cssi/SciSciGPT-SciSciNet huggingface dataset:
A Nomogram Derived by Combination of Demographic and Biomarker Data Improves the Noninvasive Evaluation of Patients at Risk for Bladder Cancer.

Background: Improvements in the noninvasive clinical evaluation of patients at risk for bladder cancer would be of benefit both to individuals and to health care systems. We investigated the potential utility of a hybrid nomogram that combined key demographic features with the results of a multiplex urinary biomarker assay in hopes of identifying patients at risk of harboring bladder cancer. Methods: Logistic regression analysis was used to model the probability of bladder cancer burden in a cohort of 686 subjects (394 with bladder cancer) using key demographic features alone, biomarker data alone, and the combination of demographic features and key biomarker data. We examined discrimination, calibration, and decision curve analysis techniques to evaluate prediction model performance. Results: Area under the receiver operating characteristic curve (AUC) analyses revealed that demographic features alone predicted tumor burden with an accuracy of 0.806 [95% confidence interval (CI), 0.76–0.85], while biomarker data had an accuracy of 0.835 (95% CI, 0.80–0.87). The addition of molecular data into the nomogram improved the predictive performance to 0.891 (95% CI, 0.86–0.92). Decision curve analyses showed that the hybrid nomogram performed better than demographic or biomarker data alone. Conclusion: A nomogram construction strategy that combines key demographic features with biomarker data may facilitate the accurate, noninvasive evaluation of patients at risk of harboring bladder cancer. Further research is needed to evaluate the bladder cancer risk nomogram for potential clinical utility. Impact: The application of such a nomogram may better inform the decision to perform invasive diagnostic procedures. Cancer Epidemiol Biomarkers Prev; 25(9); 1361–6. ©2016 AACR .
Genetics of gigantism and acromegaly

Gigantism and acromegaly are rare disorders that are caused by excessive GH secretion and/or high levels of its mediator, IGF-1. Gigantism occurs when excess GH or IGF-1 lead to increased linear growth, before the end of puberty and epiphyseal closure. The majority of cases arise from a benign GH-secreting pituitary adenoma, with an incidence of pituitary gigantism and acromegaly of approximately 8 and 11 per million person-years, respectively. Over the past two decades, our increasing understanding of the molecular and genetic etiologies of pituitary gigantism and acromegaly yielded several genetic causes, including multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, pituitary adenoma association due to defects in familial succinate dehydrogenase genes, and the recently identified X-linked acrogigantism. The early diagnosis of these conditions helps guide early intervention, screening, and genetic counseling of patients and their family members. In this review, we provide a concise and up-to-date discussion on the genetics of gigantism and acromegaly.
Large-scale structure non-Gaussianities with modal methods

Relying on a separable modal expansion of the bispectrum, the implementation of a fast estimator for the full bispectrum of a 3d particle distribution is presented. The computational cost of accurate bispectrum estimation is negligible relative to simulation evolution, so the bispectrum can be used as a standard diagnostic whenever the power spectrum is evaluated. As an application, the time evolution of gravitational and primordial dark matter bispectra was measured in a large suite of N-body simulations. The bispectrum shape changes characteristically when the cosmic web becomes dominated by filaments and halos, therefore providing a quantitative probe of 3d structure formation. Our measured bispectra are determined by ∼ 50 coefficients, which can be used as fitting formulae in the nonlinear regime and for non-Gaussian initial conditions. We also compare the measured bispectra with predictions from the Effective Field Theory of Large Scale Structures (EFTofLSS).
137. Viral Hitchhiking to Increase Therapeutic Potential: Autonomously Packaged Elements (APEs)

Human Immunodeficiency Virus (HIV) preferentially packages its own RNA genome and various RNA transcripts (tRNA-Lys3, 7SL, aptamers, etc.) with a broad range of consequences. For example, genome and tRNA are required for viral life cycle (positive impact on viral fitness), various cellular RNAs such as 7SL appear to “hitchhike” with no obvious essential roles (neutral), and aptamers that bind RT exert their influence by co-packaging with the viral proteins (inhibitory). While the mechanisms that promote selective incorporation of these transcripts have not been fully described, it is generally accepted that RNA secondary structures allow the RNA to associate with viral proteins during packaging. Identification of these RNA secondary structures would allow for exploitation of a range of packaging mechanisms to drive RNA incorporation for therapeutic purposes. We therefore applied a novel in vivo selection to identify RNAs specifically associated with incorporation into virus particles.We have previously demonstrated that multiple RNA aptamers selected against HIV Reverse Transcriptase (RT) are incorporated into the budding virus– potentially through interactions with the RT– and that they effectively reduce infectivity. To identify conserved features of highly efficient aptamer packagers, we have developed a cell-based protocol for the selection of Autonomously Packaging Elements (APEs). Pre-enriched RNA aptamer libraries were transfected into virus producing cells where we exploit the intracellular viral life cycles to perform the selection of APEs. We inserted an aptamer library downstream of a CMV promoter and co-transfected the library with HIV proviral plasmids. This generated pseudotyped virus particles containing the packaged RNA aptamers, while the cells retain the non-packaged RNA. By reverse transcribing the packaged RNA component, then amplifying and re-inserting it into the expression vector and iteratively transfecting fresh producer cells, we increase packaging competition and aptamer specificity. Subsequent High-Throughput Sequencing and computational analysis will allow us to probe the sequence and structural requirements of APEs. Individual aptamers will be evaluated for their packaging affinity and ability to inhibit viral replication in cell culture. Expanding on this selection scheme by swapping out the RT in the transfection with a panel of divergent RTs is expected to identify aptamer motifs which target evolutionarily conserved RT residues. Application of the APE selection system to an extended viral panel utilizing a range of starting libraries allows for nearly limitless variability in selection output.
Outcome of Diffuse Large B Cell Lymphoma in the VA System: The Rituximab Era.

