cssi/SciSciGPT-SciSciNet huggingface dataset:
MPI performance engineering with the MPI tool interface: the integration of MVAPICH and TAU

MPI implementations are becoming increasingly complex and highly tunable, and thus scalability limitations can come from numerous sources. The MPI Tools Interface (MPI_T) introduced as part of the MPI 3.0 standard provides an opportunity for performance tools and external software to introspect and understand MPI runtime behavior at a deeper level to detect scalability issues. The interface also provides a mechanism to re-configure the MPI library dynamically at runtime to fine-tune performance. In this paper, we propose an infrastructure that extends existing components - TAU, MVAPICH2 and BEACON to take advantage of the MPI_T interface to offer runtime introspection, online monitoring, recommendation generation and autotuning capabilities. We validate our design by developing optimizations for a combination of production and synthetic applications. We use our infrastructure to implement an autotuning policy for AmberMD[1] that monitors and reduces MVAPICH2 library internal memory footprint by 20% without affecting performance. For applications where collective communication is latency sensitive such as MiniAMR[2], our infrastructure is able to generate recommendations to enable hardware offloading of collectives supported by MVAPICH2. By implementing this recommendation, we see a 5% improvement in application runtime.
Intracardiac phased-array imaging: methods and initial clinical experience with high resolution, under blood visualization: initial experience with intracardiac phased-array ultrasound.

Abstract Objectives This study was designed to test the feasibility of high-resolution phased-array intracardiac imaging. Background Intracardiac echocardiographic imaging of the heart during interventional electrophysiologic (EP) procedures has been limited by inadequate ultrasound penetration and absence of Doppler hemodynamic and flow information produced by rotating mechanical ultrasound elements. Methods A 10F (3.2 mm) phased-array, variable 5.5 to 10 MHz frequency imaging catheter with a four-way deflectable tip was applied in 24 patients undergoing EP studies. Sixteen prespecified cardiac targets were imaged from a right heart venue. Results Fifteen patients had no underlying organic heart disease; nine had ischemic, cardiomyopathic, valvular or congenital heart disorders. Longitudinal and short-axis imaging readily disclosed each cardiac valve, support structures and chamber, as well as the pericardium, right and left atrial appendages, the junction of the right atrium and superior vena cava, crista terminalis, tricuspid valve isthmus, coronary sinus orifice, membranous fossa ovalis and pulmonary veins. The average target depth was 8.8 ± 1.5 cm (range 0.5 to 15 cm), with adequate penetration at a 7.5 MHz imaging frequency. Color flow and Doppler utilities clearly characterized transaortic and pulmonic valve and pulmonary vein blood flow, including during low output states. Conclusions These first human studies with this technology demonstrate the methods, feasibility and utility of intracardiac phased-array vector and Doppler imaging for long-axis, apex-to-base global cardiac imaging. High resolution of endocardial structures and catheters suggests additional utility for visualizing interventional procedures from the right heart.
Fundamentals of affinity cell separations

Cell separations using affinity methods continue to be an enabling science for a wide variety of applications. In this review, we discuss the fundamental aspects of affinity separation, including the competing forces for cell capture and elution, cell-surface interactions, and models for cell adhesion. Factors affecting separation performance such as bond affinity, contact area, and temperature are presented. We also discuss and demonstrate the effects of nonspecific binding on separation performance. Metrics for evaluating cell separations are presented, along with methods of comparing separation techniques for cell isolation using affinity capture.
Serial fictions: Urdu print culture and the novel in colonial South Asia:

Serialisation allowed for remarkable experimentation with the new genre of the novel in colonial South Asia. The open nature of serialisation in South Asia, in which novels were not planned in advance but rather could develop and change while in progress, meant that serialised versions of novels were often more experimental than their later book editions. In this article, I use the pioneering Urdu novel Fasāna-e Āzād (1878–83) as a case study to examine serialisation’s effects on the emerging novel genre in the late nineteenth-century South Asia. By comparing the serial version and later book editions, I show that Fasāna-e Āzād underwent a fundamental transformation from serial to book, changing from a set of satirical sketches critical of Westernisation, to a pro-colonial novel. The protagonist Azad’s shift from a picaresque anti-hero to a proto-nationalist hero reflected the changing nature of respectability, what in Urdu was called sharafat, in the late nineteenth-century South Asia. Finally, I suggest...
Discontinuous Finite Element Quasi-Diffusion Methods

In this paper, two-level methods for solving transport problems in one-dimensional slab geometry based on the quasi-diffusion (QD) method are developed. A linear discontinuous finite element method...
Epidemiology of Coronary Heart Disease in Patients With Human Immunodeficiency Virus

As a growing number of patients infected with human immunodeficiency virus (HIV) have access to antiretroviral therapy and achieve virologic suppression, the focus of clinical care is shifting from treating the infectious complications of advanced immunodeficiency to managing and preventing chronic disease. The aging of the HIV-positive population and increased rates of chronic disease complications in the setting of HIV infection have increased the impact of noncommunicable diseases such as coronary heart disease (CHD). The effect of HIV on CHD is independent of traditional cardiovascular risk factors and antiretroviral medications and is likely due in part to the chronic inflammation and immune activation underlying HIV infection. This article describes the current state of epidemiologic knowledge on CHD in HIV infection. It highlights key studies in the field and summarizes epidemiologic data with respect to traditional and novel CHD risk factors, specialized clinical subgroups, and broader cardiovascular outcomes.
Functional and immunologic protein S levels are decreased during pregnancy

