cssi/SciSciGPT-SciSciNet huggingface dataset:
EWS/FLI is a Master Regulator of Metabolic Reprogramming in Ewing Sarcoma

Ewing sarcoma is a bone malignancy driven by a translocation event resulting in the fusion protein EWS/FLI1 (EF). EF functions as an aberrant and oncogenic transcription factor that misregulates the expression of thousands of genes. Previous work has focused principally on determining important transcriptional targets of EF, as well as characterizing important regulatory partnerships in EF-dependent transcriptional programs. Less is known, however, about EF-dependent metabolic changes or their role in Ewing sarcoma biology. Therefore, the metabolic effects of silencing EF in Ewing sarcoma cells were determined. Metabolomic analyses revealed distinct separation of metabolic profiles in EF-knockdown versus control-knockdown cells. Mitochondrial stress tests demonstrated that knockdown of EF increased respiratory as well as glycolytic functions. Enzymes and metabolites in several metabolic pathways were altered, including de novo serine synthesis and elements of one-carbon metabolism. Furthermore, phosphoglycerate dehydrogenase (PHGDH) was found to be highly expressed in Ewing sarcoma and correlated with worse patient survival. PHGDH knockdown or pharmacologic inhibition in vitro caused impaired proliferation and cell death. Interestingly, PHGDH modulation also led to elevated histone expression and methylation. These studies demonstrate that the translocation-derived fusion protein EF is a master regulator of metabolic reprogramming in Ewing sarcoma, diverting metabolites toward biosynthesis. As such, these data suggest that the metabolic aberrations induced by EF are important contributors to the oncogenic biology of these tumors.Implications: This previously unexplored role of EWS/FLI1-driven metabolic changes expands the understanding of Ewing sarcoma biology, and has potential to significantly inform development of therapeutic strategies. Mol Cancer Res; 15(11); 1517-30. ©2017 AACR.
The Interpretation of Classical Physics

In introducing a new non-classical physics Einstein and Bohr indirectly specified the limits of classical physics. Einstein’s special relativity put constraints on all the laws of physics, giving these laws a functional unification. Bohr effectively resolved the contradictions physicists were encountering through semantic guidelines limiting the use of classical terms in quantum contexts. This is systematized as Bohrian semantics. To accommodate the interrelation of theoretical deductive inferences and informal experimental inferences we develop a dual inference system.
Effect of medicinal botanicals in breast cancer cell lines with different estrogen receptor expression

5786 Several traditional Chinese medicines (TCM) are used to stimulate the immune system, in order to maintain health and as an adjuvant to chemotherapy. Previous work has shown that certain medicinal botanicals traditionally used for gynecological complaints have estrogenic properties, likely because of phytoestrogen content. The aims of this study were to examine if certain TCM herbs altered proliferation in breast cancer cells that are estrogen receptor (ER)-positive but differ in the expression of ERα and ERβ, and if these herbs altered cellular response to estradiol (E2). The cell lines MCF-7 (60:40 ERα:ERβ) and T47D (33:67 ERα:ERβ) were treated with various dilutions of standard extracts of dang gui (DG, angelica), ling zhi (LZ, reishi mushroom), gang cao (GC, licorice), he show wu (HSW, fo-ti), huang qi (HQ, astragalus) in the presence or absence of E2 (1nm). Controls were E2 treatment only and no treatment. After 72 hours, proliferation index was determined via a standard assay; values for herbal treatments were compared to those of controls. The two cell lines differed in response to E2, in that MCF-7 responded more strongly to E2 than did T47D (1.99 vs. 1.70). The most noteworthy difference between these two cell lines was seen in their responses to HSW, LZ, and DG. MCF-7 either had no response (HSW) or a slight response (DG and LZ) to these herbal extracts. T47D, on the other hand, exhibited a dose-related increase in proliferation at higher doses of HSW, LZ and DG, with DG and LZ exceeding the E2 control levels. This differential response was also seen when both cell lines were treated with these herbs along with E2. In MCF-7, E2 tended to mask the effects, if any, of these herbs. In contrast, in T47D cells, addition of E2 to both LZ and DG produced an additive effect, with proliferation index exceeding E2 levels at the higher doses. HSW with E2 in T47D cells had no effect on E2-induced proliferation. HQ alone was biphasic in both cell lines, with proliferative effects at highest doses reaching E2 control levels in MCF-7 and exceeding E2 control values in T47D. HQ with E2 had no effect on the E2-induced proliferation in MCF-7; however, in T47D cells, it maintained a biphasic response with enhancement of proliferation at higher doses. GC alone exhibited a proliferative effect equivalent to that of the E2 control in MCF-7; in T47D, GC produced a strong dose response exceeding that of the E2 control. These responses did not change with the addition of E2 to GC for both cell lines.These results indicate that TCM herbs used for immune system support may be estrogenic, and that the response differs depending on the cell line and the presence or absence of E2. In general, T47D cells are better responders to these herbs, most likely because of their higher content of ERβ, which has a higher affinity than ERα for phytoestrogens. The estrogenicity of these herbal preparations should be taken into account by those who want to reduce their estrogen exposure.
Complex arterial patterning in an anatomical donor