Background: Addition of rituximab to chemotherapy in patients with diffuse large B cell Lymphoma (DLBCL) has been shown to improve survival in several recent clinical studies. A study from British Columbia confirmed those results in a population-based cohort. No similar population based studies were conducted in the USA. Our study aims to address outcome of DLBCL in the era of rituximab in the VA health system. Methods: This was a retrospective analysis. The VA Central Cancer Registry (VACCR) database was used to identify patients with DLBCL diagnosed between 1995 and 2005. There are approximately 120 VA medical centers diagnosing and/or treating patients with cancer. The VACCR aggregates the data collected by the medical centers’ cancer registries. Data were extrapolated and analyzed using bio-statistical software SPSS. Variables included age, sex, stage of disease, histology subtype, date of diagnosis, date of last contact, date of relapse, vital status, whether patients received chemotherapy and or radiation. Use of rituximab was not specifically recorded in the registry. Due to that we divided the patients into two groups, patients diagnosed with DLBCL before 2001 (pre rituximab era group) and patients diagnosed after 2001 (rituximab era group). The initial results of rituximab in DLBCL were presented in 2000 and published in January 2002. Independent t test was used for comparing continuous variables and chi square test for categorical variables. Wilcoxon test was used to compare survival among the two groups. Results: There were 2792 patients with DLBCL at the VACCR between 1995 and 2005, 1772 patients in pre rituximab era and 1020 patients in the rituximab era. The mean age at diagnosis was to 64 in pre rituximab group and 66 in rituximab group (P-value 0.015). Race distribution was similar between the two groups. More patients were diagnosed at advanced stage (stage III and IV) 61 % in rituximab group compared to 57% in pre rituximab group (P-value Conclusions: Overall survival of DLBCL in VA patients had improved in the rituximab era. The magnitude of improvement observed in this study is similar to what was described in previous studies. Other factors contributing to improvement in outcomes such as supportive care could not be differentiated in this study. This is a population-based study suggesting improvement in survival in DLBCL in the rituximab era.
Spinal epidural hematoma following a thoracic epidural in a child with sickle cell disease

Acute liver dysfunction in the perioperative period may increase the risk of epidural hematoma in a patient with a neuraxial catheter. Coagulation testing needs to be carefully monitored in these patients. An epidural hematoma should be ruled out urgently by CT or MRI in cases of a persistent motor block.
22‐1: Invited Paper: Biological Effects of Light: Can Self‐luminous Displays Play a Role?

Light is the major synchronizer of circadian rhythms to local time on earth. Light can also elicit an acute alerting effect on humans. This paper discusses lighting characteristics that affect the circadian system and how self-luminous displays can be used to promote entrainment and alertness.
Operating system fingerprinting via automated network traffic analysis

Operating System (OS) detection significantly impacts network management and security. Current OS classification systems used by administrators use human-expert generated network signatures for classification. In this study, we investigate an automated approach for classifying host OS by analyzing the network packets generated by them without relying on human experts. While earlier approaches look for certain packets such as SYN packets, our approach is able to use any TCP/IP packet to determine the host systems' OS. We use genetic algorithms for feature subset selection in three machine learning algorithms (i.e., OneR, Random Forest and Decision Trees) to classify host OS by analyzing network packets. With the help of feature subset selection and machine learning, we can automatically detect the difference in network behaviors of OSs and also adapt to new OSs. Results show that the genetic algorithm significantly reduces the number of packet features to be analyzed while increasing the classification performance.
STEM Bridges: Evolution of an Academic Library STEM Outreach Program

ABSTRACTBig Orange STEM Saturday (BOSS) is a sustainable model of outreach that fosters the STEM cycle of discovery and learning experiences. Through this program, the library creates and reinforces a bridge between secondary educational experiences and higher education that facilitates the transfer of knowledge from the classroom to the world. Local high school students are able to engage with experts in several different ways to explore what STEM has to offer and to look beyond their current experiences. This approach creates a venue for STEM teaching spaces outside the school classroom for enrichment and innovation. Over the past 5 years, the variety of experiences offered at BOSS have expanded and the reputation of the program has grown. This article explores the challenges, lessons, and impact that this program has had on its constituents, with a particular focus on the impact the library can have when exploring nontraditional areas of support and outreach.
Innovation Incentives and Biomarkers.

