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https://www.readbyqxmd.com/read/28647489/a-high-throughput-assay-to-identify-substrate-selective-inhibitors-of-the-erk-protein-kinases
#1
Chad J Miller, Yagmur Muftuoglu, Benjamin E Turk
Extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylate a variety of substrates important for survival and proliferation, and their activity is frequently deregulated in tumors. ERK pathway inhibitors have shown clinical efficacy as anti-cancer drugs, but most patients eventually relapse due to reactivation of the pathway. One factor limiting the efficacy of current therapeutics is the difficulty in reaching clinically effective inhibition of the ERK pathway in the absence of on-target toxicities...
June 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28647265/evaluation-of-co-metabolic-removal-of-trichloroethylene-in-a-biotrickling-filter-under-acidic-conditions
#2
Dhawal Chheda, George A Sorial
This study investigated the removal of hydrophobic trichloroethylene (TCE) in the presence of methanol (co-metabolite) in a biotrickling filter, which was seeded with fungi at pH4. Starvation was chosen as the biomass control strategy. Two systems, Biofilter I (methanol:TCE 70:30) and Biofilter II (methanol:TCE 80:20) were run in parallel, each with varying composition ratios. The TCE loading rates for both biofilters ranged from 3.22 to 12.88g/m(3)/hr. Depending on the ratio, methanol concentrations varied from 4...
July 2017: Journal of Environmental Sciences (China)
https://www.readbyqxmd.com/read/28647218/the-environmental-performance-of-smes-in-the-brazilian-textile-industry-and-the-relationship-with-their-financial-performance
#3
Wagner Cezar Lucato, Elpidio Moreira Costa, Geraldo Cardoso de Oliveira Neto
Currently, the concern with the environment is increasing and organizations seek solutions to preserve nature and at the same time earn higher profits or competitiveness. For this, they make frequent use of structured procedures in order to reduce their costs and expenses. However, it has not been always considered the environmental performance related to the financial performance of these processes. Therefore, this study aimed to investigate the relationship between environmental performance measured by eco-efficiency level with the financial performance of small and medium textile manufacturing companies...
June 21, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/28647204/return-to-competition-after-an-achilles-tendon-rupture-using-both-on-and-off-the-field-load-monitoring-as-guidance-a-case-report-of-a-top-level-soccer-player
#4
Maurizio Fanchini, Franco M Impellizzeri, Karin Grävare Silbernagel, Franco Combi, Franco Benazzo, Mario Bizzini
OBJECTIVES: To describe the Return to competition after Achilles Tendon rupture (ATR) in an elite soccer player. DESIGN: Case report. SETTING: Return to sport (RTS) of a professional soccer player who suffered an ATR during a match. The RTS phase started 15 weeks after surgery and specific on-field activities were gradually introduced. Criteria used to monitor the transition through the different phases were strength and endurance of the calf muscle and ability to sustain specific on-field training loads (TL) monitored with Global Positioning System and heart-rate system...
April 29, 2017: Physical Therapy in Sport
https://www.readbyqxmd.com/read/28647091/phenotypic-screening-the-fast-track-to-novel-antibody-discovery
#5
REVIEW
Ralph R Minter, Alan M Sandercock, Steven J Rust
The majority of antibody therapeutics have been isolated from target-led drug discovery, where many years of target research preceded drug program initiation. However, as the search for validated targets becomes more challenging and target space becomes increasingly competitive, alternative strategies, such as phenotypic drug discovery, are gaining favour. This review highlights successful examples of antibody phenotypic screens that have led to clinical drug candidates. We also review the requirements for performing an effective antibody phenotypic screen, including antibody enrichment and target identification strategies...
March 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/28646788/muscle-dysmorphia-and-psychopathology-findings-from-an-italian-sample-of-male-bodybuilders
#6
Claudio Longobardi, Laura Elvira Prino, Matteo Angelo Fabris, Michele Settanni
The aim of this study is to investigate the relationship between the risk of muscle dysmorphia and psychopathological symptoms in an Italian sample of male bodybuilders. METHOD: The sample was recruited online (145 men with a mean age of 30.0 years) and participants were asked to fill out the Muscle Dysmorphic Disorder Inventory (MDDI), Symptom Cheklist-90-R (SCL-90-R), Dissociative Experiences Scale (DES-II), and to provide other socio-demographic data. Bodybuilders at risk of muscle dysmorphia display greater global psychopathology and present higher scores on all SCL-90-R dimensions when compared to bodybuilders not at risk of muscle dysmorphia...
