bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shear stress–induced unfolding of VWF accelerates oxidation of key methionine residues in the A1A2A3 region
Authors: Fu Xiaoyun , Chen Junmei , Gallagher Ryan , Zheng Ying , Chung Dominic W. , López José A. 
Published: September 2011

Abstract
VWF is required for platelet adhesion to sites of vessel injury, a process vital for both hemostasis and thrombosis. Enhanced VWF secretion and oxidative stress are both hallmarks of inflammation. We recently showed that the neutrophil oxidant hypochlorous acid (HOCl) inhibits VWF proteolysis by ADAMTS13 by oxidizing VWF methionine 1606 (M1606) in the A2 domain. M1606 was readily oxidized in a substrate peptide, but required urea in multimeric plasma VWF. In the present study, we examined whether shear stress enhances VWF oxidation. With an HOCl-generating system containing myeloperoxidase (MPO) and H2O2, we found that shear stress accelerated M1606 oxidation, with 56% becoming oxidized within 1 hour. Seven other methionine residues in the VWF A1A2A3 region (containing the sites for platelet and collagen binding and ADAMTS13 cleavage) were variably oxidized, one completely. Oxidized methionines accumulated preferentially in the largest VWF multimers. HOCl-oxidized VWF was hyperfunctional, agglutinating platelets at ristocetin concentrations that induced minimal agglutination using unoxidized VWF and binding more of the nanobody AU/VWFa-11, which detects a gain-of-function conformation of the A1 domain. These findings suggest that neutrophil oxidants will both render newly secreted VWF uncleavable and alter the largest plasma VWF forms such that they become hyperfunctional and resistant to proteolysis by ADAMTS13.
Homeobox gene Dlx-2 is implicated in metabolic stress-induced necrosis
Authors: Lee Su Yeon , Jeon Hyun Min , Kim Cho Hee , Ju Min Kyung , Bae Hye Sun , Park Hye Gyeong , Lim Sung-Chul , Han Song Iy , Kang Ho Sung 
Published: September 2011

Abstract

Background
In contrast to tumor-suppressive apoptosis and autophagic cell death, necrosis promotes tumor progression by releasing the pro-inflammatory and tumor-promoting cytokine high mobility group box 1 (HMGB1), and its presence in tumor patients is associated with poor prognosis. Thus, necrosis has important clinical implications in tumor development; however, its molecular mechanism remains poorly understood.

Results
In the present study, we show that Distal-less 2 (Dlx-2), a homeobox gene of the Dlx family that is involved in embryonic development, is induced in cancer cell lines dependently of reactive oxygen species (ROS) in response to glucose deprivation (GD), one of the metabolic stresses occurring in solid tumors. Increased Dlx-2 expression was also detected in the inner regions, which experience metabolic stress, of human tumors and of a multicellular tumor spheroid, an in vitro model of solid tumors. Dlx-2 short hairpin RNA (shRNA) inhibited metabolic stress-induced increase in propidium iodide-positive cell population and HMGB1 and lactate dehydrogenase (LDH) release, indicating the important role(s) of Dlx-2 in metabolic stress-induced necrosis. Dlx-2 shRNA appeared to exert its anti-necrotic effects by preventing metabolic stress-induced increases in mitochondrial ROS, which are responsible for triggering necrosis.

Conclusions
These results suggest that Dlx-2 may be involved in tumor progression via the regulation of metabolic stress-induced necrosis.
Genetic mutations in non-syndromic deafness patients of uyghur and han chinese ethnicities in xinjiang, China: a comparative study
Authors: Chen Yu , Tudi Mayila , Sun Jie , He Chao , Lu Hong-li , Shang Qing , Jiang Di , Kuyaxi Pilidong , Hu Bin , Zhang Hua 
Published: September 2011

Abstract

Background
The deafness-associated gene mutation profile varies greatly among regions and races. Due to the multi-ethnic coalition of over one thousand years, non-syndromic deafness (NSD) patients of Uyghur ethnicity may exhibit a unique deafness-associated gene mutation spectrum as compared to Han Chinese deaf population.

Methods
In order to characterize nine loci of four deafness-associated genes of Uyghur NSD patients in comparison with Chinese Han deaf population, NSD patients (n = 350) were enrolled, including Uyghur (n = 199) and Han Chinese (n = 151). Following the history taking, blood samples were collected for DNA extraction. DNA microarray was performed on nine loci of four deafness-associated genes, including 35delG, 176-191del16, 235delC, 299-300delAT, 538C > T, 1555A > G, 1494C > T, 2168A > G, and IVS7-2A > G. The samples that showed the absence of both wild and mutant probe signals were tested for further DNA sequencing analysis.