Previously, we have discussed the importance of economic incentives in shaping markets for precision medicines.[1] Here we consider incentives for biomarker development, including discovery and establishment. Biomarkers can reveal valuable information regarding diagnosis and prognosis, predict treatment efficacy or toxicity, serve as markers of disease progression, and serve as auxiliary endpoints for clinical trials. Some have multiple uses, while others have a specialized role, resulting in diverse incentives across players in the healthcare system.
Ground state M1 strengths of d5/2-1 levels in 39K.

Resonant photon scattering from /sup 39/K has been studied with bremsstrahlung produced by electrons with end-point energies of 6.6, 8.5, and 9.4 MeV. Values of gGAMMA/sub 0//sup 2/GAMMA for 24 levels below 9 MeV were measured and the gGAMMA/sub 0/ values of 17 levels were deduced. The widths of some levels above 4 MeV were found to be much larger (on the average, more than a factor of 10) than those reported from experiments using the Doppler shift attenuation method. Three of these levels are known from studies of the (d,/sup 3/He) reaction to carry most of the d/sub 5/2/sup -1/ proton strength in /sup 39/K. The B(M1up-arrow) strength of J = (52/sup +/ levels below 7 MeV is compared with predictions based on simple single-particle shell-model wave functions coupled with free-nucleon and empirically renormalized M1 operators and weighted by single-proton pickup spectroscopic factors.
Models of retinal diseases and their applicability in drug discovery

ABSTRACTIntroduction: The impact of vision debilitating diseases is a global public health concern, which will continue until effective preventative and management protocols are developed. Two reti...
Recurrent Spontaneous Coronary Artery Dissection in 4 Vascular Territories

Spontaneous coronary artery dissection, a rare cause of acute coronary syndrome, is due to nonatherosclerotic coronary events and is probably underrecognized as a cause of myocardial infarction. The condition typically affects premenopausal women who are otherwise healthy. Among more than 1,200 reported cases, recurrent dissection has been described 63 times, and only 3 reports have documented multiple episodes of dissection involving different vascular territories. We present the case of a woman in her 30s who, over a 9-year period, presented 4 times with coronary dissection in different vascular territories. She was first treated conservatively, then with stents, and ultimately by means of coronary artery bypass grafting. In addition to this case, we discuss this rare condition and its management.
Specific Proteolytic Processing of Poly(ADP-Ribose) Polymerase in Human Lymphocytes

Four enzymatic systems have been described that directly and selectively affect cellular metabolism of poly(ADP-ribosyl)ated proteins. (1) The enzyme poly(ADP-ribose) polymerase cleaves nicotinamide from NAD and then forms a covalent linkage between the residual ADP-ribose moiety and specific protein acceptor molecules [1,2]. The same enzyme can add successive ADP-ribose moieties to form homopolymers in excess of 100 residues with alternating phosphodiester and O-glycosidic linkages. (2) Poly(ADP-ribose) glycohydrolase degrades poly(ADP-ribose) at the O-glycosidic linkages in an exoglycosidic fashion [3,4]. This appears to be the major cellular enzyme responsible for polymer degradation. (3) Phosphodiesterases degrade the polymer at the phosphodiester bonds. Some phosphodiesterases function as endonucleases and others as exonucleases [5,6]. However, these enzymes do not appear to play an important role in cellular modulation of poly(ADP-ribose) levels. (4) Poly(ADP-ribose)-protein hydrolase specifically hydrolyzes the covalent linkage between proteins and ADP-ribose [7]. The physiological importance of this enzyme has recently been suggested by the identification of a lysosomal storage disease in which glutamyl ribose 5-phosphate accumulates in tissues, presumably due to a genetic deficiency of this enzyme [8]. Our studies in human lymphocytes reveal that a nucleotide and/or pyrophosphate stimulated proteolytic processing system constitutes a fifth enzymatic pathway for selective modulation of poly(ADP-ribosyl)ated proteins.
Angiotensin II Signaling in Vascular Physiology and Pathophysiology

Initially recognized as a physiologic regulator of blood pressure and body fluid homeostasis, angiotensin (Ang) II has now been shown in innumerable experiments and clinical studies to contribute to the development and maintenance of cardiovascular disease. Dissection of its signaling mechanisms over the past decades has led to the discovery of several novel concepts, such as tissue-specific metabolism of Ang peptides. Identification and cloning of the various receptors through which Ang II acts on almost all tissues has led to the development of specific pharmacologic inhibitors with proven clinical benefit in patients with cardiovascular disorders. Work on the G-protein-coupled Ang II Type 1 receptor has demonstrated that different receptors interact through oligomerization, compartmentalization, and transactivation, and may explain how Ang II can activate G-protein-independent pathways. Unraveling the downstream effects of Ang II in specific cell types corroborates the importance of the cellular redox state on certain signaling pathways. Finally, the effects of Ang II on cell function and phenotype, such as the expression of inflammatory cytokines and receptors promoting the recruitment of inflammatory cells into vascular tissues, have indicated its role in local inflammation as a general pathogenetic basis of cardiovascular disease. The recognition of Ang II as a contributor to such fundamental pathophysiologic mechanisms, which are believed to be a common pathway for diverse cardiovascular risk factors like hypertension and diabetes, has greatly advanced our knowledge of pathologic signaling in vascular tissues and may help to eventually define novel targets for pharmacologic interventions.
Chapter 3 – Somatosensory Cortex and Tactile Perceptions

