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https://www.readbyqxmd.com/read/29191968/contextualising-safety-in-numbers-a-longitudinal-investigation-into-change-in-cycling-safety-in-britain-1991-2001-and-2001-2011
#1
Rachel Aldred, Rahul Goel, James Woodcock, Anna Goodman
Introduction The 'Safety in Numbers' (SiN) phenomenon refers to a decline of injury risk per time or distance exposed as use of a mode increases. It has been demonstrated for cycling using cross-sectional data, but little evidence exists as to whether the effect applies longitudinally -that is, whether changes in cycling levels correlate with changes in per-cyclist injury risks.Methods This paper examines cross-sectional and longitudinal SiN effects in 202 local authorities in Britain, using commuting data from 1991, 2001 and 2011 censuses plus police -recorded data on 'killed and seriously injured' (KSI) road traffic injuries...
November 30, 2017: Injury Prevention: Journal of the International Society for Child and Adolescent Injury Prevention
https://www.readbyqxmd.com/read/29054256/drug-target-interaction-prediction-a-bayesian-ranking-approach
#2
Ladislav Peska, Krisztian Buza, Júlia Koller
BACKGROUND AND OBJECTIVE: In silico prediction of drug-target interactions (DTI) could provide valuable information and speed-up the process of drug repositioning - finding novel usage for existing drugs. In our work, we focus on machine learning algorithms supporting drug-centric repositioning approach, which aims to find novel usage for existing or abandoned drugs. We aim at proposing a per-drug ranking-based method, which reflects the needs of drug-centric repositioning research better than conventional drug-target prediction approaches...
December 2017: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/28980075/reliability-of-the-kinematic-steadiness-index-during-one-leg-standing-in-subjects-with-recurrent-low-back-pain
#3
Paul S Sung, Pamela Danial, Dongchul C Lee
PURPOSE: To assess the reliability of standing time and the Kinematic Steadiness Index (KSI) in one-leg standing compared with the Timed Up and Go (TUG) test while considering anthropometric factors in subjects with recurrent low back pain (LBP). METHODS: Sixty-six individuals participated in the study. The data were collected on two different days, 1 week apart. The KSI of the core spine, using video motion-capture techniques, was based on the relative standing time and relative standstill time...
October 4, 2017: European Spine Journal
https://www.readbyqxmd.com/read/28891599/expression-in-escherichia-coli-of-fusion-protein-comprising-%C3%AE-conotoxin-txib-and-preservation-of-selectivity-to-nicotinic-acetylcholine-receptors-in-the-purified-product
#4
Jinpeng Yu, Xiaopeng Zhu, Yang Yang, Sulan Luo, Dongting Zhangsun
Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels, which are widely distributed in the central and peripheral nervous system. The α6β2* nAChR is an important subtype, which is closely associated with nicotine addiction and movement disorders etc. α-conotoxin TxIB with 16-amino acid residues specifically targets α6β2* nAChR with no obvious effect on other nAChR subtypes. However, chemical synthesis of TxIB is expensive, and the quantity of native TxIB extracted from cone snail is limited...