Abstract Case reports of individuals with a single variant or a limited number of localized variants are plentiful; however, systematic, whole-body study of cerebral, axial, and peripheral arterial variants in a single anatomical donor is lacking. This case report describes widespread arterial variants in a single donor. We report several remarkable variants in this case and then, discuss these finding with regards to clinical relevance, prior vascular variant studies and embryologic development. Additionally, combined probability calculations reveal that the probability of possessing this constellation of arterial variants, by chance, is 0.0001. Given this low probability, we hypothesize that our donor had a propensity for developing arterial variants and further, that the presence of multiple variants is related to disruption in vascular developmental pathways during the embryonic period. Such information has direct clinical relevance, particularly during invasive diagnostic and surgical procedures.
Powers, causation, and modality

A complex theory concerning powers, natures, and causal necessity has emerged from the writings of P. H. Hare, E. H. Madden, and R. Harre. In the course of rebutting objections that other critics have raised to the power account of causation, I correct three of its genuine difficulties: its attempt to analyze power attributions in terms of conditional statements; its characterization of the relation between something's powers and its nature; and its doctrines concerning conceptual necessity. The resulting interpretation of causal modalities is then subsumed under a more general power account of modality, related at a number of points to considerations concerning powers, and further illustrating their philosophical importance.
A Woman with Slurred Speech and Thrombocytopenia

An 18-year-old woman presented in emergency department with fever, headache, and progressively slurred speech. She was in good health until 3 days before admission. Blood counts showed hemoglobin of 8.8 g/dl, WBC 7.1 × 109/l, and platelet count of 11 × 109/l. Blood film showed numerous red cell fragments and spherocytes.
Using Social Network Analysis to Identify Systems of Systems in a Network of Systems

This paper presents findings from applying social network analysis tools and techniques to a network of Department of Defense (DoD) systems. The network of systems includes 349 systems that serve as the nodes in the networks and the edges represent shared operational activities. This method captures the versatility of these systems as it identifies systems that can perform the same function for the DoD. Additionally, the visualization of the network enables the identification of potential systems of systems that emerge from the larger network of systems. These systems of systems cluster together around the edge of the overall network and include a logistics, electronic warfare, and force protection system of system. Like most system of systems, these potential groups of system of systems are composed of independent systems, demonstrate emergent behavior, are managed by different services, and interoperate to provide value to the DoD stakeholders. Additionally, these system of systems demonstrate the characteristics of systems of systems from the literature. It appears that applying social network analysis visualization techniques could assist systems engineers in the identification of systems of systems.
The Market Scene: Physical Interaction with Multiple Agents

This demonstration presents "The Market Scene," a virtual-reality scene in which the user interacts with multiple virtual agents and initiates conversations with these agents via proxemics and gaze. The application is implemented in Unity with the VAIF authoring tool for rapid development of social agents. In the Market Scene, the user learns the background of the "Gods of the Neon City" adventure story through interaction in a crowded market rather than by listening to a narrator. The application demonstrates a form of mixed-initiative interaction, in that the user can initiate a conversation by coming near to and gazing at an agent, and an agent can initiate a conversation if a user approaches.
Formation processes for large ejecta and interactions with melt pool formation in powder bed fusion additive manufacturing.

Ejecta with a size much larger than the mean particle size of feedstock powder have been observed in powder bed fusion additive manufacturing, both during post-process sieving and embedded within built components. However, their origin has not been adequately explained. Here, we test a hypothesis on the origin of large (much larger than the mass-median-diameter of feedstock powder) ejecta—that, in part, they result from stochastic, inelastic collisions of ejecta and coalescence of partially-sintered agglomerates. The hypothesis is tested using direct observation of ejecta behavior, via high-speed imaging, to identify interactions between ejecta and consequences on melt pool formation. We show that stochastic collisions occur both between particles which are nearly-simultaneously expelled from the laser interaction zone and between particles ejected from distant locations. Ejecta are also shown to perturb melt pool geometry, which is argued to be a potential cause of lack-of-fusion flaws.
A Feasibility Study of a School-Based Social Emotional Learning Program: Informing Program Development and Evaluation

The Peace Program is a school-based social emotional learning program. Despite increased efforts to develop, implement, and evaluate school-based SEL programs in the past few decades, the short- and long-term effectiveness of such programs remains unclear. Considering the previously identified gaps that may contribute to modest effect sizes and erosion of initial effects over time, we conducted a feasibility study to better understand adoption and implementation of a local SEL program in order to inform future program design, delivery, and evaluation. Using mixed-methods, feasibility indicators: program acceptability, facilitator competence, and students’ social–emotional outcomes were examined. Qualitative data were analyzed using thematic analysis. Outcome analyses were conducted on facilitator competence measures and student outcomes using mixed-model repeated measures analysis of variance. Qualitative results indicated acceptance for the Peace Program. Facilitators demonstrated competence, with no difference across grade, classroom, or schools. Significant interactions effects were found for students’ aggression, concentration/attention, and emotional competence. School-level associations were found for students’ concentration/attention. Implications of results and future directions are discussed, including the critical role of teachers and social workers in promoting SEL among socioeconomically disadvantaged children; the impact on SEL programming on children in early elementary grades; and the potential effects of school climate and culture.
GDGT cyclization proteins identify the dominant archaeal sources of tetraether lipids in the ocean