Results
The mutations in the nine loci of prevalent deafness-associated genes were detected in 13.06% of Uyghur NSD patients and 32.45% of Han Chinese patients (P < 0.05), respectively. GJB2 mutation was detected in 9.05% of Uyghur patients and 16.56% of Han Chinese patients (P > 0.05), respectively. 235delC was the hotspot mutation region in NSD patients of the two ethnicities, whereas 35delG was the mutation hotspot in Uyghur patients. 187delG mutation was detected for the first time in Uyghur NSD patients and considered as an unreported pathological variant of GJB2. SLC26A4 mutation was found in 2.01% of Uyghur patients and 14.57% of Han Chinese patients (P < 0.05), respectively. The frequencies of mtDNA 12S rRNA mutation in Uyghur and Han Chinese patients were 2.01% and 2.65% (P > 0.05), respectively. The NSD patients exhibited a low frequency of GJB3 mutation regardless of ethnicity.

Conclusion
Prevalent deafness-associated gene mutations in the nine loci studied were less frequently detected in Uyghur NSD patients than in Han Chinese patients. GJB2 was the most common mutant gene in the two ethnicities, whilst the two ethnicities differed substantially in hotspot mutations. A low-frequency SLC26A4 mutation was detected in Uyghur NSD patients. Uyghur NSD patients differed significantly from Han Chinese patients in gene mutation profile.
An overview of the rare parotid gland cancer
Authors: Ho Kimberley , Lin Helen , Ann David K , Chu Peiguo G , Yen Yun 
Published: September 2011

AbstractCancer of the parotid gland is relatively rare, but carries poor prognosis owing to its prevailing distant metastases. In addition to the disease's basic epidemiology and pathology, we review some current discoveries of its tumorigenesis molecular mechanism. Based on published salivary gland cancer clinical trial data, non-surgical antitumor efficacies amongst a range of chemotherapy, radiation, and concurrent therapy regimens are compared. We also present the current development status of novel radiation therapy and targeted therapeutics, focusing on intensity-modulated radiation therapy (IMRT), and epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) blockages, which are showing promise for improving parotid gland cancer management.
Population pharmacodynamic model of bicarbonate response to acetazolamide in mechanically ventilated chronic obstructive pulmonary disease patients
Authors: Heming Nicholas , Faisy Christophe , Urien Saïk 
Published: September 2011

Abstract
Introduction
Acetazolamide is commonly given to chronic obstructive pulmonary disease (COPD) patients with metabolic alkalosis. Little is known of the pharmacodynamics of acetazolamide in the critically ill. We undertook the pharmacodynamic modeling of bicarbonate response to acetazolamide in COPD patients under mechanical ventilation.

Methods
This observational, retrospective study included 68 invasively ventilated COPD patients who received one or multiple doses of 250 or 500 mg of acetazolamide during the weaning period. Among the 68 investigated patients, 207 time-serum bicarbonate observations were available for analysis. Population pharmacodynamics was modeled using a nonlinear mixedeffect model. The main covariates of interest were baseline demographic data, Simplified Acute Physiology Score II (SAPS II) at ICU admission, cause of respiratory failure, co-prescription of drugs interfering with the acid-base equilibrium, and serum concentrations of protein, creatinin, potassium and chloride. The effect of acetazolamide on serum bicarbonate levels at different doses and in different clinical conditions was subsequently simulated in silico.

Results
The main covariates interacting with acetazolamide pharmacodynamics were SAPS II at ICU admission (P = 0.01), serum chloride (P < 0.001) and concomitant administration of corticosteroids (P = 0.02). Co-administration of furosemide significantly decreased bicarbonate elimination. Acetazolamide induced a decrease in serum bicarbonate with a dose-response relationship. The amount of acetazolamide inducing 50% of the putative maximum effect was 117 ± 21 mg. According to our model, an acetazolamide dosage > 500 mg twice daily is required to reduce serum bicarbonate concentrations > 5 mmol/L in the presence of high serum chloride levels or coadministration of systemic corticosteroids or furosemide.

