cssi/SciSciGPT-SciSciNet huggingface dataset:
Optimization of the investment cost of solar based grid

Abstract A new optimization method of the investment cost of a distribution grid supplied by photovoltaic (PV) sources. This method consists of determining the optimal grid cables cross sections and the optimal grid supply point (GSP) position, such that the sum of the joule losses and the cables investment costs are optimized. The determination of these parameters are performed by the programming of analytical equations using Matlab software, taking into account the influence of technical and economical requirements on the choice of the cables cross sections and the possibility of using several photovoltaic generators (PVG) with separated grids for spaced loads from a long distance, by optimizing the grouping loads combination. The obtained results show that: for a lowest global investment cost, the optimal GSP is referred to the minimum cost center (MCC), for the grid joule losses minimization, it can be in the minimum joule losses cost center (MJLCC); or in the center of the minimum investment cost of cables (CMICC) in the case of the cables investment cost minimization. The adoption of the optimal cross sections, the optimal PVGs (GSPs) number and their optimal positions achieve significant economic gains in terms of the investment cost.
Perinatal mortality. Overview and current trends.

Perinatal mortality remains a problem of concern in the United States. An important focus of the joint endeavor of the medical profession, hospitals, parents, and government institutions lies in the prevention of low birth weight and the provision of medical care required for infants weighing 2500 gm. or less at birth.
C57BL/6J bone marrow transplant increases sociability in BTBR T+ Itpr3tf/J mice

Associative studies across a range of neurodevelopmental disorders have revealed a relationship between immune system function and behavioral deficits. These correlations are particularly evident in individuals with autism spectrum disorders (ASD), a developmental disorder characterized by social behavior deficits and noted for its high instances of immune system dysfunction. Mouse models provide a unique opportunity to explore causal links between immune and nervous system function and reveal how changes in these systems alter behavioral profiles. The BTBR T+ Itpr3tf/J (BTBR) mouse strain is characterized by both social behavior impairments and aberrant immune responses, affording the unique opportunity to investigate the causal relationship between behavior and immunity through direct manipulation of these systems. Using bone marrow from the highly social C57BL/6J (C57) mouse strain, BTBR mice were tested for changes in social approach behavior and repetitive grooming following irradiation and bone marrow transplant. BTBR recipient mice treated with allogeneic bone marrow from C57 donor mice, but not syngeneic BTBR bone marrow, displayed increased sociability as measured by the three-chamber social approach task and total time spent social sniffing. In addition, C57 recipient mice given allogeneic bone marrow from BTBR donors showed a significant increase in repetitive grooming behavior. These data provide evidence for a causal relationship between peripheral immune phenotype and social behavior in the BTBR mouse strain and further strengthen and expand on our existing understanding of the role of immune function in behavior.
Research Design and Method

Chapter 2 focuses on the methodologies used while collecting data for this project. It specifically addresses the oral narratives that I collected on my two participants (Luis and Quetzin), and how their historias de exito are often grounded in Latino practices like buena gente, buen trabajador, and bien educado that are often not understood within many White European Americans (WEAs). This chapter also spends ample time in explaining the process of structured and unstructured interviews and the important role they played in collecting my participants’ counter stories.
The effects of neoadjuvant therapy on morbidity and mortality of esophagectomy for esophageal cancer: American college of surgeons national surgical quality improvement program (ACS–NSQIP) 2005–2012

Objective This study used a multi-center database to evaluate the impact of neoadjuvant therapy on the 30-day morbidity and mortality following esophagectomy for esophageal cancer. Methods The NSQIP database was queried for 2005–2012 for patients, who had esophagectomy for esophageal cancer. Patients were divided into two groups: neoadjuvant therapy and esophagectomy only. Results The neoadjuvant group had a lower rates of sepsis (8% vs. 13%, unadjusted P = 0.004) and acute renal failure (0.4% vs. 2%, unadjusted P = 0.01), and a higher rate of pulmonary embolism (PE) (3% vs. 1%, unadjusted P = 0.04). The adjusted odds of PE for patients, who received neoadjuvant therapy were 2.8 times the odds of PE for patients in the esophagectomy group, controlling for BMI. The association with renal failure was not significant, when one adjusted for race. There was no difference in the rates of reoperation, readmission, stroke, cardiac arrest, MI, surgical site and deep organ infections, anastomosis failure, blood transfusions, DVT, septic shock, pneumonia, UTI, respiratory failure, and 30-day mortality between the two groups. Conclusions We conclude that neoadjuvant therapy followed by esophagectomy for esophageal cancer does not have a negative impact on 30-day mortality. Neoadjuvant therapy is associated with increased odds of PE. J. Surg. Oncol. 2017;115:296–300. © 2016 Wiley Periodicals, Inc.
Strategic Positioning for Market Entry in Different Technological Environments

Current research suggests that an understanding of the technological environment is necessary to gaining a competitive advantage. In this paper, a model is developed to analyze the relationship bet...
What is motivating middle-school science teachers to teach climate change?*

