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Brian T Donovan, Deepak Bandyopadhyay, Chaya Duraiswami, Christopher J Nixon, Claire Y Townsend, Stan F Martens
Despite the importance of the hERG channel in drug discovery and the sizable number of antagonist molecules discovered, only a few hERG agonists have been discovered. Here we report a novel hERG agonist; SKF-32802 and a structural analog of the agonist NS3623, SB-335573. These were discovered through a similarity search of published hERG agonists. SKF-32802 incorporates an amide linker rather than NS3623's urea, resulting in a compound with a different mechanism of action. We find that both compounds decrease the time constant of open channel kinetics, increase the amplitude of the envelope of tails assay, mildly increased the amplitude of the IV curve, bind the hERG channel in either open or closed states, increase the plateau of the voltage dependence of activation and modulate the effects of the hERG antagonist, quinidine...
October 16, 2017: European Journal of Pharmacology
Nikola Stan, Frederick Seng, LeGrand Shumway, Rex King, Stephen Schultz
Voltage in a coaxial cable is measured by an electric-field optical fiber sensor exploiting the proportionality of voltage and electric field in a fixed structure. The sensor is inserted in a hole drilled through the dielectric of the RG-218 coaxial cable and sealed with epoxy to displace all air and prevent the adverse effects of charge buildup during high-voltage measurements. It is shown that the presence of the sensor in the coaxial cable does not significantly increase electrical reflections in the cable...
August 20, 2017: Applied Optics
Frederick Seng, Zhenchao Yang, Rex King, LeGrand Shumway, Nikola Stan, Alec Hammond, Karl F Warnick, Stephen Schultz
This work introduces a passive dipole antenna integrated into the packaging of a slab-coupled optical sensor to enhance the directional sensitivity of electro-optic electric field measurements parallel to the fiber axis. Using the passive integrated dipole antenna described in this work, a sensor that can typically only sense fields transverse to the fiber direction is able to sense a 1.25 kV/m field along the fiber direction with a gain of 17.5. This is verified through simulation and experiment.
June 10, 2017: Applied Optics
Maimuna S Majumder, John S Brownstein, Stan N Finkelstein, Richard C Larson, Lydia Bourouiba
Background: Nosocomial amplification resulted in nearly 200 cases of Middle East respiratory syndrome (MERS) during the 2015 South Korean MERS-coronavirus outbreak. It remains unclear whether certain types of cases were more likely to cause secondary infections than others, and if so, why. Methods: Publicly available demographic and transmission network data for all cases were collected from the Ministry of Health and Welfare. Statistical analyses were conducted to determine the relationship between demographic characteristics and the likelihood of human-to-human transmission...
June 1, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
Murray M Humphries, Emily K Studd, Allyson K Menzies, Stan Boutin
From a trophic perspective, a seasonal increase in air temperature and photoperiod propagates as bottom-up pulse of primary production by plants, secondary production by herbivores, and tertiary production by carnivores. However, food web seasonality reflects not only abiotic variation in temperature and photoperiod, but also the composition of the biotic community and their functional responses to this variation. Some plants and animals-here referred to as seasonal specialists-decouple from food webs in winter through migration or various forms of metabolic arrest (e...
October 12, 2017: Integrative and Comparative Biology
Stan J Monstrey
No abstract text is available yet for this article.
September 9, 2017: Aesthetic Surgery Journal
Christoph Hirche, Antonella Citterio, Henk Hoeksema, Ján Koller, Martina Lehner, José Ramón Martinez, Stan Monstrey, Alexandra Murray, Jan A Plock, Frank Sander, Alexandra Schulz, Benjamin Ziegler, Ulrich Kneser
Early debridement and/or eschar removal is regarded as a significant step in the treatment of deep partial and full thickness burns. It aims to control wound bioburden and allows early wound closure by conservative treatment or skin grafting. Preservation of viable dermis accompanied by early wound closure, is regarded as a necessary step to reduce scar related complication, e.g. functional limitations and/or unaesthetic scar formation. Aside from the classical techniques of surgical excision as tangential excision for eschar removal, hydro-surgery, maggot therapy, laser, enzymatic debridement have been described as additional techniques in the burn surgeon's armamentarium...