Glycerol dibiphytanyl glycerol tetraethers (GDGTs) are distinctive archaeal membrane-spanning lipids with up to eight cyclopentane rings and/or one cyclohexane ring. The number of rings added to the GDGT core structure can vary as a function of environmental conditions, such as changes in growth temperature. This physiological response enables cyclic GDGTs preserved in sediments to be employed as proxies for reconstructing past global and regional temperatures and to provide fundamental insights into ancient climate variability. Yet, confidence in GDGT-based paleotemperature proxies is hindered by uncertainty concerning the archaeal communities contributing to GDGT pools in modern environments and ambiguity in the environmental and physiological factors that affect GDGT cyclization in extant archaea. To properly constrain these uncertainties, a comprehensive understanding of GDGT biosynthesis is required. Here, we identify 2 GDGT ring synthases, GrsA and GrsB, essential for GDGT ring formation in Sulfolobus acidocaldarius. Both proteins are radical S-adenosylmethionine proteins, indicating that GDGT cyclization occurs through a free radical mechanism. In addition, we demonstrate that GrsA introduces rings specifically at the C-7 position of the core GDGT lipid, while GrsB cyclizes at the C-3 position, suggesting that cyclization patterns are differentially controlled by 2 separate enzymes and potentially influenced by distinct environmental factors. Finally, phylogenetic analyses of the Grs proteins reveal that marine Thaumarchaeota, and not Euryarchaeota, are the dominant source of cyclized GDGTs in open ocean settings, addressing a major source of uncertainty in GDGT-based paleotemperature proxy applications.
Fitness-To-Drive Screening (FTDS) Measure©: Clinical Utility for OTs Identifying At-Risk Older Drivers

OTs are well positioned to support older drivers (65+) with determining their fitness to drive but are in need of an evidence-informed method to identify at-risk older drivers. This presentation will discuss 10 years of research and development of the Fitness-to-Drive Screening Measure (FTDS) for identifying at-risk older drivers. The FTDS may aid OTs with initial fitness-to-drive decisions and in determining an older driver’s risk probability. Primary Author and Speaker: Shabnam Medhizadah Additional Authors and Speakers: Sherrilene Classen, Sandra Winter
Partial purification and characterization of oestrogen receptors in subfractions of hepatocyte plasma membranes

To assess the subcellular distribution of oestrogen-binding components in their native state, plasma membrane and other cell fractions were prepared from hepatocytes in the absence of [3H]oestradiol-17β. Cells from livers of ovariectomized rats were disrupted, with submaximal homogenization in buffered isotonic sucrose with CaCl2 and proteinase inhibitor, and fractionated by using isotonic media. Fractions were characterized by determinations of enzyme activities, biochemical constituents and ligand binding. Specific binding of 2nm-[3H]oestradiol-17β to intact cells and their fractions was detemined after equilibration for 1.5h at 4°C. More than 92% of the radioactivity from representative preparations was verified as authentic oestradiol by thin-layer chromatography. Activities of plasma-membrane marker enzymes as well as binding sites for oestrogen and for wheat germ agglutinin were present principally in particulate fractions, rather than in 105000g-supernatant fractions. However, by using alternative homogenization procedures (i.e. hypotonic media), known to fragment and strip structural components, oestradiol-binding sites and activities of plasma-membrane marker enzymes were distributed predominantly into cytosol. By using the more conservative procedures, plasma membranes of low (ρ=1.13–1.16) and high (ρ=1.16–1.18) density were purified from crude nuclear fractions. A second low-density subfraction of plasma membrane was prepared from microsome-rich fractions. Activities of plasma-membrane marker enzymes were enriched to about 28 and four times that of the homogenate in plasma membranes of low and high density respectively. Binding sites for wheat germ agglutinin and oestradiol were concentrated in low-density plasma membranes to 46–63 times that of the homogenate. Specific binding of oestrogen in low-density plasma membranes purified from crude nuclei was saturable, with an apparent association constant of 3.5nm. At saturation, such oestradiol receptors corresponded to 526fmol/mg of membrane protein. A Hill plot showed a moderate degree of positive co-operativity in the interaction of hormone with plasma membranes. Specific binding of [3H]oestradiol-17β was reduced by a 200-fold molar excess of unlabelled oestradiol-17β, oestriol or diethylstilbestrol, but not by oestradiol-17α, cortisol, testosterone or progesterone. Binding was also blocked by prior exposure of membranes to trypsin or to 60°C, but remained essentially undiminished by extraction of membranes with either hypotonic or high-salt buffers. Extraction with 0.1% (v/v) Triton X-100 partially solubilized the oestrogen-binding component(s) of plasma membranes. Particle-free extracts were resolved on 5–20% (w/v) sucrose density gradients with either 0.01m- or 0.4m-KCl, and the fractions were analysed by adsorption to hydroxyapatite. In low-salt gradients macromolecule-bound oestrogen sedimented at predominantly 7.4S and binding was 1560 times that of the homogenate. Under high-salt conditions oestradiol-binding activity occurred at both 3.6S and 4.9S.
Assembly and Integration Process of the High-Density Detector Array Readout Modules for the Simons Observatory

