bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calcium Channel Blocker Use and Risk of Prostate Cancer by TMPRSS2:ERG Gene Fusion Status
Authors: Geybels Milan S. , McCloskey Karen D. , Mills Ian G. , Stanford Janet L. 
Published: October 2016

BACKGROUNDCalcium channel blockers (CCBs) may affect prostate cancer (PCa) growth by various mechanisms including those related to androgens. The fusion of the androgen‐regulated gene TMPRSS2 and the oncogene ERG (TMPRSS2:ERG or T2E) is common in PCa, and prostate tumors that harbor the gene fusion are believed to represent a distinct disease subtype. We studied the association of CCB use with the risk of PCa, and molecular subtypes of PCa defined by T2E status.METHODSParticipants were residents of King County, Washington, recruited for population‐based case–control studies (1993–1996 or 2002–2005). Tumor T2E status was determined by fluorescence in situ hybridization using tumor tissue specimens from radical prostatectomy. Detailed information on use of CCBs and other variables was obtained through in‐person interviews. Binomial and polytomous logistic regression were used to generate odds ratios (ORs) and 95% confidence intervals (CIs).RESULTSThe study included 1,747 PCa patients and 1,635 age‐matched controls. A subset of 563 patients treated with radical prostatectomy had T2E status determined, of which 295 were T2E positive (52%). Use of CCBs (ever vs. never) was not associated with overall PCa risk. However, among European‐American men, users had a reduced risk of higher‐grade PCa (Gleason scores ≥7: adjusted OR = 0.64; 95% CI: 0.44–0.95). Further, use of CCBs was associated with a reduced risk of T2E positive PCa (adjusted OR = 0.38; 95% CI: 0.19–0.78), but was not associated with T2E negative PCa.CONCLUSIONSThis study found suggestive evidence that use of CCBs is associated with reduced relative risks for higher Gleason score and T2E positive PCa. Future studies of PCa etiology should consider etiologic heterogeneity as PCa subtypes may develop through different causal pathways. Prostate 77:282–290, 2017. © 2016 Wiley Periodicals, Inc.
Structure of a glycoside hydrolase family 50 enzyme from a subfamily that is enriched in human gut microbiome bacteroidetes
Authors: Giles Kaleigh , Pluvinage Benjamin , Boraston Alisdair B. 
Published: October 2016

ABSTRACTThe polysaccharide utilization locus in Bacteroides plebeius that confers the ability to catabolize porphyran contains a putative GH50 β‐agarase (BACPLE_01683, BpGH50). BpGH50 did not show any clear activity on agarose or on the related algal galactans porphyran and carrageenan. However, the 1.4 Å resolution X‐ray crystal structure of BpGH50 confirmed its possession of the core (α/β)8 barrel fold found in GH50 enzymes as well as the structural conservation of the catalytic residues and some substrate binding residues. Examination of the structure supports assignment of this protein as a β‐galactosidase but suggests that it may utilize a different, possibly hybrid, algal galactan substrate. Proteins 2016; 85:182–187. © 2016 Wiley Periodicals, Inc.
Perspectives on the agrochemical industry and agrochemical discovery
Authors: Sparks Thomas C , Lorsbach Beth A 
Published: October 2016

AbstractAgrochemicals have been critical to the production of food and fiber, as well as the control of vectors of disease. The need for the discovery and development of new agrochemicals continues unabated due to the loss of existing products through the development of resistance, the desire for products with more favorable environmental and toxicological profiles, shifting pest spectra, and changing agricultural needs and practices. As presented in the associated analysis of the agrochemical industry, the rising costs and complexities of agrochemical discovery have, in part, led to increasing consolidation, especially in the USA and Europe. However, as demonstrated by the present analysis, the discovery of new agrochemicals continues in spite of the challenges. © 2016 Society of Chemical Industry
Self‐similarity based DDoS attack detection using Hurst parameter
Authors: Deka Rup K. , Bhattacharyya Dhruba K. 
Published: October 2016

