cssi/SciSciGPT-SciSciNet huggingface dataset:
GENETIC DIVERGENCE AND HYBRID SPECIATION

Although the evolutionary importance of natural hybridization has been debated for decades, it has become increasingly clear that hybridization plays a fundamental role in the evolution of many plant and animal taxa, sometimes resulting in the formation of entirely new species. Although some hybrid species retain the base chromosome number of their parents, others combine the full chromosomal complements of their progenitors. Hybrid speciation can thus produce two fundamentally different types of evolutionary lineages, yet relatively little is known about the factors influencing ploidy level in hybrid neospecies. We estimated genetic divergence between species pairs that have given rise to homoploid and polyploid hybrid species and found that divergence is significantly greater for the parents of polyploids, even after controlling for potentially confounding factors. Our data thus provide the first direct evidence in support of the notion that the extent of genomic divergence between hybridizing species influences the likelihood of diploid versus polyploid hybrid speciation.
Short- and long-term effects of Ginkgo biloba extract on sexual dysfunction in women.

Ginkgo biloba extract (GBE) facilitates blood flow, influences nitric oxide systems, and has a relaxant effect on smooth muscle tissue. These processes are important to the sexual response in women and, hence, it is feasible that GBE may have a therapeutic effect. The present study was the first to provide an empirical examination of the effects of both short- and long-term GBE administration on subjective and physiological (vaginal photoplethysmography) measures of sexual function in women with Sexual Arousal Disorder. A single dose of 300 mg GBE had a small but significant facilitatory effect on physiological, but not subjective, sexual arousal compared to placebo in 99 sexually dysfunctional women. The long-term effects of GBE on sexual function were assessed in 68 sexually dysfunctional women who were randomly assigned to 8 weeks treatment of either (1) GBE (300 mg/daily), (2) placebo, (3) sex therapy which focused on training women to attend to genital sensations, or (4) sex therapy plus GBE. When combined with sex therapy, but not alone, long-term GBE treatment significantly increased sexual desire and contentment beyond placebo. Sex therapy alone significantly enhanced orgasm function compared with placebo. Long-term GBE administration did not significantly enhance arousal responses beyond placebo. It was concluded that (1) neither short- or long-term administration of GBE alone substantially impacts sexual function in women, (2) a substantial placebo effect on sexual function exists in women with sexual concerns, and (3) teaching women to focus on genital sensations during sex enhances certain aspects of women’s sexual functioning.
International resource flows and construction movements in the atlantic economy: the kuznets cycle in Italy, 1861–1913

Nineteenth-century Italy experienced the long swings in migration, capital flows, and construction characteristic of the international Kuznets cycle, but in an unusual combination: its external migration swing may have resembled Britain's, but its capital flows and construction swing resembled America's. Construction in Italy was finance-sensitive rather than population-sensitive, and reacted primarily to exogenous shifts in the supply of foreign capital. The Italian experience suggests that changes in perceived risk altered the relative supply of capital in Britain and abroad and thereby induced the opposite swings in construction and the swing in migration.
Extended-release dalfampridine in the management of multiple-sclerosis-related walking impairment.

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system that causes neurological impairment in young adults. As part of the disease, ambulation remains one of the most disabling features of multiple sclerosis. Extended-release dalfampridine is a long-acting form of 4-aminopyridine that has been shown in two phase III trials to increase ambulation speed in a subset of patients with multiple sclerosis (timed walk responders). The primary endpoint of these studies was ‘responder status’, analyzing difference in the proportion of timed walk responders between extended-release dalfampridine and placebo groups. Extended-release dalfampridine exerts its effects by inhibiting voltage-activated K+ channels and has been previously demonstrated to improve action potential propagation in demyelinated nerve fibers in vitro. Side effects of extended-release dalfampridine include increased urinary tract infections, insomnia, headache, asthenia, dizziness, back pain, and paresthesias. Rare seizure events are also reported on the approved dose of 10 mg every 12 h. In this review we will summarize the results of key phase II and phase III trials of extended-release dalfampridine, its safety, and potential use in patients with multiple sclerosis.
Active Tamoxifen Metabolite Plasma Concentrations After Coadministration of Tamoxifen and the Selective Serotonin Reuptake Inhibitor Paroxetine

