneity in effect size estimates using study and sample characteristics as moderators. However, moderators commonly have...
Energetics based epitope screening in SARS CoV-2 (COVID 19) spike glycoprotein by Immuno-informatic analysis aiming to a suitable vaccine development.

Abstract The recent outbreak by SARS-CoV-2 has generated a chaos in global health and economy and claimed/infected a large number of lives. Closely resembling with SARS CoV, the present strain has manifested exceptionally higher degree of spreadability, virulence and stability possibly due to some unidentified mutations. The viral spike glycoprotein is very likely to interact with host Angiotensin-Converting Enzyme 2 (ACE2) and transmits its genetic materials and hijacks host machinery with extreme fidelity for self propagation. Few attempts have been made to develop a suitable vaccine or ACE2 blocker or virus-receptor inhibitor within this short period of time. Here, attempt was taken to develop some therapeutic and vaccination strategies with a comparison of spike glycoproteins among SARS-CoV, MERS-CoV and the SARS-CoV-2. We verified their structure quality (SWISS-MODEL, Phyre2, Pymol) topology (ProFunc), motifs (MEME Suite, GLAM2Scan), gene ontology based conserved domain (InterPro database) and screened several epitopes (SVMTrip) of SARS CoV-2 based on their energetics, IC50 and antigenicity with regard to their possible glycosylation and MHC/paratopic binding (Vaxigen v2.0, HawkDock, ZDOCK Server) effects. We screened here few pairs of spike protein epitopic regions and selected their energetic, IC50, MHC II reactivity and found some of those to be very good target for vaccination. A possible role of glycosylation on epitopic region showed profound effects on epitopic recognition. The present work might be helpful for the urgent development of a suitable vaccination regimen against SARS CoV-2.
Anthropogenic vanadium-chromium-iron and cerium-lanthanum-iron particles in settled urban house dust: CCSEM identification and analysis

There is continuing concern over the health threat posed by theinhalation of ambient, transition-metal-containing particulatematter. Here, we report on the collection of two types ofanthropogenic, airborne particles, composed of iron with vanadiumand chromium (FeVCr) and iron with the rare earth metals ceriumand lanthanum (FeCeLa), respectively. Bi-weekly deposition platesamples were collected on indoor window sills of residentiallocations in inner-city Syracuse, NY. Sampling was continuous ateach location for two months during the spring of 1999. Themetal-bearing particles were identified, analyzed, and sizedin situ on each deposition plate using computer controlledscanning electron microscopy (CCSEM). Approximately 17% of thoseanalyzed by CCSEM fell into the inhalable size fraction. Particle loading varied between locations and changed over time.This was probably a function of various factors affectingparticle deposition rates. Notwithstanding, the plate loadingsfor the FeVCr-bearing particles tended to peak during the middleof the sampling period, suggesting that a single source/processwas operating to produce the FeVCr particles. The large sizeattained by some of these particles (greater than 50 μm inaggregates) suggest that long range transport was probably notinvolved.
Exploratory research on impact of different data multiplexing schemes on activity recovery in cerebral SPECT imaging with AdaptiSPECT-C multi-pinhole brain-dedicated scanner

315 Objectives: SPECT can image a radiopharmaceutical distribution in brain according to cerebral perfusion, neurotransmitter, or cell density and therefore has many clinical applications [1]. We are developing a multi-detector multi-pinhole brain-dedicated SPECT scanner - AdaptiSPECT-C. Our selectable pinhole module technology [2] is used to adapt the collimator configuration such that each pinhole can be closed or open and image with a selectable aperture size. In this work, we explored the effects of 3 data acquisition (DAcq) schemes with different amounts of projection data overlap (i.e. multiplexing (MUX)) on activity recovery in brain perfusion imaging. Methods: The prototype design used in this work for AdaptiSPECT-C consists of 25 8” square detectors arranged in a truncated sphere with 3 rings of 10, 10, and 5 detector heads along caudal-cranial direction. Each detector is coupled with a 5-pinhole collimator consisting of one central and 4 diagonal pinholes of 2.5 mm diameter. We simulated 3 DAcq schemes as follows. Scheme #1 has 3 temporal frames: in the 1st frame, only the 1st pairs of the diagonal apertures are open; in the 2nd frame, only the 2nd pairs of the diagonal apertures are open; and in the 3rd frame, only the central apertures are open. In scheme #2, all apertures are open while in scheme #3, the 4 diagonal apertures are open, and the central apertures are not used. The digital XCAT phantom [3] was modified to simulate a brain perfusion distribution for the head size of 99th percentile male to investigate the near worst case in terms of MUX. Simulation and image reconstruction were performed by our generalizable multi-pinhole SPECT simulation and reconstruction software [4]. Defining the MUX% as the percentage of overlapped projection pixel counts to total acquired counts, schemes #1-3 have Conclusions: Based on a preliminary analysis of AR% of a brain perfusion phantom, we showed that in the current prototype design of AdaptiSPECT-C, opening 4 and 5 apertures per detector which allows high levels of MUX can be used to reconstruct images of AR% close to AR% in the gold standard image. Future investigations including simulating multiple noise realizations will be needed to do statistical analysis of quantification by different DAcq schemes. Research Support: National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Grant No R01 EB022521.
Ifnβ Reprograms Th2 Promoting Mature Lung TNFR2+ cDC2 Subset in vivo to Generate Regulatory T Cells and Restore Lung Mucosal Tolerance

