bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clearing the clouds
Authors: Ferdman Michael , Adileh Almutaz , Kocberber Onur , Volos Stavros , Alisafaee Mohammad , Jevdjic Djordje , Kaynak Cansu , Popescu Adrian Daniel , Ailamaki Anastasia , Falsafi Babak 
Published: April 2012

Emerging scale-out workloads require extensive amounts of computational resources. However, data centers using modern server hardware face physical constraints in space and power, limiting further expansion and calling for improvements in the computational density per server and in the per-operation energy. Continuing to improve the computational resources of the cloud while staying within physical constraints mandates optimizing server efficiency to ensure that server hardware closely matches the needs of scale-out workloads.
In this work, we introduce CloudSuite, a benchmark suite of emerging scale-out workloads. We use performance counters on modern servers to study scale-out workloads, finding that today's predominant processor micro-architecture is inefficient for running these workloads. We find that inefficiency comes from the mismatch between the workload needs and modern processors, particularly in the organization of instruction and data memory systems and the processor core micro-architecture. Moreover, while today's predominant micro-architecture is inefficient when executing scale-out workloads, we find that continuing the current trends will further exacerbate the inefficiency in the future. In this work, we identify the key micro-architectural needs of scale-out workloads, calling for a change in the trajectory of server processors that would lead to improved computational density and power efficiency in data centers.
Iterative optimization for the data center
Authors: Chen Yang , Fang Shuangde , Eeckhout Lieven , Temam Olivier , Wu Chengyong 
Published: April 2012

Iterative optimization is a simple but powerful approach that searches for the best possible combination of compiler optimizations for a given workload. However, each program, if not each data set, potentially favors a different combination. As a result, iterative optimization is plagued by several practical issues that prevent it from being widely used in practice: a large number of runs are required for finding the best combination; the process can be data set dependent; and the exploration process incurs significant overhead that needs to be compensated for by performance benefits.Therefore, while iterative optimization has been shown to have significant performance potential, it is seldomly used in production compilers.
In this paper, we propose Iterative Optimization for the Data Center (IODC): we show that servers and data centers offer a context in which all of the above hurdles can be overcome. The basic idea is to spawn different combinations across workers and recollect performance statistics at the master, which then evolves to the optimum combination of compiler optimizations. IODC carefully manages costs and benefits, and is transparent to the end user. We evaluate IODC using both MapReduce and throughput compute-intensive server applications. In order to reflect the large number of users interacting with the system, we gather a very large collection of data sets (at least 1000 and up to several million unique data sets per program), for a total storage of 10.7TB, and 568 days of CPU time. We report an average performance improvement of 1.48×, and up to 2.08×, for the MapReduce applications, and 1.14×, and up to 1.39×, for the throughput compute-intensive server applications.
Data races vs. data race bugs
Authors: Kasikci Baris , Zamfir Cristian , Candea George 
Published: April 2012

Even though most data races are harmless, the harmful ones are at the heart of some of the worst concurrency bugs. Alas, spotting just the harmful data races in programs is like finding a needle in a haystack: 76%-90% of the true data races reported by state-of-the-art race detectors turn out to be harmless [45]. We present Portend, a tool that not only detects races but also automatically classifies them based on their potential consequences: Could they lead to crashes or hangs? Could their effects be visible outside the program? Are they harmless? Our proposed technique achieves high accuracy by efficiently analyzing multiple paths and multiple thread schedules in combination, and by performing symbolic comparison between program outputs.
We ran Portend on 7 real-world applications: it detected 93 true data races and correctly classified 92 of them, with no human effort. 6 of them are harmful races. Portend's classification accuracy is up to 88% higher than that of existing tools, and it produces easy-to-understand evidence of the consequences of harmful races, thus both proving their harmfulness and making debugging easier. We envision Portend being used for testing and debugging, as well as for automatically triaging bug reports.
Forced Mitotic Entry of S-Phase Cells as a Therapeutic Strategy Induced by Inhibition of WEE1
Authors: Aarts Marieke , Sharpe Rachel , Garcia-Murillas Isaac , Gevensleben Heidrun , Hurd Melissa S. , Shumway Stuart D. , Toniatti Carlo , Ashworth Alan , Turner Nicholas C. 
Published: April 2012

