bluuebunny/crossref_metadata_2025_split huggingface dataset:
CAR1deletion by CRISPR/Cas9 reduces formation of ethyl carbamate from ethanol fermentation bySaccharomyces cerevisiae
Authors: Chin Young-Wook , Kang Woo-Kyung , Jang Hae Won , Turner Timothy L , Kim Hyo Jin 
Published: August 2016

AbstractEnormous advances in genome editing technology have been achieved in recent decades. Among newly born genome editing technologies, CRISPR/Cas9 is considered revolutionary because it is easy to use and highly precise for editing genes in target organisms. CRISPR/Cas9 technology has also been applied for removing unfavorable target genes. In this study, we used CRISPR/Cas9 technology to reduce ethyl carbamate (EC), a potential carcinogen, which was formed during the ethanol fermentation process by yeast. Because the yeast CAR1 gene encoding arginase is the key gene to form ethyl carbamate, we inactivated the yeast CAR1 gene by the complete deletion of the gene or the introduction of a nonsense mutation in the CAR1 locus using CRISPR/Cas9 technology. The engineered yeast strain showed a 98 % decrease in specific activity of arginase while displaying a comparable ethanol fermentation performance. In addition, the CAR1-inactivated mutants showed reduced formation of EC and urea, as compared to the parental yeast strain. Importantly, CRISPR/Cas9 technology enabled generation of a CAR1-inactivated yeast strains without leaving remnants of heterologous genes from a vector, suggesting that the engineered yeast by CRISPR/Cas9 technology might sidestep GMO regulation.
Regional variation of white matter development in the cat brain revealed by ex vivo diffusion MR tractography
Authors: Dai Guangping , Das Avilash , Hayashi Emiko , Chen Qin , Takahashi Emi 
Published: August 2016

AbstractThree‐dimensional reconstruction of developing fiber pathways is essential to assessing the developmental course of fiber pathways in the whole brain. We applied diffusion spectrum imaging (DSI) tractography to five juvenile ex vivo cat brains at postnatal day (P) 35, when the degree of myelination varies across brain regions. We quantified diffusion properties (fractional anisotropy [FA] and apparent diffusion coefficient [ADC]) and other measurements (number, volume, and voxel count) on reconstructed pathways for projection (cortico‐spinal and thalamo‐cortical), corpus callosal, limbic (cingulum and fornix), and association (cortico‐cortical) pathways, and characterized regional differences in maturation patterns by assessing diffusion properties. FA values were significantly higher in cortico‐cortical pathways within the right hemisphere compared to those within the left hemisphere, while the other measurements for the cortico‐cortical pathways within the hemisphere did not show asymmetry. ADC values were not asymmetric in both types of pathways. Interestingly, tract count and volume were significantly larger in the left thalamo‐cortical pathways compared to the right thalamo‐cortical pathways. The bilateral thalamo‐cortical pathways showed high FA values compared to the other fiber pathways. On the other hand, ADC values did not show any differences across pathways studied. These results demonstrate that DSI tractography successfully depicted regional variations of white matter tracts during development when myelination is incomplete. Low FA and high ADC values in the cingulum bundle suggest that the cingulum bundle is less mature than the others at this developmental stage.
Examination of Individual Differences in Outcomes From a Randomized Controlled Clinical Trial Comparing Formal and Informal Individual Auditory Training Programs
Authors: Smith Sherri L. , Saunders Gabrielle H. , Chisolm Theresa H. , Frederick Melissa , Bailey Beth A. 
Published: August 2016

Purpose
The purpose of this study was to determine if patient characteristics or clinical variables could predict who benefits from individual auditory training.

Method
A retrospective series of analyses were performed using a data set from a large, multisite, randomized controlled clinical trial that compared the treatment effects of at-home auditory training programs in bilateral hearing aid users. The treatment arms were (a) use of the 20-day computerized Listening and Communication Enhancement program, (b) use of the 10-day digital versatile disc Listening and Communication Enhancement program, (c) use of a placebo “books-on-tape” training, and (d) educational counseling (active control). Multiple linear regression models using data from 263 participants were conducted to determine if patient and clinical variables predicted short-term improvement on word-recognition-in-noise abilities, self-reported hearing handicap, and self-reported hearing problems.

Results
Baseline performance significantly predicted performance on each variable, explaining 11%–17% of the variance in improvement. The treatment arm failed to emerge as a significant predictor with other clinical variables explaining less than 9% of the variance.

