cssi/SciSciGPT-SciSciNet huggingface dataset:
Computational Cell Cycle Profiling of Cancer Cells for Prioritizing FDA-Approved Drugs with Repurposing Potential

Discovery of first-in-class medicines for treating cancer is limited by concerns with their toxicity and safety profiles, while repurposing known drugs for new anticancer indications has become a viable alternative. Here, we have developed a new approach that utilizes cell cycle arresting patterns as unique molecular signatures for prioritizing FDA-approved drugs with repurposing potential. As proof-of-principle, we conducted large-scale cell cycle profiling of 884 FDA-approved drugs. Using cell cycle indexes that measure changes in cell cycle profile patterns upon chemical perturbation, we identified 36 compounds that inhibited cancer cell viability including 6 compounds that were previously undescribed. Further cell cycle fingerprint analysis and 3D chemical structural similarity clustering identified unexpected FDA-approved drugs that induced DNA damage, including clinically relevant microtubule destabilizers, which was confirmed experimentally via cell-based assays. Our study shows that computational cell cycle profiling can be used as an approach for prioritizing FDA-approved drugs with repurposing potential, which could aid the development of cancer therapeutics.
The impact of defendants' race in competency to stand trial referrals.

Abstract In the United States, competency to stand trial (CST) evaluations ensure that criminal defendants are capable of participating in their defenses, thus ensuring an important legal right. However, some research has suggested that the CST process may be impacted by legally irrelevant factors such as a defendant's race and cultural background. However, the majority of researchers examined factors that are predictive of CST recommendations and decisions. Few studies have focused on potential racial discrepancies in attorney referrals for CST evaluations and whether they are exacerbated by professional experience. The current study examined potential racial disparities in referrals for CST evaluations among 322 law students and 102 attorneys. Participants were randomly assigned to read vignettes describing either African American or Caucasian defendants who varied in their fitness to stand trial. The participants were asked to indicate whether they would refer the client for a CST evaluation and to describe their reasoning. The results indicated that both law students and attorneys were generally more likely to refer unfit rather than fit defendants, indicating an understanding of the legal criteria. Law students displayed a racial bias, only when referring the defendants who were unfit due to the lack of a rational understanding of the relevant legal case, χ2(1) = 4.90, p = 0.03, Φ = 0.13. Fitness condition was the only significant predictor of attorney referrals. The generally encouraging results indicated that professional experience did not increase racial biases.
Quark Confinement Schemes in Field Theory

Evidence supporting the idea of quarks as the hadronic constituents has been strengthening since they were first proposed by Gell-Mann and Zweig in the 1960’s. In particular there are the successes of the SU(3) symmetry scheme. Hadrons of the same spin and parity form multiplets each of which corresponds to an irreducible representation of SU(3). Experimentally the multiplets are observed to be octets, decuplets, and singlets, whereas the fundamental representation of SU(3) is a triplet. Therefore the simplest picture of hadrons is to build them as bound states of triplet quarks from which they derive their individual quantum numbers of electric charge, strangeness, etc.
The Role of International Treaties in the Interpretation of Canadian Intellectual Property Statutes

The relationship between domestic intellectual property statutes and international law in growing in scope and depth. This paper is a chapter in a book that emphasizes that international law is not only used to interpret domestic law but in fact may itself become a guide for international tribunals, such as the World Trade Organization Dispute-Settlement Body. The Paper considers mostly the role that international norms have played in recent decisions of the Supreme Court of Canada and the Federal Court.
Early Development of Oral, Olfactory and Adenohypophyseal Structures of Agnathans and Its Evolutionary Implications

Ideas concerning the earliest evolution of the vertebrate head must be based on paleontological evidence as well as on adult and embryonic morphology of present day agnathans. Unfortunately, paleontological evidence for evolution of certain soft structures of the head is not really available, so that embryonic development of such structures is often the basis for speculation in this field (e.g. Stensio, 1968). Here, we would like to address one phase of this problem; the formation of the agnathan adenohypophysis and some contiguous structures from the nasopharyngeal canal, and the presumed homology of the nasopharyngeal canal with the adenohypophyseal anlage, or Rathke’s pouch, of higher vertebrates.
Obstetric outcomes in women with rheumatoid arthritis: Results from Nationwide Inpatient Sample Database 2003–2011✰

Abstract Objective Fertility is reduced in patients with Rheumatoid Arthritis due to unknown cause. Few studies have addressed pregnancy outcomes in RA. This study was undertaken to determine the frequency of complications occurring during pregnancy for women with RA and compare with the general obstetric population by using the largest inpatient care database. Methods By using the 2003–2011 Nationwide Inpatient Sample of Healthcare Cost and Utilization Project, we estimated the number of obstetric hospitalization in women with RA between the age group 18–50 years. Demographic characteristics and in-hospital obstetric complications for all pregnancy-related admissions for women with and without RA were compared. Multivariate logistic regression analysis was used to obtain adjusted odds ratio. Results The total number of obstetric hospitalization was 42.32 million of which 31,439 were women with RA. The maternal age of RA population was higher (30.5 years) than that in the control group (27 years). After adjusting for potential confounders, maternal RA population had a significantly higher prevalence of hypertensive diseases, premature rupture of membranes, antepartum hemorrhage, preterm delivery, intrauterine growth retardation and cesarean delivery. The prevalence of postpartum hemorrhage and the risk of inpatient mortality were not different between two groups. Conclusion Women with RA have a higher risk of adverse outcomes of pregnancy and thus close antenatal and post-delivery monitoring need to be performed in order to reduce complications. Further studies are needed to examine these findings in relation to severity of disease, medications used and the presence of other comorbidities.
Cooperative unmanned aerial vehicles with privacy preserving deep vision for real-time object identification and tracking

