cssi/SciSciGPT-SciSciNet huggingface dataset:
How proteins bind macrocycles

The potential utility of synthetic macrocycles (MCs) as drugs, particularly against low-druggability targets such as protein-protein interactions, has been widely discussed. There is little information, however, to guide the design of MCs for good target protein-binding activity or bioavailability. To address this knowledge gap, we analyze the binding modes of a representative set of MC-protein complexes. The results, combined with consideration of the physicochemical properties of approved macrocyclic drugs, allow us to propose specific guidelines for the design of synthetic MC libraries with structural and physicochemical features likely to favor strong binding to protein targets as well as good bioavailability. We additionally provide evidence that large, natural product-derived MCs can bind targets that are not druggable by conventional, drug-like compounds, supporting the notion that natural product-inspired synthetic MCs can expand the number of proteins that are druggable by synthetic small molecules.
Dynamic changes in Wnt signaling are required for neuronal differentiation of mouse embryonic stem cells

Embryonic stem cells (ESC) and the epiblast share a similar gene expression profile and an attenuated cell cycle, making them an accessible and tractable model system to study lineage choice at gastrulation. Differentiation of the epiblast and ESC to the mesendodermal lineage has been shown to rely on Wnt/β-catenin signaling; which counterintuitively, is also required to inhibit differentiation and maintain pluripotency. To examine these seemingly contradictory roles, we developed a mouse ESC (ESC) line that inducibly expresses a dominant negative Tcf4 (dnTcf4) protein to block canonical Wnt signaling. Cells expressing the dnTcf4 protein differentiated largely to Sox3 positive neural precursors but were unable to progress to βIII tubulin positive neurons unless Wnt signaling was derepressed, demonstrating a sequential requirement for Wnt signaling in lineage differentiation. To determine if Wnt/β-catenin signaling is similarily required at sequential stages of neural differentiation in the intact embryo, we delivered shRNA targeting β-catenin to pregnant mice on E5.5 of development. Blocking canonical Wnt signaling during post-implantation development increased the number of neural precursors which failed to differentiate to mature neurons, and produced defects of embryonic axis elongation, neurulation and neural tube closure that phenocopy the β-catenin null embryo. These results demonstrate that lineage differentiation relies on sequential repression and derepression of critical signaling pathways involved in maintaining pluripotency versus differentiation.
HEALING OF BROKEN LINEAR DICENTRIC CHROMOSOMES IN YEAST

In yeast, meiotic recombination between a linear chromosome III and a haploid-viable circular chromosome will yield a dicentric, tandemly duplicated chromosome. Spores containing apparently intact dicentric chromosomes were recovered from tetrads with three viable spores. The spore containing the dicentric inherited URA3 (part of the recombinant DNA used to join regions near the ends of the chromosome into a circle) as well as HML, HMR and MAL2 (located near the two ends of a linear but deleted from the circle). The Ura+ Mal+ colonies were highly variegated, giving rise to as many as seven distinctly different stable ("healed") derivatives, some of which were Ura+ Mal +, others Ura+ Mal- and others Ura - Mal+. The colonies were also sectored for five markers (HIS4, LEU2, CRY1, MAT and THR4) initially heterozygous in the tandemly duplicated dicentric chromosome.—Southern blot and genetic analyses have demonstrated that these stable derivatives arose from mitotic break-age of the dicentric chromosome, followed by one of several different healing events. The majority of the stable derivatives contained circular or linear chromosomes apparently resulting from homologous recombination between a broken chromosome end and a homologous region on the other end of the original dicentric duplicated chromosome. A smaller proportion of events resulted in apparently uniquely healed linear chromosomes in which the broken chromosome acquired a new telomere. In two instances we recovered chromosome III partially duplicated with a novel right end. We have also found one derivative that had also experienced rearrangement of repeated DNA sequences found adjacent to yeast telomeres.
Interaction of cationic liposomes with cells of electrically active neuronal networks in culture

Incubation of rhodamine-labeled cationic liposomes with mature murine spinal cultures results in strong fluorescence that is evenly distributed on somata and neurites of neurons in 7 different cultures. Staining of the glial carpet is minimal. Rhodamine-labeled dextran, encapsulated in liposomes, also stains neurons. Electron microscope data show external attachment and intact internalization of liposomes. Spontaneous electrical bursting activity is altered but not lost after incubation.
Interactions of a horizontal flexible membrane with oblique incident waves

The interaction of oblique monochromatic incident waves with a horizontal flexible membrane is investigated in the context of two-dimensional linear hydro-elastic theory. First, analytic diffraction and radiation solutions for a submerged impermeable horizontal membrane are obtained using an eigenfunction expansion method. Secondly, a multi-domain boundary element method (BEM) is developed to confirm the analytic solutions. The inner solution based on a discrete membrane dynamic model and simple-source distribution over the entire fluid boundaries is matched to the outer solution based on an eigenfunction expansion. The numerical solutions are in excellent agreement with the analytic solutions. The theoretical prediction was then compared to a series of experiments conducted in a two-dimensional wave tank at Texas A&M University. The measured reflection and transmission coefficients reasonably follow the trend of predicted values. Using the computer program developed, the performance of surface-mounted or submerged horizontal membrane wave barriers is tested with various system parameters and wave characteristics. It is found that the horizontal flexible membrane can be an effective wave barrier if properly designed.
Managing Change: Party Competition in the New Ireland

