bluuebunny/crossref_metadata_2025_split huggingface dataset:
Night work, long working hours, psychosocial work stress and cortisol secretion in mid-life: evidence from a British birth cohort
Authors: Thomas C , Hertzman C , Power C 
Published: June 2009

Objectives:To examine the relationships between exposure to workplace factors (night work, extended working hours, psychosocial work stress) and cortisol secretion, and to test whether workplace factors interact, resulting in combined effects.Methods:Multiple linear and logistic regression was used to test relationships between workplace factors and cortisol secretion in the 1958 British birth cohort at 45 years. Salivary cortisol was measured twice on the same day to capture the post-waking decline, facilitating the analysis of different cortisol patterns: (1) time 1 (T1, 45 minutes post-waking); (2) time 2 (T2, 3 h after T1); (3) average 3 h exposure from T1 to T2 cortisol; and (4) T1 to T2 change. To identify altered diurnal cortisol patterns we calculated: (1) flat T1–T2 change in cortisol; (2) top 5% T1; (3) bottom 5% T1; and (4) T1 hypo-secretion or hyper-secretion. Models were adjusted for socioeconomic position at birth and in adulthood, qualifications, marital status, dependent children, and smoking status.Results:25% of men and 8% of women were exposed to >1 workplace factor (night work, extended work hours, job strain). Night work was associated with a 4.28% (95% CI 1.21 to 7.45) increase in average 3 h cortisol secretion independently of job strain or work hours. Night workers not exposed to job strain had elevated T1 cortisol (5.81%, 95% CI 1.61 to 10.19), although for T2 cortisol it was night workers exposed to low job control who had elevated levels (11.72%, 95% CI 4.40 to 19.55). Men (but not women) working >48 h/week had lower average 3 h cortisol secretion (4.55%, 95% CI −8.43 to −0.50). There were no main effects for psychosocial work stress. All associations for T2 and average 3 h cortisol secretion weakened slightly after adjustment for confounding factors, but associations for T1 cortisol were unaffected by adjustment.Conclusions:Our study suggests that night work in particular is associated with elevated cortisol secretion and that cortisol dysregulation may exist in subgroups with specific combinations of stressors.
A prospective cohort study of exposure-response relationship for vibration-induced white finger
Authors: Bovenzi M 
Published: June 2009

Objectives:To investigate prospectively the relation between vibration-induced white finger (VWF) and measures of cumulative (lifetime) exposure to hand-transmitted vibration (HTV).Methods:Two hundred and forty-nine HTV workers and 138 control men of the same companies participated in a 3-year follow-up study. The diagnosis of VWF (Raynaud’s phenomenon in the controls) was based on the medical history, the administration of colour charts and the results of a cold test. Tool vibration magnitudes were expressed as root-mean-square (r.m.s.) acceleration, frequency-weighted according to international standard ISO 5349-1 and also unweighted over the frequency range 6.3–1250 Hz. From the vibration magnitudes and exposure durations, alternative measures of cumulative vibration dose were calculated for each HTV worker, according to the expression: dose  =  Σaimti, whereaiis the acceleration magnitude on tooli,tiis the lifetime exposure duration (hours) for tooli, andm =  0, 1, 2 or 4.Results:The incidence of VWF varied from 5 to 6% in the HTV workers versus 0 to 1.5% for Raynaud’s phenomenon in the controls. After adjusting for potential confounders, measures of cumulative vibration dose derived from total operating hours and high powers of unweighted acceleration (ie,, withm>1) gave better predictions of the occurrence of VWF than dose measures calculated from frequency-weighted acceleration (ie,). These findings were observed in the entire sample of HTV workers, in those with no VWF at the initial investigation, and in those with normal cold test results at baseline.Conclusions:This prospective cohort study suggests that measures of cumulative vibration doses constructed from unweighted r.m.s. acceleration perform better for the prediction of VWF than dose measures calculated according to the recommendations of current standards. These findings should contribute to the improvement of the ISO frequency weighting for evaluating the severity of hand-transmitted vibration.
VIDEO-BASED FACE RECOGNITION AND TRACKING FROM A ROBOT COMPANION
Authors: GERMA T. , LERASLE F. , SIMON T. 
Published: June 2009

