bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential regulation of spontaneous and evoked inhibitory synaptic transmission in somatosensory cortex by retinoic acid
Authors: Yee Ada X. , Chen Lu 
Published: June 2016

AbstractRetinoic acid (RA), a developmental morphogen, has emerged in recent studies as a novel synaptic signaling molecule that acts in mature hippocampal neurons to modulate excitatory and inhibitory synaptic transmission in the context of homeostatic synaptic plasticity. However, it is unclear whether RA is capable of modulating neural circuits outside of the hippocampus, and if so, whether the mode of RA's action at synapses is similar to that within the hippocampal network. Here we explore for the first time RA's synaptic function outside the hippocampus and uncover a novel function of all‐trans retinoic acid at inhibitory synapses. Acute RA treatment increases spontaneous inhibitory synaptic transmission in L2/3 pyramidal neurons of the somatosensory cortex, and this effect requires expression of RA's receptor RARα both pre‐ and post‐synaptically. Intriguingly, RA does not seem to affect evoked inhibitory transmission assayed with either extracellular stimulation or direct activation of action potentials in presynaptic interneurons at connected pairs of interneurons and pyramidal neurons. Taken together, these results suggest that RA's action at synapses is not monotonous, but is diverse depending on the type of synaptic connection (excitatory versus inhibitory) and circuit (hippocampal versus cortical). Thus, synaptic signaling of RA may mediate multi‐faceted regulation of synaptic plasticity. In addition to its classic roles in brain development, retinoic acid (RA) has recently been shown to regulate excitatory and inhibitory transmission in the adult brain. Here, the authors show that in layer 2/3 (L2/3) of the somatosensory cortex (S1), acute RA induces increases in spontaneous but not action‐potential evoked transmission, and that this requires retinoic acid receptor (RARα) both in presynaptic PV‐positive interneurons and postsynaptic pyramidal (PN) neurons.
Selected mapping technique for reducing PAPR of single‐carrier signals
Authors: Boonkajay Amnart , Adachi Fumiyuki 
Published: June 2016

AbstractSingle‐carrier transmission with frequency‐domain equalization (SC‐FDE) is widely known as a promising transmission technique providing low error probability with low peak‐to‐average power ratio (PAPR) of transmit signal. However, the low‐PAPR property of SC‐FDE cannot be maintained if multi‐level data modulation is introduced. The low‐PAPR property of SC‐FDE can be maintained by applying transmit filtering with roll‐off factor at the expense of spectrum efficiency. In this paper, we propose two types of selected mapping (SLM) to reduce the PAPR of SC‐FDE transmit signal. The first SLM technique is conducted in the frequency domain, where the phase rotation is applied to subcarriers similar to the SLM technique for orthogonal frequency division multiplexing transmission. The second SLM technique is conducted in the time domain, where the phase rotation is applied directly to data‐modulated symbol sequence. Computer simulation confirms that both SLM techniques are able to reduce the PAPR of SC‐FDE signal without significant degradation of bit‐error rate performance and spectrum efficiency. Copyright © 2016 John Wiley & Sons, Ltd.
A phase I study of BI 811283, an Aurora B kinase inhibitor, in patients with advanced solid tumors
Authors: Mross Klaus , Richly Heike , Frost Annette , Scharr Dirk , Nokay Bahar , Graeser Ralph , Lee Chooi , Hilbert James , Goeldner Rainer-George , Fietz Oliver , Scheulen Max E. 
Published: June 2016

Abstract

Purpose
This phase I study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics, and antitumor activity of the Aurora B kinase inhibitor BI 811283 in patients with advanced solid tumors.

Methods
BI 811283 was administered via 24-h infusion on Days 1 and 15 of a 4-week cycle (schedule A) or Day 1 of a 3-week cycle (schedule B) in a modified 3 + 3 dose-escalation design. Pharmacodynamic assessments included immunohistochemistry for phosphorylated histone H3 (pHH3) on skin biopsies to determine Aurora B kinase inhibition and plasma concentrations of caspase-cleaved CK-18 (apoptosis marker).