Abstract
Inhibition of the protein kinase WEE1 synergizes with chemotherapy in preclinical models and WEE1 inhibitors are being explored as potential cancer therapies. Here, we investigate the mechanism that underlies this synergy. We show that WEE1 inhibition forces S-phase–arrested cells directly into mitosis without completing DNA synthesis, resulting in highly abnormal mitoses characterized by dispersed chromosomes and disorganized bipolar spindles, ultimately resulting in mitotic exit with gross micronuclei formation and apoptosis. This mechanism of cell death is shared by CHK1 inhibitors, and combined WEE1 and CHK1 inhibition forces mitotic entry from S-phase in the absence of chemotherapy. We show that p53/p21 inactivation combined with high expression of mitotic cyclins and EZH2 predispose to mitotic entry during S-phase with cells reliant on WEE1 to prevent premature cyclin-dependent kinase (CDK)1 activation. These features are characteristic of aggressive breast, and other, cancers for which WEE1 inhibitor combinations represent a promising targeted therapy.
Significance: Here, we describe a novel mechanism of inducing cancer cell death by WEE1 inhibition, forcing mitotic entry directly from S-phase. This mechanism represents a potential therapeutic approach for aggressive breast cancers, and in particular triple-negative and basal-like breast cancers, as WEE1 inhibition specifically targets the features inherent in these cancers: frequent TP53 mutation and high expression of mitotic cyclins and the polycomb protein EZH2. Cancer Discov; 2(6); 524–39. © 2012 AACR.
This article is highlighted in the In This Issue feature, p. 473
Noncoding RNA Expression in Myocardium From Infants With Tetralogy of Fallot
Authors: O'Brien James E. , Kibiryeva Nataliya , Zhou Xin-Gang , Marshall Jennifer A. , Lofland Gary K. , Artman Michael , Chen Jie , Bittel Douglas C. 
Published: April 2012

Background—
The importance of noncoding RNAs (ncRNA), especially microRNAs (miRNAs), for maintaining stability in the developing vertebrate heart has recently become apparent; however, there is little known about the expression pattern of ncRNA in the human heart with developmental anomalies.

Methods and Results—
We examined the expression of miRNAs and small nucleolar RNAs (snoRNAs) in right ventricular myocardium from 16 infants with nonsyndromic tetralogy of Fallot (TOF) without a 22q11.2 deletion, 3 fetal heart samples, and 8 normally developing infants. We found 61 miRNAs and 135 snoRNAs to be significantly changed in expression in myocardium from children with TOF compared with normally developing comparison subjects. The pattern of ncRNA expression in TOF myocardium had a surprising resemblance to expression patterns in fetal myocardium, especially for the snoRNAs. Potential targets of miRNAs with altered expression were enriched for gene networks of importance to cardiac development. We derived a list of 229 genes known to be critical to heart development and found 44 had significantly changed expression in TOF myocardium relative to normally developing myocardium. These 44 genes had significant negative correlation with 33 miRNAs, each of which also had significantly changed expression. The primary function of snoRNAs is targeting specific nucleotides of ribosomal RNAs and spliceosomal RNAs for biochemical modification. The targeted nucleotides of the differentially expressed snoRNAs were concentrated in the 28S and 18S ribosomal RNAs and 2 spliceosomal RNAs, U2 and U6. In addition, in myocardium from children with TOF, we observed splicing variants in 51% of genes that are critical for cardiac development. Taken together, these observations suggest a link between levels of snoRNA that target spliceosomal RNAs, spliceosomal function, and heart development.