Abstract Human tracking is an important challenge in a wide variety of applications, including but not limited to, surveillance, military operations, and disaster relief services. Unmanned Aerial Vehicles (UAVs) allow the surveying of dangerous or impassable areas from a safe distance. They also provide a machine-based capability, which may not only solve resource constraint issues, but can also improve effectiveness and efficiency in the tracking task. The effectiveness of tracking is directly related to the angle of view and degree of freedom of the camera system. In this paper, we introduce a decentralized, distributed deep learning algorithm for Real-Time Privacy-preserving Target Tracking Re-Identification (RPTT-ReID) used by cooperative UAVs in complex and adversarial environments involving motion, crowded scenes, and varied camera angles. The efficiency of RPTT-ReID makes it amenable to edge computing applications. The proposed algorithmic approach resolves shortfalls with current tracking algorithms, specifically challenges in maintaining tracking when subjects cross paths, switch identity, or are occluded in a frame of view. We demonstrate the power of our approach both in single and multi-UAV scenarios to track movable targets by extracting the facial embedding information in crowds, in order to ensure the privacy of individuals captured by the UAVs without compromising the capability for target re-identification. We validate RPTT-ReID on a challenging video dataset of crowded scenes. Our experimental evaluation shows that the proposed approach is capable of tracking and re-identifying people in crowds despite blended trajectories with minimum and maximum accuracy of 79.91 ± 0.2% and 93.27 ± 0.1% respectively. The proposed approach is 18% faster than previous methods for tracking in crowded urban environments.
Enhanced ductility of III-V covalent semiconductors from electrons and holes

Covalent semiconductors exhibit low ductility arising from the resistance of the strong chemical bonds to deformation slip. It is important to soften these strong covalent bonds to improve the ductility of covalent semiconductors for their extended engineering applications. Here, we demonstrate from quantum mechanics simulations that the free carriers, including electrons and holes, can significantly weaken the strong covalent bonds of III-V covalent semiconductors, resulting in the modified general stacking fault energy surface and enhanced ductility. Furthermore, we establish the relationship between the carrier density and the energy barriers of deformation slip, in which the increased carrier concentration leads to an increased tendency of dislocation nucleation and higher ductility. The physical origin of this phenomenon arises from the contributions of extra carriers to the formation of new weak bonds at stacking fault layers along the slip plane, decreasing the energy barrier of deformation slip. Our results indicate that free electrons and holes play an important role in the mechanical properties of covalent semiconductors at high carrier concentrations. This provides the theoretical foundation to tune the mechanical properties of covalent semiconductors using injected carriers.Covalent semiconductors exhibit low ductility arising from the resistance of the strong chemical bonds to deformation slip. It is important to soften these strong covalent bonds to improve the ductility of covalent semiconductors for their extended engineering applications. Here, we demonstrate from quantum mechanics simulations that the free carriers, including electrons and holes, can significantly weaken the strong covalent bonds of III-V covalent semiconductors, resulting in the modified general stacking fault energy surface and enhanced ductility. Furthermore, we establish the relationship between the carrier density and the energy barriers of deformation slip, in which the increased carrier concentration leads to an increased tendency of dislocation nucleation and higher ductility. The physical origin of this phenomenon arises from the contributions of extra carriers to the formation of new weak bonds at stacking fault layers along the slip plane, decreasing the energy barrier of deformation slip. O...
Examining Diverse Perspectives of edTPA Policy Implementation Across States: The Good, the Bad, and the Ugly:

Since 2009, the Educative Teacher Performance Assessment (edTPA) has been rapidly implemented as a policy tool for strengthening teacher professionalization across the United States. However, its n...
Short-Reach and Pin-Efficient Interfaces Using Correlated NRZ

Correlated Non-Return-to-Zero (CNRZ) signaling exhibits better pin-efficiency compared to the conventional binary differential NRZ signaling, while it does not compromise the sensitivity to Inter-Symbol Interference (ISI). This article analyzes performance of CNRZ transceivers, and provides experimental data for an Ultra-Short Reach (USR) link at 20.83 Gb/s/wire, implemented in FinFET 16 nm technology, consuming 1.02 pJ/b, As CNRZ is based on an orthogonal transformation, both encoding and decoding can be performed in analog, without any cost in terms of latency.
BET bromodomain inhibition attenuates cardiac phenotype in myocyte-specific lamin A/C-deficient mice