Background: Tamoxifen, a selective estrogen receptor modulator (SERM), is converted to 4-hydroxy-tamoxifen and other active metabolites by cytochrome P450 (CYP) enzymes. Selective serotonin reuptake inhibitors (SSRIs), which are often prescribed to alleviate tamoxifen-associated hot flashes, can inhibit CYPs. In a prospective clinical trial, we tested the effects of coadministration of tamoxifen and the SSRI paroxetine, an inhibitor of CYP2D6, on tamoxifen metabolism. Methods: Tamoxifen and its metabolites were measured in the plasma of 12 women of known CYP2D6 genotype with breast cancer who were taking adjuvant tamoxifen before and after 4 weeks of coadministered paroxetine. We assessed the inhibitory activity of pure tamoxifen metabolites in an estradiol-stimulated MCF7 cell proliferation assay. To determine which CYP isoforms were involved in the metabolism of tamoxifen to specific metabolites, we used CYP isoform‐specific inhibitors. All statistical tests were two-sided. Results: We separated, purified, and identified the metabolite 4-hydroxy-N-desmethyl-tamoxifen, which we named endoxifen. Plasma concentrations of endoxifen statistically significantly decreased from a mean of 12.4 ng/mL before paroxetine coadministration to 5.5 ng/mL afterward (difference 6.9 ng/mL, 95% confidence interval [CI] 2.7 to 11.2 ng/mL) (P .004). Endoxifen concentrations decreased by 64% (95% CI 39% to 89%) in women with a wild-type CYP2D6 genotype but by only 24% (95% CI 23% to 71%) in women with a variant CYP2D6 genotype (P .03). Endoxifen and 4-hydroxy-tamoxifen inhibited estradiol-stimulated MCF7 cell proliferation with equal potency. In vitro, troleandomycin, an inhibitor of CYP3A4, inhibited the demethylation of tamoxifen to N-desmethyl-tamoxifen by 78% (95% CI 65% to 91%), and quinidine, an inhibitor of CYP2D6, reduced the subsequent hydroxylation of N-desmethyl-tamoxifen to endoxifen by 79% (95% CI 50% to 108%). Conclusions: Endoxifen is an active tamoxifen metabolite that is generated via CYP3A4-mediated N-demethylation and CYP2D6-mediated hydroxylation. Coadministration of paroxetine decreased the plasma concentration of endoxifen. Our data suggest that CYP2D6 genotype and drug interactions should be considered in women treated with tamoxifen. [J Natl Cancer Inst 2003;95:1758 ‐ 64]
Stored-product insects associated with a retail pet store chain in Kansas.

The types and numbers of insect species associated with eight Kansas retail stores belonging to a pet store chain were surveyed during February to August 2001. Insects were monitored at 1-3-wk intervals using food- and pheromone-baited pitfall traps for beetles and pheromone-baited sticky traps for moths. Thirty traps of each type were placed within a store. Thirty insect species belonging to 20 families in four orders were recorded from the eight stores. The weevils, Sitophilus spp.; Indianmeal moth, Plodia interpunctella (Hubner); and merchant grain beetle, Oryzaephilus mercator (Fauvel), were the most common and abundant species in all stores, whereas the red-legged ham beetle, Necrobia rufipes (Degeer), and red flour beetle, Tribolium castaneum (Herbst), were abundant only in one store. The numbers of each insect species captured varied from store to store. In each of the stores, a total of 12-19 stored-product species were captured in traps, and seven of the eight stores had relatively high species diversity. With the exception of one store, the different types of insect species found among the remaining seven stores were essentially similar. The mean density of insects in infested bulk-stored and bagged pet food products removed from a store ranged from 65 to 656 adults/kg. The types and numbers of insect species captured in traps indicated that infestations were well established in the surveyed stores. Early detection and management of these infestations is critical for maintaining quality and integrity of food products sold in the pet stores.
The Metalloprotease of Listeria monocytogenes Is Regulated by pH

Listeria monocytogenes is an intracytosolic bacterial pathogen. Among the factors contributing to escape from vacuoles are a phosphatidylcholine phospholipase C (PC-PLC) and a metalloprotease (Mpl). Both enzymes are translocated across the bacterial membrane as inactive proproteins, whose propeptides serve in part to maintain them in association with the bacterium. We have shown that PC-PLC maturation is regulated by Mpl and pH and that Mpl maturation occurs by autocatalysis. In this study, we tested the hypothesis that Mpl activity is pH regulated. To synchronize the effect of pH on bacteria, the cytosolic pH of infected cells was manipulated immediately after radiolabeling de novo-synthesized bacterial proteins. Immunoprecipitation of secreted Mpl from host cell lysates revealed the presence of the propeptide and catalytic domain in samples treated at pH 6.5 but not at pH 7.3. The zymogen was present in small amounts under all conditions. Since proteases often remain associated with their respective propeptide following autocatalysis, we aimed at determining whether pH regulates autocatalysis or secretion of the processed enzyme. For this purpose, we used an Mpl construct that contains a Flag tag at the N terminus of its catalytic domain and antibodies that can distinguish N-terminal and non-N-terminal Flag. By fluorescence microscopy, we observed the Mpl zymogen associated with the bacterium at physiological pH but not following acidification. Mature Mpl was not detected in association with the bacterium at either pH. Using purified proteins, we determined that processing of the PC-PLC propeptide by mature Mpl is also pH sensitive. These results indicate that pH regulates the activity of Mpl on itself and on PC-PLC.
Loss minimization of distribution feeders: optimality and algorithms

