bluuebunny/crossref_metadata_2025_split huggingface dataset:
Irradiation Capabilities at the Halden Reactor and Testing Possibilities Under Supercritical Water Conditions
Authors: Van Nieuwenhove Rudi 
Published: June 2015

Different types of instruments have been developed both for in-pile fuel and materials studies at the Halden Reactor Project. In recent years, several of the standard instruments have been upgraded to be able to tolerate much higher temperatures. In particular, several instruments are now able to operate up to 650°C and 25 MPa, thus in the range suitable for supercritical water (SCW) studies. In addition, a feasibility study for an in-pile SCW loop has been carried out that shows that such a loop can be realized in the Halden reactor, allowing for all the instrumentation possibilities that are presently carried out in pressurized water reactor (PWR) and boiling water reactor (BWR) conditions. Another, and cheaper, alternative is to perform corrosion experiments inside a small capsule in which SCW is maintained by means of gamma heating and external pressure lines. The conceptual designs of the SCW loop and SCW capsule will be highlighted.
Determining the in vivo elastic properties of dermis layer of human skin using the supersonic shear imaging technique and inverse analysis
Authors: Luo Cheng‐Cheng , Qian Lin‐Xue , Li Guo‐Yang , Jiang Yi , Liang Si , Cao Yanping 
Published: June 2015

Purpose:Human skin consists of several layers including epidermis, dermis, and hypodermis. The determination of the in vivo mechanical properties of an individual skin layer represents a great challenge to date. In this study, the authors explore the use of the supersonic shear imaging (SSI) technique and inverse analysis to determine the in vivo elastic properties of the dermis layer of human skin.Methods:The measurements are conducted on the volar forearms and dorsal forearms of 18 healthy volunteers (nine females and nine males) using the SSI technique that gives the velocities of the shear wave generated by the acoustic force. Finite element analysis is carried out to simulate the propagation of the shear wave in the multilayer soft media and the results are used to interpret the experimental data and deduce the shear modulus of the dermis layer.Results:The shear moduli of the skin dermis layer obtained for the 18 healthy volunteers exhibit significant anisotropy. A standard statistical analysis demonstrates the differences between sexes.Conclusions:This study demonstrates that the SSI technique together with the inverse analysis represents a useful tool to characterize the in vivo elastic properties of human skin.
Beyond Agar: Gel Substrates with Improved Optical Clarity and Drug Efficiency and Reduced Autofluorescence for Microbial Growth Experiments
Authors: Jaeger Philipp A. , McElfresh Cameron , Wong Lily R. , Ideker Trey 
Published: June 2015

ABSTRACTAgar, a seaweed extract, has been the standard support matrix for microbial experiments for over a century. Recent developments in high-throughput genetic screens have created a need to reevaluate the suitability of agar for use as colony support, as modern robotic printing systems now routinely spot thousands of colonies within the area of a single microtiter plate. Identifying optimal biophysical, biochemical, and biological properties of the gel support matrix in these extreme experimental conditions is instrumental to achieving the best possible reproducibility and sensitivity. Here we systematically evaluate a range of gelling agents by using the yeastSaccharomyces cerevisiaeas a model microbe. We find that carrageenan and Phytagel have superior optical clarity and reduced autofluorescence, crucial for high-resolution imaging and fluorescent reporter screens. Nutrient choice and use of refined Noble agar or pure agarose reduce the effective dose of numerous selective drugs by >50%, potentially enabling large cost savings in genetic screens. Using thousands of mutant yeast strains to compare colony growth between substrates, we found no evidence of significant growth or nutrient biases between gel substrates, indicating that researchers could freely pick and choose the optimal gel for their respective application and experimental condition.
Draft Genome Sequence of
Paenibacillus
sp. Strain DMB20, Isolated from Alang Ship-Breaking Yard, Which Harbors Genes for Xenobiotic Degradation
Authors: Shah Binal , Jain Kunal , Patel Namrata , Pandit Ramesh , Patel Anand , Joshi Chaitanya G. , Madamwar Datta 
Published: June 2015

ABSTRACT

Paenibacillus
sp. strain DMB20, in cometabolism with other
Proteobacteria
and
Firmicutes
, exhibits azoreduction of textile dyes. Here, we report the draft genome sequence of this bacterium, consisting of 6,647,181 bp with 7,668 coding sequences (CDSs). The data presented highlight multiple sets of functional genes associated with xenobiotic compound degradation.
Draft Genome Sequences of Clinical Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus Strain APS211 and Its Daptomycin-Susceptible Progenitor APS210
Authors: Cameron David R. , Jiang Jhih-Hang , Abbott Iain J. , Spelman Denis W. , Peleg Anton Y. 
Published: June 2015

