cssi/SciSciGPT-SciSciNet huggingface dataset:
CS-30PROTEIN KINASE CK2 IS IMPORTANT FOR THE FUNCTION OF GLIOBLASTOMA BRAIN TUMOR INITIATING CELLS

Casein kinase 2 (CK2) is an ubiquitously expressed serine/threonine kinase composed of two catalytic subunits (α and/or α') and two regulatory (β) subunits. The expression and kinase activity of protein kinase CK2 are elevated in many different cancers, including glioblastoma (GBM). Brain tumor initiating cells (BTICs) are a subset of cells that are tumorigenic and are considered to promote the resistance of GBM to current therapies. Previously our lab has reported that CK2 activity promotes prosurvival signaling in GBM; however, the role of CK2 in BTICs has not been examined. In this study, we found that the expression of CK2α was increased in CD133+ BTICs compared to CD133− cells from GBM xenografts. We found that GBM cells are sensitive to cell death caused by CX-4945, an ATP-competitive inhibitor of CK2. Inhibition of CK2 also reduced the frequency of CD133+ BTICs over the course of 7 days, indicating a role for CK2 in BTIC persistence and survival. Additionally, using an in vitro limiting dilution assay, we found that CX-4945 reduced neurosphere formation in bulk cells from GBM xenografts. On the other hand, inhibition of CK2 had no effect on the proliferation or neurosphere formation of normal murine neural precursor cells. We are currently investigating the mechanism of cell death and reduced neurosphere formation and have found a reduction in the constitutive activation of signal transduction pathways dysregulated in GBM including NF-kB and MAPK pathways. Due to the integration of CK2 in multiple signaling pathways important for BTIC survival, protein kinase CK2 is a promising target in GBM.
Derocheilocaris Typicus Pennak & Zinn (Mystacocarida) Revisited

[Derocheilocaris typicus Pennak & Zinn, 1943, est refigure et sa description originale corrigee. Dans une serie graduelle neuf stades sont etudies dont six sont des metanauplii, un est un juvenile et deux sont adultes. Les mâles completement developpes different des femelles par la structure des troisiemes et quatriemes appendices thoracoabdominaux et par la taille plus grande. Les D. remanei et D. typicus se ressemblent etroitement, encore que leurs plans de developpement soient tout a fait differents. Derocheilocaris typicus est maintenant connu de Miami, Floride, a Falmouth, Massachusetts, et est trouve dans des microclimats variant du subtropical a l'arctique., Derocheilocaris typicus Pennak & Zinn, 1943, est refigure et sa description originale corrigee. Dans une serie graduelle neuf stades sont etudies dont six sont des metanauplii, un est un juvenile et deux sont adultes. Les mâles completement developpes different des femelles par la structure des troisiemes et quatriemes appendices thoracoabdominaux et par la taille plus grande. Les D. remanei et D. typicus se ressemblent etroitement, encore que leurs plans de developpement soient tout a fait differents. Derocheilocaris typicus est maintenant connu de Miami, Floride, a Falmouth, Massachusetts, et est trouve dans des microclimats variant du subtropical a l'arctique.]
Regulation of T cells by mTOR: the known knowns and the known unknowns

Mammalian/mechanistic target of rapamycin (mTOR) is emerging as an important integrator of environmental cues critical for the regulation of T cell activation, differentiation, and function. Recent studies leveraging pharmacologic inhibition or T cell specific genetic deletion of signaling components in the mTOR pathway have provided important insights into the mechanisms involved, and have been informative in defining targets downstream of mTOR that promote immune regulation. However, these studies have also presented confusing and, at times, contradictory findings, highlighting the complexities involved in examining the mTOR pathway in distinct contexts. Here, we review current understanding of the roles of mTOR in T cell biology, highlighting emerging concepts and areas of investigation where the precise role of mTOR has yet to be fully discerned.
Steering law design for redundant single-gimbal control moment gyroscopes

Two steering laws are presented for single-gimbal control moment gyroscopes. An approach using the Moore-Penrose pseudoinverse with a nondirectional null-motion algorithm is shown by example to avoid internal singularities for unidirectional torque commands, for which existing algorithms fail. Because this is still a tangent-based approach, however, singularity avoidance cannot be guaranteed. The singularity robust inverse is introduced as an alternative to the pseudoinverse for computing torque-producing gimbal rates near singular states. This approach, coupled with the nondirectional null algorithm, is shown by example to provide better steering law performance by allowing torque errors to be produced in the vicinity of singular states.
Early Development of Prosocial Behavior: Current Perspectives

Prosocial behavior first appears in the second year of life. How can prosociality so early in life be explained? One possibility is that infants possess specialized cognitive and/or social capacities that drive its emergence. A second possibility is that prosocial behavior emerges out of infants’ shared activities and relationships with others. These possibilities have motivated a number of current explanatory efforts, with a focus on two complementary questions. First, what is evolutionarily prepared in the very young child and how does it give rise to prosocial behavior? Second, how do proximal mechanisms, including social experiences, contribute to the early development of prosociality? The papers in this special issue represent some of the most recent work on these questions. They highlight a diverse array of new methods and bring them to bear on the nature and development of early prosocial understanding and behavior.
Specific down-regulation of the alpha-bungarotoxin binding component on chick autonomic neurons by ciliary neuronotrophic factor