Conclusion
These results suggest that hearing aid users who have poorer aided word-recognition-in-noise scores and greater residual activity limitations and participation restrictions will show the largest improvement in these areas.
Charge‐domain switched‐gm‐C CBPF using semi‐passive charge‐sharing technique
Authors: Xu Y. , Moon U. 
Published: August 2016

A highly reconfigurable charge‐domain switched‐gm‐C complex bandpass filter (CBPF) topology that utilises a semi‐passive charge‐sharing technique is proposed. It uses only switches, capacitors, digital circuitry for three‐phase non‐overlapping clock generation and efficient gm‐stages. Simulated in a 65 nm CMOS, a first‐order CBPF operating at 1 GS/s sampling rate demonstrates flexible tunability of the centre frequency and bandwidth with a highly passive/digital implementation. The presented filter architecture features excellent power efficiency and compatibility with process scaling.
Carbon nanotubes pickup by van der Waals force based on nanorobotics manipulation inside SEM
Authors: Yang Zhan , Chen Tao , Wang Yaqiong , Sun Lining , Fukuda Toshio 
Published: August 2016

A method of picking up carbon nanotubes (CNTs) from nanotube bulk by van der Waals force inside a scanning electron microscopy is presented. An atomic force microscope cantilever was employed as end effector of nanorobotics manipulators for CNT picking up. A manipulation strategy was established by analysing the van der Waals force of three different types of contacting models. Three groups of experiments were designed and carried out to investigate the effects of different factors. Factors including pickup angle, pickup contact area between the CNT and the cantilever and pickup speed of the end effector were discussed. The results shown that a pickup angle at 90.1° and a pickup speed lower than 10 nm/step with a pickup contact length more than 1.5 µm would increase the probability of picking up CNT successfully.
Preparation and oxygen sensing properties of Ti3O5 submicron rods
Authors: Zhang Xiaoyan , Liu Wanying , Yu Hua , Zhong Xiaoxi , Wang Lijun , Singh Ambrish , Lin Yuanhua 
Published: August 2016

Ti3O5 submicron rods, typically 0.5–2 µm in length and 100–300 nm in diameter, have been successfully synthesised via a facile approach combined hydrothermal and carbothermal reduction route. H3TiO5 nanofibres blended with nano‐sized carbon black were first prepared by the direct hydrothermal processing, and then Ti3O5 submicron rods could be obtained by sintering the prepared nanofibres at 1250°C for 3 h. The microstructure and formation of phases in the reduction process were investigated, respectively. In addition, the oxygen sensing properties of the synthesised materials were preliminarily investigated by gas‐sensing measurement. The results indicated that the electrical conductivity of the Ti3O5 submicron rods varied with the oxygen concentration, and the responses increased as the oxygen concentration increased at 200°C.
Comprehensive structural and dynamical view of an unfolded protein from the combination of single-molecule FRET, NMR, and SAXS
Authors: Aznauryan Mikayel , Delgado Leonildo , Soranno Andrea , Nettels Daniel , Huang Jie-rong , Labhardt Alexander M. , Grzesiek Stephan , Schuler Benjamin 
Published: August 2016

Significance
Proteins are the most versatile components of the molecular machinery of life. Synthesized as linear polymers of amino acids, proteins start out in their unfolded state and perform their function either in well-defined folded conformations or as intrinsically disordered proteins (IDPs) lacking tertiary structure. Both for the folding process and the properties of IDPs, a quantitative understanding of the conformational distributions and dynamics of unfolded proteins is thus essential. However, reaching this goal has been challenging owing to the large conformational heterogeneity and rapid dynamics of these systems. Here we combine three of the most powerful biophysical methods available to obtain a comprehensive view of an unfolded protein that would not be available from any of the individual methods.
Genotype‐Phenotype Effects of Bmpr2 Mutations on Disease Severity in Mouse Models of Pulmonary Hypertension
Authors: Frump Andrea L. , Datta Arunima , Ghose Sampa , West James , de Caestecker Mark P. 
Published: August 2016

