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https://www.readbyqxmd.com/read/28641400/cytosolic-delivery-of-sirna-by-ultra-high-affinity-dsrna-binding-proteins
#1
Nicole J Yang, Monique J Kauke, Fangdi Sun, Lucy F Yang, Katie F Maass, Michael W Traxlmayr, Yao Yu, Yingda Xu, Robert S Langer, Daniel G Anderson, K Dane Wittrup
Protein-based methods of siRNA delivery are capable of uniquely specific targeting, but are limited by technical challenges such as low potency or poor biophysical properties. Here, we engineered a series of ultra-high affinity siRNA binders based on the viral protein p19 and developed them into siRNA carriers targeted to the epidermal growth factor receptor (EGFR). Combined in trans with a previously described endosome-disrupting agent composed of the pore-forming protein Perfringolysin O (PFO), potent silencing was achieved in vitro with no detectable cytotoxicity...
June 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28641392/alcohol-is-not-protective-against-mortality-following-traumatic-brain-injury
#2
Jennifer S Albrecht, Majid Afshar, Deborah M Stein, Gordon S Smith
Alcohol exposure results in reduced mortality following traumatic brain injury (TBI) in animal models, yet clinical studies reported conflicting results and clinical trials based on proposed mechanisms have been disappointing. Methodological issues common to many of the clinical studies may have contributed to spurious results. Our objective was to evaluate the association between blood alcohol concentration (BAC) and in-hospital mortality following TBI, overcoming methodological problems of prior studies. We conducted a retrospective cohort study on individuals treated for isolated TBI at the R Adams Cowley Shock Trauma Center between 1997-2012 (n = 1,084)...
June 21, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28641383/neuroprotection-in-stroke-the-importance-of-collaboration-and-reproducibility
#3
Ain A Neuhaus, Yvonne Couch, Gina Hadley, Alastair M Buchan
Acute ischaemic stroke accounts for 6.5 million deaths per year, and by 2030 will result in the annual loss of over 200 million disability-adjusted life years globally. There have been considerable recent advances in the gold standard of acute ischaemic stroke treatment, some aspects of which-aspirin to prevent recurrence, and treating patients in specialized stroke wards-are widely applicable. Recanalization of the occluded artery through thrombolysis and/or endovascular thrombectomy is restricted to only a small proportion of patients, due to contra-indications and the costs associated with establishing the infrastructure to deliver these treatments...
June 20, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28641374/intergenerational-socioeconomic-mobility-and-adult-depression-the-constances-study
#4
Maria Melchior, Abdelkrim Ziad, Emilie Courtin, Marcel Goldberg, Marie Zins, Judith van der Waerden
Socioeconomic mobility from childhood onwards may predict depression risk in adulthood. Using data from the nationally representative CONSTANCES study in France (2012-2014, n = 67,057), we assessed the relationship between intergenerational socioeconomic mobility and adult depression (Center for Epidemiological Studies-Depression scale, > = 16 in men, > = 20 in women) and antidepressant use. Socioeconomic position was ascertained by occupational grade (childhood: maternal and paternal measures prior to age 15 years combined; adult: participant own)...
June 21, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28641369/markers-of-inflammation-and-incident-breast-cancer-risk-in-the-women-s-health-study
#5
Deirdre K Tobias, Akintunde O Akinkuolie, Paulette D Chandler, Patrick R Lawler, JoAnn E Manson, Julie E Buring, Paul M Ridker, Lu Wang, I-Min Lee, Samia Mora
Chronic inflammation may be a risk factor for breast cancer development and progression, yet which inflammatory biomarkers and pathways are relevant is unknown. The study included 27,071 Women's Health Study participants (mean, 54.5 years old) free of cancer and cardiovascular disease at enrollment (1992 to 1995) with baseline measures of four inflammatory biomarkers: high sensitivity C-reactive protein (hsCRP), fibrinogen, N-acetyl side-chains of acute phase proteins (GlycA), and soluble intercellular adhesion molecule-1 (sICAM-1)...