Chick ciliary ganglion neurons have a cholinergic membrane component that binds alpha-bungarotoxin with high affinity but has no known function. The component is different from the nicotinic ACh receptor on the neurons that mediates cholinergic transmission through the ganglion. Ciliary neuronotrophic factor (CNTF) has been shown to enhance the survival of ciliary ganglion neurons in cell culture and has been postulated to act as a target-derived trophic factor for the neurons in vivo. We show here that a factor indistinguishable from CNTF specifically down-regulates alpha-bungarotoxin binding sites on the neurons while increasing cell growth and the number of ACh receptors on the cells. Similar effects, though reduced in magnitude, are seen with chick sympathetic neurons. CNTF has no effect on the number of ACh receptors found on chick myotubes in culture. The down-regulation of alpha-bungarotoxin binding sites on neurons caused by CNTF occurs with a half-time of about 19 hr and is largely reversed within a 4 d period following CNTF removal. It is distinct from the down-regulation caused by cholinergic agonists. Nerve growth factor and fibroblast growth factor have no apparent effect on the number of alpha-bungarotoxin binding sites on the neurons, though fibroblast growth factor does stimulate neuronal growth. The results indicate that the effects of CNTF on the alpha-bungarotoxin binding component are both novel for a growth factor and specific, and they suggest a relationship between the component and the regulation of growth by the target tissue.
Enantiospecific Synthesis and Pharmacological Evaluation of a Series of Super-Potent, Conformationally Restricted 5-HT2A/2C Receptor Agonists

The affinity of ligands for either the 5-HT2A or 5-HT2C agonist binding site was enhanced by modification of the 2,5-oxygen substituents that are found in typical hallucinogenic amphetamines such as 4b (DOB). Restriction of the conformationally flexible 2,5-dimethoxy substituents into fused dihydrofuran rings generally resulted in increased potency relative to the parent 2,5-dimethoxy compounds. The pure enantiomers of these arylalkylamines were obtained by enantiospecific synthesis that involved acylation of the heterocyclic nucleus 7 with N-trifluoroacetyl-protected d- or l-alanyl chloride, followed by ketone reduction and N-deprotection. The enantiomers demonstrated modest stereoselectivity at the two receptors. Several general trends within these classes of new compounds were observed during their pharmacological investigation. For most pairs of optical isomers tested, the R-enantiomers of the compounds containing heterocycle 7 bound with only slightly higher affinity than their S-antipodes at the 5-H...
Hormone-independent ovarian influence on adhesion development

Abstract Objective: To determine which ovarian sex steroid(s), when removed from an intact organism, reduce(s) postoperative adhesion development. Design: Randomized, prospective, blinded study. Setting: University vivarium. Patient(s): One hundred twenty sexually mature female Sprague-Dawley rats, 226–250 g. Intervention(s): Day 0, sham ovariectomy or bilateral ovariectomy, accompanied by continuous-release sex steroid replacement of either no steroids (control), 17β-E 2 , natural P (P4), or combined E 2 /P4. Day 7, standardized cecal abrasion; day 14, necropsy with assessment of adhesion presence or absence. Main Outcome Measure(s): Adhesion formation. Result(s): Three rats died because of anesthesia or surgical complications, and 117 rats reached necropsy. The ovary-intact (sham) rats adhesion incidence was 60.9%; ovariectomized control rats, 20.8%; E 2 , 28.6%; P4, 33.3%; and combined E 2 /P4, 24.0%. Despite differing sex steroid replacement, two-tailed χ 2 testing with correction for multiple comparisons showed no statistical difference in adhesion incidence among the four ovariectomy groups. A statistically significant lower adhesion incidence was noted between the ovary-intact sham cohort and the collective ovariectomy groups and between the sham and ovariectomized control cohorts. Conclusion(s): Ovarian presence or absence at the time of surgical wounding, and not the 17β-E 2 or P milieu, modulates adhesion development. This implicates other ovarian factor(s) in postoperative adhesion development.
Contribution of the M1 Transmembrane Helix and Pre-M1 Region to Positive Allosteric Modulation and Gating of N-Methyl-D-Aspartate Receptors

