cssi/SciSciGPT-SciSciNet huggingface dataset:
Axonal BACE1 dynamics and targeting in hippocampal neurons: a role for Rab11 GTPase

BACE1 is one of the two enzymes that cleave amyloid precursor protein to generate Alzheimer's disease (AD) beta amyloid peptides. It is widely believed that BACE1 initiates APP processing in endosomes, and in the brain this cleavage is known to occur during axonal transport of APP. In addition, BACE1 accumulates in dystrophic neurites surrounding brain senile plaques in individuals with AD, suggesting that abnormal accumulation of BACE1 at presynaptic terminals contributes to pathogenesis in AD. However, only limited information is available on BACE1 axonal transport and targeting. By visualizing BACE1-YFP dynamics using live imaging, we demonstrate that BACE1 undergoes bi-directional transport in dynamic tubulo-vesicular carriers along axons in cultured hippocampal neurons and in acute hippocampal slices of transgenic mice. In addition, a subset of BACE1 is present in larger stationary structures, which are active presynaptic sites. In cultured neurons, BACE1-YFP is preferentially targeted to axons over time, consistent with predominant in vivo localization of BACE1 in presynaptic terminals. Confocal analysis and dual-color live imaging revealed a localization and dynamic transport of BACE1 along dendrites and axons in Rab11-positive recycling endosomes. Impairment of Rab11 function leads to a diminution of total and endocytosed BACE1 in axons, concomitant with an increase in the soma. Together, these results suggest that BACE1 is sorted to axons in endosomes in a Rab11-dependent manner. Our results reveal novel information on dynamic BACE1 transport in neurons, and demonstrate that Rab11-GTPase function is critical for axonal sorting of BACE1. Thus, we suggest that BACE1 transcytosis in endosomes contributes to presynaptic BACE1 localization.
World Englishes and applied linguistics

ABSTRACT: This paper addresses the issue of the relationship between world Englishes (WE) and applied linguistics. The diffusion of English is seen in terms of three concentric circles: the Inner Circle (L1 varieties, e.g. the USA and the UK), the Outer Circle (ESL varieties), and the Expanding Circle (EFL varieties). The discussion is essentially restricted to the Outer Circle in which the institutionalized non-native varieties of English are used in multilingual and multicultural contexts. The discussion is about four major issues: theoretical, applied, societal and ideological, and focuses specifically on: (a) attitudes concerning the ontological status of the varieties of English, (b) generalizations about the creative strategies used for learning English in multilingual/multicultural contexts, (c) descriptions of the pragmatic and interactional contexts of WEs and their implications, (d) assumptions concerning multicultural identities of WEs, (e) assumptions about the role of English in initiating ideological and social change, and (f) assumptions about communicative competence in English. This paper is divided into the following sections: ontological issues, conflict between idealization and reality, acquisition and creativity, the ‘leaking paradigms’, cultural content of English, ideological change, where applied linguistics fails the Outer Circle of English, and types of fallacies about WEs. This study does not view applied linguistics as divorced from social concerns: the concerns of relevance to the society in which we live. This view, then, entails social responsibility and accountability for research in applied linguistics.
MOUNTAIN PLOVER POPULATION RESPONSES TO BLACK-TAILED PRAIRIE DOGS IN MONTANA

Abstract We studied a local population of mountain plovers (Charadrius montanus) in southern Phillips County, Montana, USA, from 1995 to 2000 to estimate annual rates of recruitment rate (f) and population change (λ). We used Pradel models, and we modeled λ as a constant across years, as a linear time trend, as year-specific, and with an additive effect of area occupied by prairie dogs (Cynomys ludovicianus). We modeled recruitment rate (f) as a function of area occupied by prairie dogs with the remaining model structure identical to the best model used to estimate λ. Our results indicated a strong negative effect of area occupied by prairie dogs on both λ (slope coefficient on a log scale was −0.11; 95% CI was −0.17, −0.05) and f (slope coefficient on a logit scale was −0.23; 95% CI was −0.36, −0.10). We also found good evidence for a negative time trend on λ; this model had substantial weight (wi = 0.31), and the slope coefficient on the linear trend on a log scale was −0.10 (95% CI was −0.15, −0.05). Y...
Associations Between Marital Conflict and Adolescent Conflict Appraisals, Stress Physiology, and Mental Health.

The goal of the current study was to examine conflict appraisals and diurnal cortisol production as mediators of the robust association between marital conflict and adolescent adjustment problems. Parents reported their marital conflict and were observed engaging in a marital conflict discussion; they also reported adolescent internalizing and externalizing behaviors. Adolescents (n = 105, 52% female, 10–17 years of age) appraised their parents’ marital conflict and reported their internalizing and externalizing behaviors. After the laboratory visit, adolescents provided four saliva samples on each of 2 consecutive days to assess diurnal cortisol production. More-negative marital conflict predicted more self-blame for parental conflict, which in turn predicted less robust decreases in cortisol across the day. Further, this flattened cortisol production pattern mediated the relationship between greater self-blame for parental conflict and adolescents’ elevated internalizing behaviors. Feeling responsible f...
A Gossip-Style Crash Faults Detection Protocol for Wireless Ad-Hoc and Mesh Networks

