cssi/SciSciGPT-SciSciNet huggingface dataset:
Mutagen resistance and mutation restriction of St. Louis encephalitis virus

The error rate of the RNA-dependent RNA polymerase (RdRp) of RNA viruses is important in maintaining genetic diversity for viral adaptation and fitness. Numerous studies have shown that mutagen-resistant RNA virus variants display amino acid mutations in the RdRp and other replicase subunits, which in turn exhibit an altered fidelity phenotype affecting viral fitness, adaptability and pathogenicity. St. Louis encephalitis virus (SLEV), like its close relative West Nile virus, is a mosquito-borne flavivirus that has the ability to cause neuroinvasive disease in humans. Here, we describe the successful generation of multiple ribavirin-resistant populations containing a shared amino acid mutation in the SLEV RdRp (E416K). These E416K mutants also displayed resistance to the antiviral T-1106, an RNA mutagen similar to ribavirin. Structural modelling of the E416K polymerase mutation indicated its location in the pinky finger domain of the RdRp, distant from the active site. Deep sequencing of the E416K mutant revealed lower genetic diversity than wild-type SLEV after growth in both vertebrate and invertebrate cells. Phenotypic characterization showed that E416K mutants displayed similar or increased replication in mammalian cells, as well as modest attenuation in mosquito cells, consistent with previous work with West Nile virus high-fidelity variants. In addition, attenuation was limited to mosquito cells with a functional RNA interference response, suggesting an impaired capacity to escape RNA interference could contribute to attenuation of high-fidelity variants. Our results provide increased evidence that RNA mutagen resistance arises through modulation of the RdRp and give further insight into the consequences of altered fidelity of flaviviruses.
Estimating the Prevalence of Sexual Minority Adolescents.

The Viewpoint by Dr Zaza and colleagues1 on US lesbian, gay, or bisexual (ie, sexual minority) high school students and their health-related behaviors represents “an important starting point” by describing understudied communities at risk for poor health. However, there are limitations in the Youth Risk Behavior Surveys (YRBS) worthy of comment.
Hurricane Katrina and the chōric object of rhetorical studies

ABSTRACTThis essay reads former New Orleans mayor Ray Nagin’s infamous radio interview given during the aftermath of Hurricane to rethink both the popular narrative about the federal response to Katrina and, more broadly, the displacement of rhetorical objects both popularly and within rhetorical scholarship. Drawing upon Julia Kristeva’s early work, I advocate for a turn to a particular understanding of chōra, which positions critics in provisional relation objects of rhetorical study. Finally, I tender a reading of Nagin’s post-Katrina radio interview. The essay ultimately argues that: (1) the chōric function of Nagin’s interview simultaneously spurred political change and displaced the appearance of having done so; and (2) if rhetorical studies is to avoid remaining complicit with the politics of such displacement, scholars should attend carefully not only to what counts as rhetorical, but also to those objects that do not count but nevertheless function rhetorically. Reconsidering the object domain of...
Propionic acid production from corn stover hydrolysate by Propionibacterium acidipropionici

The production of value-added chemicals alongside biofuels from lignocellulosic hydrolysates is critical for developing economically viable biorefineries. Here, the production of propionic acid (PA), a potential building block for C3-based chemicals, from corn stover hydrolysate is investigated using the native PA-producing bacterium Propionibacterium acidipropionici. A wide range of culture conditions and process parameters were examined and experimentally optimized to maximize titer, rate, and yield of PA. The effect of gas sparging during fermentation was first examined, and N2 was found to exhibit improved performance over CO2. Subsequently, the effects of different hydrolysate concentrations, nitrogen sources, and neutralization agents were investigated. One of the best combinations found during batch experiments used yeast extract (YE) as the primary nitrogen source and NH4OH for pH control. This combination enabled PA titers of 30.8 g/L with a productivity of 0.40 g/L h from 76.8 g/L biomass sugars, while successfully minimizing lactic acid production. Due to the economic significance of downstream separations, increasing titers using fed-batch fermentation was examined by changing both feeding media and strategy. Continuous feeding of hydrolysate was found to be superior to pulsed feeding and combined with high YE concentrations increased PA titers to 62.7 g/L and improved the simultaneous utilization of different biomass sugars. Additionally, applying high YE supplementation maintains the lactic acid concentration below 4 g/L for the duration of the fermentation. Finally, with the aim of increasing productivity, high cell density fed-batch fermentations were conducted. PA titers increased to 64.7 g/L with a productivity of 2.35 g/L h for the batch stage and 0.77 g/L h for the overall process. These results highlight the importance of media and fermentation strategy to improve PA production. Overall, this work demonstrates the feasibility of producing PA from corn stover hydrolysate.
A 3.2 ppm/°C Second-Order Temperature Compensated CMOS On-Chip Oscillator Using Voltage Ratio Adjusting Technique