Determining open switch positions for the minimum-loss configuration of a radial distribution system is a discrete optimization problem. The authors present a global optimality condition of the problem and two algorithms: one is based on the uniformly distributed load model and the other on the concentrated current (or power) demand model. The derivation of the optimality condition relies on a concept of 'basic' current profiles of feeder sections and a transformation of the optimization problem. In the first algorithm, a closed form of the minimum-loss open point of a feeder pair can be found since the loss function is piecewise-parabolic. The algorithm obtains the optimal solution when the minimum is obtained for every feeder pair. In the second algorithm, a similar procedure is performed by moving open points, one at a time, from an actual switch position to another until no further loss reduction can be achieved. The proposed algorithm can be utilized as an online aid to distribution system operators. >
Overexpression of nicastrin increases Abeta production.

SPECIFIC AIMSIn this study, we examined the effects of the overexpression of the γ-secretase enzyme component Nicastrin on Aβ production in whole cells and in a broken cell assay.PRINCIPAL FINDINGS...
Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease

Abstract The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale – the Clinical Dementia Rating Scale in particular – for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving.
Placing bounds on extreme temperature response of maize

Plant water availability is a key factor that determines maize yield response to excess heat. Lack of available data has limited researchers' ability to estimate this relationship at regional and global scales. Using a new soil moisture data set developed by running a crop growth simulator over historical data we demonstrate how current estimates of maize yield sensitivity to high temperature are misleading. We develop an empirical model relating observed yields to climate variables and soil moisture in a high maize production region in the United States to develop bounds on yield sensitivity to high temperatures. For the portion of the region with a relatively long growing season, yield reduction per °C is 10% for high water availability and 32.5% for low water availability. Where the growing season is shorter, yield reduction per °C is 6% for high water availability and 27% for low water availability. These results indicate the importance of using both water availability and temperature to model crop yield response to explain future climate change on crop yields.
Selecting and Weighting N-Grams to Identify 1100 Languages

This paper presents a language identification algorithm using cosine similarity against a filtered and weighted subset of the most frequent n-grams in training data with optional inter-string score smoothing, and its implementation in an open-source program. When applied to a collection of strings in 1100 languages containing at most 65 characters each, an average classification accuracy of over 99.2% is achieved with smoothing and 98.2% without. Compared to three other open-source language identification programs, the new program is both much more accurate and much faster at classifying short strings given such a large collection of languages.
Transmembrane Interactions as Immunotherapeutic Targets: Lessons from Viral Pathogenesis

Multichain immune recognition receptors (MIRRs) represent a family of structurally related but functionally different surface receptors expressed on different cells of the immune system. A distinctive and common structural characteristic of MIRR family members is that the extracellular recognition domains and intracellular signaling domains are located on separate subunits. How extracellular ligand binding triggers MIRRs and initiates intracellular signal transduction processes is not clear. A novel model of immune signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) model, suggests possible molecular mechanisms and reveals the MIRR transmembrane interactions as universal therapeutic targets for a variety of MIRR-mediated immune disorders. Intriguingly, these interactions have been recently shown to play an important role in human immunodeficiency virus and cytomegalovirus pathogenesis. In this chapter, I demonstrate how the SCHOOL model, together with the lessons learned from viral pathogenesis, can be used practically for rational drug design and the development of new therapeutic approaches to treat a variety of seemingly unrelated disorders, such as T cell-mediated skin diseases and platelet disorders.
The purine DNA base cation and anion radicals: an e.s.r. study.

(1974). The Purine DNA Base Cation and Anion Radicals: An E.S.R. Study. International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine: Vol. 25, No. 6, pp. 635-638.
An Investigation Of Security Analysts Use Of Non-Accounting Data For Decision Making

This research evaluates the responses of Chartered Financial Analysts (CFAs) asked what additional information considered useful to make a buy/sell decision regarding equity securities. The information is dichotomized into quantitative/qualitative and internal/external groups. The results show that for the total sample of CFAs, the information requests are not significantly different form a 50/50 split. The inference drawn is that since almost 50% of the information used is external (qualitative), additional mandatory disclosures of accounting information should be carefully reviewed before implementation.
Impact of Head Start's Entry Age and Enrollment Duration on Children's Health

This secondary data analysis examined the association of Head Start children's entry age and enrollment duration on children's dental, vision, and hearing health based on data from 60 local Head Start classrooms. Children were divided into three groups: One group of children entered Head Start at age three and maintained enrollment for one year (Group 1). The second group of children entered Head Start at age four and stayed one year (Group 2). The third group of children entered at age three and stayed in Head Start for two years (Group 3). Compared with Group 3, Group 1 had fewer dental problems and Group 2 had less identified hearing problems. Children's gender, ethnicity, and program characteristics and family risk factors were associated with health problems.
HOW WHITE-THROATED MAGPIE-JAY HELPERS CONTRIBUTE DURING BREEDING