ABSTRACT

To assess the genetic factors contributing to daptomycin resistance in
Staphylococcus aureus
, the draft genome of a clinically derived daptomycin-nonsusceptible isolate APS211 was generated and compared to the draft sequence of its susceptible progenitor strain APS210. Four genetic differences were identified including a previously described mutation within the
mprF
gene.
Complete Genome Sequence of Pseudoxanthomonas suwonensis Strain J1, a Cellulose-Degrading Bacterium Isolated from Leaf- and Wood-Enriched Soil
Authors: Hou Liyuan , Jiang Jingwei , Xu Zhihui , Zhou Yun , Leung Frederick Chi-Ching 
Published: June 2015

ABSTRACT

We report here the complete genome sequence of the cellulose-degrading bacterium
Pseudoxanthomonas suwonensis
strain J1, isolated from soil enriched with rotten leaves and wood from the Zhong Mountain Scenic Area in Nanjing, China. This complete genome may contribute to further investigation of plant biomass degradation.
Complete Genome Sequence of Listeria monocytogenes Strain DPC6895, a Serotype 1/2b Isolate from Bovine Raw Milk
Authors: Casey Aidan , McAuliffe Olivia , Coffey Aidan , Hunt Karen , Fanning Seamus , Fox Edward , Jordan Kieran 
Published: June 2015

ABSTRACT

Listeria monocytogenes
is a foodborne pathogen and is the causative agent of listeriosis among humans and animals. The draft genome sequence of
L. monocytogenes
DPC6895, a serotype 1/2b strain isolated from the raw milk of a cow with subclinical bovine mastitis, is reported.
Making sense of the shadows: priorities for creating a learning healthcare system based on routinely collected data
Authors: Deeny Sarah R , Steventon Adam 
Published: June 2015

Socrates described a group of people chained up inside a cave, who mistook shadows of objects on a wall for reality. This allegory comes to mind when considering ‘routinely collected data’—the massive data sets, generated as part of the routine operation of the modern healthcare service. There is keen interest in routine data and the seemingly comprehensive view of healthcare they offer, and we outline a number of examples in which they were used successfully, including the Birmingham OwnHealth study, in which routine data were used with matched control groups to assess the effect of telephone health coaching on hospital utilisation.Routine data differ from data collected primarily for the purposes of research, and this means that analysts cannot assume that they provide the full or accurate clinical picture, let alone a full description of the health of the population. We show that major methodological challenges in using routine data arise from the difficulty of understanding the gap between patient and their ‘data shadow’. Strategies to overcome this challenge include more extensive data linkage, developing analytical methods and collecting more data on a routine basis, including from the patient while away from the clinic. In addition, creating a learning health system will require greater alignment between the analysis and the decisions that will be taken; between analysts and people interested in quality improvement; and between the analysis undertaken and public attitudes regarding appropriate use of data.
Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach
Authors: Cerasuolo Marianna , Paris Debora , Iannotti Fabio A. , Melck Dominique , Verde Roberta , Mazzarella Enrico , Motta Andrea , Ligresti Alessia 
Published: June 2015

Abstract
Prostate cancer is highly sensitive to hormone therapy because androgens are essential for prostate cancer cell growth. However, with the nearly invariable progression of this disease to androgen independence, endocrine therapy ultimately fails to control prostate cancer in most patients. Androgen-independent acquisition may involve neuroendocrine transdifferentiation, but there is little knowledge about this process, which is presently controversial. In this study, we investigated this question in a novel model of human androgen-dependent LNCaP cells cultured for long periods in hormone-deprived conditions. Strikingly, characterization of the neuroendocrine phenotype by transcriptomic, metabolomic, and other statistically integrated analyses showed how hormone-deprived LNCaP cells could transdifferentiate to a nonmalignantneuroendocrine phenotype. Notably, conditioned media from neuroendocrine-like cells affected LNCaP cell proliferation. Predictive in silico models illustrated how after an initial period, when LNCaP cell survival was compromised by an arising population of neuroendocrine-like cells, a sudden trend reversal occurred in which the neuroendocrine-like cells functioned to sustain the remaining androgen-dependent LNCaP cells. Our findings provide direct biologic and molecular support for the concept that neuroendocrine transdifferentiation in prostate cancer cell populations influences the progression to androgen independence. Cancer Res; 75(15); 2975–86. ©2015 AACR.
SRRM4 Expression and the Loss of REST Activity May Promote the Emergence of the Neuroendocrine Phenotype in Castration-Resistant Prostate Cancer
Authors: Zhang Xiaotun , Coleman Ilsa M. , Brown Lisha G. , True Lawrence D. , Kollath Lori , Lucas Jared M. , Lam Hung-Ming , Dumpit Ruth , Corey Eva , Chéry Lisly , Lakely Bryce , Higano Celestia S. , Montgomery Bruce , Roudier Martine , Lange Paul H. , Nelson Peter S. , Vessella Robert L. , Morrissey Colm 
Published: June 2015