June 17, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28646754/free-energy-analysis-of-cell-spreading
#7
Eóin McEvoy, Vikram S Deshpande, Patrick McGarry
In this study we present a steady-state adaptation of the thermodynamically motivated stress fiber (SF) model of Vigliotti et al. (2015). We implement this steady-state formulation in a non-local finite element setting where we also consider global conservation of the total number of cytoskeletal proteins within the cell, global conservation of the number of binding integrins on the cell membrane, and adhesion limiting ligand density on the substrate surface. We present a number of simulations of cell spreading in which we consider a limited subset of the possible deformed spread-states assumed by the cell in order to examine the hypothesis that free energy minimization drives the process of cell spreading...
June 7, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28646749/mutually-facilitated-co-transport-of-two-different-viruses-through-reactive-porous-media
#8
Shuang Xu, Ramesh Attinti, Elizabeth Adams, Jie Wei, Kalmia Kniel, Jie Zhuang, Yan Jin
In this study, we quantified transport and retention behaviors of a human pathogenic virus (Adenovirus 41, abbreviated as Ad-41) and a model bacteriophage (ϕX174) through metal oxide-removed and goethite-coated sand under saturated flow conditions. Two sets of bench scale column experiments were conducted: transport of each type of viruses alone and co-transport of both viruses. All experiments were conducted at pH 7.5 using 2 mM artificial ground water (AGW) buffer as background solution. Experimental results revealed that goethite-coated sand (i...
June 18, 2017: Water Research
https://www.readbyqxmd.com/read/28646631/synthesis-of-novel-and-functionally-selective-non-competitive-muscarinic-antagonists-as-chemical-probes
#9
John F Boulos, Jan Jakubik, John M Boulos, Jelena Momirov, Alena Randakova
Muscarinic receptors are known to play important biological roles and are drug targets for several human diseases. In a pilot study, novel muscarinic antagonists were synthesized and used as chemical probes to obtain additional information of the muscarinic pharmacophore. The design of these ligands made use of current orthosteric and allosteric models of drug-receptor interactions together with chemical motifs known to achieve muscarinic receptor selectivity. This approach has led to the discovery of several non-competitive muscarinic ligands that strongly bind at a secondary receptor site...
June 24, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28646419/repetition-blindness-in-priming-in-perceptual-identification-competitive-effects-of-a-word-intervening-between-prime-and-target
#10
Jennifer S Burt, Jessica Jolley
University students named a 72-ms masked target word that was preceded by two 120-ms consecutively presented words, a prime word followed by a distractor. In Experiment 1, all words were in lowercase letters, whereas in Experiment 2, the target word was changed to uppercase letters. In both experiments there was an accuracy and latency cost (repetition blindness: RB) when the prime was the same word as the target, with the cost much less severe in Experiment 2 than in Experiment 1. A low-frequency distractor impaired target identification compared with a high-frequency distractor...
June 23, 2017: Memory & Cognition
https://www.readbyqxmd.com/read/28646384/lipophilicity-influences-drug-binding-to-%C3%AE-1-acid-glycoprotein-f1-s-variants-but-not-to-the-a-variant
#11
Kazuhiko Hanada
OBJECTIVE: Human α1-acid glycoprotein has genetic variants, the F1, S, and A variants, which can be separated isoelectrophoretically. These variants show differences in their affinity of binding to several drugs. In this study, we investigated the factors determining drug binding to these α1-acid glycoprotein genetic variants using disopyramide, warfarin, and tamsulosin as marker compounds. METHODS: Binding of the marker drugs to human α1-acid glycoprotein was determined by ultra-filtration in the presence or absence of various other drugs...
