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Sheng-Ren Chen, Yi-Yu Ke, Teng-Kuang Yeh, Shu-Yu Lin, Li-Chin Ou, Shu-Chun Chen, Wan-Ting Chang, Hsiao-Fu Chang, Zih-Huei Wu, Chih-Chien Hsieh, Ping-Yee Law, Horace H Loh, Chuan Shih, Yiu-Kay Lai, Shiu-Hwa Yeh, Shau-Hua Ueng
μ-Opioid receptor (MOR) agonists are analgesics used clinically for the treatment of moderate to severe pain, but their use is associated with severe adverse effects such as respiratory depression, constipation, tolerance, dependence, and rewarding effects. In this study, we identified N-({2-[(4-bromo-2-trifluoromethoxyphenyl)sulfonyl]-1,2,3,4-tetrahydro-1-isoquinolinyl}methyl)cyclohexanecarboxamide (1) as a novel opioid receptor agonist by high-throughput screening. Structural modifications made to 1 to improve potency and blood-brain-barrier (BBB) penetration resulted in compounds 45 and 46...
September 20, 2016: European Journal of Medicinal Chemistry
Kerry L Gagnon, Anne P DePrince
OBJECTIVE: While the importance of traumatic brain injury (TBI) has gained public attention in recent years, relatively little attention has been paid to head injuries among women who have experienced intimate partner violence (IPV). The present study screened for lifetime exposure to mild traumatic brain injuries (mTBI) among a sample of women who experienced recent IPV (median days since target incident = 26). METHOD: Participants included ethnically diverse women whose IPV experiences were reported to law enforcement...
October 24, 2016: Journal of Trauma & Dissociation
Andreas Widder, Christian Kuehn
In this paper, we focus on the influence of heterogeneity and stochasticity of the population on the dynamical structure of a basic susceptible-infected-susceptible (SIS) model. First we prove that, upon a suitable mathematical reformulation of the basic reproduction number, the homogeneous system and the heterogeneous system exhibit a completely analogous global behaviour. Then we consider noise terms to incorporate the fluctuation effects and the random import of the disease into the population and analyse the influence of heterogeneity on warning signs for critical transitions (or tipping points)...
October 1, 2016: Mathematical Biosciences and Engineering: MBE
Norihiko L Okamoto, Shu Fujimoto, Yuki Kambara, Marino Kawamura, Zhenghao M T Chen, Hirotaka Matsunoshita, Katsushi Tanaka, Haruyuki Inui, Easo P George
High-entropy alloys (HEAs) comprise a novel class of scientifically and technologically interesting materials. Among these, equatomic CrMnFeCoNi with the face-centered cubic (FCC) structure is noteworthy because its ductility and strength increase with decreasing temperature while maintaining outstanding fracture toughness at cryogenic temperatures. Here we report for the first time by single-crystal micropillar compression that its bulk room temperature critical resolved shear stress (CRSS) is ~33-43 MPa, ~10 times higher than that of pure nickel...
October 24, 2016: Scientific Reports
Enrico Ubaldi, Nicola Perra, Márton Karsai, Alessandro Vezzani, Raffaella Burioni, Alessandro Vespignani
The dynamic of social networks is driven by the interplay between diverse mechanisms that still challenge our theoretical and modelling efforts. Amongst them, two are known to play a central role in shaping the networks evolution, namely the heterogeneous propensity of individuals to i) be socially active and ii) establish a new social relationships with their alters. Here, we empirically characterise these two mechanisms in seven real networks describing temporal human interactions in three different settings: scientific collaborations, Twitter mentions, and mobile phone calls...
October 24, 2016: Scientific Reports
Murat Akbaba, Vedat Davutoğlu
The relationship between patients and physicians has maintained its importance throughout human history because of special features of the medical profession. This relationship engendered true loyalty of patients to their physicians as well as serious legal conflicts. Medical malpractice has gained importance among physicians and ignited discussion because of new articles added to the Turkish Penal Code in 2005. In a very short time, the penalties mandated had a chilling, negative effect on doctors, resulting in loss of affection for the profession, hesitation to intervene, and burnout syndrome...
