bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the design of perturbation-resilient atomic commit protocols for mobile transactions
Authors: Ayari Brahim , Khelil Abdelmajid , Suri Neeraj 
Published: August 2011

Distributed mobile transactions utilize commit protocols to achieve atomicity and consistent decisions. This is challenging, as mobile environments are typically characterized by frequent perturbations such as network disconnections and node failures. On one hand environmental constraints on mobile participants and wireless links may increase the resource blocking time of fixed participants. On the other hand frequent node and link failures complicate the design of atomic commit protocols by increasing both the transaction abort rate and resource blocking time. Hence, the deployment of classical commit protocols (such as two-phase commit) does not reasonably extend to distributed infrastructure-based mobile environments driving the need for perturbation-resilient commit protocols.
In this article, we comprehensively consider and classify the perturbations of the wireless infrastructure-based mobile environment according to their impact on the outcome of commit protocols and on the resource blocking times. For each identified perturbation class a commit solution is provided. Consolidating these subsolutions, we develop a family of fault-tolerant atomic commit protocols that are tunable to meet the desired perturbation needs and provide minimized resource blocking times and optimized transaction commit rates. The framework is also evaluated using simulations and an actual testbed deployment.
An Iron Regulatory Gene Signature Predicts Outcome in Breast Cancer
Authors: Miller Lance D. , Coffman Lan G. , Chou Jeff W. , Black Michael A. , Bergh Jonas , D'Agostino Ralph , Torti Suzy V. , Torti Frank M. 
Published: August 2011

Abstract
Changes in iron regulation characterize the malignant state. However, the pathways that effect these changes and their specific impact on prognosis remain poorly understood. We capitalized on publicly available microarray datasets comprising 674 breast cancer cases to systematically investigate how expression of genes related to iron metabolism is linked to breast cancer prognosis. Of 61 genes involved in iron regulation, 49% were statistically significantly associated with distant metastasis-free survival. Cases were divided into test and training cohorts, and the supervised principal component method was used to stratify cases into risk groups. Optimal risk stratification was achieved with a model comprising 16 genes, which we term the iron regulatory gene signature (IRGS). Multivariable analysis revealed that the IRGS contributes information not captured by conventional prognostic indicators (HR = 1.61; 95% confidence interval: 1.16–2.24; P = 0.004). The IRGS successfully stratified homogeneously treated patients, including ER+ patients treated with tamoxifen monotherapy, both with (P = 0.006) and without (P = 0.03) lymph node metastases. To test whether multiple pathways were embedded within the IRGS, we evaluated the performance of two gene dyads with known roles in iron biology in ER+ patients treated with tamoxifen monotherapy (n = 371). For both dyads, gene combinations that minimized intracellular iron content [anti-import: TFRCLow/HFEHigh; or pro-export: SLC40A1 (ferroportin)High/HAMPLow] were associated with favorable prognosis (P &lt; 0.005). Although the clinical utility of the IRGS will require further evaluation, its ability to both identify high-risk patients within traditionally low-risk groups and low-risk patients within high-risk groups has the potential to affect therapeutic decision making. Cancer Res; 71(21); 6728–37. ©2011 AACR.
Proteolytic Activation of Pro-Macrophage-Stimulating Protein by Hepsin
Authors: Ganesan Rajkumar , Kolumam Ganesh A. , Lin S. Jack , Xie Ming-Hong , Santell Lydia , Wu Thomas D. , Lazarus Robert A. , Chaudhuri Amitabha , Kirchhofer Daniel 
Published: August 2011

