bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statins ameliorate pulmonary hypertension secondary to left ventricular dysfunction through the Rho‐kinase pathway and NADPH oxidase
Authors: Chen I‐Chen , Tan Mian‐Shin , Wu Bin‐Nan , Chai Chee‐Yin , Yeh Jwu‐Lai , Chou Shah‐Hwa , Chen Ing‐Jun , Dai Zen‐Kong 
Published: December 2016

SummaryBackgroundPulmonary hypertension (PH) is a devastating disorder, for which no therapy is curative. It has been reported that pulmonary vascular remodeling, associated with increasing mean pulmonary arterial pressure and upregulated expression of endothelial nitric oxide synthase (eNOS), endothelin‐1 (ET‐1), RhoA/RhoH‐kinase results in the development of PH. Oxidative stress and the RhoA/Rho‐kinase pathway are also thought to be involved in the pathophysiology of PH. Statins are 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (HMG‐CoA reductase inhibitors) with pleiotropic effects and are potential agents for the treatment of PH. In this study, we investigated the beneficial effects of simvastatin on the development of PH secondary to left ventricular dysfunction.MethodsA PH secondary to left ventricular dysfunction model was established in 6‐week‐old aortic‐banded rats. The pulmonary expression of Rho kinase, ET‐1, eNOS, p‐eNOS, nitrite/nitrate (NOx), cGMP, p47Phox, and p67Phox were investigated in the early‐treatment group, to which was administered simvastatin (30 mg/kg/day) from days 1 to 42 or the late‐treatment group, to which was administered simvastatin (30 mg/kg/day) from days 29 to 42.ResultsSimvastatin attenuated the mean pulmonary artery pressure, pulmonary arteriolar remodeling, plasma brain natriuretic peptide, ET‐1, reactive oxygen species, and the NADPH oxidase 2 regulatory subunits, p47Phox and p67Phox, and upregulated pulmonary p‐eNOS, NOx, and cGMP in both the early‐ and late‐treated groups.ConclusionsInhibiting HMG‐CoA reductase may have therapeutic potential for preventing and attenuating the development of PH in left ventricular dysfunction through the Rho‐kinase pathway and NADPH oxidase. A translational study in humans is needed to substantiate these findings. Pediatr Pulmonol. 2017;52:443–457. © 2016 Wiley Periodicals, Inc.
Pulmonary hemorrhage as a complication of Respiratory Syncyntial Virus (RSV) bronchiolitis
Authors: Soo Audrey K.S. , Inwald David P. 
Published: December 2016

SummaryRespiratory Syncytial Virus (RSV) is a common cause of bronchiolitis. Although there are a number of recognized complications, pulmonary hemorrhage has not been reported previously. A retrospective case notes review was performed through an electronic search of a Pediatric Intensive Care Unit's medical records. Seven patients with RSV infection and pulmonary hemorrhage were identified and included in this case series. Six of the seven patients were born prematurely (30–36 weeks gestation). All patients required blood transfusion. The pulmonary hemorrhage events all occurred after a period of mechanical ventilation and following extubation. All of the patients required reintubation with a mean of 5 further days of mechanical ventilation. Pulmonary hemorrhage is an uncommon complication of RSV infection, which has not been reported previously in the literature. Further studies are required to determine incidence, pathogenesis, and outcome. Pediatr Pulmonol. 2017;52:E32–E36. © 2016 Wiley Periodicals, Inc.
In vitro labeling strategies for in cellulo fluorescence microscopy of single ribonucleoprotein machines
Authors: Custer Thomas C. , Walter Nils G. 
Published: December 2016

