bluuebunny/crossref_metadata_2025_split huggingface dataset:
Termination of Replication Stress Signaling via Concerted Action of the Slx4 Scaffold and the PP4 Phosphatase
Authors: Jablonowski Carolyn M , Cussiol José R , Oberly Susannah , Yimit Askar , Balint Attila , Kim TaeHyung , Zhang Zhaolei , Brown Grant W , Smolka Marcus B 
Published: September 2015

Abstract
In response to replication stress, signaling mediated by DNA damage checkpoint kinases protects genome integrity. However, following repair or bypass of DNA lesions, checkpoint signaling needs to be terminated for continued cell cycle progression and proliferation. In budding yeast, the PP4 phosphatase has been shown to play a key role in preventing hyperactivation of the checkpoint kinase Rad53. In addition, we recently uncovered a phosphatase-independent mechanism for downregulating Rad53 in which the DNA repair scaffold Slx4 decreases engagement of the checkpoint adaptor Rad9 at DNA lesions. Here we reveal that proper termination of checkpoint signaling following the bypass of replication blocks imposed by alkylated DNA adducts requires the concerted action of these two fundamentally distinct mechanisms of checkpoint downregulation. Cells lacking both SLX4 and the PP4-subunit PPH3 display a synergistic increase in Rad53 signaling and are exquisitely sensitive to the DNA alkylating agent methyl methanesulfonate, which induces replication blocks and extensive formation of chromosomal linkages due to template switching mechanisms required for fork bypass. Rad53 hypersignaling in these cells seems to converge to a strong repression of Mus81-Mms4, the endonuclease complex responsible for resolving chromosomal linkages, thus explaining the selective sensitivity of slx4Δ pph3Δ cells to alkylation damage. Our results support a model in which Slx4 acts locally to downregulate Rad53 activation following fork bypass, while PP4 acts on pools of active Rad53 that have diffused from the site of lesions. We propose that the proper spatial coordination of the Slx4 scaffold and PP4 action is crucial to allow timely activation of Mus81-Mms4 and, therefore, proper chromosome segregation.
The development of second language critical thinking in a virtual language learning environment: A process-oriented mixed-method study
Authors: Mroz Aurore 
Published: September 2015

This article presents a process-oriented mixed-method study, focusing on the emergence of second language (L2) critical thinking (CT) skills in the collaborative discourse produced by a focal group of five college-level students of French working in a virtual language learning environment (the VLLE Cinet Second Life). Levels of CT ability were elicited through episodes of L2 negotiation and co-construction of meaning. The study also examines the perception by students of the impact of the VLLE on the emergence of their L2 CT skills. Motivated by the need advocated in recent CALL research for a shift in paradigm and in method to alleviate the limitations inherent to quantitative studies, the study was situated at the juncture of sociocultural theory and ecological perspective, and this article focuses on the theoretical rationale behind the selection of a mixed-method methodology.
Field Treatment To Stimulate an Oil Well in an Offshore Sandstone Reservoir Using a Novel, Low-Corrosive, Environmentally Friendly Fluid
Authors: Nasr-El-Din Hisham A. , Dana Halina , Tomos Vassilis , Stanitzek Theo , De Wolf Corine A. , Alex Alan K. 
Published: September 2015