ABSTRACTAdoption of science content standards that include anthropogenic climate change has prompted widespread instruction in climate change for the first time. However, the controversial nature of the topic can be daunting and many teachers share misconceptions that lead to weak treatment of climate change in classrooms. Nevertheless, numerous teachers have embraced the topic and are providing illustrations of deliberate climate change education. In this study we investigated teacher motivation using focus groups with middle school teachers who currently teach climate change. Qualitative analysis of the collective teacher voices yielded underlying motivations. Our findings suggest that these teachers’ interest in environmentalism naturally translates to climate change advocacy and motivates teaching the topic. Their knowledge and expertise gives them confidence to teach it. These teachers see themselves as scientists, therefore their views align with the scientific consensus. They practice authentic sci...
Introduction to TNF/pathophysiology of TNF

The complex organization of cellular functions in the human body requires a precise interplay of activity. Cell to cell communications must be sent and received in an efficient system. When the distance over which a signal must travel is greater then an intracellular space, soluble polypeptide factors called cytokines are employed as messenger proteins [1]. Cytokines are small proteins released by cells that trigger specific effects on target cells equipped to respond. Cytokines can be broadly categorized as primary and secondary cytokines. Primary cytokines, such as IL-1 and Tumor Necrosis Factor alpha (TNF-α), are considered part of the innate immune system and can independently initiate inflammatory cascades in human tissues. Secondary cytokines are produced later in the cascade, after the primary cytokines. They have a more limited range of activity.
Narcolepsy in the Older Adult

Narcolepsy is generally considered an illness of youth because its incidence peaks around the second to third decade of life. Despite this it should still be on the differential of an older adult presenting with excessive daytime sleepiness. A small percentage of patients with narcolepsy have onset beyond age 35 with case reports of patients developing narcolepsy as late as the ninth decade. In addition to late onset of narcolepsy, cases of narcolepsy diagnosed after age 35 are sometimes due to delayed diagnosis despite symptom onset at a more typical age. Late-onset narcolepsy can also be due to symptomatic narcolepsy or narcolepsy-like symptoms that are due to another medical condition such as sarcoidosis, demyelinating disease, paraneoplastic disorders, or stroke.
Importance of nasality measures for speaker recognition data selection and performance prediction.

We improve upon our measures relating feature vector distributions to speaker recognition (SR) performances for performance prediction and potential arbitrary data selection for SR, as described in [1]. In particular, we examine the means and variances of 11 features pertaining to nasality (each of which is denoted as a measure), computing them on feature vectors of phones to determine which measures give good SR performance prediction of phones. We’ve found that the combination of nasality measures give a 0.917 correlation with the Equal Error Rates (EERs) of phones on SRE08, exceeding the correlation of our previous best measure (mutual information) by 12.7%. When implemented in our data-selection scheme (which does not require a SR system to be run), the nasality measures allow us to select data with combined EER better than data selected via running a SR system in certain cases, at a fortieth of the computational costs. The nasality measures also require a tenth of the computational costs to compute compared to our previous best measure.
Strange Harvest: a Cross-sectional Ecological Analysis of the Association Between Historic Lynching Events and 2010-2014 County Mortality Rates.

While the causes of lynching, a violent expression of racism, have been explored, little research has addressed the long-term consequences of this phenomenon. We examined the associaton between living in a county with a history of lynching and contemporary mortality rates within Southern US states. County-level data for lynchings between 1877 and 1950 were available for 1221 counties. Lynching rates were standardized to the 1930 population. Age-adjusted mortality rates were aggregated over 2010–2014 to allow sufficient observations in small counties. Multivariable linear regression examined the association between lynching rate categories and mortality while holding other county characteristics constant. Overall age-adjusted mortality ranged from 863 deaths per 100,000 persons in counties with no recorded lynchings to 910 in the highest lynching rate counties (p < 0.000). In adjusted models, living in the highest versus lowest lynching category was associated with 34.9 (95% confidence interval 13.3–56.7) additional deaths per 100,000 per year for white males, 23.7 (95% CI 7.48–40.0) deaths for white females, and 31.0 (95% CI 3.6–58.4) deaths for African American females. No association was found for African American male death rates (31.3; 95% CI − 13.6 to 76.1). The mechanisms through which historic lynching events might be associated with contemporary mortality rates are not clear. We advocate further research into structural characteristics of counties that may influence such disparities.
Flipping the classroom: a national pilot curriculum for physiology in neonatal-perinatal medicine.

To explore interest, feasibility, perceived effectiveness, and acceptability of a standardized, national physiology curriculum for neonatal–perinatal medicine (NPM) fellows using online videos for knowledge acquisition paired with flipped classrooms (FCs) for knowledge application. Two educational programs pairing online videos with FCs were developed and peer-reviewed. These programs were piloted at five institutions. Fellows completed surveys, and fellows and educators participated in focus groups after their FC experiences. Thirty-five fellows responded to the survey. Forty-one fellows and six educators participated in focus groups. Fellows and educators preferred online videos paired with FCs over didactic teaching and perceived them to be effective for knowledge acquisition and application. Fellows and educators preferred FC learning over traditional didactics and reported that FCs facilitated creation of a learning community, fostering active learning. The favorable response toward this pilot project and the feasibility of its use supports further development of a standardized NPM physiology curriculum for fellowship training.
A life cycle assessment-based multi-objective optimization of the purchased, solar, and wind energy for the grocery, perishables, and general merchandise multi-facility distribution center network

