bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scalable and systematic detection of buggy inconsistencies in source code
Authors: Gabel Mark , Yang Junfeng , Yu Yuan , Goldszmidt Moises , Su Zhendong 
Published: February 2011

Software developers often duplicate source code to replicate functionality. This practice can hinder the maintenance of a software project: bugs may arise when two identical code segments are edited inconsistently. This paper presents DejaVu, a highly scalable system for detecting these general syntactic inconsistency bugs.
DejaVu operates in two phases. Given a target code base, a parallel /inconsistent clone analysis/ first enumerates all groups of source code fragments that are similar but not identical. Next, an extensible /buggy change analysis/ framework refines these results, separating each group of inconsistent fragments into a fine-grained set of inconsistent changes and classifying each as benign or buggy.
On a 75+ million line pre-production commercial code base, DejaVu executed in under five hours and produced a report of over 8,000 potential bugs. Our analysis of a sizable random sample suggests with high likelihood that at this report contains at least 2,000 true bugs and 1,000 code smells. These bugs draw from a diverse class of software defects and are often simple to correct: syntactic inconsistencies both indicate problems and suggest solutions.
A study of Java's non-Java memory
Authors: Ogata Kazunori , Mikurube Dai , Kawachiya Kiyokuni , Trent Scott , Onodera Tamiya 
Published: February 2011

A Java application sometimes raises an out-of-memory ex-ception. This is usually because it has exhausted the Java heap. However, a Java application can raise an out-of-memory exception when it exhausts the memory used by Java that is not in the Java heap. We call this area non-Java memory. For example, an out-of-memory exception in the non-Java memory can happen when the JVM attempts to load too many classes. Although it is relatively rare to ex-haust the non-Java memory compared to exhausting the Java heap, a Java application can consume a considerable amount of non-Java memory.
This paper presents a quantitative analysis of non-Java memory. To the best of our knowledge, this is the first in-depth analysis of the non-Java memory. To do this we cre-ated a tool called Memory Analyzer for Redundant, Unused, and String Areas (MARUSA), which gathers memory statis-tics from both the OS and the Java virtual machine, break-ing down and visualizing the non-Java memory usage.
We studied the use of non-Java memory for a wide range of Java applications, including the DaCapo benchmarks and Apache DayTrader. Our study is based on the IBM J9 Java Virtual Machine for Linux. Although some of our results may be specific to this combination, we believe that most of our observations are applicable to other platforms as well.
Instrumentation and sampling strategies for cooperative concurrency bug isolation
Authors: Jin Guoliang , Thakur Aditya , Liblit Ben , Lu Shan 
Published: February 2011

Fixing concurrency bugs (or "crugs") is critical in modern software systems. Static analyses to find crugs such as data races and atomicity violations scale poorly, while dynamic approaches incur high run-time overheads. Crugs manifest only under specific execution interleavings that may not arise during in-house testing, thereby demanding a lightweight program monitoring technique that can be used post-deployment.
We present Cooperative Crug Isolation (CCI), a low-overhead instrumentation framework to diagnose production-run failures caused by crugs. CCI tracks specific thread interleavings at run-time, and uses statistical models to identify strong failure predictors among these. We offer a varied suite of predicates that represent different trade-offs between complexity and fault isolation capability. We also develop variant random sampling strategies that suit different types of predicates and help keep the run-time overhead low. Experiments with 9 real-world bugs in 6 non-trivial C applications show that these schemes span a wide spectrum of performance and diagnosis capabilities, each suitable for different usage scenarios.
The two-state solution
Authors: McCarthy Jay A. 
Published: February 2011

Continuation-based Web servers provide advantages over traditional Web application development through the increase of expressive power they allow. This leads to fewer errors and more productivity for the programmers that adopt them. Unfortunately, existing implementation techniques force a hard choice between scalability and expressiveness.
Our technique allows a smoother path to scalable, continuation-based Web programs. We present a modular program transformation that allows scalable Web applications to use third-party, higher-order libraries with higher-order arguments that cause Web interaction. Consequently, our system provides existing Web applications with more scalability through significantly less memory use than the traditional technique.
Performance analysis of idle programs
Authors: Altman Erik , Arnold Matthew , Fink Stephen , Mitchell Nick 
Published: February 2011