Conclusions—
This is the first report characterizing ncRNA expression in a congenital heart defect. The striking shift in expression of ncRNAs reflects a fundamental change in cell biology, likely impacting expression, transcript splicing, and translation of developmentally important genes and possibly contributing to the cardiac defect.
Diabetes and Reduced Risk for Thoracic Aortic Aneurysms and Dissections: A Nationwide Case‐Control Study
Authors: Prakash Siddharth K. , Pedroza Claudia , Khalil Yameen A. , Milewicz Dianna M. 
Published: April 2012

Background
Vascular diseases are the principal causes of death and disability in people with diabetes. At the same time, studies suggest a protective role of diabetes in the development of abdominal aortic aneurysms. We sought to determine whether diabetes is associated with decreased hospitalization due to thoracic aortic aneurysms and dissections (TAAD).

Methods and Results
We used the 2006 and 2007 Nationwide Inpatient Sample (NIS) to determine TAAD discharge rates. Control subjects were randomly selected to achieve three controls per case. Predictor variables in multilevel logistic regression included age, race, median income, diabetes, and hypertension. We estimated that the average rate of hospital discharge for TAAD among individuals diagnosed with diabetes was 9.7 per 10 000, compared to 15.6 per 10 000 among all discharges. The prevalence of diabetes was substantially lower in TAAD (13%) than in control (22%) records. After adjustment for demographic characteristics, the negative association between diabetes and TAAD remained highly significant in both NIS datasets. Compared to discharges without diabetes, those with chronic complications of diabetes were least likely to be diagnosed with TAAD (OR [odds ratio] 0.17, 95% CI, 0.12–0.23). A significant association remained between uncomplicated diabetes and TAAD. We replicated these findings in an independent group of patients who were hospitalized with acute thoracic aortic dissections.

Conclusions

The principal implication of our findings is that diabetes is independently associated with a decreased rate of hospitalization due to TAAD in proportion to the severity of diabetic complications. Future studies should consider diabetes in predictive models of aneurysm expansion or dissection.

(
J Am Heart Assoc
. 2012;1:e000323 doi: 10.1161/JAHA.111.000323.)
Predicting clinically significant change in an inpatient program for people with severe mental illness
Authors: Gonda Talia , Deane Frank P , Murugesan Ganapathi 
Published: April 2012

Objective: The first aim of this study was to assess the proportion of patients who achieved reliable and clinically significant change over the course of treatment in an inpatient psychosocial rehabilitation program. The second aim was to determine whether age, gender, length of stay, and diagnosis and co-morbid diagnosis predicted those who were classified as improved or not improved, using clinical significance criteria. Method: Three hundred and thirty-seven patients from inpatient units at Bloomfield Hospital, Orange, New South Wales, Australia were assessed at admission, 3-month reviews and discharge using the expanded Brief Psychiatric Rating Scale, the Health of the Nation Outcome Scales and the Kessler 10. Results: Reliable and clinically significant improvement was found for 32.4% of inpatients on psychiatric symptomatology, 19.5% on psychosocial functioning and 20.2% on psychological distress. Logistic regression analyses found that the predictor variables collectively predicted those who made reliable and clinically significant improvement on psychiatric symptomatology, but not on psychosocial functioning or psychological distress. Those with a primary diagnosis of schizo-affective disorder had higher rates of improvement in psychiatric symptomatology compared to those with a diagnosis of schizophrenia. Those with co-morbid substance abuse disorders showed a trend towards greater improvement. Conclusions: Inpatient treatment is associated with clinically significant improvements for some patients with a severe mental illness. Patients with schizo-affective disorders are proportionally more likely to make improvement.
The Effect of Cartilaginous Reinforcing Sutures on Initial Tracheal Anastomotic Strength
Authors: Schilt Peter N. , Musunuru Swapna , Kokoska Mimi , McRae Bryan , O’Neill Daniel , Halum Stacey L. 
Published: April 2012