N-methyl-d-aspartate (NMDA) receptors are glutamate-gated ion channels whose function is critical for normal excitatory synaptic transmission in the brain and whose dysfunction has been implicated in several neurologic conditions. NMDA receptor function is subject to extensive allosteric regulation both by endogenous compounds and by exogenous small molecules. Elucidating the structural determinants and mechanism of action by which allosteric regulators control gating will enhance our understanding of NMDA receptor activation and facilitate the development of novel therapeutics. Here, we investigated the structural determinants for (3-chlorophenyl)(6,7-dimethoxy-1-((4-methoxyphenoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone (CIQ), a GluN2C/2D-selective positive allosteric modulator. We show that CIQ does not bind to the amino-terminal domain of the NMDA receptor and does not share structural determinants with modulators acting at the agonist-binding domain dimer interface or ion channel pore. Rather, we identified critical determinants of CIQ modulation in the region near the first transmembrane helix of GluN2D, including in a putative pre-M1 cuff helix that may influence channel gating. We also show that mutations within the GluN2D pre-M1 region alter open probability of the NMDA receptor. These results suggest a novel site of action for potentiation of NMDA receptors by small molecules and implicate the pre-M1 region in NMDA receptor gating.
CS05-04 - Reconsidering the definitions of sexual disorders in DSM-V

The research of neurobiology and treatment of various disorders requires certain degree of homogeneity of the studied entities. In an ideal word, common etiology and/or pathogenesis would help to define homogenous entities. As our understanding of etiology and/or pathogenesis of mental disorders and diseases is lacking, we rely on various diagnostic systems to help us reach some degree of homogeneity. The diagnostic criteria of sexual dysfunction(s) in the DSM-IV are rather vague and imprecise. Interestingly, we are not even clear when a sexual problem becomes a sexual dysfunction. As the new versions of the diagnostic systems (e.g., DSM-V) are being prepared, the classification and definitions of sexual disorders/dysfunctions are being considered. The general classification issues that need to be and are addressed are specific duration of sexual dysfunctions, use of distress s a diagnostic criterion and quantification of severity and frequency. Strengthening and clarifying these three classification issues would probably help in defining more homogenous entities. The broader yet more specific issues to be considered are inclusions of new diagnostic entities (persistent genital arousal disorder in women; adjustment disorder with disturbed sexual functioning; coercive paraphilic disorder), possible removal or reclassification of some sexual dysfunctions (e.g., sexual aversion disorder - remove or reclassify as specific phobia); collapsing some entities into one (dyspareunia and vaginismus into genitor-pelvic pain/penetration disorder) changing the names of some dysfunctions (premature ejaculation to rapid ejaculation); and redefining some dysfunctions (e.g. sexual desire and subjective sexual arousal in women).
Human mesenchymal stem cells promote human osteoclast differentiation from CD34+ bone marrow hematopoietic progenitors.

Interactions between osteoclast progenitors and stromal cells derived from mesenchymal stem cells (MSCs) within the bone marrow are important for osteoclast differentiation. In vitro models of osteoclastogenesis are well established in animal species; however, such assays do not necessarily reflect human osteoclastogenesis. We sought to establish a reproducible coculture model of human osteoclastogenesis using highly purified human marrow-derived MSCs (hMSCs) and CD34+ hematopoietic stem cells (HSCs). After 3 weeks, coculture of hMSCs and HSCs resulted in an increase in hematopoietic cell number with formation of multinucleated osteoclast-like cells (Ocls). Coculture of hMSCs with HSCs, transduced with a retroviral vector that expresses enhanced green fluorescent protein, produced enhanced green fluorescent protein+ Ocls, further demonstrating that Ocls arise from HSCs. These Ocls express calcitonin and vitronectin receptors and tartrate-resistant acid phosphatase and possess the ability to resorb bone. O...
The Potential Implications of Web-Based Marketing Communications for Consumers’ Implicit and Explicit Brand Attitudes: A Call for Research

Two developments in the last two decades frame the importance of Web-based marketing communications for firms. First is the phenomenal growth of the Internet as a viable commerce and communication option and second is the clear shift in attitude research toward recognizing the pervasive role of automatic processes in almost all the social psychological processes. Therefore, this article discusses the potential implications of Web-based marketing communications for consumers' implicit and explicit attitudes. In doing so, first, this article reviews the emergence of research on implicit attitudes, distinguishes implicit attitudes from explicit attitudes, and discusses research on explicit and implicit attitudes relative to branding. Second, a brief discussion of marketing research on attitude is provided. Third, five empirically testable research propositions are developed and presented. Finally, given the potential implications for research and practice, the article concludes with a call for research. ©2010 Wiley Periodicals, Inc.
Effects of dietary energy density and feeding frequency on total daily energy intakes of recovering malnourished children.

To develop recommendations for the design of special foods for young children, we measured total daily energy consumption from semisolid food mixtures with energy densities of 1.67, 2.93, 4. 18, or 6.28 kJ/g (0.4, 0.7, 1.0, or 1.5 kcal/g) and that were fed ad libitum three, four, or five times per day to 18 fully weaned children from 6 to 18 mo of age who were recovering in the hospital from malnutrition. The diets were generally indis- tinguishable by sensory qualities, and were fed in a randomized sequence. The mean amounts consumed (g . kg body wt ' � d 1) were significantly less with successively greater energy density of the diet (P < 0.001). The total daily consumption was = 16% more when the number of meals was increased from three to four per day, with energy density controlled for (P < 0.001), and 7% more when the feeding frequency rose from four to five meals per day (P = 0.005). The total daily energy intakes (kJ . kg body wt ' � d i) increased significantly with the more concentrated diets (P < 0.001) and varied positively in relation to feeding frequency (P < 0.001). Approximately 15-20 mm were required per meal for the children to reach satiety. The total amount of time required to feed the children each day was related to the number of meals served (P < 0.001) and not to energy density. Implications for child feeding are discussed. Am J Clin Nutr 1995;62:13-8.
The temporal stability of electrodermal variables over a one-year period in patients with recent-onset schizophrenia and in normal subjects