In this paper, we introduce a new failure detector for wireless ad-hoc and mesh networks that adapts the detection parameters to the current state of the network. This new crash faults detector implements a variant of the heartbeat approach on top of a gossip-style failure detection protocol. Our failure detector is shown be eventually perfect by satisfying both properties: strong completeness (i.e., there is a time after which every faulty mobile is permanently suspected by every fault-free host) and eventual strong accuracy (i.e., no host will be suspected before it crashes).
Frequency-controlled series-resonant DC-DC converter with center-tapped synchronous rectifier

A frequency-controlled series resonant DC-DC converter is presented. It consists a Class-D zero-voltage switching series resonant inverter and a center-tapped synchronous rectifier. If the DC output voltage is low, the efficiency of the converter is dominated by the efficiency of the rectifier. Low on-resistance MOSFETs are used in the rectifier instead of diodes. Therefore, the forward voltage drop is low, resulting in a high-efficiency. The DC output voltage is regulated against variations in the load resistance and the DC input voltage by varying the operating frequency. Experimental results are presented for a converter with a DC input voltage of 150 V, an output voltage of 5 V, and a DC load resistance ranging from 0.5 to 5 /spl Omega/. The measured efficiency was 80% for a 50 W output and 89% for a 25 W output. The theoretical results were in good agreement with the measured results.
Encoding of Intention and Spatial Location in the Posterior Parietal Cortex

The posterior parietal cortex is functionally situated between sensory cortex and motor cortex. The responses of cells in this area are difficult to classify as strictly sensory or motor, since many have both sensory- and movement-related activities, as well as activities related to higher cognitive functions such as attention and intention. In this review we will provide evidence that the posterior parietal cortex is an interface between sensory and motor structures and performs various functions important for sensory-motor integration. The review will focus on two specific sensory-motor tasks-the formation of motor plans and the abstract representation of space. Cells in the lateral intraparietal area, a subdivision of the parietal cortex, have activity related to eye movements the animal intends to make. This finding represents the lowest stage in the sensory-motor cortical pathway in which activity related to intention has been found and may represent the cortical stage in which sensory signals go "over the hump" to become intentions and plans to make movements. The second part of the review will discuss the representation of space in the posterior parietal cortex. Encoding spatial locations is an essential step in sensory-motor transformations. Since movements are made to locations in space, these locations should be coded invariant of eye and head position or the sensory modality signaling the target for a movement Data will be reviewed demonstrating that there exists in the posterior parietal cortex an abstract representation of space that is constructed from the integration of visual, auditory, vestibular, eye position, and propriocaptive head position signals. This representation is in the form of a population code and the above signals are not combined in a haphazard fashion. Rather, they are brought together using a specific operation to form "planar gain fields" that are the common foundation of the population code for the neural construct of space.
Academic Service Learning as Pedagogy: An Approach to Preparing Preservice Teachers for Urban Classrooms

ABSTRACT ACADEMIC SERVICE-LEARNING AS PEDAGOGY: AN APPROACH TO PREPARING PRESERVICE TEACHERS FOR URBAN CLASSROOMS Teacher education struggles with multifaceted and increasingly complex issues surrounding preparing majority (White) teachers to work effectively with minority (non-White) students, families and communities. Novice teachers entering the workforce need to be culturally responsive. What are the benefits to students, community, and university when academic service learning (AS-L) is a course component? How does AS-L impact the personal intellectual growth of preservice teachers? This phenomenological qualitative study examined dispositions of 177 preservice teachers engaged in literacy and multicultural education courses with AS-L components. A nesting design was selected for this study situating preservice teachers in the center, surrounded by university teacher education coursework, which in turn, is surrounded by a larger circle encompassing local K-12 public schools and the community at large, where all are located. Data were collected over the course of five consecutive semesters, using four different data sources, with written reflections the primary source. Ethnographic techniques of participant observation, informal and formal interviewing were also used to collect data. Artifacts and field notes resulting from observations and interview transcripts were considered when triangulating reflection data, comparing evidence from different sources and using multiple perceptions to clarify meaning. Using different data sources permitted examination of the same phenomena through different lens. Data were analyzed using open coding, an inductive content analysis, and the constant comparative method, both systematic yet dynamic approaches. Comparing different data sources allowed for the comparison of views, situations, actions, and experiences of different individuals. Data analysis led to four significant categories: displacement, transformation, acceptance, and moving from negative, judgmental attitudes to positive, non-judgmental attitudes. This investigation suggested that AS-L components improved and strengthened teacher education courses in terms of adequately preparing preservice teachers to teach successfully in urban environments. This study resulted in preservice teachers whose dispositions and appreciation of diversity and culturally responsive teaching increased.
Patient counseling increases postpartum follow-up in women with gestational diabetes mellitus