This paper presents an approach for performance analysis of modern enterprise-class server applications. In our experience, performance bottlenecks in these applications differ qualitatively from bottlenecks in smaller, stand-alone systems. Small applications and benchmarks often suffer from CPU-intensive hot spots. In contrast, enterprise-class multi-tier applications often suffer from problems that manifest not as hot spots, but as
idle time
, indicating a lack of forward motion. Many factors can contribute to undesirable idle time, including locking problems, excessive system-level activities like garbage collection, various resource constraints, and problems driving load.

We present the design and methodology for WAIT, a tool to diagnosis the root cause of idle time in server applications. Given lightweight samples of Java activity on a single tier, the tool can often pinpoint the primary bottleneck on a multi-tier system. The methodology centers on an informative abstraction of the states of idleness observed in a running program. This abstraction allows the tool to distinguish, for example, between hold-ups on a database machine, insufficient load, lock contention in application code, and a conventional bottleneck due to a hot method. To compute the abstraction, we present a simple expert system based on an extensible set of declarative rules.
WAIT can be deployed on the fly, without modifying or even restarting the application. Many groups in IBM have applied the tool to diagnosis performance problems in commercial systems, and we present a number of examples as case studies.
Registration-based language abstractions
Authors: Davis Samuel , Kiczales Gregor 
Published: February 2011

Programming language innovation has been hindered by the difficulty of making changes to existing languages. A key source of difficulty is the tyrannical nature of existing approaches to realizing languages -- adding a new language construct means that any tool, document or programmer that works with the language must be prepared to deal with that construct.
A registration-based approach makes it possible to define language constructs that are not tyrannical. They are instead transient -- the program appears to be written using the constructs only so long as a given programmer wants to see it that way. This approach may have the potential to greatly facilitate programming language innovation.
Anti-IL-23 Monoclonal Antibody Synergizes in Combination with Targeted Therapies or IL-2 to Suppress Tumor Growth and Metastases
Authors: Teng Michele W.L. , von Scheidt Bianca , Duret Helene , Towne Jennifer E. , Smyth Mark J. 
Published: February 2011

AbstractImmunosuppressive barricades erected by tumors during the evolution of immune escape represent a major obstacle to many potentially effective cancer therapies and vaccines. We have shown that host interleukin (IL)-23 suppresses the innate immune response during carcinogenesis and metastasis, independently of effects on the proinflammatory cytokine IL-17A. Based on these findings, we envisioned that IL-23 neutralization might offer a promising strategy to modulate immunosuppression, particularly in combination with immunostimulatory agents. Here we show that by itself a neutralizing monoclonal antibody (mAb) to IL-23 suppressed early experimental lung metastases in the B16F10 mouse model of melanoma and also modestly inhibited the subcutaneous growth of primary tumors. These antitumor effects were respectively mediated by natural killer cells or CD8+ T cells. More notably, combinatorial treatments of anti-IL-23 mAb with IL-2 or anti-erbB2 mAb significantly inhibited subcutaneous growth of established mammary carcinomas and suppressed established experimental and spontaneous lung metastases. Overall, our results suggest the potential of anti-human IL-23 mAbs to improve the immunostimulatory effects of IL-2 and trastuzumab in the current management of some advanced human cancers. Cancer Res; 71(6); 2077–86. ©2011 AACR.
Radiosensitization of Head and Neck Squamous Cell Carcinoma by a SMAC-Mimetic Compound, SM-164, Requires Activation of Caspases
Authors: Yang Jie , McEachern Donna , Li Wenyan , Davis Mary A. , Li Hua , Morgan Meredith A. , Bai Longchuan , Sebolt Jonathan T. , Sun Haiying , Lawrence Theodore S. , Wang Shaomeng , Sun Yi 
Published: February 2011