Protein S, is a natural anticoagulant protein which serves as a cofactor for activated protein C. During pregnancy and in the postpartum period, functional protein S levels are significantly reduced (38% +/- 17.3%, mean +/- 1 SD) when compared to nonpregnant females (97% +/- 31.6%) (P less than 0.001). In plasma an equilibrium exists between functionally active free protein S and protein S complexed with C4b-binding protein, which is functionally inactive. As a result of this equilibrium either a decreased level of total protein S antigen or an elevation of C4b-binding protein could lead to reduced protein S activity. C4b-binding protein levels measured by enzyme-linked immunoassay are not significantly different in pregnant women versus nonpregnant controls (103.5% +/- 21.2% v 100% +/- 16.9%). However, during pregnancy and in the postpartum period, total protein S levels are reduced (68% +/- 10.7%) compared to nonpregnant controls (100% +/- 17.0%). This difference is significant at P less than 0.001. These data demonstrated that the reduction in protein S activity observed during pregnancy is a result of reduced total protein S antigen.
Las historias de Camille: los niños del compost

espanolResumen El articulo presenta la ficcion futurista "Las historias de Camille" como propuesta de futuros cercanos, posibles, y presentes reales y al tiempo improbables. El texto promociona Las historias de Camille como un proyecto piloto, un modelo de trabajo y a la vez un objeto para jugar, para componer proyectos colectivos, no solo en la imaginacion, sino concretamente en las practicas escriturales. El escrito propone la figura de los palabreros de la muerte, cuya tarea es sentipensar y traer a la vida las cosas nuevas de la tierra, las formas de vida emergentes y nuevas clases de seres, habitantes de un planeta en constante evolucion. portuguesResumo O artigo apresenta a ficcao futurista "As historias de Camille" como uma proposta de futuros proximos, possiveis e de presentes reais e ao mesmo tempo improvaveis. O texto promove As historias de Camille como um projeto piloto, um modelo de trabalho e, ao mesmo tempo, um objeto para brincar, para compor projetos coletivos, nao apenas na imaginacao, mas concretamente nas praticas escriturarias. A escrita propoe a figura dos palaveiros da morte, cuja tarefa e senti--pensar e trazer a vida as novas coisas da terra, as formas de vida emergentes e novas classes de seres, habitantes de um planeta em constante evolucao. EnglishAbstract The article presents the futuristic fiction, "The Camille Stories," as a proposal of immediate possible futures as well as real and improbable present-day contexts. The text positions "The Camille Stories" as a pilot project, a work model and also as an object of play in order to compose collective projects, not only in the imagination, but specifically in writing practices. The article proposes the figure of the palabreros (leaders) of death, whose task it is to feel-think and bring to life new things of the earth, and emerges new forms of life and types of beings who are inhabitants of a planet that is in constant evolution.
Non-Intrusive In-Situ Requirements Monitoring of Embedded System

Accounting for all operating conditions of a system at the design stage is typically infeasible for complex systems. Monitoring and verifying system requirements at runtime enable a system to continuously and introspectively ensure the system is operating correctly in the presence of dynamic execution scenarios. In this article, we present a requirements-driven methodology enabling efficient runtime monitoring of embedded systems. The proposed approach extracts a runtime monitoring graph from system requirements specified using UML sequence diagrams. Non-intrusive, on-chip hardware dynamically monitors the system execution, verifies the execution adheres to the requirements model, and in the event of a failure provides detailed information that can be analyzed to determine the root cause. Using case studies of an autonomous vehicle and pacemaker prototypes, we analyze the relationship between event coverage, detection rate, and hardware requirements
Advanced Imaging in Adult Congenital Heart Disease

As the congenital heart disease (CHD) population enters adulthood, significant hemodynamic changes either due to physiologic changes or as a result of long-term complications from initial surgical repair often lead to imaging beyond the conventional echocardiography. The most recent appropriateness criteria and consensus statements consider both cardiac MRI (CMR) and cardiac CT more appropriate than invasive coronary angiography and scintigraphic evaluation in adult congenital heart disease (ACHD) also known as grown-up adult with congenital heart disease (Figs. 33.1, 33.2, 33.3) [1]. Increased availability and technical advances in both ECG-gated cardiac CT and CMR can offer both a complementary and a problem-solving noninvasive assessment of complex anatomy and function [2]. Patient-centric and tailored image acquisition protocols are needed to fully characterize the complex anatomy and answer the diagnostic question while keeping the radiation dose in accordance with ALARA (as low as reasonably achievable) with CT and optimizing the scan time with CMR. This chapter will provide a concise overview of imaging protocols and highlight imaging appearances of commonly encountered complex CHD.
Trap Tree and Interception Trap Techniques for Management of Ambrosia Beetles (Coleoptera: Curculionidae: Scolytinae) in Nursery Production