The Simons Observatory will measure the cosmic microwave background temperature and polarization using a suite of new telescopes in the Atacama Desert in Chile. The Simons Observatory will use dichroic transition edge sensor (TES) bolometer arrays spanning six frequency bands from 27 to 280 GHz. The Simons Observatory will pioneer the use of a densely packed multiplexing architecture based on the microwave SQUID multiplexer ($$\mu $$mux), housing $$\sim \! 2000$$ microwave resonators, each coupled to a TES. The Simons Observatory aims to multiplex each array of $$\sim \! 2000$$ detectors with a single pair of coaxial cables and requires a multiplexing factor of $$\sim \! 1000$$. The Simons Observatory cryogenic readout system is called the universal microwave multiplexing module (UMM). The UMM couples to both horn and lenslet-coupled detector arrays and is integrated into the universal focal-plane module (UFM) after being independently characterized. We present processes we have developed for highly repeatable and automated integration methods of UMMs, which will be needed for the production of the 49 UFMs required for the first stage of the Simons Observatory.
The baby-making black hole

Trying to get pregnant felt like a series of two-week-long emotional rollercoasters for this queer woman.
Stem Cell Clinical Trials in Spinal Cord Injury: A Brief Review of Studies in the United States.

Background: Although many therapeutic approaches have been attempted to treat spinal cord injury, cellular transplantation offers the greatest promise in reconstituting the architecture of the damaged cord. Methods: A literature review was conducted to search for clinical trials investigating stem cells as treatment for spinal cord injury in the United States. Results: Overall, eight studies met inclusion criteria. Of the included studies, four were identified as being terminated, suspended, or not yet recruiting. Two studies were identified as currently recruiting, including one phase one trial evaluating stereotactic injections of human spinal cord-derived neural stem cells in patients with chronic spinal cord injuries, and one trial of transplantation of autologous bone marrow derived stem cells via paraspinal injections, intravenous injections, and intranasal placement. One study was identified as an active study, a phase one trial of intrathecal injection of 100 million autologous, ex-vivo expanded, adipose-derived mesenchymal stem cells. One trial that was listed as completed is a phase 1/2a, dose escalation study, investigating stereotactic injection of human embryonic stem cell derived oligodendrocyte progenitor cells. Conclusions: Although few significant publications have emerged to this point, current trial results are promising.
NONTHERMAL X-RAY EMISSION IN THE N11 SUPERBUBBLE IN THE LARGE MAGELLANIC CLOUD

We present the results of X-ray spectral analysis of the superbubble (SB) around the OB association LH9 in the H II complex N11 in the Large Magellanic Cloud. Using observations from Suzaku, we have modeled the X-ray emission over the energy range 0.2-7.5 keV. We constrained the thermal spectrum below 2 keV using a thermal plasma model found in a previous XMM-Newton study of the N11 region. We find that the hard X-ray emission (>2 keV) requires a nonthermal power-law component. The photon index of this component was found to be Γ = 1.72 ± 0.15. We performed an energy budget analysis for N11 using the known stellar content of LH9. We found that the observed thermal and kinetic energy in the SB is only half of the expected mechanical energy injected by stars.
Alerting patients via health information system considering trust-dependent patient adherence

The internet of things has ushered in a world of possibilities in chronic disease management. Connected to the health information network, a health device can monitor and provide intervention recommendations to patients in real time. However, this new health information system may face the risk of patients not following the system’s recommendations depending on their perception of the system. In this paper, we consider patients’ trust in the system a key factor driving their adherence to the system’s recommendation and develop an analytical model to design the optimal alerting strategy in the context of asthma management. Our method acknowledges that patient’s trust may change over time based on their experience of using the system, which may influence their future adherence behavior. We derive a set of structural properties of our solution and demonstrate that our approach can significantly improve patients’ quality of life compared to the current practice of asthma management. Furthermore, we investigate various real-world scenarios, such as the case that patients may have different level of tolerance for receiving alerts. Based on our findings, valuable insights can be shared with patients, healthcare practitioners, and companies in the technology-enabled healthcare business sector.
Application of Wavelet Unfolding Technique in Neutron Spectroscopic Analysis

