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Double robustness

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https://www.readbyqxmd.com/read/28542620/elevated-catalase-expression-in-a-fungal-pathogen-is-a-double-edged-sword-of-iron
#1
Arnab Pradhan, Carmen Herrero-de-Dios, Rodrigo Belmonte, Susan Budge, Angela Lopez Garcia, Aljona Kolmogorova, Keunsook K Lee, Brennan D Martin, Antonio Ribeiro, Attila Bebes, Raif Yuecel, Neil A R Gow, Carol A Munro, Donna M MacCallum, Janet Quinn, Alistair J P Brown
Most fungal pathogens of humans display robust protective oxidative stress responses that contribute to their pathogenicity. The induction of enzymes that detoxify reactive oxygen species (ROS) is an essential component of these responses. We showed previously that ectopic expression of the heme-containing catalase enzyme in Candida albicans enhances resistance to oxidative stress, combinatorial oxidative plus cationic stress, and phagocytic killing. Clearly ectopic catalase expression confers fitness advantages in the presence of stress, and therefore in this study we tested whether it enhances fitness in the absence of stress...
May 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542439/host-mediated-inflammatory-influence-on-glioblastoma-multiforme-recurrence-following-high-dose-ionizing-radiation
#2
J Tyson McDonald, Xuefeng Gao, Cole Steber, Jawon Lee Breed, Caitlin Pollock, Lili Ma, Lynn Hlatky
Despite optimal clinical treatment, glioblastoma multiforme (GBM) inevitably recurs. Standard treatment of GBM, exposes patients to radiation which kills tumor cells, but also modulates the molecular fingerprint of any surviving tumor cells and the cross-talk between those cells and the host. Considerable investigation of short-term (hours to days) post-irradiation tumor cell response has been undertaken, yet long-term responses (weeks to months) which are potentially even more informative of recurrence, have been largely overlooked...
2017: PloS One
https://www.readbyqxmd.com/read/28541575/xenobiotic-car-activators-induce-dlk1-dio3-locus-non-coding-rna-expression-in-mouse-liver
#3
Lucie Pouché, Antonio Vitobello, Michael Römer, Milica Glogovac, A Kenneth MacLeod, Heidrun Ellinger-Ziegelbauer, Magdalena Westphal, Valérie Dubost, Daniel Philipp Stiehl, Bérengère Dumotier, Alexander Fekete, Pierre Moulin, Andreas Zell, Michael Schwarz, Rita Moreno, Jeffrey T J Huang, Cliff R Elcombe, Colin J Henderson, C Roland Wolf, Jonathan G Moggs, Rémi Terranova
Derisking xenobiotic-induced non-genotoxic carcinogenesis (NGC) represents a significant challenge during the safety assessment of chemicals and therapeutic drugs. The identification of robust mechanism-based NGC biomarkers has the potential to enhance cancer hazard identification. We previously demonstrated Constitutive Androstane Receptor (CAR) and WNT signaling-dependent up-regulation of the pluripotency associated Dlk1-Dio3 imprinted gene cluster non-coding RNAs (ncRNAs) in the liver of mice treated with tumor-promoting doses of phenobarbital (PB)...
May 25, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28540870/atorvastatin-as-adjunctive-therapy-for-chronic-plaque-type-psoriasis-versus-betamethasone-valerate-alone-a-randomized-double-blind-placebo-controlled-trial
#4
Sharlene Helene H Chua, Giselle Marie S Tioleco, Carmela Augusta F Dayrit, Winlove P Mojica, Belen L Dofitas, Lorna F Frez
BACKGROUND: Psoriasis is a T helper 1 cell-mediated chronic inflammation. Statins have been found to have anti-inflammatory and immunomodulatory effects targeting T helper 1 cells and thus, are being investigated as treatments for psoriasis. AIMS: To investigate the efficacy and safety of atorvastatin as adjunctive treatment for mild to moderate chronic plaque psoriasis; and the impact of atorvastatin on quality of life. The study also aimed to correlate the beneficial effects of atorvastatin with its lipid-lowering effects...