AbstractRNA plays a fundamental, ubiquitous role as either substrate or functional component of many large cellular complexes—“molecular machines”—used to maintain and control the readout of genetic information, a functional landscape that we are only beginning to understand. The cellular mechanisms for the spatiotemporal organization of the plethora of RNAs involved in gene expression are particularly poorly understood. Intracellular single‐molecule fluorescence microscopy provides a powerful emerging tool for probing the pertinent mechanistic parameters that govern cellular RNA functions, including those of protein coding messenger RNAs (mRNAs). Progress has been hampered, however, by the scarcity of efficient high‐yield methods to fluorescently label RNA molecules without the need to drastically increase their molecular weight through artificial appendages that may result in altered behavior. Herein, we employ T7 RNA polymerase to body label an RNA with a cyanine dye, as well as yeast poly(A) polymerase to strategically place multiple 2′‐azido‐modifications for subsequent fluorophore labeling either between the body and tail or randomly throughout the tail. Using a combination of biochemical and single‐molecule fluorescence microscopy approaches, we demonstrate that both yeast poly(A) polymerase labeling strategies result in fully functional mRNA, whereas protein coding is severely diminished in the case of body labeling.
Streptococcus pneumoniae IgA1 protease: A metalloprotease that can catalyze in a split manner in vitro
Authors: Chi Ying‐Chih , Rahkola Jeremy T. , Kendrick Agnieszka A. , Holliday Michael J. , Paukovich Natasia , Roberts Thomas S. , Janoff Edward N. , Eisenmesser Elan Z. 
Published: December 2016

AbstractIgA1 proteases (IgA1P) from diverse pathogenic bacteria specifically cleave human immunoglobulin A1 (IgA1) at the hinge region, thereby thwarting protective host immune responses. Streptococcus pneumoniae (S. pneumoniae) IgA1P shares no sequence conservation with serine or cysteine types of IgA1Ps or other known proteins, other than a conserved HExxH Zn‐binding motif (1604‐1608) found in metalloproteases. We have developed a novel expression system to produce the mature S. pneumoniae IgA1P and we have discovered that this form is both attached to the bacterial cell surface and released in its full form. Our data demonstrate that the S. pneumoniae IgA1P comprises two distinct regions that associate to form an active metalloprotease, the first such example of a metalloprotease that can be split in vitro and recombined to form an active enzyme. By capitalizing on this novel domain architecture, we show that the N‐terminal region of S. pneumoniae IgA1P comprises the primary binding region for IgA1, although the C‐terminal region of S. pneumoniae IgA1P is necessary for cleavage of IgA1. Our findings lend insight into the protein domain architecture of the S. pneumoniae IgA1P and function of this important virulence factor for S. pneumoniae infection.
Electron and electron–hole excitations in a driven Fermi sea
Authors: Vanević Mihajlo , Nazarov Yuli V. , Belzig Wolfgang 
Published: December 2016

AbstractWe study the response of a degenerate Fermi sea to a time‐dependent perturbation. We find that elementary excitations in the Fermi sea are electrons and electron–hole quasiparticle pairs whose number and probability of creation depend on amplitude and shape of the drive. The excitations can be probed in a driven quantum contact at low temperature. While electronic excitations are associated to the dc voltage offset and determine the average current, the electron–hole pairs are created by the ac voltage component and give rise to the excess current noise power in a junction. We also obtain the many‐body state created by the drive. The constituent quasiparticle states can be probed by a Hong–Ou–Mandel type of correlation experiment where electrons emitted from the terminals with a relative time delay collide at the contact. The current noise power in the junction is directly related to the wave packet overlap at the contact. This is confirmed in recent experiments, demonstrating an unprecedented degree of control of elementary excitations in a coherent mesoscopic junction.
Point estimation and p‐values in phase II adaptive two‐stage designs with a binary endpoint
Authors: Kunzmann K. , Kieser M. 
Published: December 2016

Clinical trials in phase II of drug development are frequently conducted as single‐arm two‐stage studies with a binary endpoint. Recently, adaptive designs have been proposed for this setting that enable a midcourse modification of the sample size. While these designs are elaborated with respect to hypothesis testing by assuring control of the type I error rate, the topic of point estimation has up to now not been addressed. For adaptive designs with a prespecified sample size recalculation rule, we propose a new point estimator that both assures compatibility of estimation and test decision and minimizes average mean squared error. This estimator can be interpreted as a constrained posterior mean estimate based on the non‐informative Jeffreys prior. A comparative investigation of the operating characteristics demonstrates the favorable properties of the proposed approach. Copyright © 2016 John Wiley & Sons, Ltd.
Deciphering long‐term records of natural variability and human impact as recorded in lake sediments: a palaeolimnological puzzle
Authors: Mills Keely , Schillereff Daniel , Saulnier‐Talbot Émilie , Gell Peter , Anderson N. John , Arnaud Fabien , Dong Xuhui , Jones Matthew , McGowan Suzanne , Massaferro Julieta , Moorhouse Heather , Perez Liseth , Ryves David B. 
Published: December 2016

