bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of novel macropinocytosis inhibitors using a rational screen of Food and Drug Administration‐approved drugs
Authors: Lin Hui‐Ping , Singla Bhupesh , Ghoshal Pushpankur , Faulkner Jessica L , Cherian‐Shaw Mary , O'Connor Paul M , She Jin‐Xiong , Belin de Chantemele Eric J , Csányi Gábor 
Published: June 2018

Background and PurposeMacropinocytosis is involved in many pathologies, including cardiovascular disorders, cancer, allergic diseases, viral and bacterial infections. Unfortunately, the currently available pharmacological inhibitors of macropinocytosis interrupt other endocytic processes and have non‐specific endocytosis‐independent effects. Here we have sought to identify new, clinically relevant inhibitors of macropinocytosis, using an FDA‐approved drug library.Experimental ApproachIn the present study, 640 FDA‐approved compounds were tested for their ability to inhibit macropinocytosis. A series of secondary assays were performed to confirm inhibitory activity, determine IC50 values and investigate cell toxicity. The ability of identified hits to inhibit phagocytosis and clathrin‐mediated and caveolin‐mediated endocytosis was also investigated. Scanning electron microscopy and molecular biology techniques were utilized to examine the mechanisms by which selected compounds inhibit macropinocytosis.Key ResultsThe primary screen identified 14 compounds that at ~10 μM concentration inhibit >95% of macropinocytotic solute internalization. Three compounds ‐ imipramine, phenoxybenzamine and vinblastine ‐ potently inhibited (IC50 ≤ 131 nM) macropinocytosis without exerting cytotoxic effects or inhibiting other endocytic pathways. Scanning electron microscopy imaging indicated that imipramine inhibits membrane ruffle formation, a critical early step leading to initiation of macropinocytosis. Finally, imipramine has been shown to inhibit macropinocytosis in several cell types, including cancer cells, dendritic cells and macrophages.Conclusions and ImplicationsOur results identify imipramine as a new pharmacological tool to study macropinocytosis in cellular and biological systems. This study also suggests that imipramine could be a good candidate for repurposing as a therapeutic agent in pathological processes involving macropinocytosis.
Tobacco and cannabis use in college students are predicted by sex‐dimorphic interactions between MAOA genotype and child abuse
Authors: Fite Paula J. , Brown Shaquanna , Hossain Waheeda , Manzardo Ann , Butler Merlin G. , Bortolato Marco 
Published: June 2018

SummaryBackgroundPostsecondary students in Western countries exhibit a high prevalence of cannabis and tobacco use disorders. The etiology of these problems is contributed by several psychosocial factors, including childhood adversity and trauma; however, the mechanisms whereby these environmental determinants predispose to the use of these substances remain elusive, due to our poor knowledge of genetic and biological moderators. Converging evidence points to the monoamine oxidase A (MAOA) gene as a moderator of the effects of lifetime stress on the initiation of substance use.AimsBuilding on these premises, in this study, we analyzed whether MAOA upstream variable number tandem repeat (uVNTR) alleles interact with child maltreatment history to predict for lifetime cannabis and tobacco consumption.Materials and methodsFive hundred college students (age: 18–25 years) from a large Midwestern University were surveyed for their child maltreatment history (encompassing emotional, physical, and sexual abuse, as well as emotional and physical neglect) and lifetime consumption of cannabis and tobacco. Saliva samples were obtained to determine the MAOA uVNTR genotype of each participant.ResultsIn female students, lifetime tobacco and cannabis use was predicted by the interaction of physical and emotional abuse with high‐activity MAOA allelic variants; conversely, in males, the interaction of low‐activity MAOA alleles and physical abuse was associated with lifetime use of tobacco, but not cannabis.DiscussionThese findings collectively suggest that the vulnerability to smoke tobacco and cannabis is predicted by sex‐dimorphic interactions of MAOA gene with childhood abuse.ConclusionThese biosocial underpinnings of tobacco and cannabis use may prove important in the development of novel personalized preventive strategies for substance use disorders in adolescents.
The impact of brain‐derived neurotrophic factor Val66Met polymorphism on cognition and functional brain networks in patients with intractable partial epilepsy
Authors: Sidhu Meneka K. , Thompson Pamela J. , Wandschneider Britta , Foulkes Alexandra , de Tisi Jane , Stretton Jason , Perona Marina , Thom Maria , Bonelli Silvia B. , Burdett Jane , Williams Elaine , Duncan John S. , Matarin Mar 
Published: June 2018