We investigated the mechanisms by which helpers contribute to breeder re- production in a Costa Rican population of White-throated Magpie-Jays (Calocitta formosa). Helpers provided a substantial proportion of all feedings to female breeders and their off- spring, proportionately more than most species of cooperatively breeding New World jays. Breeding males typically fed breeding females and offspring less frequently than expected, however. There was little evidence of brood division in the sense of individual provisioners (breeders or helpers) preferentially feeding particular fledglings within a brood. The rate of provisioning per recipient increased as a function of group size only during the pre-incu- bation period (provisioning of the laying female). Provisioning rates per nestling and per fledgling were not correlated with group size, and the number of offspring fledged per suc- cessful nest did not increase with group size. Helpers did reduce the provisioning burden on breeders, however, and occasionally were the primary care-providers of fledglings, which allowed breeders to renest. More successful nests were produced in groups with many help- ers than few, resulting in more fledged young per year. Mechanisms contributing to this "helper-effect" included more nesting attempts per year and a higher likelihood of renesting after a successful attempt. We conclude that the contributions of magpie- jay helpers in- creased breeder fitness, and the indirect and direct benefits gained by helping probably fa- vored its expression by nonbreeding group members. Received 30 October 1997, accepted 18 June 1998.
Dissecting Role of Sleep in Abnormal Neurocognitive Development in an Animal Model of Prenatal Alcohol Exposure

Dissecting Role of Sleep in Abnormal Neurocognitive Development in an Animal Model of Prenatal Alcohol Exposure It has been well established that human conditions with insufficient or restricted sleep have detrimental consequences, including cognitive, affective, cardiovascular and endocrine, and contribute to poor quality of life. Development of insomnia depends on genetic, epigenetic and environmental factors, and may have origins in early ontogenesis. Existing data suggest that poor sleep and increased behavioral arousal can result from prenatal adversities such as exposure to psychoactive substances or malnutrition. One of the major risk factors during the prenatal period is maternal alcohol consumption. It occurs in over 10% of pregnancies, leading to adverse consequences such as the Fetal Alcohol Spectrum Disorders (FASD) affecting 2-5% of births in the United States and Western European countries.
Quantitative evaluation of environmental surface cleanliness in pediatrics intensive care unit

OBJECTIVE To quantitatively evaluate the environmental surface cleanliness in the pediatrics intensive care unit(PICU) of the hospital and to monitor the efficacy of the cleaning methods used and standardize the cleaning procedure.METHODS A total of 22 different kinds of environmental surfaces in PICU,Fuwai Heart Hospital Cardiovascular Institute were chosen based on the hand contact frequency and contamination risk level.Their cleanliness was evaluated using an ATP bioluminescence method.RESULTS It was shown that the average ATP values of simple respirator,physiological bedside monitor panel,infusion pump panel,pressurized infusion bag ball and nurse′s table were 500 relative light units(RLU) before the cleaning,indicating high contamination risk,while the RLUs of all environmental surfaces reduced to 500 after cleaning.However,ATP values of physiological bedside monitor panel,infusion pump panel,simple respirator and bedside table showed a rapid increase after the cleaning and RLU readings reached 500 4 hours after cleaning.It was surprising to discover that the average RLU of a blood-gas analyzer panel,screen and injection port were 15 000.CONCLUSION It is concluded that in a PICU the use of an ATP method could provide quantitative information of cleaning efficacy and ATP trends,to allow the identification of environmental surfaces that require the additional cleaning or cleaning schedule amendments.
Sudden cardiac death in school athletes

C athletes are those who participate in an organized team or individual sports that require regular competition against others. Athletic activities substantially increase the sympathetic drive, resulting in surge in catecholamine level that increases blood pressure, heart rate, myocardial contractility and oxygen demand. This can cause myocardial ischemia and arrhythmia that may lead to sudden death in athletes with known and unrecognized heart conditions during athletic activities. There are many structural and acquired heart conditions that are not clinically manifested. Many physicians are involved in medical clearance of children for participations in school sports activities. Physicians have to recognize them to protect athletes from catastrophic events. In order to prevent sudden cardiac death, physicians should be aware of cardiac conditions that may cause problem. Also physicians should be familiar with general guidelines for evaluation of an athlete and clearance for participation in athletic activities. Guidelines vary in different parts of the world. In this presentation I will discuss guidelines for European, Italian and in USA outlined by American heart Association. In this presentation the causes of congenital and acquired heart conditions and arrhythmias that can cause sudden cardiac death will be discussed with authors experience and literature review.
Comparative evaluation of IGCT and GTO thyristor for series connection in high power voltage source inverter based FACTS applications