Objective The objective of the study was to evaluate the efficacy of an educational intervention at increasing the rates of postpartum (PP) follow-up for women with gestational diabetes mellitus (GDM). Study Design A retrospective cohort study of all patients with GDM delivering during 2002-2009 was conducted. The primary outcome was obtaining PP diabetes testing. The 2002-2006 cohort was advised to obtain PP testing by their providers. The 2007-2009 cohort received educational counseling at the 37-38 week visit by a nurse educator. Univariate and multivariable statistical tests were utilized. Results The PP testing frequency was 53% for the 2007-2009 cohort, compared with 33% for the 2002-2006 cohort ( P P P P = .005). There was a nonsignificant decrease in the African American follow-up, 28% to 17% ( P = .414). Conclusion GDM precedes the development of type 2 diabetes. Antepartum education counseling increases postpartum diabetes testing. More efforts are needed to obtain universal screening.
ACTIVATION OF ESCHERICHIA COLI RRNA TRANSCRIPTION BY FIS DURING A GROWTH CYCLE

rRNA transcription in Escherichia coli is activated by the FIS protein, which binds upstream of rrnp1 promoters and interacts directly with RNA polymerase. Analysis of the contribution of FIS to rrn transcription under changing physiological conditions is complicated by several factors: the wide variation in cellular FIS concentrations with growth conditions, the contributions of several other regulatory systems to rRNA synthesis, and the pleiotropy of fis mutations. In this report, we show by in vivo footprinting and Western blot analysis that occupancy of the rrnBp1 FIS sites correlates with cellular levels of FIS. We find, using two methods of measurement (pulse induction of a FIS-activated hybrid promoter and primer extension from an unstable transcript made from rrnBp1), that the extent of transcription activation by FIS parallels the degree of FIS site occupancy and therefore cellular FIS levels. FIS activates transcription throughout exponential growth at low culture density, but rrnp1 transcription increases independently of FIS immediately following upshift, before FIS accumulates. These results support the model that FIS is one of a set of overlapping signals that together contribute to transcription from rrnp1 promoters during steady-state growth.
State-level differences in breast and cervical cancer screening by disability status: United States, 2008.

Introduction and Background Despite reported disparities in the use of preventive services by disability status, there has been no national surveillance of breast and cervical cancer screening among women with disabilities in the United States. To address this, we used state-level surveillance data to identify disparities in breast and cervical cancer screening among women by disability status. Methods Data from the 2008 Behavioral Risk Factor Surveillance System were used to estimate disability prevalence and state-level differences in breast and cervical cancer screening among women by disability status. Results Overall, modest differences in breast cancer screening were found; women with a disability were less likely than those without to report receiving a mammogram during the past 2 years (72.2% vs. 77.8%; p Discussion This epidemiologic evidence identifies an opportunity for federal and state programs, as well as other stakeholders, to form partnerships to align disability and women's health policies. Furthermore, it identifies the need for increased public awareness and resource allocation to reduce barriers to breast and cervical cancer screening experienced by women with disabilities.
Chronic administration of aldosterone depresses baroreceptor reflex function in the dog.

In a previous study it was shown that acute perfusion of aldosterone into the isolated carotid sinus decreased baroreceptor activity. The aim of the present study was to determine whether chronic, systemic administration of aldosterone also depresses baroreflex function. In six conscious dogs, the baroreflex was determined before and 10 days after an osmotic minipump containing aldosterone (100 micrograms/kg in 2 mL) was implanted. The slope of the relation between systolic arterial pressure and heart rate was significantly blunted after aldosterone administration (9.1 +/- 0.7 versus 13.3 +/- 1.2 for nitroglycerin, P < .01; 23.4 +/- 5.0 versus 40.1 +/- 5.0 for phenylephrine, P < .01). Baroreflex slopes did not change in a sham group (minipump with saline) and an aldosterone plus spironolactone (600 mg/d) group. Plasma aldosterone levels were significantly elevated after the aldosterone minipump was implanted (443 +/- 72 versus 37 +/- 11 pg/mL, P < .001). Mean arterial pressure was not significantly increased after aldosterone (106.5 +/- 3.8 versus 100.4 +/- 2.6 mm Hg, P = .2). On the 10th day after aldosterone or saline infusion, an acute experiment was carried out. Single baroreceptor fibers were recorded from the carotid sinus nerve. Compared with the sham group, the threshold was significantly elevated in the aldosterone group (111.3 +/- 2.1 versus 85.8 +/- 2.8 mm Hg), and the peak discharge rate was markedly decreased (32.5 +/- 1.5 versus 54.7 +/- 2.5 spikes per second, P < .01). The depressed baroreceptor function could be partially restored after a bolus injection of the Na+,K(+)-ATPase inhibitor ouabain (5 micrograms/kg i.v.).(ABSTRACT TRUNCATED AT 250 WORDS)
Time synchronization via lunar radar

The advent of round-trip radar measurements has permitted the determination of the ranges to the nearby planets with greater precision than was previously possible. When the distances to the planets are known with high precision, the propagation delay for electromagnetic waves reflected by the planets may be calculated and used to synchronize remotely located clocks. Details basic to the operation of a lunar radar indicate a capability for clock synchronization to ±20 µs. One of the design goals for this system was to achieve a simple semiautomatic receiver for remotely located tracking stations. The lunar radar system is in operational use for deep space tracking at Jet Propulsion Laboratory and synchronizes five world-wide tracking stations with a master clock at Goldstone, Calif. Computers are programmed to correct the Goldstone transmissions for transit time delay and Doppler shifts so as to be received on time at the tracking stations; this dictates that only one station can be synchronized at a given time period and that the moon must be simultaneously visible to both the transmitter and receiver for a minimum time of 10 min. Both advantages and limitations of the system are given. Finally, an experiment is described which has detected the effects of lunar topography and libration on radar results; a monthly cyclic effect in time synchronization of about ± 6 µs is shown.
Molecular characterization of catalytic-subunit cDNA sequences encoding protein phosphatases 1 and 2A and study of their roles in the gibberellin-dependent Osamy-c expression in rice.