Test-retest stability of electrodermal (EDA) variables indexing both general autonomic arousal (e.g., skin conductance level, number of nonspecific skin conductance responses) and attention to external stimuli (e.g., number of skin conductance orienting responses, electrodermal responder/nonresponder status) was assessed in 71 young, recent-onset schizophrenia patients and 36 demographically matched normal subjects. Significant stability over a 1-year period was found for both patients and normal subjects for most EDA variables and for responder/nonresponder status, with test-retest correlations generally being higher for normal subjects. The lower reliability for patients was not attributable to symptomatic fluctuations during the follow-up period and may reflect poorer arousal regulation among the patients. Among measures of responding to nontask stimuli, a simple count of the number of orienting responses occurring was more stable than was a traditional trials-to-habituation measure.
First Names and Crime: Does Unpopularity Spell Trouble?*

Objective. We investigate the relationship between first name popularity and juvenile delinquency to test the hypothesis that unpopular names are positively correlated with crime. Methods. To compare the names of juveniles in a state's population with the names of juveniles who received substantiated charges in that state's juvenile justice system, we construct a popularity name index. Regression analysis is used to examine the relationship among names, crime, and socioeconomic background of juveniles. Results. The distribution of first names in the state's population is different from the names of juvenile delinquents. Our results show that unpopular names are positively correlated with juvenile delinquency for both blacks and whites. Conclusions. Unpopular names are likely not the cause of crime but correlated with factors that increase the tendency toward juvenile delinquency, such as a disadvantaged home environment and residence in a county with low socioeconomic status.
Status of various sns diagnostic systems

The spallation neutron source (SNS) accelerator systems are ramping up to deliver a 1.0 GeV, 1.4 MW proton beam to a liquid mercury target for neutron scattering research. Enhancements or additions have been made to several instrument systems to support the ramp up in intensity, improve reliability, and/or add functionality. The beam current monitors now support increased rep rates, the Harp system now includes charge density calculations for the target, and a new system has been created to collect data for the beam accounting and present the data over the web and to the operator consoles. The majority of the SNS beam instruments are PC-based and their configuration files are now managed through the Oracle relational database. A new version for the wire scanner software was developed to add features to correlate the scan with beam loss, parking in the beam, and measuring the longitudinal beam current. This software is currently being tested. This paper also includes data from the selected instruments.
Cold War fictions : gender, anticommunism, and the reconfiguration of the post-war United States

At the height of the Cold War, films and books that focused on anticommunist themes used depictions of communism as a way to promote a certain understanding of the roles of men and women in the post-war United States. The end of World War Two caused a reconfiguration of American society, providing a context in which cultural productions, such as these anticommunist Cold War narratives, could provide competing interpretations for what this transformation of society meant for men and women's roles in the United States. These films and books collectively construct an ideology that idolized the family as the most important unit of American life. At the same time, they condemned men who focused on work life instead of the family, in particular expressing the view that modern society turns men in conformists and effeminizes them. In the case of women, these narratives praised strong women who were wives, but stigmatized unmarried women who showed independence. This response to the changes in post-war America was one of a range of responses, but an important one. By exploring the relationship between anticommunism and a critique of gender, we better understand the nature of the Cold War, and how it was focused not only on political battles but also cultural ones concerning gender roles.
Dust in Galaxies

The past decade has heralded a revolution in our understanding of dust in galaxies due largely to the extraordinary success of the Infrared Astronomical Satellite (IRAS). The satellite, launched in 1983, surveyed 96% of the sky yielding continuum flux measurements at 12, 25, 60 and 100μm for literally thousands of galaxies (Cataloged Galaxies & Quasars in the IRAS Survey 1985). Complimentary 60, 100 and 160μm observations have also been obtained for a limited number of galaxies with the Kuiper Airborne Observatory (KAO). The past decade has also witnessed a dramatic development in the field of submillimeter astronomy with the commissioning of several new submillimeter telescopes including the JCMT, CSO, IRAM and SEST, all of which have yielded new results on the 300 to 1300μm continuum emission from galaxies. The goal of this review is to discuss the new observations within the context of the origin of the far infrared luminosity, the temperature of dust in galaxies and the implications of the new data for the opacity of spiral galaxy disks.
Abstract A66: KRas-mediated modulation of the immune response in pancreatic neoplasia.