The majority of wood-boring ambrosia beetles are strongly attracted to ethanol, a behavior which could be exploited for management within ornamental nurseries. A series of experiments was conducted to determine if ethanol-based interception techniques could reduce ambrosia beetle pest pressure. In two experiments, trap trees injected with a high dose of ethanol were positioned either adjacent or 10-15 m from trees injected with a low dose of ethanol (simulating a mildly stressed tree) to determine if the high-dose trap trees could draw beetle attacks away from immediately adjacent stressed nursery trees. The high-ethanol-dose trees sustained considerably higher attacks than the low-dose trees; however, distance between the low- and high-dose trees did not significantly alter attack rates on the low-dose trees. In a third experiment, 60-m length trap lines with varying densities of ethanol-baited traps were deployed along a forest edge to determine if immigrating beetles could be intercepted before reaching sentinel traps or artificially stressed sentinel trees located 10 m further in-field. Intercept trap densities of 2 or 4 traps per trap line were associated with fewer attacks on sentinel trees compared to no traps, but 7 or 13 traps had no impact. None of the tested intercept trap densities resulted in significantly fewer beetles reaching the sentinel traps. The evaluated ethanol-based interception techniques showed limited promise for reducing ambrosia beetle pressure on nursery trees. An interception effect might be enhanced by applying a repellent compound to nursery trees in a push-pull strategy.
Fixing Yesterday’s Solutions: Data Cleanup in Serials Solutions 360 Core

ABSTRACTManaging electronic serials is a vital part of modern academic librarianship. In 2014, the College of Staten Island (CSI) faced a serious serials access problem. A number of subscribed titles were temporarily not accessible through library interfaces. To quickly solve the problem, a set of over 5,000 custom records were uploaded (using Microsoft Excel) to Serials Solutions 360 Core, CSI’s serial management system. This solution provided access to current and back-file (perpetual ownership) titles but introduced a number of significant new problems, including duplicate records, records with holdings dates that were invalid at the end of the calendar year, back-file records that were difficult to identify or edit, and unmanageable sets of records for large subscription packages. This article will describe how and why the custom records caused these issues and describe the project that addressed them. The project (ongoing) was designed to fix the problems while maintaining access to all current and b...
Cellular versus acellular matrix devices in the treatment of diabetic foot ulcers: Interim results of a comparative efficacy randomized controlled trial

Healing of diabetic foot ulcers is a major challenge. Despite adhering to optimal standard of care (SOC), less than 30% of wounds heal after 20 weeks. Advanced cellular tissue-based products have shown better healing over SOC, albeit with great cost and modest improvement. We hypothesized no difference in healing effected by either cellular (Dermagraft), noncellular (Oasis) devices, relative to SOC in treating diabetic foot ulcer in a randomized controlled trial. The primary and secondary outcomes were the percentage of subjects that achieved complete wound closure by study endpoint (12 weeks of treatment) and study completion, respectively. During the 2-week screening phase with SOC, subjects with 40% change in ulcer size were excluded. After randomization, 56 patients entered an active treatment phase (8 weeks) followed by a maintenance phase (4-week SOC), with endpoint at visit 15, and 4 monthly follow-up visits. There was equal distribution of demographic data (p>.05) and no difference in initial wound characteristics (p>.05) between all groups. No differences were observed in complete wound closure by 12 and 28 weeks of treatment, nor were there any difference in percentage area reduction from treatment weeks 1 to 12 and from treatment weeks 1 to 28 between the groups. Each of the treatment arms showed statistically significant reduction in wound area from treatment weeks 1 to 28 (p<.05). This exploratory analysis suggests that the outcomes of treatment with either Dermagraft or Oasis matrix are comparable. We have completed enrollment, and the final data analysis is underway to make definitive conclusions.
Melon Flies: Dosage-Response and Sexual Competitiveness After Treatment with Gamma Irradiation in a Nitrogen Atmosphere

Doses of 18-19 krad of gamma irradiation were needed to produce a level of sterility of 99.5% or higher in males Dacus cucurbitae Coquillett treated in nitrogen as pupae 2 days before eclosion or as 2- or 5-day-old adults. The same level of sterility was obtained with 6-8 krad when pupae or 2-day-old adults were irradiated in air. Males irradiated in nitrogen either as pupae or as 2-day-old adults were fully competitive with normal males, but males treated in nitrogen as 5-day-old adults and males irradiated in air as 2-day-old adults or as pupae were only 40-60% as competitive as normal males. Recovery of fertility with time occurred in males treated in nitrogen as 2-day-old adults, although not in males treated in nitrogen in the late pupal stage. However, mortality in males treated in nitrogen in the pupal stage at 6 wk was about twice that of the former groups. (auth)
Bio-oil co-processing can substantially contribute to renewable fuel production potential and meet air quality standards