Abstract Nonproliferation of nuclear materials is important in nuclear power industry and fuel cycle facilities. It requires technologies capable of measuring and assessing the radiation signatures of fission events. Neutrons produced in spontaneous or induced fission reactions are mainly fast. The neutron energy information allows characterization of nuclear materials and neutron sources. It can also be applied in remote sensing and source search tasks. The plastic scintillator EJ-299-33A was studied as a fast neutron detector. The detector response to a polyenergetic flux was unfolded usingthe multiple linear regression method. It yields the intensities of neutron flux of particular energy, hence, enabling the spectroscopic analysis. The wavelet technique was evaluated for the unfolding of neutron spectrum using the scintillator's response functions between 1 MeV and 14 MeV computed with the MCNPX code. This paperpresents the computational results of the wavelet-based spectrum unfolding applied to a scintillator detector with neutron / photon pulse shape discrimination properties.
Effect of relative humidity on dynamic aerosols of adenovirus 12.

Dynamic aerosols of adenovirus 12 were generated in the same Henderson apparatus under conditions of high, medium, and low relative humidity. High relative humidities resulted in more recovery of adenovirus 12 from aerosols and lungs of newborn Syrian hamsters. At 89, 51, and 32% relative humidity, the total infectious virus recovered from a 20-min aerosol was 106.7, 106.0, and 104.3 TCD50, respectively. Hamsters exposed to these 20-min aerosols retained measured lung doses of 103.0, 102.4, and 101.0 TCD50, respectively. The measured retained lung doses were compared to calculated inhaled lung doses based on both total virus aerosolized and total virus recovery from the aerosols.
Against Civil Gideon (and for Pro Se Court Reform)

This Article argues that the pursuit of a civil Gideon (a civil guarantee of counsel to match Gideon v. Wainright’s guarantee of appointed criminal counsel) is an error logistically and jurisprudentially and advocates an alternate route for ameliorating the execrable state of pro se litigation for the poor in this country: pro se court reform. Gideon itself has largely proven a disappointment. Between overworked and underfunded lawyers and a loose standard for ineffective assistance of counsel the system has been degraded. As each player becomes anesthetized to cutting corners a system designed as a square becomes a circle.There is little in indigent criminal defense that makes one think that a guarantee of civil counsel will work very well. If Courts have not required funding for meaningful representation in the serious cases covered in Gideon (including felony and death penalty prosecutions), it is extremely unlikely that they would do so in civil cases like eviction or deportation. Moreover, focusing our attention on pro se court reform is a much, much more promising and likely palliative to the legal problems of the poor. Lastly, and most importantly, civil Gideon is a deeply conservative and backward looking solution to this problem, while pro se court reform has the potential to do more than just help the poor. It has the potential to radically reshape our justice system in ways that assist everyone.
Quinonoid dihydropterin reductase--II. Regional and subcellular distribution of rat brain enzyme.

Abstract The regional and subcellular distribution of quinonoid dihydropterin reductase (DHPR, EC 1.6.99.7) was studied in the rat brain. In addition, the subcellular distribution of the enzyme was studied in the rat liver. The activity of rat brain DHPR was found to be lowest in the cerebral cortex (0.14 unit mg −1 ) and highest in the posterior colliculus (2.35 units mg −1 ). The distribution of brain DHPR correlated positively with the distribution of aromatic- l -amino acid decarboxylase but not with the distribution of tyrosine hydroxylase or tryptophan deearboxylase. However, this correlation was not observed in the caudate nucleus which contains low DHPR activity and high aromatic- l -amino acid decarboxylase and tyrosine hydroxylase activities. This finding is an indication that the amount of DHPR in the caudate nucleus may be rate limiting. The distribution profiles of brain and liver DHPR were found to be similar to that of lactate dehydrogenase; for both enzymes the greatest specific activity was found in the soluble fraction, indicating that DHPR is a cytoplasmic enzyme.
Electromagnetic Components of Auroral Hiss and Lower Hybrid Waves in the Polar Magnetosphere

DE-1 has frequently observed waves in the whistler and lower hybrid frequencies range. Besides the electrostatic components, these waves also exhibit electromagnetic components. It is generally believed that these waves are excited by the electron acoustic instability and the electron-beam-driven lower hybrid instability. Because the electron acoustic and the lower hybrid waves are predominately electrostatic waves, they cannot account for the observed electromagnetic components. In this work, it is suggested that these electromagnetic components can be explained by waves that are generated near the resonance cone and that propagate away from the source. The role that these electromagnetic waves can play in particle acceleration processes at low altitude is discussed.
Who is Paying for Health Care in Eastern Europe and Central Asia