Mutation in the LMNA gene, encoding lamin A/C, causes a diverse group of diseases called laminopathies. Cardiac involvement is the major cause of death and manifests as dilated cardiomyopathy, heart failure, arrhythmias, and sudden death. There is no specific therapy for LMNA-associated cardiomyopathy. We report that deletion of Lmna in cardiomyocytes in mice leads to severe cardiac dysfunction, conduction defect, ventricular arrhythmias, fibrosis, apoptosis, and premature death within 4 weeks. The phenotype is similar to LMNA-associated cardiomyopathy in humans. RNA sequencing, performed before the onset of cardiac dysfunction, led to identification of 2338 differentially expressed genes (DEGs) in Lmna-deleted cardiomyocytes. DEGs predicted activation of bromodomain-containing protein 4 (BRD4), a regulator of chromatin-associated proteins and transcription factors, which was confirmed by complementary approaches, including chromatin immunoprecipitation sequencing. Daily injection of JQ1, a specific BET bromodomain inhibitor, partially reversed the DEGs, including those encoding secretome; improved cardiac function; abrogated cardiac arrhythmias, fibrosis, and apoptosis; and prolonged the median survival time 2-fold in the myocyte-specific Lmna-deleted mice. The findings highlight the important role of LMNA in cardiomyocytes and identify BET bromodomain inhibition as a potential therapeutic target in LMNA-associated cardiomyopathy, for which there is no specific effective therapy.
Atmospheric Coalitions: Shifting the Middle in Late Industrial Baltimore

STS scholars offer the atmosphere as an antidote to the homogenizing Anthropocene. They teach us that atmospheres are good to think because they are both diffuse and differential; they reflect the scale of planetary problems without forgetting that those problems manifest unevenly. The atmosphere has, then, become a useful tool for theory work. But it is also being picked up on the ground as a model for grassroots coalition building. This article follows one group we might call an atmospheric coalition , which coalesced to fight a trash incinerator proposed in south Baltimore City. That incinerator would have had a major impact on the local air, particularly due to heavy-metal toxics that land close to their source. But it also would have affected a large regional airshed and released thousands of tons of greenhouse gases. Taking a cue from these multi-scalar impacts, the coalition to stop the incinerator both used the medium of air to trouble insider/outsider dichotomies and valued an uneven distribution of power, letting youth from the frontline community lead. Participants, in other words, built a flexible alliance—and they utilized its flexibility. Sometimes it was advantageous to call the incinerator “everyone’s problem.” Sometimes it was necessary to underscore its differential effects on local people. And sometimes the transience of atmospheric claims worked to transfer jurisdiction over the plant from one group to another. In the process of exploring these maneuvers, I argue that activists used the atmosphere to define a problem-space with pliant parameters of authority and vulnerability.
Semi-metals as potential thermoelectric materials

The best thermoelectric materials are believed to be heavily doped semiconductors. The presence of a band gap is assumed to be essential to achieve large thermoelectric power factor and figure of merit. In this work, we propose semi-metals with large asymmetry between conduction and valence bands as an alternative class of thermoelectric materials. To illustrate the idea, we study semi-metallic HgTe in details experimentally and theoretically. We employ ab initio calculations with hybrid exchange-correlation functional to accurately describe the electronic band structure in conjunction with the Boltzmann Transport theory to investigate the electronic transport properties. We calculate the lattice thermal conductivity using first principles calculations and evaluate the overall figure of merit. To validate our theoretical approach, we prepare semi-metallic HgTe samples and characterize their transport properties. Our first-principles calculations agree well with the experimental data. We show that intrinsic HgTe, a semimetal with large disparity in its electron and hole masses, has a high thermoelectric power factor that is comparable to the best known thermoelectric materials. Finally, we propose other possible materials with similar band structures as potential candidates for thermoelectric applications.
Motivational Strategies to Engage Learners in Desirable Difficulties

Learning strategies that create “desirable difficulties” by slowing or hindering improvement during learning often produce superior long-term retention and transfer ( Bjork, 1994 , Bjork, 1999 ). Despite the desirability of difficulties for learning, many learners choose not to use the learning strategies and/or disengage when they are implemented by a teacher. Knowledge of these learning strategies is necessary but insufficient for behavior change—learners must be motivated to embrace or, at minimum cope, with difficulties. To identify ways to help students engage with learning strategies that produce desirable difficulties, the present article briefly reviews five areas of psychological research on motivation that provide strategies for increasing engagement and persistence: finding value, reducing cost, reframing appraisals and attributions, creating appropriate challenges, and providing choice. Looking forward, there is a clear need for empirical work to investigate and theoretical frameworks to explain the interplay between motivation and learning strategies that create desirable difficulties.
Tribute to Barbara Murphy