May 23, 2017: Indian Journal of Dermatology, Venereology and Leprology
https://www.readbyqxmd.com/read/28538186/an-engineered-virus-library-as-a-resource-for-the-spectrum-wide-exploration-of-virus-and-vector-diversity
#5
Wenli Zhang, Jun Fu, Jing Liu, Hailong Wang, Maren Schiwon, Sebastian Janz, Lukas Schaffarczyk, Lukas von der Goltz, Eric Ehrke-Schulz, Johannes Dörner, Manish Solanki, Philip Boehme, Thorsten Bergmann, Andre Lieber, Chris Lauber, Andreas Dahl, Andreas Petzold, Youming Zhang, A Francis Stewart, Anja Ehrhardt
Adenoviruses (Ads) are large human-pathogenic double-stranded DNA (dsDNA) viruses presenting an enormous natural diversity associated with a broad variety of diseases. However, only a small fraction of adenoviruses has been explored in basic virology and biomedical research, highlighting the need to develop robust and adaptable methodologies and resources. We developed a method for high-throughput direct cloning and engineering of adenoviral genomes from different sources utilizing advanced linear-linear homologous recombination (LLHR) and linear-circular homologous recombination (LCHR)...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28537617/buoyancy-increase-and-drag-reduction-through-a-simple-superhydrophobic-coating
#6
Gi Byoung Hwang, Adnan Patir, Kristopher Page, Yao Lu, Elaine Allan, Ivan P Parkin
A superhydrophobic paint was fabricated using 1H,1H,2H,2H-perfluorooctyltriethoxysilane (PFOTES), TiO2 nanoparticles and ethanol. The paint has potential for aquatic application of a superhydrophobic coating as it induces increased buoyancy and drag reduction. Buoyance testing showed that the reduction of surface energy by superhydrophobic coating made it feasible that glass, a high density material, was supported by the surface tension of water. In a miniature boat sailing test, it was shown that the low energy surface treatment decreased the adhesion of water molecules to the surface of the boat resulting in a reduction of the drag force...
May 24, 2017: Nanoscale
https://www.readbyqxmd.com/read/28535670/ultrafast-spectroscopy-reveals-electron-transfer-cascade-that-improves-hydrogen-evolution-with-carbon-nitride-photocatalysts
#7
Kathryn L Corp, Cody W Schlenker
Solar hydrogen generation from water represents a compelling component of a future sustainable energy portfolio. Recently, chemically-robust heptazine-based polymers known as graphitic carbon nitrides (g-C3N4) have emerged as promising photocatalysts for hydrogen evolution using visible light while withstanding harsh chemical environments. However, since g-C3N4 electron transfer dynamics are poorly understood, rational design rules for improving activity remain unclear. Here, we use visible and near-infrared femtosecond transient absorption (TA) spectroscopy to reveal an electron transfer cascade that correlates with a near-doubling in photocatalytic activity from 2050 µmol h(-1)g(-1) to 3810 µmol h(-1)g(-1) when we infuse a suspension of bulk g-C3N4 with 10% mass loading of chemically exfoliated carbon nitride...
May 23, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28534609/au-promoted-nickel-iron-layered-double-hydroxide-nanoarrays-a-modular-catalyst-enabling-high-performance-oxygen-evolution
#8
Wenxin Zhu, Lizhi Liu, Zhihao Yue, Wentao Zhang, Xiaoyue Yue, Jing Wang, Shaoxuan Yu, Li Wang, Jianlong Wang
Oxygen evolution reaction (OER) has played a pivotal role in many energy conversion and storage technologies like water electrolysis, fuel cells, and metal-air batteries. However, the slow kinetics of OER limit the performance and commercialization of such devices. Herein, we report on NiFe LDH@Au hybrid nanoarrays on Ni foam for much enhanced OER. By hybridization of electronegative Au and NiFe LDH with intrinsic remarkable OER catalytic activity, this modular electrode could drive an overall ultrahigh-performance and robust OER in base with the demand of overpotentials of only 221, 235 and 270 mV to afford 50, 100 and 500 mA cm-2, respectively...
May 23, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28533548/lack-of-inflammatory-gene-expression-in-bats-a-unique-role-for-a-transcription-repressor
#9
Arinjay Banerjee, Noreen Rapin, Trent Bollinger, Vikram Misra
In recent years viruses similar to those that appear to cause no overt disease in bats have spilled-over to humans and other species causing serious disease. Since pathology in such diseases is often attributed to an over-active inflammatory response, we tested the hypothesis that bat cells respond to stimulation of their receptors for viral ligands with a strong antiviral response, but unlike in human cells, the inflammatory response is not overtly activated. We compared the response of human and bat cells to poly(I:C), a viral double-stranded RNA surrogate...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28532387/robust-estimation-of-the-expected-survival-probabilities-from-high-dimensional-cox-models-with-biomarker-by-treatment-interactions-in-randomized-clinical-trials
#10
Nils Ternès, Federico Rotolo, Stefan Michiels
BACKGROUND: Thanks to the advances in genomics and targeted treatments, more and more prediction models based on biomarkers are being developed to predict potential benefit from treatments in a randomized clinical trial. Despite the methodological framework for the development and validation of prediction models in a high-dimensional setting is getting more and more established, no clear guidance exists yet on how to estimate expected survival probabilities in a penalized model with biomarker-by-treatment interactions...