Summary
Acidizing sandstone formations is a real challenge for the oil and gas industry. Fines migration, sand production, and additional damages caused by precipitation are some of the common concerns related to sandstone treatments. Furthermore, the complexities of sandstone formations require a mixture of acids and loadings of several additives. The environmentally friendly chelating agent glutamic acid N,N-diacetic acid (GLDA) was used successfully to stimulate deep gas wells in carbonate reservoirs. It was tested extensively in the laboratory to stimulate sandstone cores with various mineralogies. Significant permeability improvements were reported in previous papers over a wide range of conditions. In this paper, the result of the first field application is evaluated with a fluid based on this chelating agent to acidize an offshore, sour oil well in a sandstone reservoir.
The field treatment included pumping a preflush of xylene to remove oil residues and any possible asphaltene deposited in the wellbore region, followed by the main stage that contained 25 wt% GLDA, a corrosion inhibitor, and a water-wetting surfactant. The treatment fluids were displaced into the formation by pumping diesel. The treatment fluids were allowed to soak for 6 hours, then the well was put into production, and samples of flowback fluids were collected. The concentrations of key cations were determined using inductively coupled plasma, and the chelant concentration was measured using a titration method with ferric chloride solutions.
Corrosion tests conducted on low-carbon-steel tubulars indicated that this chelant has low corrosion rates under bottomhole conditions. No corrosion-inhibitor intensifier was needed. The treatment was applied in the field without encountering any operational problems. A significant gain in oil production was achieved without causing sand production, or fines migration. Analysis of flowback samples confirmed the ability of the chelating-agent solution to dissolve various types of carbonates, oxides, and sulphides, while keeping the dissolved species in solution without causing unwanted precipitation. Unlike previous treatments conducted on this well, where 15 wt% hydrochloric acid (HCl) or 13.5 wt%/1.5 wt% HCl/hydrofluoric acid (HF) acids were used, the concentrations of iron and manganese in the flowback samples were negligible, confirming the low corrosion rates of well tubulars when using GLDA solutions.
Ensemble-Based Multiobjective Optimization of On/Off Control Devices Under Geological Uncertainty
Authors: Fonseca R.-M. , Leeuwenburgh O. , Della Rossa E. , Van den Hof P. M. , Jansen J.-D. 
Published: September 2015

Summary
We consider robust ensemble-based (EnOpt) multiobjective production optimization of on/off inflow-control devices (ICDs) for a sector model inspired by a real-field case. The use of on/off valves as optimization variables leads to a discrete control problem. We propose a reparameterization of such discrete controls in terms of switching times (i.e., we optimize the time at which a particular valve is either open or closed). This transforms the discrete control problem into a continuous control problem that can be efficiently handled with the EnOpt method. In addition, this leads to a significant reduction in the number of controls that is expected to be beneficial for gradient quality when using approximate gradients. We consider an ensemble of sector models where the uncertainty is described by different permeability, porosity, net/gross ratios, and initial water-saturation fields. The controls are the ICD settings over time in the three horizontal injection wells, with approximately 15 ICDs per well. Different optimized strategies resulting from different initial strategies were compared. We achieved a mean 4.2% increase in expected net present value (NPV) at a 10% discount rate compared with a traditional pressure-maintenance strategy. Next, we performed a sequential biobjective optimization and achieved an increase of 9.2% in the secondary objective (25% discounted NPV to emphasize short-term production gains) for a minimal decrease of 1% in the primary objective (0% discounted NPV to emphasize long-term recovery gains), as averaged over the 100 geological realizations. The work flow was repeated for alternative numbers of ICDs, showing that having fewer control options lowers the expected value for this particular case. The results demonstrate that ensemble-based optimization work flows are able to produce improved robust recovery strategies for realistic field-sector models against acceptable computational cost.
Incidence of Fractures in Patients With Type 2 Diabetes in the SAVOR-TIMI 53 Trial
Authors: Mosenzon Ofri , Wei Cheryl , Davidson Jaime , Scirica Benjamin M. , Yanuv Ilan , Rozenberg Aliza , Hirshberg Boaz , Cahn Avivit , Stahre Christina , Strojek Krzysztof , Bhatt Deepak L. , Raz Itamar 
Published: September 2015

OBJECTIVE
Patients with type 2 diabetes have an increased risk of bone fractures, the predisposing factors for which are unknown. Treatment with thiazolidinediones (TZDs) further increases the incidence of osteoporotic fractures. In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial, fractures were considered an adverse event of special interest, and information regarding fractures was collected.

RESEARCH DESIGN AND METHODS
We compared the incidence of fractures among the 8,280 patients who were assigned to treatment with saxagliptin with that in the 8,212 patients who were assigned to placebo. We further analyzed the participants’ baseline characteristics and fracture risk.

RESULTS
During a median follow-up of 2.1 years, 241 patients (2.9%) in the saxagliptin group and 240 (2.9%) in the placebo group experienced a fracture (hazard ratio [HR] 1.00 [95% CI 0.83–1.19]). Event rates for fractures were the same in both treatment arms: 14.7 per 1,000 patient-years in the entire population and 14.0 in the on-treatment population (first event only). Fracture risk was similar in patients treated with saxagliptin or placebo across different subgroups defined by race, cardiovascular risk, and renal function. A multivariable Cox regression analysis showed that risk of fracture was associated with female sex (P &lt; 0.0001), longer diabetes duration (P &lt; 0.0001), older age (P = 0.002), major hypoglycemic events (P = 0.01), noncompliance with study drug (P = 0.01), and treatment with TZDs (P = 0.03).