It is becoming increasingly clear that stromal responses elicited by early-stage neoplastic lesions can promote tumor progression towards a more invasive and potentially metastatic state. However, the molecular mechanisms that underlie the early recruitment of stroma, and in particular immune cells, to sites of neoplasia remain poorly understood. To address this question in the context of pancreatic adenocarcinoma, we make use of orthotopic pancreatic grafts of primary murine pancreatic ductal epithelial cells (PDEC) harboring oncogenic KRas (KRasG12D). We find that engrafted KRasG12D-expressing PDEC can elicit a significant immunological response. The nature and composition of immune infiltrates was assessed using FACS sorting as well as immunohistochemical techniques and was directly compared to those derived from p48Cre;LSL-KRasG12D mice. Our observations to date indicate that the expression of KRasG12D promotes the recruitment of immunosuppressive leukocytes in the absence of a notable increase in the cytotoxic T cell population. These results support the hypothesis that effective tumor immunity mediated by an adaptive T cell response is actively suppressed at the very early stage of pancreatic neoplasia. We are currently investigating the molecular mechanisms by which oncogenic KRas modulates the intratumoral immune response. Citation Format: Yuliya Pylayeva-Gupta, Kyoung Eun Lee, George Miller, Dafna Bar-Sagi. KRas-mediated modulation of the immune response in pancreatic neoplasia. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr A66.
Epidemiological analysis of rabies in Huanggang City(2005-2010)

Objective To understand the epidemiological characteristics,trends and influencing factors of rabies during the period of six years in Huanggang city,so as to provide suggestions for the prevention and control of rabies. Methods All rabies cases in Huanggang city from 2005-2010 were analyzed by descriptive epidemiology. Results 130 cases have been reported in Huanggang city since 2005.The average annual incidence was 0.316/105 and the case fatality was 100%.The cases were distributed in all the counties of Huanggang city,while the majority was in Huangmei,Qichun and Macheng,69 patients were reported(53.08%).Most patients were in the 40～70-year-old group,accounted for 60.77 percent of the total number of incidence.Farmers were the high risk population,accounting for 71.54% of the total.Most cases were hurt by dogs.After exposure,most patients(78.37%) did not receive any treatment,or just handled simply by themselves;75.68% of the patients did not receive vaccination or anti-serum injection.Conclusions Although the incidence of rabies of Huanggang has declined in recent years,the case fatality of rabies was still as high as 100%.Therefore,it is vital to strengthen the control and prevention of rabies,especially in rural areas.
High e+/e− Ratio Dense Pair Creation with 1021W.cm−2 Laser Irradiating Solid Targets

We report results of new pair creation experiments using ~100 Joule pulses of the Texas Petawatt Laser to irradiate solid gold and platinum targets, with intensities up to ~1.9 × 1021 W.cm−2 and pulse durations as short as ~130 fs. Positron to electron (e+/e−) ratios >15% were observed for many thick disk and rod targets, with the highest e+/e− ratio reaching ~50% for a Pt rod. The inferred pair yield was ~ few ×1010 with emerging pair density reaching ~1015/cm3 so that the pair skin depth becomes < pair jet transverse size. These results represent major milestones towards the goal of creating a significant quantity of dense pair-dominated plasmas with e+/e− approaching 100% and pair skin depth ≪ pair plasma size, which will have wide-ranging applications to astrophysics and fundamental physics.
Aural rehabilitation in noise induced hearing loss

The patient with noise induced hearing loss presents complex aural rehabilitative problems. Such patients are not generally good candidates for "traditional" aural rehabilitation involving speech reading therapy and auditory training. Instead aural rehabilitation efforts involve individual evaluation of the communication handicap, non-medical relief for tinnitus, possible hearing aid use with carefully selected amplification and earmold, and counseling on hearing and listening.
Reasons and Emotions

This chapter outlines the importance of reasons-giving in, and for, Ethical Counselling. By reason-giving, we refer to that particular dialogical process whereby an agent comes to identify, articulate and appraise the various moral reasons structuring an ethical dilemma. In particular, within this chapter, we describe (i) the role of emotions with respect to reason-giving; (ii) why we should rely on reason-giving; (iii) how reason-giving enables to make explicit patients’ Personal Philosophy; and (iv) why reason-giving is always an open-ended process.
The Stimulus of War

The passion for war news was a leading feature of the 1850s and 1860s, and it further transformed the nature of transatlantic journalism. War correspondents (“specials”) dominated these decades, with military news taking precedence over more commonplace kinds of information. In the United States the Civil War marked a decisive turning point in the history of journalism. It propelled the American press into new areas, including the regular use of wired news, the beginnings of the front-page news spread and the introduction of the inverted pyramid. At the same time, war correspondents injected an aura of romance into the “sensational” side of journalism, in a seeming challenge to the increased tendency towards “objective” press writing. These twin poles of diversity and sameness were to become complementary integuments of journalism in both Britain and America during these crucial years of transition.
A novel approach to detect localized muscle fatigue during isometric exercises