May 22, 2017: BMC Medical Research Methodology
https://www.readbyqxmd.com/read/28530287/microfluidic-self-assembly-of-folate-targeted-monomolecular-sirna-lipid-nanoparticles
#11
R Krzysztoń, B Salem, D J Lee, G Schwake, E Wagner, J O Rädler
Non-viral delivery of nucleic acids for therapies based on RNA interference requires a rational design and optimal self-assembly strategies. Nucleic acid particles need to be small, stable and functional in terms of selective cell uptake and controlled release of encapsulated nucleic acids. Here we report on small (∼38 nm) monomolecular nucleic acid/lipid particles (mNALPs) that contain single molecules of short double-stranded oligonucleotides covered by a tight, highly curved lipid bilayer. The particles consist of DOPE, DOTAP, DOPC and DSPE-PEG(2000) and are assembled with 21 bp double-stranded DNA or small interfering RNA by solvent exchange on a hydrodynamic-focusing microfluidic chip...
May 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28530231/constraining-climate-sensitivity-and-continental-versus-seafloor-weathering-using-an-inverse-geological-carbon-cycle-model
#12
Joshua Krissansen-Totton, David C Catling
The relative influences of tectonics, continental weathering and seafloor weathering in controlling the geological carbon cycle are unknown. Here we develop a new carbon cycle model that explicitly captures the kinetics of seafloor weathering to investigate carbon fluxes and the evolution of atmospheric CO2 and ocean pH since 100 Myr ago. We compare model outputs to proxy data, and rigorously constrain model parameters using Bayesian inverse methods. Assuming our forward model is an accurate representation of the carbon cycle, to fit proxies the temperature dependence of continental weathering must be weaker than commonly assumed...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529839/estimating-effects-with-rare-outcomes-and-high-dimensional-covariates-knowledge-is-power
#13
Laura Balzer, Jennifer Ahern, Sandro Galea, Mark van der Laan
Many of the secondary outcomes in observational studies and randomized trials are rare. Methods for estimating causal effects and associations with rare outcomes, however, are limited, and this represents a missed opportunity for investigation. In this article, we construct a new targeted minimum loss-based estimator (TMLE) for the effect or association of an exposure on a rare outcome. We focus on the causal risk difference and statistical models incorporating bounds on the conditional mean of the outcome, given the exposure and measured confounders...
December 2016: Epidemiologic Methods
https://www.readbyqxmd.com/read/28524678/filling-enforced-magnetic-dirac-semimetals-in-two-dimensions
#14
Steve M Young, Benjamin J Wieder
Filling-enforced Dirac semimetals, or those required at specific fillings by the combination of crystalline and time-reversal symmetries, have been proposed in numerous materials. However, Dirac points in these materials are not generally robust against breaking or modifying time-reversal symmetry. We present a new class of two-dimensional Dirac semimetal protected by the combination of crystal symmetries and a special, antiferromagnetic time-reversal symmetry. Systems in this class of magnetic layer groups, while having broken time-reversal symmetry, still respect the operation of time-reversal followed by a half-lattice translation...
May 5, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28511660/simvastatin-for-patients-with-acute-respiratory-distress-syndrome-long-term-outcomes-and-cost-effectiveness-from-a-randomised-controlled-trial
#15
A Agus, C Hulme, R M Verghis, C McDowell, C Jackson, C M O'Kane, J G Laffey, D F McAuley
BACKGROUND: Simvastatin therapy for patients with acute respiratory distress syndrome (ARDS) has been shown to be safe and associated with minimal adverse effects, but it does not improve clinical outcomes. The aim of this research was to report on mortality and cost-effectiveness of simvastatin in patients with ARDS at 12 months. METHODS: This was a cost-utility analysis alongside a multicentre, double-blind, randomised controlled trial carried out in the UK and Ireland...