A CMOS on-chip oscillator for the local interconnection network bus is presented. The temperature dependence of the output frequency is compensated by the voltage ratio adjusting technique. The frequency variation with supply voltage is reduced by a voltage regulator with a wide input range of 1.8–5 V. The frequency shift caused by package stress is minimized by resistor placement. Over a temperature range of −40 °C to 150 °C, the measured temperature coefficients of the output frequency are 3.2 ppm/°C without the effect of the package stress and 14.2 ppm/°C with the effect of the package stress, respectively. The measured frequency variation with supply voltage is within ±0.015%.
The Uses (and Abuses) of the Economic Community of Central African States: The Hidden Functions of Regional Economic Community Membership for African Regimes

This paper examines the “hidden” functions of the Economic Community of Central African States (ECCAS) for its member regimes. While the economic benefits of membership in ECCAS remain marginal, we argue that the organization ECCAS still serves important functions for its member states. Firstly, membership in ECCAS has provided savvy regimes with another avenue through which they can access donor funding. Secondly, membership in ECCAS has allowed some regimes to utilize the organization as a vehicle for exerting power in neighboring states. Thirdly, membership in ECCAS aids regimes in their continual efforts to build domestic and international legitimacy. “Overall, we argue that ECCAS’s promotion of collective security” tends not to be so much a genuine expression of communal efforts at peacebuilding, but more of a reflection of its members’ domestic insecurity and their narrow regime interests.
Healthcare and the Politics of Race

Straw men are large players in the debate over racial disparity in American medicine. Most have been deployed by the disparities-denying right, but progressives intent on “outing” racism have sent forth their share. In this chapter, I devote some effort to flushing them out. But my larger aim is to understand the competing moral premises that drive the politics of healthcare disparity. At the bottom, I contend, arguments about the scope of disparity and discrimination in medical care are disputes about the appropriate scope of personal responsibility for life circumstances. Further research into the factors that correlate with racial differences in healthcare can shed light on the circumstances that bring about these differences. But whether these circumstances, once understood, should be deemed acceptable is a moral and political matter. Sharp disagreements over the scope of personal and public responsibility for these circumstances are inevitable. These disagreements make it harder to pursue common ground solutions to racial and other inequities in healthcare.
Introduction : Back to the future: origins of polycystic ovary syndrome

In this Views and Reviews section we explore the ontogeny of polycystic ovary syndrome (PCOS) from in utero through puberty linking together, where possible, basic and clinical scientists to explore the implications of basic research for our clinical understanding of the syndrome.
Astrocyte Swelling in Liver Failure: Role of Glutamine and Benzodiazepines

We examined the effect of methionine sulfoximine (MSO) and peripheral benzodiazepine (BZD) ligands on ammonia-induced swelling of primary astrocyte cultures. Swelling was completely abolished by co-treatment with MSO, an inhibitor of glutamine synthetase. We also established that many of the effects caused by ammonia, including the reduction in K+ uptake, increase in Cl- uptake and reduction in myo-inosito uptake were diminished by cotreatment with MSO. Agonists of the peripheral-type BZD receptor aggravated ammonia-induced swelling, whereas a peripheral BZD receptor blocker, PK 11195, diminished the extent of swelling. Our findings implicate glutamine and the peripheral-type benzodiazepine receptor in the pathogenesis of the edema associated with fulminant hepatic failure.
Review and update of WFIRST coronagraph instrument design and technology (Conference Presentation)

Review and update of WFIRST Coronagraph Instrument Design and Technology Richard T. Demers Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena 91109, CA ABSTRACT NASA’s Wide Field InfraRed Survey Telescope (WFIRST) is a proposed flagship astrophysical observatory that would investigate dark energy, carry out wide-field near infrared (NIR) galactic surveys, and image and characterize extrasolar planets in visible reflected light. The WFIRST observatory would utilize an existing 2.4-m aperture telescope integrated with a baseline Coronagraph Instrument to image and spectrally characterize extrasolar planets in visible reflected light. The WFIRST Coronagraph is designed to directly image and characterize mature planets analogous to those in our solar system. In so doing it would advance what is currently possible in exoplanet spectral characterization and imaging using innovative wavefront and pointing jitter sensing and control algorithms, photolithographically fabricated pupil and occulting masks, precise mask positioning mechanisms, a fast steering mirror mechanism, state of the art polished optics, high actuator count deformable mirrors, electron multiplying CCDs and a lenslet-based integral field spectrograph. We present the system design concept and an overview of the current formulation phase design including structural, thermal, optical, pointing and wavefront controls as well as development of deformable mirrors and detectors for the science and engineering cameras.
Religious Support for Pacifism

When pacifism is understood as the acceptance of nonviolence and the rejection of all war and violence in personal relations and in all its expressions, religious support for pacifism can be found in various world traditions. The subject of this chapter is the multiplicity of religious support for pacifism. That support is presented in its breadth as found in traditions ranging from Islam and Judaism to Taoism, Hinduism, Buddhism, and Jainism. In addition, in a treatment of Christianity’s support for pacifism, it is argued that the Christian message of love provides a deeper support for pacifism than the moral support offered by utilitarianism and deontological ethics.
Long-term experience with diaphragm pacing for traumatic spinal cord injury: Early implantation should be considered.