The purpose of this study is to develop a localized muscle fatigue detection system to assist patients during isometric exercise. A mobile device is fastened to the forehand of the subject to receive electromyography (EMG) signals sent wirelessly from BITalino board. Our proposed system then uses surface electromyography (sEMG) technique to capture electromyography (EMG) signals that are processed in time-frequency domain using short-term Fourier transform. The vibration speed received through accelerometer sensor caused by the muscle fatigue at biceps brachii of a subject is calculated in parallel. The downward shift in Median Frequency and increase in vibration speed are taken as parameters to determine the localized muscle fatigue. Results indicate that localized muscle fatigue can be observed effectively with these two parameters combined together.
Imaginary Vantage Points: The Invisible Hand and the Rise of Political Economy

In eighteenth-century British aesthetics, landscape painting came to embody a set of important social values, serving among other things as catalogue of country house styles, elegy for lost civilizations, and creator of the cult of unspoiled Nature. But as John Barrell has argued, the ideal of visibility, of viewing a whole landscape scene at once from a distant location, also implies a certain class position. Especially at the beginning of the century, gentlemen of landed property justified their political power as magistrates through their disinterested ability to view their whole society from a distance. Any ‘specific profession, trade, or occupation’, it was presumed, ‘might occlude [the gentleman’s] view of society as a whole’. To take part in society, then, is to be partially blind to its workings, according to much eighteenth-century social philosophy.1 This paradox troubled Adam Smith in The Wealth of Nations particularly in regards to the role of philosophy itself. On the one hand he boasts of the philosopher’s leisure to survey his society: ‘These varied occupations present an almost infinite variety of objects to the contemplation of those few, who, being attached to no particular occupation themselves, have leisure and inclination to examine the occupations of other people. The contemplation of so great a variety of objects necessarily exercises their minds … and renders their understandings, in an extraordinary degree, both acute and comprehensive’ (WN II, 783). On the other hand, since philosophy is not labour, it produces no value and must be considered economically ‘unproductive’ along with the work of ‘churchmen’ and ‘opera-singers’ (WN I, 331).
Emerging Epigenetic Therapies in Neuroscience: Focus on Bromodomain-Containing Drug Targets

Emerging Epigenetic Therapies in Neuroscience: Focus on Bromodomain-Containing Drug Targets
Point Mutation and Alternative Splicing in the ABL Kinase Domain as a Mechanism for Imatinib Resistance.

Missense point mutations in the region encoding the ABL tyrosine kinase domain have been reported in approximately 35% of patients with imatinib-resistant chronic myeloid leukemia (CML). The reported mutations result in reactivation of the BCR-ABL tyrosine kinase. Screening patients with imatinib-resistant CML, we identified 42 different mutations in the ABL tyrosine kinase domain-encoding region, 2 of which were silent (no amino acid change): A864G and G909A. The A864G mutation was associated with a 54-nucleotide reduction in the length of the mRNA transcript, representing a loss of nucleotides 1089-1143; the G909A mutation was associated with a normal-length transcript. The nt1089-1143 transcript deletion represents a partial exon deletion in which the first half of exon 8 is skipped, suggesting that A864G leads to abnormal splicing. Splicing is regulated by 6- to 8-nucleotide exonic splicing enhancer (ESE) and exonic splicing silencer (ESS) motifs recognized by the SR proteins (a family of splicing factors). We therefore used ESEfinder to examine whether A864G or G909A alter ESE motifs, which could block the ability of SR proteins to recognize and bind. This search showed that A864G is at the 7 th position of an AGCTGCAG ESE motif, a binding site for SR35, and is within 35 bp of the intron-exon junction. In total, ESEfinder predicted 18 putative SR35-binding ESEs within 50 bp of the intron-exon junction, covering 20% of the kinase domain. The AGCTGCAG motif is conserved in primates (chimpanzees and monkeys) but not in rodents, while A864G is found in mice Although similar links cannot be made with the G909A mutation, these data suggest that imatinib resistance may develop in some patients through alternative splicing and the expression of a truncated (or potentially elongated) protein.
The Neuropsychology of Perceptual Category Learning

Abstract There is widespread agreement that multiple qualitatively different category learning systems mediate the learning of different category structures. Two systems that have received support are a frontal-based explicit system that uses logical reasoning, depends on working memory and executive attention, and is mediated primarily by the anterior cingulate, the prefrontal cortex and the associative striatum, including the head of the caudate. The second is a basal ganglia-mediated implicit system that uses procedural learning, requires a dopamine reward signal and is mediated primarily by the sensorimotor striatum (i.e., the tail of the caudate and putamen). This chapter reviews a large body of work conducted in our laboratory and others that examines the details of the two proposed systems using neurological patients as experimental participants. Collectively the studies suggest significant involvement of the striatum and less involvement of the medial temporal lobes in category learning. They also suggest that, in striatal-damaged patients, the need to ignore irrelevant information is predictive of a rule-based category learning deficit, whereas the complexity of the rule is predictive of an information-integration category learning deficit.
Towards understanding hikers' technology preferences