AbstractDistributed denial‐of‐service attack is a serious concern in this era of voluminous Internet world. The challenge is to find difference between distributed denial‐of‐service attack traffic of all types and legitimate traffic at the earliest, as we can see high‐rate attack traffic and low rate attack traffic resembles with bursty legitimate traffic and normal legitimate traffic, respectively. Self‐similarity exists in ethernet traffic. Using Hurst parameter, we have differentiated legitimacy of any traffic irrespective of network traffic protocol. We have validated our method using both benchmark and real‐life datasets, and the results are highly satisfactory. Copyright © 2016 John Wiley & Sons, Ltd.
Distributed key generation protocol with a new complaint management strategy
Authors: Neji Wafa , Blibech Kaouther , Ben Rajeb Narjes 
Published: October 2016

AbstractA distributed key generation (DKG) protocol is a fundamental building block for many threshold cryptosystems. It allows a set of participants to jointly generate a shared secret key without using a trusted party. In 1991, Pedersen proposed the first DKG protocol called Joint‐Feldman DKG. However, it was proved later that this protocol does not guarantee a uniformly random distribution of generated keys. Despite this flaw in the security requirements, Pedersen's DKG protocol has been used for several years as central component to design threshold cryptosystems. Note that most of the solutions proposed in the literature to improve the Pedersen's DKG protocol have several disadvantages. They use private channels, require participants to reveal their secret shares to solve complaints, and use costly computations. This makes them complex and not easy to use in practical situations. In this paper, we present at first an extended version of Joint‐Feldman DKG that ensures a uniform distribution of the generated keys. Then we present a DKG protocol with public channels that use a new strategy to manage complaints without revealing the shares of the secrets held by honest participants and that clearly identifies dishonest participants. We prove that our solution satisfies the security requirements of DKG protocols. Copyright © 2016 John Wiley & Sons, Ltd.
Portfolio Entrepreneurship and Resource Orchestration
Authors: Baert Caroline , Meuleman Miguel , Debruyne Marion , Wright Mike 
Published: October 2016

Research summaryThis study examines the role of resource orchestration for the exploration and exploitation of opportunities through portfolio entrepreneurship. Adopting a single‐case study approach, we identify eight distinctive resource orchestration subprocesses that we group into three aggregate resource orchestration processes that enable the development and exploitation of a set of resources and capabilities across a portfolio of ventures. Our findings extend the literature on enduring entrepreneurship by building theory on how resource orchestration across a portfolio of ventures facilitates the emergence of synergies when exploring and exploiting opportunities.Managerial summaryThis study examines the processes through which an entrepreneur structures and rearranges resources and capabilities across multiple firms as he/she grows a portfolio of firms to engage in the exploration and exploitation of market opportunities. Entrepreneurs can obtain insights for building their businesses from the eight processes we identify; these processes allow entrepreneurs to develop synergies as they create and put to use a set of resources and capabilities across their businesses. Through these synergies, entrepreneurs can share, transform, and harmonize resources and capabilities across their firms. This can enable them to continuously and simultaneously explore and exploit market opportunities, which ultimately facilitates the sustainability of their businesses. Copyright © 2016 Strategic Management Society.
Pre-Transplantation Blockade of TNF-α-Mediated Oxygen Species Accumulation Protects Hematopoietic Stem Cells
Authors: Ishida Takashi , Suzuki Sachie , Lai Chen-Yi , Yamazaki Satoshi , Kakuta Shigeru , Iwakura Yoichiro , Nojima Masanori , Takeuchi Yasuo , Higashihara Masaaki , Nakauchi Hiromitsu , Otsu Makoto 
Published: October 2016