Abstract Co-processing raw bio-oil derived from lignocellulosic biomass in existing petroleum refineries represents a near-term greenhouse gas mitigation strategy by producing partially renewable and infrastructure-compatible hydrocarbon fuel with minimal capital requirements. One deterrent for risk-averse refinery owners is that a modification to their air permit may be required prior to any changes to refinery operations due to potential air emission changes. However, a lack of information on potential air emission changes resulting from bio-oil co-processing yields uncertainty, which could cause delay in obtaining required permit. To address this concern, we perform a quantitative evaluation of air emission changes across a range of bio-oil co-processing fractions in refineries’ fluid catalytic cracking units. We find that 92% of U.S. petroleum refineries could co-process 5% or more (up to 20%, by weight) raw bio-oil without triggering major permitting requirements. We then develop an upper bound estimate of the potential for co-processing bio-oil considering permitting and technical limits; our results suggest that U.S. refineries could co-process 573,000 barrels per day (0.79 cubic meter per second) of raw bio-oil, implying ~1.92 billion gallons gasoline equivalent of renewable fuel per year (0.23 cubic meter per second), equivalent to 1.4% of U.S. gasoline consumption or 18% of ethanol production in 2018. This first-of-its-kind analysis integrates process and environmental engineering with air permitting analysis and demonstrates the importance of coupling regulatory considerations with engineering analysis to guide informed decision-making to minimize investment risks while fully leveraging refinery infrastructure. This novel approach is also applicable to refineries in other jurisdictions.
Superheroes social skills

Abstract As deficits in social communication represent a primary characteristic of autism spectrum disorder (ASD), a substantial number of strategies have been evaluated to promote social development in individuals with ASD. Superheroes Social Skills is a manualized social skills curriculum that incorporates multiple evidence-based social skills training strategies into one intervention package. Specifically, interventions strategies in the curriculum include video modeling, behavioral skills training, self-monitoring, social stories, and inclusion of peers within social skills training groups. Originally designed for elementary-age children with ASD, the program has been found to be effective in promoting social skill use within this and other populations. Lessons learned from published evaluations of the curriculum are described as a means of promoting efficient utilization of the curriculum.
Gene Therapy with Cord Blood Hematopoietic Stem Cells for Adenosine Deaminase Deficiency: An Update

Gene therapy for ADA deficiency has been a model disease in which to evaluate hematopoietic stem cells for clinical gene therapy [1]. ADA deficiency has been a candidate disease because 1. ADA is a single polypeptide protein, 2. a clinically normal phenotype is associated with a wide range of enzymatic function (5–500% of normal), and 3. ADA is widely expressed so that tissue specific expression is not required.
Implication of TIGIT + human memory B cells in immune regulation

Regulatory B cells (Bregs) contribute to immune regulation. However, the mechanisms of action of Bregs remain elusive. Here, we report that T cell immunoreceptor with Ig and ITIM domains (TIGIT) expressed on human memory B cells especially CD19+CD24hiCD27+CD39hiIgD−IgM+CD1c+ B cells is essential for effective immune regulation. Mechanistically, TIGIT on memory B cells controls immune response by directly acting on T cells and by arresting proinflammatory function of dendritic cells, resulting in the suppression of Th1, Th2, Th17, and CXCR5+ICOS+ T cell response while promoting immune regulatory function of T cells. TIGIT+ memory B cells are also superior to other B cells at expressing additional inhibitory molecules, including IL-10, TGFβ1, granzyme B, PD-L1, CD39/CD73, and TIM-1. Lack or decrease of TIGIT+ memory B cells is associated with increased donor-specific antibody and TFH response, and decreased Treg response in renal and liver allograft patients. Therefore, TIGIT+ human memory B cells play critical roles in immune regulation. Regulatory B cells have been shown to play critical roles in the modulation of the immune system. Here, the authors implicate TIGIT expression in B cells with the process of immuno-regulation.
Soil microbes mediate the effects of nitrogen supply and co-inoculation on Barley Yellow Dwarf Virus in Avena sativa

O_LINutrient supply rates to hosts can mediate host-pathogen interactions. In terrestrial systems, nutrient supply to plants is mediated by soil microbes, suggesting a potential indirect effect of soil microbes on plant-pathogen interactions. Soil microbes also may affect plant pathogens by inducing plant defenses. C_LIO_LIWe tested the role of soil microbes, nitrogen supply to plant hosts, and co-inoculation on infection by aphid-vectored RNA viruses, Barley Yellow Dwarf Virus (BYDV-PAV) and Cereal Yellow Dwarf Virus (CYDV-RPV), in a grass host grown in soil microbes collected from a long-term nitrogen enrichment experiment. C_LIO_LIBYDV-PAV incidence declined with high nitrogen supply, co-inoculation, or presence of soil microbes exposed to long-term low nitrogen enrichment. However, when combined, the negative effects of these treatments were sub-additive: nitrogen and co-inoculation did not reduce BYDV-PAV incidence in plants grown with the soil microbes. While soil microbes impacted leaf chlorophyll, they did not alter biomass or CYDV-RPV incidence. C_LIO_LISoil microbes mediated the effects of nitrogen supply and co-inoculation on infection incidence and the effects of infection on host symptoms. Thus, soil microbial communities can indirectly control disease dynamics, altering the effects of nitrogen enrichment on plant-pathogen and pathogen-pathogen interactions in terrestrial systems. C_LI
Joint Beamforming and Interference Cancellation in MmWave Wideband Full-Duplex Systems