Results
A total of 121 patients were treated. The MTDs of BI 811283 were 125 mg (schedule A) and 230 mg (schedule B). Dose-limiting toxicities were primarily hematological (febrile neutropenia and grade 4 neutropenia); the most common drug-related adverse effects included neutropenia, fatigue, leukopenia, nausea, alopecia, diarrhea, and decreased appetite. A trend toward a decrease in pHH3 was observed, with increasing BI 811283 doses, indicating target engagement; there was no consistent trend regarding caspase-cleaved CK-18 levels. No objective response was observed although 19 patients in each schedule achieved clinical benefit (stable disease).

Conclusions
BI 811283 demonstrated a generally manageable safety profile and disease stabilization in some patients.

Trial registration
EudraCT No: 2007-000191-17, ClinicalTrials.gov Identifier: NCT00701324.
Multiplex gene editing of the Yarrowia lipolytica genome using the CRISPR-Cas9 system
Authors: Gao Shuliang , Tong Yangyang , Wen Zhiqiang , Zhu Li , Ge Mei , Chen Daijie , Jiang Yu , Yang Sheng 
Published: June 2016

Abstract
Yarrowia lipolytica is categorized as a generally recognized as safe (GRAS) organism and is a heavily documented, unconventional yeast that has been widely incorporated into multiple industrial fields to produce valuable biochemicals. This study describes the construction of a CRISPR-Cas9 system for genome editing in Y. lipolytica using a single plasmid (pCAS1yl or pCAS2yl) to transport Cas9 and relevant guide RNA expression cassettes, with or without donor DNA, to target genes. Two Cas9 target genes, TRP1 and PEX10, were repaired by non-homologous end-joining (NHEJ) or homologous recombination, with maximal efficiencies in Y. lipolytica of 85.6 % for the wild-type strain and 94.1 % for the ku70/ku80 double-deficient strain, within 4 days. Simultaneous double and triple multigene editing was achieved with pCAS1yl by NHEJ, with efficiencies of 36.7 or 19.3 %, respectively, and the pCASyl system was successfully expanded to different Y. lipolytica breeding strains. This timesaving method will enable and improve synthetic biology, metabolic engineering and functional genomic studies of Y. lipolytica.
Functional characterization of a geraniol synthase-encoding gene from Camptotheca acuminata and its application in production of geraniol in Escherichia coli
Authors: Chen Fei , Li Wei , Jiang Liangzhen , Pu Xiang , Yang Yun , Zhang Guolin , Luo Yinggang 
Published: June 2016

Abstract
Geraniol synthase (GES) catalyzes the conversion of geranyl diphosphate (GPP) into geraniol, an acyclic monoterpene alcohol that has been widely used in many industries. Here we report the functional characterization of CaGES from Camptotheca acuminata, a camptothecin-producing plant, and its application in production of geraniol in Escherichia coli. The full-length cDNA of CaGES was obtained from overlap extension PCR amplification. The intact and N-terminus-truncated CaGESs were overexpressed in E. coli and purified to homogeneity. Recombinant CaGES showed the conversion activity from GPP to geraniol. To produce geraniol in E. coli using tCaGES, the biosynthetic precursor GPP should be supplied and transferred to the catalytic pocket of tCaGES. Thus, ispA(S80F), a mutant of farnesyl diphosphate (FPP) synthase, was prepared to produce GPP via the head-to-tail condensation of isoprenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). A slight increase of geraniol production was observed in the fermentation broth of the recombinant E. coli harboring tCaGES and ispA(S80F). To enhance the supply of IPP and DMAPP, the encoding genes involved in the whole mevalonic acid biosynthetic pathway were introduced to the E. coli harboring tCaGES and the ispA(S80F) and a significant increase of geraniol yield was observed. The geraniol production was enhanced to 5.85 ± 0.46 mg L−1 when another copy of ispA(S80F) was introduced to the above recombinant strain. The following optimization of medium composition, fermentation time, and addition of metal ions led to the geraniol production of 48.5 ± 0.9 mg L−1. The present study will be helpful to uncover the biosynthetic enigma of camptothecin and tCaGES will be an alternative to selectively produce geraniol in E. coli with other metabolic engineering approaches.
A brief review of co-doping
Authors: Zhang Jingzhao , Tse Kinfai , Wong Manhoi , Zhang Yiou , Zhu Junyi 
Published: June 2016