Abstract Walmart Inc., the U.S. and world’s largest grocery retailer, owns a perishables, grocery, and general merchandise distribution center network, which stores and distributes refrigerated and non-refrigerated food. Finding cost-effective strategies to implement solar and wind-powered electricity in their distribution centers was the central objective of this research. The study analyzed the tradeoffs and effects on costs and climate change impact related to the increase of renewable energy use in the distribution centers. The research combined the life cycle assessment and quantitative methods including the Monte Carlo uncertainty analysis and the multi-objective optimization. A life cycle assessment-based multi-objective optimization model was built to find cost-effective strategies to minimize fossil energy use and mitigate the impact of the Walmart Inc. distribution center network on climate change. The bi-objective and the triple-objective optimization included a number of combinations of minimal costs, non-renewable fossil energy use, and climate change impact criteria. The results of the multi-objective optimizations were Pareto-optimal solutions obtained by weighing the importance of chosen criteria from the baseline to the zero energy scenarios. A selection of the Pareto-optimal solutions included the good, the better, and the zero energy building scenarios. A better building was a Pareto-optimal set of buildings, which demonstrated superiority from the life cycle assessment perspective. The superiority of Pareto-optimal solutions was evaluated using the Monte Carlo pairwise comparison. The good distribution centers were characterized by the Pareto-optimal solutions between the baseline and the better distribution centers. Finally, the zero energy general merchandise distribution centers were mostly the Pareto-optimal solutions with a 100% share of solar energy. For the zero energy grocery and perishables distribution centers the solutions were a combination of solar and supplemental wind energy because refrigerated warehouses are more energy intensive. The study provided the benchmark results that may improve distribution centers and other buildings and a framework to test environmental and renewable energy policies in buildings.
Evolving Trends in Liver Transplant for Metabolic Liver Disease in the United States

Indications for liver transplantation (LT) in metabolic disease are evolving. We reviewed the US experience with primary LT for metabolic disease in the Scientific Registry for Transplant Recipients (October 1987 to June 2017) to determine the following: temporal changes in indications, longterm outcomes, and factors predicting survival. Patients were grouped by the presence of structural liver disease (SLD) and whether the defect was confined to the liver. There were 5996 patients who underwent LT for metabolic disease, 2354 (39.3%) being children. LT for metabolic disease increased in children but not in adults. Children experienced a 6-fold increase in LT for metabolic disease without SLD. Indications for LT remained stable in adults. Living donor liver transplantation increased between era 1 and era 3 from 5.6% to 7.6% in children and 0% to 4.5% in adults. Patient and graft survival improved with time. The latest 5-year patient survival rates were 94.5% and 81.5% in children and adults, respectively. Outcomes were worse in adults and in those with extrahepatic disease (P < 0.01), whereas SLD did not affect outcomes. Survival improved with younger age at LT until age <2 years. On multivariate analysis, diagnostic category, inpatient status, age at LT, and transplant era significantly predicted outcomes in all ages with male sex predicting survival in childhood only. Children without structural disease were less likely to die awaiting LT and had improved post-LT survival compared with children with chronic liver disease. In conclusion, LT for metabolic disease is increasingly used for phenotypic correction in children; extrahepatic manifestations significantly impact survival at all ages; where indicated, transplantation should not be unnecessarily delayed; and the development of new allocation models may be required.
Food-grade Pickering emulsions stabilized by ovotransferrin fibrils

Abstract The present work aimed to explore the feasibility of fabricating stable food-grade Pickering emulsions stabilized by ovotransferrin (OVT) fibrils. Raman imaging microscopy and confocal laser scanning microscopy confirmed that Pickering emulsion droplets stabilized by OVT fibrils were successfully prepared. Visual observation revealed that OVT fibril-stabilized Pickering emulsions at different fibril concentrations and oil fractions had high emulsified phase volume, and these Pickering emulsions had high stability index during 20-day storage at 20 °C. OVT fibrils could be employed to stabilize Pickering emulsions at broad ionic strengths (i.e., 0–1000 mM) and pHs (i.e., 2–7). Increasing either ionic strength or pH was helpful for the formation of emulsions with higher emulsified phase volume fraction, smaller emulsion droplets, and larger gel strength. In terms of thermal stability, OVT fibril-stabilized Pickering emulsions were stable during 10-day storage at 50 °C. The acquired knowledge in this study may provide new insight into fabrication of food-grade Pickering emulsions with excellent stability.
Who’s Looking Out for the Consumer? A Profile of Concerned Marketers

This study investigated one aspect of marketer’s acceptance of their responsibility for the well-being of consumers. It considered the extent to which retailers are oriented toward protecting their customers from counterfeit products. The empirical segment of the study identified both "accepting" and "rejecting" groupings of retailers and provided a profile of each group. Portraying concerned, accepting marketers made it possible to draw conclusions about the nature of involvement by the marketing system in consumer welfare. It also aided suggesting means by which marketers can be motivated to accept greater responsibility for the welfare of the consuming public.
Riparian forest recovery following a decade of cattle exclusion in the Colombian Andes

