bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compiler aided manual speculation for high performance concurrent data structures
Authors: Xiang Lingxiang , Scott Michael Lee 
Published: August 2013

Speculation is a well-known means of increasing parallelism among concurrent methods that are usually but not always independent. Traditional nonblocking data structures employ a particularly restrictive form of speculation. Software transactional memory (STM) systems employ a much more general---though typically blocking---form, and there is a wealth of options in between.
Using several different concurrent data structures as examples, we show that manual addition of speculation to traditional lock-based code can lead to significant performance improvements. Successful speculation requires careful consideration of profitability, and of how and when to validate consistency. Unfortunately, it also requires substantial modifications to code structure and a deep understanding of the memory model. These latter requirements make it difficult to use in its purely manual form, even for expert programmers. To simplify the process, we present a compiler tool, CSpec, that automatically generates speculative code from baseline lock-based code with user annotations. Compiler-aided manual speculation keeps the original code structure for better readability and maintenance, while providing the flexibility to chose speculation and validation strategies. Experiments on UltraSPARC and x86 platforms demonstrate that with a small number annotations added to lock-based code, CSpec can generate speculative code that matches the performance of best-effort hand-written versions.
A Comparative Genomic Approach for Identifying Synthetic Lethal Interactions in Human Cancer
Authors: Deshpande Raamesh , Asiedu Michael K. , Klebig Mitchell , Sutor Shari , Kuzmin Elena , Nelson Justin , Piotrowski Jeff , Ho Shin Seung , Yoshida Minoru , Costanzo Michael , Boone Charles , Wigle Dennis A. , Myers Chad L. 
Published: August 2013

Abstract
Synthetic lethal interactions enable a novel approach for discovering specific genetic vulnerabilities in cancer cells that can be exploited for the development of therapeutics. Despite successes in model organisms such as yeast, discovering synthetic lethal interactions on a large scale in human cells remains a significant challenge. We describe a comparative genomic strategy for identifying cancer-relevant synthetic lethal interactions whereby candidate interactions are prioritized on the basis of genetic interaction data available in yeast, followed by targeted testing of candidate interactions in human cell lines. As a proof of principle, we describe two novel synthetic lethal interactions in human cells discovered by this approach, one between the tumor suppressor gene SMARCB1 and PSMA4, and another between alveolar soft-part sarcoma-associated ASPSCR1 and PSMC2. These results suggest therapeutic targets for cancers harboring mutations in SMARCB1 or ASPSCR1 and highlight the potential of a targeted, cross-species strategy for identifying synthetic lethal interactions relevant to human cancer. Cancer Res; 73(20); 6128–36. ©2013 AACR.
Preclinical Efficacy of the Anti-Hepatocyte Growth Factor Antibody Ficlatuzumab in a Mouse Brain Orthotopic Glioma Model Evaluated by Bioluminescence, PET, and MRI
Authors: Mittra Erik S. , Fan-Minogue Hua , Lin Frank I. , Karamchandani Jason , Sriram Venkataraman , Han May , Gambhir Sanjiv S. 
Published: August 2013