June 23, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28646311/removal-of-arsenic-iii-v-by-a-granular-mn-oxide-doped-al-oxide-adsorbent-surface-characterization-and-performance
#12
Kun Wu, Jin Zhang, Bing Chang, Ting Liu, Furong Zhang, Pengkang Jin, Wendong Wang, Xiaochang Wang
In order to remove arsenic (As) from contaminated water, granular Mn-oxide-doped Al oxide (GMAO) was fabricated using the compression method with the addition of organic binder. The analysis results of XRD, SEM, and BET indicated that GMAO was microporous with a large specific surface area of 54.26 m(2/)g, and it was formed through the aggregation of massive Al/Mn oxide nanoparticles with an amorphous pattern. EDX, mapping, FTIR, and XPS results showed the uniform distribution of Al/Mn elements and numerous hydroxyl groups on the adsorbent surface...
June 23, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28646153/giant-rashba-effect-at-the-topological-surface-of-prge-revealing-antiferromagnetic-spintronics
#13
Soma Banik, Pranab Kumar Das, Azzedine Bendounan, Ivana Vobornik, A Arya, Nathan Beaulieu, Jun Fujii, A Thamizhavel, P U Sastry, A K Sinha, D M Phase, S K Deb
Rashba spin-orbit splitting in the magnetic materials opens up a new perspective in the field of spintronics. Here, we report a giant Rashba spin-orbit splitting on the PrGe [010] surface in the paramagnetic phase with Rashba coefficient α R  = 5 eVÅ. We find that α R can be tuned in this system as a function of temperature at different magnetic phases. Rashba type spin polarized surface states originates due to the strong hybridization between Pr 4f states with the conduction electrons. Significant changes observed in the spin polarized surface states across the magnetic transitions are due to the competition between Dzyaloshinsky-Moriya interaction and exchange interaction present in this system...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645941/a-first-time-in-human-study-of-gsk2636771-a-phosphoinositide-3-kinase-beta-selective-inhibitor-in-patients-with-advanced-solid-tumors
#14
Joaquin Mateo, Gopinath Ganji, Charlotte Lemech, Howard A Burris, Sae-Won Han, Karen E Swales, Shaun Decordova, Maurice P DeYoung, Deborah A Smith, Shanker Kalyana-Sundaram, Jiuhua Wu, Monica Motwani, Rakesh Kumar, Jerry M Tolson, Sun Young Rha, Hyun Cheol Chung, Joseph Paul Eder, Sunil Sharma, Yung-Jue Bang, Jeffrey R Infante, Li Yan, Johann S de Bono, Hendrik-Tobias Arkenau
The phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT) pathway is commonly activated in several tumor types. Selective targeting of p110β could result in successful pathway inhibition while avoiding the on and off target effects of pan-PI3K inhibitors. GSK2636771 is a potent, orally bioavailable, adenosine triphosphate-competitive, selective inhibitor of PI3Kβ.<br /><br />Experimental Design: <p>We evaluated the safety, pharmacokinetics, pharmacodynamics and antitumor activity of GSK2636771 to define the recommended Phase II dose (RP2D)...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28645641/homogenizing-bacterial-cell-factories-analysis-and-engineering-of-phenotypic-heterogeneity
#15
REVIEW
Dennis Binder, Thomas Drepper, Karl-Erich Jaeger, Frank Delvigne, Wolfgang Wiechert, Dietrich Kohlheyer, Alexander Grünberger
In natural habitats, microbes form multispecies communities that commonly face rapidly changing and highly competitive environments. Thus, phenotypic heterogeneity has evolved as an innate and important survival strategy to gain an overall fitness advantage over cohabiting competitors. However, in defined artificial environments such as monocultures in small- to large-scale bioreactors, cell-to-cell variations are presumed to cause reduced production yields as well as process instability. Hence, engineering microbial production toward phenotypic homogeneity is a highly promising approach for synthetic biology and bioprocess optimization...