Abstract To meet their large-scale forest and landscape restoration targets, countries must find ways to accommodate areas for conservation alongside agricultural production. In some pasture-dominated regions of Latin America, intensive silvopastoral systems (SPS) are being promoted to increase cattle productivity on certain lands while facilitating the removal of cattle from marginal areas for forest restoration. However, the recovery of these forests and their contribution to the overall conservation value of the landscape has not been assessed rigorously. We evaluated forest structure and composition in 20 sites in a region of the Colombian Andes where a decade ago farmers transitioned to SPS and fenced off riparian areas to enable forest recovery. We compared these restored forests to a reference model based on the remaining riparian forest across the region, all of which has been subjected to human management. We found that woody species richness was higher in restored than in reference forests, and the proportion of large-seeded, later successional, animal-dispersed species were similar in both forest types. Whereas we found a similar suite of dominant tree species in restored and reference forest, Guadua angustifolia, a native giant bamboo was more abundant in the reference forests due to human management. Total tree basal area was higher in restored forests due to a small number of very large trees likely present in the pastures at the time of site protection. These findings highlight (1) the potential for recovery of diverse forests in riparian sites despite previous grazing use and (2) the role of remnant trees in facilitating natural succession. Overall, rapid forest recovery with minimal intervention in previously farmed lands is good news for conservation in a region that still harbors significant biodiversity despite high levels of fragmentation and the influence of human management.
Pulse-and-Glide Operation for Parallel Hybrid Electric Vehicles with Step-Gear Transmission in Automated Car-Following Scenario with Ride Comfort Consideration

In this paper, the pulse and glide (PnG) operation for parallel hybrid electric vehicles (HEVs) with step-gear transmission in cruising scenario is considered. The PnG operation is an eco-driving technique that alternately turns on and off the engine to achieve better fuel economy. For HEVs, the batteries can serve as yet another energy buffer in addition to the vehicle body. However, due to the power loss during battery charging and discharging, the fuel saving performance of PnG using only battery is much degraded, even though it can lead to better ride comfort. Therefore, in this work, we introduce speed oscillation to SOC-PnG that originally only oscillates the state-of-charge (SOC) of the battery. Meanwhile, desired ride comfort and SOC sustenance requirements need to be fulfilled. To achieve this goal, two optimal control problems are formulated, one for the gliding phase and the other for the pulsing phase. By linearizing the vehicle dynamics and applying the McCommick envelop approach, the problems can be transcribed into quadratic programming (QP) problems using the Legendre pseudo-spectral (PS) method. The resultant QP problems can be solved efficiently. Therefore, this framework is suitable for real-time on-line implementation. Numerical simulations are conducted to show the ability of the proposed method to improve fuel economy, while maintaining desired ride comfort and sustaining the battery SOC.
A Pitch Detection Method

Auto-correction function is a simple and effective method in pitch estimate, but it needs a number of multiplication. Center clipping is a method, which used to wipe off the effect of track, in order to acquire a more exact pitch period. A new method is brought forward, which avoids a mass of multiplication. So it improves the effect of auto-correction.
High-Rayleigh-number thermal convection of compressed gases in inclined rectangular enclosures

High-Rayleigh-number convection is experimentally studied using compressed gases for a wide range of Rayleigh numbers (1.85 × 106 ≤ Ra ≤ 1.04 × 1011) and angles of inclination (θ = 0°, 30°, 60°, 90°, 120°, and 150°) with rectangular enclosures of varied aspect ratios (AR = 1, 3, 6, and 10). Experimental results reveal that the Nusselt number decreases monotonically with increasing angle of inclination. Furthermore, for any angle of inclination and a given Rayleigh number, the Nusselt number is observed to follow a decreasing trend with an increase in aspect ratio, which gradually amplifies as the angle of inclination is increased. Z-type shadowgraph flow visualization experiments, employed to characterize buoyant flow behavior at various angles of inclination, confirm the observed heat transfer trends.
Weight loss as an untapped early detection marker in pancreatic cancer.

643Background: Pancreatic cancer has the worst survival of common cancers and there are no reliable early detection tests. While prior reports link unintentional weight loss (>5% decrease from base...
5.14 – Leukocyte Trafficking

Leukocyte migration from the blood into tissues is essential for effective host responses to tissue damage, infection, and other insults. Likewise, the continuous recirculation of lymphocytes from the blood into lymphoid tissues, the collection in lymphatics, and the entry back into the blood via the thoracic duct are essential for effective immune responses. The migration of immune cells from the blood into various organs manifests in inflammation, tissue, and leukocyte specificities, and is controlled in large part by specific adhesive interactions between the leukocyte in circulation and the endothelial cells. Soluble factors (chemotactic factors) released by tissues attract the immune cell bound to the endothelium into the extravascular spaces. The intent of this chapter is to provide a brief overview of the role of leukocyte adhesion molecules and chemotactic factors in leukocyte trafficking and to discuss possible effects of various toxicants on the migration of cells from the blood into tissues. A comprehensive presentation of the structure/function of the molecules involved in trafficking is not given here, but some key articles and reviews are cited for access to this information.
Health Beliefs and Breast Cancer Screening Practices Among African American Women in California

