cssi/SciSciGPT-SciSciNet huggingface dataset:
Maximum Likelihood Fitting of Tidal Streams With Application to the Sagittarius Dwarf Tidal Tails

We present a maximum likelihood method for determining the spatial properties of tidal debris and of the Galactic spheroid. With this method we characterize Sagittarius debris using stars with the colors of blue F turnoff stars in SDSS stripe 82. The debris is located at (α, δ, R) = (31.37 ◦ ± 0.26 ◦ ,0.0,29.22± 0.20 kpc), with a (spatial) direction given by the unit vector , in Galactocentric Cartesian coordinates, and with FWHM = 6.74± 0.06 kpc. This 2.5 ◦ -wide stripe contains 0.892% as many F turnoff stars as the current Sagittarius dwarf galaxy. Over small spatial extent, the debris is modeled as a cylinder with a density that falls off as a Gaussian with distance from the axis, while the smooth component of the spheroid is modeled with a Hernquist profile. We assume that the absolute magnitude of F turnoff stars is distributed as a Gaussian, which is an improvement over previous methods which fixed the absolute magnitude at ¯ Mg0 = 4.2. The effectiveness and correctness of the algorithm is demonstrated on a simulated set of F turnoff stars created to mimic SDSS stripe 82 data, which shows that we have a much greater accuracy than previous studies. Our algorithm can be applied to divide the stellar data into two catalogs: one which fits the stream density profile and one with the characteristics of the spheroid. This allows us to effectively separate tidal debris from the spheroid population, both facilitating the study of the tidal stream dynamics and providing a test of whether a smooth spheroidal population exists.
Exercise testing confirms the role of impaired central circulatory function and elevated right ventricular stroke work index in patients undergoing lung transplantation

Introduction: Right ventricular (RV) workload assessed by RV Stroke Work Index (RVSWI) is a negative predictor of outcome in acute respiratory failure. Cardiopulmonary exercise testing (CPET) may have a role in detecting central circulatory impairment (CCI) in patients before lung transplantation (LTx) at risk for impaired RV function. Aims and Objectives: To demonstrate correlation of ventilatory inefficiency (VI) on CPET for detection of CCI in patients before LTx with RVSWI. Methods: 172 patients undergoing evaluation for LTx who had CPET and right heart catheterization were included. RVSWI (stroke volume index*(mean pulmonary arterial pressure - mean right atrial pressure)*0.0136) was calculated from invasive hemodynamic data. Pearson9s correlation, significance 0.05, was assessed between RVSWI and CPET parameters. Results: RVSWI correlates highly with VI and inversely with hemodynamics on CPET, but not with peak capacity or workload. Conclusions: High right ventricular workload correlates with ventilatory inefficiency and impaired hemodynamics on CPET. Thus, exercise parameters may predict right ventricular work and LTx outcomes.
Abnormal frontostriatal activity in recently abstinent cocaine users during implicit moral processing

Investigations into the neurobiology of moral cognition are often done by examining clinical populations characterized by diminished moral emotions and a proclivity toward immoral behavior. Psychopathy is the most common disorder studied for this purpose. Although cocaine abuse is highly co-morbid with psychopathy and cocaine-dependent individuals exhibit many of the same abnormalities in socio-affective processing as psychopaths, this population has received relatively little attention in moral psychology. To address this issue, the authors used functional magnetic resonance imaging (fMRI) to record hemodynamic activity in 306 incarcerated male adults, stratified into regular cocaine users (n = 87) and a matched sample of non-cocaine users (n = 87), while viewing pictures that did or did not depict immoral actions and determining whether each depicted scenario occurred indoors or outdoors. Consistent with expectations, cocaine users showed abnormal neural activity in several frontostriatial regions during implicit moral picture processing compared to their non-cocaine using peers. This included reduced moral/non-moral picture discrimination in the vACC, vmPFC, lOFC, and left vSTR. Additionally, psychopathy was negatively correlated with activity in an overlapping region of the ACC and right lateralized vSTR. These results suggest that regular cocaine abuse may be associated with affective deficits which can impact relatively high-level processes like moral cognition.
Mechanisms of coronary microvascular adaptation to obesity

The metabolic syndrome (MetS) is associated with clustering of cardiovascular risk factors in individuals that may greatly increase their risk of developing coronary artery disease. Obesity and related metabolic dysfunction are the driving forces in the prevalence of MetS. It is believed that obesity has detrimental effects on cardiovascular function, but its overall impact on the vasomotor regulation of small coronary arteries is still debated. Emerging evidence indicates that in obesity coronary arteries adapt to hemodynamic changes via maintaining and/or upregulating cellular mechanism(s) intrinsic to the vascular wall. Among other factors, endothelial production of cyclooxygenase-2-derived prostacyclin and reactive oxygen species, as well as increased nitric oxide sensitivity and potassium channel activation in smooth muscle cells, have been implicated in maintaining coronary vasodilator function. This review aims to examine studies that have been primarily focused on alterations in coronary vasodilator function in obesity. A better understanding of cellular mechanisms that may contribute to coronary microvascular adaptation may provide insight into the sequence of pathological events in obesity and may allow the harnessing of these effects for therapeutic purposes.
Temporal reasoning with constraints on fluents and events