Abstract
Purpose: Ficlatuzumab is a novel therapeutic agent targeting the hepatocyte growth factor (HGF)/c-MET pathway. We summarize extensive preclinical work using this agent in a mouse brain orthotopic model of glioblastoma.
Experimental Design: Sequential experiments were done using eight- to nine-week-old nude mice injected with 3 × 105 U87 MG (glioblastoma) cells into the brain. Evaluation of ficlatuzumab dose response for this brain tumor model and comparison of its response to ficlatuzumab and to temozolamide were conducted first. Subsequently, various small-animal imaging modalities, including bioluminescence imaging (BLI), positron emission tomography (PET), and MRI, were used with a U87 MG-Luc 2 stable cell line, with and without the use of ficlatuzumab, to evaluate the ability to noninvasively assess tumor growth and response to therapy. ANOVA was conducted to evaluate for significant differences in the response.
Results: There was a survival benefit with ficlatuzumab alone or in combination with temozolamide. BLI was more sensitive than PET in detecting tumor cells. Fluoro-D-thymidine (FLT) PET provided a better signal-to-background ratio than 2[18F]fluoro-2-deoxy-d-glucose (FDG) PET. In addition, both BLI and FLT PET showed significant changes over time in the control group as well as with response to therapy. MRI does not disclose any time-dependent change. Also, the MRI results showed a temporal delay in comparison to the BLI and FLT PET findings, showing similar results one drug cycle later.
Conclusions: Targeting the HGF/c-MET pathway with the novel agent ficlatuzumab appears promising for the treatment of glioblastoma. Various clinically applicable imaging modalities including FLT, PET, and MRI provide reliable ways of assessing tumor growth and response to therapy. Given the clinical applicability of these findings, future studies on patients with glioblastoma may be appropriate. Clin Cancer Res; 19(20); 5711–21. ©2013 AACR.
Arginine Deiminase Resistance in Melanoma Cells Is Associated with Metabolic Reprogramming, Glucose Dependence, and Glutamine Addiction
Authors: Long Yan , Tsai Wen-Bin , Wangpaichitr Medhi , Tsukamoto Takashi , Savaraj Niramol , Feun Lynn G. , Kuo Macus Tien 
Published: August 2013

AbstractMany malignant human tumors, including melanomas, are auxotrophic for arginine due to reduced expression of argininosuccinate synthetase-1 (ASS1), the rate-limiting enzyme for arginine biosynthesis. Pegylated arginine deiminase (ADI-PEG20), which degrades extracellular arginine, resulting in arginine deprivation, has shown favorable results in clinical trials for treating arginine-auxotrophic tumors. Drug resistance is the major obstacle for effective ADI-PEG20 usage. To elucidate mechanisms of resistance, we established several ADI-PEG20–resistant (ADIR) variants from A2058 and SK-Mel-2 melanoma cells. Compared with the parental lines, these ADIR variants showed the following characteristics: (i) all ADIR cell lines showed elevated ASS1 expression, resulting from the constitutive binding of the transcription factor c-Myc on the ASS1 promoter, suggesting that elevated ASS1 is the major mechanism of resistance; (ii) the ADIR cell lines exhibited enhanced AKT signaling and were preferentially sensitive to PI3K/AKT inhibitors, but reduced mTOR signaling, and were preferentially resistant to mTOR inhibitor; (iii) these variants showed enhanced expression of glucose transporter-1 and lactate dehydrogenase-A, reduced expression of pyruvate dehydrogenase, and elevated sensitivity to the glycolytic inhibitors 2-deoxy-glucose and 3-bromopyruvate, consistent with the enhanced glycolytic pathway (the Warburg effect); (iv) the resistant cells showed higher glutamine dehydrogenase and glutaminase expression and were preferentially vulnerable to glutamine inhibitors. We showed that c-Myc, not elevated ASS1 expression, is involved in upregulation of many of these enzymes because knockdown of c-Myc reduced their expression, whereas overexpressed ASS1 by transfection reduced their expression. This study identified multiple targets for overcoming ADI-PEG resistance in cancer chemotherapy using recombinant arginine-degrading enzymes. Mol Cancer Ther; 12(11); 2581–90. ©2013 AACR.
Dietary Energy Balance Modulation of Kras- and Ink4a/Arf+/−-Driven Pancreatic Cancer: The Role of Insulin-like Growth Factor-I
Authors: Lashinger Laura M. , Harrison Lauren M. , Rasmussen Audrey J. , Logsdon Craig D. , Fischer Susan M. , McArthur Mark J. , Hursting Stephen D. 
Published: August 2013