Abstract
Macrophage-stimulating protein (MSP) is a plasminogen-related growth factor and ligand for the receptor tyrosine kinase RON. The MSP/RON system promotes wound healing and invasive tumor growth and suppresses proinflammatory immune response. MSP binding to RON requires proteolytic conversion of the inactive single-chain form (pro-MSP) into the disulfide-linked α/β heterodimer. The pro-MSP cleavage sequence (Ser-Lys-Leu-Arg483↓Val484) closely matches the substrate recognition sequences of hepsin, a type II transmembrane serine protease, that is overexpressed in several cancers. Here, we show that recombinant hepsin cleaves pro-MSP at the consensus site Arg483-Val484 with superior efficiency compared with the known activators MT-SP1 and hepatocyte growth factor activator (HGFA). At least 50% of pro-MSP was processed within 1 hour at a hepsin concentration of 2.4 nmol/L and at a molar enzyme to substrate ratio of 1:500. An uncleavable single-chain variant of MSP weakly bound to a RON–Fc fusion protein, whereas hepsin-cleaved MSP bound with a KD of 10.3 nmol/L, suggesting that the high-affinity binding site in MSP β-chain was properly formed. LNCaP prostate cancer cells overexpressing hepsin on the cell surface efficiently activated pro-MSP, which was blocked by a specific anti-hepsin antibody. Incubation of pro-MSP with hepsin led to robust RON-mediated phosphorylation of mitogen-activated protein kinase, ribosomal S6 protein, and Akt in human A2780 ovarian carcinoma cells stably expressing RON protein. In macrophages, pro-MSP with hepsin induced chemotaxis and attenuated lipopolysaccharide-dependent production of nitric oxide. These findings suggest that the MSP/RON signaling pathway may be regulated by hepsin in tissue homeostasis and in disease pathologies, such as in cancer and immune disorders. Mol Cancer Res; 9(9); 1175–86. ©2011 AACR.
ADAM12 Produced by Tumor Cells Rather than Stromal Cells Accelerates Breast Tumor Progression
Authors: Fröhlich Camilla , Nehammer Camilla , Albrechtsen Reidar , Kronqvist Pauliina , Kveiborg Marie , Sehara-Fujisawa Atsuko , Mercurio Arthur M. , Wewer Ulla M. 
Published: August 2011

Abstract
Expression of ADAM12 is low in most normal tissues but is markedly increased in numerous human cancers, including breast carcinomas. We have previously shown that overexpression of ADAM12 accelerates tumor progression in a mouse model of breast cancer (PyMT). In this study, we found that ADAM12 deficiency reduces breast tumor progression in the PyMT model. However, the catalytic activity of ADAM12 seems to be dispensable for its tumor-promoting effect. Interestingly, we show that ADAM12 endogenously expressed in tumor-associated stroma in the PyMT model does not influence tumor progression, but that ADAM12 expression by tumor cells is necessary for tumor progression in these mice. This finding is consistent with our observation that in human breast carcinoma, ADAM12 is almost exclusively located in tumor cells and, only rarely, seen in the tumor-associated stroma. We hypothesized, however, that the tumor-associated stroma may stimulate ADAM12 expression in tumor cells, on the basis of the fact that TGF-β1 stimulates ADAM12 expression and is a well-known growth factor released from tumor-associated stroma. TGF-β1 stimulation of ADAM12-negative Lewis lung tumor cells induced ADAM12 synthesis, and growth of these cells in vivo induced more than 200-fold increase in ADAM12 expression. Our observation that ADAM12 expression is significantly higher in the terminal duct lobular units (TDLU) adjacent to human breast carcinoma compared with TDLUs found in normal breast tissue supports our hypothesis that tumor-associated stroma triggers ADAM12 expression. Mol Cancer Res; 9(11); 1449–61. ©2011 AACR.
Long-Term Outcome of Patients With Isolated Thin Discrete Subaortic Stenosis Treated by Balloon Dilation
Authors: de Lezo José Suárez , Romero Miguel , Segura José , Pan Manuel , de Lezo Javier Suárez , Pavlovic Djordje , Mazuelos Francisco , Delgado Mónica , Mesa Dolores 
Published: August 2011

Background—
Transluminal balloon tearing of the membrane in a thin discrete subaortic stenosis is an alternative to membrane surgical resection. However, the long-term outcome of patients with isolated thin discrete subaortic stenosis treated by transluminal balloon tearing remains unknown.

Methods and Results—

This 25-year study describes findings from 76 patients with isolated thin discrete subaortic stenosis who underwent percutaneous transluminal balloon tearing of the membrane and were followed up for a mean period of 16±6 years. The age at presentation had a wide range (2–67 years). The mean age at treatment was 19±16 years. Immediately after treatment, the subvalvular gradient decreased from 70±27 to 18±12 mm Hg (
P
<0.001). No significant postprocedural aortic regurgitation was observed. After a mean follow-up time of 16±6 years, 11 patients (15%) developed restenosis, 3 patients (4%) progressed to muscular obstructive disease, and 1 patient (1.3%) developed a new distant obstructive membrane. Twelve patients (16%) were redilated at a mean of 5±3 years after their first treatment, and 4 patients (5%) underwent surgery at a mean of 3±2 years after their first treatment. Fifty-eight patients (77%) remained alive and free of redilation or surgery at follow-up. Larger annulus diameter and thinner membranes were independent factors associated with better long-term results.