Abstract Ireland represents a useful case for studying political parties and their strategies as independent variables. In a context of unprecedented social and economic change, party leaders have demonstrated unusual organisational creativity in adopting strategies to manage the political consequences of these changes. While the potential for new issues, cleavages and parties surely exists in this changing environment, and while elections have been hotly contested in the recent era of increasing floating voters and declining party membership, the traditional political parties have maintained their overall electoral dominance through it all. They have done so by systematically removing potentially contentious issues from the domain of electoral politics. This article is about political agency, focusing on the strategic choices of political party entrepreneurs. The current Irish party literature’s emphasis on electoral outcomes fails to appreciate sufficiently the various ways parties adopt strategies alon...
The Global Impact of Quotas: On the Fast Track to Increased Female Legislative Representation

Quotas have become an important mechanism through which women today are entering legislatures worldwide. This study shows that the introduction of quotas has helped overcome constraints on women's representation posed by economic underdevelopment, cultural influences, and even electoral systems. This study also demonstrates that the introduction of quotas offers the most explanatory power for women's representation today, together with electoral systems that allow for greater candidate turnover (i.e., party-list proportional representation systems). The majority of studies explaining women's legislative representation prior to 2000 focused on electoral systems, cultural considerations, and the strength of leftist political parties. Since the mid-1990s, however, an increasing number of countries have introduced gender quotas, which this article incorporates into older models in cross-national multivariate analysis.
Unemployment and the Democratic Electoral Advantage

This article calls into question the conventional wisdom that incumbent parties are rewarded when unemployment is low and punished when it is high. Using county-level data on unemployment and election returns for 175 midterm gubernatorial elections and 4 presidential elections from 1994 to 2010, the analysis finds that unemployment and the Democratic vote for president and governor move together. Other things being equal, higher unemployment increases the vote shares of Democratic candidates. The effect is greatest when Republicans are the incumbent party, but Democrats benefit from unemployment even when they are in control. The explanation for these findings is that unemployment is a partisan issue for voters, not a valence issue, and that the Democratic Party “owns” unemployment. When unemployment is high or rising, Democratic candidates can successfully convince voters that they are the party best able to solve the problem.
Left ventricular vortex formation is unaffected by diastolic impairment

Normal left ventricular (LV) filling occurs rapidly early in diastole caused by a progressive pressure gradient within the ventricle and with a low left atrial pressure. This normal diastolic function is altered in patients with heart failure. Such impairment of diastolic filling is manifested as an abrupt deceleration of the early filling wave velocity. Although variations within the early filling wave have been observed previously, the underlying hydrodynamic mechanisms are not well understood. Previously, it was proposed that the mitral annulus vortex ring formation time was the total duration of early diastolic filling and provided a measure of the efficiency of diastolic filling. However, we found that the favorable LV pressure difference driving early diastolic filling becomes zero simultaneously with the deceleration of the early filling wave propagation velocity and pinch-off of the LV vortex ring. Thus we calculated the vortex ring formation time using the duration of the early diastolic filling wave from its initiation to the time of the early filling wave propagation velocity deceleration when pinch-off occurs. This formation time does not vary with decreasing intraventricular pressure difference or with degree of diastolic dysfunction. Thus we conclude the vortex ring pinch-off occurs before the completion of early diastole, and its formation time remains invariant to changes of diastolic function.
Medical examination for asbestos-related disease

There are millions of workers whose exposure to asbestos dust prior to the implementation of asbestos regulation and improved control measures places them at risk of asbestos-related disease today. In addition, workers are still being exposed to significant amounts of asbestos, when asbestos materials in place are disturbed during renovation, repair, or demolition. Given the continued presence of asbestos-containing materials in industrial, commercial, and residential settings throughout the U.S., a sizeable population remains at risk of asbestos-related disease. This article reviews the health effects associated with exposure to asbestos and delineates the steps necessary for the comprehensive screening and clinical assessment for asbestos-related disease, in order to assist physicians in identifying and preventing illness associated with exposure to asbestos among their patients. Am. J. Ind. Med. 37:6–22, 2000. © 2000 Wiley-Liss, Inc.
Human vascular endothelial cells stimulate a lower frequency of alloreactive CD8+ pre-CTL and induce less clonal expansion than matching B lymphoblastoid cells: development of a novel limiting dilution analysis method based on CFSE labeling of lymphocytes.