Lung dendritic cells and regulatory T cells control lung mucosal tolerance. Here, we identified a lung-resident IDO-1+TNFR2+ conventional DC2 (iR2D2) subset that induces antigen-specific regulatory T cells in the lung. iR2D2 is a microenvironment specialized DC subset whose existence depends on its constitutive TNFR2-pRelB-IDO-1 signaling. The iR2D2 intrinsic IFNAR-TGFβ1 signaling is necessary and sufficient for regulatory T cells induction in vivo. Surprisingly, iR2D2 is plastic. In a house dust mite (HDM) model of asthma, iR2D2 generates lung Th2 responses. Remarkably, intranasally administration of IFNβ reprogramed HDM-induced Th2-promoting iR2D2 back to generate regulatory T cells, reversed lung inflammation and protected mice from subsequent asthma exacerbation. Healthy human lung has a phenotypically similar tolerogenic iR2D2, which became IL-4+ in emphysema patients. Finally, IFNβ successfully reprogramed human emphysema iR2D2 ex vivo. These findings elucidate a fundamental mechanism controlling lung tolerance and a strategy to restore lung tolerance in inflammatory lung diseases.
Health insurance impacts on health and non-medical consumption in a developing country

The authors examine the effects of the introduction of Vietnam's health insurance (VHI) program on health outcomes, health care utilization, and non-medical household consumption. The use of panel data collected before and after the insurance program's introduction allows them to eliminate any confounding effects due to selection on time-invariant un-observables, and their coupling of propensity score matching with a double-difference estimator allows them to reduce the risk of biases due to inappropriate specification of the outcome regression model. The authors' results suggest that Vietnam's health insurance program impacted favorably on height-for-age and weight-for-age of young school children, and on body mass index among adults. Their results suggest that among young children, VHI increases use of primary care facilities and leads to a substitution away from the use of pharmacists as a source of advice and non-prescribed medicines toward the use of them as a supplier of medicines prescribed by a health professional. Among older children and adults, VHI results in a marked increase in the use of hospital inpatient and outpatient departments. The results also suggest that VHI causes a reduction in annual out-of-pocket expenditures on health and an increase in non-medical household consumption, including food consumption, but mostly nonfood consumption. The authors' estimate of the VHI-induced reduction in out-of-pocket health spending is considerably smaller than their estimate of the VHI-induced increase in non-medical consumption, which is consistent with the idea that households hold back their consumption considerably if, through lack of health insurance, they are exposed to the risk of large out-of-pocket expenditures. This is especially plausible in a country where at the time (1993), a single visit to a public hospital cost on average the equivalent of 20 percent of a person's annual nonfood consumption.
Automatic Timing Closure for Relative Timed Designs

Relative timing is a universal representation of the sequencing property of time. Relative timing can be applied to specify the correctness and performance properties of digital circuits in the form of a set of timing constraints. These constraints are passed to commercial synthesis, place and route, and timing verification tools to optimize the robustness, power, and performance of digital integrated circuits. This paper presents an algorithm for the automatic convergence of a set of relative timing constraints in the synthesis and place and route flows to create a timing closed design. The algorithm can perform timing closure for a design starting with zero maximum delay targets. This tool produces improved results compared to a start point with delay values close to final closed values.
Research note: authoritarianism, racial resentment, and attitudes on the Colin Kaepernick protests

In 2016, then-NFL quarterback Colin Kaepernick triggered ongoing political controversies by kneeling during the United States National Anthem to protest police brutality against African Americans. ...
Lipid droplets modulate proteostasis, SQST-1/SQSTM1 dynamics, and lifespan in C. elegans