We propose a propositional language for temporal reasoning that is computationally effective yet expressive enough to describe information about fluents, events and temporal constraints. Although the complete inference algorithm is exponential, we characterize a tractable core with limited expressibility and inferential power. Our results render a variety of constraint propagation techniques applicable for reasoning with constraints on fluents.
Efficacy of N-acetylcysteine in phenotypic suppression of mouse models of Niemann–Pick disease, type C1

Niemann-Pick disease, type C1 (NPC1), which arises from a mutation in the NPC1 gene, is characterized by abnormal cellular storage and transport of cholesterol and other lipids that leads to hepatic disease and progressive neurological impairment. Oxidative stress has been hypothesized to contribute to the NPC1 disease pathological cascade. To determine whether treatments reducing oxidative stress could alleviate NPC1 disease phenotypes, the in vivo effects of the antioxidant N-acetylcysteine (NAC) on two mouse models for NPC1 disease were studied. NAC was able to partially suppress phenotypes in both antisense-induced (NPC1ASO) and germline (Npc1-/-) knockout genetic mouse models, confirming the presence of an oxidative stress-related mechanism in progression of NPC1 phenotypes and suggesting NAC as a potential molecule for treatment. Gene expression analyses of NAC-treated NPC1ASO mice suggested NAC affects pathways distinct from those initially altered by Npc1 knockdown, data consistent with NAC achieving partial disease phenotype suppression. In a therapeutic trial of short-term NAC administration to NPC1 patients, no significant effects on oxidative stress in these patients were identified other than moderate improvement of the fraction of reduced CoQ10, suggesting limited efficacy of NAC monotherapy. However, the mouse model data suggest that the distinct antioxidant effects of NAC could provide potential treatment of NPC1 disease, possibly in concert with other therapeutic molecules at earlier stages of disease progression. These data also validated the NPC1ASO mouse as an efficient model for candidate NPC1 drug screening, and demonstrated similarities in hepatic phenotypes and genome-wide transcript expression patterns between the NPC1ASO and Npc1-/- models.
Parents concordant for major depressive disorder and the effect of psychopathology in offspring.

Background. Concordance for major depressive disorder (MDD) between parents could happen for dierent reasons. Regardless of the origin and the frequency of the concordance, the eect on ospring of having two parents aected with MDD may be serious. The sex of the aected parent and ospring may also be a important risk factor for MDD in ospring. Methods. We examined the increased risk of psychopathology among ospring of the four parental mating groups: both parents aected with MDD (N fl 53); only mother aected (N fl 31); only father aected (N fl 65); and, neither parents aected (N fl 33). Parents and ospring were assessed by direct interview, conducted blind and independently of each other. Results. Among the four parental mating groups, ospring of both parents aected had the highest risk of MDD, anxiety disorder and alcohol dependence, and the earliest age of onset for MDD. There were two exceptions: the highest risk of conduct disorder and of drug dependence was in the groups where only the father was aected and where only the mother was aected, respectively. Mother’s MDD was a stronger predictor of MDD in male compared to female ospring. Father’s MDD was a stronger predictor of MDD in female compared to male ospring. Conclusion. Having two parents with MDD increases the risk of psychiatric disorders in ospring. A clear dose‐response relationship between the number of aected parents and psychiatric disorders in ospring was observed. The sex of the aected parent and of the ospring is important in determining the risk to ospring. For an examination of the risk to psychopathology in ospring, diagnosis status of both parents should be considered.
PKCε Contributes to Chronic Ethanol-Induced Steatosis in Mice but not Inflammation and Necrosis

Alcoholic liver disease (ALD) is a serious concern for the world’s population, causing millions of deaths per year (Grant et al., 1988). Whereas the pathological steps of ALD are well understood, our knowledge of the mechanisms involved in causing the disease is lacking; as a result, there is no FDA-approved therapy to treat or reverse ALD. Steatosis is a critical stage in the pathology of alcoholic liver disease. Although steatosis was once thought to be an benign pathology of ALD, more recent evidence has indicated that blunting or blocking steatosis could help prevent the progression of ALD (Teli et al., 1995; Day and James 1998). Therefore, pharmacologically targeting the cause(s) of ethanol-induced steatosis is potentially a promising therapy for ALD. Recent evidence has suggested that protein kinases c-e (PKCe), can contribute to steatosis in experimental non-alcoholic fatty liver disease (NAFLD) (Samuel et al., 2004). Work from this group showed that PKCe also plays a causal role in acute ethanol-induced steatosis in mice (Kaiser et al., 2009). Results from that study support the working hypothesis that the inhibition of β-oxidation of fatty acids caused by ethanol metabolism increases the fatty acid supply for diacylglycerol (DAG) synthesis. This increase in DAG allosterically activates PKCe, which then contributes to the increase in hepatic triglycerides caused by ethanol by inducing insulin resistance (Kaiser et al., 2009). Thus, PKCe activation may be a shared mechanism of hepatic steatosis in ALD and NAFLD. Whereas acute bolus ethanol causes a robust steatotic response in the liver (Kaiser et al., 2009), there is little or no inflammation or necrosis caused by this dose regimen of ethanol in rodents. PKCe has been shown to contribute to inflammation in response to various insults (e.g. LPS), which suggests that PKCe may also contribute to more advanced stages of ALD (e.g. steatohepatitis) (Aksoy et al., 2004). Furthermore, as mentioned above, blunting steatosis caused by alcohol may in and of itself prevent later phases of ALD. This potential role of PKCe in these later stages of experimental ALD has not yet been directly studied. Therefore, the purpose of this study was to determine the role of PKCe in chronic ethanol-induced liver damage.
Endoscopic Management of Anorectal Stenosis and Strictures