Abstract
New molecular targets and intervention strategies for breaking the obesity–pancreatic cancer link are urgently needed. Using relevant spontaneous and orthotopically transplanted murine models of pancreatic cancer, we tested the hypothesis that dietary energy balance modulation impacts pancreatic cancer development and progression through an insulin-like growth factor (IGF)-I−dependent mechanism. In LSL-KrasG12D/Pdx-1-Cre/Ink4a/Arflox/+ mice, calorie restriction versus overweight- or obesity-inducing diet regimens decreased serum IGF-I, tumoral Akt/mTOR signaling, pancreatic desmoplasia, and progression to pancreatic ductal adenocarcinoma (PDAC), and increased pancreatic tumor-free survival. Serum IGF-I, Akt/mTOR signaling, and orthotopically transplanted PDAC growth were decreased in liver-specific IGF-I−deficient mice (vs. wild-type mice), and rescued with IGF-I infusion. Thus, dietary energy balance modulation impacts spontaneous pancreatic tumorigenesis induced by mutant Kras and Ink4a deficiency, the most common genetic alterations in human pancreatic cancer. Furthermore, IGF-I and components of its downstream signaling pathway are promising mechanistic targets for breaking the obesity–pancreatic cancer link. Cancer Prev Res; 6(10); 1046–55. ©2013 AACR.
Dispatcher-Assisted Cardiopulmonary Resuscitation
Authors: Lewis Miranda , Stubbs Benjamin A. , Eisenberg Mickey S. 
Published: August 2013

Background—
Dispatcher-assisted cardiopulmonary resuscitation (DA-CPR), in which 9-1-1 dispatchers provide CPR instructions over the telephone, has been shown to nearly double the rate of bystander CPR. We sought to identify factors that hampered the identification of cardiac arrest by 9-1-1 dispatchers and prevented or delayed the provision of dispatcher-assisted CPR chest compressions.

Methods and Results—
We reviewed dispatch recordings for 476 out-of-hospital cardiac arrests occurring between January 1, 2011, and December 31, 2011. We found that the dispatcher correctly identified cardiac arrest in 80% of reviewed cases and 92% of cases in which they were able to assess patient consciousness and breathing. The median time to recognition of the arrest was 75 seconds. Chest compressions following dispatcher-assisted CPR instructions occurred in 62% of cases when the dispatcher had the opportunity to asses for consciousness and breathing and bystander CPR was not already started. The median time to first dispatcher-assisted CPR chest compression was 176 seconds.

Conclusions—
Dispatchers are able to accurately diagnose cardiac arrest over the telephone, but recognition is likely not possible in all circumstances. In some cases, recognition of cardiac arrest may be improved through training in the detection of agonal respirations. Delays in the delivery of dispatcher-assisted CPR chest compressions are common and are attributable to a mixture of dispatcher behavior and factors beyond the control of the dispatcher. Performance standards for the successful and quick recognition of cardiac arrest and delivery of first chest compressions should be adopted as metrics against which emergency medical services systems can measure their performance.
Modelling the Efficiency of Local Versus Central Provision of Intravenous Thrombolysis After Acute Ischemic Stroke
Authors: McMeekin Peter , Gray Jo , Ford Gary A. , Rodgers Helen , Price Christopher I. 
Published: August 2013

Background and Purpose—
Prehospital redirection of stroke patients to a regional center is used as a strategy to maximize the provision of intravenous thrombolysis. We developed a model to quantify the benefit of redirection away from local services that were already providing thrombolysis.

Methods—
A microsimulation using hospital and ambulance data from consecutive emergency admissions to 10 local acute stroke units estimated the effect of redirection to 2 regional neuroscience centers. Modeled outcomes reflected additional journey time and accuracy of stroke identification in the prehospital phase, and the relative efficiency of patient selection and door-needle time for each local site compared with the nearest regional neuroscience center.

Results—
Thrombolysis was received by 223/1884 emergency admissions. Based on observed site performance, 68 additional patients would have been treated after theoretical redirection of 1269 true positive cases and 363 stroke mimics to the neuroscience center. Over 5 years redirection of this cohort generated 12.6 quality-adjusted life years at a marginal cost of £6730 ($10 320, €8347). The average additional cost of a quality-adjusted life year gain was £534 ($819, €673).