Global aquatic ecosystems are under increasing threat from anthropogenic activity, as well as being exposed to past (and projected) climate change, however, the nature of how climate and human impacts are recorded in lake sediments is often ambiguous. Natural and anthropogenic drivers can force a similar response in lake systems, yet the ability to attribute what change recorded in lake sediments is natural, from that which is anthropogenic, is increasingly important for understanding how lake systems have, and will continue to function when subjected to multiple stressors; an issue that is particularly acute when considering management options for aquatic ecosystems. The duration and timing of human impacts on lake systems varies geographically, with some regions of the world (such as Africa and South America) having a longer legacy of human impact than others (e.g., New Zealand). A wide array of techniques (biological, chemical, physical and statistical) is available to palaeolimnologists to allow the deciphering of complex sedimentary records. Lake sediments are an important archive of how drivers have changed through time, and how these impacts manifest in lake systems. With a paucity of ‘real‐time’ data pre‐dating human impact, palaeolimnological archives offer the only insight into both natural variability (i.e., that driven by climate and intrinsic lake processes) and the impact of people. While there is a need to acknowledge complexity, and temporal and spatial variability when deciphering change from sediment archives, a palaeolimnological approach is a powerful tool for better understanding and managing global aquatic resources. WIREs Water 2017, 4:e1195. doi: 10.1002/wat2.1195This article is categorized under:

Water and Life > Stresses and Pressures on Ecosystems
Science of Water > Water and Environmental Change
Water and Life > Methods
First-dose and steady-state pharmacokinetics of orally administered crizotinib in children with solid tumors: a report on ADVL0912 from the Children’s Oncology Group Phase 1/Pilot Consortium
Authors: Balis Frank M. , Thompson Patrick A. , Mosse Yael P. , Blaney Susan M. , Minard Charles G. , Weigel Brenda J. , Fox Elizabeth 
Published: December 2016

Abstract
Purpose

Characterize the pharmacokinetics of oral crizotinib in children with cancer.

Methods
Sixty-four children with solid tumors or anaplastic large-cell lymphoma (ALCL) enrolled on a phase 1/2 trial of the ALK, MET and ROS1 inhibitor, crizotinib, had pharmacokinetic sampling after the first dose (n = 15) or at steady state (n = 49). Dose levels studied were 100, 130, 165, 215, 280 and 365 mg/m2/dose administered twice daily. Two capsule and two oral liquid formulations were used over the course of the trial. Crizotinib was quantified with a validated HPLC/tandem mass spectrometry method with a lower limit of detection of 0.2 ng/mL. Pharmacokinetic parameters were derived using non-compartmental analysis.

Results
Time to peak plasma concentration was 4 h. At 280 mg/m2 (MTD), mean (±SD) steady-state peak plasma concentration was 717 ± 201 ng/mL, and steady-state trough plasma concentration was 480 ± 176 ng/mL. At steady state, AUC0–τ
was proportional to dose over the dose range of 215–365 mg/m2/dose. Apparent clearance of crizotinib was 731 ± 241 mL/min/m2. Steady-state AUC0–τ
at 280 mg/m2/dose was 2.5-fold higher than the AUC0–∞
in adults receiving 250 mg (~140 mg/m2). Age, sex and drug formulation do not account for the inter-subject variability in AUC0–τ
at steady state. The accumulation index was 4.9, and the half-life estimated from the accumulation index was 36 h.

Conclusions
The pharmacokinetics of oral crizotinib in children is similar to that in adults. Steady-state trough-free crizotinib concentrations in plasma at the MTD exceed inhibitory concentrations of crizotinib in ALCL cell lines.

ClinicalTrials.gov identifier
NCT00939770.
Model of Silicon Refining During Tapping: Removal of Ca, Al, and Other Selected Element Groups
Authors: Olsen Jan Erik , Kero Ida T. , Engh Thorvald A. , Tranell Gabriella 
Published: December 2016