BackgroundAfrican American women continue to have higher mortality rates of breast cancer when compared to other women, and evidence suggests that early detection of breast cancer can lead to favor...
Psychosocial risk and body dysmorphic disorder: A systematic review

Body dysmorphic disorder (BDD) is a psychiatric diagnosis characterized by a debilitating preoccupation with perceived appearance defects that are not noticeable to others. The International OCD Fo...
Roses or Lemons: Adverse Selection in the Market for ThoroughbredYearlings

This paper tests for the presence of adverse selection in thoroughbred yearling auction markets. Thoroughbred auctions consist of two seller types: sellers who breed horses to race and sell (racers) and sellers who take all their yearlings to auction (breeders). If racers use private information, keeping those yearlings with a higher probability of on-track success, they are likely to receive a lower price for similar yearlings as compared to breeders. Using data from Keeneland's 1994 September yearling sale, we find support for this hypothesis. We improve on previous studies by analyzing the distinction between seller types on a continuous scale.
Overcoming Blind Spots to Promote Environmental Justice Research.

Ecological research includes social–ecological–evolutionary processes, but the intersectionality and feedbacks between ecology and environmental justice (EJ) remain low. We here present opportunities for ecological research contributions to EJ. Ultimately, such work can reduce racial and social disparities in environmental provisioning and improve global environmental sustainability.
Thermo-mechanical buckling of stepped circular bi-laminates

Abstract Thermo-mechanical buckling of stepped circular bi-laminates subjected to a uniform temperature field is investigated analytically. The governing equations are derived via the Principal of Stationary Potential Energy, resulting in self-consistent constitutive equations of the composite structure, as well as the equations of motion and the associated matching and boundary conditions for the composite structure. A loading parameter is identified, and closed form analytical solutions to the non-linear problem are obtained, yielding exact results within the context of the formulation. A stability criterion is established based on the second variation of the total potential energy of the system in order to identify regions of stable and unstable equilibrium configurations, and a critical temperature and a critical membrane force are determined. Simulation results based on the analytical solutions are generated and a critical and characteristic behavior is assessed for both clamped-fixed supports and hinged-fixed supports conditions. The phenomenon of “sling-shot buckling” is observed. Results of parameter studies are also presented, which demonstrate the influence that material and geometric parameters of the system have on critical behavior. In particular, thermal expansion coefficient ratio, modulus ratio and thickness ratio all play a non-trivial role in the temperature carrying capacity of the structure for relatively large patches. Because the loading parameters and geometric parameters appear explicitly in the analytical solution and simulations, the model and results will be useful towards the design of micro-electromechanical systems, smart structures and related configurations.
Spectrum of Mechanisms of Resistance to Crizotinib and Lorlatinib in ROS1 Fusion–Positive Lung Cancer

Purpose: Current standard initial therapy for advanced, ROS proto-oncogene 1, receptor tyrosine kinase fusion (ROS1)-positive (ROS1+) non–small cell lung cancer (NSCLC) is crizotinib or entrectinib. Lorlatinib, a next-generation anaplastic lymphoma kinase/ROS1 inhibitor, recently demonstrated efficacy in ROS1+ NSCLC, including in crizotinib-pretreated patients. However, mechanisms of lorlatinib resistance in ROS1+ disease remain poorly understood. Here, we assessed mechanisms of resistance to crizotinib and lorlatinib. Experimental Design: Biopsies from patients with ROS1+ NSCLC progressing on crizotinib or lorlatinib were profiled by genetic sequencing. Results: From 55 patients, 47 post-crizotinib and 32 post-lorlatinib biopsies were assessed. Among 42 post-crizotinib and 28 post-lorlatinib biopsies analyzed at distinct timepoints, ROS1 mutations were identified in 38% and 46%, respectively. ROS1 G2032R was the most commonly occurring mutation in approximately one third of cases. Additional ROS1 mutations included D2033N (2.4%) and S1986F (2.4%) post-crizotinib and L2086F (3.6%), G2032R/L2086F (3.6%), G2032R/S1986F/L2086F (3.6%), and S1986F/L2000V (3.6%) post-lorlatinib. Structural modeling predicted ROS1L2086F causes steric interference to lorlatinib, crizotinib, and entrectinib, while it may accommodate cabozantinib. In Ba/F3 models, ROS1L2086F, ROS1G2032R/L2086F, and ROS1S1986F/G2032R/L2086F were refractory to lorlatinib but sensitive to cabozantinib. A patient with disease progression on crizotinib and lorlatinib and ROS1 L2086F received cabozantinib for nearly 11 months with disease control. Among lorlatinib-resistant biopsies, we also identified MET amplification (4%), KRAS G12C (4%), KRAS amplification (4%), NRAS mutation (4%), and MAP2K1 mutation (4%). Conclusions: ROS1 mutations mediate resistance to crizotinib and lorlatinib in more than one third of cases, underscoring the importance of developing next-generation ROS1 inhibitors with potency against these mutations, including G2032R and L2086F. Continued efforts are needed to elucidate ROS1-independent resistance mechanisms.
Mechanism of Gene-Environment Interactions Driving Glial Activation in Parkinson's Diseases.