To understand the molecular mechanism of gibberellin-dependent gene regulation, the effect of three phosphatase inhibitors on the germination of rice seeds and the expression of a target gene, the α-amylase gene, Osamy-c, were measured. We found that okadaic acid, microcystin-LR, and calyculin A, which are known to specifically inhibit Ser/Thr phosphatases 1 and 2A, strongly inhibit the expression of the Osamy-c and may be involved in the germination of rice seeds.
The role of crustal and eruptive processes versus source variations in controlling the oxidation state of iron in Central Andean magmas

Abstract The composition of the continental crust is closely tied to subduction zone magmatism. Elevated oxygen fugacity ( f O 2 ) plays a central role in fostering crystallization of oxide minerals and thereby aids in generating the calc-alkaline trend of iron depletion that characterizes the continents. Along continental margins, arc magmas erupt through continental crust and often undergo extensive differentiation that may modify magmatic f O 2 . The importance of the subducting slab and mantle wedge relative to the effects of this differentiation on the f O 2 recorded by continental arc magmas remains relatively unconstrained. Here, we focus on the effect of differentiation on magmatic f O 2 using a suite of 14 samples from the Central Volcanic Zone (CVZ) of the Andes where the continental crust is atypically thick (60–80 km). The samples range in composition from ∼55 to 74 wt% SiO2 and represent the Neogene history of the arc. Samples are basaltic andesite to rhyolite and span a range of radiogenic isotopic compositions (87Sr/86Sr = ∼0.705–0.712) that represent 30 to 100% crustal assimilation. We use several proxies to estimate the f O 2 recorded by lavas, pumice, and scoria: (1) whole rock Fe 3 + / Σ Fe ratios, (2) Fe 3 + / Σ Fe ratios in quartz-hosted melt inclusions, and (3) Fe–Ti oxide oxygen-barometry. Comparison of the f O 2 calculated from bulk Fe 3 + / Σ Fe ratios (post-eruptive) with that derived from Fe–Ti oxides or melt inclusion Fe 3 + / Σ Fe ratios (pre-eruptive), enables us to quantify the effect of syn- or post-eruptive alteration, and to select rocks for bulk analysis appropriate for the determination of pre-eruptive magmatic f O 2 using a strict criterion developed here. Across our sample suite, and in context with samples from the literature, we do not find evidence for systematic oxidation due to crystal fractionation or crustal contamination. Less evolved samples, ranging from 55 to 61 wt% SiO2, record a range of >3 orders of magnitude in f O 2 , spanning the f O 2 range recorded by all samples in our suite. Among these less evolved magmas, we find that those erupted from volcanic centers located closer to the trench, closer to the Benioff Zone, and with more geochemical evidence of subducted components in the mantle source (elevated La/Nb) result in magmas that record systematically higher f O 2 . We conclude that the slab/mantle source can exert greater control on magmatic f O 2 than processes occurring in even the thickest continental crust. Thus, the f O 2 of arc magmas, and hence their calc-alkaline nature, may be inherited from the mantle.
Transnational Structures and Protest: Linking Theories and Assessing Evidence

Despite the burgeoning literature on globalization, the effects of transnational processes on collective action remain under-theorized. Linking concepts from world-system, dependency, and international relations theories with political process theory, I generate sixteen propositions about transnational structural sources of protest. Five facets of political opportunity structure are examined: institutional access, unstable political alignments, divided elites, influential allies, and repression. Drawing from a wide range of sources, I then assess the validity of each proposition. The available evidence indicates that cyclical phases in the capitalist world economy, economic and political dependency, and competition and conflict among states significantly affect dimensions of political opportunity.
The Biology and Taxonomy of Some Immature Nearctic Tabanidae (Diptera)

Larvae and pupae of 11 species of Chrysops , 3 species of Tabanus, 4 species of Hybomitra, and 1 species of Atylotus (Tabanidae: Diptera) were reared to the adult stage. All field-collected larvae were reared individually in plastic containers, and were fed maggots of the common house fly, Musca domestica L. Descriptions of the larvae and pupae are given for the first time for Chrysops aberrans Philip, C. pikei Whitney, Hybomitra metabola (McDunnough) and H. nuda (McDunnough). An original description of the pupa of C. aestuans abaestuans Philip is given, and a clarification is made for the larval and pupal stages of Tabanus similis Macquart. All new descriptions are supported by drawings of taxonomic characters. Larval and pupal keys are presented for the identification of all known immature stages of Nearctic species.
Integrated Propeller-Wing Design Exploration for Distributed Propulsion Concepts