SummaryIntroductionMedial temporal lobe epilepsy (mTLE) is the most common refractory focal epilepsy in adults. Around 30%‐40% of patients have prominent memory impairment and experience significant postoperative memory and language decline after surgical treatment. BDNF Val66Met polymorphism has also been associated with cognition and variability in structural and functional hippocampal indices in healthy controls and some patient groups.AimsWe examined whether BDNF Val66Met variation was associated with cognitive impairment in mTLE.MethodsIn this study, we investigated the association of Val66Met polymorphism with cognitive performance (n = 276), postoperative cognitive change (n = 126) and fMRI activation patterns during memory encoding and language paradigms in 2 groups of patients with mTLE (n = 37 and 34).ResultsmTLE patients carrying the Met allele performed more poorly on memory tasks and showed reduced medial temporal lobe activation and reduced task‐related deactivations within the default mode networks in both the fMRI memory and language tasks than Val/Val patients.ConclusionsAlthough cognitive impairment in epilepsy is the result of a complex interaction of factors, our results suggest a role of genetic factors on cognitive impairment in mTLE.
Inventory Management and Endogenous Demand: Investigating the Role of Customer Referrals, Defections, and Product Market Failure
Authors: Sokolinskiy Oleg , Sopranzetti Ben , Rogers Dale S. , Leuschner Rudolf 
Published: June 2018

ABSTRACTThis article optimizes a finite population, dynamic, stochastic inventory model where future demand is endogenous to inventory policy. Specifically, satisfied customers are not only likely to remain with the firm, but may also refer new customers. In contrast, backorders and lost sales may cause disgruntled customers to defect and potentially cause them to dissuade new customers from doing business with the firm. Thus, inventory policy and customer demand are endogenous. Further, the model allows for the possibility that too many customer defections may lead to product market failure. The incorporation of these innovations into our model yields inventory policies that differ substantially from those reported in the literature, with the greatest differences occurring when the firm has low to medium market share.
Managing Television Commercial Inventory under Competition: An Equilibrium Analysis
Authors: Geng Qin , Mallik Suman 
Published: June 2018

ABSTRACTWe develop a game theoretic model for managing prime time on‐air ad inventory in the television industry. The ad inventory in this industry is priced based on rating points or the number of viewers that watch a commercial. The rating points are sold through two distinct processes: the upfront, which occurs before the broadcast season, and the scatter, which occurs throughout during the broadcast season. Television networks need to allocate their total rating points inventory to these two markets before knowing either the performance rating of their shows or the scatter market price, both of which are ex ante uncertain. The television networks offer performance guarantees on the inventory that is sold in the upfront market while such guarantees are not offered in the scatter market. We consider the inventory competition between two television networks under such a setting. To the best of our knowledge, ours is the first article to consider competition in media revenue management. We establish the existence of unique Nash equilibrium under quantity competition and describe the sensitivity of the equilibrium outcome with respect to various problem parameters. We show that choosing quantity over price during the upfront is a dominant strategy for a television network. We compare our competitive model with a centralized system and discuss the managerial implications for our work.
Testing for constant correlation of filtered series under structural change
Authors: Demetrescu Matei , Wied Dominik 
Published: June 2018

SummaryThe paper proposes a test for constant correlations that allow for breaks at unknown times in the marginal means and variances. Theoretically and in an application to US and German stock returns, we find that not accounting for changes in the marginal moments has severe consequences. This is because incorrect standardization of the series transfers to the sample correlations onto which the tests are built. Correcting for variance breaks at unknown time will have an asymptotic effect. To discuss adjustments, we tackle the issue more generally by considering partial-sums-based inference on moment properties of unobserved processes that is conducted on the basis of estimated counterparts obtained in a preliminary step. The paper gives a characterization of the conditions under which the effect of filtering does not vanish asymptotically. The analysis extends to models with breaks in parameters at estimated time.
The diagnostic accuracy of laser Doppler flowmetry in assessing pulp blood flow in permanent teeth: A systematic review
Authors: Ghouth Nahar , Duggal Monty S. , BaniHani Alaa , Nazzal Hani 
Published: June 2018