This is a tribute to the late Dr. Barbara T. Murphy, the Murray M. Rosenberg Professor of Medicine and Chair of Medicine at the Icahn School of Medicine at Mount Sinai in New York city, the Dean for Clinical and Population Management, and Councilor and the President-Elect for the American Society of Nephrology (ASN). Accounts of Dr. Murphy’s many accomplishments have already been detailed in other glowing tributes (1⇓–3). One of her most notable feats was that in 2012, she became the first female chair for a major academic center in New York city and, at the time, was only the second female chair of any department at a top-20 medical school in the United States. During the 9 years with Dr. Murphy at the helm, the prestige and accomplishments of the Mount Sinai Department of Medicine also grew. For example, funding levels per year placed the department of medicine in the top 15th among graduate medical departments in the country (4). Dr. Murphy’s research focused on genetics and genomics in transplantation. Using high-throughput genomic technologies, she generated data that increased the understanding of the immune mechanisms that lead to kidney graft rejection (5,6), injury, and loss (7). Importantly, she aimed to identify gene expression profiles or genetic variants that would predict patients’ risk for disease and identified genetic drivers of fibrosis (8, …
Visudyne™: a new therapeutic strategy for the treatment of ovarian cancer

Objectives: Yes-associated protein (YAP) is a transcriptional coactivator regulated via the Hippo pathway that has been shown to be tumorigenic in ovarian cancer (OC). YAP has also been identified to be uniquely expressed within induced regulatory T cells (Tregs). A conditional knockout of YAP in T cells decreased Tregs within the tumor microenvironment and increased antitumor immune response in a subcutaneous mouse melanoma model. Visudyne™ is a liposomal derivative of verteporfin (VP), a known YAP inhibitor that is FDA approved for the treatment of adult macular degeneration. The objective of our study is to: 1) evaluate the effect of Visudyne™ on YAP and its transcriptional targets, 2) determine cytotoxic effects of Visudyne™ in platinum sensitive and resistant OC cell lines, and 3) to evaluate its effect on immune regulatory cells. Methods: Western blot analysis and immunofluorescence were performed to determine YAP expression and localization in R182 and MR182 OC cell lines using specific antibodies for YAP, phosphorylated YAP (pYAP), and connective tissue growth factor (CTGF), a transcriptional target of YAP. Cell proliferation was measured using Incucyte real-time imaging following treatment with increasing doses of cisplatin, VP and Visudyne™ in A2780 wildtype and platinum resistant OC cells. IC50 was calculated using GraphPad PRISM. Three C57/B6 mice were injected intraperitoneally (IP) with triple knockout p53mut/PTENmut/mCherry OC cells. Tumor progression was monitored by mCherry signal with fluorescence spectroscopy. Visudyne™ was administered IP at 2 mg/kg and 3 days later at 4 mg/kg. Flow cytometry was performed using antibodies for CD4, CD8, FOXP3, and interferon gamma to identify Treg and cytolytic T cells in peritoneal lavage and spleen of the control and Visudyne™ treated mice. Download : Download high-res image (329KB) Download : Download full-size image Results: Treatment of OC cells with 1uM Visudyne™ is associated with a significant decrease expression of total YAP, pYAP, and CTGF (Figure 1A). Immunofluorescence demonstrated loss of nuclear YAP and increased pYAP in the cytoplasm of R182 and MR182 cells after VP treatment (Figure 1B). Increasing doses of Visudyne™ significantly decreased cell growth in platinum resistant A2780 OC cells when compared to cells treated with cisplatin alone. In vivo treatment of tumor bearing mice with Visudyne™ is associated with a significant decrease of Treg CD4+/FOXP3+ cells in peritoneal lavage of treated mice compared to the control (85.5% vs. 92.9%, Figure IC). No changes were observed in the spleen in treated mice vs. control. Conclusions: We propose that Visudyne™ should be further investigated as a novel therapeutic agent for the treatment of OC. Its effect on immune function, specifically Tregs, suggests a promising effect either as a single agent or in combination with other checkpoint inhibitors in platinum sensitive and resistant OC.
Textbooks of doubt, tested: the effect of a denialist framing on adolescents’ certainty about climate change

In US school settings and materials, climate change is often framed as an uncertain phenomenon. However, the effect of such denialist representations on youth’s perceptions of climate change has no...
Boredom in the Classroom: Addressing Student Motivation, Self-Regulation, and Engagement in Learning

Chapter 1: The Academic Emotion of Boredom: The Elephant in the Classroom.- Chapter 2: Unmasking Boredom: It's Not so Simple or Uninteresting - Boredom is Both Interesting and Complex.- Chapter 3: The Many Faces of Boredom: A Negative Emotion that is so Common, It Is Simply Accepted, or Brushed Off .- Chapter 4: Theory: What Is Causing Our Students to Tune Out and Turn Off?.- Chapter 5: Interventions for External Variables: What Can Teachers Do to Add a Bit of Excitement to Learning in the Classroom?.- Chapter 6: Interventions for Internal Variables: Some Students Cannot Turn It on - They Need More than Great Teachers and Interesting Lessons.
Waveform window #18. Troubleshoot this.