This paper deals with video-based face recognition and tracking from a camera mounted on a mobile robot companion. All persons must be logically identified before being authorized to interact with the robot while continuous tracking is compulsory in order to estimate the person's approximate position. A first contribution relates to experiments of still-image-based face recognition methods in order to check which image projection and classifier associations give the highest performance of the face database acquired from our robot. Our approach, based on Principal Component Analysis (PCA) and Support Vector Machines (SVM) improved by genetic algorithm optimization of the free-parameters, is found to outperform conventional appearance-based holistic classifiers (eigenface and Fisherface) which are used as benchmarks. Relative performances are analyzed by means of Receiver Operator Characteristics which systematically provide optimized classifier free-parameter settings. Finally, for the SVM-based classifier, we propose a non-dominated sorting genetic algorithm to obtain optimized free-parameter settings. The second and central contribution is the design of a complete still-to-video face recognition system, dedicated to the previously identified person, which integrates face verification, as intermittent features, and shape and clothing color, as persistent cues, in a robust and probabilistically motivated way. The particle filtering framework, is well-suited to this context as it facilitates the fusion of different measurement sources. Automatic target recovery, after full occlusion or temporally disappearance from the field of view, is provided by positioning the particles according to face classification probabilities in the importance function. Moreover, the multi-cue fusion in the measurement function proves to be more reliable than any other individual cues. Evaluations on key-sequences acquired by the robot during long-term operations in crowded and continuously changing indoor environments demonstrate the robustness of the tracker against such natural settings. Mixing all these cues makes our video-based face recognition system work under a wide range of conditions encountered by the robot during its movements. The paper concludes with a discussion of possible extensions.
Laminar
Authors: Roy Indrajit , Porter Donald E. , Bond Michael D. , McKinley Kathryn S. , Witchel Emmett 
Published: June 2009

Decentralized information flow control (DIFC) is a promising model for writing programs with powerful, end-to-end security guarantees. Current DIFC systems that run on commodity hardware can be broadly categorized into two types: language-level and operating system-level DIFC. Language level solutions provide no guarantees against security violations on system resources, like files and sockets. Operating system solutions can mediate accesses to system resources, but are inefficient at monitoring the flow of information through fine-grained program data structures.
This paper describes Laminar, the first system to implement decentralized information flow control using a single set of abstractions for OS resources and heap-allocated objects. Programmers express security policies by labeling data with secrecy and integrity labels, and then access the labeled data in lexically scoped security regions. Laminar enforces the security policies specified by the labels at runtime. Laminar is implemented using a modified Java virtual machine and a new Linux security module. This paper shows that security regions ease incremental deployment and limit dynamic security checks, allowing us to retrofit DIFC policies on four application case studies. Replacing the applications' ad-hoc security policies changes less than 10% of the code, and incurs performance overheads from 1% to 56%. Whereas prior DIFC systems only support limited types of multithreaded programs, Laminar supports a more general class of multithreaded DIFC programs that can access heterogeneously labeled data.
TAJ
Authors: Tripp Omer , Pistoia Marco , Fink Stephen J. , Sridharan Manu , Weisman Omri 
Published: June 2009

Taint analysis, a form of information-flow analysis, establishes whether values from untrusted methods and parameters may flow into security-sensitive operations. Taint analysis can detect many common vulnerabilities in Web applications, and so has attracted much attention from both the research community and industry. However, most static taint-analysis tools do not address critical requirements for an industrial-strength tool. Specifically, an industrial-strength tool must scale to large industrial Web applications, model essential Web-application code artifacts, and generate consumable reports for a wide range of attack vectors.
We have designed and implemented a static Taint Analysis for Java (TAJ) that meets the requirements of industry-level applications. TAJ can analyze applications of virtually any size, as it employs a set of techniques designed to produce useful answers given limited time and space. TAJ addresses a wide variety of attack vectors, with techniques to handle reflective calls, flow through containers, nested taint, and issues in generating useful reports. This paper provides a description of the algorithms comprising TAJ, evaluates TAJ against production-level benchmarks, and compares it with alternative solutions.
LiteRace
Authors: Marino Daniel , Musuvathi Madanlal , Narayanasamy Satish 
Published: June 2009

Data races are one of the most common and subtle causes of pernicious concurrency bugs. Static techniques for preventing data races are overly conservative and do not scale well to large programs. Past research has produced several dynamic data race detectors that can be applied to large programs. They are precise in the sense that they only report actual data races. However, dynamic data race detectors incur a high performance overhead, slowing down a program's execution by an order of magnitude.
In this paper we present LiteRace, a very lightweight data race detector that samples and analyzes only selected portions of a program's execution. We show that it is possible to sample a multithreaded program at a low frequency, and yet, find infrequently occurring data races. We implemented LiteRace using Microsoft's Phoenix compiler. Our experiments with several Microsoft programs, Apache, and Firefox show that LiteRace is able to find more than 70% of data races by sampling less than 2% of memory accesses in a given program execution.
SoftBound
Authors: Nagarakatte Santosh , Zhao Jianzhou , Martin Milo M.K. , Zdancewic Steve 
Published: June 2009