AbstractHematopoietic stem cell (HSC) transplantation (HSCT) for malignancy requires toxic pre-conditioning to maximize anti-tumor effects and donor-HSC engraftment. While this induces bone marrow (BM)-localized inflammation, how this BM environmental change affects transplanted HSCs in vivo remains largely unknown. We here report that, depending on interval between irradiation and HSCT, residence within lethally irradiated recipient BM compromises donor-HSC reconstitution ability. Both in vivo and in vitro we demonstrate that, among inflammatory cytokines, TNF-α plays a role in HSC damage: TNF-α stimulation leads to accumulation of reactive oxygen species (ROS) in highly purified hematopoietic stem/progenitor cells (HSCs/HSPCs). Transplantation of flow-cytometry—sorted murine HSCs reveals damaging effects of accumulated ROS on HSCs. Short-term incubation either with an specific inhibitor of tumor necrosis factor receptor 1 signaling or an antioxidant N-acetyl-L-cysteine (NAC) prevents TNF-α-mediated ROS accumulation in HSCs. Importantly, pre-transplantation exposure to NAC successfully demonstrats protective effects in inflammatory BM on graft-HSCs, exhibiting better reconstitution capability than that of nonprotected control grafts. We thus suggest that in vivo protection of graft-HSCs from BM inflammation is a feasible and attractive approach, which may lead to improved hematopoietic reconstitution kinetics in transplantation with myeloablative conditioning that inevitably causes inflammation in recipient BM.
Structural insights into the recognition of phosphorylated FUNDC1 by LC3B in mitophagy
Authors: Lv Mengqi , Wang Chongyuan , Li Fudong , Peng Junhui , Wen Bin , Gong Qingguo , Shi Yunyu , Tang Yajun 
Published: October 2016

AbstractMitophagy is an essential intracellular process that eliminates dysfunctional mitochondria and maintains cellular homeostasis. Mitophagy is regulated by the post-translational modification of mitophagy receptors. Fun14 domain-containing protein 1 (FUNDC1) was reported to be a new receptor for hypoxia-induced mitophagy in mammalian cells and interact with microtubule-associated protein light chain 3 beta (LC3B) through its LC3 interaction region (LIR). Moreover, the phosphorylation modification of FUNDC1 affects its binding affinity for LC3B and regulates selective mitophagy. However, the structural basis of this regulation mechanism remains unclear. Here, we present the crystal structure of LC3B in complex with a FUNDC1 LIR peptide phosphorylated at Ser17 (pS17), demonstrating the key residues of LC3B for the specific recognition of the phosphorylated or dephosphorylated FUNDC1. Intriguingly, the side chain of LC3B Lys49 shifts remarkably and forms a hydrogen bond and electrostatic interaction with the phosphate group of FUNDC1 pS17. Alternatively, phosphorylated Tyr18 (pY18) and Ser13 (pS13) in FUNDC1 significantly obstruct their interaction with the hydrophobic pocket and Arg10 of LC3B, respectively. Structural observations are further validated by mutation and isothermal titration calorimetry (ITC) assays. Therefore, our structural and biochemical results reveal a working model for the specific recognition of FUNDC1 by LC3B and imply that the reversible phosphorylation modification of mitophagy receptors may be a switch for selective mitophagy.
Fathers’ Imprisonment and Mothers’ Multiple-Partner Fertility
Authors: Cancian Maria , Chung Yiyoon , Meyer Daniel R. 
Published: October 2016

AbstractWe consider the intersection between two striking U.S. trends: dramatic increases in the imprisonment of fathers and increases in the proportion of mothers who have children with more than one partner (multiple-partner fertility, or MPF). Using matched longitudinal administrative data that provide unusually comprehensive and accurate information about the occurrence and timing of imprisonment, fertility, and MPF for the population of the state of Wisconsin, we consider the relationship between paternal imprisonment and MPF among unwed mothers. Employing discrete-time event history analysis with multinomial logistic regression, we model the occurrence and timing of the mother’s second birth, distinguishing between a birth with the same father and a birth with a different father, and distinguishing between current imprisonment and a history of imprisonment. We find that current imprisonment is associated with an increased likelihood of MPF and a decreased likelihood of fertility with the same father (compared with no additional birth) and that a history of imprisonment is associated with increased MPF in some models but not in our preferred model. To control for unobserved heterogeneity among mothers and assess the evidence of a causal effect of fathers’ imprisonment, we also employ the case-time-control method, a fixed-effects method for the analysis of nonrepeated events. Results suggest that fathers’ current imprisonment may increase mothers’ MPF. Policy implications are discussed.
Ready, Willing, and Able? Impediments to the Onset of Marital Fertility Decline in the United States
Authors: Hacker J. David 
Published: October 2016

