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https://www.readbyqxmd.com/read/27914946/design-synthesis-and-biological-evaluation-of-alkylamino-biphenylamides-as-hsp90-c-terminal-inhibitors
#1
Gaurav Garg, Huiping Zhao, Brian S J Blagg
Hsp90 is a promising therapeutic target for the development of anti-cancer agents due to its integral role in the stability and function of proteins associated with all ten hallmarks of cancer. Novobiocin, a coumarin antibiotic, was the first natural product identified that targeted the Hsp90 C-terminal domain and manifested anti-proliferative activity (SKBr3 IC50∼700μM). Subsequent structural investigations on novobiocin led to analogues with significantly improved anti-proliferative activity against multiple cancer cell lines...
November 19, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27913545/what-have-we-learned-from-large-population-studies-of-von-willebrand-disease
#2
Robert R Montgomery, Veronica H Flood
Von Willebrand factor (VWF) is a critical regulator of hemostatic processes, including collagen binding, platelet adhesion, and platelet aggregation. It also serves as a carrier protein to normalize plasma factor VIII synthesis, release, and survival. While VWF protein measurements by immunoassay are reasonably comparable between institutions, the measurement of VWF ristocetin cofactor activity (VWF:RCo) has significant variability. Other tests of VWF function, including collagen binding or platelet glycoprotein IIb-IIIa binding, are not universally available, yet these functional defects may cause major bleeding even with normal VWF antigen (VWF:Ag) and VWF:RCo assays...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913480/thrombosis-in-the-setting-of-cancer
#3
Michael B Streiff
Venous thromboembolism (VTE) is a common cause of adverse outcomes in patients with cancer. The risk of VTE varies with cancer type, stage and grade, cancer therapy, and supportive care, as well as patient characteristics including age, ethnicity, and inherited and acquired comorbid conditions. VTE prophylaxis should be provided to all hospitalized cancer patients and high-risk outpatients. Low-molecular-weight heparin (LMWH) remains the first-line therapy for VTE in patients with active cancer. Anticoagulation should be continued as long as there is evidence of active disease or patients are receiving cancer treatment...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27910697/sensitivity-of-magnetic-field-line-pitch-angle-measurements-to-sawtooth-events-in-tokamaks
#4
J Ko
The sensitivity of the pitch angle profiles measured by the motional Stark effect (MSE) diagnostic to the evolution of the safety factor, q, profiles during the tokamak sawtooth events has been investigated for Korea Superconducting Tokamak Advanced Research (KSTAR). An analytic relation between the tokamak pitch angle, γ, and q estimates that Δγ ∼ 0.1° is required for detecting Δq ∼ 0.05 near the magnetic axis (not at the magnetic axis, though). The pitch angle becomes less sensitive to the same Δq for the middle and outer regions of the plasma (Δγ ∼ 0...
November 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/27910365/impulse-responses-of-visible-phototubes-used-in-national-ignition-facility-neutron-time-of-flight-diagnostics
#5
P S Datte, M Eckart, A S Moore, W Thompson, G Vergel de Dios
Neutron-induced visible scintillation in neutron time of flight (NToF) diagnostics at the National Ignition Facility (NIF) is measured with 40 mm single stage micro-channel plate photomultipliers and a 40 mm vacuum photodiode, outside the neutron line of sight. In NIF experiments with 14 MeV neutron yields above Y > 10 × 10(15) these tubes are configured to deliver of order 1 nC of charge in the nominally 5 ns NToF into a 50 Ω load. We have examined a number of 40 mm tubes manufactured by Photek Ltd. of St...