More than 350 mutations in the type‐2 BMP (bone morphogenetic protein) receptor, BMPR2, have been identified in patients with heritable pulmonary arterial hypertension (HPAH). However, only 30% of BMPR2 mutation carriers develop PAH, and we cannot predict which of these carriers will develop clinical disease. One possibility is that the nature of the BMPR2 mutation affects disease severity. This hypothesis has been difficult to test clinically, given the rarity of HPAH and the complexity of the confounding genetic and environmental risk factors. To test this hypothesis, therefore, we evaluated the susceptibility to experimental pulmonary hypertension (PH) of mice carrying different HPAH‐associated Bmpr2 mutations on otherwise identical genetic backgrounds. Mice with Bmpr2ΔEx4–5 mutations (Bmpr2+/−), in which the mutant protein is not expressed, develop less severe PH in response to hypoxia or hypoxia with vascular endothelial growth factor receptor inhibition than mice with an extracellular‐domain Bmpr2ΔEx2 mutation (Bmpr2ΔEx2/+), in which the mutant protein is expressed. This was associated with a marked decrease in stabilizing phosphorylation of threonine 495 endothelial nitric oxide synthase (pThr495 eNOS) in Bmpr2ΔEx2/+ compared to wild‐type and Bmpr2+/− mouse lungs. These findings provide the first experimental evidence that BMPR2 mutation types influence the severity of HPAH and suggest that patients with BMPR2 mutations who express mutant BMPR2 proteins by escaping non‐sense‐mediated messenger RNA decay (NMD– mutations) will develop more severe disease than HPAH patients with NMD+ mutations who do not express BMPR2 mutant proteins. Since decreased levels of pThr495 eNOS are associated with increased eNOS uncoupling, our data also suggest that this effect may result from defects in eNOS function.
Three‐Dimensional Micro Computed Tomography Analysis of the Lung Vasculature and Differential Adipose Proteomics in the Sugen/Hypoxia Rat Model of Pulmonary Arterial Hypertension
Authors: Shields Kelly J. , Verdelis Kostas , Passineau Michael J. , Faight Erin M. , Zourelias Lee , Wu Changgong , Chong Rong , Benza Raymond L. 
Published: August 2016

Pulmonary arterial hypertension (PAH) is a rare disease characterized by significant vascular remodeling. The obesity epidemic has produced great interest in the relationship between small visceral adipose tissue depots producing localized inflammatory conditions, which may link metabolism, innate immunity, and vascular remodeling. This study used novel micro computed tomography (microCT) three‐dimensional modeling to investigate the degree of remodeling of the lung vasculature and differential proteomics to determine small visceral adipose dysfunction in rats with severe PAH. Sprague‐Dawley rats were subjected to a subcutaneous injection of vascular endothelial growth factor receptor blocker (Sugen 5416) with subsequent hypoxia exposure for 3 weeks (SU/hyp). At 12 weeks after hypoxia, microCT analysis showed a decrease in the ratio of vascular to total tissue volume within the SU/hyp group (mean ± standard deviation: 0.27 ± 0.066;P= 0.02) with increased vascular separation (0.37 ± 0.062 mm;P= 0.02) when compared with the control (0.34 ± 0.084 and 0.30 ± 0.072 mm). Differential proteomics detected an up‐regulation of complement protein 3 (C3; SU/hyp: control ratio = 2.86) and the adipose tissue–specific fatty acid binding protein‐4 (FABP4, 2.66) in the heart adipose of the SU/hyp. Significant remodeling of the lung vasculature validates the efficacy of the SU/hyp rat for modeling human PAH. The upregulation of C3 and FABP4 within the heart adipose implicates small visceral adipose dysfunction. C3 has been associated with vascular stiffness, and FABP4 suppresses peroxisome proliferator–activated receptor, which is a major regulator of adipose function and known to be downregulated in PAH. These findings reveal that small visceral adipose tissue within the SU/hyp model provides mechanistic links for vascular remodeling and adipose dysfunction in the pathophysiology of PAH.
Modeling the Interplay between Sanitary and Phytosanitary Measures and Tariff‐rate Quotas under Partial Trade Liberalization
Authors: Beckman Jayson , Arita Shawn 
Published: August 2016

AbstractNon‐tariff measures, particularly sanitary and phytosanitary measures and tariff‐rate quotas, are two critical policy barriers that impede agricultural trade. Unlike simple tariffs, both measures contain non‐linear effects and binding conditions that make their treatment in modeling trade liberalization challenging. In addition, the coexistence of these measures carries important interactive effects that restrict trade. This study investigates these joint effects by developing a conceptual framework that considers different partial liberalization scenarios. Our framework points to three cases that may arise: (a) binding tariff‐rate quota, non‐prohibitive sanitary and phytosanitary measure; (b) non‐binding tariff‐rate quota, non‐prohibitive sanitary and phytosanitary measure; and (c) non‐binding tariff‐rate quota, prohibitive sanitary and phytosanitary measure. We then use a Computable General Equilibrium model to examine partial trade liberalization scenarios for these cases, using the ongoing Transatlantic Trade and Investment Partnership negotiations as our motivation. Our simulations provide a more nuanced analysis of complex trade liberalization and demonstrate the importance of modeling the interplay between these different types of barriers.
Adverse Effect of High-Fat Diet on Metabolic Programming in Offspring Born to a Murine Model of Maternal Hypertension
Authors: Longo Monica , Refuerzo Jerrie S. , Mann Lovepreet , Leon Mateo , Moussa Hind N. , Sibai Baha M. , Blackwell Sean C. 
Published: August 2016