(2010). Waveform Window #18: Troubleshoot This. American Journal of Electroneurodiagnostic Technology: Vol. 50, No. 3, pp. 246-249.
Chapter 35. Medicinal Chemistry: Through a Glass Darkly

Publisher Summary The production of transgenic plants, whilst generating less immediate ethical attention, can prove of value to the generation of medicinal products of natural origin, such as scopolamine, through the introduction of the hyoscyamine hydroxylase gene into Atropa belladonna . Some 37 gene transfer trials have been approved worldwide and eighteen of these are designed to produce immediate therapeutic benefits. These include several trials, inserting the gene for adenosine deaminase to alleviate the absence of a natural immune system, and interleukin genes for several cancer types. The potential benefits of alleviating dopamine deficiency in the brains of Parkinson's patients by tissue implantation have been widely discussed from both clinical and ethical perspectives. It is clear that the issues of ethics raised by the rapid approach to the human genome are of increasing importance to definition of any new clinical interface. The concept of specific receptors and sites of drug action has many origins. The definition of receptors as specific sites for drug action owes much to the work of John Newton Langley and Paul Ehrlich. Their work on the autonomic nervous system, toxins, and chemotherapeutic agents led to the concept of a receptor, possessing both recognition and transduction components, and of drugs possessing discrete regions subserving specific functions. The emergence of both old and new diseases focuses continuing efforts on drug discovery and the central role of medicinal chemistry. These foci are switching increasingly from the empirical and intuitive discovery processes to structure- and mechanism-based discovery routes.
Role of Commensal Enteric Bacteria in Intestinal Inflammation: Lessons from Animal Models

This chapter outlines evidence supporting the hypothesis that chronic immune-mediated intestinal inflammation in genetically susceptible hosts is a consequence of overly aggressive cell-mediated immune responses to a subset of commensal luminal bacteria. The most compelling evidence that normal luminal bacteria induce colitis is the fact that in at least 11 separate models of induced or spontaneous intestinal inflammation, no disease occurs in the absence of bacteria (germ free or sterile state). Recent results in several independent gnotobiotic models demonstrate that commensal enteric bacterial species differ in their capacity to induce chronic intestinal inflammation. Chronic intestinal inflammation is mediated by T lymphocytes, based on the absence of experimental colitis in T-cell-deficient hosts, induction of disease by transfer of CD4 + T lymphocytes, and prevention and reversal of chronic inflammation by blockade of products of TH1 cytokines. A key factor in the induction of chronic immune-mediated intestinal inflammation is the loss of tolerance to luminal bacterial antigens in genetically susceptible hosts. Many studies discussed in the chapter support the hypothesis that chronic intestinal inflammation is a consequence of an overly aggressive cell mediated immune response to a subset of the complex resident enteric bacterial population in genetically susceptible hosts. Results in animal models indicate that manipulation of the luminal microflora by antibiotics, probiotics, and prebiotics can treat established disease and prevent recurrent inflammation. These physiologic bacterial manipulations may have additive and perhaps synergistic activities with more widely used immunosuppressive therapies and emerging growth factor treatments.
Postnatal development of electrophysiological properties of principal neurons in the rat basolateral amygdala

The basolateral amygdala (BLA) is critically involved in the pathophysiology of psychiatric disorders, which often emerge during brain development. Several studies have characterized postnatal changes to the morphology and biochemistry of BLA neurons, and many more have identified sensitive periods of emotional maturation. However, it is impossible to determine how BLA development contributes to emotional development or the aetiology of psychiatric disorders because no study has characterized the physiological maturation of BLA neurons. We addressed this critical knowledge gap for the first time using whole-cell patch clamp recording in rat BLA principal neurons to measure electrophysiological properties at postnatal day (P)7, P10, P14, P21, P28 and after P35. We show that intrinsic properties of these neurons undergo significant transitions before P21 and reach maturity around P28. Specifically, we observed significant reductions in input resistance and membrane time constant of nearly 10-and 4-fold, respectively, from P7 to P28. The frequency selectivity of these neurons to input also changed significantly, with peak resonance frequency increasing from 1.0 Hz at P7 to 5.7 Hz at P28. In the same period, maximal firing frequency significantly increased and doublets and triplets of action potentials emerged. Concomitantly, individual action potentials became significantly faster, firing threshold hyperpolarized 6.7 mV, the medium AHP became faster and shallower, and a fast AHP emerged. These results demonstrate neurons of the BLA undergo vast change throughout postnatal development, and studies of emotional development and treatments for juvenile psychiatric disorders should consider the dynamic physiology of the immature BLA.
Deuterium and Tritium

Deuterium (2H or D) the heavier, stable isotope of hydrogen (1H) occurs in nature, and is always present in all hydrogen-containing compounds. Deuterium oxide, known as heavy water, is the most important deuterium compound. Heavy water differs from ordinary water in structure of the liquid phase, in nuclear spin, ionic equilibria, and in various spectroscopic properties. Kinetic isotope effects occur in chemical reactions involving bond rupture of H and D. This effect in hydrogen exchange between water and hydrogen sulfide is the basis for the most important separation process for large-scale deuterium production. Infrared absorption is the method of choice for the analysis of heavy water. Deuterium has far-reaching biological effects, and it is possible to grow living organisms in which all of the hydrogen normally present is replaced by deuterium. The nuclear properties of deuterium are such that heavy water is the most efficient neutron moderator known for nuclear fission reactors. Deuterium is also important in nuclear fusion technology. Tritium (3H or T) is the heaviest isotope of hydrogen. Unlike hydrogen or deuterium, T undergoes radioactive decay (B−, ∼ 12 yr half-life). Thus T compounds experience radiation damage at elevated tritium levels. Tritium is produced by cosmic rays in the higher atmosphere, and by neutron capture in lithium–aluminum alloy in nuclear fission reactors. Tritium can be purified by distillation, by thermal diffusion, by diffusion through palladium-silver-nickel membranes, or by chromatography on coated molecular sieves. Tritium is widely used as a tracer in molecular biology experiments. Tritium is a key element in nuclear fusion, in which energy is produced by the controlled fusion of tritium with deuterium. Keywords: deuterium; tritium; isotopes; heavy hydrogen; heavy water; neutron moderator; superconductivity; deuterium fusion; nuclear fusion; tracers; nuclear magnetic resonance
Protein-carbohydrate interaction : VIII. A turbidimetric method for the analysis of D-mannose