Abstract
Purpose: The neuroendocrine phenotype is associated with the development of metastatic castration-resistant prostate cancer (CRPC). Our objective was to characterize the molecular features of the neuroendocrine phenotype in CRPC.
Experimental Design: Expression of chromogranin A (CHGA), synaptophysin (SYP), androgen receptor (AR), and prostate-specific antigen (PSA) was analyzed by IHC in 155 CRPC metastases from 50 patients and in 24 LuCaP prostate cancer patient-derived xenografts (PDX). Seventy-one of 155 metastases and the 24 LuCaP xenograft lines were analyzed by whole-genome microarrays. REST splicing was verified by PCR.
Results: Coexpression of CHGA and SYP in &gt;30% of cells was observed in 22 of 155 metastases (9 patients); 11 of the 22 metastases were AR+/PSA+ (6 patients), 11/22 were AR–/PSA– (4 patients), and 4/24 LuCaP PDXs were AR−/PSA−. By IHC, of the 71 metastases analyzed by whole-genome microarrays, 5 metastases were CHGA+/SYP+/AR−, and 5 were CHGA+/SYP+/AR+. Only CHGA+/SYP+ metastases had a neuroendocrine transcript signature. The neuronal transcriptional regulator SRRM4 transcript was associated with the neuroendocrine signature in CHGA+/SYP+ metastases and all CHGA+/SYP+ LuCaP xenografts. In addition, expression of SRRM4 in LuCaP neuroendocrine xenografts correlated with a splice variant of REST that lacks the transcriptional repressor domain.
Conclusions: (i) Metastatic neuroendocrine status can be heterogeneous in the same patient, (ii) the CRPC neuroendocrine molecular phenotype can be defined by CHGA+/SYP+ dual positivity, (iii) the neuroendocrine phenotype is not necessarily associated with the loss of AR activity, and (iv) the splicing of REST by SRRM4 could promote the neuroendocrine phenotype in CRPC. Clin Cancer Res; 21(20); 4698–708. ©2015 AACR.
ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors
Authors: Shen Jianfeng , Peng Yang , Wei Leizhen , Zhang Wei , Yang Lin , Lan Li , Kapoor Prabodh , Ju Zhenlin , Mo Qianxing , Shih Ie-Ming , Uray Ivan P. , Wu Xiangwei , Brown Powel H. , Shen Xuetong , Mills Gordon B. , Peng Guang 
Published: June 2015

Abstract
ARID1A, SWI/SNF chromatin remodeling complex subunit, is a recently identified tumor suppressor that is mutated in a broad spectrum of human cancers. Thus, it is of fundamental clinical importance to understand its molecular functions and determine whether ARID1A deficiency can be exploited therapeutically. In this article, we report a key function of ARID1A in regulating the DNA damage checkpoint. ARID1A is recruited to DNA double-strand breaks (DSB) via its interaction with the upstream DNA damage checkpoint kinase ATR. At the molecular level, ARID1A facilitates efficient processing of DSB to single-strand ends and sustains DNA damage signaling. Importantly, ARID1A deficiency sensitizes cancer cells to PARP inhibitors in vitro and in vivo, providing a potential therapeutic strategy for patients with ARID1A-mutant tumors.
Significance: ARID1A has been identified as one of the most frequently mutated genes across human cancers. Our data suggest that clinical utility of PARP inhibitors might be extended beyond patients with BRCA mutations to a larger group of patients with ARID1A-mutant tumors, which may exhibit therapeutic vulnerability to PARP inhibitors. Cancer Discov; 5(7); 752–67. ©2015 AACR.
This article is highlighted in the In This Issue feature, p. 681
Prolongation of Action Potential Duration and QT Interval During Epilepsy Linked to Increased Contribution of Neuronal Sodium Channels to Cardiac Late Na
+
Current
Authors: Biet Michael , Morin Nathalie , Lessard-Beaudoin Melissa , Graham Rona K. , Duss Sandra , Gagné Jonathan , Sanon Nathalie T. , Carmant Lionel , Dumaine Robert 
Published: June 2015