November 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/27910344/icrf-wave-field-measurements-in-the-presence-of-scrape-off-layer-turbulence-on-the-asdex-upgrade-tokamak-invited
#6
R Ochoukov, V Bobkov, H Faugel, H Fünfgelder, J Jacquot, J-M Noterdaeme, G Suárez López
A new array of B-dot probes was installed on ASDEX Upgrade. The purpose of the new diagnostic is to study Ion Cyclotron Range-off Frequencies (ICRF) wave field distributions in the evanescent scrape-off layer (SOL) plasma region on the low field side of ASDEX Upgrade. The vacuum measurements (no gas, BT = 0 T) reveal ICRF wave field measurements consistent with the profiles expected from the newly installed 3-strap ICRF antennas outside the antenna box: the shape of the toroidal distribution of both the amplitude and the phase is the same for the case of only the central straps being active, as for the case of only the side straps being active...
November 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/27910097/chronic-migraine-an-update-on-physiology-imaging-and-the-mechanism-of-action-of-two-available-pharmacologic-therapies
#7
Sheena K Aurora, Mitchell F Brin
Several lines of research support the hypothesis that migraine is a spectrum of illness, with clinical symptoms that vary along a continuum from episodic migraine to chronic migraine. Physiologic changes may result in episodic migraine evolving into chronic migraine over months to years in susceptible individuals. With chronification, headache frequency increases, becoming more disabling and less responsive to therapy. Neurophysiologic and functional imaging research has reported that chronic migraine may be associated with severity-specific metabolic, functional, and structural abnormalities in the brainstem...
December 2, 2016: Headache
https://www.readbyqxmd.com/read/27909576/zika-antiviral-chemotherapy-identification-of-drugs-and-promising-starting-points-for-drug-discovery-from-an-fda-approved-library
#8
Bruno S Pascoalino, Gilles Courtemanche, Marli T Cordeiro, Laura H V G Gil, Lucio Freitas-Junior
Background The recent epidemics of Zika virus (ZIKV) implicated it as the cause of serious and potentially lethal congenital conditions such microcephaly and other central nervous system defects, as well as the development of the Guillain-Barré syndrome in otherwise healthy patients. Recent findings showed that anti-Dengue antibodies are capable of amplifying ZIKV infection by a mechanism similar to antibody-dependent enhancement, increasing the severity of the disease. This scenario becomes potentially catastrophic when the global burden of Dengue and the advent of the newly approved anti-Dengue vaccines in the near future are taken into account...
2016: F1000Research
https://www.readbyqxmd.com/read/27909423/how-do-you-play-a-comparison-among-children-aged-4-10
#9
Elisa Delvecchio, Jian-Bin Li, Chiara Pazzagli, Adriana Lis, Claudia Mazzeschi
Pretend play has a central role for children's development and psychological well-being. However, there is a paucity of standardized and valid measures specifically devoted to assess the core domains involved in play activities in preschool and primary school children. The Affect in Play Scale-Preschool (4-5 years) and the Affect in Play Scale-Preschool Extended Version (6-10 years) are semi-structured parallel tools designed to explore child's cognitive and affective processes using a standardized play task...
2016: Frontiers in Psychology
https://www.readbyqxmd.com/read/27909235/a-simple-and-sensitive-high-content-assay-for-the-characterization-of-antiproliferative-therapeutic-antibodies
#10
Andreas Stengl, David Hörl, Heinrich Leonhardt, Jonas Helma
Monoclonal antibodies (mAbs) have become a central class of therapeutic agents in particular as antiproliferative compounds. Their often complex modes of action require sensitive assays during early, functional characterization. Current cell-based proliferation assays often detect metabolites that are indicative of metabolic activity but do not directly account for cell proliferation. Measuring DNA replication by incorporation of base analogues such as 5-bromo-2'-deoxyuridine (BrdU) fills this analytical gap but was previously restricted to bulk effect characterization in enzyme-linked immunosorbent assay formats...
December 1, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27909134/what-is-the-morbidity-of-a-non-invasive-growing-prosthesis
#11
M M Gilg, C L Gaston, M C Parry, L Jeys, A Abudu, R M Tillman, S R Carter, R J Grimer
AIMS: Extendible endoprostheses have been available for more than 30 years and have become more sophisticated with time. The latest generation is 'non-invasive' and can be lengthened with an external magnetic force. Early results have shown a worryingly high rate of complications such as infection. This study investigates the incidence of complications and the need for further surgery in a cohort of patients with a non-invasive growing endoprosthesis. PATIENTS AND METHODS: Between 2003 and June 2014, 50 children (51 prostheses) had a non-invasive growing prosthesis implanted for a primary bone sarcoma...