Abstract
This study relies on IPUMS samples of the 1850, 1860, 1870, and 1880 censuses, aggregate census data, and the timing of state laws criminalizing abortion to construct regional estimates of marital fertility in the United States and estimate correlates of marital fertility. The results show a significant lag between the onset of marital fertility decline in the nation’s northeastern census divisions and its onset in western and southern census divisions. Empirical models indicate the presence of cultural, economic, and legal impediments to the diffusion of marital fertility control and illustrate the need for more inclusive models of fertility decline.
How a&nbsp;teaching rotation in medical school affects graduates’ subsequent careers
Authors: Kloek Anne T. , Van Zijl Angela C.M. , Ten Cate Olle T.J. 
Published: October 2016

Introduction Teaching opportunities and teacher courses for medical students are increasingly offered by medical schools but little has been investigated about their long-term effect. The aim of our study was to investigate the long-term career effect of an intensive elective teaching experience for final year medical students.
Methods We approached UMC Utrecht medical graduates who had taken a final year, 6‑week full time student teaching rotation (STR) elective, 6 to 9 years after graduation, with an online survey to ask about their educational activities and obtained teaching certificates, their current roles related to education, and their appreciation of the rotation, even if this was a long time ago. In addition, we surveyed control groups of students who had not taken the STR, divided into those who had expressed interest in the STR but had not been placed and those who had not expressed such interest.
Results We received responses from 50 STR graduates and 88 non-STR graduates (11 with interest and 77 without interest in the STR). STR graduates were more educationally active, had obtained more university teaching certificates and were more enthusiastic teachers. However, we could not exclude confounding, caused by a general interest in education even before the STR.
Conclusions Our findings indicate a high appreciation of the student teaching rotation and a likely but not proven long-term association between STR participation and building an educational career.
Etanercept, an inhibitor of TNF‐a, prevents propofol‐induced neurotoxicity in the developing brain
Authors: Chen Bo , Deng Xiaoyuan , Wang Bin , Liu Hongliang 
Published: October 2016

AbstractPropofol can induce acute neuronal apoptosis, neuronal loss or long‐term cognitive impairment when exposed in neonatal rodents, but the mechanisms by which propofol induces developmental neurotoxicity are unclear. Recent studies have demonstrated that propofol can increase the TNF‐α level in the developing brain, but there is a lack of direct evidence to show whether TNF‐α is partially or fully involved in propofol‐induced neurotoxicity. The present study shows that propofol exposure in neonatal rats induces an increase of TNF‐α in the cerebral spinal fluid, hippocampus and prefrontal cortex (PFC). Etanercept, a TNF‐α inhibitor, prevents propofol‐induced short‐ or long‐term neuronal apoptosis, neuronal loss, synaptic loss and long‐term cognitive impairment. Furthermore, mTNF‐α (precursor of TNF‐α) expression in microglia cells is increased after propofol anaesthesia in either the hippocampus or PFC, but mTNF‐α expression in neurons is only increased in the PFC. These findings suggest that TNF‐α may mediate propofol‐induced developmental neurotoxicity, and etanercept can provide neural protection. Microglia are the main cellular source of TNF‐α after propofol exposure, while the synthesis of TNF‐α in neurons is brain‐region selective.
Analysis of first and second trimester maternal serum analytes for the prediction of morbidly adherent placenta requiring hysterectomy
Authors: Oztas Efser , Ozler Sibel , Caglar Ali Turhan , Yucel Aykan 
Published: October 2016