Conclusions—
Most patients (77%) with isolated thin discrete subaortic stenosis treated with transluminal balloon tearing of the membrane had sustained relief at subsequent follow-ups without restenosis, the need for surgery, progression to muscular obstructive disease, or an increase in the degree of aortic regurgitation.
Exercise Oscillatory Ventilation in Systolic Heart Failure
Authors: Murphy Ryan M. , Shah Ravi V. , Malhotra Rajeev , Pappagianopoulos Paul P. , Hough Stacyann S. , Systrom David M. , Semigran Marc J. , Lewis Gregory D. 
Published: August 2011

Background—
Exercise oscillatory ventilation (EOV) is a noninvasive parameter that potently predicts outcomes in systolic heart failure (HF). However, mechanistic insights into EOV have been limited by the absence of studies relating EOV to invasive hemodynamic measurements and blood gases performed during exercise.

Methods and Results—

Fifty-six patients with systolic HF (mean±SEM age, 59±2 years; left ventricular ejection fraction, 30±1%) and 19 age-matched control subjects were studied with incremental cardiopulmonary exercise testing. Fick cardiac outputs, filling pressures, and arterial blood gases were measured at 1-minute intervals during exercise. We detected EOV in 45% of HF (HF+EOV) patients and in none of the control subjects. The HF+EOV group did not differ from the HF patients without EOV (HF−EOV) in age, sex, body mass index, left ventricular ejection fraction, or origin of HF. Univariate predictors of the presence of EOV in HF, among measurements performed during exercise, included higher right atrial pressure and pulmonary capillary wedge pressure and lower cardiac index (CI) but not Pa
co
2
or Pa
o
2
. Multivariate logistic regression identified that low exercise CI is the strongest predictor of EOV (odds ratio, 1.39 for each 1.0-L · min
−1
· m
−2
decrement in CI; 95% confidence interval, 1.14–1.70;
P
=0.001). Among HF patients with EOV, exercise CI was inversely related to EOV cycle length (
R
=−0.71) and amplitude (
R
=−0.60; both
P
<0.001). In 11 HF+EOV subjects treated with 12 weeks of sildenafil, EOV cycle length and amplitude decreased proportionately to increases in CI.

Conclusion—
Exercise oscillatory ventilation is closely related to reduced CI and elevated filling pressures during exercise and may be an important surrogate for exercise-induced hemodynamic impairment in HF patients.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00309790.
Adolescents With d-Transposition of the Great Arteries Corrected With the Arterial Switch Procedure
Authors: Bellinger David C. , Wypij David , Rivkin Michael J. , DeMaso David R. , Robertson Richard L. , Dunbar-Masterson Carolyn , Rappaport Leonard A. , Wernovsky Gil , Jonas Richard A. , Newburger Jane W. 
Published: August 2011

Background—
We report neuropsychological and structural brain imaging assessments in children 16 years of age with d-transposition of the great arteries who underwent the arterial switch operation as infants. Children were randomly assigned to a vital organ support method, deep hypothermia with either total circulatory arrest or continuous low-flow cardiopulmonary bypass.

Methods and Results—
Of 159 eligible adolescents, 139 (87%) participated. Academic achievement, memory, executive functions, visual-spatial skills, attention, and social cognition were assessed. Few significant treatment group differences were found. The occurrence of seizures in the postoperative period was the medical variable most consistently related to worse outcomes. The scores of both treatment groups tended to be lower than those of the test normative populations, with substantial proportions scoring ≥1 SDs below the expected mean. Although the test scores of most adolescents in this trial cohort are in the average range, a substantial proportion have received remedial academic or behavioral services (65%). Magnetic resonance imaging abnormalities were more frequent in the d-transposition of the great arteries group (33%) than in a referent group (4%).