December 2016: Bone & Joint Journal
https://www.readbyqxmd.com/read/27909049/control-of-secreted-protein-gene-expression-and-the-mammalian-secretome-by-the-metabolic-regulator-pgc-1%C3%AE
#12
Neri Minsky, Robert G Roeder
Secreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes and signal molecules. However, how the secretome is regulated remains incompletely understood. Here we demonstrate, unexpectedly, that peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate expression of diverse genes encoding secreted molecules and extracellular matrix (ECM) components to modulate the secretome...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27908433/central-venous-catheter-infections-in-home-parenteral-nutrition-patients-outcomes-from-sustain-american-society-for-parenteral-and-enteral-nutrition-s-national-patient-registry-for-nutrition-care
#13
Vicki M Ross, Peggi Guenter, Mandy L Corrigan, Debra Kovacevich, Marion F Winkler, Helaine E Resnick, Tina L Norris, Lawrence Robinson, Ezra Steiger
BACKGROUND: Home parenteral nutrition (HPN) is a high-cost, complex nutrition support therapy that requires the use of central venous catheters. Central line-associated bloodstream infections (CLABSIs) are among the most serious risks of this therapy. Sustain: American Society for Parenteral and Enteral Nutrition's National Patient Registry for Nutrition Care (Sustain registry) provides the most current and comprehensive data for studying CLABSI among a national cohort of HPN patients in the United States...
December 1, 2016: American Journal of Infection Control
https://www.readbyqxmd.com/read/27908432/safety-and-utilization-of-peripherally-inserted-central-catheters-versus-midline-catheters-at-a-large-academic-medical-center
#14
Tianyuan Xu, Lawrence Kingsley, Susan DiNucci, Gwen Messer, Jong-Hyeon Jeong, Brian Morgan, Kathleen Shutt, Mohamed H Yassin
BACKGROUND: Peripherally inserted central catheters (PICCs) are a commonly used central intravenous (IV) access device, which can be associated with significant complications. Midline catheters (MCs) are peripheral IV access devices that may reduce the need for central lines and hence decrease central line-associated bloodstream infections. The objective of this study is to compare the utilization and safety of PICCs and MCs. METHODS: This was a retrospective study comparing the use and outcomes of PICCs and MCs at a large academic medical center between January and May 2015...
December 1, 2016: American Journal of Infection Control
https://www.readbyqxmd.com/read/27908383/the-insecticide-spinosad-induces-dna-damage-and-apoptosis-in-hek293-and-hepg2-cells
#15
Mingjun Yang, Guanggang Xiang, Diqiu Li, Yang Zhang, Wenping Xu, Liming Tao
Spinosad, a pesticide acting on the central nervous system of insects, is classified as a pesticide with reduced risk. However, spinosad-induced toxicological effects on non-target organisms must not be ignored. This study aimed to evaluate the cytotoxicity and potential genotoxicity of spinosad in HEK293 and HepG2 cell lines. The results showed that spinosad caused a concentration- and time-dependent decrease in cell viability of HEK293 and HepG2 cells. Spinosad-induced p53 accumulation thereby upregulates the expression of Bax and downregulates the expression of Bcl-2...
December 2016: Mutation Research
https://www.readbyqxmd.com/read/27908285/prevalence-and-location-of-the-secondary-mesiobuccal-canal-in-1-100-maxillary-molars-using-cone-beam-computed-tomography
#16
Pablo Betancourt, Pablo Navarro, Gonzalo Muñoz, Ramón Fuentes
BACKGROUND: Several articles have used cone beam computed tomography (CBCT) to study the morphology of the maxillary molars and to ascertain its ability to visualize the second mesiobuccal canal (MB2); however, its geometric location has not been examined in depth. The aim of this study was to describe in vivo the prevalence and location of the MB2 in the mesiobuccal root of the first maxillary molar (1MM) and the second maxillary molar (2MM) through CBCT imaging. METHODS: Five hundred fifty CBCT images of the 1MM and 550 of the 2MM were analyzed...