September 11, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28736549/cloning-expression-isotope-labeling-and-purification-of-transmembrane-protein-merf-from-mercury-resistant-enterobacter-sp-az-15-for-nmr-studies
#5
Aatif Amin, Zakia Latif
Mercury resistant (Hg(R)) Enterobacter sp. AZ-15 was isolated from heavy metal polluted industrial wastewater samples near to districts Kasur and Sheikhupura, Pakistan. 16S rDNA ribotyping and phylogentic analysis showed 98% homology with already reported Enterobacter species. The merF gene encoding transmembrane protein-MerF was amplified from genomic DNA and ligated into pET31b+ vector using restriction endonucleases, SphI and XhoI. The genetic codons of merF gene encoding cysteine residues were mutated into codons, translating into serine residues by site-directed mutagenesis...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28732050/a-heckman-selection-model-for-the-safety-analysis-of-signalized-intersections
#6
Xuecai Xu, S C Wong, Feng Zhu, Xin Pei, Helai Huang, Youjun Liu
PURPOSE: The objective of this paper is to provide a new method for estimating crash rate and severity simultaneously. METHODS: This study explores a Heckman selection model of the crash rate and severity simultaneously at different levels and a two-step procedure is used to investigate the crash rate and severity levels. The first step uses a probit regression model to determine the sample selection process, and the second step develops a multiple regression model to simultaneously evaluate the crash rate and severity for slight injury/kill or serious injury (KSI), respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28728062/investigation-of-factors-affecting-the-injury-severity-of-single-vehicle-rollover-crashes-a-random-effects-generalized-ordered-probit-model
#7
Alireza Jafari Anarkooli, Mehdi Hosseinpour, Adele Kardar
Rollover crashes are responsible for a notable number of serious injuries and fatalities; hence, they are of great concern to transportation officials and safety researchers. However, only few published studies have analyzed the factors associated with severity outcomes of rollover crashes. This research has two objectives. The first objective is to investigate the effects of various factors, of which some have been rarely reported in the existing studies, on the injury severities of single-vehicle (SV) rollover crashes based on six-year crash data collected on the Malaysian federal roads...
July 17, 2017: Accident; Analysis and Prevention
https://www.readbyqxmd.com/read/28719738/an-activator-blocker-pair-provides-a-controllable-on-off-switch-for-a-ketosteroid-isomerase-active-site-mutant
#8
Vandana Lamba, Filip Yabukarski, Daniel Herschlag
Control of enzyme activity is fundamental to biology and represents a long-term goal in bioengineering and precision therapeutics. While several powerful molecular strategies have been developed, limitations remain in their generalizability and dynamic range. We demonstrate a control mechanism via separate small molecules that turn on the enzyme (activator) and turn off the activation (blocker). We show that a pocket created near the active site base of the enzyme ketosteriod isomerase (KSI) allows efficient and saturable base rescue when the enzyme's natural general base is removed...
August 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28710973/identification-of-high-risk-metropolitan-intersection-sites-in-perth-australia
#9
Michelle Hobday, Kyle Chow, Lynn Meuleners, Fritha Argus
As convergence points for road users approaching from multiple directions, intersections have more opportunities for conflicts, thus higher crash risk than other parts of the road network. Given the limited resources available for road safety, it is important to identify high risk intersections so that they can be prioritised for infrastructure improvement. This study used a three-stage approach to identify intersections in Perth, Western Australia: using Road Trauma Risk Analysis, then Comparative Safety Performance Analysis and finally ranking the intersections by the KSI (Killed and Serious Injury) metric...
July 12, 2017: Accident; Analysis and Prevention
https://www.readbyqxmd.com/read/28161946/methyl-and-p-bromobenzyl-esters-of-hydrogenated-kaurenoic-acid-for-controlling-anthracnose-in-common-bean-plants
#10
Suellen F Mota, Denilson F Oliveira, Vladimir C G Heleno, Ana Carolina F Soares, Jacob O Midiwo, Elaine A Souza
Kaurenoic acid derivatives were prepared and submitted to in vitro assays with the fungus Colletotrichum lindemuthianum, which causes anthracnose disease in the common bean. The most active substances were found to be methyl and p-bromobenzylesters, 7 and 9, respectively, of the hydrogenated kaurenoic acid, which presented a minimum inhibitory concentration (MIC) of 0.097 and 0.131 mM, respectively, while the commercial fungicide methyl thiophanate (MT) presented a MIC of 0.143 mM. Substances 7 (1.401 mM) and 9 (1...
March 1, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28045505/kemp-eliminase-activity-of-ketosteroid-isomerase
#11
Vandana Lamba, Enis Sanchez, Lauren Rose Fanning, Kathryn Howe, Maria Alejandra Alvarez, Daniel Herschlag, Marcello Forconi
Kemp eliminases represent the most successful class of computationally designed enzymes, with rate accelerations of up to 10(9)-fold relative to the rate of the same reaction in aqueous solution. Nevertheless, several other systems such as micelles, catalytic antibodies, and cavitands are known to accelerate the Kemp elimination by several orders of magnitude. We found that the naturally occurring enzyme ketosteroid isomerase (KSI) also catalyzes the Kemp elimination. Surprisingly, mutations of D38, the residue that acts as a general base for its natural substrate, produced variants that catalyze the Kemp elimination up to 7000-fold better than wild-type KSI does, and some of these variants accelerate the Kemp elimination more than the computationally designed Kemp eliminases...