AbstractDopants and defects are important in semiconductor and magnetic devices. Strategies for controlling doping and defects have been the focus of semiconductor physics research during the past decades and remain critical even today. Co-doping is a promising strategy that can be used for effectively tuning the dopant populations, electronic properties, and magnetic properties. It can enhance the solubility of dopants and improve the stability of desired defects. During the past 20 years, significant experimental and theoretical efforts have been devoted to studying the characteristics of co-doping. In this article, we first review the historical development of co-doping. Then, we review a variety of research performed on co-doping, based on the compensating nature of co-dopants. Finally, we review the effects of contamination and surfactants that can explain the general mechanisms of co-doping.
Comparison of perinatal outcomes following fresh and frozen‐thawed blastocyst transfer
Authors: Pereira Nigel , Petrini Allison C. , Lekovich Jovana P. , Schattman Glenn L. , Rosenwaks Zev 
Published: June 2016

AbstractObjectiveTo investigate the effect of ovarian stimulation on endometrial receptivity by comparing singleton pregnancy and perinatal outcomes following fresh or frozen‐thawed blastocyst transfers.MethodsA retrospective cohort study enrolled patients undergoing fresh or frozen‐thawed blastocyst transfers that resulted in live deliveries between January 1, 2010 and September 30, 2013 at a single academic center. Implantation, clinical pregnancy, spontaneous abortion, and live delivery rates were calculated. The incidence of term delivery, preterm delivery, low birth weight, term low birth weight, and very low birth weight were also recorded. To detect a 10% difference in the implantation rate, a minimum sample size of at least 415 transfer cycles in each group was estimated.ResultsThe study included data from 918 fresh and 1273 frozen‐thawed cycles. Patients in both groups were of similar age and there was no difference in the grading of blastocysts. No differences were observed in the implantation (37.3% vs 37.7%), clinical pregnancy (50.2% vs 49.4%), spontaneous abortion (7.3% vs 9.3%), and live delivery (42.9% vs 40.6%) rates of the two groups. A sub‐analysis of all live singleton and twin deliveries revealed no difference in perinatal outcomes between the two techniques.ConclusionsThe present study demonstrated equivalent singleton pregnancy and perinatal outcomes when comparing frozen‐thawed and fresh blastocyst transfer procedures.
Comparison of the clinical outcomes of transobturator and single‐incision slings for stress urinary incontinence
Authors: Wu Ling‐Ying , Yang Tsai‐Hwa , Kung Fu‐Tsai , Chuang Fei‐Chi , Huang Kuan‐Hui 
Published: June 2016

AbstractThe aim of this study was to compare the clinical outcomes of anti‐incontinence surgeries employing the transobturator sling and single‐incision sling (SIS). Our hypothesis is that the outcome of the SIS is not inferior to the obturator sling. This retrospective study reviewed the medical records of patients who underwent anti‐incontinence surgery with the transobturator sling or SIS from July 2005 to November 2014. Patients who underwent concomitant pelvic organ reconstruction with an artificial mesh were excluded. Assessments included preoperative and postoperative urodynamic examinations, perioperative complications, and postoperative urogenital symptoms. A total of 122 women were recruited according to the inclusion and exclusion criteria. Among them, 68 patients underwent transobturator sling procedures while 54 patients underwent SIS procedures. The subjective failure rate of the transobturator sling and SIS were 10.2% and 18.5%, respectively (p = 0.292). The objective failure rate, defined as a pad test showing more than 2 g of urine, was 10.2% for the transobturator sling and 12.9% for the SIS (p = 0.777). SIS resulted in less blood loss, operative time, length of hospital stay, and transient voiding dysfunction after the operation. No major complication occurred after either surgical intervention. In conclusion, SIS and transobturator slings might have similar efficacy, safety, and effects on new‐onset urogenital symptoms.
Predictors for the Number of Warning Information Sources During Tornadoes
Authors: Cong Zhen , Luo Jianjun , Liang Daan , Nejat Ali 
Published: June 2016