In this paper, comparative evaluation between 4.5 kV, 4 kA GTO thyristor and IGCT for series connection in high power three-level Neutral Point Clamped (NPC) voltage source inverter applications is reported. Turn-off tests for GTO and IGCT are compared with RCD snubber at high dc voltage and current. Small RC snubber design is optimized and series connection issues for IGCT are addressed. Experimental results are compared for a two three-level NPC inverter poles operated as H-bridge with three series connected 4.5 kV, 4 kA GTO Thyristors and IGCTsper switch.
RPA Stabilization of Single-Stranded DNA Is Critical for Break-Induced Replication

DNA double-strand breaks (DSBs) are cytotoxic lesions that must be accurately repaired to maintain genome stability. Replication protein A (RPA) plays an important role in homology-dependent repair of DSBs by protecting the single-stranded DNA (ssDNA) intermediates formed by end resection and by facilitating Rad51 loading. We found that hypomorphic mutants of RFA1 that support intra-chromosomal homologous recombination are profoundly defective for repair processes involving long tracts of DNA synthesis, in particular break-induced replication (BIR). The BIR defects of the rfa1 mutants could be partially suppressed by eliminating the Sgs1-Dna2 resection pathway, suggesting that Dna2 nuclease attacks the ssDNA formed during end resection when not fully protected by RPA. Overexpression of Rad51 was also found to suppress the rfa1 BIR defects. We suggest that Rad51 binding to the ssDNA formed by excessive end resection and during D-loop migration can partially compensate for dysfunctional RPA.
Total Hip Arthroplasty in the Spinal Deformity Population: Does Degree of Sagittal Deformity Affect Rates of Safe Zone Placement, Instability, or Revision?

Abstract Background Changes in spinal alignment and pelvic tilt alter acetabular orientation in predictable ways, which may have implications on stability of total hip arthroplasty (THA). Patients with sagittal spinal deformity represent a subset of patients who may be at particularly high risk of THA instability because of postural compensation for abnormal spinal alignment. Methods Using standing stereoradiography, we evaluated the spinopelvic parameters, acetabular cup anteversion, and inclination of 139 THAs in 107 patients with sagittal spinal deformity. Standing images were compared with supine pelvic radiographs to evaluate dynamic changes in acetabular cup position. Dislocation and revision rates were procured through retrospective chart review. The spinal parameters and acetabular cup positions among dislocators were compared with those who did not dislocate. Results The rate of THA dislocation in this cohort was 8.0%, with a revision rate of 5.8% for instability. Patients who sustained dislocations had significantly higher spinopelvic tilt, T1-pelvic angle, and mismatch of lumbar lordosis and pelvic incidence. Among all patients, 78% had safe anteversion while supine, which decreased significantly to 58% when standing due to increases in spinopelvic tilt. Among dislocating THA, 80% had safe anteversion, 80% had safe inclination, and 60% had both parameters within the safe zone. Conclusion In this cohort, patients with THA and concomitant spinal deformity have a particularly high rate of THA instability despite having an acetabular cup position traditionally thought of as within acceptable alignment. This dislocation risk may be driven by the degree of spinal deformity and by spinopelvic compensation. Surgeons should anticipate potential instability after hip arthroplasty and adjust their surgical plan accordingly.
Interactive Semi-automated Method Using Non-negative Matrix Factorization and Level Set Segmentation for the BRATS Challenge

The 2016 BRATS includes imaging data on 191 patients diagnosed with low and high grade gliomas. We present a novel method for multimodal brain segmentation, which consists of (1) an automated, accurate and robust method for image segmentation, combined with (2) semi-automated and interactive multimodal labeling. The image segmentation applies Non-negative Matrix Factorization (NMF), a decomposition technique that reduces the dimensionality of the image by extracting its distinct regions. When combined with the level-set method (LSM), NMF-LSM has proven to be an efficient method for image segmentation. Segmentation of the BRATS images by NMF-LSM is computed by the Cheaha supercomputer at the University of Alabama at Birmingham. The segments of each image are ranked by maximal intensity. The interactive labeling software, which identifies the four targets of the challenge, is semi-automated by cross-referencing the normal segments of the brain across modalities.
Specializing a Planet's Computation: ASIC Clouds

GPU- and FPGA-based clouds have been deployed to accelerate computationally intensive workloads. ASIC-based clouds are a natural evolution as cloud services expand across the planet. ASIC Clouds are purpose-built datacenters comprising large arrays of ASIC accelerators that optimize the total cost of ownership (TCO) of large, high-volume scale-out computations. On the surface, ASIC Clouds may seem improbable due to high nonrecurring engineering (NRE) costs and ASIC inflexibility, but large-scale ASIC Clouds have been deployed for the Bitcoin cryptocurrency system. This article distills lessons from these Bitcoin ASIC Clouds and applies them to other large-scale workloads, including YouTube-style video-transcoding and Deep Learning, showing superior TCO versus CPU and GPU. It derives Pareto-optimal ASIC Cloud servers based on accelerator properties, by jointly optimizing ASIC architecture, DRAM, motherboard, power delivery, cooling, and operating voltage. Finally, the authors examine the impact of ASIC NRE and when it makes sense to build an ASIC Cloud.
Identification of Proteins Involved in Endosome Fusion: Implications for Toxin Activity