June 21, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28641367/annual-crop-yield-variation-child-survival-and-nutrition-among-subsistence-farmers-in-burkina-faso
#6
Kristine Belesova, Antonio Gasparrini, Ali Sié, Rainer Sauerborn, Paul Wilkinson
Whether year to year variation in crop yields affects the nutrition, health, and survival of subsistence farming populations is relevant to the understanding of the potential impacts of climate change. However, the empirical evidence is limited. We examined the association of child survival with inter-annual variation in food crop yield and middle-upper arm circumference (MUAC) in a subsistence farming population of rural Burkina Faso. The study was of 44,616 children < 5 years of age included in the Nouna Health and Demographic Surveillance System, 1992-2012, whose survival was analysed in relation to the food crop yield in the year of birth (which ranged from 65% to 120% of the period average) and, for a subset of 16,698 children, to MUAC, using shared frailty Cox proportional hazards models...
June 21, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28641366/human-papillomavirus-vaccine-dose-effectiveness-against-incident-genital-warts-in-a-cohort-of-insured-us-females
#7
Susan Hariri, Megan S Schuler, Allison L Naleway, Matthew F Daley, Sheila Weinmann, Bradley Crane, Sophia R Newcomer, Dennis Tolsma, Lauri E Markowitz
We examined effectiveness of HPV vaccination by dose number and interval against incident genital warts in a cohort of 64,517 females in the United States during 8/2006-9/2012. Eligible females were classified into 0, 1-dose, 2-dose < 6 months apart, 2-dose ≥6 months apart, and 3-dose groups and followed until genital wart diagnosis, loss to follow-up, or end of study. Propensity score weights were used to balance baseline differences across groups. To account for latent genital warts before vaccination, 6-month and 12-month buffer periods from last and first vaccine dose, respectively, were applied...
June 21, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28641362/estimating-the-potential-cost-of-a-high-dose-immune-tolerance-induction-iti-therapy-relative-to-the-cost-of-a-combined-therapy-of-a-low-dose-iti-therapy-with-bypassing-agent-prophylaxis
#8
G Kenet, A Oladapo, J D Epstein, C Thompson, A Novack, D J Nugent
INTRODUCTION: The International Immune Tolerance Study (I-ITI) demonstrated comparable success rates between low (FVIII 50 IU/kg/TIW) and high dose (FVIII 200 IU/kg/day) regimens. While costlier, the high dose ITI regimen achieved shorter time-to-treatment success with fewer bleeding episodes compared to the low dose ITI regimen. Adding bypassing agent prophylaxis (BAP) to a low dose ITI regimen may reduce bleeding while still being less costly than high dose ITI. AIM AND METHODS: An economic model was developed to compare high dose ITI to low dose ITI with BAP...
June 22, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28641352/-do-general-surgeons-feel-adequately-prepared-for-the-complex-questions-associated-with-the-handling-of-multi-resistant-pathogens-results-of-the-mr2-survey
#9
Matthias May, Philipp J Spachmann, Steffen Lebentrau, Harald Schumacher, Christian Gilfrich, Hans-Martin Fritsche, Malte Vetterlein, Sabine Brookman-May, Martin Schostak, Florian M Wagenlehner, Maximilian Burger, Alexander Novotny, Robert Obermaier
Background At the present time, there is no evidence available as to the knowledge of general surgeons regarding multi-resistant pathogens (MRP) and the rational use of antibiotic medication (antibiotic stewardship/ABS) compared with physicians from other disciplines. Methods As part of the MR2 survey (Multiinstitutional Reconnaissance of practice with MultiResistant bacteria - a survey focussing on German hospitals), a questionnaire comprising 4 + 35 items was distributed to urologists, internists, gynaecologists and general surgeons in 18 hospitals...