Conclusions
This study identified several covariates that influenced acetazolamide pharmacodynamics and could allow a better individualization of acetazolamide dosing when treating COPD patients with metabolic alkalosis.
Mutation discovery in mice by whole exome sequencing
Authors: Fairfield Heather , Gilbert Griffith J , Barter Mary , Corrigan Rebecca R , Curtain Michelle , Ding Yueming , D'Ascenzo Mark , Gerhardt Daniel J , He Chao , Huang Wenhui , Richmond Todd , Rowe Lucy , Probst Frank J , Bergstrom David E , Murray Stephen A , Bult Carol , Richardson Joel , Kile Benjamin T , Gut Ivo , Hager Jorg , Sigurdsson Snaevar , Mauceli Evan , Di Palma Federica , Lindblad-Toh Kerstin , Cunningham Michael L , Cox Timothy C , Justice Monica J , Spector Mona S , Lowe Scott W , Albert Thomas , Donahue Leah Rae , Jeddeloh Jeffrey , Shendure Jay , Reinholdt Laura G 
Published: September 2011

AbstractWe report the development and optimization of reagents for in-solution, hybridization-based capture of the mouse exome. By validating this approach in a multiple inbred strains and in novel mutant strains, we show that whole exome sequencing is a robust approach for discovery of putative mutations, irrespective of strain background. We found strong candidate mutations for the majority of mutant exomes sequenced, including new models of orofacial clefting, urogenital dysmorphology, kyphosis and autoimmune hepatitis.
Revised Reference Curves for Bone Mineral Content and Areal Bone Mineral Density According to Age and Sex for Black and Non-Black Children: Results of the Bone Mineral Density in Childhood Study
Authors: Zemel Babette S. , Kalkwarf Heidi J. , Gilsanz Vicente , Lappe Joan M. , Oberfield Sharon , Shepherd John A. , Frederick Margaret M. , Huang Xiangke , Lu Ming , Mahboubi Soroosh , Hangartner Thomas , Winer Karen K. 
Published: September 2011

Abstract

Context:
Deficits in bone acquisition during growth may increase fracture risk. Assessment of bone health during childhood requires appropriate reference values relative to age, sex, and population ancestry to identify bone deficits.

Objective:
The objective of this study was to provide revised and extended reference curves for bone mineral content (BMC) and areal bone mineral density (aBMD) in children.

Design:
The Bone Mineral Density in Childhood Study was a multicenter longitudinal study with annual assessments for up to 7 yr.

Setting:
The study was conducted at five clinical centers in the United States.

Participants:
Two thousand fourteen healthy children (992 males, 22% African-Americans) aged 5–23 yr participated in the study.

Intervention:
There were no interventions.

Main Outcome Measures:
Reference percentiles for BMC and aBMD of the total body, lumbar spine, hip, and forearm were obtained using dual-energy x-ray absorptiometry for Black and non-Black children. Adjustment factors for height status were also calculated.

Results:
Extended reference curves for BMC and aBMD of the total body, total body less head, lumbar spine, total hip, femoral neck, and forearm for ages 5–20 yr were constructed relative to sex and age for Black and non-Black children. Curves are similar to those previously published for 7–17 year olds. BMC and aBMD values were greater for Black vs. non-Black children at all measurement sites.

Conclusions:
We provide here dual-energy x-ray absorptiometry reference data on a well-characterized cohort of 2012 children and adolescents. These reference curves provide the most robust reference values for the assessment and monitoring of bone health in children and adolescents in the literature to date.
Stem cells in rhythmology — Short communication
Authors: Földes G. 
Published: September 2011

Abstract
Use of stem cells may transform the medical therapy for acute and chronic heart disease, with a predictable impact rivalling the results of revascularization and device therapies. Many cell types have been studied recently, and promising preclinical and clinical data are available on their efficacy and safety in the setting of various disorders such as arrhythmia and conduction disease. However, there are still many hurdles to be tackled for the routine clinical application of these cells. A better understanding of the biology of stem cells will help in the design of future strategies.
Antiarrhythmic drugs for maintaining of sinus rhythm
Authors: Petrač D. 
Published: September 2011