Background—

Arrhythmias associated with QT prolongation on the ECG often lead to sudden unexpected death in epilepsy. The mechanism causing a prolongation of the QT interval during epilepsy remains unknown. Based on observations showing an upregulation of neuronal sodium channels in the brain during epilepsy, we tested the hypothesis that a similar phenomenon occurs in the heart and contributes to QT prolongation by altering cardiac sodium current properties (I
Na
).

Methods and Results—

We used the patch clamp technique to assess the effects of epilepsy on the cardiac action potential and I
Na
in rat ventricular myocytes. Consistent with QT prolongation, epileptic rats had longer ventricular action potential durations attributable to a sustained component of I
Na
(I
NaL
). The increase in I
NaL
was because of a larger contribution of neuronal Na channels characterized by their high sensitivity to tetrodotoxin. As in the brain, epilepsy was associated with an enhanced expression of the neuronal isoform Na
V
1.1 in cardiomyocyte. Epilepsy was also associated with a lower I
Na
activation threshold resulting in increased cell excitability.

Conclusions—
This is the first study correlating increased expression of neuronal sodium channels within the heart to epilepsy-related cardiac arrhythmias. This represents a new paradigm in our understanding of cardiac complications related to epilepsy.
E/e′ Ratio in Patients With Unexplained Dyspnea
Authors: Santos Mário , Rivero Jose , McCullough Shane D. , West Erin , Opotowsky Alexander R. , Waxman Aaron B. , Systrom David M. , Shah Amil M. 
Published: June 2015

Background—
Elevated left ventricular filling pressure is a cardinal feature of heart failure with preserved ejection fraction. Mitral E/e′ ratio has been proposed as a noninvasive measure of left ventricular filling pressure. We studied the accuracy of E/e′ to estimate and track changes of left ventricular filling pressure in patients with unexplained dyspnea.

Methods and Results—

We performed supine and upright transthoracic echocardiography in 118 patients with unexplained dyspnea who underwent right heart catheterization. Supine E/e′ ratio modestly but significantly correlated with supine pulmonary arterial wedge pressure (PAWP;
r
=0.36;
P
<0.001) and demonstrated poor agreement with PAWP values (Bland–Altman limits of agreement of −8.3 to 8.3 mm Hg; range, 6.5–21.2 mm Hg). Similarly, E/e′ ratio cut off of 13 performed poorly in identifying patients with elevated left ventricular filling pressure (sensitivity 6%, specificity 90%). The receiver-operating characteristic area of E/e′ was 0.65 (95% confidencce interval, 0.50–0.79). With change from the supine to upright position, PAWP decreased (−5±4 mm Hg;
P
<0.001) as did both E wave (−17±15 cm/s;
P
<0.001) and e′ (−2.7±2.7 cm/s;
P
<0.001) velocities, whereas E/e′ remained stable (+0.2±2.6;
P
=0.57). Positional change in PAWP correlated modestly with change in E-wave (
r
=0.37;
P
<0.001) velocity. There was no appreciable relationship between change in PAWP and change in average E/e′ (
r
=−0.04;
P
=0.77) and in half the patients the change in PAWP and E/e′ were directionally opposite.