Publisher Summary This chapter considers the cerebral cortical areas responsible for low-threshold touch perception in primates. It emphasizes on cognitive factors in tactile perception, discusses receptive field organization in the cortex, and highlights the issues that may benefit from future study. On the basis of anatomical and physiological criteria, approximately ten parietal cortical areas involve somatosensory processing. These areas display separable cytoarchitecture and form a connected somatosensory network because they share thalamic and cortical connections. All ten areas respond in some way to cutaneous or deep receptor stimulation and most contain somatotopically-organized maps. The physiological perspective primarily focuses on the isolated elements responsible for perceptions of well-controlled tactile stimuli.
Assessing the effect of data integration on predictive ability of cancer survival models

Cancer is the second leading cause of death in the United States. To improve cancer prognosis and survival rates, a better understanding of multi-level contributory factors associated with cancer survival is needed. However, prior research on cancer survival has primarily focused on factors from the individual level due to limited availability of integrated datasets. In this study, we sought to examine how data integration impacts the performance of cancer survival prediction models. We linked data from four different sources and evaluated the performance of Cox proportional hazard models for breast, lung, and colorectal cancers under three common data integration scenarios. We showed that adding additional contextual-level predictors to survival models through linking multiple datasets improved model fit and performance. We also showed that different representations of the same variable or concept have differential impacts on model performance. When building statistical models for cancer outcomes, it is important to consider cross-level predictor interactions.
Multi-Operator Production Cost Modeling

While contiguous power systems are often operated by several regional system operators, optimization models have traditionally been designed to generate optimal system-wide scheduling decisions. This paper presents an approach to reflect the existence of multiple system operators making scheduling decisions within an interconnected power system. This approach is explicitly designed to reflect each operator's limited knowledge about other regions when making scheduling decisions. Detailed analysis using a modified IEEE Reliability Test System reveals that the approach mimics real system operations by providing imperfect information to each operator about external operations and external constraints. This approach scales to a 78 000-bus model of the Eastern Interconnection, where a regression analysis provides quantitative insight into which constraints cause inefficiencies when improperly managed in a multi-operator simulation. Because the approach generates distinct regional scheduling problems, unit commitment, and economic dispatch simulations can be applied to individual regions and solved in parallel, enabling production cost simulations at a previously intractable scale.
Magnetic Cell Sorting for In Vivo and In Vitro Astrocyte, Neuron, and Microglia Analysis

Interest in evaluating individual cellular populations in the central nervous system has prompted the development of several techniques enabling the enrichment of single-cell populations. Herein we detail a relatively inexpensive method to specifically isolate neurons, astrocytes, and microglia from a mixed homogenate utilizing magnetic beads conjugated to cell-type specific antibodies. We have used this technique to isolate astrocytes across development and into late adulthood. Finally, we detail the utilization of this technique in novel astrocyte and astrocyte/neuron co-culture paradigms. © 2019 by John Wiley & Sons, Inc.
Day 30: The Tacit Quarterly Information Event in the Banking Industry

We investigate the timing of bank regulatory report releases and their role in the information environment of banks. We find that: (1) Call Reports, but not FR Y-9Cs, elicit economically significant stock price and volume reactions when they are publicly released despite the fact that Call Reports usually follow earnings announcements; (2) the release of the Call Reports is tightly clustered around the 30th day after quarter-end; and, (3) after bank regulators undertook a “modernization project” to speed the processing and public dissemination of regulatory reports, the banking industry routinely experiences abnormal stock price volatility and trading volume on the 30th day of the quarter. Overall, our findings indicate that equity investors derive incremental information from regulatory filings, and they highlight a market-moving information event that occurs in a tight window around the 30th day of the quarter.
Impact of Spin Torque Oscillator Frequency in Microwave-Assisted Magnetic Recording

In this article, we present a systematic modeling investigation for some important physical insights in microwave-assisted magnetic recording (MAMR). Specifically, the characteristics of the effective write field in the presence of the ac field generated by the embedded spin torque oscillator (STO) is analyzed in terms of field strength and field-gradient gain for recording, as well as the enhancement of reverse erasure field. It is found that the rotating frequency of the field generating layer (FGL) of the STO plays a very important role. The effective write field enhancement for both recording and erasure due to the rotating ac field increase with increasing the ac field frequency with a rate close to 1 T per 28 GHz. Either the recording field gain or erasure field enhancement rolls off at high frequencies. The roll-off frequency for the recording field gain is significantly higher, approximately 20 GHz, than that for erasure field enhancement, leaving a broader frequency range for the ac field over which substantial gains for the recording field strength and gradients can be obtained while avoiding any erasure field enhancement. The understanding also provides guidelines for both head and media designing.
Neuropsychological functioning following surgery for pediatric low-grade glioma: a prospective longitudinal study.