October 12, 2017: Burns: Journal of the International Society for Burn Injuries
Adam G Kreutzer, Ryan K Spencer, Kate J McKnelly, Stan Yoo, Imane L Hamza, Patrick J Salveson, James S Nowick
The absence of high-resolution structures of amyloid oligomers constitutes a major gap in our understanding of amyloid diseases. Increasing evidence indicates that oligomers of the β-amyloid peptide Aβ are especially important in the progression of Alzheimer's disease. In many Aβ oligomers, the Aβ monomer components are thought to adopt a β-hairpin conformation. This paper describes the design and study of a macrocyclic β-hairpin peptide derived from Aβ16-36. SDS-PAGE and size exclusion chromatography studies show that the Aβ16-36 β-hairpin peptide assembles in solution to form hexamers, trimers, and dimers...
October 13, 2017: Biochemistry
Muhammad H Alu'datt, Taha Rababah, Mohammad N Alhamad, Ghaid J Al-Rabadi, Carole C Tranchant, Ali Almajwal, Stan Kubow, Inteaz Alli
Phenolic phytochemicals have become of interest due to their therapeutic potential, particularly with regards to their anti-cancer, anti-inflammatory, hypolipidemic, and hypoglycemic properties. An evolving area of research involving phenolics in foods and their products pertains to the functional, biological, and nutritional consequences resulting from the binding between certain phenolic compounds and the macronutrient and micronutrient constituents of foods. The goal of this review is to provide a summary of studies investigating endogenous phenolic interactions with major components in food systems, including carbohydrates, proteins, lipids, minerals and vitamins, with a focus on the phenolic compounds and nutrients in oil-bearing plants...
October 13, 2017: Critical Reviews in Food Science and Nutrition
Stan Skinner, Robert Holdefer, John J McAuliffe, Francesco Sala
Error avoidance in medicine follows similar rules that apply within the design and operation of other complex systems. The error-reduction concepts that best fit the conduct of testing during intraoperative neuromonitoring are forgiving design (reversibility of signal loss to avoid/prevent injury) and system redundancy (reduction of false reports by the multiplication of the error rate of tests independently assessing the same structure). However, error reduction in intraoperative neuromonitoring is complicated by the dichotomous roles (and biases) of the neurophysiologist (test recording and interpretation) and surgeon (intervention)...
October 10, 2017: Journal of Clinical Neurophysiology: Official Publication of the American Electroencephalographic Society
Richard R Watkins, Stan Deresinski
Early and appropriate empiric antibiotics are essential for achieving the best possible outcomes in sepsis. Yet, the choice of antibiotic therapy has become more challenging due to recent reports of nephrotoxicity with the combination of vancomycin and piperacillin/tazobactam, the "workhorse" regimen at many institutions. In this article we assess the evidence for nephrotoxicity and its possible mechanisms, provide recommendations for risk mitigation, address the advantages and disadvantages of alternative antibiotic choices, and suggest areas for future research...
July 29, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Jingyi Ma, L Stan Leung
The involvement of posterior cingulate cortex (PCC) on ketamine-induced psychosis relevant behaviors was investigated in rats. Bilateral infusion of muscimol, a GABAA receptor agonist, into the PCC significantly antagonized ketamine-induced deficit in prepulse inhibition of a startle reflex (PPI), deficit in gating of hippocampal auditory evoked potentials, and behavioral hyperlocomotion in a dose dependent manner. Local infusion of ketamine directly into the PCC also induced a PPI deficit. Systemic injection of ketamine (3mg/kg,s...
October 7, 2017: Behavioural Brain Research
Matthew Y Lim, Jonathon O'Brien, Joao A Paulo, Steven P Gygi
Phosphorylation stoichiometry, or occupancy, is one element of phosphoproteomics that can add useful biological context(1). We previously developed a method to assess phosphorylation stoichiometry on a proteome-wide scale(2). The stoichiometry calculation relies on identifying and measuring the levels of each nonphosphorylated counterpart peptide with and without phosphatase treatment. The method, however, is problematic in that low stoichiometry phosphopeptides can return negative stoichiometry values if measurement error is larger than the percent stoichiometry...
October 6, 2017: Journal of Proteome Research
Clayton T Lamb, Garth Mowat, Sophie L Gilbert, Bruce N McLellan, Scott E Nielsen, Stan Boutin
Brown bears are known to use rubbing behavior as a means of chemical communication, but the function of this signaling is unclear. One hypothesis that has gained support is that male bears rub to communicate dominance to other males. We tested the communication of dominance hypothesis in a low-density brown bear population in southeast British Columbia. We contrasted rubbing rates for male and female bears during and after the breeding season using ten years of DNA-mark-recapture data for 643 individuals. Here we demonstrate that male brown bears rub 60% more during the breeding than the non-breeding season, while female rubbing had no seasonal trends...