Parkinson’s disease (PD) is the most prevalent motor disorder and is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) region of the brain. Though the pathology of PD is well established, the cause of this neuronal loss is not well understood. Approximately 90% of PD cases are sporadic, and the environment plays a significant role in disease pathogenesis. The etiology of PD is highly complex, with neuroinflammation being one of the most critical factors implicated in PD. However, the signaling mechanisms underlying neuroinflammation and its interaction with environmental factors are unclear. Astroglia and microglia are the two principal cells that play an essential role in maintaining neuronal health in many ways, including through immunological means. Exposure to environmental stressors from various sources affects these glial cells leading to chronic and sustained inflammation. Recent epidemiological studies have identified an interaction among environmental factors and glial genes in Parkinson’s disease. Mechanistic studies have shown that exposure to pesticides like rotenone and paraquat, neurotoxic metals like manganese and lead, and even diesel exhaust fumes induce glial activation by regulating various key inflammatory pathways, including the inflammasomes, NOX pathways, and others. This review aims to discuss the recent advances in understanding the mechanism of glial induction in response to environmental stressors and discuss the potential role of gene-environment interaction in driving glial activation.
Increased excitation-inhibition balance and loss of GABAergic synapses in the serine racemase knockout model of NMDA receptor hypofunction

There is substantial evidence that both N-methyl-D-aspartate receptor (NMDAR) hypofunction and dysfunction of GABAergic neurotransmission contribute to schizophrenia, though the relationship between these pathophysiological processes remains largely unknown. Although models using cell-type-specific genetic deletion of NMDARs have been informative, they display overly pronounced phenotypes extending beyond those of schizophrenia. Here, we used the serine racemase knockout (SRKO) mice, a model of reduced NMDAR activity rather than complete receptor elimination, to examine the link between NMDAR hypofunction and decreased GABAergic inhibition. The SRKO mice, in which there is a >90% reduction in the NMDAR coagonist d-serine, exhibit many of the neurochemical and behavioral abnormalities observed in schizophrenia. We found a significant reduction in inhibitory synapses onto CA1 pyramidal neurons in the SRKO mice. This reduction increases the excitation/inhibition balance resulting in enhanced synaptically driven neuronal excitability without changes in intrinsic excitability. Consistently, significant reductions in inhibitory synapse density in CA1 were observed by immunohistochemistry. We further show, using a single-neuron genetic deletion approach, that the loss of GABAergic synapses onto pyramidal neurons observed in the SRKO mice is driven in a cell-autonomous manner following the deletion of SR in individual CA1 pyramidal cells. These results support a model whereby NMDAR hypofunction in pyramidal cells disrupts GABAergic synapses leading to disrupted feedback inhibition and impaired neuronal synchrony.NEW & NOTEWORTHY Recently, disruption of excitation/inhibition (E/I) balance has become an area of considerable interest for psychiatric research. Here, we report a reduction in inhibition in the serine racemase knockout mouse model of schizophrenia that increases E/I balance and enhances synaptically driven neuronal excitability. This reduced inhibition was driven cell-autonomously in pyramidal cells lacking serine racemase, suggesting a novel mechanism for how chronic NMDA receptor hypofunction can disrupt information processing in schizophrenia.
Abstract 1205: Clinical and genomic features of advanced urothelial carcinoma with 9p21 deletion

Chromosome 9p21 deletion occurs in 25% of urothelial carcinomas (UC). 9p21 includes the MTAP gene that encodes methylthioadenosine phosphorylase, a critical enzyme in the alternate pathway of adenine synthesis. MTAP-deleted UC tumors are very sensitive to pemetrexed-induced blockage of purine synthesis. MTAP is commonly co-deleted with CDKN2A, an immediately adjacent gene associated with sensitivity to CDK4/6 inhibitors. We describe clinical and molecular features of a 9p21-deleted subgroup of UC to better inform targeted therapy approaches. We retrospectively analyzed 46 patients (pts) with UC treated at our institution. All tumor specimens were submitted to next-generation sequencing (NGS). Patient demographics, clinic-pathological and genomic features, and clinical outcomes were summarized with descriptive statistics. MTAP/CDKN2A co-deletion was defined as a surrogate for 9p21 deletion. Fifteen (32%) pts with 9p21-deleted UC were identified. The median age was 68 years-old (range 54-79), 80% of pts were former or active smokers. Fifty-three percent (8 of 15) of these tumors showed squamous differentiation. Other histology variants were papillary differentiation (6), micropapillary (1), and sarcomatoid (1). Sites of tumor specimens submitted to NGS included bladder (11), lymph node (1), abdominal wall (1), renal pelvis mass (1), and bone (1). All pts had metastatic disease involving bone (9), lung (8), lymph nodes (7), liver (3), abdominal wall (2), penis (2), peritoneum (1), and pararenal mass (1). Most pts (8) underwent curative surgery and later developed metastases; seven pts presented with de novo metastases. Among 9 pts with progression-free survival (PFS) data available, median PFS was 2 months (range 1-17). Median overall survival was 6 months (range 1-35). Median PD-L1 expression on tumor cells was 1% (range 1-20); 4 tumors were PD-L1 (-). All evaluable patients (14) had stable microsatellite tumors. The most common genomic alterations co-occurring with 9p21 deletion affected CDKN2B (100%), TERT (87%), KDM6A (60%), TP53 (40%), and FGFR3 (20%). The best response associated with immune checkpoint inhibitors among 7 patients with 9p21 deletion was a disease control rate of 28.5%. Our cohort with UC and 9p21 deletion had predominantly squamous cell differentiation. Thus, MTAP is always co-deleted with CDKN2A and is a potential biomarker for pemetrexed-based combinations. Molecular characterization of 9p21 deleted UC may in the future inform targeted therapeutic approaches. Citation Format: Andre L. De Souza, Praveen Srinivasan, Luke B. Soliman, Dragan J. Golijanin, Ali Amin, Howard Safran, Anthony E. Mega, Wafik S. El-Deiry, Benedito A. Carneiro. Clinical and genomic features of advanced urothelial carcinoma with 9p21 deletion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1205.
An exit without strategy: learning from the Soviet Bloc’s retreat from the Horn of Africa and Central America