October 2016: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
Jeremy M Law, Jan Wouters, Pol Ghesquière
The direct influence of phonological awareness (PA) on reading outcomes has been widely demonstrated, yet PA may also exert indirect influence on reading outcomes through other cognitive variables such as morphological awareness (MA). However, PA's own development is dependent and influenced by many extraneous variables such as auditory processing, which could ultimately impact reading outcomes. In a group of pre-reading children with a family risk of dyslexia and low-risk controls, this study sets out to answer questions surrounding PA's relationship at various grain sizes (syllable, onset/rime and phoneme) with measures of auditory processing (frequency modulation (FM) and an amplitude rise-time task (RT)) and MA, independent of reading experience...
October 23, 2016: Developmental Science
Robert Mark Simpson
Murrow and Murrow offer a novel account of dehumanization, by synthesizing data which suggest that where subject S has a dehumanized view of group G, S's neural mechanisms of empathy show a dampened response to the suffering of members of G, and S's judgments about the humanity of members of G are largely non-conscious. Here I examine Murrow and Murrow's suggestions about how identity-based hate speech bears responsibility for dehumanization in the first place. I identify a distinction between (i) accounts of the nature of the harm effected by identity prejudice, and (ii) accounts of how hate speech contributes to the harms of identity prejudice...
April 2016: Journal of Law and the Biosciences
Morris B Hoffman
The Murrows' paper, 'A hypothetical link between dehumanization and human rights abuses', in which they propose that neuroscience may answer some difficult public policy questions, including questions about the First Amendment, is an unfortunate foray into law and public policy unjustified by the current state of neuroscience. Neuroscientific insights may one day have important implications for the law, and for some of the folk psychological assumptions embedded in the law, but they will never change the words of the written Constitution, or answer difficult policy questions in the interstices of those words...
April 2016: Journal of Law and the Biosciences
Joshua D Sarnoff
This comment on The mouse that trolled by Tania Bubela, Saurabh Vishnubhakat, and Robert Cook-Deegan discusses the authors' description of how patents relating to the gene coding for a protein involved in Alzheimer's disease were obtained and used to sue scientific researchers, of how conflicts can arise among groups of researchers, and of how important research can be delayed or foregone by the exercise of patent rights. The authors sought to counter with evidence the optimistic views that patents on such research tools are not used to sue researchers and thus do not impede sequential innovation...
November 2015: Journal of Law and the Biosciences
Joan H Krause
Fueled by massive settlements and concerns about pharmaceutical company influence over medical practice, the fight over off-label promotion has become a rancorous one with little middle ground. For some, off-label restrictions are both bad law and bad medicine, violating the First Amendment while denying physicians access to crucial information. For others, the battle pits the very soul of the FDA against the excesses of a profit-driven marketplace. Far from ameliorating concerns over manufacturer influence, the New Model proposed by Bennett et al...
November 2015: Journal of Law and the Biosciences
Anna Wexler
Several recent articles have called for the regulation of consumer transcranial direct current stimulation (tDCS) devices, which provide low levels of electrical current to the brain. However, most of the discussion to-date has focused on ethical or normative considerations; there has been a notable absence of scholarship regarding the actual legal framework in the United States. This article aims to fill that gap by providing a pragmatic analysis of the consumer tDCS market and relevant laws and regulations...
November 2015: Journal of Law and the Biosciences
C H de Kogel, E J M C Westgeest
In this contribution an empirical approach is used to gain more insight into the relationship between neuroscience and criminal law. The focus is on case law in the Netherlands. Neuroscientific information and techniques have found their way into the courts of the Netherlands. Furthermore, following an Italian case in which a mentally ill offender received a penalty reduction in part because of a 'genetic vulnerability for impulsive aggression', the expectation was expressed that such 'genetic defenses' would appear in the Netherlands too...
November 2015: Journal of Law and the Biosciences
Nita A Farahany
The goal of this study was to examine the growing use of neurological and behavioral genetic evidence by criminal defendants in US criminal law. Judicial opinions issued between 2005-12 that discussed the use of neuroscience or behavioral genetics by criminal defendants were identified, coded and analysed. Criminal defendants are increasingly introducing such evidence to challenge defendants' competency, the effectiveness of defense counsel at trial, and to mitigate punishment.