Background Cervical spinal cord injury can result in catastrophic respiratory failure requiring mechanical ventilation with high morbidity, mortality, and cost. Diaphragm pacing was developed to replace/decrease mechanical ventilation. We report the largest long-term results in traumatic cervical spinal cord injury. Methods In this retrospective review of prospective institutional review board protocols, all patients underwent laparoscopic diaphragm mapping and implantation of electrodes for diaphragm strengthening and ventilator weaning. Results From 2000 to 2017, 92 patients out of 486 diaphragm pacing implants met the criteria. The age at time of injury ranged from birth to 74 years (average: 27 years). Time on mechanical ventilation was an average of 47.5 months (range, 6 days to 25 years, median = 1.58 years). Eighty-eight percent of patients achieved the minimum of 4 hours of pacing. Fifty-six patients (60.8%) used diaphragm pacing 24 hours a day. Five patients had full recovery of breathing with subsequent diaphragm pacing removal. Median survival was 22.2 years (95% confidence interval: 14.0–not reached) with only 31 deaths. Subgroup analysis revealed that earlier diaphragm pacing implantation leads to greater 24-hour use of diaphragm pacing and no need for any mechanical ventilation. Conclusion Diaphragm pacing can successfully decrease the need for mechanical ventilation in traumatic cervical spinal cord injury. Earlier implantation should be considered.
Preclinical Assessment of Cardiac Valve Substitutes: Current Status and Considerations for Engineered Tissue Heart Valves

Tissue engineered heart valve (TEHV) technology may overcome deficiencies of existing available heart valve substitutes. The pathway by which TEHVs will undergo development and regulatory approval has several challenges. In this communication, we review: (1) the regulatory framework for regulation of medical devices in general and substitute heart valves in particular; (2) the special challenges of preclinical testing using animal models for TEHV, emphasizing the International Standards Organization (ISO) guidelines in document 5840; and (3) considerations that suggest a translational roadmap to move TEHV forward from pre-clinical to clinical studies and clinical implementation.
The Changing Social Landscape of the City

When the Van Voorhis family returned to New York after the Revolution, they opened their silversmith shop on fashionable Hanover Square in the East Ward of the city (see Plate 1), the ward where most of the city’s wealthy families lived. In 1788, they moved to Queen Street, a block to the north in the same neighborhood, where they stayed until the mid-1790s. From then until 1803, when Van Voorhis left the trade, the family moved almost every year. Most years, they lived above the store, but some years, they lived away from it, in less expensive neighborhoods to the west or north of the East Ward. Each year, however, they kept their shop in or near the East Ward so that it would be accessible to their wealthy customers. Perhaps they lived away from the store when they could not find a house they could afford in the East Ward that was large enough to accommodate both their domestic and their work space.
Bee diversity in tallgrass prairies affected by management and its effects on above- and below-ground resources

Habitat management methods are crucial to maintaining habitats in the long term and ensuring vital resources are available for declining species. However, when management focuses on a single resource there is the potential to reduce or degrade other critical resources and negatively affect species of concern. Although both floral and nesting resources are critical to supporting bee populations, little consideration is given to the availability of nesting resources. Given known effects of management methods on soils, where the majority of bees nest, and floral food resources, increasing our understanding of management effects on both soils and floral resources is important to improving bee conservation efforts. In 20 tallgrass prairie plots managed under 1 of 3 common methods: burning, haying and patch‐burn grazing, we assessed effects on bee communities and necessary above‐ and below‐ground resources. We also considered how management and resources affected below‐ground nesting in each prairie. Management type affected both soil conditions and floral resources with patch‐burn grazing sites providing overall worse resources for bees compared to ungrazed sites. Soil conditions were also important for predicting most aspects of the bee community including abundance and community composition. Soil conditions also decreased floral richness and Floristic Quality Index (FQI). This suggests management affects bee communities both directly and indirectly through soil. Increased nesting was observed in sites with greater floral abundance and soil conditions that correspond to increased bare ground, lower soil moisture and warmer soil temperatures suggesting management that helps increase floral abundance and improve soil conditions could be critical to increasing bee nesting. Synthesis and applications. Measuring and tracking bare ground, Floristic Quality Index (FQI) and floral richness may help managers determine if their management methods are adversely affecting bees. Grazing and haying management negatively affected the bee community, vital nesting and floral resources and nesting rate. These managements may need to be avoided to meet bee conservation goals in prairies. Additionally, while soils have been largely overlooked, we found soil conditions to be an important predictor for bee communities and floral resources, and should be considered more explicitly in conserved areas.
A genomic dominion with regulatory dependencies on human-specific single-nucleotide changes in Modern Humans