AbstractPeople may receive tornado warnings from multiple information sources, but little is known about factors that affect the number of warning information sources (WISs). This study examined predictors for the number of WISs with a telephone survey on randomly sampled residents in Tuscaloosa, Alabama, and Joplin, Missouri, approximately 1 year after both cities were struck by violent tornadoes (EF4 and EF5) in 2011. The survey included 1006 finished interviews and the working sample included 903 respondents. Poisson regression and Zero-Inflated Poisson regression showed that older age and having an emergency plan predicted more WISs in both cities. Education, marital status, and gender affected the possibilities of receiving warnings and the number of WISs either in Joplin or in Tuscaloosa. The findings suggest that social disparity affects the access to warnings not only with respect to the likelihood of receiving any warnings but also with respect to the number of WISs. In addition, historical and social contexts are important for examining predictors for the number of WISs. We recommend that the number of WISs should be regarded as an important measure to evaluate access to warnings in addition to the likelihood of receiving warnings. (Disaster Med Public Health Preparedness. 2017;11:168–172)
Impact of low-carbohydrate diet on renal function: a meta-analysis of over 1000 individuals from nine randomised controlled trials
Authors: Oyabu Chikako , Hashimoto Yoshitaka , Fukuda Takuya , Tanaka Muhei , Asano Mai , Yamazaki Masahiro , Fukui Michiaki 
Published: June 2016

AbstractWe aimed to clarify the effect of low-carbohydrate diet (LCD) on renal function in overweight and obese individuals without chronic kidney disease (CKD). Literature searches were performed using EMBASE, MEDLINE and Cochrane Library until December 2015. We selected articles that reported human studies from their inception until December 2015 in English using the following searching terms: ‘Low carbohydrate diet’ AND (‘Clinical trial’ OR ‘Clinical study’ OR ‘Clinical investigation’ OR ‘Observational study’ OR ‘Cohort study’). We compared the effects of LCD on renal function, defined as change in estimated glomerular filtration rate (eGFR), assessed in randomised-controlled trials. We calculated the mean change in eGFR and the mean change in standard deviations by eGFR or creatinine clearance, and compared the mean change in eGFR and standard deviations in LCD with those in the control diet using fixed-effects models. We selected nine randomised controlled trials including 1687 participants (861 were fed LCD and 826 were fed the control diet). The mean change in eGFR in the LCD group was −4·7 to 24·0 ml/min per 1·73 m2and that in the control diet group was −4·1 to 10·8 ml/min per 1·73 m2. The mean change in eGFR in the LCD group was greater than that in the control diet (0·13 ml/min per 1·73 m2; 95 % CI 0·00, 0·26). In the present meta-analysis, we identified that the increase in eGFR was greater in LCD compared with the control diet in overweight and obese individuals without CKD.
‘How to stop a nosebleed’: an assessment of the quality of epistaxis treatment advice on YouTube
Authors: Haymes A T , Harries V 
Published: June 2016

AbstractObjective:Video hosting websites are increasingly being used to disseminate health education messages. This study aimed to assess the quality of advice contained within YouTube videos on the conservative management of epistaxis.Method:YouTube.com was searched using the phrase ‘how to stop a nosebleed’. The first 50 videos were screened. Objective advice scores and subjective production quality scores were attributed by independent raters.Results:Forty-five videos were analysed. The mean advice score was 2.0 out of 8 and the mean production quality score was 1.6 out of 3. There were no correlations between a video's advice score and its search results rank (ρ = −0.28, p = 0.068), its view count (ρ = 0.20, p = 0.19) or its number of ‘likes’ (ρ = 0.21, p = 0.18).Conclusion:The quality of information on conservative epistaxis management within YouTube videos is extremely variable. A high search rank is no indication of video quality. Many videos proffer inappropriate and dangerous ‘alternative’ advice. We do not recommend YouTube as a source for patient information.
An overview of the epidemiology of notifiable infectious diseases in Australia, 1991–2011
Authors: GIBNEY K. B. , CHENG A. C. , HALL R. , LEDER K. 
Published: June 2016

SUMMARYWe reviewed the first 21 years (1991–2011) of Australia's National Notifiable Diseases Surveillance System (NNDSS). All nationally notified diseases (except HIV/AIDS and Creutzfeldt–Jakob disease) were analysed by disease group (n= 8), jurisdiction (six states and two territories), Indigenous status, age group and notification year. In total, 2 421 134 cases were analysed. The 10 diseases with highest notification incidence (chlamydial infection, campylobacteriosis, varicella zoster, hepatitis C, influenza, pertussis, salmonellosis, hepatitis B, gonococcal infection, and Ross River virus infection) comprised 88% of all notifications. Annual notification incidence was 591 cases/100 000, highest in the Northern Territory (2598/100 000) and in children aged <5 years (698/100 000). A total of 8·4% of cases were Indigenous Australians. Notification incidence increased by 6·4% per year (12% for sexually transmissible infections and 15% for vaccine-preventable diseases). The number of notifiable diseases also increased from 37 to 65. The number and incidence of notifications increased throughout the study period, partly due to addition of diseases to the NNDSS and increasing availability of sensitive diagnostic tests. The most commonly notified diseases require a range of public health responses addressing high-risk sexual and drug-use behaviours, food safety and immunization. Our results highlight populations with higher notification incidence that might require tailored public health interventions.
Gender disparities in mortality from infectious diseases in Serbia, 1991–2014: a time of civil wars and global crisis
Authors: ILIC M. , ILIC I. 
Published: June 2016