Abstract
A mathematical model for industrial refining of silicon alloys has been developed for the so-called oxidative ladle refining process. It is a lumped (zero-dimensional) model, based on the mass balances of metal, slag, and gas in the ladle, developed to operate with relatively short computational times for the sake of industrial relevance. The model accounts for a semi-continuous process which includes both the tapping and post-tapping refining stages. It predicts the concentrations of Ca, Al, and trace elements, most notably the alkaline metals, alkaline earth metal, and rare earth metals. The predictive power of the model depends on the quality of the model coefficients, the kinetic coefficient, τ, and the equilibrium partition coefficient, L for a given element. A sensitivity analysis indicates that the model results are most sensitive to L. The model has been compared to industrial measurement data and found to be able to qualitatively, and to some extent quantitatively, predict the data. The model is very well suited for alkaline and alkaline earth metals which respond relatively fast to the refining process. The model is less well suited for elements such as the lanthanides and Al, which are refined more slowly. A major challenge for the prediction of the behavior of the rare earth metals is that reliable thermodynamic data for true equilibrium conditions relevant to the industrial process is not typically available in literature.
Development and Characterization of DOPEPEG2000 Coated Oleic Acid Liposomes Encapsulating Anticancer Drugs
Authors: Eh Suk Vicit Rizal , Misran Misni 
Published: December 2016

AbstractLiposomes have been widely investigated as drug carriers for a broad range of anticancer drugs. However, their application as a drug delivery system may be challenging due to low encapsulation of active ingredient and poor stability which leads to uncontrolled delivery of bioactive ingredients. The present study aims at incorporating 1,2‐dioleoyl‐sn‐glycero‐3‐phosphoethanolamide‐N‐[methoxy(polyethylene glycol)‐2000 (DOPEPEG2000) into oleic acid (OA) liposomes in order to prolong the lifetime in blood circulation. The pH transition curve of oleic was obtained by titration of sodium oleate solution with 0.05 mol dm−3 HCl to determine the region where liposomes were abundantly present. The critical vesicle concentration (CVC) was then determined by surface tension measurements. Dry lipid liposomes were hydrated with phosphate buffer at just over twice the CVC value. Optical polarizing microscopy (OPM) showed the presence of liposomes while transmission electron microscopy (TEM) confirmed that the liposomes prepared were spherical in shape and less than 200 nm in size. The incorporation of DOPEPEG2000 into the oleic acid liposomes reduced the average particle size and zeta potential to mimic the red blood cells. The encapsulation efficiency of various anticancer drugs was more than 60% while more than 20% of the drugs were released after 24 h. The results suggest that DOPEPEG2000: oleic acid at a molar ratio of 1:50 fulfilled the requirements for intravenous drug delivery.
Effectiveness of one-to-one peer support for patients with severe mental illness – a randomised controlled trial
Authors: Mahlke C.I. , Priebe S. , Heumann K. , Daubmann A. , Wegscheider K. , Bock T. 
Published: December 2016

AbstractBackgroundOne-to-one peer support is a resource-oriented approach for patients with severe mental illness. Existing trials provided inconsistent results and commonly have methodological shortcomings, such as poor training and role definition of peer supporters, small sample sizes, and lack of blinded outcome assessments.MethodsThis is a randomised controlled trial comparing one-to-one peer support with treatment as usual. Eligible were patients with severe mental illnesses: psychosis, major depression, bipolar disorder or borderline personality disorder of more than two years’ duration. A total of 216 patients were recruited through in- and out-patient services from four hospitals in Hamburg, Germany, with 114 allocated to the intervention group and 102 to the control group. The intervention was one-to-one peer support, delivered by trained peers and according to a defined role specification, in addition to treatment as usual over the course of six months, as compared to treatment as usual alone. Primary outcome was self-efficacy measured on the General Self-Efficacy Scale at six-month follow-up. Secondary outcomes included quality of life, social functioning, and hospitalisations.ResultsPatients in the intervention group had significantly higher scores of self-efficacy at the six-month follow-up. There were no statistically significant differences on secondary outcomes in the intention to treat analyses.ConclusionsThe findings suggest that one-to-one peer support delivered by trained peer supporters can improve self-efficacy of patients with severe mental disorders over a one-year period. One-to-one peer support may be regarded as an effective intervention. Future research should explore the impact of improved self-efficacy on clinical and social outcomes.
Distribution of Central Line-Associated Bloodstream Infections Determined From Washington State’s Annual Reporting Validation Program, 2009–2013
Authors: Lempp Jason M. , Cummings M. Jeanne , Birnbaum David W. 
Published: December 2016