June 2017: Zentralblatt Für Chirurgie
https://www.readbyqxmd.com/read/28641308/detection-of-phosphatidylserine-positive-exosomes-for-the-diagnosis-of-early-stage-malignancies
#10
Raghava Sharma, Xianming Huang, Rolf A Brekken, Alan J Schroit
BACKGROUND: There has been increasing interest in the detection of tumour exosomes in blood for cancer diagnostics. Most studies have focussed on miRNA and protein signatures that are surrogate markers for specific tumour types. Because tumour cells and tumour-derived exosomes display phosphatidylserine (PS) in their outer membrane leaflet, we developed a highly sensitive ELISA-based system that detects picogram amounts of exosomal phospholipid in plasma as a cancer biomarker. METHODS: This report describes the development of a highly specific and sensitive ELISA for the capture of PS-expressing tumour exosomes in the blood of tumour-bearing mice...
June 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28641303/microrna-122a-regulates-zonulin-by-targeting-egfr-in-intestinal-epithelial-dysfunction
#11
Bin Zhang, Yinghai Tian, Ping Jiang, Yanqiong Jiang, Chao Li, Ting Liu, Rujian Zhou, Ning Yang, Xinke Zhou, Zhihua Liu
BACKGROUND/AIMS: This study aimed to investigate the role of microRNA (miR)-122a in regulating zonulin during the modulation of intestinal barrier. METHODS: Zonulin proteins and their target gene expression were analyzed in miR-122a-overexpressing cell lines and in the target gene of epidermal growth factor receptor (EGFR). An mmu-miR-122a intestinal epithelial conditional transgenic (miR-122a-TG) mouse model was established to investigate EGFR and zonulin expression...
June 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28641299/monocyte-subsets-are-differentially-lost-from-the-circulation-during-acute-inflammation-induced-by-human-experimental-endotoxemia
#12
Tamar Tak, Roger van Groenendael, Peter Pickkers, Leo Koenderman
Three human monocyte subsets are recognized with different functions in the immune system: CD14++/CD16- classical monocytes (CM), CD14++/CD16+ intermediate monocytes (IM) and CD14+/CD16++ non-classical monocytes (NCM). Increased IM and NCM percentages have been reported under inflammatory conditions, yet little is known about monocyte subsets at the onset of inflammation. The human endotoxemia model is uniquely capable of studying the first phases of acute inflammation induced by intravenous injection of 2 ng/kg bodyweight lipopolysaccharide (LPS) into healthy volunteers...
June 23, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28641297/factor-analysis-and-psychometric-properties-of-the-minnesota-nicotine-withdrawal-scale-and-the-minnesota-nicotine-withdrawal-scale-revised-italian-version
#13
Andrea Svicher, Agnese Beghè, Giacomo Mangiaracina, Fiammetta Cosci
BACKGROUND/AIMS: We run Exploratory and Confirmatory Factor Analyses of the Minnesota Nicotine Withdrawal Scale (MNWS) and of the MNWS-Revised (MNWS-R). Psychometric properties were also explored. METHODS: Adult Italian smokers, 366 in all, were assessed via the MNWS-R together with rating scales measuring cigarette dependence, alcohol use, anxiety sensitivity and negative affect at baseline and after 3 months. RESULTS: The MNWS showed good psychometric properties (α = 0...
June 23, 2017: European Addiction Research
https://www.readbyqxmd.com/read/28641269/a-model-based-tool-for-the-analysis-and-design-of-gene-regulatory-network
#14
Liliana Ironi, Ettore Lanzarone
Computational and mathematical models have significantly contributed to the rapid progress in the study of gene regulatory networks (GRN), but researchers still lack a reliable model-based framework for computer-aided analysis and design. Such tool should both reveal the relation between network structure and dynamics and find parameter values and/or constraints that enable the simulated dynamics to reproduce specific behaviors. This paper addresses these issues and proposes a computational framework that facilitates network analysis or design...