Distributed Electric Propulsion (DEP) technology uses a series of electrically-driven propellers distributed along the leading edge of an aircraft wing as a means to augment lowspeed lift. This enables design of a much smaller wing, leading to large improvements in aircraft cruise efficiency. The design of these “high-lift” propellers challenges current semiempirical and analytical methods for propeller design, since the primary requirement of these devices is to produce a large induced velocity over a unit span at low power and low swirl. Thrust, the byproduct of this large induced velocity, is not necessarily desired due to the requirement for the aircraft to descend at low speeds with this slipstream-induced lift augmentation. This paper builds upon prior research that investigates the salient trades for high-lift propellers to be used by DEP-enabled concepts, and includes an updated parametric blade shape representation, an ability to parametrically vary blade airfoil geometry, and a means to account for the vertical offset of the propeller streamtube due to nacelle integration into the wing. Using space-filling designs, the high-lift propeller tradespace is systematically explored, and the relevant design freedom and trades associated with these new parameters is established using a probabilistic Compromise Programming ranking approach. The results indicate that a significant increase in design freedom is established through the new approach, enabling wider application of DEP technology.
Analysis and Damage Sensitivity of Design Pathfinder for Inflatable Systems

Engineered inflatable systems are designed to precisely control internal or external surfaces, or both, to achieve a desired response or structure. The dynamics and structure of inflatable systems are directly related to the configuration of interfacing boundaries. A design pathfinder for inflatable systems has been developed over the past three years and this paper presents nonlinear finite element (FE) simulations performed to evaluate the performance of the pathfinder and its sensitivity to imposed damage. The static deflection response of the design pathfinder was compared with performance standards for terrestrial and space-based radar reflectors and radar decoys. Further, damage was introduced as thread loss along seams of the internal structure of the design pathfinder. It was found that the design pathfinder met or exceeded all performance standards and the static response remained unchanged under a significant level of damage. The work presented in this paper verifies the development of the design pathfinder. Further, the methods used in development of the pathfinder can be used to improve efficiency of design and analysis techniques for future inflatable structures.
HIV, Syphilis, hepatitis B and hepatitis C infections and related risk factors among migrant workers at construction sites in Fangchenggang City

Objective To understand the prevalence of HIV, syphilis, hepatitis B and hepatitis C infections and related risk factors among migrant workers at construction sites in Fangchenggang City. Methods With stratified cluster random sampling method, the migrant workers from large, medium and small construction sites in Fangchenggang City were interviewed through a structured questionnaire. Then blood samples were collected to detect HIV, syphilis, hepatitis B, and hepatitis C infections. Results We investigated a total of 500 migrant workers including 458 males, 42 females, with mean age of(31.83 ± 9.14) years. The infection rates of HIV, syphilis,hepatitis B, hepatitis C were 0.40%, 1.00%, 17.80% and 1.00%, respectively. The awareness rate about HIV was75.40%,and there was no statistically significant difference in the awareness rate between men and women(χ2=0.015, P =0.901),neither significant difference between the migrant workers from Guangxi and those from other provinces outside of Guangxi(χ2=0.124, P =0.725). Only 29.60% of the migrant workers were willing to work with HIV-infected persons, and 43.80% of the investigated participants hoped that AIDS patients should be isolated. In458 male workers, 58(12.66%)persons had a history of commercial sex behavior with only 58.62%(34/58) of consistent condom using rate, 39 people(8.52%) had a history of sex behavior with temporary partners.Conclusions There are some risk factors of infecting HIV and sexually transmitted diseases among migrant workers at construction sites in Fangchenggang City. Health education, behavioral intervention and disease monitoring among the migrant workers at construction sites should be strengthen.
Identification of receptor domains that modify ligand binding to 5-hydroxytryptamine2 and 5-hydroxytryptamine1c serotonin receptors

Serotonin [5-hydroxytryptamine (5-HT)] receptors are distinguished pharmacologically by their characteristic affinities for agonists and antagonists. Two serotonin receptors, the 5-HT2 and 5-HT1c, share a number of pharmacologic and structural properties while differing in their affinities for certain agonists and antagonists. To identify regions of the 5-HT2 and 5-HT1c receptors important for specifying their unique pharmacology, we constructed six chimeric 5-HT2/5-HT1c receptors in which domains of each receptor were exchanged. The abilities of several drugs to inhibit [3H]mesulergine bound to the chimeric and parent receptors transiently expressed in COS-7 cells were then examined. For spiperone and haloperidol (both butyrophenones), chimeras that exchanged transmembrane (TM) domains I and II or TMs I-III had the greatest effects on binding affinity. The binding affinity of cinanserin (a cinnamanilide) was significantly changed in all the chimeras studied. In contrast, the binding of ketanserin (a 4-fluorobenzoylpiperidine) was strongly influenced by chimeras that exchanged TMs I-III (but not I and II) and by chimeras that exchanged intracellular loop 3 to TM VII. 5-HT binding affinity was greatly altered for chimeras that exchanged domains of intracellular loop 3 to TM VII, with minor effects being noted for chimeras that exchanged TMs I and II and I-III. The affinities of the nonselective drugs mesulergine, mianserin, and m-chlorophenylpiperazine were relatively unaffected when domains of the 5-HT2 and 5-HT1c receptors were exchanged. Taken together, these results imply that structurally diverse 5-HT2 antagonists utilize distinct regions of the 5-HT2 receptor for high affinity binding.
Peasants, Population and Progress