We have previously shown that human endothelial cells (EC) are less efficient than professional APC, e.g., B lymphoblastoid cells (BLC), at stimulating allogeneic CD8(+) T cells to develop into CTL. In this study we describe FACS-based limiting dilution analyses using the dilution of the intracellular dye CFSE as an indicator of CD8(+) T cell alloactivation and expansion with significantly increased sensitivity compared with conventional, cytotoxicity-based assays. In addition, this assay permits the relative size of clonal CTL populations that are generated in individual CD8(+) T cell cultures to be determined (clonal burst size). We have applied this method to quantitatively compare the generation of CTL at the clonal level following stimulation of allogeneic CD8(+) T cells by either BLC or HUVEC derived from the same donor. CD8(+) T cells expanded by allostimulation were identified as CD8(+), CFSE(low) cells and were categorized as CTL by the expression of intracellular perforin and IFN-gamma. Precursor frequencies for EC-stimulated CTL were 5- to 40-fold (mean, 7.5-fold) lower compared with BLC-stimulated CTL (p < 0.01). Concomitantly, the average clonal burst sizes in EC-stimulated CTL cultures were significantly smaller than those in conventional CTL cultures, primarily due to the occurrence of some very large clone sizes exclusively with BLC stimulation. Although EC-stimulated CTL were generated only from the memory subset of CD8(+) T cells, BLC-stimulated very large burst sizes of CTL were observed from both naive and memory CD8(+) T cell precursors. These data establish that both a lower frequency of reactive precursors and more limited clonal expansion, but not regulatory T cells, contribute to the reduced capacity of EC to promote alloreactive CTL differentiation compared with that of professional APC.
Reduction of TRAIL-Induced Mcl-1 and cIAP2 by c-Myc or Sorafenib Sensitizes Resistant Human Cancer Cells to TRAIL-Induced Death

Summary Cells expressing oncogenic c-Myc are sensitized to TNF superfamily proteins. c-Myc also is an important factor in determining whether a cell is sensitive to TRAIL-induced apoptosis, and it is well established that the mitochondrial pathway is essential for apoptosis induced by c-Myc. We investigated whether c-Myc action on the mitochondria is required for TRAIL sensitivity and found that Myc sensitized cells with defective intrinsic signaling to TRAIL. TRAIL induced expression of antiapoptotic Mcl-1 and cIAP2 through activation of NF-κB. Both Myc and the multikinase inhibitor sorafenib block NF-κB. Combining sorafenib with TRAIL in vivo showed dramatic efficacy in TRAIL-resistant tumor xenografts. We propose the combination of TRAIL with sorafenib holds promise for further development.
Resonant Mie scattering from a layered sphere

The theory of Aden and Kerker is used to compute the resonant response of large layered spheres to an incident linearly polarized plane wave. Cases considered include hollow spheres and those with transparent and absorbing cores whose diameters range from zero up to that of the particle. Both core and layer resonances are studied. The results are presented as partial wave amplitudes, energy densities, and scattered light intensities for a typical resonant mode, TE39.
The role of laparoscopy in abdominal trauma

Since the advent of minimally invasive surgery, the use of laparoscopy for both diagnostic as well as therapeutic interventions has continued to expand in all of the surgical disciplines. In fact, this modality provides a viable alternative for the diagnosis of occult intra-abdominal injury following both penetrating and blunt trauma. The increased use of laparoscopy coupled with defined management algorithms has decreased the rate of negative and/or nontherapeutic laparotomy. This is particularly important in those patients where the potential for peritoneal violation exists without other clear indications for laparotomy. As technology and instrumentation continue to advance, future directions will include more attempts at therapeutic and ‘awake’ laparoscopy to embrace the advantages of minimally invasive surgery including decreased pain, expedited discharge and reduction of unnecessary laparotomy in suitable patients.
MPI Ruby: scripting in a parallel environment

Most of the work in scientific computing today is done in parallel algorithms, often via message-passing architectures such as the message-passing interface (MPI). A newly emerging language called Ruby, which maintains a strict adherence to object oriented principles and a clean, intuitive syntax. The author created MPI Ruby, a complete binding of MPI to Ruby. In this article, he introduces Ruby and MPI Ruby. Some applications and information on the project's current status and its availability are described.
Necrotizing Sarcoid Granulomatosis

Twelve cases of necrotizing sarcoid granulomatosis are presented as a retrospective study. The population of patients consisted of ten women and two men, with an average age of 50 years. Nine patients initially had a variety of pulmonary and nonpulmonary complaints, while three were asymptomatic. Chest roentgenograms demonstrated bilateral nodules in seven patients, solitary nodules in four, and a miliary pattern progressing to nodules in one. Enlarged hilar nodes were found in six. Histologically, all biopsies showed a combination of individual granulomas, confluent masses of granulomas which formed the nodular masses seen on the roentgenograms, a variable amount of necrosis of tissue and hyalinization, and a granulomatous vasculitis. Follow-up periods ranged from four months to 11 years. Eleven patients are alive and asymptomatic. The sole death occurred in a patient treated with an immunosuppressive agent (cyclophosphamide). We conclude that the clinical behavior of necrotizing sarcoid granulomatosis is not similar to that of the other angiocentric granulomatoses and that most patients with this disease can be left untreated or be treated with steroids alone. We suggest the possibility that necrotizing sarcoid granulomatosis may be the histologic counterpart of so-called nodular sarcoid.
Preservando La Propiedad a Través Del Poder De Lo Colectivo: Lecciones Para Barcelona (Preserving Homeownership Through the Power of the Collective: Lessons for Barcelona)