Gene set enrichment analyses of 8,405 genes linked with 35,074 human-specific (hs) regulatory single-nucleotide changes (SNCs) revealed the staggering breadth of significant associations with morphological structures, physiological processes, and pathological conditions of Modern Humans. Significant enrichment traits include more than 1,000 anatomically-distinct regions of the adult human brain, many different types of human cells and tissues, more than 200 common human disorders and more than 1,000 records of rare diseases. Thousands of genes connected with regulatory hsSNCs have been identified in this contribution, which represent essential genetic elements of the autosomal inheritance and survival of species phenotypes: a total of 1,494 genes linked with either autosomal dominant or recessive inheritance as well as 2,273 genes associated with premature death, embryonic lethality, as well as pre-, peri-, neo-, and post-natal lethality of both complete and incomplete penetrance. Therefore, thousands of heritable traits and critical genes impacting the offspring survival appear under the human-specific regulatory control in genomes of Modern Humans. These observations highlight the remarkable translational opportunities afforded by the discovery of genetic regulatory loci harboring hsSNCs that are fixed in humans, distinct from other primates, and located in differentially-accessible (DA) chromatin regions during human brain development.
Functional traits of the gut microbiome correlated with host lipid content in a natural population of Drosophila melanogaster

Most research on the nutritional significance of the gut microbiome is conducted on laboratory animals, and its relevance to wild animals is largely unknown. This study investigated the microbiome correlates of lipid content in individual wild fruit flies, Drosophila melanogaster. Lipid content varied 3.6-fold among the flies and was significantly correlated with the abundance of gut-derived bacterial DNA sequences that were assigned to genes contributing to 16 KEGG pathways. These included genes encoding sugar transporters and enzymes in glycolysis/gluconeogenesis, potentially promoting sugar consumption by the gut microbiome and, thereby, a lean fly phenotype. Furthermore, the lipid content of wild flies was significantly lower than laboratory flies, indicating that, as for some mammalian models, certain laboratory protocols might be obesogenic for Drosophila. This study demonstrates the value of research on natural populations to identify candidate microbial genes that influence ecologically important host traits.
Connectivity Maintenance for Next-Generation Decentralized Vehicle Platoon Networks

Always keeping a certain distance between vehicles in a platoon system is important for collision avoidance. Centralized platoon systems let the leader vehicle determine and notify the velocities of all the vehicles in the platoon. Unfortunately, such a centralized method generates high packet drop rate and communication delay due to the leader vehicle’s limited communication capability. Therefore, we propose a decentralized platoon network, in which each vehicle determines its velocity by only communicating with the vehicles in a short range. However, the multiple simultaneous transmissions between different pairs of vehicles may interfere with each other. By leveraging a typical feature of a platoon, we devise a channel allocation algorithm, called the Fast and Lightweight Autonomous channel selection algorithm (FLA), in which each vehicle determines its channel simply based on its distance to the leader vehicle. We also devise a strategy, in which a succeeding vehicle uses its stored common velocity profile when it is disconnected from its preceding vehicle and then adjusts its velocity once the connection is built. We conduct experiments on NS-3 and Matlab to evaluate the performance of our proposed methods and implement a real-world prototype by equipping vehicles with Android mobile devices. The experimental results demonstrate the superior performance of our decentralized platoon network over the previous centralized platoon networks.
LATERAL FEMORAL CONDYLE OSTEOCHONDRITIS DISSECANS: DOES WEIGHTBEARING ZONE LOCATION PREDICT HEALING?:

Background:Osteochondritis dissecans (OCD) is a focal, idiopathic alteration of subchondral bone with potential for instability and disruption of adjacent articular cartilage that may result in pre...
Association of Low Socioeconomic Status With Premature Coronary Heart Disease in US Adults.

Importance Individuals with low socioeconomic status (SES) bear a disproportionate share of the coronary heart disease (CHD) burden, and CHD remains the leading cause of mortality in low-income US counties. Objective To estimate the excess CHD burden among individuals in the United States with low SES and the proportions attributable to traditional risk factors and to other factors associated with low SES. Design, Setting, and Participants This computer simulation study used the Cardiovascular Disease Policy Model, a model of CHD and stroke incidence, prevalence, and mortality among adults in the United States, to project the excess burden of early CHD. The proportion of this excess burden attributable to traditional CHD risk factors (smoking, high blood pressure, high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, type 2 diabetes, and high body mass index) compared with the proportion attributable to other risk factors associated with low SES was estimated. Model inputs were derived from nationally representative US data and cohort studies of incident CHD. All US adults aged 35 to 64 years, stratified by SES, were included in the simulations. Exposures Low SES was defined as income below 150% of the federal poverty level or educational level less than a high school diploma. Main Outcomes and Measures Premature (before age 65 years) myocardial infarction (MI) rates and CHD deaths. Results Approximately 31.2 million US adults aged 35 to 64 years had low SES, of whom approximately 16 million (51.3%) were women. Compared with individuals with higher SES, both men and women in the low-SES group had double the rate of MIs (men: 34.8 [95% uncertainty interval (UI), 31.0-38.8] vs 17.6 [95% UI, 16.0-18.6]; women: 15.1 [95% UI, 13.4-16.9] vs 6.8 [95% UI, 6.3-7.4]) and CHD deaths (men: 14.3 [95% UI, 13.0-15.7] vs 7.6 [95% UI, 7.3-7.9]; women: 5.6 [95% UI, 5.0-6.2] vs 2.5 [95% UI, 2.3-2.6]) per 10 000 person-years. A higher burden of traditional CHD risk factors in adults with low SES explained 40% of these excess events; the remaining 60% of these events were attributable to other factors associated with low SES. Among a simulated cohort of 1.3 million adults with low SES who were 35 years old in 2015, the model projected that 250 000 individuals (19%) will develop CHD by age 65 years, with 119 000 (48%) of these CHD cases occurring in excess of those expected for individuals with higher SES. Conclusions and Relevance This study suggested that, for approximately one-quarter of US adults aged 35 to 64 years, low SES was substantially associated with early CHD burden. Although biomedical interventions to modify traditional risk factors may decrease the disease burden, disparities by SES may remain without addressing SES itself.
P853 Single cell transcriptome analysis identifies unique features in circulating CD8+ T cells that can predict immunotherapy response in melanoma patients