AbstractBackground/AimPulp necrosis is a frequent complication following dental trauma. The diagnosis of the state of the dental pulp can be challenging as most commonly used diagnostic tools are subjective and rely on a response from the patient, potentially making their use unreliable, especially in the child population. The aim of the study was to systematically review the evidence on the use of laser Doppler flowmetry in the assessment of the pulp status of permanent teeth compared to other sensibility and/or vitality tests.MethodsA systematic literature search, using MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, www.clinicaltrials.gov and www.controlled-trials.com, in addition to citation and manual reference list searches, was conducted up to 15th January 2018. A risk of bias assessment was performed using the quality assessment for diagnostic accuracy studies tool (QUADAS‐2) with all steps performed independently by two reviewers.ResultsFour studies with a high risk of bias were included in the final analysis. Laser Doppler flowmetry was reported to be more accurate in differentiating between teeth with normal pulps and pulp necrosis with a sensitivity of (81.8%‐100%) and specificity of 100% in comparison to other vitality tests such as pulp oximetry (sensitivity = 81.3%, specificity = 94.9%) and sensibility tests such as electric pulp testing (sensitivity = 63.3%‐91.5%, specificity = 88%‐100%).ConclusionDespite the higher reported sensitivity and specificity of laser Doppler flowmetry in assessing pulp blood flow, these data are based on studies with a high level of bias and serious shortfalls in study designs. More research is needed to study the effect of different laser Doppler flowmetry's parameters on its diagnostic accuracy and the true cut‐off ratios over which a tooth could be diagnosed as having a normal pulp.
“My Child, My Choice”? Mandatory Curriculum, Sex, and the Conscience of Parents
Authors: Bialystok Lauren 
Published: June 2018

ABSTRACTIn this essay Lauren Bialystok argues that the standard liberal defense of parental opt‐outs is inconsistent in the case of comprehensive sex education. Using the recent controversy over a new sex education curriculum in Ontario, Canada, as a case study, Bialystok examines the aims and effects of sex education and the self‐described conscience of opposing parents to reveal that children's interests may be harmed by deferring to parents' views on sexuality. The opt‐out strategy is a merely formal solution, which appears to be indifferent to both the strength of the justification for sex education and the content of the grounds on which parents oppose it. Being overly respectful of parental conscience in the case of sex education risks reproducing the illiberal paradigms that the curriculum is intended to erode, and thus subverts its own liberal intentions. Bialystok concludes by suggesting ways of honoring parents' right to involvement in their children's education while delivering a mandatory curriculum.
Lying in Politics: Fake News, Alternative Facts, and the Challenges for Deliberative Civics Education
Authors: Gordon Mordechai 
Published: June 2018

ABSTRACTInspired by Orwell's chilling account of brainwashing, propaganda, and the obliteration of the lines between fiction and truth, Mordechai Gordon attempts to make sense of the phenomenon of lying in politics as a challenge to deliberative civics education. His analysis begins with a detailed consideration of the distinctions Hannah Arendt draws between factual truth, lying, and opinions in several works but with particular reference to her essays “Lying in Politics” and “Truth and Politics.” Gordon shows that although Arendt recognized many of the dangers to the vitality of a democracy when the lines that distinguish between facts, lies, and opinions become blurred, she could not have anticipated the extent to which the advent of modern technology and online media would exacerbate this problem in contemporary society. Next, he draws on the theory of deliberative democracy to argue that the lack of a clear distinction between fiction and factual truths serves to undermine the quality of political debates in a democratic society. In the final part of the essay, Gordon discusses the challenges that the advent of fake news organizations and the dissemination of alternative facts as truth pose to deliberative civics education, specifically how the trend of a diminishing space of truth and fact undermines efforts to teach students how to engage effectively and productively in democratic deliberations.
Turbid water induces refuge behaviour of a commercially important ayu: A field experiment for interstream movement using multiple artificial streams
Authors: Mori Terutaka , Kato Yasumitsu , Takagi Tetsuya , Onoda Yukio , Kayaba Yuichi 
Published: June 2018