Spanish Abstract: El lugar de reunion era pequeno y lleno de gente ansiosa para poder hablar de sus preocupaciones: desempleo, pagos hipotecarios en mora y, sobretodo, desahucios pendientes. En la reunion asistimos un grupo de academicos, politicos, abogados y promotores de vivienda, que tuvimos que entrar a la sala casi a empujones de lo llena que estaba, para poder asi escuchar a todos los testimonios que iban hablando. La reunion no tuvo ningun lider, ni ninguna agenda preparada. Fue una mas de las reuniones recurrentes y periodicas que llevan a cabo en Barcelona propietarios que han sufrido y quen sufren la misma indignidad de ejecucion hipotecaria y el horror de sentirse impotentes para poder evitarlo. La informalidad de la reunion y el intercambio de experiencias sin guion es parte de la fuerza de estas reuniones organizadas por la Plataforma de Afectados por la Hipoteca (en adelante, "PAH"), un moviemiento creciente en Espana que tiene por objecto ofrecer mas derechos a los propietarios de viviendas que padecen - o pueden padecer - una ejecucion hipotecaria.Este arti pretende evaluar el poder do lo colectivo y su capacidad para lograr un cambio social y legal.English Abstract: The gathering space was cramped and crowded with anxious people nervously waiting to speak and tell of their heartbreak. Stories of unemployment, delinquent mortgage payments and pending evictions. A group of us, academics, policy makers, attorneys and housing developers, filed into the room jostling to find an empty space to stand witness to their heartache. The meeting had no leader, nor any prepared agenda. It was a regular gathering of current and former homeowners suffering the same indignity of foreclosure and the awfulness of feeling helpless to prevent it. The informality of the gathering and the unscripted sharing of experiences are part of the strength of these meetings organized by the Plaftorm for People Affected by Mortgages (“PAH”), a growing movement in the Catalan region of Spain to provide greater rights to homeowners experiencing foreclosure. This article seeks to evaluate the power of the collective and its ability to effect social and legal change.
Online smoking cessation program for Korean Americans: Randomized trial to test effects of incentives for program completion and interim surveys.

Abstract Introduction Smoking is prevalent among Korean American men. Quitting is Winning, an Internet-based, cognitive-behavioral smoking cessation program, was developed using community-based participatory research principles. Methods A randomized controlled trial was used to evaluate whether participants were more likely to complete the program and quit smoking at 6-months of follow-up with additional reinforcement. The main outcomes were the proportion of participants who completed the online program and the proportion who quit smoking for at least 30 days, 26 weeks after enrollment, among those randomized into the high-reinforcement (HR) condition compared with those in the low-reinforcement (LR) condition. Results The study achieved a final enrollment of 403 participants including 56 women. Program completion was greater for the HR as compared to the LR condition (17% vs. 10%, p = .035). There was no significant difference in 30-day smoking cessation (intent-to-treat [ITT]) between the HR and LR conditions (9% vs. 8%, ns). Smoking cessation was greater among program completers as compared to those who did not complete the program (28% vs. 5%, p Conclusions The addition of interim surveys and financial incentives for interim survey completion and program completion significantly increased the likelihood of program completion. Moreover, program completers were significantly more likely to quit smoking. Although smoking cessation rates did not significantly differ between the HR and LR conditions, the results suggest that future studies should explore the efficacy of larger financial incentives for program completion (Clinical Trial # NCT02584127 ).
X-Ray Diffraction Patterns of Hevea, Manihot and Other Rubbers

Abstract When rubber from Hevea brasiliensis is stretched quickly and exposed to a beam of x-rays, a crystal fiber diffraction pattern is obtained.” During previous work, done jointly by the National Bureau of Standards and the University of Illinois on sol and gel fractions of this rubber, no pattern was produced by the stretched sol fraction. With the stretched gel fraction, however, the pattern was sharp and intense. Rubber from Manihot glaziovii also may be separated into sol and gel fractions, and in recent work they, too, have been stretched and examined by x-rays. With the stretched Manihot sol, a few interferences were obtained, but many more resulted with the stretched gel. When crystallized by “freezing” at low temperatures for 24 hours, the interferences from the gel again outnumbered those from the sol. The x-ray measurements of Manihot rubber agree with those of Hevea rubber and indicate that the same structure exists in each. Rubbers obtained from latices of Funtumia elastica, Cryptostegia g...
Clinical Evaluation of Bleeding and Bruising in Primary Care