Full-duplex (FD) systems have the capability to transmit and receive at the same time in the same frequency band. FD systems can reduce congestion and latency and improve coverage and spectral efficiency. As a relay, they can increase range and decrease outages. Full-duplex (FD) wireless systems have been emerging as a practical solution to provide high bandwidth, low latency, and big data processing in millimeter wave and Terahertz systems to support cellular networks, autonomous driving, platooning, advanced driving assistance and other systems. However, FD systems suffer from loopback self-interference that can swamp the analog-to-digital converters (ADCs) resulting in very low spectral efficiency. In this context, we consider a cellular system wherein uplink and downlink users independently communicate with FD base station. The proposed contributions are (1) three hybrid beamforming algorithms to cancel self-interference and increase the received power, and (2) evaluation of outage probability, spectral efficiency, and energy efficiency of the proposed algorithms. We consider full-digital beamforming and upper bound as benchmarks. Finally, we show the resiliency of Algorithm 2 against self-interference in comparison with Algorithms 1 and 3, as well as conventional approaches such as beam steering, angle search and singular value decomposition.
Reactive binder jet additive manufacturing for microstructural control and dimensional stability of ceramic materials

Abstract Binder jet additive manufacturing (BJAM) is particularly suited to processing brittle materials such as ceramics as its process flow separates the steps of shaping and densification. Polymer binders are typically used in BJAM, including for the processing of ceramics. However, ceramic components in the green state are especially prone to distortion or fracture during sintering, due to the low strength of polymer-bound parts after polymer decomposition and high sintering temperatures of ceramics. This paper presents the development and use of reactive metal salt binders for BJAM of ceramic components. Using aluminum oxide as the feedstock powder, we compare the performance of aluminum nitrate and magnesium nitrate metal salts as binders, and polyethylene glycol as a reference polymer binder. Test components are fabricated using a custom BJAM testbed, sintered, and characterized for density and deformation. The metal salt binders form solid interparticle bridges after decomposition, which provide continued strength to printed components during sintering. Additionally, increased densification results from the use of magnesium nitrate binders and reduced shrinkage results from use of aluminum nitrate binders, showcasing the utility of reactive binders that convert into ceramic sintering aids upon decomposition and sustain part strength during sintering.
Chinese: A Linguistic Introduction

Introduction 1. Historical background 2. Phonetics of standard Chinese 3. Morphology 1 4. Morphology 2 5. Chinese writing 6. Chinese language and culture 7. Chinese syntax 1 8. Chinese syntax 2.
Evaluating performance of new quad-core Intel®Xeon®5500 family processors for HPC

In this paper we take a look at what the new Quad-Core Intel Xeon Processor code name Nehalem brings to high performance computing. We compare Intel Xeon 5400 series based system with a server utilizing his successor the new Intel Xeon X5560. We compare both CPU generations utilizing dual socket platforms using a number of HPC benchmarks. The results clearly prove that the new Intel Xeon processor 5500 family provide significant performance advantage on typical HPC workloads and demonstrate to be a right choice for many of HPC installations.
The Factor Compatibility and Communality of Coded-Expressed and Inventoried Interests.

An investigation of the relationships and underlying constructs between expressed and inventoried interests across the occupational classification scheme of Holland, Roe and Strong was undertaken. The canonical correlations calculated on each scheme were statistically significant, yet the redundancy indices demonstrated a relatively low amount of variance overlap. The canonical factor structures that were calculated indicated two similar bipolar structures underlying the occupational schema studied.
Myovascular innervation: axon loss in small-fiber neuropathies.

Introduction Vascular denervation occurs in some neuropathies, but measurement of small perivascular axons has been difficult. Methods We evaluated 31 consecutive patients who had both muscle and skin biopsies. We quantitated myovascular innervation by staining unmyelinated axons with peripherin and non-myelinating Schwann cells with neural cell adhesion molecule and comparing their areas. Results Perivascular unmyelinated axon−Schwann (UAS) ratios correlated with axon density in skin (r = 0.679; P < 0.0001). Low UAS ratios (≤0.25) had a sensitivity of 90% and specificity of 91% for a clinical diagnosis of small-fiber neuropathy (P < 0.0001). Autonomic features were more common in patients with low perivascular UAS ratios (P = 0.002). A patient subgroup with myovascular, but not skin, denervation commonly had muscle discomfort and autonomic features. Conclusions UAS ratio measurements, comparing axons and associated non-myelinating Schwann cells, can quantitate perivascular innervation. Small-fiber neuropathies are often associated with myovascular denervation. Some patients with muscle discomfort have selective myovascular denervation. Muscle Nerve 51: 514–521, 2015
Influence of cyclodextrin ring substituents on folding‐related aggregation of bovine carbonic anhydrase