Background Immune checkpoint blockade (ICB) has greatly advanced the treatment of melanoma. A key component of ICB is the stimulation of CD8+ T cells in the tumor. However, ICB therapy only benefits a subset of patients and a reliable prediction method that does not require invasive biopsies is still a major challenge in the field. Methods We conducted a set of comprehensive single-cell transcriptomic analyses of CD8+ T cells in the peripheral blood (mPBL) and tumors (mTIL) from 8 patients with metastatic melanoma. Results Compared to circulating CD8+ T cells from healthy donors (hPBL), mPBLs contained subsets resembling certain features of mTIL. More importantly, three clusters (2, 6 and 15) were represented in both mPBL and mTIL. Cluster 2 was the major subset of the majority of hPBL, which phenocopied hallmark parameters of resting T cells. Cluster 6 and 15 were uniquely presented in melanoma patients. Cluster 15 had the highest PD-1 levels, with elevated markers of both activation and dysfunction/exhaustion; while Cluster 6 was enriched for ‘dormant’ cells with overall toned-down transcriptional activity except PPAR signaling, a known suppressor for T cell activation. Interestingly, unlike other mTIL clusters that would classically be defined as exhausted, Cluster 15 exhibited the highest metabolic activity (oxidative-phosphorylation and glycolysis). We further analyzed total sc-transcriptomics using cell trajectory algorithms and identified that these three clusters were the most distinct subtypes of CD8 T cells from each other, representing: resting (cluster 2), metabolically active-dysfunctional (cluster 15), and dormant phenotypes (cluster 6). Further, three unique intracellular programs in melanoma drive the transition of resting CD8+ T cells (cluster 2) to both metabolic/dysfunctional (cluster 15) and dormant states (cluster 6) that are unique to tumor bearing conditions. Based on these high-resolution analyses, we developed original algorithms to build a novel ICB response predictive model using immune-blockade co-expression gene patterns. The model was trained and tested using previously published GEO datasets containing CD8 T cells from anti-PD-1 treated patients and presented an AUC of 0.82, with 92% and 89% accuracy of ICB response in the two datasets. Conclusions We identified and analyzed unique populations of CD8+ T cells in circulation and tumor using high-resolution single-cell transcriptomics to define the landscape of CD8+ T cell states, revealing critical subsets with shared features in PBLs and TILs. Most importantly, we established an innovative model for ICB response prediction by using peripheral blood lymphocytes. Ethics Approval This study was performed under an IRB approved protocol.
Redesigning Fellowship Curriculum Amidst The Covid-19 Pandemic: Our Shared Experiences.

Notably, while some patients did not have access to video conferencing for telemedicine visits (most often due to lack of access to internet, an electronic device, or technological expertise), assistance from office staff, as well as close communication with family members, greatly facilitated access for those with limitations [ ]remote conferencing facilitated collaboration with colleagues at peer institutions to share our educational offerings, thereby maximizing fellows’ educational opportunities and the impact of faculty expertise [ ]it allowed adjunct faculty currently working in other parts of the world to continue with fellow teaching [ ]for fellows engaged in research, close communication with mentors was encouraged, with time refocused on completion of analyses and manuscripts, where feasible
Polygenic Scores of Obesity and Income: Evidence from Health and Retirement Study

With an increasing prevalence of obesity, the association between obesity and income is of increasing interest. Building on recent Genome Wide Association Studies (GWAS) on polygenic risk scores of obesity, after instrumenting individual-year BMI on BMI polygenic score, BMI lowers income between 2-3%. The effects are also robust to using polygenic risk scores of waist-to-hip ratio or waist circumference. The effects are robust to controlling for polygenic scores related to depression, education, and cognition. The conjecture that higher genetic risk of obesity could mitigate income penalty, under higher polygenic cognition score or higher polygenic education score is not supported. Similarly, with higher levels of polygenic BMI scores, higher polygenic score for major depression or depression symptoms do not further reduce income. Additional heterogeneity analyses show that white males with a higher BMI had a more significantly lower income, however, white females with a higher BMI had no significant association with lower income. Possibly due to smaller subsample, neither Black males nor females had a significantly negative association with income.
Pregnancy outcomes of refractory epilepsy patients treated with Brain-responsive neurostimulation.