AbstractChemoradiation is the treatment of choice for locally advanced head and neck squamous cell carcinoma (HNSCC). However, radioresistance, which contributes to local recurrence, remains a significant therapeutic problem. In this study, we characterized SM-164, a small second mitochondria-derived activator of caspase -mimetic compound that promotes degradation of cellular inhibitor of apoptosis-1(cIAP-1; also known as baculoviral IAP repeat–containing protein 2, BIRC2) and releases active caspases from the X-linked inhibitor of apoptosis inhibitory binding as a radiosensitizing agent in HNSCC cells. We found that SM-164 at nanomolar concentrations induced radiosensitization in some HNSCC cell lines in a manner dependent on intrinsic sensitivity to caspase activation and apoptosis induction. Blockage of caspase activation via short interfering RNA knockdown or a pan-caspase inhibitor, z-VAD-fmk, largely abrogated SM-164 radiosensitization. On the other hand, the resistant lines with a high level of Bcl-2 that blocks caspase activation and apoptosis induction became sensitive to radiation on Bcl-2 knockdown. Mechanistic studies revealed that SM-164 radiosensitization in sensitive cells was associated with NF-κB activation and TNFα secretion, followed by activation of caspase-8 and -9, leading to enhanced apoptosis. Finally, SM-164 also radiosensitized human tumor xenograft while causing minimal toxicity. Thus, SM-164 is a potent radiosensitizer via a mechanism involving caspase activation and holds promise for future clinical development as a novel class of radiosensitizer for the treatment of a subset of head and neck cancer patients. Mol Cancer Ther; 10(4); 658–69. ©2011 AACR.
Cancer-Targeted BikDD Gene Therapy Elicits Protective Antitumor Immunity against Lung Cancer
Authors: Sher Yuh-Pyng , Liu Shih-Jen , Chang Chun-Mien , Lien Shu-Pei , Chen Chien-Hua , Han Zhenbo , Li Long-Yuan , Chen Jin-Shing , Wu Cheng-Wen , Hung Mien-Chie 
Published: February 2011

AbstractTargeted cancer-specific gene therapy is a promising strategy for treating metastatic lung cancer, which is a leading cause of lung cancer–related deaths. Previously, we developed a cancer-targeted gene therapy expression system with high tumor specificity and strong activity that selectively induced lung cancer cell killing without affecting normal cells in immunocompromised mice. Here, we found this cancer-targeted gene therapy, SV-BikDD, composed of the survivin promoter in the VP16-GAL4-WPRE integrated systemic amplifier system to drive the apoptotic gene BikDD, not only caused cytotoxic effects in cancer cells but also elicited a cancer-specific cytotoxic T lymphocyte response to synergistically increase the therapeutic effect and further develop an effective systemic antitumoral immunity against rechallenges of tumorigenic dose of parental tumor cells inoculated at distant sites in immunocompetent mice. In addition, this cancer-targeted gene therapy does not elicit an immune response against normal tissues, but CMV-BikDD treatment does. The therapeutic vector could also induce proinflammatory cytokines to activate innate immunity and provide some benefits in antitumor gene therapy. Thus, this study provides a promising strategy with benefit of antitumoral immune response worthy of further development in clinical trials for treating lung cancer via cancer-targeted gene therapy. Mol Cancer Ther; 10(4); 637–47. ©2011 AACR.
Rapamycin Reverses Splenomegaly and Inhibits Tumor Development in a Transgenic Model of Epstein-Barr Virus–Related Burkitt's Lymphoma
Authors: Cen Osman , Longnecker Richard 
Published: February 2011