A common obstacle to proper renaturation of an unfolded protein is aggregation, an intermolecular side reaction of immense importance in biotechnology and in the pathogenesis of several neurodegenerative diseases. Cyclic sugars known as cyclodextrins have been used as protein-folding aids. The effect of cyclodextrin chemistry on aggregation and refolding of carbonic anhydrase was evaluated in this study. Size-exclusion HPLC showed that cyclodextrins inhibit aggregate formation without interfering with the correct renaturation of carbonic anhydrase. PAGE of refolded enzyme provides further evidence of inhibition of folding-related aggregation by natural and chemically modified cyclodextrins. Although the amount of aggregate formed and recovery of active enzyme was dependent on cavity size, the nature of the chemical substituents found on the rims of the sugar molecule seems to play a more important role in cyclodextrin-assisted refolding of carbonic anhydrase. In general, neutral or cationic cyclodextrins with small cavities were found to be better folding aids than anionic cyclodextrins with larger holes. Although the exact prediction of the effect of a cyclodextrin substitution on protein refolding is not possible at present, these results clearly show that modified cyclodextrins can be designed that effectively inhibit protein aggregation.
American time use survey: sleep time and its relationship to waking activities.

Study Objectives: To gain some insight into how various behavioral (lifestyle) factors influence sleep duration, by investigation of the relationship of sleep time to waking activities using the American Time Use Survey (ATUS).
Biochemical and Kinetic Characterization of the Eukaryotic Phosphotransacetylase Class IIa Enzyme from Phytophthora ramorum

Phosphotransacetylase (Pta), a key enzyme in bacterial metabolism, catalyzes the reversible transfer of an acetyl group from acetyl phosphate to CoA to produce acetyl-CoA and P i . Two classes of Pta have been identified based on the absence (Pta I ) or presence (Pta II ) of an N-terminal regulatory domain. Pta I has been fairly well studied in bacteria and one genus of archaea; however, only the Escherichia coli and Salmonella enterica Pta II enzymes have been biochemically characterized, and both are allosterically regulated. Here we describe the first biochemical and kinetic characterization of a eukaryotic Pta from the oomycete Phytophthora ramorum . The two Ptas from P. ramorum , designated as PrPta II 1 and PrPta II 2, both belong to class II. PrPta II 1 displayed positive cooperativity for both acetyl phosphate and CoA and is allosterically regulated. We compared the effect of different metabolites on PrPta II 1 and the S. enterica Pta II and found that although the N-terminal regulatory domains share only 19% identity, both enzymes are inhibited by ATP, NADP, NADH, PEP, and pyruvate in the acetyl-CoA/P i –forming direction but are differentially regulated by AMP. Phylogenetic analysis of bacterial, archaeal, and eukaryotic sequences identified four subtypes of Pta II based on the presence or absence of the P-loop and DRTGG subdomains within the N-terminal regulatory domain. Although the E. coli , S. enterica , and P. ramorum enzymes all belong to the IIa subclass, our kinetic analysis has indicated that enzymes within a subclass can still display differences in their allosteric regulation.
Third-Sector Organizations, Population Dynamics, and Changing Vulnerabilities Following the 2011 Earthquake in Christchurch, New Zealand

Communities and individuals rely on third-sector organizations (TSOs) following natural disasters to complement formal government recovery activities by providing targeted support. In this way, TSOs can fulfill important niche roles, but the picture becomes complicated if residents and organizations relocate and connectivity is lost. Recovery might be compromised, especially for vulnerable and marginalized individuals, if communities are displaced from the service provision area of the TSOs that are most sensitive to their needs. This study focuses on TSOs in Christchurch, New Zealand, where an earthquake in February 2011 devastated parts of the city, precipitating a migration of residents from northeast neighborhoods to suburbs in the west and southwest of the central business district. Traditional social vulnerability metrics, derived from the 2006 and 2013 New Zealand censuses, show shifting ethnic, livelihood, and household structure related vulnerabilities throughout the city and comparisons of ward ...
Distinguishing incident and prevalent diabetes in an electronic medical records database.

Purpose To develop a method to identify incident diabetes mellitus (DM) using an electronic medical records (EMR) database and test this classification by comparing incident and prevalent DM with common outcomes related to DM duration. Methods Incidence rates (IRs) of DM (defined as a first diagnosis or prescription) were measured in 3-month intervals through 36 months after registration in The Health Improvement Network, a primary care database, from 1994 to 2012. We used Joinpoint regression to identify the point where a statistically significant change in the trend of IRs occurred. Further analyses used this point to distinguish those likely to have incident (n = 50 315) versus prevalent (n = 28 337) DM. Incident and prevalent cohorts were compared using Cox regression for all-cause mortality, cardiovascular disease (CVD), diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. Analyses were adjusted for age, sex, smoking, obesity, hyperlipidemia, hypertension, and calendar year. Results Trends in DM IRs plateaued 9 months after registration (p = 0.04). All cause-mortality was increased (hazard ratio (HR) 1.62, 95% CI 1.53–1.70) among patients diagnosed with DM prior to 9 months following registration (prevalent DM) compared to those diagnosed after 9 months (incident DM). Similarly, the risk of DM-related complications was higher in prevalent versus incident DM patients [CVD, HR 2.24 (2.08–2.40); diabetic retinopathy, HR 1.31 (1.24–1.38); diabetic nephropathy, HR 2.30 (1.95–2.72); diabetic neuropathy, HR 1.28 (1.16–1.41)]. Conclusion Joinpoint regression can be used to identify patients with newly diagnosed diabetes within EMR data. Failure to exclude patients with prevalent DM can lead to exaggerated associations of DM-related outcomes. Copyright © 2013 John Wiley & Sons, Ltd.
An ethical framework for responding to drug shortages in pediatric oncology