November 2015: Journal of Law and the Biosciences
Jason M Law, Sebastian C Stark, Ke Liu, Norah E Liang, Mahmud M Hussain, Matthias Leiendecker, Daisuke Ito, Oscar Verho, Andrew M Stern, Stephen E Johnston, Yan-Ling Zhang, Gavin P Dunn, Alykhan F Shamji, Stuart L Schreiber
Evidence suggests that specific mutations of isocitrate dehydrogenases 1 and 2 (IDH1/2) are critical for the initiation and maintenance of certain tumor types and that inhibiting these mutant enzymes with small molecules may be therapeutically beneficial. In order to discover mutant allele-selective IDH1 inhibitors with chemical features distinct from existing probes, we screened a collection of small molecules derived from diversity-oriented synthesis. The assay identified compounds that inhibit the IDH1-R132H mutant allele commonly found in glioma...
October 13, 2016: ACS Medicinal Chemistry Letters
En-Ming He, Cheng-Wen Chen, Yong Guo, Mei-Hua Hsu, Liang Zhang, Hsiu-Ling Chen, Guo-Ping Zhao, Cheng-Hsun Chiu, Yan Zhou
Streptococcus agalactiae (GBS) causes serious infections in humans and other species. A total of 25 complete GBS genomes, including the first sequenced serotype VI genome (GBS-M002), were compared in this study. The power law model suggested that the pan-genome of GBS is open, with approximately 1300 genes in the core genome of GBS, accounting for approximately 60% of the average genome content. GBS-M002 has 73 specific genes and is one of the five strains containing >60 specific genes. Based on COG (Cluster of Orthologous Groups of proteins) functional classification, 24% of the genes related to defense mechanisms are specific among the strains...
October 20, 2016: Gene
Nandan S Gokhale, Alexa B R McIntyre, Michael J McFadden, Allison E Roder, Edward M Kennedy, Jorge A Gandara, Sharon E Hopcraft, Kendra M Quicke, Christine Vazquez, Jason Willer, Olga R Ilkayeva, Brittany A Law, Christopher L Holley, Mariano A Garcia-Blanco, Matthew J Evans, Mehul S Suthar, Shelton S Bradrick, Christopher E Mason, Stacy M Horner
The RNA modification N6-methyladenosine (m(6)A) post-transcriptionally regulates RNA function. The cellular machinery that controls m(6)A includes methyltransferases and demethylases that add or remove this modification, as well as m(6)A-binding YTHDF proteins that promote the translation or degradation of m(6)A-modified mRNA. We demonstrate that m(6)A modulates infection by hepatitis C virus (HCV). Depletion of m(6)A methyltransferases or an m(6)A demethylase, respectively, increases or decreases infectious HCV particle production...
October 18, 2016: Cell Host & Microbe
Cara Angelotta, Carol J Weiss, John W Angelotta, Richard A Friedman
OBJECTIVE: The relationship between use of medication-assisted treatment (MAT) in pregnant women with opioid use disorders, the standard of care, and state laws that permit child abuse charges for illicit drug use during pregnancy has not been described. METHODS: Using publicly available data on substance abuse treatment in the United States, we describe patterns in the use of MAT for pregnant women with opioid use disorders in states with prenatal child abuse laws compared with states without such laws...
October 20, 2016: Women's Health Issues: Official Publication of the Jacobs Institute of Women's Health
A H Tahoun
In this paper, the stabilization problem of actuators saturation in uncertain chaotic systems is investigated via an adaptive PID control method. The PID control parameters are auto-tuned adaptively via adaptive control laws. A multi-level augmented error is designed to account for the extra terms appearing due to the use of PID and saturation. The proposed control technique uses both the state-feedback and the output-feedback methodologies. Based on Lyapunov׳s stability theory, new anti-windup adaptive controllers are proposed...
October 20, 2016: ISA Transactions
Huirong Zhao, Jiong Shen, Yiguo Li, Joseph Bentsman
This paper proposes a new preference adjustable multi-objective model predictive control (PA-MOMPC) law for constrained nonlinear systems. With this control law, a reasonable prioritized optimal solution can be directly derived without constructing the Pareto front by solving a minimal optimization problem, which is a novel development of recently proposed utopia tracking approaches by additionally considering objective preferences with more flexible terminal and stability constraints. The tracking point of the proposed PA-MOMPC law is represented by a parametric vector with the parameters adjustable on the basis of objective preferences...
October 21, 2016: ISA Transactions
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