Abstract
Epstein-Barr virus (EBV) infection and latency has been associated with malignancies, including nasopharyngeal carcinoma and Burkitt's lymphoma. EBV encoded latent membrane protein 2A (LMP2A) is expressed in most EBV-associated malignancies and as such provides a therapeutic target. Burkitt's lymphoma is a hematopoietic cancer associated with the translocation of c-MYC to one of the immunoglobulin gene promoters leading to abnormally high expression of MYC and development of lymphoma. Our laboratory has developed a murine model of EBV-associated Burkitt's lymphoma by crossing LMP2A transgenic mice with MYC transgenic mice. Since LMP2A has been shown to activate the PI3K/Akt/mTOR pathway, we tested the therapeutic efficacy of mTOR inhibitor rapamycin on the tumors and splenomegaly in these double transgenic mice (Tg6/λ-MYC). We found that rapamycin reversed splenomegaly in Tg6/λ-MYC mice prior to tumor formation by targeting B cells. In a tumor transfer model, we also found that rapamycin significantly decreased tumor growth, splenomegaly, and metastasis of tumor cells in the bone marrow of tumor recipients. Our data show that rapamycin may be a valuable candidate for the development of a treatment modality for EBV-positive lymphomas, such as Burkitt's lymphoma, and more importantly, provides a basis to develop inhibitors that specifically target viral gene function in tumor cells that depend on LMP2A signaling for survival and/or growth. Mol Cancer Ther; 10(4); 679–86. ©2011 AACR.
PITX2c Is Expressed in the Adult Left Atrium, and Reducing Pitx2c Expression Promotes Atrial Fibrillation Inducibility and Complex Changes in Gene Expression
Authors: Kirchhof Paulus , Kahr Peter C. , Kaese Sven , Piccini Ilaria , Vokshi Ismail , Scheld Hans-Heinrich , Rotering Heinrich , Fortmueller Lisa , Laakmann Sandra , Verheule Sander , Schotten Ulrich , Fabritz Larissa , Brown Nigel A. 
Published: February 2011

Background—
Intergenic variations on chromosome 4q25, close to the PITX2 transcription factor gene, are associated with atrial fibrillation (AF). We therefore tested whether adult hearts express PITX2 and whether variation in expression affects cardiac function.

Methods and Results—

mRNA for PITX2 isoform c was expressed in left atria of human and mouse, with levels in right atrium and left and right ventricles being 100-fold lower. In mice heterozygous for
Pitx2c
(
Pitx2c
+/−
), left atrial Pitx2c expression was 60% of wild-type and cardiac morphology and function were not altered, except for slightly elevated pulmonary flow velocity. Isolated
Pitx2
c
+/−
hearts were susceptible to AF during programmed stimulation. At short paced cycle lengths, atrial action potential durations were shorter in
Pitx2c
+/−
than in wild-type. Perfusion with the β-receptor agonist orciprenaline abolished inducibility of AF and reduced the effect on action potential duration. Spontaneous heart rates, atrial conduction velocities, and activation patterns were not affected in
Pitx2c
+/−
hearts, suggesting that action potential duration shortening caused wave length reduction and inducibility of AF. Expression array analyses comparing
Pitx2c
+/−
with wild-type, for left atrial and right atrial tissue separately, identified genes related to calcium ion binding, gap and tight junctions, ion channels, and melanogenesis as being affected by the reduced expression of Pitx2c.

Conclusions—
These findings demonstrate a physiological role for PITX2 in the adult heart and support the hypothesis that dysregulation of PITX2 expression can be responsible for susceptibility to AF.
Proteomic Analysis of Coronary Sinus Serum Reveals Leucine-Rich α2-Glycoprotein as a Novel Biomarker of Ventricular Dysfunction and Heart Failure
Authors: Watson Chris J. , Ledwidge Mark T. , Phelan Dermot , Collier Patrick , Byrne Jennifer C. , Dunn Michael J. , McDonald Kenneth M. , Baugh John A. 
Published: February 2011

Background—
Heart failure (HF) prevention strategies require biomarkers that identify disease manifestation. Increases in B-type natriuretic peptide (BNP) correlate with increased risk of cardiovascular events and HF development. We hypothesize that coronary sinus serum from a high BNP hypertensive population reflects an active pathological process and can be used for biomarker exploration. Our aim was to discover differentially expressed disease-associated proteins that identify patients with ventricular dysfunction and HF.

Methods and Results—

Coronary sinus serum from 11 asymptomatic, hypertensive patients underwent quantitative differential protein expression analysis by 2-dimensional difference gel electrophoresis. Proteins were identified using mass spectrometry and then studied by enzyme-linked immunosorbent assay in sera from 40 asymptomatic, hypertensive patients and 105 patients across the spectrum of ventricular dysfunction (32 asymptomatic left ventricular diastolic dysfunction, 26 diastolic HF, and 47 systolic HF patients). Leucine-rich α2-glycoprotein (LRG) was consistently overexpressed in high BNP serum. LRG levels correlate significantly with BNP in hypertensive, asymptomatic left ventricular diastolic dysfunction, diastolic HF, and systolic HF patient groups (
P
≤0.05). LRG levels were able to identify HF independent of BNP. LRG correlates with coronary sinus serum levels of tumor necrosis factor-α (
P
=0.009) and interleukin-6 (
P
=0.021). LRG is expressed in myocardial tissue and correlates with transforming growth factor-βR1 (
P
<0.001) and α-smooth muscle actin (
P
=0.025) expression.