CONCLUSIONS
In a large population of older patients with type 2 diabetes, treatment with saxagliptin was not associated with an increased risk of fractures. The association between longer diabetes duration and increased risk of bone fracture is an intriguing finding.
Causes of 30-day readmission after aneurysmal subarachnoid hemorrhage
Authors: Greenberg Jacob K. , Washington Chad W. , Guniganti Ridhima , Dacey Ralph G. , Derdeyn Colin P. , Zipfel Gregory J. 
Published: September 2015

OBJECT
Hospital readmission is a common but controversial quality measure increasingly used to influence hospital compensation in the US. The objective of this study was to evaluate the causes for 30-day hospital readmission following aneurysmal subarachnoid hemorrhage (SAH) to determine the appropriateness of this performance metric and to identify potential avenues for improved patient care.

METHODS
The authors retrospectively reviewed the medical records of all patients who received surgical orendovas-cular treatment for aneurysmal SAH at Barnes-Jewish Hospital between 2003 and 2013. Two senior faculty identified by consensus the primary medical/surgical diagnosis associated with readmission as well as the underlying causes of rehospitalization.

RESULTS
Among 778 patients treated for aneurysmal SAH, 89 experienced a total of 97 readmission events, yielding a readmission rate of 11.4%. The median time from discharge to readmission was 9 days (interquartile range 3–17.5 days). Actual hydrocephalus or potential concern for hydrocephalus (e.g., headache) was the most frequent diagnosis (26/97, 26.8%), followed by infections (e.g., wound infection [5/97, 5.2%], urinary tract infection [3/97, 3.1%], and pneumonia [3/97, 3.1%]) and thromboembolic events (8/97, 8.2%). In most cases (75/97, 77.3%), we did not identify any treatment lapses contributing to readmission. The most common underlying causes for readmission were unavoidable development of SAH-related pathology (e.g., hydrocephalus; 36/97, 37.1%) and complications related to neurological impairment and immobility (e.g., thromboembolic event despite high-dose chemoprophylaxis; 21/97, 21.6%). The authors determined that 22/97 (22.7%) of the readmissions were likely preventable with alternative management. In these cases, insufficient outpatient medical care (for example, for hyponatremia; 16/97, 16.5%) was the most common shortcoming.

CONCLUSIONS
Most readmissions after aneurysmal SAH relate to late consequences of hemorrhage, such as hydrocephalus, or medical complications secondary to severe neurological injury. Although a minority of readmissions may potentially be avoided with closer medical follow-up in the transitional care environment, readmission after SAH is an insensitive and likely inappropriate hospital performance metric.
Carotid artery plaque assessment using quantitative expansive remodeling evaluation and MRI plaque signal intensity
Authors: Kurosaki Yoshitaka , Yoshida Kazumichi , Fukumitsu Ryu , Sadamasa Nobutake , Handa Akira , Chin Masaki , Yamagata Sen 
Published: September 2015

OBJECT
Plaque characteristics and morphology are important indicators of plaque vulnerability. MRI-detected intraplaque hemorrhage has a great effect on plaque vulnerability. Expansive remodeling, which has been considered compensatory enlargement of the arterial wall in the progression of atherosclerosis, is one of the criteria of vulnerable plaque in the coronary circulation. The purpose of this study was risk stratification of carotid artery plaque through the evaluation of quantitative expansive remodeling and MRI plaque signal intensity.

METHODS
Both preoperative carotid artery T1-weighted axial and long-axis MR images of 70 patients who underwent carotid endarterectomy (CEA) or carotid artery stenting (CAS) were studied. The expansive remodeling ratio (ERR) was calculated from the ratio of the linear diameter of the artery at the thickest segment of the plaque to the diameter of the artery on the long-axis image. Relative plaque signal intensity (rSI) was also calculated from the axial image, and the patients were grouped as follows: Group A = rSI ≥ 1.40 and ERR ≥ 1.66; Group B = rSI< 1.40 and ERR ≥ 1.66; Group C = rSI ≥ 1.40 and ERR < 1.66; and Group D = rSI < 1.40 and ERR < 1.66. Ischemic events within 6 months were retrospectively evaluated in each group.