Abstract
The pharmacological strategy to treat atrial fibrillation (AF) has been studied in the last years by a number of randomized studies. The overall results showed that the rhythm control strategy is not superior to the rate control strategy in terms of mortality or stroke, mostly due to limited efficacy and toxicity of antiarrhyhtmic drugs in the rhythm control patients. Regarding to these data, current antiarrhythmic therapy for recurrent AF is recommended on the basis of choosing safer, although possibly less efficacious drug. Flecainide, propafenone, sotalol and dronedarone are the first-line drugs for patients with a minimal or no heart disease, or hypertension without left ventricular hypertrophy. Sotalol and dronedarone are recommended as first-line drugs for patients with a coronary artery disease. Dronedarone should be considered in order to reduce cardiovascular hospitalizations related to AF/flutter. It can also be used safely in patients with hypertensive heart disease and stable NYHA class I-II heart failure. Amiodarone is the most effective antiarrhythmic in all clinical settings, but because of its toxicity profile should generally be used when other agents have failed or are contraindicated. Amiodarone is recommended as drug of choice in patients with severe heart failure or recently unstable NYHA class II.
Lessons Learned and Experiences Gained in Developing the Waterflooding Concept of a Fractured Basement-Granite Reservoir: A 20-Year Case Study
Authors: Dang Cuong T.Q. , Chen Zhangxing John , Nguyen Ngoc T.B. , Bae Wisup , Phung Thuoc H. 
Published: September 2011

Summary
Naturally fractured reservoirs (NFRs) represent more than 20% of the world's oil and gas reserves. However, their characterization is complex and presents unique challenges in comparison with conventional reservoirs. It is immensely difficult to achieve the best results in the secondary-recovery process for NFRs.
This paper presents a successful development of waterflooding to overcome the complex geological characterization of the White Tiger field, the largest fractured basement reservoir to date on the continental shelf of Vietnam. This reservoir has a complicated geological structure, with high heterogeneity, high temperature, and high closure stress. The total oil initially in place (OIIP) of this field reached nearly 4 billion bbl from 2000 m of oil-bearing thickness, and the field has been produced by more than 100 wells, 10 of which have flowed at the rate of approximately 1,000 B/D.
The geological study and fractured model have been carefully investigated in both micro- and macroscale to improve waterflooding performance. The authors have analyzed the advantages and disadvantages of injection systems in this basement reservoir during 20 years of production history, and an artificial water buffer solution has been proposed to improve the waterflooding process. The authors have described the establishment and association of local artificial water buffer in the basement reservoir. An effective method to optimize the injected-water volume has also been discussed. Promising results from the White Tiger field have shown that the average reservoir pressure and total oil recovery have increased significantly in comparison with previous injection schemes.
This paper presents useful guidelines to solve some typical problems of waterflooding in fractured basement reservoirs:
What can be applied in waterflooding for a fractured basement reservoir?
What is the optimal injection rate and injected volume for the fractured basement reservoir?
How do we evaluate the probability of high water cut in production wells during the waterflooding process?
How do we predict the rise of an artificial water/oil contact (AWOC)?
Ongoing Development of Cementing Practices and Technologies for Kuwait Oil Company's Deep HP/HT Exploration and Gas Wells: Case History
Authors: Al-Saeedi M.J.. J. , Al-Enezi D.. , Al-Mudhaf M.N.A.. N.A. , Modak T.. , McKinnell D.C.. C. 
Published: September 2011

Summary
Exploration activities in Kuwait have been focused on the search for high-quality oil from the Jurassic formations and gas in the Triassic/Permian series. The wells drilled to these prospects are very challenging because of high-pressure/high-temperature (HP/ HT) conditions, large casing sizes, oil-based mud, the presence of high levels of H2S and CO2, and a narrow pore-/fracture-pressure window. In particular, the cementing of the deep strings in these wells has been extremely challenging. Over the last 8 years, a concentrated effort has been made to introduce new technologies and materials to improve the cementing practices both from operational and safety aspects.
In 2003, the success ratio for deep cementations was highly variable. The Kuwait Oil Company (KOC), along with one of their cementing service providers, worked on a series of changes to practices and materials with the aim of improving job quality with high repeatability. This was based primarily on the technologies being developed in HP/HT wells around the globe, especially in the North Sea, and it resulted in a notable improvement in cementing performance.
Technologies and practices that had been developed include spacer technology, application of synthetic retarders, fluid-loss and antigas-migration additive improvements, development of finegrained weighting additives, use of HP/HT rheometers, systematic product control, the minimizing of handling, and safer mixing practices at the wellsite.
This paper will discuss the application of these technologies, materials, and practices over an 8-year period as a case history to illustrate the improvements made in achieving consistent cement quality and final slurry placement for the deep-casing and liner strings, and will conclude with recommendations and lessons learned during this process.
Integrated Reservoir Modeling of a Large Sour-Gas Field With High Concentrations of Inerts
Authors: Huang N.S.. S. , Aho G.E.. E. , Baker B.H.. H. , Matthews T.R.. R. , Pottorf R.J.. J. 
Published: September 2011