January 31, 2017: Biochemistry
https://www.readbyqxmd.com/read/28039182/national-10-year-trend-in-road-injuries-involving-school-children-on-the-way-to-and-from-school-in-japan-2003-2012
#12
Haruhiko Inada, Jun Tomio, Shinji Nakahara, Xin Xu, Ayako Taniguchi, Masao Ichikawa
OBJECTIVES: To quantitatively describe the recent longitudinal trend in road injuries involving school children while commuting to and from school in Japan and to identify groups or situations with particularly large or small decreasing trends. METHODS: Data on the number of children aged 6-15 years who sustained road injuries while commuting were obtained, stratified by year, demographic characteristics, mode of transport and other variables. The rates of killed or seriously injured (KSI) children were calculated from the number of KSI cases (the numerator) and the product of population and the proportion of each mode of transport estimated using the Person Trip Survey data (the denominator)...
October 2017: Injury Prevention: Journal of the International Society for Child and Adolescent Injury Prevention
https://www.readbyqxmd.com/read/27647541/a-randomized-double-blind-placebo-controlled-study-of-efficacy-and-tolerability-of-withaina-somnifera-extracts-in-knee-joint-pain
#13
G S H Ramakanth, C Uday Kumar, P V Kishan, P Usharani
BACKGROUND: Root extracts of Withania somnifera (Ashwagandha) are known to possess analgesic, anti-inflammatory and chondroprotective effects. An aqueous extract of roots plus leaves of this plant has shown to yield higher percentages of withanolide glycosides and, accordingly, may possess better analgesic, anti-inflammatory and chondroprotective effects than root alone extracts. OBJECTIVES: To evaluate efficacy and tolerability of a standardized aqueous extract of roots plus leaves of W...
July 2016: Journal of Ayurveda and Integrative Medicine
https://www.readbyqxmd.com/read/27545569/a-critical-test-of-the-electrostatic-contribution-to-catalysis-with-noncanonical-amino-acids-in-ketosteroid-isomerase
#14
Yufan Wu, Steven G Boxer
The vibrational Stark effect (VSE) has been used to measure the electric field in the active site of ketosteroid isomerase (KSI). These measured fields correlate with ΔG(⧧) in a series of conventional mutants, yielding an estimate for the electrostatic contribution to catalysis (Fried et al. Science 2014, 346, 1510-1513). In this work we test this result with much more conservative variants in which individual Tyr residues in the active site are replaced by 3-chlorotyrosine via amber suppression. The electric fields sensed at the position of the carbonyl bond involved in charge displacement during catalysis were characterized using the VSE, where the field sensitivity has been calibrated by vibrational Stark spectroscopy, solvatochromism, and MD simulations...
September 14, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27541577/vibrational-stark-effects-of-carbonyl-probes-applied-to-reinterpret-ir-and-raman-data-for-enzyme-inhibitors-in-terms-of-electric-fields-at-the-active-site
#15
Samuel H Schneider, Steven G Boxer
IR and Raman frequency shifts have been reported for numerous probes of enzyme transition states, leading to diverse interpretations. In the case of the model enzyme ketosteroid isomerase (KSI), we have argued that IR spectral shifts for a carbonyl probe at the active site can provide a connection between the active site electric field and the activation free energy (Fried et al. Science 2014, 346, 1510-1514). Here we generalize this approach to a much broader set of carbonyl probes (e.g., oxoesters, thioesters, and amides), first establishing the sensitivity of each probe to an electric field using vibrational Stark spectroscopy, vibrational solvatochromism, and MD simulations, and then applying these results to reinterpret data already in the literature for enzymes such as 4-chlorobenzoyl-CoA dehalogenase and serine proteases...