Conclusions—
Under these specific circumstances, redirection would have improved outcomes from thrombolysis at little additional cost.
Calibration and Validation of a Distributed Energy–Water Balance Model Using Satellite Data of Land Surface Temperature and Ground Discharge Measurements
Authors: Corbari Chiara , Mancini Marco 
Published: August 2013

Abstract
Distributed hydrological models of energy and mass balance need as inputs many soil and vegetation parameters, which are usually difficult to define. This paper will try to approach this problem by performing a pixel to pixel calibration procedure of soil hydraulic and vegetation parameters based on satellite land surface temperature data as a complementary method to the traditional calibration with ground discharge measurements at river control cross sections. These analyses are performed for the upper Po River basin (Italy) closed at the river cross section of Ponte della Becca with a total catchment area of about 38 000 km2, for a calibration period from 2000 to 2003, and a validation period from 2004 to 2010. Moderate Resolution Imaging Spectroradiometer (MODIS) land surface temperature data and a distributed hydrological model, Flash-Flood Event-Based Spatially Distributed Rainfall-Runoff Transformation Energy Water Balance model (FEST-EWB), that solves the system of energy and mass balance equations as a function of the representative equilibrium temperature will be used. This equilibrium surface temperature is comparable to the land surface temperature as retrieved from operational remote sensing data. Results suggest that a combined calibration based on satellite land surface temperature and ground discharge is needed to correctly reproduce volume discharge and also spatially distributed maps of representative equilibrium temperature and evapotranspiration. Improvements of about 10 mm/8 days are obtained on evapotranspiration from the model calibrated with Q and land surface temperature (LST) respect to the calibration based only on discharge.
Why Did Large Differences Arise in the Sea Surface Temperature Datasets across the Tropical Pacific during 2012?
Authors: Huang Boyin , L’Heureux Michelle , Lawrimore Jay , Liu Chunying , Zhang Huai-Min , Banzon Viva , Hu Zeng-Zhen , Kumar Arun 
Published: August 2013

AbstractDuring June–November 2012, pronounced differences in tropical Pacific sea surface temperature (SST) anomalies were observed between three widely used SST products: the extended reconstructed SST version 3b (ERSSTv3b), and the optimum interpolation SST version 2 analyses (OISST), produced weekly (OISSTwk) and daily (OISSTdy). During June–August 2012, the Niño-3.4 SST anomaly (SSTA) index was 0.2°–0.3°C lower in ERSSTv3b than in OISSTwk and OISSTdy, while it was 0.3°–0.4°C higher from September to November 2012. Such differences in the Niño-3.4 SSTA index can impact the assessment of the status of the El Niño–Southern Oscillation, which is determined using a threshold of ±0.5°C in the Niño-3.4 SSTA index.To investigate the reasons for the differences between ERSSTv3b and OISSTdy/OISSTwk, an experimental analysis (called ERSSTsat) is created that is similar to ERSSTv3b but includes satellite-derived SSTs. However, significant differences in the Niño-3.4 SSTA index remained between ERSSTsat and OISSTdy/OISSTwk. Comparisons of ERSSTsat and OISSTdy indicate that their differences are mostly associated with the different schemes for bias adjustment applied to the satellite-based SSTs. It is therefore suggested that the differences in the Niño-3.4 SSTA index between ERSSTv3b and OISSTdy cannot be solely due to the inclusion of but by the bias adjustment methodology of satellite data in OISSTdy.Finally, the SST products are compared with observations from ships, buoys, and satellites. On the monthly time scale, the area-averaged Niño-3.4 SSTA index in the tropical Pacific is more consistent with in situ observations in ERSSTv3b than in OISSTdy. In contrast, pointwise observations across the tropical Pacific are more consistent with OISSTdy than ERSSTv3b. It is therefore suggested that the differences among SST products are partially due to a structural uncertainty of various SST estimates.
The Effect of Pelvic Tilt on Radiographic Markers of Acetabular Coverage
Authors: Henebry Andrew , Gaskill Trevor 
Published: August 2013