The word “peasant” is now an anthropological concept designating a particular mode of production and its concomitant culture in terms so general that we may use it with equal propriety of societies in eighteenth-century Poland, medieval China and contemporary India. Alan Macfarlane1 has summarized the evolution of this concept since the Second World War and concluded, on the basis of his own historical investigations, that: England has been inhabited since at least the thirteenth century by a people whose social, economic and legal system was in essence different not only from that of peoples in Asia and Eastern Europe, but also in all probability from the Celtic and Continental countries of the same period.2
Development of a Style Guide for the Traffic Flow Management Traffic Situation Display Graphical User Interface

Traffic Flow Management (TFM) functions to minimize airspace congestion and maximize safety and efficiency. TFM personnel at the U.S. Federal Aviation Administration use Traffic Situation Display (...
Prostate Health Index density improves detection of clinically significant prostate cancer.

Objectives To explore the utility of prostate health index (PHI) density for detection of clinically-significant prostate cancer (PCa) in a contemporary cohort of men presenting for diagnostic workup of PCa. Patients & Methods The study cohort included patients with elevated PSA (>2 ng/ml) and negative digital rectal examination who underwent PHI testing and prostate biopsy at our institution in 2015. Serum markers were prospectively measured per standard clinical pathway. PHI was calculated as [([-2]proPSA/free PSA) x (PSA)½], and density calculations were performed using prostate volume as determined on transrectal ultrasound. Logistic regression was used to assess the ability of serum markers to predict clinically-significant PCa, defined as any Gleason score ≥7 cancer or Gleason score 6 cancer in >2 cores or >50% of any positive core. Results Of 118 men with PHI testing who underwent biopsy, 47 (39.8%) were found to have clinically-significant PCa on biopsy. The median PHI density was 0.70 (IQR 0.43-1.21); it was 0.53 (IQR 0.36-0.75) in men with negative biopsy or clinically-insignificant PCa and 1.21 (IQR 0.74-1.88) in men with clinically-significant PCa (p 1.21 (p<0.001). Using a threshold of 0.43, PHI density was 97.9% sensitive and 38.0% specific for clinically-significant PCa, and 100% sensitive for Gleason score ≥7 disease. Compared to PSA (AUC 0.52), PSAD (AUC 0.70), %free PSA (AUC 0.75), the product of %free PSA and prostate volume (AUC 0.79), and PHI (AUC 0.76), PHI density demonstrated the highest discriminative ability for clinically-significant PCa (AUC 0.84). Conclusions Based on this prospective single-center experience, PHI density could be used to avoid 38% of unnecessary biopsies while failing to detect only 2% of clinically-significant cancers. This article is protected by copyright. All rights reserved.
Clinical Outcomes of Metformin Use in Populations With Chronic Kidney Disease, Congestive Heart Failure, or Chronic Liver Disease: A Systematic Review.

Background Recent changes to the U.S. Food and Drug Administration boxed warning for metformin will increase its use in persons with historical contraindications or precautions. Prescribers must understand the clinical outcomes of metformin use in these populations. Purpose To synthesize data addressing outcomes of metformin use in populations with type 2 diabetes and moderate to severe chronic kidney disease (CKD), congestive heart failure (CHF), or chronic liver disease (CLD) with hepatic impairment. Data sources MEDLINE (via PubMed) from January 1994 to September 2016, and Cochrane Library, EMBASE, and International Pharmaceutical Abstracts from January 1994 to November 2015. Study selection English-language studies that: 1) examined adults with type 2 diabetes and CKD (with estimated glomerular filtration rate less than 60 mL/min/1.73 m2), CHF, or CLD with hepatic impairment; 2) compared diabetes regimens that included metformin with those that did not; and 3) reported all-cause mortality, major adverse cardiovascular events, and other outcomes of interest. Data extraction 2 reviewers abstracted data and independently rated study quality and strength of evidence. Data synthesis On the basis of quantitative and qualitative syntheses involving 17 observational studies, metformin use is associated with reduced all-cause mortality in patients with CKD, CHF, or CLD with hepatic impairment, and with fewer heart failure readmissions in patients with CKD or CHF. Limitations Strength of evidence was low, and data on multiple outcomes of interest were sparse. Available studies were observational and varied in follow-up duration. Conclusion Metformin use in patients with moderate CKD, CHF, or CLD with hepatic impairment is associated with improvements in key clinical outcomes. Our findings support the recent changes in metformin labeling. Primary funding source U.S. Department of Veterans Affairs. (PROSPERO: CRD42016027708).
Stroke Hospital Characteristics in the Florida-Puerto Rico Collaboration to Reduce Stroke Disparities Study.