Many people enjoy hiking as an outdoor escape from everyday life. However, in our survey of 1002 respondants in the United States, 95% of respondents indicate that they prefer to bring their cell phone when hiking. This potentially creates distractions by reminding hikers of the daily pressures they sought to escape. We believe technology has the ability to enable or enhance outdoor activities, such as hiking, without taking away from the experience. But to begin to realize this vision we must first understand current attitudes towards technology in the outdoors. We present data from a nationwide survey conducted within the United States. We have used this data to identify clusters around attitudes towards hiking and technology use while hiking. We present initial results and analysis of this data as well as direction for future work.
Teaching the Core Concepts of Physiology: What, Why, and How

In a new book, Joel Michael and colleagues argue that we can teach physiology better by infusing our curricula with specific core concepts developed and refined in faculty workshops and surveys. Af...
Emotional Appeals and Moral Standards: Rhetorical Arguments in Court Cases

In this article, I analyze 73 circuit court opinions in which due process rights are weighed according to a little-known legal test called shocks the conscience. I also offer my observations of a f...
Implementation of an Opioid Detoxification Management Pathway Reduces Emergency Department Length of Stay.

OBJECTIVES With the rise of opioid use in the United States, the increasing demand for treatment for opioid use disorders presents both a challenge and an opportunity to develop new care pathways for emergency department (ED) patients seeking opioid detoxification. We set out to improve the care of patients presenting to our ED seeking opioid detoxification by implementing a standardized management pathway and to measure the effects of this intervention. METHODS We conducted a before-after study of the effects of an opioid detoxification management pathway on ED length of stay (EDLOS), use of resources (social worker consultation, laboratory tests obtained), and return visits to the same ED within 30 days of discharge. All data were collected retrospectively by review of the electronic health record. RESULTS Ultimately, 107 patients presented to the ED that met criteria, 52 in the intervention period and 55 in the preintervention period. Median EDLOS in the intervention period was 152 (interquartile range [IQR] = 93-237) minutes compared to 312 (IQR = 187-468) minutes in the preintervention period (p < 0.001). Patients in the intervention period less frequently had a social work consultation (32.7% vs. 83.6%, p < 0.001) or had laboratory tests obtained (32.7% vs 74.5%, p < 0.001) and more frequently were prescribed a medication for withdrawal symptoms (57.7% vs. 29.1%, p = 0.003). CONCLUSIONS Implementation of an opioid detoxification management pathway reduced EDLOS, reduced utilization of resources, and increased the proportion of patients prescribed medications for symptom relief.
The Role of Interracial Interaction in the Development of Leadership Skills and Cultural Knowledge and Understanding

While higher education leaders tout the benefits of racial diversity for developing culturally knowledgeable civic leaders, our understanding of these benefits and, in particular, the role of interracial interaction in realizing them, is still emerging. In this study, differences between the effects of interracial contact among students that are close friends versus more casual interracial interactions are examined for their affect on students' leadership skills and cultural knowledge and understanding. Findings suggest that casual interracial interaction is particularly beneficial among students with more racially homogeneous friendship circles, especially with regard to developing leadership skills. In addition, findings indicate that frequent interracial interaction among students may be more important in developing cultural knowledge than involvement in formal activities such as cultural awareness workshops.
Photolithographic Patterning and Doping of Silica Xerogel Films

This study shows that conventional photolithography can be applied for patterning native or organic dye-doped silica films (∼0.5 μm thick) obtained via a base-catalyzed sol-gel process. Photoresist was spin-coated onto high optical quality xerogel films, soft-baked, exposed to UV irradiation through a photomask, and developed with a commercial photoresist developing solution. Etching away of the photoresist-unprotected areas of the silica films was carried out with a dilute HF solution, while the remaining unexposed photoresist was removed with acetone. Interdigitated array patterns with features as small as 0.5 mm show a smooth surface and extremely sharp interfaces. Densification of the films at 550°C for 2 h decreases the film thickness by ∼11%, increases the refractive index from 1.420 to 1.456, and allows for well-defined patterning down to length scales of 10 μm. Since the densification conditions are incompatible with organic dopants, it is demonstrated that sol-gel films can be doped after pattering (post-doping) by adsorption of cationic dyes from solution. Scanning electron microscopy reveals that the microstructure of patterned sol-gel films is similar to that of bulk monoliths, indicating that the photolithographic procedure is not harmful to the film quality. All patterned films demonstrate highly regular light diffraction patterns.
Critical Investments: AIDS, Christopher Reeve, and Queer/Disability Studies

In his contribution, “Critical Investments: AIDS, Christopher Reeve, and Queer/Disability Studies,” Robert McRuer calls for the recognition of the points of convergence between AIDS theory, queer theory, and disability theory. McRuer points out ways in which minority identity groups such as people with AIDS, gays, lesbians, and bisexuals, and those with so-called disabilities, whose status has been described by others as “impaired,” have resisted this judgment by calling its ideological underpinnings into question. He contends that a critical alliance between AIDS theory, queer theory, and disability theory will ultimately help us to realize the full range of different kinds of bodies and corporeal experiences, while also combating the application of normativizing judgments.
"Why Me?" Understanding the HCV Care Continuum Among People With Serious Mental Illness.