September 15, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27410422/evaluation-of-the-catalytic-contribution-from-a-positioned-general-base-in-ketosteroid-isomerase
#16
Vandana Lamba, Filip Yabukarski, Margaux Pinney, Daniel Herschlag
Proton transfer reactions are ubiquitous in enzymes and utilize active site residues as general acids and bases. Crystal structures and site-directed mutagenesis are routinely used to identify these residues, but assessment of their catalytic contribution remains a major challenge. In principle, effective molarity measurements, in which exogenous acids/bases rescue the reaction in mutants lacking these residues, can estimate these catalytic contributions. However, these exogenous moieties can be restricted in reactivity by steric hindrance or enhanced by binding interactions with nearby residues, thereby resulting in over- or underestimation of the catalytic contribution, respectively...
August 10, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27375051/role-of-conserved-met112-residue-in-the-catalytic-activity-and-stability-of-ketosteroid-isomerase
#17
Hyung Jin Cha, Do Soo Jang, Jae-Hee Jeong, Bee Hak Hong, Young Sung Yun, Eun Ju Shin, Kwan Yong Choi
Ketosteroid isomerase (3-oxosteroid Δ(5)-Δ(4)-isomerase, KSI) from Pseudomonas putida catalyzes allylic rearrangement of the 5,6-double bond of Δ(5)-3-ketosteroid to 4,5-position by stereospecific intramolecular transfer of a proton. The active site of KSI is formed by several hydrophobic residues and three catalytic residues (Tyr14, Asp38, and Asp99). In this study, we investigated the role of a hydrophobic Met112 residue near the active site in the catalysis, steroid binding, and stability of KSI. Replacing Met112 with alanine (yields M112A) or leucine (M112L) decreased the kcat by 20- and 4-fold, respectively...
October 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/26992790/enhanced-bioconversion-rate-and-released-substrate-inhibition-in-r-phenylephrine-whole-cell-bioconversion-via-partial-acetone-treatment
#18
Shu-Chen Kan, Chi-Zong Zang, Chiung-Wen Yeh, Wei-Feng Chang, Chia-Chi Lin, Tzu-Hsiang Hung, Chwen-Jen Shieh, Yung-Chuan Liu
An approach was developed to enhance the efficiency for the bioconversion of 1-(3-hydroxyphenyl)-2-(methyamino)-ethanone to (R)-phenylephrine. The strain Serratia marcescens N10612, giving the benefit of 99% enantiomeric excess in (R)-PE conversion, was used. The fermentation was devised to harvest cells with high hydrophobic prodigiosin content inside the cells. Then, the partial acetone extraction was applied to remove prodigiosin from the cells. The treatment was found to increase the cells conversion rate without loss of the cells NADPH redox system...
May 2016: Enzyme and Microbial Technology
https://www.readbyqxmd.com/read/26788959/how-would-increasing-seat-belt-use-affect-the-number-of-killed-or-seriously-injured-light-vehicle-occupants
#19
Alena Høye
The expected effects of increasing seat belt use on the number of killed or seriously injured (KSI) light vehicle occupants have been estimated for three scenarios of increased seat belt use in Norway, taking into account current seat belt use, the effects of seat belts and differences in crash risk between belted and unbelted drivers. The effects of seat belts on fatality and injury risk were investigated in a meta-analysis that is based on 24 studies from 2000 or later. The results indicate that seat belts reduce both fatal and non-fatal injuries by 60% among front seat occupants and by 44% among rear seat occupants...
March 2016: Accident; Analysis and Prevention
https://www.readbyqxmd.com/read/26571340/dissecting-proton-delocalization-in-an-enzyme-s-hydrogen-bond-network-with-unnatural-amino-acids
#20
Yufan Wu, Stephen D Fried, Steven G Boxer
Extended hydrogen bond networks are a common structural motif of enzymes. A recent analysis proposed quantum delocalization of protons as a feature present in the hydrogen bond network spanning a triad of tyrosines (Y(16), Y(32), and Y(57)) in the active site of ketosteroid isomerase (KSI), contributing to its unusual acidity and large isotope shift. In this study, we utilized amber suppression to substitute each tyrosine residue with 3-chlorotyrosine to test the delocalization model and the proton affinity balance in the triad...
December 8, 2015: Biochemistry
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