Endocytosis of proteins is a fundamental aspect of protein transport required for cell survival. Binding of a number of ligands including hormones, growth factors, nutrients and antigens to cell-surface receptors initiates internalization of these macromolecules. The receptor-ligand complexes that form at the cell surface sequester within clathrin-coated pits and the pits pinch off the plasma membrane to form coated vesicles1. After uncoating, the vesicles fuse with other endocytic vesicles, the compartment acidifies and the ligands dissociate from their receptors2. The lumenal contents of the endocytic vesicles are commonly delivered to lysosomes or the Golgi apparatus while the majority of the membrane components are recycled to the plasma membrane3.
PySeqLab: an open source Python package for sequence labeling and segmentation.

Motivation Text and genomic data are composed of sequential tokens, such as words and nucleotides that give rise to higher order syntactic constructs. In this work, we aim at providing a comprehensive Python library implementing conditional random fields (CRFs), a class of probabilistic graphical models, for robust prediction of these constructs from sequential data. Results Python Sequence Labeling (PySeqLab) is an open source package for performing supervised learning in structured prediction tasks. It implements CRFs models, that is discriminative models from (i) first-order to higher-order linear-chain CRFs, and from (ii) first-order to higher-order semi-Markov CRFs (semi-CRFs). Moreover, it provides multiple learning algorithms for estimating model parameters such as (i) stochastic gradient descent (SGD) and its multiple variations, (ii) structured perceptron with multiple averaging schemes supporting exact and inexact search using 'violation-fixing' framework, (iii) search-based probabilistic online learning algorithm (SAPO) and (iv) an interface for Broyden-Fletcher-Goldfarb-Shanno (BFGS) and the limited-memory BFGS algorithms. Viterbi and Viterbi A* are used for inference and decoding of sequences. Using PySeqLab, we built models (classifiers) and evaluated their performance in three different domains: (i) biomedical Natural language processing (NLP), (ii) predictive DNA sequence analysis and (iii) Human activity recognition (HAR). State-of-the-art performance comparable to machine-learning based systems was achieved in the three domains without feature engineering or the use of knowledge sources. Availability and implementation PySeqLab is available through https://bitbucket.org/A_2/pyseqlab with tutorials and documentation. Contact ahmed.allam@yale.edu or michael.krauthammer@yale.edu. Supplementary information Supplementary data are available at Bioinformatics online.
Programmed Death Ligand-1 (PD-L1) Expression in Either Tumor Cells or Tumor-Infiltrating Immune Cells Correlates With Solid and High-Grade Lung Adenocarcinomas.

Context.— Programmed death ligand-1 (PD-L1) expression in non–small cell lung carcinoma (NSCLC) is heterogeneous and known to be underestimated on small biopsies. Correlation of PD-L1 expression with clinicopathologic features may provide additional useful information. To our knowledge, the clinicopathologic features of NSCLC have not been reported for subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells. Objective.— To investigate the clinicopathologic characteristics of NSCLC subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells. Design.— PD-L1 immunohistochemistry with the SP142 clone was performed on whole-tissue sections and given semiquantitative scores (0/1/2/3) according to percent of PD-L1+ tumor cells (TCs) and percent tumor area with PD-L1+ tumor-infiltrating immune cells (ICs). Results.— Adenocarcinoma cases that were scored either TC 1/2/3 or IC 1/2/3 included most (22 of 34; 65%) high–histologic grade cases and mo...
Mechanistic Insights into the Alternating Copolymerization of Epoxides and Cyclic Anhydrides Using a (Salph)AlCl and Iminium Salt Catalytic System

Mechanistic studies involving synergistic experiment and theory were performed on the perfectly alternating copolymerization of 1-butene oxide and carbic anhydride using a (salph)AlCl/[PPN]Cl catalytic pair. These studies showed a first-order dependence of the polymerization rate on the epoxide, a zero-order dependence on the cyclic anhydride, and a first-order dependence on the catalyst only if the two members of the catalytic pair are treated as a single unit. Studies of model complexes showed that a mixed alkoxide/carboxylate aluminum intermediate preferentially opens cyclic anhydride over epoxide. In addition, ring-opening of epoxide by an intermediate comprising multiple carboxylates was found to be rate-determining. On the basis of the experimental results and analysis by DFT calculations, a mechanism involving two catalytic cycles is proposed wherein the alternating copolymerization proceeds via intermediates that have carboxylate ligation in common, and a secondary cycle involving a bis-alkoxide s...
Characterization of the Rotating Exercise Quantification System (REQS), a novel Drosophila exercise quantification apparatus