Healthcare-associated infection reporting validation is essential because this information is increasingly used in public healthcare quality assurances and care reimbursement. Washington State’s validation of central line-associated bloodstream infection reporting applies credible quality sciences methods to ensure that hospital reporting accuracy is maintained. This paper details findings and costs from our experience.Infect Control Hosp Epidemiol 2017;38:489–492
Unit-Specific Rates of Hand Hygiene Opportunities in an Acute-Care Hospital
Authors: Han Angela , Conway Laurie J. , Moore Christine , McCreight Liz , Ragan Kelsey , So Jannice , Borgundvaag Emily , Larocque Mike , Coleman Brenda L. , McGeer Allison ,   the MSH Infection Control and Hand Hygiene Observer Teams
Published: December 2016

OBJECTIVETo explore the frequency of hand hygiene opportunities (HHOs) in multiple units of an acute-care hospital.DESIGNProspective observational study.SETTINGThe adult intensive care unit (ICU), medical and surgical step-down units, medical and surgical units, and the postpartum mother–baby unit (MBU) of an academic acute-care hospital during May–August 2013, May–July 2014, and June–August 2015.PARTICIPANTSHealthcare workers (HCWs).METHODSHHOs were recorded using direct observation in 1-hour intervals following Public Health Ontario guidelines. The frequency and distribution of HHOs per patient hour were determined for each unit according to time of day, indication, and profession.RESULTSIn total, 3,422 HHOs were identified during 586 hours of observation. The mean numbers of HHOs per patient hour in the ICU were similar to those in the medical and surgical step-down units during the day and night, which were higher than the rates observed in medical and surgical units and the MBU. The rate of HHOs during the night significantly decreased compared with day (P<.0001). HHOs before an aseptic procedure comprised 13% of HHOs in the ICU compared with 4%–9% in other units. Nurses contributed >92% of HHOs on medical and surgical units, compared to 67% of HHOs on the MBU.CONCLUSIONSAssessment of hand hygiene compliance using product utilization data requires knowledge of the appropriate opportunities for hand hygiene. We have provided a detailed characterization of these estimates across a wide range of inpatient settings as well as an examination of temporal variations in HHOs.Infect Control Hosp Epidemiol2017;38:411–416
Helical propulsion in shear-thinning fluids
Authors: Gómez Saúl , Godínez Francisco A. , Lauga Eric , Zenit Roberto 
Published: December 2016

Swimming micro-organisms often have to propel themselves in complex non-Newtonian fluids. We carry out experiments with self-propelling helical swimmers driven by an externally rotating magnetic field in shear-thinning inelastic fluids. Similarly to swimming in a Newtonian fluid, we obtain for each fluid a locomotion speed that scales linearly with the rotation frequency of the swimmer, but with a prefactor that depends on the power index of the fluid. The fluid is seen to always increase the swimming speed of the helix, up to 50 % faster, and thus the strongest of such type reported to date. The maximum relative increase is for a fluid power index of approximately 0.6. Using simple scalings, we argue that the speed increase is not due directly to the local decrease of the flow viscosity around the helical filament, but hypothesise instead that it originates from confinement-like effect due to viscosity stratification around the swimmer.
Climate and surface mass balance of Mocho Glacier, Chilean Lake District, 40°S
Authors: SCHAEFER MARIUS , RODRIGUEZ JOSE LUIS , SCHEITER MATTHIAS , CASASSA GINO 
Published: December 2016

ABSTRACTWe present climate data, direct surface mass balance (SMB) observations and model results for Mocho Glacier in the Chilean Lake District. Mean annual temperature on a nunatak of Mocho Glacier at an elevation of ~2000 m was +2.6°C in 2006–15 and mean annual precipitation in Puerto Fuy (13 km from the glacier, at an elevation of 600 m) was 4000 mm for the same period. High interannual variations in the SMB of Mocho Glacier were observed. A simple SMB model is able to reproduce the observed annual variations in SMB, but fails to predict the steep observed mass-balance gradient. The average of the measured annual glacier mass balances in the four hydrological years 2009/10–2012/13 was −0.90 m w.e. a−1and the average modelled annual glacier mass balance 2006/07–2014/15 was −1.05 m w.e. a−1. The observed distributed ablation shows a clear altitudinal dependency, while accumulation is determined by patterns of snow drift as well. These patterns are only poorly represented in the model and have to be included in order to be able to reproduce a realistic SMB map of the glacier.