Background: Radiographic indices of acetabular coverage are crucial to objectively characterize femoroacetabular impingement and plan bony decompression. It is established that changes in pelvic inclination result in alterations of acetabular crossover; however, it is unclear what influence this has on other measures of acetabular anatomy. Hypothesis: The objective of the present study was to determine if, and to what degree, a variation in pelvic tilt alters 4 measures of acetabular anatomy: the angle of Sharp, Tönnis angle, percentage of acetabular crossover, and lateral center edge angle (LCEA). The hypothesis was that pelvic tilt would significantly alter all measures of acetabular coverage. Study Design: Descriptive laboratory study. Methods: Fluoroscopic images of 8 adult hemipelvises were obtained at 7 positions of rotation in the sagittal plane to investigate the change of each measurement in response to pelvic orientation. Two reviewers obtained measurements from each image at 2 separate time points. Results: Each increment of pelvic inclination resulted in increased measures of acetabular coverage for all measurements, whereas each increment of decreased pelvic inclination resulted in decreased measures of acetabular coverage for all measurements. Significant differences in the measured LCEA, acetabular crossover, and Tönnis angle were identified at each increment of tilt as compared with neutral radiographs. No significant differences could be identified for the angle of Sharp. Conclusion: Pelvic tilt significantly alters the measures of LCEA, crossover, and Tönnis angle in this cadaveric study. Pelvic inclination results in increased measures of acetabular coverage, whereas decreasing inclination decreases each measure. Clinical Relevance: Given the known individual and positional pelvic tilt variability, standing anteroposterior pelvic radiographs may provide a more physiological representation of acetabular coverage in the young adult population.
Risk Factors for Posterior Shoulder Instability in Young Athletes
Authors: Owens Brett D. , Campbell Scot E. , Cameron Kenneth L. 
Published: August 2013

Background: While posterior glenohumeral instability is becoming increasingly common among young athletes, little is known of the risk factors for injury. Purpose: To determine the modifiable and nonmodifiable risk factors for posterior shoulder instability in a high-risk cohort. Study Design: Case-control study (prognosis); Level of evidence, 2. Methods: A prospective cohort study in which 714 young athletes were followed from June 2006 through May 2010 was conducted. Baseline testing included a subjective history of instability, instability testing by a sports medicine fellowship–trained orthopaedic surgeon, range of motion, strength measurement with a handheld dynamometer, and bilateral noncontrast magnetic resonance imaging of the shoulder. A musculoskeletal radiologist measured glenoid version, height, depth, rotator interval (RI) height, RI width, RI area, and RI index. Participants were followed to document all acute posterior shoulder instability events during the 4-year follow-up period. The time to the posterior shoulder instability event during the follow-up period was the primary outcome of interest. Univariate and multivariable Cox proportional hazards regression models were used to analyze the data. Results: Complete data on 714 participants were obtained. During the 4-year surveillance period, 46 shoulders sustained documented glenohumeral instability events, of which only 7 were posterior in direction. The baseline factors that were associated with subsequent posterior instability during follow-up were increased glenoid retroversion ( P < .0001), increased external rotation strength in adduction ( P = .029) and at 45° of abduction ( P = .015), and increased internal rotation strength in adduction ( P = .038). Conclusion: This is the largest known prospective study to follow healthy participants in the development of posterior shoulder instability. Posterior instability represents 10% of all instability events. The most significant risk factor was increased glenoid retroversion. While increased internal/external strength was also associated with subsequent instability, it is unclear whether these strength differences are causative or reactive to the difference in glenoid anatomy. This work confirms that increased glenoid retroversion is a significant prospective risk factor for posterior instability.
Battling demons with medical authority: werewolves, physicians and rationalization
Authors: Metzger Nadine 
Published: August 2013

Werewolves and physicians experienced their closest contact in the context of early modern witch and werewolf trials. For medical critics of the trials, melancholic diseases served as reference points for medical explanations of both individual cases and werewolf beliefs in general. This paper attempts to construct a conceptual history of werewolf beliefs and their respective medical responses. After differentiating the relevant terms, pre-modern werewolf concepts and medical lycanthropy are introduced. The early modern controversy between medical and demonological explanations forms the main part of this study. The history of werewolves and their medical explanations is then traced through to present times. An important point of discussion is to what extent the physicians’ engagements with werewolves can be characterized as rationalization.