Obesity is a disease that has reached epidemic proportions in the United States and has prompted international legislation in an attempt to curtail its prevalence. Despite the fact that one of the most prescribed treatment options for obesity is exercise, the genetic mechanisms underlying exercise response in individuals are still largely unknown. The fruit fly Drosophila melanogaster is a promising new model for studying exercise genetics. Currently, the lack of an accurate method to quantify the amount of exercise performed by the animals is limiting the utility of the Drosophila model for exercise genetics research. To address this limitation, we developed the Rotational Exercise Quantification System (REQS), a novel apparatus that is able to simultaneously induce exercise in flies while recording their activity levels. Thus, the REQS provides a method to standardize Drosophila exercise and ensure that all animals irrespective of genotype and sex experience the same level of exercise. Here, we provide a basic characterization of the REQS, validate its measurements using video-tracking technology, illustrate its potential use by presenting a comparison of two different exercise regimes, and demonstrate that it can be used to detect genotype-dependent variation in activity levels.
Lasiodiplodia theobromae in Citrus Fruit (Diplodia Stem-End Rot)

Abstract Citrus is one of the most important fruit crops in Florida and in the world. Diplodia stem-end rot caused by Lasiodiplodia theobromae (synonyms: Botryodiplodia theobromae and Diplodia natalensis) is an economically important postharvest fruit decay that occurs on all types of citrus grown in Florida and other hot, humid tropical and subtropical regions in the world. Postharvest Diplodia stem-end rot develops from latent infections of the fungus established in necrotic tissues of the fruit button (calyx and disk) on citrus trees in groves. After harvest, L. theobromae reactivates, grows and infects the fruit through the natural openings formed between the fruit and button during the button separation upon abscission. Fungal latent infection levels on immature fruit in groves are favored by many factors such as high amounts of deadwood on trees, high temperature, high and frequent rainfall, and less fungicide applied in the grove. Postharvest L. theobromae infection and stem-end rot development can be enhanced by ethylene degreening treatment and excess delay and holding of the fruit before packing and treatment with appropriate postharvest fungicides. The effective control of Diplodia stem-end rot can be achieved through an integrated disease management system with chemical application as the core component during both the preharvest and postharvest stages. This decay control system could include: (1) performing good cultural practices growing citrus trees with minimal amounts of deadwood; (2) delaying harvest for better natural color development or spot picking better colored fruit to minimize the amount of time needed for postharvest degreening treatment; (3) spraying trees with a benzimidazole fungicide (if there is one registered for preharvest use) or drenching fruit with thiabendazole, imazalil or fludioxonil before degreening; (4) minimizing the degreening time and ethylene concentration used; (5) applying fungicides on fruit during packing line processing; and (6) precooling or storing fruit immediately after packing at temperatures of 10°C or less. There are several other citrus postharvest decays that also need to be controlled at the same time as Diplodia stem-end rot. Therefore, the Diplodia stem-end rot control system should be integrated into the overall citrus postharvest decay control system to reduce all citrus postharvest diseases and to protect fresh citrus fruit values.
Integrating Physical Activity Into Clinical Cancer Care

Physical activity is an important target for improving health and well-being among cancer survivors. Cancer clinicians are uniquely positioned to promote physical activity among survivors through follow-up visits for treatment planning and surveillance. Providers should prioritize assessment of guideline-concordant physical activity and facilitate achievement of physical activity guidelines through exercise prescription, goal setting, addressing barriers, and capitalizing on support systems.
Characterization of Rate-Dependent Constitutive Behavior of Copper Free-Air Ball and Its Use for Wire Bonding Process Simulation

Copper (Cu) wire bond technology is an increasingly popular alternative to gold (Au) wire bond in microelectronic devices due to its superior electrical performance and low cost. Cu wires are also approximately 25% more thermally conductive than gold wires, resulting in better heat dissipation. At present, validated constitutive models for the strain rate and temperature-dependent behavior of Cu free-air ball (FAB) appear to be largely missing in the literature. The lack of reliable constitutive models for the Cu FAB has hampered the modeling of the wire bonding process and the ability to assess risk of fracture in ultralow-k dielectric stacks. The challenge to FAB characterization is primarily due to the difficulty in performing mechanical tests on spherical FAB of micrometer size. To address this challenge, we describe a custom-built microscale tester and carry out compression tests on the FAB in this paper. The Anand viscoplastic constitutive model is developed for Cu FAB through an inverse modeling procedure. In the inverse procedure, constitutive model parameter values are iterated through an automated optimization procedure, until the load–displacement response matches the experimentally observed response. Using the estimated Anand model parameters, a finite-element analysis of the impact and ulatrasonic vibration stages of wire bonding process is carried out, and the resulting dielectric fracture risk is analyzed.
Brass-matrix silicon carbide whisker composites prepared by powder metallurgy