SUMMARYInfectious diseases remain one of the leading causes of death worldwide. The aim of this descriptive epidemiological study was to analyse the trends in mortality from infectious diseases in Serbia (excluding the Autonomous Province of Kosovo & Metohia) from 1991 to 2014 using joinpoint regression analysis. The mortality rates from infectious diseases were found to have increased markedly from 1991 to 1994 (+12·4% per year), followed by a significant decline from 1994 to 2009 (–4·6% per year) and then another increase from 2009 to 2014 (+4·3% per year). Throughout the study period, mortality rates were consistently higher in men than in women. Although a substantial decline was observed for young people of both sexes, no consistent pattern was evident for the middle-aged nor the elderly. Since 1991, septicaemia has emerged as a leading cause of infectious disease mortality, particularly in older men. The Yugoslav civil wars in the 1990s and the global financial crisis in 2008 corresponded with changes in the trends in mortality from infectious diseases in Serbia, with the elderly showing particular vulnerability during those time periods. Data presented in this study might be useful to improve control of infectious diseases in Serbia.
Composable scheduler activations for Haskell
Authors: SIVARAMAKRISHNAN K. C. , HARRIS TIM , MARLOW SIMON , PEYTON JONES SIMON 
Published: June 2016

AbstractThe runtime for a modern, concurrent, garbage collected language like Java or Haskell is like an operating system: sophisticated, complex, performant, but alas very hard to change. If more of the runtime system were in the high-level language, it would be far more modular and malleable. In this paper, we describe a novel concurrency substrate design for the Glasgow Haskell Compiler that allows multicore schedulers for concurrent and parallel Haskell programs to be safely and modularly described as libraries in Haskell. The approach relies on abstracting the interface to the user-implemented schedulers through scheduler activations, together with the use of Software Transactional Memory to promote safety in a multicore context.
Physician-Assisted Death in Canada
Authors: BROWNE ALISTER , RUSSELL J. S. 
Published: June 2016

Abstract:The Criminal Code of Canada prohibits persons from aiding or abetting suicide and consenting to have death inflicted on them. Together, these provisions have prohibited physicians from assisting patients to die. On February 6, 2015, the Supreme Court of Canada declared void these provisions insofar as they “prohibit physician-assisted death for a competent adult person who (1) clearly consents to the termination of life and (2) has a grievous and irremediable medical condition (including an illness, disease or disability) that causes enduring suffering that is intolerable to the individual in the circumstances of his or her condition.” This declaration of invalidity was scheduled to take effect one year (later extended by six months) after the ruling, to give the government time to put legislation in place. We trace the history of this decision, discuss how it has forever changed the debate on physician-assisted dying, and identify the issues that must be resolved to write the legislation. Of special importance here are the topics of access, safeguards, and conscientious objection.
Euthanasia for Detainees in Belgium
Authors: DEVOLDER KATRIEN 
Published: June 2016

Abstract:In 2011, Frank Van Den Bleeken became the first detainee to request euthanasia under Belgium’s Euthanasia Act of 2002. This article investigates whether it would be lawful and morally permissible for a doctor to accede to this request. Though Van Den Bleeken has not been held accountable for the crimes he committed, he has been detained in an ordinary prison, without appropriate psychiatric care, for more than 30 years. It is first established that Van Den Bleeken’s euthanasia request plausibly meets the relevant conditions of the Euthanasia Act and that, consequently, a doctor could lawfully fulfill it. Next, it is argued that autonomy-based reasons for euthanizing him outweigh complicity-based reasons against doing so, and that, therefore, it is also morally permissible for a doctor to carry out the euthanasia request.