Conclusions—
Adolescents with d-transposition of the great arteries who have undergone the arterial switch operation are at increased neurodevelopmental risk. These data suggest that children with congenital heart disease may benefit from ongoing surveillance to identify emerging difficulties.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00000470.
Platelet Reactivity and Cardiovascular Outcomes After Percutaneous Coronary Intervention
Authors: Price Matthew J. , Angiolillo Dominick J. , Teirstein Paul S. , Lillie Elizabeth , Manoukian Steven V. , Berger Peter B. , Tanguay Jean-François , Cannon Christopher P. , Topol Eric J. 
Published: August 2011

Background—
In the Gauging Responsiveness With A VerifyNow P2Y12 Assay: Impact on Thrombosis and Safety (GRAVITAS) trial, 6 months of high-dose clopidogrel did not reduce cardiovascular events compared with standard-dose clopidogrel in patients with high on-treatment platelet reactivity (OTR) after percutaneous coronary intervention, defined as OTR ≥230 P2Y12 reaction units according to the VerifyNow P2Y12 platelet function test. The aim of this analysis was to examine the relationship between outcomes and OTR over the course of the trial.

Methods and Results—

OTR was measured at 12 to 24 hours and 30±7 days after percutaneous coronary intervention. Cox proportional hazards models with OTR as a time-varying covariate were used to determine the association between OTR and the primary end point of cardiovascular death, myocardial infarction, and stent thrombosis. Of the 2800 enrolled patients, 2796 (99.98%) had evaluable platelet function data. OTR <208 P2Y12 reaction units was significantly associated with a lower risk of the primary end point at 60 days (hazard ratio, 0.18; 95% confidence interval, 0.04 to 0.79;
P
=0.02) and at 6 months (hazard ratio, 0.43; 95% confidence interval, 0.23 to 0.82;
P
=0.01). After adjustment for other significant predictors of outcome, OTR <208 P2Y12 reaction units remained independently associated with the primary end point at 60 days (hazard ratio, 0.23; 95% confidence interval, 0.05 to 0.98;
P
=0.047) and tended to be associated at 6 months (adjusted hazard ratio, 0.54; 95% confidence interval, 0.28 to 1.04;
P
=0.065).

Conclusions—
In the GRAVITAS trial, achievement of on-clopidogrel reactivity <208 P2Y12 reaction units at 12 to 24 hours after percutaneous coronary intervention or during follow-up was associated with a lower risk for cardiovascular events. The efficacy of an individualized strategy to target a level of OTR below this threshold merits investigation.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier: NCT00645918.
Cigarette Smoking and Inflammation
Authors: Lee J. , Taneja V. , Vassallo R. 
Published: August 2011

Cigarette smoke (CS) causes considerable morbidity and mortality by inducing cancer, chronic lung and vascular diseases, and oral disease. Despite the well-recognized risks associated with smoking, the habit remains unacceptably prevalent. Several toxins present in CS have immunomodulatory effects. CS also contains trace amounts of microbial cell components, including bacterial lipopolysaccharide. These and other CS constituents induce chronic inflammation at mucosal surfaces and modify host responses to exogenous antigens. The effects of CS on immunity are far-reaching and complex; both pro-inflammatory and suppressive effects may be induced. The net effect of CS on immunity depends on many variables, including the dose and type of tobacco, the route and chronicity of exposure, and the presence of other factors at the time of immune cell stimulation, such as Toll receptor ligands or other inflammatory mediators. CS impairs innate defenses against pathogens, modulates antigen presentation, and promotes autoimmunity. CS also impairs immunity in the oral cavity and promotes gingival and periodontal disease and oral cancer. The recognition of specific mechanisms by which CS affects host immunity is an important step toward elucidating mechanisms of tobacco-induced disease and may identify novel therapeutic approaches for the management of diseases that afflict smokers. Abbreviations: AP-1, activator protein-1; CD, cluster of differentiation; COPD, chronic obstructive pulmonary disease; HLA, human leukocyte antigen; IFNγ, interferon gamma; IL, interleukin; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor kappa-B; RAGE, receptors for advanced glycation end-products; ROS, reactive oxidative species; RORγτ, retinoic acid receptor-related orphan receptor transcription factor; STAT, signal transducer and activator of transcription; T-bet, T-box transcription factor; Th, T-helper; TLR, Toll-like receptors; TNFα, Tumor necrosis factor alpha; and TSLP, thymic stromal lymphopoeitin.
Glenohumeral Muscle Activation During Provocative Tests Designed to Diagnose Superior Labrum Anterior-Posterior Lesions
Authors: Wood Vanessa J.C. , Sabick Michelle B. , Pfeiffer Ron P. , Kuhlman Seth M. , Christensen Jason H. , Curtin Michael J. 
Published: August 2011