Bleeding and bruising are common symptoms in the primary care setting. The patient history can help determine whether the bruising or bleeding is abnormal. The International Society on Thrombosis and Hemostasis has developed a bleeding assessment tool that can be used to indicate possible pathology. A family history of bleeding problems may suggest a hereditary coagulation defect. Such a history is especially important in children who may not have experienced a major bleeding episode. Medication review can identify pharmacologic causes of the bleeding or bruising. Physical examination findings such as mucocutaneous bleeding suggest that the underlying condition is caused by platelet dysfunction, whereas hemarthroses or hematomas are more common in coagulopathy. If the history and physical examination findings suggest a bleeding diathesis, initial laboratory testing includes a complete blood count, peripheral blood smear, prothrombin time (PT), and partial thromboplastin time (PTT). A normal PT and PTT indicate a platelet disorder, the most common of which is von Willebrand disease. A normal PT and prolonged PTT signal a deficit in the intrinsic pathway, and a mixing study should be performed. A vitamin K challenge is indicated in patients with an abnormal PT and normal PTT. A workup for liver failure is warranted in patients with prolonged PT and PTT. If initial testing does not reveal an etiology in a patient with a high suspicion for a bleeding disorder, the patient should be referred to a hematologist for additional evaluation.
Components and correlates of mental well-being.

The feeling state of well-being is probably the reflection of a complex interaction among psychological processes. Evidence is presented that at least three affects may take part in this process: negative affect, positive sense of involvement, and long-term satisfaction. Different patterns of association are demonstrated between these three affects and variables such as social participation, cultivation of hobbies, planfulness, emotional reactivity, physical health, and expert ratings of psychiatric disorder. These associations demonstrate the heuristic value in attempting to conceptualize and measure the dimensions of psychological well-being, as opposed to dealing with such a global construct in empirical research.
Hematology: Molecular Testing for the Factor V-Leiden Mutation in the Clinical Laboratory

Activated protein C (APC) resistance is a major cause of deep venous thrombosis. Most cases of APC resistance are due to a variant of factor V (FV), known as FV-Leiden, that is resistant to degradation by APC. The FVLeiden mutation can be detected by a simple and reliable polymerase chain reaction method. During the past year we tested 355 patients for FV-Leiden. Twenty-six were heterozygous, and 3 were homozygous for the mutation. The prevalence of FV-Leiden was substantially higher in patients <30 years of age.
Lithography aware overlay metrology target design method

We present a metrology target design (MTD) framework based on co-optimizing lithography and metrology performance. The overlay metrology performance is strongly related to the target design and optimizing the target under different process variations in a high NA optical lithography tool and measurement conditions in a metrology tool becomes critical for sub-20nm nodes. The lithography performance can be quantified by device matching and printability metrics, while accuracy and precision metrics are used to quantify the metrology performance. Based on using these metrics, we demonstrate how the optimized target can improve target printability while maintaining the good metrology performance for rotated dipole illumination used for printing a sub-100nm diagonal feature in a memory active layer. The remaining challenges and the existing tradeoff between metrology and lithography performance are explored with the metrology target designer’s perspective. The proposed target design framework is completely general and can be used to optimize targets for different lithography conditions. The results from our analysis are both physically sensible and in good agreement with experimental results.
Deformation Monitoring and Numerical Analysis of Surface Subsidence of a Deep Foundation Pit in Construction

Based on a deep foundation pit of a subway station,the paper introduces the project's surroundings,structural type and the geological conditions of the proposed field.According to the engineering characteristics,the project was divided into four typical operating conditions.Based on the results of surface subsidence measured in the end of each condition,the paper analyzes the variation of surface subsidence in the excavation process.Through the establishment of three-dimensional model of the subway station,the surface subsidence is simulated by numerical analysis,and compared with experimental results,eventually the regularity of surface subsidence of a deep foundation pit and the influence sphere of earth excavation are obtained.The results of the paper can provide references for deep foundation pit design and construction.
Interactions of Leucine Enkephalin and Narcotics with Opioid Receptors

In superfusion experiments in vitro , facilitation of naloxone-releasable morphine was observed with slices of corpus striatum which were obtained from mice pretreated in vivo with leucine enkephalin (20 mg/kg) i.p. 15 min prior to killing. Preincubation of striatal slices for 15 min with leucine enkephalin in vitro at concentrations ranging from 1.0 nM to 0.1 pM also enhanced the morphine-releasing effect of naloxone. Thus, very minute concentrations of leucine enkephalin are required to produce this effect. Methionine enkephalin pretreatment either in vivo or in vitro did not exhibit any of the above effects. Simultaneous incubation of an equimolar concentration of naloxone blocked this enhancing effect of leucine enkephalin. Prior incubation with leucine enkephalin did not influence naltrexone-releasable [ 3 H]naltrexone but markedly enhanced morphine-releasable [ 3 H]naltrexone and morphine- or levorphanol-releasable [ 3 H]morphine. We suggest that the apparent increase in naloxone potency is mediated by narcotic agonists and that leucine enkephalin potentiates this agonistic effect via a receptor-mediated process. Similar effects of leucine enkephalin on the narcotic-induced enhancement of naloxone potency were observed in vivo . These data also indicate a possible modulatory effect of leucine enkephalin on the opioid receptor.
Transitions in Smokers' Social Networks After Quit Attempts: A Latent Transition Analysis.