AbstractRiverine systems are inherently dendritic in nature, and turbid water may not necessarily flow equally throughout an entire catchment. Tributaries have the potential to serve as refugia from temporarily turbid water in the main stem. As ayu (Plecoglossus altivelis) are one of the important species for the inland fisheries industry and recreational fishing, their behaviour in a branched river network is a primary concern. We released ayu with radio‐transmitting tags into two experimental streams that joined at a downstream pool. Turbid water was released into one of the streams, and we identified whether avoidance movement of ayu between the two experimental streams was triggered by flowing turbid water. The suspended solid concentration elevated rapidly after adding the turbid water and was maintained at more than 400 mg/L for 3 hr. Avoidance movement of ayu was triggered when the suspended solid concentration exceeded approximately 200 mg/L. Then, most ayu moved from the turbid stream to the nonturbid one, leading to a difference in ayu density between the two streams. Therefore, we demonstrated that turbid water induced interstream movement of a commercially important ayu as refuge behaviour, suggesting that river connectivity is important for the persistence of the ayu.
Contrasting changes in freshwater fish assemblages and food webs follow modification of tropical waterways
Authors: Liew Jia Huan , Giam Xingli , Clews Esther , Tan Kenrick Y. W. , Tan Heok Hui , Kho Zi Yi , Yeo Darren C. J. 
Published: June 2018

AbstractFresh waters are increasingly threatened by flow modification. Knowledge about the impacts of flow modification is incomplete, especially in the tropics where ecological studies are only starting to emerge in recent years. Using presence/absence data dated approximately four decades apart (~1966 to ~2010) from 10 tropical rivers, we assessed the changes in freshwater fish assemblage and food web after flow modification. The sites were surveyed with methods best suited to habitat conditions (e.g., tray/push netting for low‐order forest streams, visual surveys for canalised rivers and net casting for impounded rivers). With the presence/absence data, we derived and compared six measures of fish assemblage and food web structure: species richness, proportion of native species, overall functional diversity, native functional diversity, food web complexity and maximum trophic level. We found that changes in community assemblage and food web structure were not generalisable across modification regimes. In canalised sites, species richness and maximum trophic levels were lower in the second time period while the opposite was true for impounded sites. However, proportion of native species was consistently lower in the second time period across modification regimes. Changes in fish assemblages and food webs appear to be driven by species turnover. We recorded 79 cases of site‐specific extirpation and 117 cases of site‐specific establishment. Our data further suggest that turnover in assemblage is again contingent on flow‐modification regime. While the process was stochastic in canalised rivers, benthopelagic species were more likely to be extirpated from impounded rivers where species lost were replaced by predominantly alien fish taxa.
ATP6V0A2‐related cutis laxa in 10 novel patients: Focus on clinical variability and expansion of the phenotype
Authors: Beyens Aude , Moreno‐Artero Ester , Bodemer Christine , Cox Helen , Gezdirici Alper , Yilmaz Gulec Elif , Kahloul Najoua , Khau Van Kien Philippe , Ogur Gonul , Harroche Annie , Vasse Marc , Salhi Aïcha , Symoens Sofie , Hadj‐Rabia Smail , Callewaert Bert 
Published: June 2018

AbstractIn ATP6V0A2‐related cutis laxa, the skin phenotype varies from a wrinkly skin to prominent cutis laxa and typically associates with skeletal and neurological manifestations. The phenotype remains incompletely characterized, especially in adult patients. Glycosylation defects and reduced acidification of secretory vesicles contribute to the pathogenesis, but the consequences at the clinical level remain to be determined. Moreover, the morphology of the elastic fibres has not been studied in ATP6V0A2‐related cutis laxa, nor its relation with potential clinical risks. We report on the extreme variability in ATP6V0A2‐related cutis laxa in 10 novel patients, expand the phenotype with emphysema and von Willebrand disease and hypothesize on the pathogenesis that might link both with deficiency of glycosylation and with elastic fibre anomalies. Our data will affect clinical management of patients with ATP6V0A2‐related cutis laxa.
Microstructure‐sensitive fatigue modelling of medical‐grade fine wire
Authors: Clark B.C. , Castelluccio G.M. , Reiterer M.W. , McDowell D.L. , Neu R.W. 
Published: June 2018