BACKGROUND
We previously reported that offspring heterozygous mice partially lacking endothelial nitric oxide synthase (eNOS) gene, and born to hypertensive eNOS−/− Knockout mother, are hypertensive. We hypothesized that those offspring when placed on high-fat diet (HFD) will undergo altered metabolic programming increasing their risk for developing metabolic syndrome.

METHODS
eNOS−/−KO and wild-type mice (eNOS+/+WT) were cross-bred to produce heterozygous offspring: maternal heterozygous (Mat, eNOS−/+), born from hypertensive eNOS−/−KO mothers; and paternal heterozygous (Pat, eNOS−/+), born from normotensive WT mothers. Mat, eNOS−/+ and Pat, eNOS−/+ female were allocated to HFD or control diet (CD) until 8 weeks of age. Then a metabolic profile was obtained: weight, glucose/insulin tolerance test (GTT, ITT), systolic blood pressure (SBP), serum fasting levels of insulin, adiponectin, leptin, and a lipid panel.

RESULTS
Weight was not different between all offspring within each diet. GTT curve was higher in Mat, eNOS−/+ vs. Pat, eNOS−/+ offspring on both diet (P &lt; 0.001). In ITT, glucose level at 15 minutes was higher in Mat, eNOS−/+ on HFD. Insulin level was increased in Mat, eNOS−/+ vs. Pat, eNOS−/+ on either diet. SBP was elevated in Mat, eNOS−/+ vs. Pat, eNOS−/+ on CD and was further raised in Mat, eNOS−/+ offspring on HFD (P &lt; 0.001). No other differences were seen except for lower high-density lipoprotein levels in Mat, eNOS−/+ fed HFD (P &lt; 0.003).

CONCLUSIONS
Mat, eNOS−/+ offspring exposed in utero to maternal hypertension and fed HFD postnatally have increased susceptibility for metabolic abnormalities. Thus, maternal HTN is a risk factor for altered fetal metabolic programming.
PseKRAAC: a flexible web server for generating pseudo K-tuple reduced amino acids composition
Authors: Zuo Yongchun , Li Yuan , Chen Yingli , Li Guangpeng , Yan Zhenhe , Yang Lei 
Published: August 2016

Abstract

Summary
The reduced amino acids perform powerful ability for both simplifying protein complexity and identifying functional conserved regions. However, dealing with different protein problems may need different kinds of cluster methods. Encouraged by the success of pseudo-amino acid composition algorithm, we developed a freely available web server, called PseKRAAC (the pseudo K-tuple reduced amino acids composition). By implementing reduced amino acid alphabets, the protein complexity can be significantly simplified, which leads to decrease chance of overfitting, lower computational handicap and reduce information redundancy. PseKRAAC delivers more capability for protein research by incorporating three crucial parameters that describes protein composition. Users can easily generate many different modes of PseKRAAC tailored to their needs by selecting various reduced amino acids alphabets and other characteristic parameters. It is anticipated that the PseKRAAC web server will become a very useful tool in computational proteomics and protein sequence analysis.

Availability and Implementation
Freely available on the web at http://bigdata.imu.edu.cn/psekraac

Supplementary information
Supplementary data are available at Bioinformatics online.
STR-324, a Stable Analog of Opiorphin, Causes Analgesia in Postoperative Pain by Activating Endogenous Opioid Receptor–dependent Pathways
Authors: Sitbon Philippe , Van Elstraete Alain , Hamdi Leila , Juarez-Perez Victor , Mazoit Jean-Xavier , Benhamou Dan , Rougeot Catherine 
Published: August 2016

Abstract

Background
Opiorphin is a naturally occurring potent analgesic human peptide. It protects enkephalins from degradation and inhibits pain perception in various acute pain models via activation of endogenous opioid pathways. However, the efficacy of opiorphin continuous infusion and its chemically stable form, STR-324, in postoperative pain is unknown.

Methods
Using the Brennan model of plantar incision–induced hypersensitivity, the authors examined the postsurgical analgesic response to mechanical and thermal stimuli of 7-day continuously intravenously infused drugs (8 to 10 rats per group). Antinociception from opiorphin with reference to morphine and STR-324 was assessed. Spinal c-Fos expression and the involvement of opioid receptor–dependent pathways were investigated. The occurrence of respiratory and hemodynamic adverse effects of opiorphin was also tested.