Objective:Despite possible cure rates of >90% with new treatment, people with serious mental illness are rarely screened for hepatitis C virus (HCV). A colocated approach may help patients navigate...
Neurobehavioral symptom validity and performance validity in veterans: Evidence for distinct outcomes across data types.

Self-reported traumatic brain injury (TBI) is common in combat veterans, and identification of psychiatric and neuropsychological consequences following TBI has become a priority for veteran health...
Simple analytic model for optimally sizing thermoelectric generator module arrays for waste heat recovery

Abstract Thermoelectric generators (TEGs) are commonly used in waste heat recovery (WHR) applications. Counter-intuitively, recent studies have demonstrated that there is an optimal number of TEG modules to use in a WHR system for maximum power output. General rules for identifying this limit have not yet been proposed. In this study, a simple analytic model is derived to describe WHR systems, and predict the optimal TEG module array size. This model incorporates a new thermal-fluid figure of merit ( H T ), which accounts for coupled effects of TEG module thermal conductance, heat exchanger performances, and coupling fluid stream thermal capacity rates. The model is experimentally validated with data from a small-scale test facility. The model is used to predict performance trends of (1) TEG arrays with varying module counts at low and high fluid thermal capacity rates, (2) TEG arrays with fixed overall heat exchanger conductances (UAs) and UAs proportional to module-count, and (3) multi-row TEG arrays. Guidelines for selecting optimal numbers of TEG modules are recommended for these cases. The application of this model is illustrated through analysis of a vehicle WHR system. This analytic model can guide preliminary WHR system designs, which can be refined with sophisticated computational and experimental approaches.
Dietary weight loss in insulin-resistant non-obese humans: Metabolic benefits and relationship to adipose cell size.

Abstract Background and Aims Overweight and obesity increase risk for diabetes and cardiovascular disease, largely through development of insulin resistance. Benefits of dietary weight loss are documented for obese individuals with insulin resistance. Similar benefits have not been shown in overweight individuals. We sought to quantify whether dietary weight loss improves metabolic risk profile in overweight insulin-resistant individuals, and evaluated potential mediators between weight loss and metabolic response. Methods and Results Healthy volunteers with BMI 25–29.9 kg/m2 underwent detailed metabolic phenotyping including insulin-mediated-glucose disposal, fasting/daylong glucose, insulin, triglycerides, FFA, and cholesterol. Subcutaneous fat biopsies were performed for measurement of adipose cell size. After 14 weeks of hypocaloric diet and 2 weeks of weight maintenance, cardiometabolic measures and biopsies were repeated. Changes in weight, % body fat, waist circumference, adipose cell size and FFA were evaluated as predictors of change in insulin resistance. Weight loss (4.3 kg) yielded significant improvements in insulin resistance and all cardiovascular risk markers except glucose, HDL-C, and LDL-C. Improvement in insulin sensitivity was greater among those with 2 cardiovascular risk factors at baseline. Decrease in adipose cell size and waist circumference, but not weight or body fat, independently predicted improvement in insulin resistance. Conclusions Weight loss yields metabolic health benefits in insulin-resistant overweight adults, even in the absence of classic cardiovascular risk factors. Weight loss-related improvement in insulin sensitivity may be mediated through changes in adipose cell size and/or central distribution of body fat. The insulin-resistant subgroup of overweight individuals should be identified and targeted for dietary weight loss. Clinical trials identifier NCT00186459.
Incidence of Traumatic Brain Injury in the U.S. Military, 2010-2014.

INTRODUCTION Traumatic brain injury (TBI) is a significant health issue that affects U.S. military service members (SM) at home and in combat deployments. We estimated the TBI incidence rate in the deployed and non-deployed setting between 2010 and 2014 and identified subgroups with elevated rates for prevention efforts. METHODS Retrospective population-based study of all active duty U.S. military SM that sustained a first active duty TBI diagnosis between January 2010 and December 2014 collected and analyzed in 2017. Using Armed Forces Health Surveillance Branch data we calculated the Mantel-Haenszel (MH) standardized TBI incidence rate in the deployed and non-deployed setting, adjusting for service and demographic factors. RESULTS From 2010 to 2014, the MH standardized incidence rate for deployed SMs was 3,265 TBIs per 100 thousand p-yrs (95% CI: 3,222-3,307) and 1,705.2 (95% CI: 1,694.0-1,716.5) for non-deployed SMs. The youngest deployed male Army soldiers, those ages 17-24, especially White and Hispanic soldiers, had the highest TBI incidence rate (IR) of 5,748.7 (95% CI: 5,585.8-5,916.4) and 5,010.3 (95% CI: 4,647.5-5,401.4), respectively. The IR for all branches was 1,972.6 (95% CI: 1,959.5-1,985.7) and 724.0 (95% CI: 714.9-733.0) for Reserve/Guard Service members. CONCLUSIONS Across all years, Marines and Army Soldiers experience the highest rates of injury with deployed SMs having elevated IRs of TBI. The TBI IR among deployed SMs was 91% higher than among those in the non-deployed setting, due to continued exposures to combat. Deployed Reserve/Guard component SMs seem to have an above average rate, a finding with implications for training and prevention.