Conclusions—
LRG was identified as a serum biomarker that accurately identifies patients with HF. Multivariable modeling confirmed that LRG is a stronger identifier of HF than BNP and this is independent of age, sex, creatinine, ischemia, β-blocker therapy, and BNP.
Pathologic Evaluation of Routine Pediatric Tonsillectomy Specimens
Authors: Nelson Marc E. , Gernon T. J. , Taylor Joseph C. , McHugh Jonathan B. , Thorne Marc C. 
Published: February 2011

ObjectiveEvaluate the utility and explore the cost‐effectiveness of mandatory gross or pathologic analysis of routine tonsillectomy specimens in children.Study DesignCase series with chart review.SettingTertiary care children’s hospital.Subjects and MethodsRetrospective case series of results of pathologic analysis of tonsillectomy specimens from all pediatric patients who underwent tonsillectomy between 1996 and 2008 (n = 5235). The results of pathologic evaluation of routine and nonroutine specimens were evaluated, and an economic analysis of alternative methods of specimen handling was performed.ResultsZero cases of unsuspected pathology were identified on planned gross specimen evaluation (n = 4186), resulting in an estimated prevalence of 0 to 0.00088 (95% confidence interval [CI]). Positive pathologic findings on microscopic analysis (n = 1066) were only identified in posttransplant patients (10/63; 95% CI, 0.079‐0.27) and cases of surgeon suspicion (8/78; 0.045‐0.19). No cases were identified among the 17 undergoing microscopic pathologic analysis on the basis of pathologist suspicion on gross evaluation (95% CI, 0‐0.20). From an economic standpoint, microscopic evaluation of routine pediatric tonsillectomy specimens appears to be superior to gross evaluation but with an estimated cost of $766 500 per case of unsuspected lymphoma identified.ConclusionsThis study identifies a very low prevalence of unsuspected pathology on gross pathologic analysis of routine tonsillectomy specimens in children. Exploration of the cost implications suggests that such a practice is not a cost‐effective use of limited health care resources. Microscopic examination is appropriate for posttransplantation patients and in cases of surgeon suspicion.
Neuropathological correlates of late-life depression in older
people
Authors: Tsopelas Christos , Stewart Robert , Savva George M. , Brayne Carol , Ince Paul , Thomas Alan , Matthews Fiona E. 
Published: February 2011

BackgroundDepression is common in old age and is associated with risk of dementia,
but its neuropathological correlates in the community are unknown.AimsTo investigate for the first time in a population-representative sample
of people with no dementia the association between depression observed
during life and neurofibrillary tangles, diffuse and neuritic plaques,
Lewy bodies, brain atrophy and cerebrovascular disease found in the brain
at post-mortem.MethodOut of 456 donations to a population-based study, 153 brains were
selected where donors had no dementia measured in life. Alzheimer and
vascular pathology measures, Lewy bodies and neuronal loss were compared
between those with (n = 36) and without
(n = 117) depression ascertained using a fully
structured diagnostic interview during life. Brain areas examined
included frontal, parietal, temporal and occipital cortical areas as well
as the entorhinal cortex, hippocampus and brain-stem monoaminergic
nuclei.ResultsDepression was significantly associated with the presence of subcortical
Lewy bodies. No association was found between depression and
cerebrovascular or Alzheimer pathology in cortical or subcortical areas,
although depression was associated with neuronal loss in the hippocampus
as well as in some of the subcortical structures investigated (nucleus
basalis, substantia nigra, raphe nucleus).ConclusionsLate-life depression was associated with subcortical and hippocampal
neuronal loss but not with cerebrovascular or Alzheimer pathology.