Results
Intravenous infusion of opiorphin significantly reduced responses to mechanical stimuli from days 1 to 4 post surgical period at 143 to 175-kPa mean ranges compared with 23 to 30-kPa mean ranges for vehicle (P &lt; 0.05). During the 3-day postoperative period, no respiratory rate, oxygen saturation, arterial pressure, or heart rate adverse effects were induced by opiorphin. STR-324 consistently inhibited mechanical and thermal hyperalgesia with similar potency as that of opiorphin. Mechanistic analyses demonstrated that the STR-324 antinociceptive effect was reversed by the opioid antagonist, naloxone. Also, STR-324 significantly reduced the number of pain-evoked spinal cFos-immunoreactive nuclei.

Conclusion
Intravenous infusion of opiorphin and STR-324 produced significant antinociceptive effect in a postoperative pain model. This study demonstrates that STR-324 is effective in postoperative pain management due to its strong antihyperalgesic effects mediated via opioid-dependent antinociceptive pathways. Opiorphin analog should represent a new class of potent and safe analgesics.
Body Mass Index: A Reliable Predictor of Subcutaneous Fat Thickness and Needle Length for Ventral Gluteal Intramuscular Injections
Authors: Holliday Rex M. , Gupta Vivek , Vibhute Prasanna G. 
Published: August 2016

Background:
With rising prevalence of obesity, increasing number of gluteal injections would be expected to fail in intramuscular (IM) drug delivery.

Study Question:
This study evaluated ventral gluteal fat thickness (VGT) on adult magnetic resonance imaging of pelvis and correlated it with the subjects' body mass index (BMI), weight, and height to establish evidence-based clinical estimates of individualized needle length and suitability of ventral gluteal site for IM injections.

Design:
Retrospective review.

Study Design, Measures and Outcomes:
Three hundred fifty adult (224 women, 126 men) magnetic resonance imaging scans of pelvis were reviewed to measure the VGT as the distance between the skin and the nearest edge of the gluteus medius muscle at the recommended ventral gluteal injection site. VGT was correlated with BMI, weight, and height by multivariate analysis.

Results:
Fifty-three (49 women, 4 men) subjects had VGT greater than 3.3 cm, and 146 (106 women, 40 men) subjects had VGT greater than 2.0 cm. The Pearson correlation coefficient between VGT and BMI was 0.82 for women and 0.81 for men. The difference between the VGT in men and women of comparable BMI was statistically significant (P < 0.001). BMI of 30 in women and 35 in men seem to be upper limits for successful ventral gluteal IM injections with 3.75-cm (1.5-inch) hypodermic needle. The expected failure rate of ventral gluteal IM delivery with the 3.75-cm needle is 71% in women with BMI >30, and 60% in men with BMI >35.

Conclusion:
BMI is reliably predictive of VGT in both men and women for selecting appropriate needle length for IM injections at this site. Standard needles would fail in IM delivery at this site in a considerable proportion of obese adults. Because of high prevalence of obesity in individuals with severe mental illness, our findings could significantly impact acute and maintenance therapy with injectable tranquillizers and antipsychotics.
Celiac Disease and Diabetes
Authors: Weiss Batia , Pinhas‐Hamiel Orit 
Published: August 2016

ABSTRACTPrevalence studies from around the world have established a substantial increase in the prevalence of celiac disease (CD) in patients with type 1 diabetes mellitus (T1DM). Approximately two‐thirds of patients with T1DM and CD are asymptomatic for CD at diagnosis. We aim to provide an up‐to‐date state‐of‐the‐art summary of the recommendations for serologic testing for CD in patients with T1DM and to clarify the debate on the need for screening and interventions. We searched Medline and Cochrane databases for studies of celiac autoimmunity and biopsy‐proven CD in people with T1DM between January 1, 2000 and December 1, 2015. CD was found to be an independent risk factor for micro‐ and macrovascular complications, as well as for increased morbidity in patients with T1DM. Publications, however, reveal controversy regarding the benefits of a gluten‐free diet (GFD) on glycemic control, bone health, and quality of life in individuals with T1DM and asymptomatic CD. A multicenter, prospective randomized controlled trial aimed to investigate this issue is currently ongoing. Until resolution of the pros and cons of screening for CD, and of the benefit versus burden of GFD treatment in T1DM patients with asymptomatic CD, we recommend repeated screening for CD during childhood and adulthood, and treatment with GFD for those with biopsy‐proven CD, even if asymptomatic.