Brass (Cu-18Zn)-matrix and copper-matrix composites containing 0–50 vol% silicon carbide whiskers were fabricated by powder metallurgy using both the admixture method and the coated filler method, such that the fabrication of the copper-matrix composites did not involve a liquid phase whereas that of the brass-matrix composites did during the sintering process. The coated filler method gave composites with lower porosity, greater hardness, higher compressive yield strength, lower coefficient of thermal expansion (CTE), higher thermal conductivity and lower electrical resistivity than the admixture method, though the differences were much larger for copper-matrix composites than brass-matrix composites due to the liquid phase present during the fabrication of the brass-matrix composites. The mechanical properties of the brass-matrix composites were similar to those of the copper-matrix composites (also made by the coated filler method) at >35 vol% SiC, but were superior to those of the copper-matrix composites at 35 vol% SiC. The thermal conductivity was lower and the electrical resistivity was higher in brass-matrix composites than copper-matrix composites at <50 vol% SiC.
Immunological Assessment of the Transplant Patient

The main objective of this chapter is to provide an overview of the immunological evaluation of all potential kidney transplant recipients. The discussion begins with the various immunologic barriers to transplantation, including ABO blood group differences, circulating anti-donor human leukocyte antigen (HLA) antibodies from previous antigen exposure, and minor histocompatibility antigens, which is why even HLA-identical siblings require at least some immunosuppression. Another important concept for readers to grasp is that allograft survival is related to the number of HLA matches. A greater degree of HLA mismatches is also related to higher rates of rejection, which underscores the importance of testing recipients for the presence of preformed antibodies against potential donor HLA antigens.
The DNA Damage Response, DNA Repair, and AML

Acute myeloid leukemia (AML)—especially when the condition arises out of a pre-existing melodysplastic syndrome or follows prior therapy with alkylating agents or ionizing radiation—is frequently associated with complex bone marrow karyotypes, including multiple numeric chromosomal abnormalities, diminutive marker chromosomes of uncertain derivation, and interstitial gains and losses of genetic material. In addition, a variety of inheritied syndromes with DNA repair defects convey a high risk of myelodysplasia and leukemia. Together, these pieces of evidence suggest that a fundamental defect in the DNA damage recognition and response pathways is an important component of leukemogenesis. Here, the basic DNA damage recognition and repair pathways are reviewed and data on known DNA repair abnormalities in acute leukemia and myelodysplastic syndrome are summarized. In addition, inherited syndromes with a DNA repair defect that predisposes to leukemia are outlined, including Fanconi anemia, Bloom syndrome, ataxia-telangiectasia and ataxia-telangiectasia-like disorder, Nijmegen breakage syndrome, Seckel syndrome, and others.
To Live Cancer with Love

I am addressing myself to considering a way to live cancer with love. This attitude reflects great understanding, which is always self-understanding. Following is a transcription of my self-views.
Abstract 107: Protein Comigration Pattern Analysis to Identify High-Density Lipoprotein Subspecies

High density lipoproteins (HDL) are micromolecular complexes composed of lipids and proteins that play critical roles in the prevention of cardiovascular disease (CVD), the major cause of mortality in the United States. Recent proteomics studies have identified about 75 distinct HDL-associated proteins. Many of the newly identified proteins mediate functions that are surprisingly outside the realm of lipid transport. Recently there is strong evidence suggesting that diverse HDL functions are mediated by distinct HDL subspecies. To study the HDL subspecies and their associated functions in CVD, we have applied three orthogonal separation chromatography techniques (gel filtration, anion exchange and isoelectric focusing) to fractionate normal human plasma to phospholipid-containing subfractions. We then isolated lipid associated proteins and determined their identities and relative distribution across subfractions using mass spectrometery. The distribution patterns of 159 proteins were determined for each separation technique. Lipid associated proteins which have similar co-migration patterns when separated by different techniques are likely to form distinct lipoprotein subspecies. Two novel correlation based score systems were developed in order to identify these subspecies: the C-Score and S-Score systems. C-Score system is based on the number of fractions that contain both proteins. S-Score system is based on the variation of two proteins’ normalized patterns, which does not require the independence assumption required by regular correlation coefficient. We built two similarity networks based on these two score systems and identified 31 overlapped cliques. These 31 identified cliques may represent consistent HDL subspecies across different human plasma samples and analysis methods. To assess the significance of these cliques, we performed random permutation test. We further did functional enrichment analysis using GO annotations. All of these analyses suggest that these candidate cliques/biomarker may reveal novel interactions among HDL proteins and provide models of the underlying molecular mechanisms of CVD. The experimental validations of the identified HDL subspecies using immunoprecipitation are under way.