Abstract Anorectal strictures and stenoses, though most often asymptomatic, can lead to disastrous sequelae in certain patient populations. Recent advances in endoscopic management of this potentially life-threatening complication successfully reduce morbidity and mortality in a cost-effective manner. Most notably, Nd:Yag lasers and metallic stents can be successfully used to relieve the symptoms of large bowel obstruction, allowing the intestines to decompress and the patient to rehydrate and get nutrition.
Infectious uveitis in Virginia.

PURPOSE: To report the causes, clinical features, and outcomes of infectious uveitis in patients managed in a mid-Atlantic tertiary care center. METHODS: Retrospective, observational study of infectious uveitis patients seen at the University of Virginia from 1984 to 2014. RESULTS: Seventy-seven of 491 patients (15.7%) were diagnosed with infectious uveitis (mean age 58 years, 71.4% female, 76.6% Caucasian). The mean follow-up was 5 years. Anterior uveitis was the most common anatomic classification (39 patients, 50.6%) followed by panuveitis (20 patients, 26.0%) and posterior uveitis (18 patients, 23.4%). The most common infectious etiology was herpetic anterior uveitis (37 patients, 48.1%) followed by toxoplasma uveitis (14 patients, 18.2%). The most prevalent viral pathogen was varicella-zoster virus (21 patients, 27.3%) followed by herpes simplex virus (20 patients, 26.0%). Acute retinal necrosis (ARN) was diagnosed in 14 patients (18.2%). Aqueous humor yielded an etiologic diagnosis in seven (50%) of ARN patients, four of whom tested positive for cytomegalovirus and three for varicella-zoster virus. On presentation, 43 patients (55.8%) had a visual acuity (VA) better than 20/40 and 17 (22.1%) had a VA worse than 20/200. VA at the final follow-up was better than 20/40 in 39 patients (50.6%) and worse than 20/200 in 22 patients (28.6%). In all, 16 (20.8%) and 10 (13.0%) patients required cataract and vitrectomy surgery, respectively. A total of 14 patients (18.2%) were on glaucoma topical treatment and four (5.2%) required glaucoma surgery. CONCLUSION: The most common type of infectious uveitis seen over the study period was herpetic anterior uveitis secondary to varicella-zoster virus or herpes simplex virus, found to be most prevalent in patients over 60 years of age. This finding is comparable to other American epidemiologic studies. Ocular toxoplasmosis and ARN were also common causes of infectious uveitis. In all, 50.6% of patients had a VA better than 20/40 at the final follow-up visit, indicating the importance of prompt referral and appropriate treatment.
Web Cartography and the Dissemination of Cartographic Information about Coastal Inundation and Sea Level Rise

This chapter examines the Web cartography used in the United States to help citizens and local officials plan for storm surge and sea level rise — coastal hazards conveniently describedby hypothetical supplementary shorelines. Storm surge is addressed principally by federal flood-insurance maps, now available over the Internet but severely encumbered by a 1970s strategy requiring a huge number of large-scale paper map sheets. In addition, some states and localities address storm surge with storm evacuation maps, typically at a smaller scale that makes Web distribution more straightforward. Dynamic graphics, though not common, provide dramatic illustrations of plausible local impacts of coastal flooding. By contrast, coverage of sea level rise is not only biased toward scientists and policy makers interested in climate change or wetlands preservation but also marked by a heavy reliance on related text and graphics to communicate uncertainty and impact. Important maps embedded in PDF files are not easily located by search engines in image-mode, and a set of spatially detailed but politically sensitive maps made available online to confidential reviewers has not been released to the public. Anecdotal evidence suggests that the United States is more proactive than Britain, Bangladesh, and other coastal nations in using Web cartography to promote geographic knowledge of their coastal hazards.
CWDM Fiber-wireless Employing a Supercontinuum Source