December 1, 2016: BMC Medical Imaging
https://www.readbyqxmd.com/read/27907154/pheromone-recognition-and-selectivity-by-comr-proteins-among-streptococcus-species
#17
Erin Shanker, Donald A Morrison, Antoine Talagas, Sylvie Nessler, Michael J Federle, Gerd Prehna
Natural transformation, or competence, is an ability inherent to bacteria for the uptake of extracellular DNA. This process is central to bacterial evolution and allows for the rapid acquirement of new traits, such as antibiotic resistance in pathogenic microorganisms. For the Gram-positive bacteria genus Streptococcus, genes required for competence are under the regulation of quorum sensing (QS) mediated by peptide pheromones. One such system, ComRS, consists of a peptide (ComS) that is processed (XIP), secreted, and later imported into the cytoplasm, where it binds and activates the transcription factor ComR...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27907105/epidemiology-of-brucellosis-and-genetic-diversity-of-brucella-abortus-in-kazakhstan
#18
Elena Shevtsova, Alexandr Shevtsov, Kasim Mukanov, Maxim Filipenko, Dinara Kamalova, Igor Sytnik, Marat Syzdykov, Andrey Kuznetsov, Assel Akhmetova, Mira Zharova, Talgat Karibaev, Pavel Tarlykov, Erlan Ramanculov
Brucellosis is a major zoonotic infection in Kazakhstan. However, there is limited data on its incidence in humans and animals, and the genetic diversity of prevalent strains is virtually unstudied. Additionally, there is no detailed overview of Kazakhstan brucellosis control and eradication programs. Here, we analyzed brucellosis epidemiological data, and assessed the effectiveness of eradication strategies employed over the past 70 years to counteract this infection. We also conducted multiple loci variable-number tandem repeat analysis (MLVA) of Brucella abortus strains found in Kazakhstan...
2016: PloS One
https://www.readbyqxmd.com/read/27906339/shaping-of-ultraviolet-femtosecond-laser-pulses-by-fourier-domain-harmonic-generation
#19
E Hertz, F Billard, G Karras, P Béjot, B Lavorel, O Faucher
We present a method to finely tailor ultraviolet femtosecond laser pulses using a pulse shaper with ability in the infrared/visible spectral range. We have developed to that end a frequency doubling module in which the up-conversion mechanism is carried out in the Fourier plane of a 4 f -line. The pulse shaper is used to imprint a spectral phase and/or amplitude onto the fundamental pulse. The shaped pulse is then frequency doubled through the module which transfers the applied spectral shaping to the second harmonic field in a predictable manner...
November 28, 2016: Optics Express
https://www.readbyqxmd.com/read/27906112/chromatin-wide-and-transcriptome-profiling-integration-uncovers-p38%C3%AE-mapk-as-a-global-regulator-of-skeletal-muscle-differentiation
#20
Jessica Segalés, Abul B M M K Islam, Roshan Kumar, Qi-Cai Liu, Pedro Sousa-Victor, F Jeffrey Dilworth, Esteban Ballestar, Eusebio Perdiguero, Pura Muñoz-Cánoves
BACKGROUND: Extracellular stimuli induce gene expression responses through intracellular signaling mediators. The p38 signaling pathway is a paradigm of the mitogen-activated protein kinase (MAPK) family that, although originally identified as stress-response mediator, contributes to establishing stem cell differentiation fates. p38α is central for induction of the differentiation fate of the skeletal muscle stem cells (satellite cells) through not fully characterized mechanisms. METHODS: To investigate the global gene transcription program regulated by p38α during satellite cell differentiation (myogenesis), and to specifically address whether this regulation occurs through direct action of p38α on gene promoters, we performed a combination of microarray gene expression and genome-wide binding analyses...
March 15, 2016: Skeletal Muscle
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