Informal payments in the health sector in Eastern Europe and Central Asia (ECA) is emerging as a fundamental aspect of health care financing and as a major impediment to health care reform. Private payments to public doctors, nurses, and other health personnel are essentially an informal market for health care occurring within the confines of public health care service networks. These expenditures are also outside the financial controls, policy rubric, and audits of countries' health care systems. Like the informal sector, it is often illegal and unreported, and despite the terminology, is a form of corruption. 'Who is Paying for Health Care in Eastern Europe and Central Asia?' outlines the key policy issues, summarizes available data on the scope and nature of informal payments across ECA and spells out the policy implications and possible strategies to address the problem.
Optical Imaging of Paramagnetic Bead-DNA Aggregation Inhibition Allows for Low Copy Number Detection of Infectious Pathogens

DNA-paramagnetic silica bead aggregation in a rotating magnetic field facilitates the quantification of DNA with femtogram sensitivity, but yields no sequence-specific information. Here we provide an original description of aggregation inhibition for the detection of DNA and RNA in a sequence-specific manner following loop-mediated isothermal amplification (LAMP). The fragments generated via LAMP fail to induce chaotrope-mediated bead aggregation; however, due to their ability to passivate the bead surface, they effectively inhibit bead aggregation by longer ‘trigger’ DNA. We demonstrate the utility of aggregation inhibition as a method for the detection of bacterial and viral pathogens with sensitivity that approaches single copies of the target. We successfully use this methodology for the detection of notable food-borne pathogens Escherichia coli O157:H7 and Salmonella enterica, as well as Rift Valley fever virus, a weaponizable virus of national security concern. We also show the concentration dependence of aggregation inhibition, suggesting the potential for quantification of target nucleic acid in clinical and environmental samples. Lastly, we demonstrate the ability to rapidly detect infectious pathogens by utilizing a cell phone and custom-written application (App), making this novel detection modality fully portable for point-of-care use.
The Role of Friends in Caregiving

Changes in the formal health care system and in the health of the population are likely to increase the need for informal care of the sick and disabled. At the same time, high rates of divorce, a retreat from marriage, and increasing participation of women in the labor force are likely to decrease the ability of families to provide care. This research uses data from the National Survey of Families and Households to examine the role that friends play in the provision of care. The authors find that among caregivers, women providing care to a friend are more likely to be age peers and less likely to be employed or married than family caregivers. Friends seem less likely than family to take on care responsibilities when those responsibilities may conflict with other roles. If friends are to become a greater part of the care network, policies that encourage and enable the participation of nonfamily members will be important.
HIV suppression by HAART preserves cognitive function in advanced, immune-reconstituted AIDS patients.

Introduction HIV can damage neurons leading to cognitive impairment. Epidemiological observations suggest that neuropsychological impairment might progress despite successful HAART therapy, but available prevalence estimates are based on populations that were selected for impairment. Methods Of 433 advanced AIDS patients with documented immune reconstitution (CD4 lymphocyte counts 100 cells/microl after HAART), 286 had brief assessments of cognition (Trailmaking A/B and Digit Symbol Tests) at least once, no confounding neurological conditions, and available neuropsychological norms with comprehensive demographic corrections. At entry, most were immune reconstituted on HAART (median CD4 cell count 230 cells/microl) and HIV was suppressed (65% 20 000 RNA copies/ml). Results Over one quarter (27%) of participants exhibited impairment at their initial neuropsychological assessment, a rate nearly twice that expected in a normal (HIV-uninfected) reference population (14%). These impaired participants did not differ from the unimpaired group with respect to age, sex, education, race, CD4 lymphocyte counts, or HIV-RNA levels. Improved performance on neuropsychological tests was documented over a 2-year period 3-5 years after initiating HAART. This improvement was marginally associated with the continued or improving control of plasma HIV-RNA levels, but not with concurrent levels of immune recovery (CD4 lymphocyte counts). Conclusion Most advanced AIDS patients responding to HAART for prolonged periods have stable or improving cognition, but remain more likely to be impaired than the general population. During HAART, improving test performance probably reflects both practice effects and continuing neurological recovery after more than 3 years of HAART.
Directive-based Programming Models for Scientific Applications - A Comparison

Accelerators have been considered a viable way by many scientific and technical programmers to program and accelerate huge scientific applications. Accelerators such as GPUs have immense potential in terms of high compute capacity but programming these devices is a challenge. CUDA, OpenCL and other vendor-specific models are definitely a way to go, but these are low-level models that demand excellent programming skills; moreover, they are time consuming to write and debug. In order to simplify GPU programming several directivebased programming models have already been proposed. In this paper, we evaluate and compare several directive-based models such as PGI, HMPP and OpenACC models involving four scientific applications. From our experimental analysis, we conclude that efficient implementations of high-level directivebased models plus user guided optimizations can actually reach the performance obtained via a hand written CUDA code. For example a computer tomography-based algorithm ported to GPUs using a directive-based approach showed that the performance achieved is about 90% to that of CUDA version of the code.
Five years' experience with iodine-125 therapy of Graves' disease.