To meet the current and future needs of the increasing bandwidth demand in wireless communications, base-to-base communication requires fast, reliable, secure and elastic bandwidth. One communication technology that meets these challenges is the fiber with wavelength division multiplexing. This technology multiplexes in a single fiber several wavelengths, each sourced by individual lasers thus adding to cost, complexity and fault management. An alternative, is a single laser source at higher power which when coupled onto a highly dispersive medium generates a wide spectral band known as supercontinuum. When this is appropriately sliced, multiple wavelength/channels are generated. In this paper, we develop a supercontinuum model, the spectrum of which is sliced The using FBGs to generate optical channels as recommended by ITU-T standards. We simulate our model at OC-48, selected for being popular in low cost applications. We also determine the longest link without amplification at performance objective 10-12 bit error rate.
Gaussian Process Models for Computer Experiments With Qualitative and Quantitative Factors

Modeling experiments with qualitative and quantitative factors is an important issue in computer modeling. We propose a framework for building Gaussian process models that incorporate both types of factors. The key to the development of these new models is an approach for constructing correlation functions with qualitative and quantitative factors. An iterative estimation procedure is developed for the proposed models. Modern optimization techniques are used in the estimation to ensure the validity of the constructed correlation functions. The proposed method is illustrated with an example involving a known function and a real example for modeling the thermal distribution of a data center.
Distribution of sex steroid hormone receptors in the brain of an African cichlid fish, Astatotilapia burtoni

Sex steroid hormones released from the gonads play an important role in mediating social behavior across all vertebrates. Many effects of these gonadal hormones are mediated by nuclear steroid hormone receptors, which are crucial for integration in the brain of external (e.g., social) signals with internal physiological cues to produce an appropriate behavioral output. The African cichlid fish Astatotilapia burtoni presents an attractive model system for the study of how internal cues and external social signals are integrated in the brain as males display robust plasticity in the form of two distinct, yet reversible, behavioral and physiological phenotypes depending on the social environment. In order to better understand where sex steroid hormones act to regulate social behavior in this species, we have determined the distribution of the androgen receptor, estrogen receptor alpha, estrogen receptor beta, and progesterone receptor mRNA and protein throughout the telencephalon and diencephalon and some mesencephalic structures of A. burtoni. All steroid hormone receptors were found in key brain regions known to modulate social behavior in other vertebrates including the proposed teleost homologs of the mammalian amygdalar complex, hippocampus, striatum, preoptic area, anterior hypothalamus, ventromedial hypothalamus, and ventral tegmental area. Overall, there is high concordance of mRNA and protein labeling. Our results significantly extend our understanding of sex steroid pathways in the cichlid brain and support the important role of nuclear sex steroid hormone receptors in modulating social behaviors in teleosts and across vertebrates.
Does Social Trust Increase Individual Happiness in Japan

Economists are mainly interested in trust as being growth enhancing, but whether trust is well-being enhancing is underexplored. This paper examines if trust is intrinsically valuable by using individual happiness data from Japan. I attempt to mitigate the problem of non-random selection of residents by restricting the sample to non-movers. I also address reverse causality by instrumenting trust with residential stability, as trust should be higher for a more stable community. I find that trust has positive and significant effects on individual happiness. The instrumental variables approach suggests that social trust has a causal effect on individual happiness.
Imaging VLSI Cross Sections by Atomic Force Microscopy

Imaging is an integral part of VLSI technology development and quality control in device manufacturing. We report a novel application of Atomic Force Microscopy to image VLSI cross sections of metallographically polished samples. The major advantage of this technique over conventional imaging techniques, such as Scanning or Transmission Electron Microscopy, is the higher resolution achievable in combination with higher throughput and an easy access to quantitative data, such as line widths or re-entrant angles. We observe a very good correlation of AFM VLSI cross section images, acquired in air, with those acquired by SEM and TEM.
Editorial: Hyposkillia & Critical Thinking: What's the Connection?

2; see forward 1 a physician-educator, while on rounds with students, interns, and residents. In t he process of discussing patients, Groopman was disturbed by the lack of depth of his student's questions a nd thinking. This glaring deficiency lead him to question "Who teaches doctors to think?" Pondering this question lead to discussions with many colleagues, and eventually to a New York Times best selling book. In reflection of his own time as a medical student, Groopman, realized that only "rarely did attending physicians actually explain the mental steps that lead him to his decisions." 1 One popular approach to help physicians diagnose problems was clinical decision t rees — preset algorithms or clinical guidelines that lead f rom maj or symptoms through a series of branching que stions and eventually to a diagnosi s and treatment plan. T hese, G roopman argued, ar e fine for "r un of t he mill diagnosis and treatment," but inadequate when symptoms or tests are vague, conflicting, or inaccurate. Algorithms have their place, he st ated, but they also "di scourage physicians from thinking independently and creatively. Instead of ex panding a doctor's thinking, they can constrain it." 1 Similarly, Groopman cautions against rigid r eliance on the current rage-evidence-based medicine (basing all treatment decisions strictly on statistically proven data). This rigidity suggests rejection of treatment that is not backed by statistical data. Such an approach "risks having the doctor choose care passively, solely by the numbers. Statistics cannot substitute for the human being before you; statistics embody averages, not individuals." 1 The 10 chapters of How D octors Think are individual case studies of various difficult cases shared with Groopman by various 1
Immune surveillance is thwarted by tumor-cell intrinsic beta-catenin signaling