This article investigates the closing years of East–West Cold War rivalry by focussing on the inconsistent implementation of Mikhail Gorbachev’s policies of de-escalating decade-long regional confl...
Haldane’s cost of selection imposes a mild constraint on adaptation, with a high proportion of deaths in A. thaliana being selective

Haldane9s Dilemma refers to the concern that the need for many "selective deaths" to complete a substitution creates a speed limit to adaptation. However, discussion of this concern has been marked by confusion over which features of substitutions produce limits to the speed of adaptation, what those limits are, and the consequences of violating speed limits. The term 9substitution load9 has been particularly unhelpful in this regard. Here we distinguish different lines of reasoning that lead to speed limits, including one line of reasoning which has not yet been fully addressed. We then apply these lines of reasoning to a dataset measuring survival and fecundity of 517 different genotypes of Arabidopsis thaliana grown in eight different environmental conditions. We estimate highly permissive limits to the speed of adaptation in all environmental conditions. We also estimate that much higher proportions of deaths contribute to adaptation than were anticipated during historical discussions of speed limits.
Overview of Anxiety Management Training

AMT was initially designed as a nonspecific behavior therapy that would be relevant for treating any condition where anxiety was a core issue. Most important, AMT was aimed at free-floating anxieties in which clients are unable specifically to identify the stimulus conditions that trigger their anxiety reactions. In order to accomplish this, we focused on the fact that although generalized anxiety disorder clients cannot concretely label their Stressors, they certainly possess first hand acquaintance with their experience of anxiety itself. Such clients, with a little help, can describe in great detail how they experience their anxiety attacks, in terms of autonomic, somatic, or cognitive syptoms. They are aware of their feelings of anxiety whether these are autonomic/affective, such as “pounding in my chest as my heart races a mile a minute and I can’t catch my breath,” or somatic/behavioral, such as general restlessness or “the shakes,” or cognitive, such as worries, negative self-dialogue, or “just knowing something bad is going to happen to me.”
Institutionalizing curriculum change: a SUCCEED case history

A freshman interdisciplinary laboratory class was recently adopted as a permanent course in the engineering curriculum at the University of Florida. This class is one of the projects developed under the Southeastern University and College Coalition for Engineering Education (SUCCEED). This class replaced the standard one-hour-per-week introductory freshman lecture. The class rotates 14 groups of 20 students each through weekly three-hour laboratory sessions in 11 engineering disciplines. Each discipline's lab exposes the students to hands-on experiments representing concepts related to the discipline's specialty. This paper discusses the efforts required to take an experimental course and make it a permanent one. Included are statistics which indicate that women experience significantly improved retention through the new course and minority retention is raised to the level of the general population.
Feshbach resonances in ultracold ^{6,7}Li + ^{23}Na atomic mixtures

We report a theoretical study of Feshbach resonances in $^{6}\mathrm{Li}+^{23}\mathrm{Na}$ and $^{7}\mathrm{Li}+^{23}\mathrm{Na}$ mixtures at ultracold temperatures using accurate interaction potentials in a full quantum coupled-channel calculation. Feshbach resonances for $l=0$ in the initial collisional open channel $^{6}\mathrm{Li}(f=1∕2,{m}_{f}=1∕2)+^{23}\mathrm{Na}(f=1,{m}_{f}=1)$ are found to agree with previous measurements, leading to precise values of the singlet and triplet scattering lengths for the $^{6,7}\mathrm{Li}+^{23}\mathrm{Na}$ pairs. We also predict additional Feshbach resonances within experimentally attainable magnetic fields for other collision channels.
Strategic Responses to Domestic and Foreign Institutional Pressures