Abstract A unique, spectrophotometric method for the quantitative of D -mannose in the presence of other sugars is described. The procedure depends on the degree to which the turbidity formed on interaction of concanavalin A with glycogen is specifically inhibited by D -mannose. The analysis, whose useful is 300 to 750 μg/ml, gives essentially the same result as other methods commonly used. A correction for the presence of D -glucose, which also inhibits glycogen-concanavalin A interaction, is readily achieved by use of the Glucostat reagent.
Abstract P3-12-10: Calcium and magnesium infusion for the prevention of taxane induced neuropathy in early stage breast cancer

Background: Taxane is an active drug in the treatment of breast cancer, but peripheral neuropathy is a major dose limiting side effect. There are currently no effective drugs or treatment modalities for the prevention or treatment of taxane-related neuropathy. We examined whether calcium and magnesium (Ca/Mg) infusions can reduce the incidence of neuropathy in patients with early stage breast cancer who are treated with paclitaxel. Methods: This was a pilot study evaluating the feasibility of Ca/Mg infusion to prevent taxane induced neuropathy in women with early stage breast cancer receiving adjuvant or neo-adjuvant paclitaxel treatment, either given every 2 weeks for 4 cycles or every week for 12 weeks. All patients received calcium gluconate and magnesium sulfate infusion, 1 g of each agent immediately before and after each dose of paclitaxel. The primary endpoint was paclitaxel-related neuropathy grade 2 or greater as measured by NCI Common Terminology Criteria Version 3 compared with historical controls. Secondary endpoints included other measures of neuropathy and quality of life such as the Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) score, taxane-related neuropathic pain as measured by the Brief Pain Inventory-Short Form (BPI-SF). The endpoints were assessed in patients midway through treatment, at the end of treatment and 4 weeks after finishing taxane therapy. Results: We enrolled 50 patients, 47 patients were evaluable, and 3 patients were taken out of the study due to non-neuropathy related side effects or progression of disease. Median age: 50.8 (range 27-71), White/Hispanic/Black/Asian/Other: 17/16/12/3/2. Two patients received paclitaxel every 2 weeks, while the remainder received weekly therapy. Eight of 47 patients (17%) had grade 2 neuropathy four weeks after treatment completed, while no patients had grade 3 or 4 neuropathy. This rate of neuropathy is significantly lower compared to that seen in historical control where approximately 30% of patients develop grade 2 or greater neuropathy. There were no significant changes in the quality of life measurements. There were no observed toxicities related to the Ca/Mg infusion. Discussion: Our study showed a decreased incidence of paclitaxel-related neuropathy in patients receiving Ca/Mg infusions when compared to historical controls. The infusions are well tolerated without any side effects. Randomized studies are warranted to further evaluate Ca/Mg infusion for the prevention of paclitaxel-related neuropathy. Citation Format: Theresa Shao, Joshua Kra, Paula Klein, Anupama Goel, Stephen Malamud, Tiffany Xing, Johnny Chan, Michael L Grossbard. Calcium and magnesium infusion for the prevention of taxane induced neuropathy in early stage breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-12-10.
Genetic effects, gene-lifestyle interactions, and type 2 diabetes

Type 2 diabetes has become a major public health challenge worldwide. It is now widely accepted that genetic components affect the development of type 2 diabetes, in concert with environmental factors such as lifestyle and diet. Traditional linkage mapping, positional cloning, and candidate gene-based association studies have identified a few genetic variants in genes such as TCF7L2, PPARG, and KCNJ11 that are reproducibly related to the risk of type 2 diabetes. To date, about ten genome-wide association (GWA) studies have been published. These studies discovered new susceptibility genes for type 2 diabetes and provide novel insight into the diabetes etiology. In addition, data especially from lifestyle intervention trials display promising evidence that the genetic variants may interact with changes of dietary habit and physical activity in predisposing to type 2 diabetes. The gene-lifestyle interactions merit extensive exploration in large, prospective studies. The findings from these areas will substantially improve the prediction and prevention of type 2 diabetes.
Measurement of Intracellular Fluorescence of Human Monocytes Relative to Oxidative Metabolism