Abstract Objective To study the pregnancy outcomes, including obstetric complications and fetal outcomes, in pregnant women with epilepsy (WWE) treated with direct brain–responsive neurostimulation (RNS System). Methods Retrospective review of obstetric outcomes and fetal outcomes in WWE treated with the RNS System at nine comprehensive epilepsy centers in the United States from 2014–2020. In addition, changes in seizure frequency, anti-seizure medications, and RNS System setting adjustments during pregnancy were investigated. Results A total of 10 subjects and 14 pregnancies were identified. The mean age at conception was 30.6 ± 4.3 years old. The mean age at implantation was 29.8 ± 4.4 years old. The mean stimulation charge densities ranged from 1.0 to 3.0 μC/cm2 during pregnancy. Obstetric complications included recurrent miscarriage (1 patient), cesarean section (3 patients) due to preeclampsia, non-reassuring fetal heart rate tracing or prolonged labor, preterm birth (1 patient), and preeclampsia (1 patient). No still birth, gestational hypertension, gestational diabetes, eclampsia, or maternal mortality were observed. No RNS System-exposed pregnancies had major congenital malformations. One offspring had a minor congenital anomaly of cryptorchidism in a pregnancy complicated with risk factors of advanced maternal age and bicornuate uterus. Significance The present study is the first report of RNS System-exposed pregnancies in WWE to date. No major congenital malformations were identified. All of the obstetric complications were within the expected range of those in WWE based on previously published data. The sample size of our study is small, so accumulation of additional cases will further help depict the safety profile of treatment with the RNS System during pregnancy.
Institutional Change and Early-Stage Startup Selection: Evidence from Applicants to Venture Accelerators

Existing research at the nexus of institutional theory and entrepreneurship suggests that lowering institutional barriers to forming, growing, and exiting new firms through legal and regulatory reforms can affect the types of startups that entrepreneurs found in a region. These institutional changes could affect entrepreneurs' willingness to partner with organizational sponsors to develop high-growth startups and potentially enhance these sponsors' ability to select high-growth startups to fund and develop. This study evaluates these ideas by developing and testing three hypotheses, that institutional reforms (a) improve entrepreneurs' perceived benefits of the resources that organizational sponsors provide, (b) increase the number, quality, and diversity of applicants for these resources within sponsors' local ecosystems, and (c) enhance sponsors' capacity to select high-growth startups into their cohorts. To evaluate these hypotheses, I analyze data from 13,770 applicants to venture accelerators over multiple application cycles between 2016-2018 in 170 countries, using a difference-in-differences design that exploits institutional reforms that aimed to reduce the time and procedures to start new firms, obtain credit, and resolve bankruptcy for entrepreneurs. The findings have important implications for how institutional reforms affect early-stage entrepreneurship and the capacity of organizational sponsors to select high-growth early-stage startups to fund and develop within their local ecosystems.
Advances in long-acting injectables, implants, and vaginal rings for contraception and HIV prevention

Abstract Worldwide, women face compounding reproductive health risks, including human immunodeficiency virus (HIV), sexually-transmitted infections (STIs), and unintended pregnancy. Multipurpose prevention technologies (MPTs) offer combined protection against these overlapping risks in singular prevention products that offer potential for simplified use, lower burden, higher acceptability, and increased public health benefits. Over the past decade, substantial progress has been made in development of extended-release MPTs, which have further potential to grant sexual and reproductive health autonomy to women globally and to offer choice for women to accommodate varying needs during their reproductive lives. Here, we highlight the advances made in injectable, implant, and ring delivery forms, and the importance of incorporating end-user preferences early in the research and development of these products.
Application of synchrotron X-ray topography to characterization of ion implanted GaN epitaxial layers for the development of vertical power devices

Ion implantation is an essential step for selective area p-type doping of GaN, which is required for the development of vertical GaN devices that will help realize the potential of wide bandgap semiconductor GaN in power electronics. Changes to the microstructure of GaN epilayers on ion implantation and subsequent annealing were characterized by synchrotron X-ray topography and high-resolution X-ray diffraction (HRXRD). Enlarged contrast of screw and edge types of threading dislocations (TDs) on X-ray topographs after homoepitaxial growth is likely due to interaction of the dislocations with point defects. X-ray topographs reveal ion implantation does not change the distribution of dislocations in the wafer. HRXRD spectra have satellite peaks from lattice damage due to implantation. This damage is completely healed upon annealing. Strain and tilt maps derived from X-ray rocking curve topographs also show that annealing leads to an improvement in lattice bending.
A Step Towards Usable Privacy Policy: Automatic Alignment of Privacy Statements

With the rapid development of web-based services, concerns about user privacy have heightened. The privacy policies of online websites, which serve as a legal agreement between service providers and users, are not easy for people to understand and therefore offer an opportunity for natural language processing. In this paper, we consider a corpus of these policies, and tackle the problem of aligning or grouping segments of policies based on the privacy issues they address. A dataset of pairwise judgments from humans is used to evaluate two methods, one based on clustering and another based on a hidden Markov model. Our analysis suggests a five-point gap between system and median-human levels of agreement with a consensus annotation, of which half can be closed with bag of words representations and half requires more sophistication.
Vibration Tests of a Nine-Story Steel Frame Building