Growing evidence has emerged that subgroups of cancer patients have a spontaneous T cell-centered immune response reflected by infiltration of antigen-specific CD8+ T cells into the tumor microenvironment. However, another major subgroup of patients completely lacks T cell infiltration. Importantly, the presence of tumor-infiltrating CD8+ T cells has been correlated with clinical response to anti-PD-1 mAb and other immunotherapies. Recent work from our laboratory has revealed that activation of the Wnt/β-catenin pathway within tumor cells can mediate exclusion of T cells from the tumor microenvironment. Using an autochthonous inducible mouse model for melanoma (BrafV600E/PTEN-/-; BP) with or without stabilized β-catenin (BrafV600E/PTEN-/-/CAT-STA; BPC) we showed that T cell exclusion from the tumor microenvironment was due to failed recruitment of Batf3-lineage dendritic cells, resulting in a defective early T cell priming and absence of systemic immunity. However, whether tumor-intrinsic β-catenin signaling might mediate tumor resistance after an anti-tumor T cell response was established is not known. To test this notion, we used a spontaneously rejected cell line (MC57.SIY) to induce immunologic memory. These tumors were implanted into naive BP and BPC mice that had been crossed to a Rosa26-LSL-SIY inducible antigen mouse and following complete regression of the primary (MC57.SIY) tumor, the genetically-induced melanomas were initiated. Although the primary SIY-specific CD8+ T cell response and the induced memory response were comparable between both tumor models, tumor protection was observed against BP-SIY tumors but not BPC-SIY tumors. Increased tumor control in BP-SIY mice was accompanied by strong T cell infiltration and a boosted memory response. These results indicate that tumor-intrinsic β-catenin signaling can mediate exclusion of effector T cell migration. To test this notion directly, we adoptively transferred in vitro-activated SIY-reactive T cell receptor transgenic T cells (2C T cells) into BP-SIY and BPC-SIY tumor-bearing hosts. In fact, primed 2C cells were only found in BP-SIY tumors but not BPC-SIY tumors. These results were confirmed using in vivo 2-photon microscopy of the tumor microenvironment. Taken together, these data provide strong evidence that up-regulation of tumor-intrinsic β-catenin is a strong mechanism of immune evasion even in the presence of immunologic memory. As such, mechanisms of immune surveillance and editing of tumors expand beyond antigen-loss but additionally via specific up-regulation of oncogene pathways. Moreover, tumor-intrinsic β-catenin activation likely can mediate resistance not only to checkpoint blockade but also T cell adoptive transfer.
Gender and entrepreneurship revisited from a community perspective: experiences in a new immigrant gateway and beyond

Women-owned enterprises have boomed significantly during the past several decades. The purpose of this study is to theorize and empirically delineate the connections between female entrepreneurship...
Chessboard distributions

We review chessboard distributions for modeling partially specified finite-dimensional random vectors. Chessboard distributions can match a given set of marginals, a given covariance structure, and various other constraints on the distribution of a random vector. It is necessary to solve a potentially large linear program to set up a chessboard distribution, but random vectors can then be rapidly generated.
What of Submarginal Areas in Regional Planning

IT HAS become tragically obvious that no one can go very far in the study of large-scale regions without coming upon the phenomena of submarginal areas. The philosophy of regionalism which has reached modulated statement at the hands of literateurs has been able to ignore submarginal zones due, no doubt, to their preoccupation with certain folk and artistic values. But if the essence of scientific regional analysis consists in the delimitation, on the basis of various indices, of physical and cultural subregions the problem becomes apparent. Not only do thiese subregions show consistent differences; certain areas prove consistently subaverage on the basis of every significant index. Such zones of economic and social inadequacy have appeared in the course of the preliminary analyses of the Southern Regional Study and the Tennessee Valley Study. The method of interand intra-regional comparison presents its peculiar difficulties, but the setting up of certain norms below which submarginality exists is likely to prove an ungrateful task. It may be somewhat lightened by a review of the standpoint, definition and criteria of submarginal areas in agriculture. The problems they present have accordingly suggested in the present paper (i) an examination of the concept of submarginal lands; (z) a review of the methods of locating submarginal areas; (3) a classification; and (4) an examination of the goals of planning for such areas.'
Quantum Transport Through Intermolecular Nanotube Junctions

Quantum transport properties of intermolecular nanotube contacts are investigated. We find that atomic structure in the contact region plays important roles and resistance of contacts varies strongly with geometry and nanotube chirality. Nanotube end-end contacts have low resistance and show negative differential resistance (NDR) behavior. Exerting small pressure/force between the tubes can dramatically decrease contact resistance, if the contact is commensurate. Significant variation and nonlinearity of contact resistance may lead to new device applications.
Portable photonic crystal fiber sensor based on surface enhanced Raman scattering (SERS)

A molecular sensing system is theoretically analyzed and experimentally demonstrated with a hollow core photonic crystal fiber surface enhanced Raman scattering (SERS) probe to achieve high sensitivity and a portable Raman spectrometer to achieve flexibility.
Abstract 4366: ShRNA-based cellular proliferation signaling analysis revealed DRD2 as a novel therapeutic target for glioblastoma.