Human monocytes (MN) produce O2- and H2O2 when stimulated by agonists. Dichlorofluorescin diacetate (DCFH-DA) has been used as a substrate for measuring intracellular oxidant production in neutrophils. DCFH-DA is hydrolyzed by esterases to dichlorofluorescin (DCFH), which is trapped within the cell. This nonfluorescent molecule is then oxidized to fluorescent dichlorofluorescin (DCF) by action of cellular oxidants. DCFH-DA can not be appreciably oxidized to a fluorescent state without prior hydrolysis. We have examined the utility of DCFH-DA for the assessment of monocyte oxidative responses. The levels of intracellular fluorescence measured by flow cytometry were considerably less than expected from reported levels of O2--production or chemiluminescence assays. Compared with neutrophils, monocytes produced minimal increases in DCF fluorescence after stimulation with phorbol myristate acetate as measured by flow cytometry, but both cell types showed increases in fluorescence when bulk cell suspensions were measured by spectrofluorometry. To determine the intracellular location of the DCFH, bulk fluorescence measurements were made on both whole and sonicated cell preparations. When intact mononuclear cells were preloaded with DCFH-DA, then sonicated and oxidized with added excess H2O2, the increase in fluorescence was only 30% of the fluorescence of mononuclear cell sonicates to which DCFH-DA was added and oxidized in a similar manner. These results suggest that a portion of the DCFH-DA incorporated by intact cells, is not susceptible to oxidation by the added H2O2. Addition of NaOH to induce hydrolysis of any residual DCFH-DA in the sonicates of DCFH-DA-loaded intact mononuclear cells resulted in a further increase in fluorescence upon addition H2O2, suggesting that a significant portion of the DCFH-DA was not hydrolyzed despite ample uptake of this dye by these cells. In contrast, no further increase in fluorescence was observed in sonicates of DCFH-DA-loaded intact neutrophils, suggesting complete hydrolysis of all incorporated DCFH-DA to DCFH. When monocytes were allowed to phagocytose DCFH-DA-loaded Staphylococcus aureus, intracellular fluorescence was measurable by flow cytometry, indicating intracellular oxidation of the fluorochromes. We therefore propose that in monocytes the mechanism of intracellular processing of these fluorochromes differs from that in neutrophils owing to differences in intracellular localization of fluorochromes, site of oxidant production, and/or accessibility of the DCFH-DA to esterolysis.
Urbanization and Carbon Emissions: A Nationwide Study of Local Countervailing Effects in the United States

Objective This study advances a theoretical framework for examining the impact of urbanization on local carbon emissions over space and time. It conceptualizes urbanization at the local level as a set of three distinct but related subprocesses of population concentration, land-use intensification, and systemic interaction, which join together to exert countervailing effects on local carbon emissions. Methods To test this framework we conduct cross-sectional and panel regression analyses of carbon emissions at the county level across the continental United States, controlling for spatial autocorrelation. Results Findings strongly support our framework and show how different dimensions of urbanization push against one another at the local level to influence carbon emissions in ways that exert far more consistent effects than household density and alternative transit use. Conclusion These findings illuminate the complexities of urbanization as a local force of environmental transformation with increasingly global consequences.
Protective role of 17β-estradiol against the development of Helicobacter pylori-induced gastric cancer in INS-GAS mice

The incidence of gastric cancer is higher in men than women. Epidemiological studies suggest that female hormones reduce gastric cancer risk. We examined the effect of ovarian-dependent female hormones on Helicobacter pylori-induced gastric cancer in hypergastrinemic INS-GAS mice. Male and female sexually intact or ovariectomized (OVX) mice were inoculated with H.pylori SS1 or vehicle-only at 10 weeks of age, and tissues were evaluated at 16 or 28 weeks post-infection (WPI). A subset of OVX females were supplemented with 17beta-estradiol (E2), beginning at 16 WPI. Stomachs were evaluated by histopathology, Ki-67 proliferation index, H.pylori quantitative culture and quantitative polymerase chain reaction for messenger RNA expression of inducible nitric oxide synthase (iNOS) and inflammatory cytokines. Infected OVX females developed significantly more severe gastritis (P < 0.05) than infected intact females at both time points. E2 treatment in infected OVX females attenuated the severity of gastritis. Gastrointestinal intraepithelial neoplasia (GIN) developed in 42% of infected males and 10% of infected OVX females by 28 WPI, whereas infected intact females and E2-treated OVX females did not develop GIN. Infected OVX females showed significantly increased iNOS expression and epithelial cell proliferation when compared with intact, infected females. Likewise, interferon-gamma, tumor necrosis factor-alpha and interleukin-1beta (IL-1beta) expression in infected OVX females were significantly increased at 28 WPI when compared with intact counterparts. E2 treatment in infected OVX females significantly decreased IL-1beta expression, increased IL-10 expression and reduced epithelial cell proliferation. These results demonstrate a protective effect of E2 in H.pylori-induced gastric cancer in a mouse model.
Interpretation of the pion-hyperon resonances

The pion-hyperon resonances at 1520 and 1580 Mev were studied; they were considered as manifestations of the dynamic structure of the closed pion-hyperon system. For a suitable choice of coupling constant values, a consistent interpretation of all resonances observed is possible.
Opportunities to Utilize the USDA‐ARS Northern Great Plains Research Laboratory Soil Sample Archive