The frequency of drug shortages has increased considerably over the last decade. Important ethical issues arise whenever the supply of an effective drug is insufficient to meet demand. Using the ethical principles of beneficence, non-maleficence, and justice, institutions can guide prioritization of drug distribution before a shortage occurs to avoid unfair and unethical distribution of resources. This analysis will give a historical context for drug shortages, identify, and explore the central ethical concerns raised by drug shortages, and propose an ethical framework for addressing them in the context of pediatric oncology. Pediatr Blood Cancer 2015;62:931–934. © 2015 Wiley Periodicals, Inc.
Intracerebroventricular pertussis toxin enhances sensitivity to N-methyl-D-aspartate-induced seizures in mice

The effect of pretreatment with pertussis toxin on N-methyl-D-aspartate (NMDA)-induced seizures was investigated in mice. In animals treated with pertussis toxin (0.5 μg/animal i.c.v) five days prior to testing the convulsant ED50 of NMDA was calculated to he 18 mg/kg whereas it was calculated to be 107 mg/kg in sham-treated animals. These results suggest the pertussis toxin enhances sensitivity to NMDA, possibly via its actions on inhibitory G-proteins.
Design-effort alloy: Boosting a highly tuned primary core with untuned alternate cores

A commercial flagship superscalar core is a highly tuned machine. Designers spend significant effort to tune the register-transfer-level (RTL) model, circuits, and layout to optimize performance and power. Nonetheless, the one-size-fits-all microarchitecture still suffers from suboptimal performance and power on individual applications. A single-ISA heterogeneous multi-core, with its multiple diverse core designs, has potential to exploit application diversity. However, tuning multiple core types will incur insurmountable design effort. This paper proposes a new class of single-ISA heterogeneous multi-core processor, called design-effort alloy (DEA). Only one of the core types, called the high-effort core (HEC), is tuned using a high-effort design flow. Much less effort is spent on tuning other core types, called low-effort cores (LECs). We begin with synthesizable RTL designs of a palette of out-of-order superscalar core types. A LEC and HEC is designed for each core type: the LEC is based on design automation and the HEC is derived from its LEC counterpart, using frequency and energy scaling factors that account for RTL, circuit, and layout optimizations. The resulting HECs have more than a 2x frequency advantage with only a 1.3× increase in energy consumption compared to their corresponding LECs. From the palette of core types, we find the best 4-core-type DEA processor for 179 SPEC SimPoints (program phases). Our study yielded the following key results: 1) The DEA processor's HEC is the same core type in the best high-effort homogeneous multi-core, owing to most program phases demonstrating “average” instruction-level behavior and favoring this balanced core. 2) The DEA processor yields a speedup in BIPS3/W of 1%–87%, and a geometric-mean speedup of 25%, on 20 out of 179 SimPoints over the best high-effort homogeneous multi-core. Thus, untuned LECs operating at less than half the frequency of the HEC nonetheless accelerate program phases with “outlier” instruction-level behavior.
Evaluation of voltage interpolation to address process variations

Post-fabrication tuning provides a promising design approach to mitigate the performance and power overheads of process variation in advanced fabrication technologies. This paper explores design considerations and VLSI-CAD support for a recently proposed post-fabrication tuning knob called voltage interpolation. The paper discusses design tradeoffs between circuit tuning range and static power overheads that can be performed within the synthesis flow of the design process. The paper explores the scheme for a 64-core chip-multiprocessor machine using industrial-grade design blocks and shows that the scheme can be used to mitigate overhead arising from random and correlated within-die process variations. The analysis shows that the scheme can match the nominal delay target with a 10% power cost, or for the same power budget, incur only a 9% delay overhead after variations.
19S IgM forssman‐type heterophhile antibodies in juvenile rheumatoid arthritis

Fifty-four sera from children with juvenile rheumatoid arthritis (JRA) were separated by gel filtration at pH 4.05. The serum and IgM- and IgG-containing fractions were analyzed for heterophile antibodies by subjecting them to a hemolytic assay in tubes with the target cell a 1% washed sheep erythrocyte (SRBC) or beef erythrocyte (BRBC) in suspension. Thirty-three of 54 sera showed hemolytic antibody titers > 1:640 against SRBC alone and 4 of 54 had titers > 1:320 against SRBC and BRBC. All positive titers against SRBC and BRBC were associated with the IgM fraction. Differential absorption with SRBC, BRBC, and tissue sediment of homogenized guinea pig kidney revealed a Forssman specificity in 33 sera and Forssman and Hanganutziu-Deicher specificity in 4. The presence of heterophile antibodies in JRA correlated with the presence of hidden rheumatoid factor. There was also an increased incidence in patients with positive antinuclear antibodies and in teenaged females with polyarticular disease.
Powered Flight Design and Performance Summary for the Mars Science Laboratory Mission