OBJECTIVES Although disparities in stroke care and outcomes have been well documented nationally, state-based registries to monitor acute stroke care in Florida (FL) and Puerto Rico (PR) have not been established. The FL-PR Collaboration to Reduce Stroke Disparities (CReSD) was developed to evaluate race-ethnicity and regional disparities in stroke care performance. The objective of this study was to assess and compare hospital characteristics within a large quality improvement registry to identify characteristics associated with better outcomes for acute ischemic stroke care. METHODS Trained personnel from 78 FL-PR CReSD hospitals (69 FL, 9 PR) completed a 50-item survey assessing institutional characteristics across seven domains: acute stroke care resource availability, emergency medical services integration, stroke center certification, data collection and use, quality improvement processes, FL-PR CReSD recruitment incentives, and hospital infrastructure. RESULTS The rate of survey completion was 100%. Differences were observed both within FL and between FL and PR. Years participating in Get With The Guidelines-Stroke (8.9 ± 2.6 years FL vs 4.8 ± 2.4 years PR, P < 0.0001) and proportion of hospitals with any stroke center certification (94.2% FL vs 11.1% PR, P < 0.0001) showed the largest variations. Smaller hospital size, fewer years in Get With The Guidelines-Stroke, and lack of stroke center designation and acute stroke care practice implementation may contribute to poorer outcomes. CONCLUSIONS Results from our survey indicated variability in hospital- and system-level characteristics in stroke care across hospitals in Florida and Puerto Rico. Identification of these variations, which may explain potential disparities, can help clinicians understand gaps in stroke care and outcomes and targeted interventions to reduce identified disparities can be implemented.
Controlling the signal: Practical privacy protection of genomic data sharing through Beacon services.

Genomic data is increasingly collected by a wide array of organizations. As such, there is a growing demand to make summary information about such collections available more widely. However, over the past decade, a series of investigations have shown that attacks, rooted in statistical inference methods, can be applied to discern the presence of a known individual’s DNA sequence in the pool of subjects. Recently, it was shown that the Beacon Project of the Global Alliance for Genomics and Health, a web service for querying about the presence (or absence) of a specific allele, was vulnerable. The Integrating Data for Analysis, Anonymization, and Sharing (iDASH) Center modeled a track in their third Privacy Protection Challenge on how to mitigate the Beacon vulnerability. We developed the winning solution for this track. This paper describes our computational method to optimize the tradeoff between the utility and the privacy of the Beacon service. We generalize the genomic data sharing problem beyond that which was introduced in the iDASH Challenge to be more representative of real world scenarios to allow for a more comprehensive evaluation. We then conduct a sensitivity analysis of our method with respect to several state-of-the-art methods using a dataset of 400,000 positions in Chromosome 10 for 500 individuals from Phase 3 of the 1000 Genomes Project. All methods are evaluated for utility, privacy and efficiency. Our method achieves better performance than all state-of-the-art methods, irrespective of how key factors (e.g., the allele frequency in the population, the size of the pool and utility weights) change from the original parameters of the problem. We further illustrate that it is possible for our method to exhibit subpar performance under special cases of allele query sequences. However, we show our method can be extended to address this issue when the query sequence is fixed and known a priori to the data custodian, so that they may plan stage their responses accordingly. This research shows that it is possible to thwart the attack on Beacon services, without substantially altering the utility of the system, using computational methods. The method we initially developed is limited by the design of the scenario and evaluation protocol for the iDASH Challenge; however, it can be improved by allowing the data custodian to act in a staged manner.
Abstract 458: Choline metabolism in cancer cells modifies PD-L1 expression

Increased expression of choline kinase-α (Chk-α), the enzyme that converts choline to phosphocholine has been observed in most cancer cells including breast (1). This increase of choline kinase results in increased production of phosphocholine that is used in the synthesis of membrane phosphatidylcholine. We investigated the relationship between Chk-α and the programmed death ligand-1 (PD-L1) expression in triple negative MDA-MB-231 human breast cancer cells. Expression of PD-L1 in response to the secretion of interferon gamma (IFNγ) by cytotoxic T cells and its binding to the immune checkpoint PD-1 on T cells results in cancer cells escaping destruction by the immune system (2). Quantitative real-time PCR analysis (q-RT-PCR) did not reveal any change in PD-L1 mRNA expression between MDA-MB-231 expressing an empty vector control plasmid (231-EV) and MDA-MB-23 stably expressing shRNA against Chk (231-Chk). However, there was a difference in the mean intensity fluorescence (MIF) between 231-EV (325 ±11.5, n=2) and 231-Chk (527±18.5, n=2) in the FACS analysis. Upon induction with IFNγ (10ng/ml) for 24h, there was 1.23 fold increase in PD-L1 mRNA in 231-Chk compared to 231-EV. Interestingly, the MIP for cell surface expression of PD-L1 was 600±21 (n=2) for 231-EV compared to 872±16 (n=2) for 231-Chk cells. Values represent mean + SE. These data suggest that the cell surface increase of PD-L1 in 231-Chk cells could be due to translocation. Increased PD-L1 expression creates an opportunity to deliver PD-L1 targeted nanoparticles carrying therapeutic cargo. Since most conventional treatments result in a decrease of Chk-α and phosphocholine, our data suggest that these treatments may also result in cancer cells escaping immune surveillance through expression of PD-L1. Acknowledgements: This work was supported by NIH R01CA136576 and P50 CA103175. Reference: 1) Glunde K et al, Cancer Res 65, 11034 (2005)., 2) Zou W, Chen L, Nat Rev Immunol 8(6), 467-77 (2008). Citation Format: Balaji Krishnamachary, Marie-France Penet, Yelena Mironchik, Zaver M. Bhujwalla. Choline metabolism in cancer cells modifies PD-L1 expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 458. doi:10.1158/1538-7445.AM2017-458
Neutral effect of body mass index on implantation rate after frozen-thawed blastocyst transfer.