Summary
The LaBarge project demonstrates the successful commercialization of a very large gas resource representative of the increasingly challenging projects faced by our industry. Three particularly distinctive aspects are (1) it is one of the largest acid-gas-reinjection projects in the world, (2) the composition is nearly 80% nonhydrocarbon, and (3) the initial compositional gradient cannot be explained by gravity segregation. This paper describes integrated reservoir modeling studies conducted to evaluate key reservoir and operational uncertainties. The integrated studies led to a new hypothesis for the initial compositional gradient and illustrated fit-for-purpose modeling approaches for reservoir fluid charging and mixing, black-oil simulation, and an integrated production network. The studies were used to optimize the drilling and depletion plan to maximize methane production with current facilities and end-of-field-life assumptions, and to analyze acid-gas injection (AGI) into the aquifer.
Comparative Evaluation of a New Gas/Oil Miscibility-Determination Technique
Authors: Ayirala Subhash C. , Rao Dandina N. 
Published: September 2011

Summary
A new experimental technique of vanishing interfacial tension (VIT) has been reported in recent literature for quick and cost-effective determination of gas/oil miscibility. However, this technique has been criticized because of the perceived absence of compositional-path specification and lack of confirmation against standard gas/oil systems. In this paper, we address these concerns by conducting interfacial-tension (IFT) measurements at elevated pressures and temperatures in two standard gas/oil systems and at varying molar compositions of gas and oil in feed mixtures.
Though gas/oil ratio was found to have an impact on mass-transfer rates, the IFT between gas and oil was unaffected in the two standard gas/oil systems as the fluid phases approached equilibrium. This indicates compositional-path independence of gas/oil IFTs measured at near-equilibrium conditions; hence, miscibilities determined using the VIT technique. The minimum miscibility pressures (MMPs) determined using the VIT technique acceptably matched (within 5 to 8%) with the reported slim tube miscibilities for both the standard gas/oil systems. These experimental results clearly support wide use of the VIT technique for rapid and cost-effective determination of MMPs and minimum miscibility enrichments (MMEs) in improved-oil-recovery applications.
Validation of a low-dose ACTH stimulation test in healthy adult horses
Authors: Stewart Allison J. , Behrend Ellen N. , Wright James C. , Martin Linda G. , Kemppainen Robert J. , Busch Katherine A. , Hanson R. Reid 
Published: September 2011

Abstract
Objective—To determine the lowest ACTH dose that would induce a maximum increase in serum cortisol concentration in healthy adult horses and identify the time to peak cortisol concentration.
Design—Evaluation study.
Animals—8 healthy adult horses.
Procedures—Saline (0.9% NaCl) solution or 1 of 4 doses (0.02, 0.1, 0.25, and 0.5 μg/kg [0.009, 0.045, 0.114, and 0.227 μg/lb]) of cosyntropin (synthetic ACTH) were administered IV (5 treatments/horse). Serum cortisol concentrations were measured before and 30, 60, 90, 120, 180, and 240 minutes after injection of cosyntropin or saline solution; CBCs were performed before and 30, 60, 120, and 240 minutes after injection.
Results—For all 4 doses, serum cortisol concentration was significantly increased, compared with the baseline value, by 30 minutes after administration of cosyntropin; no significant differences were detected among maximum serum cortisol concentrations obtained in response to administration of doses of 0.1, 0.25, and 0.5 μg/kg. Serum cortisol concentration peaked 30 minutes after administration of cosyntropin at a dose of 0.02 or 0.1 μg/kg, with peak concentrations 1.5 and 1.9 times, respectively, the baseline concentration. Serum cortisol concentration peaked 90 minutes after administration of cosyntropin at a dose of 0.25 or 0.5 μg/kg, with peak concentrations 2.0 and 2.3 times, respectively, the baseline concentration. Cosyntropin administration significantly affected WBC, neutrophil, and eosinophil counts and the neutrophil-to-lymphocyte ratio.
Conclusions and Clinical Relevance—Results suggested that in healthy horses, administration of cosyntropin at a dose of 0.1 μg/kg resulted in maximum adrenal stimulation, with peak cortisol concentration 30 minutes after cosyntropin administration.