OBJECTIVE High survival rates have led to an increased emphasis on the functional outcomes of children diagnosed with low-grade glioma. Most outcomes research has focused on risks associated with radiotherapy, but less is known about neuropsychological risks for patients treated with surgery alone. Here, the authors sought to examine the neuropsychological trajectories of children diagnosed with a low-grade glioma and monitored up to 6 years postsurgery. Secondarily, they explored demographic and clinical predictors of neuropsychological performance. METHODS The neuropsychological functioning of 32 patients (median age at diagnosis 10.0 years) was prospectively assessed annually for up to 6 years after surgery (median days from surgery at baseline = 72). Tumor location was predominately supratentorial (65.6%). A combination of performance-based and parent-reported measures was used to assess intelligence, memory, executive functioning, and fine motor control in all patients. RESULTS Binomial tests at the postoperative baseline revealed that the proportion of children falling below the average range (< 16th percentile) was significantly higher than the rate expected among healthy peers on measures of verbal memory, processing speed, executive functioning, and fine motor control (p < 0.05). Even so, linear mixed models indicated that neuropsychological functioning at the postoperative baseline did not significantly change over time for up to 6 years after surgery across all domains. A larger tumor size was associated with a slower reaction time (p < 0.01). A supratentorial tumor location and history of seizures were associated with more parent-reported executive difficulties (p < 0.01). CONCLUSIONS While radiotherapy is a known risk factor for neuropsychological deficits in pediatric brain tumor patients, findings in this study indicate that children treated for low-grade glioma with surgery alone (without radiotherapy or chemotherapy) remain susceptible to difficulties with memory, executive functioning, and motor functioning that persist over time. Over half of the children in the study sample required school support services to address neuropsychological weaknesses. Although low-grade glioma is often conceptualized as a benign tumor, children treated for this lesion require ongoing monitoring and intervention to address neuropsychological weaknesses resulting from the tumor itself as well as the surgery.
Linkages between land cover change, lake shrinkage, and sublacustrine influence determined from remote sensing of select Rift Valley Lakes in Kenya.

Abstract The Great Rift Valley system is home to many volcanic and tectonic lakes including some of the world's oldest and deepest lakes. These lakes host a rich heritage of biodiversity that is endangered by recent drastic hydrologic changes due to multiple natural and anthropogenic stressors in the catchment areas of some of the lakes. This study utilized Landsat TM, ETM+, and OLI data to conduct a systematic investigation of the relationship between hydrological dynamics in the basins of four Rift Valley lakes (Nakuru, Baringo, Bogoria, and Elementaita) and recent land cover and land-use change. The Modified Normalized Difference Water Index (MNDWI) proved to be more accurate and robust for delineating water surface areas when compared to the output of Normalized Difference Vegetation Index (NDVI) and classification algorithms. NDVI was successful when delineating water surface at Lake Baringo but not in Lakes Bogoria, Nakuru, and Elementaita, whose surfaces were dominated by algae. All the lakes expanded substantially after 2010 submerging surrounding areas leading to disruption of livelihoods, property damage, and displacement of thousands of people. The recent drastic hydrologic changes have multiple causations including land cover and land use change, increase in rainfall, and possible change in geogenic water input due to tectonic activity. The rapid rise in water levels appears to have altered the biogeochemical balance of the hypersaline lakes with severe ramifications on the rich biodiversity that is supported by the lakes.
TMPRSS2 and ADAM17 interactions with ACE2 complexed with SARS-CoV-2 and B0AT1 putatively in intestine, cardiomyocytes, and kidney