Glioblastoma remains one of the deadliest of human cancers, with most patients succumbing to the disease within one year of diagnosis. Our best current understanding of its etiology is that glioblastoma involves genetic and epigenetic changes that subvert the inherent molecular circuitry of glial cells to drive uncontrolled cellular proliferation. Unfortunately, this molecular circuitry in glioblastoma appears sufficiently complex and redundant that disruption at any particular point tends to redirects signaling through the remaining circuit. In this context, meaningful therapeutic gains will require the identification of therapeutic agents that target critical nodes within this circuit. To identify novel therapeutic agents that target critical nodes which regulate cellular proliferation, a genome-wide retroviral shRNA library screen was conducted in two glioblastoma cell lines (U87MG and A172) and two lung carcinoma lines (A549 and NCI-H460). Pathway analysis of the pro-proliferative genes using both PANTHER and Ingenuity software revealed an over-representation of G-protein coupled neurotransmitter receptors (GPCR), including dopamine receptor subtype 2 (DRD2), which was also highly expressed in glioblastoma specimens relative to the matched normal parentchymal. Further investigation demonstrated that DRD2 signal regulates cell growth by GNAI2-induced ERK activation. Moreover, Haloperidol, one of DRD2 antagonists, enhances significantly anti-tumor efficacy of EGFR inhibitor AG1478 using U87 and mesenchymal neuroshpere xenografy mouse models. Given that both AG1478 and DRD2 antagonists have been approved for the treatment of glioblastoma and psychotics, separtately, Haloperidol combined with chemotherapy represents a novel and likely conducted strategy for the treatment of glioblastoma. Citation Format: Jie Li, Shan Zhu, David Kozono, Diahnn Futulan, David Gonda, Deepa Kushwaha, Kristopher Kahle, Stephen Elledge, Clark C. Chen. ShRNA-based cellular proliferation signaling analysis revealed DRD2 as a novel therapeutic target for glioblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4366. doi:10.1158/1538-7445.AM2013-4366
Effect of 2,3-dimercaptopropanol (BAL) on acute poisoning by tervalent and quinquevalent antimonial drugs.

SummaryIn rats, the acute lethal action of tartar emetic is significantly reduced by the administration of BAL. BAL increases the mortality rate in rats receiving Fuadin, Neostam or Neostibosan. The mortality rate in rats given large doses of Stibanose is not reduced by BAL.
Rapid assessment of “eve teasing” (sexual harassment) of young women during the commute to college In India

Many countries have taken action in recent times to address harassment in the work place and violence in the home, but little attention has been paid to sexual harassment in public places, specifically during women’s journey to work and school. In developing countries, many more women are seeking education and employment than previously, which has increased the opportunity for sexual harassment in public places. In India, the study location, this harassment is known as “eve teasing”. Eve teasing includes cat calling, lewd remarks, and inappropriate sexual contact such as rubbing and fondling. Tolerance of such incidents could lead to more severe forms of abuse and encourage more individuals to participate. Necessary as laws are, they cannot bring about immediate changes in widespread public behaviors, particularly those, such as eve teasing, that are deeply rooted in the culture of a country. To date there is no systematic research on sexual harassment in public places to assist public authorities and town planners with the development of security measures, especially for college-going women in cities and towns in India. Rapid assessment methodology has been used increasingly, especially in the field of public health, to assist decision-making about appropriate interventions for social problems by examining issues within social and cultural contexts in space and time. This paper provides a case study of rapid assessment of so-called “eve teasing” of female college students in Chennai, India. Three methods were employed in this rapid assessment of the problem— focus group discussions with college students, interviews with police officers from stations nearby the campuses and safety audits of the campus surroundings. This small exploratory study of eve teasing in India succeeded in promoting understanding of the problem and in providing many suggestions for reducing it. These latter included an extensive inventory of precautions for students, particularly female students to take in order to protect themselves from eve teasing, and a list of preventive suggestions for other stakeholders—the police, local municipalities, transport agencies and the colleges themselves. The study has wider implications for the study of routine precautions, for crime in public space and for the use of rapid assessment techniques in Crime Science.
Simulated Response of Acoustic Log in Horizontal Borehole Placing on Interface of Two Formations

Based on numerical calculation of wave equation with high-order 3D staggered-grid finite difference method,simulated is the acoustic wavefield in borehole whose axis is placed on interface of two isotropic formations with different sonic velocities,and presented are acoustic wave forms received at different transmitter-receiver spacings and snapshots of acoustic wavefield at different times.Analyzed result shows that wherever which formation covering on the top of the other,the wavefield is more sensitive to the formation with faster sonic velocity,every slowness of first wave arrival received in borehole is very close to the slowness of the formation with faster compressional wave velocity.The result provides a basic reference for data process and interpretation of acoustic logging in horizontal well.
In Fission Yeast the Constriction Rate is not Set by the Cytokinetic Ring, but by the Septum Growth Machinery