Archived soil samples are an important resource for quantifying changes in soil attributes over decadal time scales. Herein, we describe a soil archive at the USDA-ARS Northern Great Plains Research Laboratory (NGPRL) near Mandan, ND with the intent of encouraging research collaboration through utilization of the archive. Over 5000 samples are included in the NGPRL soil archive, ranging in age from 4 to 90 yr. Samples were derived from both grazing and cropping studies, with the former being conducted near Mandan, and the latter as a part of an evaluation of soil C and N change at multiple locations throughout the Great Plains. Most samples are associated with soil depths above 30.5 cm, although 10 locations from the Great Plains evaluation possess archived soils below 1 m for native vegetation treatments. Collaborative research opportunities using the NGPRL soil archive abound, and may include characterizations of soil organic matter fractions, micronutrients, and soil acidity. Scientists interested in engaging in collaborative research efforts are encouraged to contact the authors of this report.
Myocardial muscarinic acetylcholine receptor: choline and tris unmask heterogeneity of antagonist binding sites.

Abstract The binding properties of myocardial muscarinic acetylcholine receptors are altered in the presence of choline or Tris. The binding of the antagonist [ 3 H]quinuclidinyl benzilate is reduced in the presence of choline or Tris buffer, when compared to parallel determinations in a physiologic salt solution or phosphate buffer. Scatchard analysis indicates the reduced binding is due to a decrease in the apparent number of receptor sites. Experiments with other organic buffers exclude the possibility that the reduced binding in Tris is due to the absence of sodium ions. In the presence of choline or Tris up to 45% of the receptors are not accessible to [ 3 H]quinuclidinyl benzilate. The remaining sites maintain their high affinity for the antagonist. A heterogeneity of antagonist sites is evident.
Spectrum of the Intensity Variations in 3C 273B

The intensity variations in radio source 3C 273B have been measured at wavelengths of 31.3, 21.2, and 10.6 centimeters. At 31.3 centimeters the variation is quite small, indicating that the variable component of the source is optically thick at this wavelength. Study of several different model sources shows that the observed dependence of the intensity variations on frequency can best be explained by an increase of the electron density in a source region about 2 parsecs in diameter. This interpretation is consistent with the distance to 3C 273 determined from Hubble's law and the observed red shift.
Integrating the supply chain through Web-enabled CAx systems

The Internet and Web technology are transforming the way many manufacturing and engineering companies do business today. Much of the focus of 'e-business' has been on providing new ways of accessing existing markets, or accessing new markets through the Internet. For aerospace companies, however, these new technologies also offer an important and exciting means to improve the integration of the supply chain in the product development process. Leading Web based CAx viewing solutions such as CATweb provide a high level of functionality today and an attractive complement to existing means of extending CAx systems in the supply chain. Integrated access to CAD and other CAx data is enabled with relatively inexpensive and easy to use 'standard' desktop products, thus extending the reach of the data to many more users both within the company and the extended enterprise. By using the native data in a 'pull based' access mode, access to the current valid level of data is assured. Full function CAD systems will still be required, however, where users require full design capability on the data.
Experimental Studies on Argasid Ticks as Possible Vectors of Tularemia

birds which are known to be naturally infected with Past. tularensis (Burroughs et al, 1945) serve as hosts of argasid ticks, especially of the genus Ornithodoros. Kamil and Bilal (1938) reported transmission of Past. tularensis by experimentally infected Ornithodoros lahorensis. Davis (1940), in studies of ticks of the genus Ornithodoros as potential vectors of various infectious agents, found that Past. tularensis may persist in the tissues of 0. turicata and 0.
Optimum foil thickness of inductors conducting DC and non-sinusoidal periodic currents

This study presents a derivation of an expression for the optimum thickness of foil inductors operating under DC and AC non-sinusoidal periodic currents. The exact equation for the DC winding power loss and approximated equations for the AC winding power loss are used to determine the optimum thickness of the foil for the single-layer and multi-layer inductors, operating with multi-harmonic AC currents superimposed on the DC component. The design procedure for inductors with minimum winding power loss is presented for a pulsewidth-modulated DC–DC buck converter operating in discontinuous conduction mode (DCM). The comparison of the total winding power loss of the designed inductor with optimum foil thickness to the total winding power loss of the inductor with non-optimised round conductor is also given. The theoretical predictions have been verified by measurements of inductors with three different foil thicknesses.
Review and impacts of climate change uncertainties

Abstract This article examines the status of the scientific uncertainties in predicting and verifying global climate change that hinder aggressive policy making. More and better measurements and statistical techniques are needed to detect and confirm the existence of greenhouse-gas-induced climate change, which currently cannot be distinguished from natural climate variability in the historical record. Uncertainties about the amount and rate of change of greenhouse gas emissions also make prediction of the magnitude and timing of climate change difficult. Because of inadequacies in the knowledge and depiction of physical processes and limited computer technology, predictions from existing computer models vary widely, particularly on a regional basis, and are not accurate enough yet for use in policy decisions. The extent of all these uncertainties is such that moving beyond no-regrets measures such as conservation will take political courage and may be delayed until scientific uncertainties are reduced.