AbstractMorbidly adherent placenta (MAP) is a growing concern currently and is still a diagnostic challenge for obstetricians. As emergency hysterectomy due to unscheduled delivery in MAP carries significant risks, we aimed to evaluate whether first and second trimester serum analytes may be used in the prediction of MAP requiring hysterectomy. A retrospective chart review of all identified cases of placenta previa totalis with and without MAP was performed. A total of 316 pregnant women diagnosed as placenta previa totalis were identified and included in the analysis. Cases were examined in three groups (Group 1: 204 nonadherent placenta previa patients; Group 2: 61 MAP patients managed with endouterine hemostatic square sutures and/or Bakri balloon tamponade; and Group 3: 51 patients with MAP requiring hysterectomy). Among all first and second trimester screening analytes only maternal serum alphafetoprotein (MS‐AFP) levels were significantly higher in patients with MAP requiring hysterectomy (p < 0.001). According to the Receiver Operating Characteristic (ROC) analysis performed for the predictive value of MS‐AFP levels, the area under the curve (AUC) was 0.742 [95% confidence interval (CI): 0.505–0.979]. The best MS‐AFP cut‐off value was 1.25 multiple of the median (MoM) with 85.94% sensitivity and 71.43% specificity (p = 0.036). The best predictors which affect the increased risk of hysterectomy, was further evaluated by multivariate logistic regression analyses. Only elevated maternal serum alphafetoprotein (MS‐AFP) was found to be an independent predictor of MAP requiring hysterectomy [odds ratio (OR) = 25.329, 95% confidence interval (CI):1.487–43.143, p = 0.025]. In conclusion, increased second trimester MS‐AFP levels independently predict morbidly adherent placenta requiring hysterectomy among women with placenta previa totalis.
NGP 555, a γ‐secretase modulator, lowers the amyloid biomarker, Aβ42, in cerebrospinal fluid while preventing Alzheimer's disease cognitive decline in rodents
Authors: Kounnas Maria Z. , Lane‐Donovan Courtney , Nowakowski Dan W. , Herz Joachim , Comer William T. 
Published: October 2016

AbstractIntroductionAlzheimer's disease (AD) is defined by the progressive accumulation of amyloid plaques and neurofibrillary tangles in the brain which precedes cognitive decline by years.MethodsUsing amyloid biomarkers, chemical modeling, mouse behavioral models, and drug development techniques, we investigate the properties of NGP 555, a clinical‐stage γ‐secretase modulator.ResultsNGP 555 shifts amyloid peptide production to the smaller, nonaggregating forms of amyloid. Our preclinical studies show beneficial effects on amyloid biomarkers, pathology, and cognition. NGP 555 has successfully completed chemistry, pharmacology, toxicity, metabolism, and safety studies.DiscussionAbundant data support Aβ42 as a target for prophylactic or early‐stage intervention therapies in AD. The γ‐secretase modulator, NGP 555 is being actively developed in human clinical trials for the prevention of Alzheimer's disease with the overall aim to achieve an appropriate balance of potency/efficacy on reducing the toxic forms of amyloid versus safety.
African Americans are less likely to enroll in preclinical Alzheimer's disease clinical trials
Authors: Zhou Yan , Elashoff David , Kremen Sarah , Teng Edmond , Karlawish Jason , Grill Joshua D. 
Published: October 2016

AbstractIntroductionAlzheimer's disease (AD) incidence is disproportionately high in African Americans, yet, recruitment of this community to AD clinical trials is challenging.MethodsWe compared 47 African Americans and 78 whites in their willingness to enroll in a hypothetical preclinical AD trial and examined barriers and facilitators in their decision making.ResultsAfrican American race (OR = 0.45; 95% CI, 0.22–0.93) and score on the research attitude questionnaire (OR = 1.12; 95% CI, 1.04–1.22) were independently associated with willingness to participate. African Americans rated study risks, the requirement of a study partner, study procedures, the ratio of drug to placebo, and study location as more important factors in the decision whether to enroll than did whites.DiscussionThese results suggest that researchers will encounter challenges in recruiting African Americans to preclinical AD trials. Future research will be necessary to understand the optimal means to improve recruitment of underrepresented populations.