Constriction of the actomyosin contractile ring is often thought to drive division of the cell into two and to set the constriction rate. We measured a tension in the cytokinetic ring of fission yeast, where ring constriction is accompanied by septation, the growth of new cell wall in the wake of the constricting ring. Using a cell wall modulus ∼ 30 MPa, we conclude ring tension produces negligible septum strains ∼ 0.01% for a ring of radius and width ∼0.1 μm. Thus the inward septum growth rate determines the constriction rate, not the ring tension.Instead, ring tension maintains the circular shape of the septum, ensuring proper closure, using a mechanism that exploits the mechanosensitivity of septum growth. Hypothesizing mechanonsensitivity of the septum growth machinery, a mathematical model showed that ring tension suppresses septum edge roughness. Measurements of septum edge roughness in live cells agreed with model predictions, implying a mechanosensitivity per beta glucan synthase (Bgs) complex, the relative synthesis rate increase per force. Estimating the density of active Bgs complexes, a ring at constriction onset () therefore exerts centripetal force per Bgs, giving a small rate of synthesis increase. A rigorous calculation, from our mathematical model, shows little effect of tension on the constriction rate throughout constriction: ring radius versus time is almost linear with a small downward curvature.Thus, ring tension has little effect on the constriction rate, which is set by the intrinsic rate of synthesis by the cell's septum synthesis machinery.
Stratification, Hypothesis Testing, and Clinical Trial Simulation in Pediatric Drug Development.

Background Pediatric drug development is plagued by small sample sizes, unvalidated clinical endpoints, and limited studies.
Effect of monetary reward and food type on accuracy and assessment time of untrained sensory panelists in triangle tests

Abstract The effect of monetary reward amount and test food type as factors of triangle test accuracy and assessment time for untrained panelists was explored. Monetary compensation is commonly used to reward panelists for their time and effort. While studies have documented that paying panelists can influence hedonic ratings, research on its possible influence on triangle test accuracy or time to assess products is lacking. Relatedly, some studies suggest that assessment time influences accuracy. Furthermore, little research has been conducted on the effect of the test food itself, and its general likeability, on biasing panelist accuracy or assessment time. Pairs of two liked foods – chocolate chip cookies and cheddar cheese, and two not-as-liked-foods – green olives and lima beans, were tested. In addition to correlating the two response variables with the main effects, interactions of overall expected hedonic liking of the test foods, panelist age, gender, time of day of the test, and day of the week the test were analyzed. Results indicate monetary compensation amount did not influence panelist accuracy or assessment time. However, accuracy increased significantly with longer assessment times; the effect of the “liked” vs. “not-as-well-liked” food categorizations were inconclusive. Expected hedonic liking, gender, age, and time of day of the test, were significant, suggesting that test accuracy and assessment time are likely influenced by multiple intrinsic and extrinsic factors. Overall results suggest that the use of broad demographics of untrained consumers for triangle tests results in data not consistently or strongly biased by payment amount or food type.
Influence of Social Identity on Self-Efficacy Beliefs Through Perceived Social Support: A Social Identity Theory Perspective

While much research documents the influence of self-efficacy on enactment of health behaviors, relatively less attention has been given to the factors that influence self-efficacy. To enhance our understanding of the various sources of self-efficacy, this study integrated social identity theory into this context and proposed and tested a model, which describes a process through which social identity can influence self-efficacy of engaging in health-related behaviors. Consistent with the proposed meditational model, the findings showed that individuals who had stronger social identity with a given social group perceived greater social support from the group, which in turn predicted higher self-efficacy of engaging in a health-related behavior advocated by the group, and ultimately predicted greater behavioral intention. Theoretical and practical implications are discussed.
Anti-Inflammatory Effects of Apolipoprotein E Mimetics Peptides in THP-1 Human Macrophages

Apolipoprotein E (apoE) plays an important role in the regulation of atherogenesis by reducing plasma cholesterol and lesion formation in experimental animals and humans. It follows that mutations in the apoE gene are associated with loss of function and disease progression. While apoE represents a potentially important therapeutic target for the treatment of lipid disorders, there are no specific therapies that increase circulating levels of the apolipoprotein. An apoE mimetic peptide (AEM) containing a lipid-associating domain and a putative apoE receptor binding sequence has been shown to reduce plasma cholesterol in apoE-/- and low-density lipoprotein receptor-/- mice. The goal of the current study was to test whether AEM, similar to apoE, exerts direct anti-inflammatory effects at the cellular level. Treatment with AEM stimulated cholesterol efflux in THP-1 human macrophage cells at concentrations from 5-50 μg/mL. In related studies, pretreatment (24hrs) of THP-1 macrophages with AEM attenuated expression of interleukin-6 and monocyte chemoattractant protein-1 in cells treated with lipopolysaccharide (1 μg/mL). Further, RNA sequencing data showed that 24 hour treatment with AEM (20μg/mL) induced the expression of humanin and the humanin-like peptides 1, 6, 8 and 10. These metabolites are known to possess antioxidant and anti-apoptotic properties potentially through a STAT3 dependent mechanism. An increase in mRNA expression for humanins was confirmed by qRT-PCR and was associated with downregulation of miR-155. These data suggest that AEM inhibits inflammatory injury by suppressing miR-155, thus allowing the expression of cytoprotective humanin-like peptides. Further studies to understand effects of AEM administration on inflammatory cytokine expression, the STAT3 pathway, and apoptosis are currently under investigation.
Inhibition of coactivator-associated arginine methyltransferase 1 modulates dendritic arborization and spine maturation of cultured hippocampal neurons