The powered flight segment of Mars Science Laboratory’s Entry, Descent, and Landing system extends from backshell separation through landing. This segment is responsible for removing the final 0.1% of the kinetic energy dissipated during entry, descent, and landing and culminates with the successful touchdown of the rover on the surface of Mars. Powered descent overcame the many challenges that exist in the powered flight segment: extracting the powered descent vehicle from the backshell, performing a 300 m divert maneuver to avoid collision with the backshell and parachute, slowing the descent from 85 m/s to 0.75 m/s successfully lowering the rover on a 7.5 m bridle beneath the rocket-powered descent stage, and gently placing it on the surface using the sky crane maneuver. Finally, the nearly spent descent stage executed a flyaway maneuver to ensure surface impact at a safe distance from the rover. The powered flight segment’s execution resulted in Mars Science Laboratory’s successful touchdown on the ...
The politics of small things: nanotechnology, risk, and uncertainty

Nanotechnology is set to change the world. Nanotechnology is increasingly talked about with the same breathless excitement that surrounded biotechnology and information technology at the start of the 1990s. Nanotechnology has caught the attention of several nongovernmental organizations (NGOs) that have spent the past decade campaigning against genetically modified (GM) crops and foods. A debate about its risks, is rapidly taking on a sharper focus around issues of nanoparticle toxicity and the need for tighter regulation. This work explores three dimensions of uncertainty in emerging debates over nanotechnology.
Induction of Grp78/BiP by Translational Block ACTIVATION OF THE Grp78 PROMOTER BY ATF4 THROUGH AN UPSTREAM ATF/CRE SITE INDEPENDENT OF THE ENDOPLASMIC RETICULUM STRESS ELEMENTS

Mammalian cells respond to endoplasmic reticulum (ER) stress by attenuation of protein translation mediated through the PERK-eIF2α pathway and transcriptional activation of genes such as Grp78/BiP encoding ER chaperone proteins. The disruption of PERK function or the blocking of eIF2α Ser51 phosphorylation fails to attenuate translation after ER stress and also results in substantial impairment of Grp78/BiP induction by ER stress. While the activation of the Grp78 promoter by the ATF6 pathway through the endoplasmic reticulum stress elements (ERSEs) is well documented, the molecular mechanism linking PERK activation to Grp78 stress induction is unknown. We report here that ATF4, a transcription factor whose translation is up-regulated by the PERK-eIF2α pathway, can activate the Grp78 promoter independent of the ERSE. The ATF4-activating site is localized to an ATF/CRE sequence upstream of the ERSEs and is distinct from the C/EBP-ATF composite site previously identified as the ATF4 binding site in the ER stress-inducible chop promoter. In vitro translated ATF4 binding to the ATF/CRE site requires other nuclear co-factors from non-stressed cells, forming a complex that exhibits identical electrophoretic mobility as a thapsigargin-stress induced complex. Here we have identified the closely related ATF1 and CREB1 as nuclear co-factors that form in vivo complexes with endogenous ATF4. ER stress induces CREB1 phosphorylation and ATF1/CREB1 binding to the Grp78 promoter. Through the use of adenoviral vector expression systems, we provide evidence that when ATF4 function is suppressed and its binding partners are not able to compensate for its function, Grp78 induction by Tg and Tu is partially inhibited. Our studies resolve a mechanism responsible for inhibition of Grp78 mRNA induction by ER stress in cells that are functionally null for PERK or devoid of eIF2α phosphorylation.
Turning of COGS moves forward findings for hormonally mediated cancers

The large-scale Collaborative Oncological Gene-environment Study (COGS) presents new findings that further characterize the genetic bases of breast, ovarian and prostate cancers. We summarize and provide insights into this collection of papers from COGS and discuss the implications of the results and future directions for such efforts.
Boosted sampling: approximation algorithms for stochastic optimization

Several combinatorial optimization problems choose elements to minimize the total cost of constructing a feasible solution that satisfies requirements of clients. In the Steiner Tree problem, for example, edges must be chosen to connect terminals (clients); in Vertex Cover, vertices must be chosen to cover edges (clients); in Facility Location, facilities must be chosen and demand vertices (clients) connected to these chosen facilities. We consider a stochastic version of such a problem where the solution is constructed in two stages: Before the actual requirements materialize, we can choose elements in a first stage. The actual requirements are then revealed, drawn from a pre-specified probability distribution π thereupon, some more elements may be chosen to obtain a feasible solution for the actual requirements. However, in this second (recourse) stage, choosing an element is costlier by a factor of σ> 1. The goal is to minimize the first stage cost plus the expected second stage cost.We give a general yet simple technique to adapt approximation algorithms for several deterministic problems to their stochastic versions via the following method. First stage: Draw σ independent sets of clients from the distribution π and apply the approximation algorithm to construct a feasible solution for the union of these sets. Second stage: Since the actual requirements have now been revealed, augment the first-stage solution to be feasible for these requirements. We use this framework to derive constant factor approximations for stochastic versions of Vertex Cover, Steiner Tree and Uncapacitated Facility Location for arbitrary distributions π in one fell swoop. For special (product) distributions, we obtain additional and improved results. Our techniques adapt and use the notion of strict cost-shares introduced in [5].