ABSTRACT The ability of organisms to live long depends largely on the maintenance of proteome stability via proteostatic mechanisms including translational regulation, protein chaperoning and degradation machineries. In several long-lived Caenorhabditis elegans strains, such as insulin/IGF-1 receptor daf-2 mutants, enhanced proteostatic mechanisms are accompanied by elevated intestinal lipid stores, but the role of lipid droplets in longevity has remained obscure. Here, while determining the regulatory network of the selective autophagy receptor SQST-1/SQSTM1, we unexpectedly uncovered a novel role for lipid droplets in proteostasis and longevity. Using an unbiased genome-wide RNAi screening approach, we identified several SQST-1 modulators, including proteins found on lipid droplets and those prone to aggregate with age. SQST-1 accumulated on lipid droplets when autophagy was inhibited, suggesting that lipid droplets may serve a role in facilitating selective autophagy. Expansion of intestinal lipid droplets by silencing the conserved cytosolic triacylglycerol lipase gene atgl-1/ATGL enhanced autophagy, and extended lifespan in an HSF-1/HSF1-dependent and CDC-48/VCP-dependent manner. Silencing atgl-1 mitigated the age-related accumulation of SQST-1 and reduced overall ubiquitination of proteins. Reducing atgl-1 also improved proteostasis in a nematode model of Alzheimer’s disease. Subcellular analyses revealed that lipid droplets unexpectedly harbor more ubiquitinated proteins than the cytosol. Accordingly, low lipid droplet levels exacerbated the proteostatic collapse when autophagy or proteasome function was compromised. Altogether, our study uncovers a key role for lipid droplets in C. elegans as a proteostatic mediator that reduces protein ubiquitination, facilitates autophagy, and promotes longevity.
The Use of daily postpartum rectal temperatures to select dairy cows for treatment with systemic antibiotics

This retrospective study analysed descriptive statistics on daily rectal temperatures of 1042 dairy cows taken for 10 days postpartum on one farm in southeastern Pennsylvania, USA, from May 1998 to February 2000. Cows were classified as NORMAL if they did not have a retained placenta, dystocia, metritis, or mastitis event and received no systemic antibiotic treatment for the first 10 days postpartum. NORMAL cows had average daily temperatures below 102.0°F during days 1 through 10 postpartum. Cows with either retained placenta, metritis, dystocia or mastitis tended to have temperatures greater than 102.0°F during days 2 through 8 postpartum. All cows had the lowest temperatures during the first two days postpartum. Those requiring systemic antibiotic treatment had their highest temperatures on days 3 through 6 postpartum. Because there were no differences in daily postpartum temperatures of normal cows by lactation, the same criteria could be used to select primiparous and multiparous cows for treatment with systemic antibiotics. Finding one rectal temperature greater than 102.0°F or 102.5°F would not be sufficiently discriminating to decide to treat with antibiotics because 48% of NORMAL cows had at least one temperature greater than 102.5°F during the first ten days postpartum. Cows with average temperatures greater than 103.5°F had a significant average 1.0°F decline in temperature the day after systemic antibiotic treatment was started. Daily temperatures should be taken for at least seven days postpartum.
Shear Distribution in a Sheet-Metal Box Spar

Within the last few years many airplane designers have become interested in the construction of wings in which the entire bending and torsion is carried by a single sheet-metal box spar. One great difficulty in designing such a spar has been the question of shear distribution along a cross-section. Hatcher, in the April issue of this Journal, outlined a logical method for determining such a shear distribution. Unfortunately, he chose for his example a symmetrical rectangular box girder, which caused him to use mathematical concepts which could not be carried over directly to other types of box spars, particularly those in which the equations of the bounding curves are unknown. I t is hoped t h a t this paper will overcome this difficulty by providing simple formulas for the shear distribution in a box spar of any shape, whether or not any portion of the skin is effective in bending.
A Successful Application of The Assessment Center Concept To The Salesperson Selection Process

The selection of successful salespeople has been a problem defying solution for American industry. In this study, an assessment center technique was applied to the selection process of newly hired ...
Handling Multiple Inheritance with Exceptions: An Alternative Approach

The design of inheritance systems that allow multiple inheritance combined with exceptions poses some difficult problems. Any good theory of inheritance should meet two, sometimes complementary, goals: it should provide answers that correspond to human intuition, and it should be backed by a simple and rational reasoning process. We propose a method for reasoning with inheritance hierarchies that focuses on differences of nodes from a common ancestor in the hierarchy to derive the set of properties inherited by a node. We show the application of the algorithm to some of the classic examples in inheritance systems, compare their results with ours, and discuss the rationale behind our approach.
Care and career: A family identity‐based typology of dual‐earner couples

Summary The rise of dual-earner couples challenges traditional gender stereotypes of women as “caregivers” and men as “breadwinners” and significantly impacts the ways in which partners define their roles as family members. The way in which individuals construe their family identities has implications not only for the decisions they make at home but also decisions in the workplace. In this paper, we propose an updated understanding of the different ways in which men and women can construe their family identity—specifically, in terms of care and/or career. Based upon this nuanced understanding of family identity, we outline five dual-earner couple types—traditional, non-traditional, family first, outsourced, and egalitarian—that stem from distinct combinations of partners' family identities. We also outline an agenda for theory and research that challenges scholars to further explore our proposed construals of family identity, work–family decisions at the couple level of analysis, and the interplay between family identity and social context. Copyright © 2014 John Wiley & Sons, Ltd.
Decidability of Deliberative Stit Theories with Multiple Agents

The purpose of this paper is to present axiomatizations for some dstit (deliberatively seeing-to-it-that) logics with multiple agents, and prove the completeness and decidability by way of finite model property. The dstit logics considered in this paper include the basic dstit logic, and for every n≥1, a logic in which every agent has at most n possible choices at every moment.