Conclusions—
In patients with unexplained dyspnea, E/e′ ratio neither accurately estimates PAWP nor identifies patients with elevated PAWP consistent with heart failure with preserved ejection fraction. Positional changes in E/e′ ratio do not reflect changes in PAWP.
Hck/Fgr Kinase Deficiency Reduces Plaque Growth and Stability by Blunting Monocyte Recruitment and Intraplaque Motility
Authors: Medina Indira , Cougoule Céline , Drechsler Maik , Bermudez Beatriz , Koenen Rory R. , Sluimer Judith , Wolfs Ine , Döring Yvonne , Herias Veronica , Gijbels Marjon , Bot Ilze , de Jager Saskia C. A. , Weber Christian , Cleutjens Jack , van Berkel Theo J.C. , Sikkink Kees-Jan , Mócsai Atilla , Maridonneau-Parini Isabelle , Soehnlein Oliver , Biessen Erik A.L. 
Published: June 2015

Background—
Leukocyte migration is critical for the infiltration of monocytes and accumulation of monocyte-derived macrophages in inflammation. Considering that Hck and Fgr are instrumental in this process, their impact on atherosclerosis and on lesion inflammation and stability was evaluated.

Methods and Results—

Hematopoietic Hck/Fgr-deficient, LDLr
−/−
chimeras, obtained by bone marrow transplantation, had smaller but, paradoxically, less stable lesions with reduced macrophage content, overt cap thinning, and necrotic core expansion as the most prominent features. Despite a Ly6C
high
-skewed proinflammatory monocyte phenotype, Hck/Fgr deficiency led to disrupted adhesion of myeloid cells to and transmigration across endothelial monolayers in vitro and atherosclerotic plaques in vivo, as assessed by intravital microscopy, flow cytometry, and histological examination of atherosclerotic arteries. Moreover, Hck/Fgr-deficient macrophages showed blunted podosome formation and mesenchymal migration capacity. In consequence, transmigrated double-knockout macrophages were seen to accumulate in the fibrous cap, potentially promoting its focal erosion, as observed for double-knockout chimeras.

Conclusions—
The hematopoietic deficiency of Hck and Fgr led to attenuated atherosclerotic plaque formation by abrogating endothelial adhesion and transmigration; paradoxically, it also promoted plaque instability by causing monocyte subset imbalance and subendothelial accumulation, raising a note of caution regarding src kinase–targeted intervention in plaque inflammation.
Intensive Care Units With Low Versus High Volume of Myocardial Infarction: Clinical Outcomes, Resource Utilization, and Quality Metrics
Authors: Stolker Joshua M. , Badawi Omar , Spertus John A. , Nasir Ammar , Kennedy Kevin F. , Harris Ilene H. , Franey Christine S. , Hsu Van Doren , Ripple Gary R. , Howell Gregory H. , Lem Vincent M. , Chan Paul S. 
Published: June 2015

Background

The volume‐outcome relationship associated with intensive care unit (
ICU
) experience with managing acute myocardial infarction (
AMI
) remains inadequately understood.

Methods and Results

Within a multicenter clinical
ICU
database, we identified patients with a primary
ICU
admission diagnosis of
AMI
between 2008 and 2010 to evaluate whether annual
AMI
volume of an individual
ICU
is associated with mortality, length‐of‐stay, or quality indicators. Patients were categorized into those treated in
ICU
s with low‐annual‐
AMI
volume (≤50th percentile, <2
AMI
patients/month, n=569 patients) versus high‐annual‐
AMI
volume (≥90th percentile, ≥8
AMI
patients/month, n=17 553 patients). Poisson regression and generalized estimating equation with negative binomial regression were used to calculate the relative risk (95%
CI
) for mortality and length‐of‐stay, respectively, associated with admission to a low‐
AMI
‐volume
ICU
. When compared with high‐
AMI
‐volume, patients admitted to low‐
AMI
‐volume
ICU
s had substantially more medical comorbidities, higher in‐hospital mortality (11% versus 4%,
P
<0.001), longer hospitalizations (6.9±7.0 versus 5.0±5.0 days,
P
<0.001), and fewer evidence‐based therapies for
AMI
(reperfusion therapy, antiplatelets, β‐blockers, and statins). However, after adjustment for baseline patient characteristics, low‐
AMI
‐volume
ICU
was no longer an independent predictor of in‐hospital mortality (relative risk 1.17 [0.87 to 1.56]) or hospital length‐of‐stay (relative risk 1.01 [0.94 to 1.08]). Similar findings were noted in secondary analyses of
ICU
mortality and
ICU
length‐of‐stay.

Conclusions

Admission to an
ICU
with lower annual
AMI
volume is associated with higher in‐hospital mortality, longer hospitalization, and lower use of evidence‐based therapies for
AMI
. However, the relationship between low‐
AMI
‐volume and outcomes is no longer present after accounting for the higher‐risk medical comorbidities and clinical characteristics of patients admitted to these
ICU
s.