ObjectiveDuring tracheal resection with primary anastomosis, cartilaginous reinforcing sutures may be placed outside of the primary anastomosis with the goal of preventing early dehiscence. The direct effect of such reinforcing sutures on anastomotic strength has not been previously investigated. The goal of this study was to determine if the addition of cartilaginous reinforcing sutures adds to tracheal anastomosis stability.Study DesignProspective cadaver study.SettingThis research was conducted at an anatomy lab at Indiana University School of Medicine.Subjects and MethodsTwelve cadaver tracheas were harvested. Each trachea was bifurcated, with 1 segment of each trachea transected and anastomosed using circumferential sutures and the remaining tracheal segment undergoing the same procedure with the addition of cartilaginous reinforcing sutures. Segments (proximal versus distal) were alternated to control for potential anatomic‐based strength differences. The force necessary for anastomotic rupture was measured, and a Wilcoxon signed‐rank test was used to compare means.ResultsAnalysis demonstrated the mean anastomotic rupture point for tracheas with reinforcing sutures was 297 N (95% confidence interval = 241.1‐352.9), while the mean for trials without reinforcing sutures was 173 N (95% confidence interval = 142.63‐203.37; P =. 0054). The point of rupture occurred at the anastomosis in 1 case with reinforcing sutures and in 8 of 11 cases without reinforcing sutures.ConclusionsCartilaginous reinforcing sutures were found to provide a higher force requirement for tracheal anastomotic rupture when compared with anastomoses without these sutures. This improved stability in tracheal anastomosis may result in a decreased risk of early tracheal rupture after anastomosis.
P2X7 receptor blockade reverses purinergic facilitation of neck muscle nociception in mice
Authors: Ristić Dejan , Ellrich Jens 
Published: April 2012

Introduction: Facilitation of neck muscle nociception mediated via purinergic signalling may play a role in the pathophysiology of tension-type headache (TTH). The present study addressed reversal of purinergic facilitation of brainstem nociception via P2X7 antagonist action in anaesthetized mice. Methods: Following administration of α,β-meATP (i.m. 20 µL/min, 20 µL each) into semispinal neck muscles, the impact of neck muscle nociceptive input on brainstem processing was monitored by the jaw-opening reflex in anaesthetized mice ( n = 20). The hypothesized involvement of the P2X7 receptor in the α,β-meATP effect was addressed with i.p. (systemic) and i.m. (semispinalis, 20 µL/min, 20 µL each) administration of P2X7 inhibitor A438079 during established facilitation; i.p. saline served as control. Results: α,β-meATP reliably induced jaw-opening reflex facilitation (256 ± 48% (mean ± SEM), n = 20). I.p. A438079 (150, 300 µmol/kg) completely reversed this α,β-meATP effect dose-dependently. Neither saline nor intramuscular A438079 (100 µM) altered facilitated brainstem nociceptive processing. Discussion: These data suggest that muscular structures are not directly involved in the P2X7 antagonist-mediated reversal of purinergic facilitation. Instead, involvement of neuronal structures, particularly of the central nervous system, seems more probable. The results from this animal experimental model may point to involvement of purinergic P2X7 receptors in TTH pathophysiology and may suggest potential future targets for its pharmacological treatment.
Brachialis muscle transfer to the forearm for the treatment of deformities in spastic cerebral palsy
Authors: Ozkan T. , Bicer A. , Aydin H. U. , Tuncer S. , Aydin A. , Hosbay Z. Y. 
Published: April 2012

The use of the brachialis muscle for tendon transfers in cerebral palsy has not been described previously. In this study, the brachialis muscle was used for transfer in 11 patients with spastic cerebral palsy for the restoration of forearm supination, wrist extension, or finger extension. Four patients underwent brachialis rerouting supinatorplasty. Active supination increased in two (60° and 50°), minimally increased in one (5°), and did not change in one patient. Five patients had a brachialis to extensor carpi radialis brevis transfer. The mean gain in postoperative active wrist extension was 65°. Two patients with finger flexion deformity and no active metacarpophalangeal joint movement underwent a brachialis to extensor digitorum communis transfer, and they attained an improved posture of finger extension although their postoperative metacarpophalangeal flexion–extension movement arc was 5° and 25°. None of the patients developed any loss of active flexion at the elbow. Our preliminary experience suggests that the brachialis muscle may serve as an alternative tendon transfer in cerebral palsy.
A new mouse model mimicking thrombotic thrombocytopenic purpura: correction of symptoms by recombinant human ADAMTS13
Authors: Schiviz Alexandra , Wuersch Kuno , Piskernik Christina , Dietrich Barbara , Hoellriegl Werner , Rottensteiner Hanspeter , Scheiflinger Friedrich , Schwarz Hans Peter , Muchitsch Eva-Maria 
Published: April 2012

AbstractDeficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), a VWF-cleaving protease, is the key factor in the pathogenesis of thrombotic thrombocytopenic purpura (TTP), a life-threatening thrombotic microangiopathy. It is well established that ADAMTS13 deficiency results in elevated plasma levels of ultra-large VWF multimers (ULVWF), which are prone to induce platelet aggregation; however, the actual trigger of TTP development remains uncertain. Here we describe a new animal model in which some TTP-like symptoms can be triggered in ADAMTS13 knockout mice by challenge with 2000 units/kg body weight of recombinant human VWF containing ULVWF multimers. Animals rapidly showed clinical symptoms and developed severe thrombocytopenia. Schistocytosis, a decrease in hematocrit, and elevated serum lactate dehydrogenase levels were observed. The heart was identified as the most sensitive target organ with rapid onset of extensive platelet aggregation in the ventricles and myocardial necrosis. Prophylactic administration of 200 units/kg recombinant human ADAMTS13 protected ADAMTS13 knockout mice from developing TTP. Therapeutic administration of 320 units/kg rhADAMTS13 reduced the incidence and severity of TTP findings in a treatment interval-dependent manner. We therefore consider this newly established mouse model of thrombotic microangiopathy highly predictive for investigating the efficacy of new treatments for TTP.
Comparative genomics and transcriptomics of lineages I, II, and III strains of Listeria monocytogenes
Authors: Hain Torsten , Ghai Rohit , Billion André , Kuenne Carsten Tobias , Steinweg Christiane , Izar Benjamin , Mohamed Walid , Mraheil Mobarak Abu , Domann Eugen , Schaffrath Silke , Kärst Uwe , Goesmann Alexander , Oehm Sebastian , Pühler Alfred , Merkl Rainer , Vorwerk Sonja , Glaser Philippe , Garrido Patricia , Rusniok Christophe , Buchrieser Carmen , Goebel Werner , Chakraborty Trinad 
Published: April 2012

AbstractBackgroundListeria monocytogenesis a food-borne pathogen that causes infections with a high-mortality rate and has served as an invaluable model for intracellular parasitism. Here, we report complete genome sequences for twoL. monocytogenesstrains belonging to serotype 4a (L99) and 4b (CLIP80459), and transcriptomes of representative strains from lineages I, II, and III, thereby permitting in-depth comparison of genome- and transcriptome -based data from three lineages ofL. monocytogenes. Lineage III, represented by the 4a L99 genome is known to contain strains less virulent for humans.ResultsThe genome analysis of the weakly pathogenic L99 serotype 4a provides extensive evidence of virulence gene decay, including loss of several important surface proteins. The 4b CLIP80459 genome, unlike the previously sequenced 4b F2365 genome harbours an intactinlBinvasion gene. These lineage I strains are characterized by the lack of prophage genes, as they share only a single prophage locus with otherL. monocytogenesgenomes 1/2a EGD-e and 4a L99. Comparative transcriptome analysis during intracellular growth uncovered adaptive expression level differences in lineages I, II and III ofListeria, notable amongst which was a strong intracellular induction of flagellar genes in strain 4a L99 compared to the other lineages. Furthermore, extensive differences between strains are manifest at levels of metabolic flux control and phosphorylated sugar uptake. Intriguingly, prophage gene expression was found to be a hallmark of intracellular gene expression. Deletion mutants in the single shared prophage locus of lineage II strain EGD-e 1/2a, thelmaoperon, revealed severe attenuation of virulence in a murine infection model.ConclusionComparative genomics and transcriptome analysis ofL. monocytogenesstrains from three lineages implicate prophage genes in intracellular adaptation and indicate that gene loss and decay may have led to the emergence of attenuated lineages.