RESULTS
Of the 70 patients, 17 (74%) in Group A, 6 (43%) in Group B, 7 (44%) in Group C, and 6 (35%) in Group D had ischemic events. Ischemic events were significantly more common in Group A than in Group D (p = 0.01).

CONCLUSIONS
In the present series of patients with carotid artery stenosis scheduled for CEA or CAS, patients with plaque with a high degree of expansion of the vessel and T1 high signal intensity were at higher risk of ischemic events. The combined assessment of plaque characterization with MRI and morphological evaluation using ERR might be useful in risk stratification for carotid lesions, which should be validated by a prospective, randomized study of asymptomatic patients.
Acute promyelocytic leukemia presenting as pulmonary thromboembolism: Not all APLs bleed
Authors: Vaid Ashok K , Batra Sandeep , Karanth Suman S , Gupta Sachin 
Published: September 2015

Abstract
We present a rare case of acute promyelocytic leukemia (APL) presenting as pulmonary thromboembolism being misdiagnosed as community.acquired pneumonia. Thrombotic phenomenon in APL are poorly understood and grossly underreported. In our case, following no response to standard antibiotic treatment, the patient was further investigated and detected to have an acute pulmonary thromboembolism following right lower limb deep vein thrombosis (DVT). Though, complete blood picture revealed only mild hyperleukocytosis, bone marrow biopsy and aspiration revealed 60% blasts and a positive t (15,17)(q22,12) and PML retinoic acid receptor alpha (RARA) fusion protein on molecular cytogenetics. He was diagnosed as APL and received treatment with all.transretinoic acid (ATRA) and arsenic trioxide (ATO) and therapeutic anticoagulation
Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis
Authors: Henry Eric , Cores Jhon , Hensley M. Taylor , Anthony Shirena , Vandergriff Adam , de Andrade James B.M. , Allen Tyler , Caranasos Thomas G. , Lobo Leonard J. , Cheng Ke 
Published: September 2015

Abstract

Lung diseases are devastating conditions and ranked as one of the top five causes of mortality worldwide according to the World Health Organization. Stem cell therapy is a promising strategy for lung regeneration. Previous animal and clinical studies have focused on the use of mesenchymal stem cells (from other parts of the body) for lung regenerative therapies. We report a rapid and robust method to generate therapeutic resident lung progenitors from adult lung tissues. Outgrowth cells from healthy lung tissue explants are self-aggregated into three-dimensional lung spheroids in a suspension culture. Without antigenic sorting, the lung spheroids recapitulate the stem cell niche and contain a natural mixture of lung stem cells and supporting cells. In vitro, lung spheroid cells can be expanded to a large quantity and can form alveoli-like structures and acquire mature lung epithelial phenotypes. In severe combined immunodeficiency mice with bleomycin-induced pulmonary fibrosis, intravenous injection of human lung spheroid cells inhibited apoptosis, fibrosis, and infiltration but promoted angiogenesis. In a syngeneic rat model of pulmonary fibrosis, lung spheroid cells outperformed adipose-derived mesenchymal stem cells in reducing fibrotic thickening and infiltration. Previously, lung spheroid cells (the spheroid model) had only been used to study lung cancer cells. Our data suggest that lung spheroids and lung spheroid cells from healthy lung tissues are excellent sources of regenerative lung cells for therapeutic lung regeneration.

Significance
The results from the present study will lead to future human clinical trials using lung stem cell therapies to treat various incurable lung diseases, including pulmonary fibrosis. The data presented here also provide fundamental knowledge regarding how injected stem cells mediate lung repair in pulmonary fibrosis.
Embedding Four-directional Paths on Convex Point Sets
Authors: Aichholzer Oswin , Hackl Thomas , Lutteropp Sarah , Mchedlidze Tamara , Vogtenhuber Birgit 
Published: September 2015