An improved understanding of the molecular mechanisms in synapse formation provides insight into both learning and memory and the etiology of neurodegenerative disorders. Coactivator-associated arginine methyltransferase 1 (CARM1) is a protein methyltransferase that negatively regulates synaptic gene expression and inhibits neuronal differentiation. Despite its regulatory function in neurons, little is known about the CARM1 cellular location and its role in dendritic maturation and synapse formation. Here, we examined the effects of CARM1 inhibition on dendritic spine and synapse morphology in the rat hippocampus. CARM1 was localized in hippocampal post-synapses, with immunocytochemistry and electron microscopy revealing co-localization of CARM1 with post-synaptic density (PSD)-95 protein, a post-synaptic marker. Specific siRNA-mediated suppression of CARM1 expression resulted in precocious dendritic maturation, with increased spine width and density at sites along dendrites and induction of mushroom-type spines. These changes were accompanied by a striking increase in the cluster size and number of key synaptic proteins, including N-methyl-d-aspartate receptor subunit 2B (NR2B) and PSD-95. Similarly, pharmacological inhibition of CARM1 activity with the CARM1-specific inhibitor AMI-1 significantly increased spine width and mushroom-type spines and also increased the cluster size and number of NR2B and cluster size of PSD-95. These results suggest that CARM1 is a post-synaptic protein that plays roles in dendritic maturation and synaptic formation and that spatiotemporal regulation of CARM1 activity modulates neuronal connectivity and improves synaptic dysfunction.
Variability and predictors of urinary concentrations of organophosphate flame retardant metabolites among pregnant women in Rhode Island

Organophospate flame retardants (PFRs) are chemicals of emerging concern due to restrictions on polybrominated diphenyl ether flame retardant formulations. We describe the occurrence, variability, and predictors of urinary metabolites of PFRs among pregnant women. In 2014–2015, 59 women from Providence, RI provided up to 3 spot urine samples during pregnancy (~12, 28, and 35 weeks’ gestation). We created a pooled urine sample per woman and measured nine relevant metabolites in individual and pooled samples. We used linear mixed models to calculate intraclass correlation coefficients (ICCs) across the 3 measurements and to assess sociodemographic and dietary predictors of PFRs. The median (IQR) of bis-2-chloroethyl phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), and diphenyl phosphate (DPhP), the metabolites most frequently detected, from pooled samples were: 0.31 μg/L (0.17–0.54), 1.18 μg/L (0.64–2.19), 0.93 μg/L (0.72–1.97), respectively. We observed fair to good reproducibility for BCEP (ICC = 0.50), BDCPP (ICC = 0.60), and DPhP (ICC = 0.43), and excellent agreement between the urinary flame retardant metabolite concentrations averaged across pregnancy versus pooled urine sample concentrations for BCEP (ICC = 0.95), BDCPP (ICC = 0.89), and DPhP (ICC = 0.93). Adjusting for pertinent sociodemographic factors and gestational week of urine collection, each 1 kg increase in pre-pregnancy weight was associated with greater BCEP (1.1%; 95% CI: 0.1, 2.1), BDCPP (1.5%; 95% CI: 0.3, 2.7), and DPhP (0.5%; 95% CI: 0.0, 1.1). Dietary factors were generally not associated with urinary flame retardant metabolites. Urinary concentrations of BCEP, BDCPP, and DPhP were frequently detected among women in this pilot study and had fair reproducibility across pregnancy. Body size may be an important predictor of urinary flame retardant metabolite concentrations.
Development of a High-Throughput Magnetic Separation Device for Malaria-Infected Erythrocytes

This study describes a non-dilutive high-gradient magnetic separation (HGMS) device intended to continuously remove malaria-infected red blood cells (iRBCs) from the circulation. A mesoscale prototype device with disposable photo-etched ferromagnetic grid and reusable permanent magnet was designed with a computationally-optimized magnetic force. The prototype device was evaluated in vitro using a non-pathogenic analog for malaria-infected blood, comprised of 24% healthy RBCs, 6% human methemoglobin RBCs (metRBCs), and 70% phosphate buffer solution (PBS). The device provided a 27.0 ± 2.2% reduction of metRBCs in a single pass at a flow rate of 77 μL min−1. This represents a clearance rate over 380 times greater throughput than microfluidic devices reported previously. These positive results encourage development of a clinical scale system that would economize time and donor blood for treating severe malaria.