ABSTRACT COVID-19 outcomes reflect organ-specific interplay of SARS-CoV-2 and its receptor, ACE2, with TMPRSS2 and ADAM17. Confirmed active tropism of SARS-CoV-2 in epithelial cells of intestine and kidney proximal tubule, and in aging cardiomyocytes, capriciously manifests extra-pulmonary organ-related clinical symptoms in about half of COVID-19 patients, occurring by poorly understood mechanisms. We approached this knowledge gap by recognizing a clue that these three particular cell types share a common denominator kindred of uniquely expressing the SLC6A19 neutral amino acid transporter B0AT1 protein (alternatively called NBB, B, B0) serving glutamine and tryptophan uptake. B0AT1 is a cellular trafficking chaperone partner of ACE2, shown by cryo-EM to form a thermodynamically-favored stabilized 2ACE2:2B0AT1 dimer-of-heterodimers. The gut is the body’s site of greatest magnitude expression depot of both ACE2 and B0AT1. This starkly contrasts with pulmonary pneumocyte expression of monomeric ACE2 with conspicuously undetectable B0AT1. We hypothesized that B0AT1 steers the organ-related interplay amongst ACE2, TMPRSS2, ADAM17, and SARS-CoV-2 RBD. The present study employed molecular docking modeling that indicated active site catalytic pocket residues of TMPRSS2 and ADAM17 each formed bonds ≤ 2 A with monomer ACE2 specific residues within a span R652-D713 involved in cleaving sACE2 soluble ectodomain release. These bonds are consistent with competitive binding interactions of experimental anti-SARS-CoV-2 drug small molecules including Camostat and Nafamostat. Without B0AT1, ACE2 residues K657 and N699 dominated docking bonding with TMPRSS2 or ADAM17 active sites, with ACE2 R710 and R709 contributing electrostatic attractions, but notably ACE2 S708 never closer than 16-44 A. However, in the dimer-of-heterodimers arrangement all ACE2 neck region residues were limited to TMPRSS2 or ADAM17 approaches 35 A, with the interference directly attributed to the presence of a neighboring B0AT1 subunit complexed to the partnering ACE2 subunit of 2ACE2:2B0AT1; ADAM17 failed to dock by bumping its active site pocket oriented dysfunctionally outwardly facing 1800 away. Results were the same whether the dimer-of-heterodimers was in either the “closed” or “open” conformation, or whether or not SARS-CoV-2 RBD was complexed to ACE2. The results implicate B0AT1-and in particular the 2ACE2:2B0AT1 complex-as a maJor player in the landscape of COVID-19 pathophysiology engaging TMPRSS2 and ADAM17, consistent with experimental evidence in the literature and in clinical reports. These findings provide a gateway to understanding the roles of B0AT1 relating to COVID-19 manifestations putatively assigned to intestinal and renal epithelial cells and cardiomyocytes, with underpinnings useful for considerations in public hygiene policy and drug development.
Survival in critically ill admissions with and without COVID-19 at an academic medical center during the height of the pandemic

Objective: Early reports demonstrate that patients with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection have high rates of hospitalization, intensive care unit (ICU) admission, and death. We sought to examine characteristics of ICU admissions with and without Coronavirus 2019 (COVID-19) and to compare outcomes between these two critically ill cohorts. Methods: A retrospective analysis of 600 unique adult ICU admissions was conducted at an academic medical center in Boston, MA from March 22 to May 31, 2020. Results: Of 600 ICU admissions, 170 (28.3%) tested positive for COVID-19. Those with COVID-19 had greater severity of illness and were more likely to require mechanical ventilation (MV). Hospital and ICU mortality rates were greater in the COVID-19 group (22.4% vs. 9.5%; 18.2% vs. 7.2%, respectively), but lower than previous reports. Unadjusted odds ratio (OR) for COVID-19 as a predictor of hospital mortality was 2.73 (95% CI 1.68 to 4.43), but when accounting for clinical characteristics and severity of illness, adjusted OR for hospital mortality was no different (1.09 [95% CI 0.50 to 2.41]) among those with and without COVID-19. Conclusions: COVID-19 admissions had greater severity of illness and suffered higher crude mortality rates compared to the non-COVID-19 cohort. However, there was no significant difference in the adjusted OR for hospital mortality between patients with and without COVID-19. This novel finding may be attributed to the “learning curve” from other healthcare system experiences, early hospital-wide preparation, and dedicated intensive care.
Solute carrier 5A5 regulates systemic glucose homeostasis by mediating glucose absorption in the Drosophila midgut

Abstract The small intestine is the first organ that is exposed to and absorbs dietary glucose and thus represents the first of a continuum of events that modulates normal systemic glucose homeostasis. A better understanding of the regulation of intestinal glucose transporters is therefore pertinent to our efforts in curbing metabolic disorders. However, so far, the mechanisms known to regulate SGLT1, the primary intestinal glucose transporter, are mainly elucidated from in vitro studies. The Drosophila midgut, functional equivalence of the small intestine, could serve as an efficient in vivo model system for studying intestinal glucose transporter regulation; however, no glucose transporter has yet been identified in the midgut. Here, we report that the Drosophila Solute Carrier 5A5 (dSLC5A5) is homologous to SGLT1 and is highly expressed in the midgut. The knockdown of dSLC5A5 decreases systemic and circulating sugar levels and decreases glucose uptake into the enterocytes. In contrary, the overexpression of dSLC5A5 elevates systemic and circulating sugar levels and promotes glucose uptake into the enterocytes. We show that dSLC5A5 undergoes dynamin-dependent endocytosis in the enterocyte apical membrane, and that dSLC5A5 endocytosis is essential for the glucose uptake capability of dSLC5A5. Moreover, we provide evidence supporting that intracellular lysosomal degradation of endocytosed dSLC5A5 plays a significant role in the maintenance of dSLC5A5 level in the enterocyte apical membrane. We further show that short-term exposure to glucose upregulates SLC5A5 abundance in the enterocyte apical membrane. Finally, we show that the loss or gain of dSLC5A5 ameliorates or exacerbates the high sugar diet (HSD)-mediated glucose metabolic defects. Together, our studies uncovered the first Drosophila glucose transporter in the midgut and reveal new mechanisms that regulate glucose transporters in the enterocyte apical membranes.
Effects of reward history on decision-making and movement vigor