Introduction Smokers' social networks vary in size, composition, and amount of exposure to smoking. The extent to which smokers' social networks change after a quit attempt is unknown, as is the relation between quitting success and later network changes. Methods Unique types of social networks for 691 smokers enrolled in a smoking-cessation trial were identified based on network size, new network members, members' smoking habits, within network smoking, smoking buddies, and romantic partners' smoking. Latent transition analysis was used to identify the network classes and to predict transitions in class membership across 3 years from biochemically assessed smoking abstinence. Results Five network classes were identified: Immersed (large network, extensive smoking exposure including smoking buddies), Low Smoking Exposure (large network, minimal smoking exposure), Smoking Partner (small network, smoking exposure primarily from partner), Isolated (small network, minimal smoking exposure), and Distant Smoking Exposure (small network, considerable nonpartner smoking exposure). Abstinence at years 1 and 2 was associated with shifts in participants' social networks to less contact with smokers and larger networks in years 2 and 3. Conclusions In the years following a smoking-cessation attempt, smokers' social networks changed, and abstinence status predicted these changes. Networks defined by high levels of exposure to smokers were especially associated with continued smoking. Abstinence, however, predicted transitions to larger social networks comprising less smoking exposure. These results support treatments that aim to reduce exposure to smoking cues and smokers, including partners who smoke. Implications Prior research has shown that social network features predict the likelihood of subsequent smoking cessation. The current research illustrates how successful quitting predicts social network change over 3 years following a quit attempt. Specifically, abstinence predicts transitions to networks that are larger and afford less exposure to smokers. This suggests that quitting smoking may expand a person's social milieu rather than narrow it. This effect, plus reduced exposure to smokers, may help sustain abstinence.
Association of RBC Antibodies with Renal Graft Survival

Objectives: In this study, we aimed to determine the independent impact of RBC antibodies on kidney allograft rejection and graft survival. Methods: At the Virginia Commonwealth University Medical Center, 1099 patients who received ABO-compatible kidney transplants between January 1998 and December 2014 were analyzed …
A Retrospective on Genomic Preprocessing for Comparative Genomics

In this paper, we present a survey of research on genomic preprocessing for comparative genomics, i.e., handling genomes with gene repetitions, missing or redundant genes, initiated by David Sankoff in 1999. The development of this research ends with several interesting results within and beyond computational biology and bioinformatics, with possible new contributions in the future. We will describe the history of development of this research and review the current status of the corresponding problems. For the problem of handling missing genes (scaffold filling), we also present some technical details which are not given in the previous papers. Some open problems will be listed at the end for further research.
Rebelocracy: Social Order in the Colombian Civil War

Conventional wisdom portrays war zones as chaotic and anarchic. In reality, however, they are often orderly. This work introduces a new phenomenon in the study of civil war: wartime social order. It investigates theoretically and empirically the emergence and functioning of social order in conflict zones. By theorizing the interaction between combatants and civilians and how they impact wartime institutions, the study delves into rebel behavior, civilian agency and their impact on the conduct of war. Based on years of fieldwork in Colombia, the theory is tested with qualitative and quantitative evidence on communities, armed groups, and individuals in conflict zones. The study shows how armed groups strive to rule civilians, and how the latter influence the terms of that rule. The theory and empirical results illuminate our understanding of civil war, institutions, local governance, non-violent resistance, and the emergence of political order.
On the arithmetic intensity of high-order finite-volume discretizations for hyperbolic systems of conservation laws:

It has been conjectured that higher-order discretizations for partial differential equations will have advantages over the lower-order counterparts commonly used today. The reasoning is that the in...
Biologic Therapy in Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is common worldwide. The predominant cause in most COPD is environmental exposure to toxicants. The inflammatory processes in COPD are multifactorial, complex, and interacting, leading to many potential therapeutic targets. Although most typically associated with neutrophilic/macrophagic inflammation (type 1), it is now known that COPD can also be associated with eosinophilic inflammation (type 2), particularly in exacerbations. Accordingly, there is an active program of investigation of highly selective biologic therapeutic agents in the management of COPD. This review summarizes clinical trials of the use of these novel agents in the management of COPD.
‘Grand Narrative’ and ‘New’ World Histories: Their Historical Challenges and Contributions in Western Scholarship