Objective To examine the effects of body mass index (BMI) on implantation rate after uniform protocol frozen-thawed blastocyst transfer in women with a homogenous uterine environment. Design Retrospective cohort study. Setting Single IVF clinic at a large academic institution. Patient(s) Four hundred sixty-one infertile women treated at a large academic institution from January 2007 to January 2014. Intervention(s) All women underwent standardized slow frozen-thawed blastocyst transfers with good-quality day 5–6 embryos, following an identical hormonal uterine preparation, with comparison groups divided according to BMI category: underweight ( 2 ), normal weight (18.5–24.9 kg/m 2 ), overweight (25.0–29.9 kg/m 2 ), and obese (≥30.0 kg/m 2 ). Main Outcome Measure(s) Implantation rate. Result(s) There were no statistically significant differences identified when comparing implantation rates among the four BMI cohorts. The implantation rate was 38.2% in normal weight patients, 41.7% in underweight patients, 45.1% in overweight patients, and 34.7% in obese patients. Adjusted odds ratios (OR) demonstrated no association between the main outcome, implantation rate, and BMI. Compared with the normal weight patients, the adjusted OR of implantation was 1.70 (95% confidence interval [CI], 0.40–7.72) for underweight patients, 1.61 (95% CI, 0.97–2.68) for overweight patients, and 0.92 (95% CI, 0.49–1.72) for obese patients. Secondary outcomes, including rates of miscarriage, clinical pregnancy, ongoing pregnancy, and live birth, were not significantly different between cohorts. While powered to detect a 16% difference between overweight and normal weight women, the study was underpowered to detect differences in the underweight and obese women, and no definitive conclusions can be drawn for these small cohorts. Patients with transfers that required the longest amount of time, greater than 200 seconds, had the highest average BMI of 27.5 kg/m 2 . Conclusion(s) Under highly controlled circumstances across 7 years of data from a single institution, using a uniform uterine preparation, following a precise transfer technique with high-quality day 5–6 slow frozen-thawed blastocysts, a BMI in the overweight range of 25–29.9 kg/m 2 is not associated with a poorer implantation rate or live-birth rate, nor is it associated with an increased risk of miscarriage when compared with a normal BMI range. The increased length of time required during transfer for women with higher BMI suggests body habitus may contribute to difficult transfers, although this may not translate into poorer implantation rates. By using a standardized protocol for slow freezing and thawing of embryos, using identical hormonal preparation and a uniform ET protocol, a homogenous uterine environment was created in this carefully selected cohort of women, thereby minimizing confounders and uniquely highlighting the neutral effect of overweight BMI on implantation rate.
Why Sc Voter Preferences Translate into Bsp Votes

Where we are strong, people will vote for us: there is a wave effect. First we were very resistant to the BSP people – we said Ambedkar [the Scheduled Caste leader from whom the BSP derives its ideology] is not a God so why should we believe in him. Most people here supported the Congress. Then later we shifted – there was no benefit from Congress for this village, and then, Congress was also getting weak. Theprevious chapter showed that the preferences of Scheduled Caste voters across parties correspond directly to their representational profile. In this chapter, I argue that for substantial numbers of Scheduled Caste voters, preferences do not automatically translate into votes. Even though they prefer the BSP, these voters are likely to vote for the BSP only when they expect their vote to install the BSP in government, or to affect the victory or defeat of one of its competitors. Where they do not expect to be able to affect the outcome in one of these two ways, they are unlikely to vote for the BSP. These Scheduled Caste voters, in other words, are strategic rather than expressive actors: They treat the vote as an instrument through which to obtain the best possible outcome rather than as an opportunity to declare their preferences. This chapter does not offer a precise estimate of the proportion of strategic voters among Scheduled Castes. However, it does provide evidence to indicate that this proportion is substantial, and that without the support of such voters, the BSP could not obtain majority support among Scheduled Castes. Expectations of efficacy, in turn, depend upon the distance between the numerical strength of the Scheduled Castes in the electorate and the threshold of winning or leverage imposed by the competitive configuration. Scheduled Castes know that others from their category also prefer the BSP to other parties. They also know that those groups not represented by the BSP (or its partner, where it contests elections in alliance) are not likely to prefer the BSP. Simply by counting heads in their constituency and in their state as a whole, therefore, they have the capacity to make some prediction about the efficacy of their vote.
Estimating degree of mechanical anisotropy in healthy and dystrophic rectus femoris of boys using VisR ultrasound, in vivo

In Duchenne muscular dystrophy (DMD), muscle fiber necrosis and subsequent progressive replacement of muscle by fibrous tissue and fat impacts the degree of anisotropy (DoA) in mechanical properties. Mechanical DoA can be assessed in skeletal muscle using Viscoelastic Response (VisR) ultrasound. We hypothesize that in vivo VisR DoA measures in the rectus femoris (RF) muscles of boys with DMD statistically differ from those in control boys. Further, we hypothesize that VisR DoA is correlated to RF functional output.