During foraging, animals decide how long to stay and harvest reward, and then abandon that site and travel with a certain speed to the next reward opportunity. One aspect of this behavior involves decision-making, while the other involves motor-control. A recent theory posits that control of decision-making and movements may be linked via a desire to maximize a single normative utility: the sum of all rewards acquired, minus all efforts expended, divided by time. If this is the case, then the history of rewards, and not just its immediate availability, should dictate how long one decides to stay and harvest reward, and how slowly one travels to the next opportunity. We tested this theory in a series of experiments in which humans used their hand to harvest tokens at a reward patch, and then used their arm to reach toward a subsequent opportunity. Following a history of poor rewards, people not only foraged for a longer period, but also moved slower to the next reward site. Thus, reward history had a consistent effect on both the decision-making process regarding when to abandon a reward site, and the motor control process regarding how fast to move to the next opportunity.
Holding a Mirror up to Nature: Shame, Guilt, and Violence in Shakespeare

Shakespeare has been dubbed the greatest psychologist of all time. This book seeks to prove that statement by comparing the playwright's fictional characters with real-life examples of violent individuals, from criminals to political actors. For Gilligan and Richards, the propensity to kill others, even (or especially) when it results in the killer's own death, is the most serious threat to the continued survival of humanity. In this volume, the authors show how humiliated men, with their desire for retribution and revenge, apocryphal violence and political religions, justify and commit violence, and how love and restorative justice can prevent violence. Although our destructive power is far greater than anything that existed in his day, Shakespeare has much to teach us about the psychological and cultural roots of all violence. In this book the authors tell what Shakespeare shows, through the stories of his characters: what causes violence and what prevents it.
An FPGA-based Hybrid Memory Emulation System

Hybrid memory systems, comprised of emerging non-volatile memory (NVM) and DRAM, have been proposed to address the growing memory demand of applications. Emerging NVM technologies, such as phase-change memories (PCM), memristor, and 3D XPoint, have higher capacity density, minimal static power consumption and lower cost per GB. However, NVM has longer access latency and limited write endurance as opposed to DRAM. The different characteristics of two memory classes point towards the design of hybrid memory systems containing multiple classes of main memory.In the iterative and incremental development of new architectures, the timeliness of simulation completion is critical to project progression. Hence, a highly efficient simulation method is needed to evaluate the performance of different hybrid memory system designs. Design exploration for hybrid memory systems is challenging, because it requires emulation of the full system stack, including the OS, memory controller, and interconnect. Moreover, benchmark applications for memory performance tests typically have much larger working sets, thus taking an even longer simulation warm-up period.In this paper, we propose an FPGA-based hybrid memory system emulation platform. We target the mobile computing system, which is sensitive to energy consumption and is likely to adopt NVM for its power efficiency. The focus of our platform is on the design of hybrid memory system, so we leverage the on-board hard IP ARM processors to enhance simulation performance while improving the accuracy of results. Thus, users can implement their data placement/migration policies with the FPGA logic elements and evaluate new designs quickly and effectively. Results show that our emulation platform provides a speedup of 9280x in simulation time compared to the software counterpart gem5.
States of Knowledge: The Co-production of Science and the Social Order

Notes on contributors Acknowledgements 1. The Idiom of Co-production Sheila Jasanoff 2. Ordering Knowledge, Ordering Society Sheila Jasanoff 3. Climate Science and the Making of a Global Political Order Clark A. Miller 4. Co-producing CITES and the African Elephant Charis Thompson 5. Knowledge and Political Order in the European Environment Agency Claire Waterton and Brian Wynne 6. Plants, Power and Development: Founding the Imperial Department of Agriculture for the West Indies, 1880-1914 William K. Storey 7. Mapping Systems and Moral Order: Constituting property in genome laboratories Stephen Hilgartner 8. Patients and Scientists in French Muscular Dystrophy Research Vololona Rabeharisoa and Michel Callon 9. Circumscribing Expertise: Membership categories in courtroom testimony Michael Lynch 10. The Science of Merit and the Merit of Science: Mental order and social order in early twentieth-century France and America John Carson 11. Mysteries of State, Mysteries of Nature: Authority, knowledge and expertise in the seventeenth century Peter Dear 12. Reconstructing Sociotechnical Order: Vannevar Bush and US science policy Michael Aaron Dennis 13. Science and the Political Imagination in Contemporary Democracies Yaron Ezrah 14. Afterword Sheila Jasanoff References Index
The sympathoadrenal lineage in avian embryos. I. Adrenal chromaffin cells lose neuronal traits during embryogenesis.