This chapter places the emergence of the ‘new world histories’ within the context of an increasingly interconnected and interdependent—i.e., globalizing—world, but questions to what extent the various approaches, themes and emphases—‘transnational’, ‘comparative’, ‘global’, ‘crosscultural’, etc.—of the ‘new world histories’ represent genuinely ‘new’ innovations in world historical scholarship. It argues that, along with defining ‘world history’ broadly in terms of a cluster of various themes and approaches, an explicit commitment in both theory and practice to ‘grand narrative’ as the overarching frame and ultimate goal of the various themes and approaches must be preserved, otherwise ‘world history’ loses its distinctiveness as a field. The chapter goes on to identify six major lines of criticism against ‘grand narrative’ world history, placing them in historical context, with emphasis on the continuing tension between ‘old’ Eurocentric and nationalistic verses ‘new’ global(ist)-multiculturalist approaches.
Brain-Wide Genome-Wide Association Study for Alzheimer's Disease via Joint Projection Learning and Sparse Regression Model

Brain-wide and genome-wide association (BW-GWA) study is presented in this paper to identify the associations between the brain imaging phenotypes (i.e., regional volumetric measures) and the genetic variants [i.e., single nucleotide polymorphism (SNP)] in Alzheimer's disease (AD). The main challenges of this study include the data heterogeneity, complex phenotype–genotype associations, high-dimensional data (e.g., thousands of SNPs), and the existence of phenotype outliers. Previous BW-GWA studies, while addressing some of these challenges, did not consider the diagnostic label information in their formulations, thus limiting their clinical applicability. To address these issues, we present a novel joint projection and sparse regression model to discover the associations between the phenotypes and genotypes. Specifically, to alleviate the negative influence of data heterogeneity, we first map the genotypes into an intermediate imaging-phenotype-like space. Then, to better reveal the complex phenotype–genotype associations, we project both the mapped genotypes and the original imaging phenotypes into a diagnostic-label-guided joint feature space, where the intraclass projected points are constrained to be close to each other. In addition, we use $\ell _{2,1}$ -norm minimization on both the regression loss function and the transformation coefficient matrices, to reduce the effect of phenotype outliers and also to encourage sparse feature selections of both the genotypes and phenotypes. We evaluate our method using AD neuroimaging initiative dataset, and the results show that our proposed method outperforms several state-of-the-art methods in term of the average root-mean-square error of genome-to-phenotype predictions. Besides, the associated SNPs and brain regions identified in this study have also been shown in the previous AD-related studies, thus verifying the effectiveness and potential of our proposed method in AD pathogenesis study.
Social Work Service to Abortion Patients

Group sessions give patients useful information, enable them to express their ambivalent feelings, and result in mutual support and relief of tension
Uncultured: Civil War and Cultural Policy

AbstractHow does cultural policy affect violence? While cultural discrimination is frequently cited as a potential grievance motivating political violence, the relationship remains under-theorised and largely untested. I weave theoretical literatures with interviews and secondary sources on the experience of Kurds in Turkey to understand the socio-economic and psychological pathways through which cultural policies impact intrastate conflict. I then analyse cross-national data on political violence, demonstrating that cultural grievances increase support for violence, raise the chance and severity of conflict and prolong violent conflicts. In short, policy matters: cultural restrictions exacerbate violence through multiple pathways.
Dynamics of Cell Adhesion Interactions during Melanoma Development

Cell adhesion interactions are important processes during normal development and malignant transformation. Recent studies have shown that in melanoma, cell adhesion interactions play a critical role in regulating melanocytic cell proliferation, differentiation, migration, apoptosis and even vasculature mimicry. In the review we will discuss recent progresses in the study of the dynamic expression and function of the adhesion molecules in melanoma development.
Kinetics of Bulk and Interfacial Ionic Motion: The Microscopic Basis and Limits for the Nernst-Planck-Poisson System

Criticisms, of, limitations on, and alternatives to the Nernst-Planck equation for ionic transport are outlined in the context of notion into and through liquids, gells, ion exchanger membranes, ionic crystals and polycrystalline materials. The origin of the equation from the point of view of Langevin, and contributions of Onsager and Schogl provide a basis for discussion of limitations on applications to non-homogeneous materials. The surprising usefulness and wide applicability are demonstrated using correlations for diverse cases including coupled transport, association (ion pairing and clustering), adsorption and concentrated electrolytes. The microscopic models for the friction coefficient, in terms of atomic properties, are discussed. New material on kinetic boundary conditions, slow ion exchange and ionic overpotential are presented.
Detection of Spread-Spectrum Signals

The ability to detect the presence of spread-spectrum signals is often required by cognitive radio, ultra-wideband, and military systems. This chapter presents an analysis of the detection of spread-spectrum signals when the spreading sequence or the frequency-hopping pattern is unknown and cannot be accurately estimated by the detector. Thus, the detector cannot mimic the intended receiver, and alternative procedures are required. The goal is limited in that only detection is sought, not demodulation or decoding. Nevertheless, detection theory leads to impractical devices for the detection of spread-spectrum signals. An alternative procedure is to use a radiometer or energy detector, which relies solely on energy measurements to determine the presence of unknown signals. The radiometer has applications not only as a detector of spread-spectrum signals, but also as a general sensing method in cognitive radio and ultra-wideband systems.
Stiff Left Atrial Syndrome; Prospects and Possibilities. Retrospective Analysis and Review of the Literature