This study investigates how firms respond to domestic institutional constraints and to host country institutional frameworks. A substantial number of firms are active in international business, and yet they remain domestic by staying in their home countries—exporters and outsource service providers come to mind. How these firms react to changes in both domestic and foreign rules of the game, as well as the interactions between these two sets of rules, remains underexplored. Taking advantage of a product recall crisis, this exploratory study probes into how firms in the Chinese toy industry strategically react to the institutional pressures from both home and abroad. Implications for a strategic response framework are discussed.
Anne Burdick, Johanna Drucker, Peter Lunenfeld, Todd Presner, & Jeffrey Schnapp, Digital_Humanities

The New York Times laid it all out in late October 2013: The humanities, in apparently precipitous decline, are worrying college and university administrations. Never mind that the drop in the percentage of degrees awarded in the humanities is measured with an abnormal spike as its starting point; never mind that the drop is accompanied by a dramatic increase in the number of degree options for students across the curriculum; never mind the number of majors that are missing from the category of the humanities (art history is grouped among the arts, while ethnic studies and other interdisciplinary fields are credited wholly to the social sciences); never mind that, of all fields, computer science seems to be experiencing a far greater drop in degrees awarded than is the humanities. Once the Old Grey Lady has decided your relevance is waning, it would seem, there’s little to do but make a cup of tea and straighten the doilies and wait for the inevitable end. Or, as Twitter would say: GUYS, the humanities are anxious about their future, and The Times is ON IT.
Infection of brain microglial cells by human immunodeficiency virus type 1 is CD4 dependent.

In the central nervous system of AIDS patients, human immunodeficiency virus (HIV) infects primarily microglia, a cell type of bone marrow origin. Moreover, microglial cells isolated from adult human brain support the replication of macrophage-adapted strains of HIV type 1 (HIV-1) (B.A. Watkins, H.H. Dorn, W.B. Kelly, R.C. Armstrong, B. Potts, F. Michaels, C.V. Kufta, and M. Dubois-Dalcq, Science 249:549-553, 1990). To determine whether the CD4 receptor, which is expressed in brain, mediates the entry of HIV-1 in microglial cells, we analyzed CD4 transcript expression in cultured microglia using highly sensitive polymerase chain reaction detection of cDNAs synthesized from RNA. With this method, CD4 transcripts could be detected in cultured microglia--as well as in various human brain regions and cultured macrophages used as positive controls--along with transcripts for the LDL and Fc receptors which are characteristic of cells of the macrophage lineage. We then attempted to block viral entry into microglial cells using anti-CD4 antibodies or soluble CD4 (sCD4), which recognize binding sites on CD4 and HIV-1 glycoprotein gp120, respectively. Cultures were pretreated with blocking antibodies (Leu-3a, OKT4A) or virus was preincubated with sCD4 prior to infection with HIV-1 strain AD87(M) or BaL. With either viral strain, these treatments resulted in the prevention of infection or significant and dose-dependent reduction in the number of infected cells and in the levels of reverse transcriptase or p24 antigen released in the medium. Thus, brain-derived microglial cells, which are the primary target of HIV-1 infection in the brain, express the CD4 receptor and this receptor is effectively used for viral entry in vitro. Images
Determining the Energy Distribution of Pulse-Radiation-Induced Charge in MOS Structures from Rapid Annealing Measurements

Activation energy distributions for the positive space charge induced in MOS structures by pulsed ionizing radiation have been calculated from shortterm, isothermal annealing data. These distributions are compared for conventional thermal oxides and oxides implanted with aluminum or sodium ions.
Attachment of astroglial cells to microfabricated pillar arrays of different geometries.

We studied the attachment of astroglial cells on smooth silicon and arrays of silicon pillars and wells with various widths and separations. Standard semiconductor industry photolithographic techniques were used to fabricate pillar arrays and wells in single-crystal silicon. The resulting pillars varied in width from 0. 5 to 2.0 micrometer, had interpillar gaps of 1.0-5.0 micrometer, and were 1.0 micrometer in height. Arrays also contained 1.0-micromter-deep wells that were 0.5 micrometer in diameter and separated by 0.5-2.0 micrometer. Fluorescence, reflectance, and confocal light microscopies as well as scanning electron microscopy were used to quantify cell attachment, describe cell morphologies, and study the distribution of cytoskeletal proteins actin and vinculin on surfaces with pillars, wells, and smooth silicon. Seventy percent of LRM55 astroglial cells displayed a preference for pillars over smooth silicon, whereas only 40% preferred the wells to the smooth surfaces. Analysis of variance statistics performed on the data sets yielded values of p > approximately.5 for the comparison between pillar data sets and < approximately.0003 in the comparison between pillar and well data sets. Actin and vinculin distributions were highly polarized in cells found on pillar arrays. Scanning electron microscopy clearly demonstrated that cells made contact with the tops of the pillars and did not reach down into the spaces between pillars even when the interpillar gap was 5.0 microm. These experiments support the use of surface topography to direct the attachment, growth, and morphology of cells. These surfaces can be used to study fundamental cell properties such as cell attachment, proliferation, and gene expression. Such topography might also be used to modify implantable medical devices such as neural implants and lead to future developments in tissue engineering.