A nine-story steel frame building has been subjected to an extensive ser of forced resonance tests. Seven translational and three torsional modes were investigated in detail. A mode in which the floor slabs vibrated horizontally as free-free beams was excited as well. Stiffness and damping matrices were calculated from the experimentally determined modal properties. Damping values were found to be considerably lower than those usually mentioned in the literature. The lowest translational modes in the two principal directions of the building had damping values of approximately 0.5%. The second lowest translational modes had damping values of approximately 1.0%. Damping was found to increase linearly with resonant frequencies. Consistent, but small increases in damping values were found as the amplitude was increased. The damping mechanism is well represented by relative dashpots.
Questions, Answers and Wait-Time: Implications for Assessment of Young Children.

While testing children for readiness to enter Kindergarten using the Peabody Individual Achievement Test-R and interview probes, a pattern of responses developed indicating that some of the children were continuing to process answers to questions and to formulate elaborations to statements long after the testing had moved to other questions and lines of inquiry. This development was then examined to determine whether young children should be given extended thinking/processing time in order to properly and completely demonstrate their abilities and knowledge. Consideration of validity and relevance must also be given to answers that may at first appear to be irrelevant to the latest question asked. The implications of the data for planning, developing, and implementing assessment as well as decisions regarding curriculum and instruction are discussed.
Learning to predict where humans look

For many applications in graphics, design, and human computer interaction, it is essential to understand where humans look in a scene. Where eye tracking devices are not a viable option, models of saliency can be used to predict fixation locations. Most saliency approaches are based on bottom-up computation that does not consider top-down image semantics and often does not match actual eye movements. To address this problem, we collected eye tracking data of 15 viewers on 1003 images and use this database as training and testing examples to learn a model of saliency based on low, middle and high-level image features. This large database of eye tracking data is publicly available with this paper.
Asymmetric α-Alkylation of Aldehydes, Ketones, and Carboxylic Acids

Asymmetric carbon–carbon, bond-forming reactions comprise one of the most important general classes of synthetic transformations. Among the various methods used for the construction of these bonds, those based on electrophilic addition to enolates (and their analogs) are especially pervasive. Indeed, the asymmetric α-alkylation of aldehydes, ketones, and carboxylic acids is firmly entrenched as a fundamental method for the stereocontrolled synthesis of natural products and drugs. This chapter provides an overview of the current state-of-the-art approaches to achieving such transformations, which includes the firmly established and well-tested auxiliary-based methods, as well as more recent nonauxiliary strategies conducted in both a stoichiometric and a catalytic fashion. Keywords: asymmetric α-alkylation; stereoselective; CC bond formation; stereocontrolled; synthesis; deprotonation; pharmaceutical; chiral auxiliary; drug; natural product
Steroid-protein interactions. XXX. A progesterone-binding protein in the uterine cytosol of the pregnant guinea pig.

Abstract The uterine cytosol of the pregnant guinea pig contains a progesterone-binding protein whose physicochemical properties are different from those reported for estrogen and progesterone receptors from the uteri of estrogen-treated ovariectomized animals. The progesterone binder in the pregnant guinea pig uterus is a protein, has a sedimentation coefficient of 5.5 S at both low and high ionic strength, and does not require free sulfhydryl groups for steroid binding. This binding protein has certain similarities with the progesterone-binding globulin from serum. Both proteins have a highly specific affinity for progesterone as well as for synthetic progestogens. Also, the size of the uterine protein is within the range of molecular sizes of the polydisperse serum glycoprotein. However, the progestogen-binding protein of the uterus and progesterone-binding globulin differ in average sedimentation coefficient, Stokes radius, and in their stability to heat or to changes in pH. The uterine cytosol binder-progesterone complex has an association constant of approx. 3 · 108-6 · 108 M−1 at 4°C. Preliminary immunochemical experiments using progesterone-binding globulin-specific antisera did not show any cross reactivity of the uterine binder with anti-progesterone-binding globulin antibody.
BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma

BACKGROUND: Uterine serous carcinoma (USC) is not recognized as part of any defined hereditary cancer syndrome, and its association with hereditary breast and ovarian carcinoma and Lynch syndrome are uncertain. METHODS: Using targeted capture and massively parallel genomic sequencing, 151 subjects with USC were assessed for germline mutations in 30 tumor suppressor genes, including BRCA1 (breast cancer 1, early onset), BRCA2, the DNA mismatch repair genes (MLH1 [mutL homolog 1], MSH2 [mutS homolog 2], MSH6, PMS2 [postmeiotic segregation increased 2]), TP53 (tumor protein p53), and 10 other genes in the Fanconi anemia–BRCA pathway. Ten cases with < 10% serous histology were also assessed. RESULTS: Seven subjects (4.6%) carried germline loss-of-function mutations: 3 subjects (2.0%) with mutations in BRCA1, 2 subjects (1.3%) with mutations in TP53, and 2 subjects (1.3%) with mutations in CHEK2 (checkpoint kinase 2). One subject with < 10% serous histology had an MSH6 mutation. Subjects with MSH6 and TP53 mutations had neither personal nor family histories suggestive of Lynch or Li-Fraumeni syndromes. Of the 22 women with USC and a personal history of breast carcinoma, the frequency of BRCA1 mutations was 9%, compared to 0.9% in 119 women with no such history. CONCLUSIONS: Approximately 5% of women with USC have germline mutations in 3 different tumor suppressor genes: BRCA1, CHEK2, and TP53. Mutations in DNA mismatch repair genes that cause Lynch syndrome are rare in USC. The germline BRCA1 mutation rate in USC subjects of 2% is higher than expected in a nonfounder population, suggesting that USC is associated with hereditary breast and ovarian carcinoma in a small proportion of cases. Women with USC and breast cancer should be offered genetic testing for BRCA1 and BRCA2 mutations. Cancer 2013. © 2012 American Cancer Society.
Chemical urolithiasis: 1. Characteristics of bladder stone induction by terephthalic acid and dimethyl terephthalate in weanling Fischer-344 rats

Abstract Bladder stone induction by terephthalic acid (TPA) and dimethyl terephthalate (DMT) was investigated using weanling Fisher-344 rats. Exposure of these rats over a 2-week period resulted in a 93.3% incidence of bladder calculi in male pups receiving 5% dietary TPA, and a 100% incidence in male pups receiving 3% dietary DMT. Female pups also developed stones, but at a lower frequency. The dose-response curves for stone induction were extremely steep and were parallel for both compounds; no stones were induced at dietary concentrations below 1.5%. Histologic examination of the urinary tract revealed extensive hyperplasia of the transitional epithelium only in the urinary bladders that contained calculi. Analysis of calculi indicated a heterogeneous chemical composition. The principal components (by weight) were: TPA, calcium, phosphate, and protein in the TPA-induced stones, and TPA, calcium, and protein in the DMT-induced stones. Concentrations of calcium, TPA, and phosphate, as well as pH, were determined in the urine of weanling rats at sacrifice. Both TPA and DMT induced urinary acidosis and hypercalciuria in the range of doses used. Urinary phosphate concentrations were reduced in DMT-treated pups, consistent with the absence of phosphate in DMT-induced calculi. The results indicate that critical saturating urinary concentrations of TPA and calcium are necessary for stones to develop following TPA or DMT exposure, and that calculus formation appears to be a prerequisite for the induction of terephthalate-induced bladder hyperplasia.
La Tragicomedia de Calisto y Melibea en la versificación de Juan Sedeño (Salamanca, 1540)

Juan Sedeno tanto admiro la prosa de Celestina que versifico sus veintiun actos, y la publico en 1540 en Salamanca, en una edicion que nunca se reimprimio. Solo se ha editado modernamente dos veces (1971 y 2009). La version se compuso en mil quinientas ochenta decimas octosilabas. Cada acto, como en las ediciones tempranas de la original en prosa, lleva un grabado. Logro su objetivo de no anadir ni quitar nada, debido a la reverencia que sentia hacia sus primeros autores. Se ofrece aqui una completa descripcion de R/6601 de la Biblioteca Nacional de Espana (Madrid) y el cotejo de cuatro muestras de la versificacion de Sedeno con la prosa que metrifico.
Making Complex Articulated Agents Dance

We discuss the tradeoffs involved in control of complex articulated agents, and present three implemented controllers for a complex task: a physically-based humanoid torso dancing the Macarena. The three controllers are drawn from animation, biological models, and robotics, and illustrate the issues of joint-space vs. Cartesian space task specification and implementation. We evaluate the controllers along several qualitative and quantitative dimensions, considering naturalness of movement and controller flexibility. Finally, we propose a general combination approach to control, aimed at utilizing the strengths of each alternative within a general framework for addressing complex motor control of articulated agents.
Microsearch: When Search Engines Meet Small Devices

In this paper, we present Microsearch, a search system suitable for small devices used in ubiquitous computing environments. Akin to a desktop search engine, Microsearch indexes the information inside a small device, and accurately resolves user queries. Given the very limited hardware resources, conventional search engine designs and algorithms cannot be used. We adopt information retrieval techniques for query resolution, and propose a space efficient algorithm to perform top-k query on limited hardware resources. Finally, we present a theoretical model of Microsearch to better understand the tradeoffs in system design parameters. By implementing Microsearch on actual hardware for evaluation, we demonstrate the feasibility of scaling down information retrieval systems onto very small devices.
Viscoelasticity and thermal analysis

DMA is a tool for studying linear viscoelastic behavior of polymers over ranges of temperature and frequency. Viscoelasticity has its origin in the complex molecular behavior of the polymer. A theoretical master curve has been constructed, based predominantly on thermodynamic theories of polymer molecular conformations, and their intermolecular cooperativity.