Background: Despite considerable medical advances, arthroscopy remains the only definitive means of superior labrum anterior-posterior (SLAP) lesion diagnosis. Natural shoulder anatomic variants limit the reliability of radiographic findings and clinical evaluations are not consistent. Accurate clinical diagnostic techniques would be advantageous because of the invasiveness, patient risk, and financial cost associated with arthroscopy. Purpose: The purpose of this study was to examine the behavior of the joint-stabilizing muscles in provocative tests for SLAP lesions. Electromyography was used to characterize the muscle behavior, with particular interest in the long head of the biceps brachii (LHBB), as activation of the long head and subsequent tension in the biceps tendon should, based on related research, elicit labral symptoms in SLAP lesion patients. Study Design: Controlled laboratory study. Methods: Volunteers (N = 21) without a history of shoulder injury were recruited. The tests analyzed were active compression, Speed’s, pronated load, biceps load I, biceps load II, resisted supination external rotation, and Yergason’s. Tests were performed with a dynamometer to improve reproducibility. Muscle activity was recorded for the long and short heads of the biceps brachii, anterior deltoid, pectoralis major, latissimus dorsi, infraspinatus, and supraspinatus. Muscle behavior for each test was characterized by peak activation and proportion of muscle activity. Results: Speed’s, active compression palm-up, bicep I, and bicep II produced higher long head activations. Resisted supination external rotation, bicep I, bicep II, and Yergason’s produced a higher LHBB proportion. Conclusion: Biceps load I and biceps load II elicited promising long head behavior (high activation and selectivity). Speed’s and active compression palm up elicited higher activation of the LHBB, and resisted supination and Yergason’s elicited selective LHBB activity. These top performing tests utilize a unique range of test variables that may prove valuable for optimal SLAP test design and performance. Clinical Relevance: This study examines several provocative tests that are frequently used in the clinical setting as a means of evaluating a potential SLAP lesion.
The practice of evidence-based medicine (EBM) in gastroenterology: discrepancies between EBM familiarity and EBM competency
Authors: Buscaglia Jonathan , Nagula Satish , Yuan Jay , Bucobo Juan Carlos , Kumar Atul , Forsmark Chris E. , Draganov Peter V. 
Published: August 2011

Introduction: Evidence-based medicine (EBM) has become increasingly important in the practice of gastroenterology and endoscopy, and the training of future gastroenterology physicians. The objectives were to assess the attitudes/opinions of gastroenterology specialists towards EBM, and evaluate possible gaps in education for certain EBM-related concepts. Methods: An internet-based survey was emailed to 4073 gastroenterology specialists. The main outcome measurements were physicians’ endorsement of EBM, impact of EBM on clinical practice, utilization of EBM-specific resources, self-assessed understanding of EBM concepts (EBM familiarity score), and actual knowledge of EBM concepts (EBM competency score). Results: A total of 337 gastroenterology specialists participated. On a sale of 1–10, there was widespread agreement that EBM improves patient care (median score = 9, interquartile range (IQR) = 7–10), and physicians should be familiar with techniques for critical appraisal of studies (median = 9, IQR = 8–10). Most (64.0%) utilized the EBM-related resource UpToDate™ regularly, as opposed to PubMed™ (47.1%) or Clinical Evidence™ (5.4%). The mean EBM familiarity score was 3.4 ± 0.6 on a scale of 1–4. Out of a maximum 49 points, the mean EBM competency score was 35 ± 4.9. There was poor concordance among EBM familiarity and competency scores ( r = 0.161; p = 0.005). Academic practice ( p < 0.001), research/teaching ( p < 0.001), advanced degree ( p = 0.012), and recent EBM training ( p = 0.001) were all associated with improved EBM competency. Conclusion: The attitudes and opinions of EBM are extremely favorable among gastroenterology physicians. Although gastroenterology physicians report familiarity with most EBM-related concepts, there is poor correlation with their actual knowledge of EBM. Further educational initiatives should be undertaken to address methods in which EBM skills are reinforced among all gastroenterology practitioners.