Abstract 5 years' experience with 123 doses of iodine-125 given to sixty-nine patients with Graves' disease (toxic diffuse goitre) is reported. The effects of systematically increasing the dose of iodine-125 were investigated. Euthyroidism was induced in thirty-seven of the sixty-three patients adequately followed at the time of final review; nineteen of the sixty-three were persistently hyperthyroid, four were permanently hypothyroid; and in three it was not possible to decide whether they were transiently or permanently hypothyroid. Transient hypothyroidism was reported 17 times in sixteen patients. There was the same wide variability in sensitivity to iodine- 125 radiation as previously observed with iodine-131 therapy. In contrast to iodine-131 treatment, ocular symptoms did not become worse and there was no consistent increase in antithyroglobulin titre after iodine-125 therapy. One of the three patients in whom hyper-triiodothyroninaemia developed after treatment with iodine-125 became thyrotoxic. It is concluded that the beneficial properties of iodine-125 treatment of Graves' disease should be further investigated.
Recentering the city

In The City and the Grassroots, Manuel Castells recentered the city as the site of distinctively urban social movements and reaffirmed the role of purposive social action in constructing a distinctively urban space. Although Castells’ recitation of five centuries of urban political activism documents the consistent failure of such movements to achieve their goals, his account is persistently optimistic on at least three counts. First, recentering the city reminds us that, despite the failure of transitory political movements, the city endures as an opportunity for renewed political activism. The continual possibility of change offered by the city's ontological persistence is separate from the fate of any given political intervention. Second, regardless of its specific success or failure, each episode of urban activism establishes a new context for the next encounter, its legacy persisting in the collective memories — the stock of mnemonic capital — of which the city is the repository. Third, Castells’ emphasis on political agency affirms that, while all action is ephemeral, its constitutive re-enactment ceaselessly provides openings for insurgency and transgression. This optimistic message is worth repeating today.
Arcing fault detection for distribution feeders: security assessment in long term field trials

A downed conductor, arcing fault detection system has been designed using multiple protection algorithms. An intelligent analysis system processes the outputs from several algorithms to determine the "confidence" that a fault exists. The design includes careful attention to discriminating arcing faults from normal system activity to ensure system security. Key to the acceptance of this system is testing under actual field conditions. The results of long term tests on five utilities are presented. The behavior of the prototype systems to staged faults, naturally occurring faults, and normal system disturbances is described. Conclusions are drawn concerning the practical viability of this system. >
Stress distribution and buckling stress of plates including edge contact-frictional force effects

Abstract The effects of edge contact-frictional force imposed by machine heads on the stress distribution in a plate are investigated. A contact-friction interface element is included in the prebuckling analysis which considers the possibility of slip between the machine heads and the plate. All analyses are performed using the incremental theory of plasticity. In the buckling formulation of the plate, element stiffness is evaluated on the basis of Hermitian interpolation polynomials. The buckling stresses are compared with those of the test results and the closed-form solutions available in the literature. The effect of edge boundary imperfections is also considered in this paper.
Analysis of the Rem2 - Voltage Dependant Calcium Channel β Subunit Interaction and Rem2 Interaction with Phosphorylated Phosphatidylinositide Lipids

Abstract Voltage dependant calcium channels (VDCC) play a critical role in coupling electrical excitability to important physiological events such as secretion by neuronal and endocrine cells. Rem2, a GTPase restricted to neuroendocrine cell types, regulates VDCC activity by a mechanism that involves interaction with the VDCC β subunit (Ca V β). Mapping studies reveal that Rem2 binds to the guanylate kinase domain (GK) of the Ca V β subunit that also contains the high affinity binding site for the pore forming and voltage sensing VDCC α subunit (Ca V α) interaction domain (AID). Moreover, fine mapping indicates that Rem2 binds to the GK domain in a region distinct from the AID interaction site, and competitive inhibition studies reveal that Rem2 does not disrupt Ca V α - Ca V β binding. Instead, the Ca V β subunit appears to serve a scaffolding function, simultaneously binding both Rem2 and AID. Previous studies have found that in addition to Ca V β binding, Rem2 must be localized to the plasma membrane to inhibit VDCC function. Plasma membrane localization requires the C-terminus of Rem2 and binding studies indicate that this domain directs phosphorylated phosphatidylinositide (PIP) lipids association. Plasma membrane localization may provide a unique point of regulation since the ability of Rem2 to bind PIP lipids is inhibited by the phosphoserine dependant binding of 14-3-3 proteins. Thus, in addition to Ca V β binding, VDCC blockade by Rem2 is likely to be controlled by both the localized concentration of membrane PIP lipids and direct 14-3-3 binding to the Rem2 C-terminus.
Ending the impasse in Kosovo: partition, decentralization, or consociationalism?