June 19, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28641268/newgoa-predicting-new-go-annotations-of-proteins-by-bi-random-walks-on-a-hybrid-graph
#15
Guoxian Yu, Guangyuan Fu, Jun Wang, Yingwen Zhao
A remaining key challenge of modern biology is annotating the functional roles of proteins. Various computational models have been proposed for this challenge. Most of them assume the annotations of annotated proteins are complete. But in fact, many of them are incomplete. We proposed a method called NewGOA to predict new Gene Ontology (GO) annotations for incompletely annotated proteins and for completely un-annotated ones. NewGOA employs a hybrid graph, composed of two types of nodes (proteins and GO terms), to encode interactions between proteins, hierarchical relationships between terms and available annotations of proteins...
June 15, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/28641265/a-new-method-for-neural-spike-alignment-the-centroid-filter
#16
Benjamin Metcalfe, Chris Clarke, Nick Donaldson, John Taylor
Recordings made directly from the nervous system are a key tool in experimental electrophysiology and the development of bioelectronic medicines. Analysis of these recordings involves the identification of signals from individual neurons, a process known as spike sorting. A critical and limiting feature of spike sorting is the need to align individual spikes in time. However, electrophysiological recordings are made in extremely noisy environments that seriously limit the performance of the spike-alignment process...
June 16, 2017: IEEE Transactions on Neural Systems and Rehabilitation Engineering
https://www.readbyqxmd.com/read/28641259/face-hallucination-using-linear-models-of-coupled-sparse-support
#17
Reuben A Farrugia, Christine Guillemot
Most face super-resolution methods assume that low- and high-resolution manifolds have similar local geometrical structure, hence learn local models on the low-resolution manifold (e.g. sparse or locally linear embedding models), which are then applied on the high- resolution manifold. However, the low-resolution manifold is distorted by the one-to-many relationship between low- and high- resolution patches. This paper presents the Linear Model of Coupled Sparse Support (LM-CSS) method which learns linear models based on the local geometrical structure on the high-resolution manifold rather than on the low-resolution manifold...
June 19, 2017: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
https://www.readbyqxmd.com/read/28641258/quality-assessment-of-perceptual-crosstalk-on-two-view-auto-stereoscopic-displays
#18
Jongyoo Kim, Taewan Kim, Sanghoon Lee, Alan C Bovik
Crosstalk is one of the most severe factors affecting the perceived quality of stereoscopic 3D (S3D) images. It arises from a leakage of light intensity between multiple views, as in auto-stereoscopic displays. Well-known determinants of crosstalk include the co-location contrast and disparity of the left and right images, which have been dealt with in prior studies. However, when a natural stereo image that contains complex naturalistic spatial characteristics is viewed on an auto-stereoscopic display, other factors may also play an important role in the perception of crosstalk...
June 19, 2017: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
https://www.readbyqxmd.com/read/28641257/fast-segmentation-from-blurred-data-in-3d-fluorescence-microscopy
#19
Martin Storath, Dennis Rickert, Michael Unser, Andreas Weinmann
We develop a fast algorithm for segmenting 3D images from linear measurements based on the Potts model (or piecewise constant Mumford-Shah model). To that end, we first derive suitable space discretizations of the 3D Potts model which are capable of dealing with 3D images defined on non-cubic grids. Our discretization allows us to utilize a specific splitting approach which results in decoupled subproblems of moderate size. The crucial point in the 3D setup is that the number of independent subproblems is so large that we can reasonably exploit the parallel processing capabilities of the graphics processing units (GPU)...
June 16, 2017: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
https://www.readbyqxmd.com/read/28641256/a-novel-fast-tensor-based-preconditioner-for-image-restoration
#20
Mansoor Rezghi
Image restoration is one of the main parts of image processing. Mathematically, this problem can be modeled as a large scale structured ill-posed linear system. Ill-posedness of this problem results in low convergence rate of iterative solvers. For speeding up the convergence, preconditioning usually is used. Despite the existing preconditioners for image restoration which are constructed based on approximations of the blurring matrix, in this paper, we propose a novel preconditioner with a different viewpoint...
June 16, 2017: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
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