A directed path whose edges are assigned labels "up", "down", "right", or "left" is called four-directional, and three-directional if at most three out of the four labels are used. A direction-consistent embedding of an n-vertex three- or four-directional path P on a set S of n points in the plane is a straight-line drawing of P where each vertex of P is mapped to a distinct point of S and every edge points to the direction specified by its label. We study planar direction-consistent embeddings of three- and four-directional paths and provide a complete picture of the problem for convex point sets.
Impacts of CME‐induced geomagnetic storms on the midlatitude mesosphere and lower thermosphere observed by a sodium lidar and TIMED/GUVI
Authors: Yuan T. , Zhang Y. , Cai X. , She C.‐Y. , Paxton L. J. 
Published: September 2015

AbstractIn this paper, we report our findings on the correlation between the neutral temperature (around the mesopause) and thermospheric column density O/N2 ratio, along with their response to geomagnetic storms above midlatitude of North America. A temperature/wind Doppler Na lidar, operating at Fort Collins, CO (41°N, 105°W), and later at Logan, UT (42°N and 112°W), observed significant temperature increases (temperature anomaly) above 95 km (as much as 55 K at 105 km altitude) during four coronal mass ejection‐induced geomagnetic storms (April 2002, November 2004, May 2005, and October 2012). Coincident Thermosphere Ionosphere Mesosphere Energetics and Dynamics/Global Ultraviolet Spectrographic Imager observations indicate significant depletion in the thermospheric O/N2 ratio at the lidar locations. These observations suggest that the local mesopause warming seen by the lidar is due to transport of the high‐latitude joule and particle heated neutrals at the E and F layers to the midlatitude region.
Numerical modeling of cold magmatic CO2 flux measurements for the exploration of hidden geothermal systems
Authors: Peiffer Loïc , Wanner Christoph , Pan Lehua 
Published: September 2015

AbstractThe most accepted conceptual model to explain surface degassing of cold magmatic CO2 in volcanic‐geothermal systems involves the presence of a gas reservoir. In this study, numerical simulations using the TOUGH2‐ECO2N V2.0 package are performed to get quantitative insights into how cold CO2 soil flux measurements are related to reservoir and fluid properties. Although the modeling is based on flux data measured at a specific geothermal site, the Acoculco caldera (Mexico), some general insights have been gained. Both the CO2 fluxes at the surface and the depth at which CO2 exsolves are highly sensitive to the dissolved CO2 content of the deep fluid. If CO2 mainly exsolves above the reservoir within a fracture zone, the surface CO2 fluxes are not sensitive to the reservoir size but depend on the CO2 dissolved content and the rock permeability. For gas exsolution below the top of the reservoir, surface CO2 fluxes also depend on the gas saturation of the deep fluid as well as the reservoir size. The absence of thermal anomalies at the surface is mainly a consequence of the low enthalpy of CO2. The heat carried by CO2 is efficiently cooled down by heat conduction and to a certain extent by isoenthalpic volume expansion depending on the temperature gradient. Thermal anomalies occur at higher CO2 fluxes (>37,000 g m−2 d−1) when the heat flux of the rising CO2 is not balanced anymore. Finally, specific results are obtained for the Acoculco area (reservoir depth, CO2 dissolved content, and gas saturation state).
Herbicide Residues in Biota, Analysis of
Authors: Headley John V. , Dickson Leslie C. , Cessna Allan J. , Peru Kerry M. , McMartin Dena W. , Adenugba Adeola A. 
Published: September 2015

AbstractHerbicides are used in agriculture to increase productivity by controlling and inhibiting production of unwanted plants interfering with proper growth and nourishment of valuable crops. Anthropogenic activities have promoted widespread occurrence of herbicide residues in various biota resulting in concerns for animal (including human) and environmental health. This article examines current extraction, cleanup, and instrumental methods available for analyzing herbicide residues in biota, integrating multiresidue methods (MRMs) and miniaturization of apparatus to reduce solvent volumes required for sample extraction and analysis. Methods using miniaturized procedures are additionally beneficial because they tend to be generally less expensive, faster, and less labor intensive than conventional methods and, furthermore, they reduce analyst exposure to hazardous materials.Mass spectrometry (MS), interfaced with high‐resolution gas chromatography (GC) and high‐performance liquid chromatography (HPLC), has become the detection and quantification method of choice for herbicide analysis with many recent improvements due to advances in ionization techniques and analyzer power. These advancements have resulted in higher levels of accuracy, sensitivity, and selectivity, as well as higher sample throughput. Immunoassay (IA) techniques have also emerged as important tools in the detection of herbicides in biota.