This paper argues that current Western-backed approaches to conflict resolution in Kosovo have failed to alter Serbia's policy toward the region and have contributed to the exacerbation of political tensions between Belgrade and Brussels, while deepening ethnic cleavages between Serb and Albanian communities. While there is no possibility of Kosovo returning to Serbia's control, there is an equal unlikelihood that Serbian-populated regions of Kosovo, especially the north, will submit to Pristina's authority. Most importantly, there is little hope that Kosovo can gain full international recognition and membership in international organizations without a compromise settlement with Serbia. While territorial partition has long been a suggested option, I conclude that the best possible solution for Kosovo, given the positions of all parties involved, is a process of significant decentralization beyond the internationally supported measures in the Ahtisaari Plan. A model of consociational power sharing is one i...
Choice and determinism: A comment

This note comments on Lawless and Finch's (1989) empirical test of Hrebiniak and Joyce's (1985) framework of business-environment relations. In doing so it extends Lawless and Finch's reasoning through the explicit incorporation of an interactionist perspective. A model is presented that amplifies the prevailing organizational adaptation logic by assigning a role to organizational learning and by suggesting how organizations act on environmental information vis-a-vis symbolic processes and environmental management strategies.
Offsets as industrial policy: Lessons from aerospace

Since 1975 “offsets” have begun to appear frequently in contracts covering international sales of aircraft and other products incorporating advanced technology. Offsets involve reciprocity beyond that normally found in an exchange of goods for money. They may involve co‐production or co‐design of the principal item to be exchanged, or acceptance by the seller of goods or services unrelated to it as partial payment (indirect offsets or countertrade). The United States has become the major provider of offsets and anti‐offset sentiment has grown. Economists interpret them as trade diverting. Politicians from regions suffering loss of employment view them as bestowing unfair advantage to foreign competitors. The authors examine offsets from both theoretical and policy perspectives and conclude that in such noncompetitive markets, second‐best considerations dominate, requiring case‐by‐case evaluation of impacts and rendering across‐the‐board determinations of welfare loss suspect.
Selection of oral contraceptives or hormone replacement therapy: patient communication and counseling issues.

Oral contraceptives and combination hormone replacement therapy are underused by most women. Among users, lack of compliance/adherence to oral contraceptive or hormone replacement therapy regimens can lead to discontinuation and deprive women of the full range of benefits achieved through hormone continuity. To prevent unintended pregnancy and to improve the health outcomes of women of all ages and the overall quality of life, adherence and continuation rates need to be improved for oral contraceptive and hormone replacement therapy use. Effective communication and counseling during the oral contraceptive and hormone replacement therapy regimen selection process and subsequent follow-up interactions are essential. Patients need to be informed in a clear and concise manner that, for most women, the benefits of oral contraceptives and hormone replacement therapy outweigh any associated health risks. Data should be presented without epidemiologic jargon and in terms that are easily understood. It is recommended that realistic expectations concerning the possible side effects, especially during the initial use of hormones, are established before use; furthermore, the selection of a formulation should take into account the unique needs of each patient. (Am J Obstet Gynecol 2001;185:S57-64.)
Abstract LB-157: VISTA deficiency synergizes with a non-redundant immune checkpoint pathway and leads to enhanced immune activation

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA V-domain Ig suppressor of T cell activation (VISTA) is a novel negative checkpoint ligand that suppresses T-cell mediated immune responses. Previous studies using VISTA-neutralizing monoclonal antibody show that VISTA-blockade enhances T cell-activation in an inflammatory disease model EAE, as well as in murine tumor models. Current study describes a comprehensive characterization of VISTA knockout (KO) mice. We show that despite the apparent normal hematopoietic development in young ko mice, VISTA genetic deficiency leads to a pro-inflammatory phenotype in aged animals, as well as enhanced T-cell activation in response to acute antigen immunization. In addition, we show that VISTA deficiency significantly enhanced disease development in a spontaneous model of autoimmune disease, which is correlated with the spontaneous activation of auto-antigen specific CD4+ T cells. Lastly, when combined with the genetic deficiency of another checkpoint molecule, synergistic or additive immune activation was observed. The implication of such enhanced immunity in cancer development and treatment will be discussed. Citation Format: Li Wang, Isabelle LeMercier, Arief Suriawinata, Wenna Chen, Randolph J. Noelle, Jiannan Li. VISTA deficiency synergizes with a non-redundant immune checkpoint pathway and leads to enhanced immune activation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-157. doi:10.1158/1538-7445.AM2014-LB-157
Collagen-induced arthritis in rats

An oil emulsion of purified type II collagen from bovine articular cartilage when injected intradermally into rats induced an inflammatory polyarthritis in 4 of 12 animals. When similarly injected, collagen purified from bonve vitreous induced arthritis in 6 of 12 animals. Studies of humoral and cell-mediated immunity to both collagen preparations demonstrated complete cross-reactivity. It is concluded that vitreous collagen shares the arthritogenic property of cartilage-derived type II collagen and that collagen from the two sources is indistinguishable in arthritogenic and immunologic properties.
Stability of strongly nonlinear normal modes

Abstract It is shown that a transformation of time can allow the periodic solution of a strongly nonlinear oscillator to be written as a simple cosine function. This enables the stability of strongly nonlinear normal modes in multidegree of freedom systems to be investigated by standard procedures such as harmonic balance.