May 17, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28510574/dose-of-antivenom-for-the-treatment-of-snakebite-with-neurotoxic-envenoming-evidence-from-a-randomised-controlled-trial-in-nepal
#16
Emilie Alirol, Sanjib Kumar Sharma, Anup Ghimire, Antoine Poncet, Christophe Combescure, Chabilal Thapa, Vijaya Prasad Paudel, Kalidas Adhikary, Walter Robert Taylor, David Warrell, Ulrich Kuch, François Chappuis
BACKGROUND: Currently, there is inadequate evidence on which to base clinical management of neurotoxic snakebite envenoming, especially in the choice of initial antivenom dosage. This randomised controlled trial compared the effectiveness and safety of high versus low initial antivenom dosage in victims of neurotoxic envenoming. METHODOLOGY/ PRINCIPAL FINDINGS: This was a balanced, randomised, double-blind trial that was conducted in three health care centers located in the Terai plains of Nepal...
May 16, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28505485/interventions-affecting-mortality-in-critically-ill-and-perioperative-patients-a-systematic-review-of-contemporary-trials
#17
Martina Baiardo Redaelli, Giovanni Landoni, Stefania Di Sanzo, Samuele Frassoni, Chiara Sartini, Luca Cabrini, Giacomo Monti, Mara Scandroglio, Alberto Zangrillo, Rinaldo Bellomo
PURPOSE: Confounders in randomized controlled trials (RCTs) reporting significant effects on mortality in critically ill patients using non-surgical techniques have not been systematically explored. We aimed to identify factors unrelated to the reported intervention that might have affected the findings and robustness of such trials. METHODS: We searched Pubmed/MEDLINE for all RCTs on any non-surgical interventions reporting an effect on unadjusted mortality in critically ill patients between 1/1/2000 and 1/12/2015...
May 4, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28503717/a-review-of-the-current-challenges-associated-with-the-development-of-an-artificial-pancreas-by-a-double-subcutaneous-approach
#18
REVIEW
Sverre Christian Christiansen, Anders Lyngvi Fougner, Øyvind Stavdahl, Konstanze Kölle, Reinold Ellingsen, Sven Magnus Carlsen
INTRODUCTION: Patients with diabetes type 1 (DM1) struggle daily to achieve good glucose control. The last decade has seen a rush of research groups working towards an artificial pancreas (AP) through the application of a double subcutaneous approach, i.e., subcutaneous (SC) continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion. Few have focused on the fundamental limitations of this approach, especially regarding outcome measures beyond time in range. METHODS: Based on insulin physiology, the limitations of CGM, SC insulin absorption, meal challenge, and physical activity in DM1 patients, we discuss the limitations of the double SC approach...
May 13, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28498808/restoration-of-p53-using-the-novel-mdm2-p53-antagonist-apg115-suppresses-dedifferentiated-papillary-thyroid-cancer-cells
#19
Haibo Chen, Dingyuan Luo, Lin Zhang, Xiaofeng Lin, Qiuyun Luo, Hanjie Yi, Jing Wang, Xianglei Yan, Baoxia Li, Yuelei Chen, Xingguang Liu, Hong Zhang, Sheng Liu, Miaozhen Qiu, Dajun Yang, Ningyi Jiang
Dedifferentiated papillary thyroid cancer (DePTC) is characterized by aggressive growth, recurrence, distant metastasis, and resistance to radioactive iodine (RAI) therapy. DePTC is also accompanied by poor prognosis and high early-mortality. Nevertheless, most DePTC cells show intact p53 downstream functionality. In cells with wild-type p53, the murine double minute2 (MDM2) protein interacts with p53 and abrogates its activity. Inhibition of the MDM2-p53 interaction restores p53 activity and leads to cell cycle arrest and apoptosis...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28498669/a-multi-scale-model-for-electrokinetic-transport-in-networks-of-pores-part-i-model-derivation
#20
Shima Alizadeh, Ali Mani
We present an efficient and robust numerical model for simulation of electrokinetic phenomena in porous media and microstructure networks considering a wide range of applications including energy conversion, deionization, and microfluidic-based lab-on-a-chip systems. Coupling between fluid flow and ion transport in these networks is governed by the Poisson-Nernst-Planck-Stokes equations. These equations describe a wide range of phenomena that can interact in a complex fashion when coupled in networks involving multiple pores with variable properties...
May 12, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
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