Abstract Cells of the sympathoadrenal lineage, including sympathetic neurons, adrenal chromaffin cells (pheochromocytes), and small intensely fluorescent (SIF) cells, arise from the neural crest. We have used antisera against catecholamine biosynthesis enzymes in conjunction with the monoclonal antibody A2B5 and an antiserum against the 160-kDa neurofilament (NF) protein, as markers of neuronal differentiation, to characterize the ontogeny of the sympathoadrenal lineage in quail embryos. The precursors of sympathetic neurons and pheochromocytes, present in the primary sympathetic chains, express neuronal traits and tyrosine hydroxylase (TH) early in development. The precursors that enter the developing adrenal gland from the primary sympathetic chain lose neuronal traits and later express the enzyme phenylethanolamine N-methyltransferase (PNMT). To TH+ cells differentiate in cultures of early (E7) embryonic adrenal glands after all A2B5+ cells have been immunoablated. When transplanted onto the neural crest migratory pathway, cells present in older (E13) embryonic adrenal glands can give rise to NF+ cells in the sympathetic ganglia. We conclude that both sympathetic neurons and pheochromocytes in avian embryos arise from a common bipotential precursor that initially expresses neuronal traits.
Probabilistic Forecast of Real-Time LMP via Multiparametric Programming

The problem of short-term probabilistic forecast of real-time locational marginal price (LMP) is considered. A new forecast technique is proposed based on a multiparametric programming formulation that partitions the uncertainty parameter space into critical regions from which the conditional probability mass function of the real-time LMP is estimated using Monte Carlo techniques. The proposed methodology incorporates uncertainty models such as load and stochastic generation forecasts and system contingency models. With the use of offline computation of multiparametric linear programming, online computation cost is significantly reduced.
Composite Events for Active Databases: Semantics, Contexts and Detection

Making a database system active entails developing an expressive event specification language with well-defined semantics, algorithms for the detection of composite events, and an architecture for an event detector along with its implementation. Thii paper presents the semantics of composite events using the notion of a global event history (or a global event-log). Parameter contexts are introduced and precisely defined to facilitate efficient management and detection of composite events. Finally, an architecture and the implementation of a composite event, detector is analyzed in the context of an object-oriented active DBMS.
Extant Scholarship in the Quality Profession: A Brief Review:

This work presents a review of causal comparative quality related research over time. With an in-depth review of research databases, the author concludes that quality related research are few and f...
Preparation and Effect of Different Adjuvants on the Immunogenic Activity of Mycobacterial Ribosomal Fraction

Several emulsified and two nonemulsified incomplete adjuvants were examined for their adjuvant activity by use of mycobacterial ribosomal fractions as a substrate. A good adjuvant is defined as one which produces a high immunological response with the ribosomal fraction in mice to infection with virulent tubercle bacilli. Freund's incomplete adjuvant, consisting of Aquaphor and heavy mineral oil, and Arlacel A plus hexadecane were the best adjuvants tested. Aquaphor plus light mineral oil and Arlacel A plus 7-n-hexyloctadecane were not quite as effective. Peanut oil was not satisfactory when emulsified with either Aquaphor or Arlacel A. A moderate degree of immunity was produced in mice vaccinated with ribosomal fraction mixed with aluminum hydroxide gel. Sodium alginate mixed with ribosomal fraction produced a low degree of immunity only with the highest vaccinating dose. It was found that the effectiveness of the emulsified type of adjuvant depended upon the method of preparation. Careful standardization of technique to produce uniform and complete emulsification was essential for maximal adjuvant activity using minimal vaccinating doses. A rapid and practical method of preparing emulsified adjuvants is given. The mode of action of incomplete adjuvants as employed in these experiments is discussed, and it is thought that they acted primarily by protecting the ribosomes from being inactivated by host ribonuclease before they were engulfed by the macrophages.
Evolutionary Economic Geography, Institutions, and Political Economy

In this response to MacKinnon et al. (2009), I argue that the theoretical development of evolutionary economic geographies is necessary in order to evaluate its unique contribution to an understanding of the uneven development of the space economy; that the distinction between evolutionary and institutional economic geographies is overdrawn; that the neglect of class, power, and the state reflect empirical rather than theoretical shortcomings of the evolutionary approach; and that there is significant potential overlap between evolutionary and political economy approaches.
Localization of a highly divergent mammalian testicular alpha tubulin that is not detectable in brain.

Abstract Sequence analysis of a mouse testicular alpha-tubulin partial cDNA, pRD alpha TT1, reveals an isotype that differs from both the somatic and the predominant testicular alpha tubulins at approximately 30% of the 212 amino acid residues determined. Although this mouse testicular cDNA retains the highly conserved sequence, Glu-Gly-Glu-Glu, found in the carboxyl termini of many alpha tubulins, the protein extends substantially beyond this sequence and does not terminate with a C-terminal tyrosine. Using rabbit antiserum prepared to a novel synthetic peptide predicted from this mouse testis alpha-tubulin cDNA, we have have detected by immunoblot and indirect immunofluorescence an antigenic epitope present in testicular alpha tubulin that is not detectable in brain alpha tubulins. We find that the antiserum specifically binds to the manchettes and meiotic spindles of the mouse testis but not with neural fibers or tubulin extracts of the adult mouse brain. These results demonstrate that at least one of the multiple alpha-tubulin isotypes of the mammalian testis is expressed and used in male germ cells but not in the brain.