2017: PloS One
Ziming Yang, Sihang Yang, Joy D Van Nostrand, Jizhong Zhou, Wei Fang, Qi Qi, Yurong Liu, Stan D Wullschleger, Liyuan Liang, David E Graham, Yunfeng Yang, Baohua Gu
Microbial decomposition of soil organic carbon (SOC) in thawing Arctic permafrost is important in determining greenhouse gas feedbacks of tundra ecosystems to climate. However, the changes in microbial community structure during SOC decomposition are poorly known. Here we examine these changes using frozen soils from Barrow, Alaska, USA, in anoxic microcosm incubation at -2 and 8°C for 122 days. The functional gene array GeoChip was used to determine microbial community structure and the functional genes associated with SOC degradation, methanogenesis, and Fe(III) reduction...
2017: Frontiers in Microbiology
Jeroen D Langereis, Peter Pickkers, Stan de Kleijn, Jelle Gerretsen, Marien I de Jonge, Matthijs Kox
The immune inhibitory checkpoint molecule programmed death ligand (PD-L)-1 is increasingly recognized as an important player in the immune suppression observed in patients with sepsis, but its role has mainly been studied in monocytes. In an earlier study, we demonstrated that experimental human endotoxemia results in mobilization of a subset of PD-L1-expressing neutrophils displaying an IFN-γ-induced transcriptome profile. Herein, we identify the source of IFN-γ production during murine endotoxemia and its role in the generation of PD-L1(+)-suppressive neutrophils...
October 3, 2017: Journal of Leukocyte Biology
Tarmo Äijö, Christian L Müller, Richard Bonneau
Motivation: The number of microbial and metagenomic studies has increased drastically due to advancements in next-generation sequencing-based measurement techniques. Statistical analysis and the validity of conclusions drawn from (time series) 16S rRNA and other metagenomic sequencing data is hampered by the presence of significant amount of noise and missing data (sampling zeros). Accounting uncertainty in microbiome data is often challenging due to the difficulty of obtaining biological replicates...
September 13, 2017: Bioinformatics
Tara M Roth, Janet Foley, Stan Wright
To characterize the inter-epidemic ecology of Francisella tularensis, we surveyed vertebrates and invertebrates for the abundance, spatial distribution, and status of infection at a site in northern California that had evidence of endemic type B tularemia. We collected 2910 mosquitoes, 77 biting flies, 704 ticks, 115 mammals, and 1911 aquatic invertebrates in 2013-2014. Real-time PCR on all mosquitoes, 40 biting flies, 113 aquatic invertebrates, and 650 ticks did not detect F. tularensis DNA. Indirect enzyme linked immunosorbent assay (ELISA) on 109 mammals revealed 2 (of 2, 100%) seropositive feral cats, 1 (of 24, 4...
October 2, 2017: Vector Borne and Zoonotic Diseases
Edward R Duranty, Timothy J Roosendaal, Stan G Pitman, Joseph C Tucker, Stanley L Owsley, Jonathan D Suter, Kyle J Alvine
High pressure hydrogen effects on the friction and wear of polymers are of importance to myriad applications. Of special concern are those used in the infrastructure for hydrogen vehicle refueling stations, including compressor sliding seals, valves, and actuators. While much is known about potentially damaging embrittlement effects of hydrogen on metals, relatively little is known about the effects of high pressure hydrogen on polymers. However, based on the limited results that are published in the literature, polymers also apparently exhibit compatibility issues with hydrogen...
September 2017: Review of Scientific Instruments
Jarrad H Van Stan, Se-Woong Park, Matthew Jarvis, Daryush D Mehta, Robert E Hillman, Dagmar Sternad
Successful voice training (e.g., singing lessons) and vocal rehabilitation (e.g., therapy for a voice disorder) involve learning complex, vocal behaviors. However, there are no metrics describing how humans learn new vocal skills or predicting how long the improved behavior will persist post-therapy. To develop measures capable of describing and predicting vocal motor learning, a theory-based paradigm from limb motor control inspired the development of a virtual task where subjects throw projectiles at a target via modifications in vocal pitch and loudness...
September 2017: Journal of the Acoustical Society of America
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