Objectives Stiff left atrial syndrome is an intriguing clinical phenomena characterized by reduced left atrial compliance, pulmonary venous hypertension and exacerbations of volume overload. We conducted a retrospective review of patients diagnosed with stiff left atrial syndrome at our center. Methods All patients admitted to our hospital with volume overload and pulmonary venous hypertension who were diagnosed with stiff left atrial syndrome based on evidence by echocardiogram and right heart catheterization between July 2011 and July 2013 were included in this retrospective review. Results Twentythree patients (mean age 73 ± 11 years, 39% male and 61% female) were diagnosed with stiff left atrial syndrome at our center. Thirty-five percent had persistent while 39% had permanent atrial fibrillation. Mean duration of atrial fibrillation was 7.6 ± 2.1 years. Forty-three percent of patients had long standing hypertension. There was no mitral regurgitation in 39% of patients while 48% had mild mitral regurgitation. On right heart catheterization, mean right atrial pressure was 12.6±4.8 mm of Hg, mean pulmonary arterial pressure was 33±7.2 mm of Hg, mean pulmonary capillary wedge pressure was 24.8± 4.2mm of Hg while peak V waves were seen at mean of 37.8± 5.3 mm of Hg. Mean left atrial volume index was 49.8±17.1 mL/m 2. After the initial diagnosis with a two year follow- up, there were no readmissions in 65% of patients who were on appropriate diuretic therapy and had regular clinical visits. Frequent readmissions were seen in 35% of patients inspite of appropriate diuretic therapy. All-cause mortality rate was 4.3% at two year follow up. Conclusion In patients with stiff left atrial syndrome, the presence of left atrial dilation, long standing atrial fibrillation and hypertension are the key factors associated with pathogenesis and clinical course. Close follow up and monitoring of volume status is essential to prevent hospital readmissions and improve long term prognosis.
Further steps for parenteral nutrition in the electronic health record.

The authors of the recent call to action for optimizing parenteral nutrition (PN) workflow in the electronic health record (EHR) are to be congratulated.[1][1] Given the reported consequences,[2][2] reducing the amount of PN order transcription in the EHR and for automated compounding devices (ACDs
Design-based research: Connecting theory and practice in pharmacy educational intervention research.

Abstract Our situation Interventional research in pharmacy education includes the study of complex challenges that can be difficult to navigate. Design-based research (DBR), is a systematic and iterative approach to interventional research that is attentive to the practical and theoretical contributions to education. Practical contributions include the creation of novel solutions to complex problems that improve learning while theoretical contributions include refining our understanding of context-specific learning. In this paper, we describe how we addressed challenges associated with student collaboration in pharmacy education by applying DBR to bridge theory and practice. Methodological literature review DBR is characterized as authentic, contextually aware, collaborative, theoretically focused, methodologically diverse, practical, iterative, and operation-oriented. DBR includes three iterative phases: (1) analysis and exploration, (2) design and construction, and (3) evaluation and reflection. Our recommendations and their applications To integrate DBR into interventional research, scholars should work collaboratively with diverse teams of experts. DBR also requires extensive planning, a toolkit of expansive research methodologies, and attention to practical and theoretical considerations. Finally, scholars should share their work as often as possible and engage in creative exercises to promote innovative solutions to challenges in education. Potential impact DBR offers an approach to generate practical, theoretical, and scholarly contributions to pharmacy education research. In summary, DBR can aid pharmacy educational scholars by using a flexible, iterative, and systematic process to generate novel and creative solutions to complex problems.
Eliciting Life Priorities of Older Adults Living in Permanent Supportive Housing.

Background and objectives Adults who have experienced chronic homelessness are considered to be "old" by age 50 due to accelerated aging. While permanent supportive housing (PSH) has been found effective for these individuals, there is limited focus on the needs of adults "aging in place" in PSH. This study examined (1) how older adults in PSH identify and rank their life priorities, (2) how they describe these priorities in their own words, and (3) how life course adversity deepens an understanding of these priorities. Research design and methods A convergent parallel mixed methods design was used in which qualitative case study analyses informed by a life course perspective provided a deeper understanding of how 14 older residents of PSH viewed their life priorities using quantitative card-sort rankings of 12 life domains. Results Housing, family, mental health, physical health, and partner were the most frequently endorsed life priorities. Four themes emerged from the cross-case analyses: "aging in, aging out," "carefully restoring relationships," "life goes on," and "housing is fundamental." Convergent findings indicated that life adversity-social losses and interrupted lives-influenced both the high- and low-ranked card-sort priorities. Discussion and implications This study demonstrated that participants were aware of their advancing years yet they sought to overcome adversity and losses through maintaining mental health and sobriety, improving physical health, and cautiously rebuilding relationships. As the numbers of older homeless rise, the inclusion of age-related services will be an important component of PSH services for residents as they age.