AbstractThis work presents a modelling methodology to assess the sensitivity to microstructure in high‐cycle fatigue performance of fine wires made from MP35N alloy (35Ni‐35Co‐20Cr‐10Mo in wt%) used as conductors in cardiac leads. The model consists of a microstructure generator that creates a mesh of a statistically representative microstructure, a finite element analysis using a crystal plasticity constitutive model to determine the local response behaviour of the microstructure, and a postprocesser using fatigue indicating parameters to assess the likelihood of fatigue crack initiation. The fatigue crack initiation potency for selected microstructure attributes, boundary and interface conditions, and loading profiles is determined by computing the Fatemi‐Socie fatigue indicating parameter over a physically relevant volume of scale. Case studies are used to investigate (1) the influence of nonmetallic inclusion proximity to the wire surface on fatigue potency and (2) the transition life demarcating lives primarily controlled by fatigue crack initiation versus microcrack fatigue growth.
Extrapolation‐based Bandwidth Selectors: A Review and Comparative Study with Discussion on Bivariate Applications
Authors: Wang Qing 
Published: June 2018

SummaryCross‐validation is a widely used tool in selecting the smoothing parameter in a non‐parametric procedure. However, it suffers from large sampling variation and tends to overfit the data set. Many attempts have been made to reduce the variance of cross‐validation. This paper focuses on two recent proposals of extrapolation‐based cross‐validation bandwidth selectors: indirect cross‐validation and subsampling‐extrapolation technique. In univariate case, we notice that using a fixed value parameter surrogate for indirect cross‐validation works poorly when the true density is hard to estimate, while the subsampling‐extrapolation technique is more robust to non‐normality. We investigate whether a hybrid bandwidth selector could benefit from the advantages of both approaches and compare the performance of different extrapolation‐based bandwidth selectors through simulation studies, real data analyses and large sample theory. A discussion on their extension to bivariate case is also presented.
Engaging with and navigating limbo: Lived experiences of siblings of adults with autism spectrum disorders
Authors: Noonan Hester , O’ Donoghue Isabelle , Wilson Charlotte 
Published: June 2018

AbstractBackgroundSupporting an adult with autism spectrum disorder (ASD) can be associated with family stress but also with personal growth and resilience. Research providing insight into how typically developing siblings make sense of their unique sibling relationships in adulthood remains limited.MethodUsing interpretative phenomenological analysis, this study explored subjective experiences of eight siblings of adults with ASD and co‐occurring intellectual disability.ResultsAnalysis of interview transcripts revealed a complex lived experience explained by the overarching theme “engaging with and navigating limbo”, which was characterized by commitment to the sibling relationship, power tensions in the family, uncertainty about the future and negotiating the tension between relational closeness and distance.ConclusionUsing family systems theory, overregulation and closed communication emerged as processes relevant to families living with ASD. Clinical opportunities to support family communication, change tolerance and belonging are discussed.
Photoonycholysis: new findings
Authors: Baran R. , Mascaro J.M. , Aguilera P. 
Published: June 2018

Abstract
First described in 1961, photoonycholysis (PO) is a rare nail alteration that may result from drug intake, from topical aminolevulinate photodynamic therapy or from photosensitive conditions such as porphyria or pseudoporphyria. Spontaneous PO is rare. This review updates the numerous causes of PO and highlights some new ways producing this condition. Four different types of PO are clearly recognized without relationship with the responsible drug. An updated list of potential inducing drug is provided. Some practical points on PO have been raised. The inability to reproduce photoonycholysis experimentally should be emphasized, and the pathogenesis of PO still needs to be clarified.