June 20, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28645161/lncrna-tug1-influences-papillary-thyroid-cancer-cell-proliferation-migration-and-emt-formation-through-targeting-mir-145
#16
Hongwei Lei, Yan Gao, Xiaoying Xu
LncRNA TUG1, a tumor oncogene associated with various human cancers, has been reported to be involved in regulating various cellular processes, such as proliferation, apoptosis and invasion through targeting multiple genes. However, its biological function in thyroid cancer cells has not been elucidated. The aim of this study is to measure TUG1 expression level and evaluate its function in thyroid cancer cells. LncRNA TUG1 expression levels in thyroid cancer tissues and three thyroid cancer cell lines (the ATC cell lines SW1736 and KAT18 and the FTC cell line FTC133) were assessed by qRT-PCR and compared with that of the human normal breast epithelial cell HGC-27...
June 22, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28645085/extending-the-functionality-of-the-slurry-ferrihydrite-dgt-method-performance-evaluation-for-the-measurement-of-vanadate-arsenate-antimonate-and-molybdate-in-water
#17
Shu Zhang, Paul N Williams, Chun-Yang Zhou, Lena Q Ma, Jun Luo
The monitoring of oxyanions in waters, presents significant challenges due to their relatively low concentrations, and a characteristically changeable/unstable/reactive geochemistry with high spatial and temporal turnover. This results in a very heterogeneous pattern of mobility and bioavailability, which is difficult to capture reliably and in a cost effective manner. The diffusive gradients in thin-films (DGT) technique is a popular analytical tool for testing water quality, primarily because it provides a time-integrated measurement...
June 18, 2017: Chemosphere
https://www.readbyqxmd.com/read/28644959/generation-and-characterization-of-aptamers-targeting-factor-xia
#18
R S Woodruff, I Ivanov, I M Verhamme, M-F Sun, D Gailani, B A Sullenger
BACKGROUND: The plasma protease factor XIa (FXIa) has become a target of interest for therapeutics designed to prevent or treat thrombotic disorders. METHODS: We used a solution-based, directed evolution approach called systematic evolution of ligands by exponential enrichment (SELEX) to isolate RNA aptamers that target the FXIa catalytic domain. RESULTS: Two aptamers, designated 11.16 and 12.7, were identified that bound to previously identified anion binding and serpin bindings sites on the FXIa catalytic domain...
June 9, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28644915/mechanistic-insights-on-the-reduction-of-co2-to-silylformates-catalyzed-by-ir-nsin-species
#19
Luis A Oro, Alejandro Julián, Jefferson Guzmán, E A Jaseer, Francisco Fernández-Alvarez, Raquel Royo, Victor Polo, María Pilar García Orduña, Fernando Lahoz
The hydrosilylation of CO2 with different silanes such as HSiEt3, HSiMe2Ph, HSiMePh2, HSiMe(OSiMe3)2 and HSi(OSiMe3)3 in presence of catalytic ammounts of the iridium(III) complex [Ir(H)(CF3CO2)(NSiN*)(coe)] (1; NSiN* = fac-bis-(4-methylpyridine-2-yloxy); coe = cis-cyclooctene) has been comparatively studied. The activity of the hydrosilylation catalytic system based on 1 depends on the nature of the reducing agent, where HSiMe(OSiMe3)2 has proven to be the most active. The aforementioned reactions were found to be highly selective to the formation of the corresponding silylformate...
June 23, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28644858/the-flame-retardant-de-71-a-mixture-of-polybrominated-diphenyl-ethers-inhibits-human-differentiated-thyroid-cell-function-in-vitro
#20
Thit Mynster Kronborg, Juliana Frohnert Hansen, Åse Krogh Rasmussen, Katrin Vorkamp, Claus Henrik Nielsen, Marie Frederiksen, Jacob Hofman-Bang, Christoffer Holst Hahn, Louise Ramhøj, Ulla Feldt-Rasmussen
BACKGROUND: Normal thyroid function is essential for general growth and metabolism, but can be affected by endocrine disrupting chemicals (EDCs). Polybrominated diphenyl ethers (PBDEs) have been used worldwide to reduce flammability in different materials and are suspected to be EDCs. The production of the commercial Penta- and OctaBDE mixtures is banned, but DecaBDEs and existing products may leak PBDEs into the environment. Our aim was to investigate the effect of the PentaBDE mixture DE-71 on human thyroid cells in vitro...
2017: PloS One
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