The serious bugs and security vulnerabilities facilitated by C/C++'s lack of bounds checking are well known, yet C and C++ remain in widespread use. Unfortunately, C's arbitrary pointer arithmetic, conflation of pointers and arrays, and programmer-visible memory layout make retrofitting C/C++ with spatial safety guarantees extremely challenging. Existing approaches suffer from incompleteness, have high runtime overhead, or require non-trivial changes to the C source code. Thus far, these deficiencies have prevented widespread adoption of such techniques.
This paper proposes SoftBound, a compile-time transformation for enforcing spatial safety of C. Inspired by HardBound, a previously proposed hardware-assisted approach, SoftBound similarly records base and bound information for every pointer as disjoint metadata. This decoupling enables SoftBound to provide spatial safety without requiring changes to C source code. Unlike HardBound, SoftBound is a software-only approach and performs metadata manipulation only when loading or storing pointer values. A formal proof shows that this is sufficient to provide spatial safety even in the presence of arbitrary casts. SoftBound's full checking mode provides complete spatial violation detection with 67% runtime overhead on average. To further reduce overheads, SoftBound has a store-only checking mode that successfully detects all the security vulnerabilities in a test suite at the cost of only 22% runtime overhead on average.
Association of Breast Cancer Stem Cells Identified by Aldehyde Dehydrogenase 1 Expression with Resistance to Sequential Paclitaxel and Epirubicin-Based Chemotherapy for Breast Cancers
Authors: Tanei Tomonori , Morimoto Koji , Shimazu Kenzo , Kim Seung Jin , Tanji Yoshio , Taguchi Tetsuya , Tamaki Yasuhiro , Noguchi Shinzaburo 
Published: June 2009

AbstractPurpose: Breast cancer stem cells have been shown to be associated with resistance to chemotherapy in vitro, but their clinical significance remains to be clarified. The aim of this study was to investigate whether cancer stem cells were clinically significant for resistance to chemotherapy in human breast cancers.Experimental Design: Primary breast cancer patients (n = 108) treated with neoadjuvant chemotherapy consisting of sequential paclitaxel and epirubicin-based chemotherapy were included in the study. Breast cancer stem cells were identified by immunohistochemical staining of CD44/CD24 and aldehyde dehydrogenase 1 (ALDH1) in tumor tissues obtained before and after neoadjuvant chemotherapy. CD44+/CD24− tumor cells or ALDH1-positive tumor cells were considered stem cells.Results: Thirty (27.8%) patients achieved pathologic complete response (pCR). ALDH1-positive tumors were significantly associated with a low pCR rate (9.5% versus 32.2%; P = 0.037), but there was no significant association between CD44+/CD24− tumor cell proportions and pCR rates. Changes in the proportion of CD44+/CD24− or ALDH1-positive tumor cells before and after neoadjuvant chemotherapy were studied in 78 patients who did not achieve pCR. The proportion of ALDH1-positive tumor cells increased significantly (P &lt; 0.001) after neoadjuvant chemotherapy, but that of CD44+/CD24− tumor cells did not.Conclusions: Our findings suggest that breast cancer stem cells identified as ALDH1-positive, but not CD44+/CD24−, play a significant role in resistance to chemotherapy. ALDH1-positive thus seems to be a more significantly predictive marker than CD44+/CD24− for the identification of breast cancer stem cells in terms of resistance to chemotherapy.
Targeting DNA Methylation
Authors: Issa Jean-Pierre J. , Kantarjian Hagop M. 
Published: June 2009

Abstract
Two nucleoside inhibitors of DNA methylation, azacitidine and decitabine, are now standard of care for the treatment of the myelodysplastic syndrome, a deadly form of leukemia. These old drugs, developed as cytotoxic agents and nearly abandoned decades ago were resurrected by the renewed interest in DNA methylation. They have now provided proof of principle for epigenetic therapy, the final chapter in the long saga to provide legitimacy to the field of epigenetics in cancer. But challenges remain; we don't understand precisely how or why the drugs work or stop working after an initial response. Extending these promising findings to solid tumors faces substantial hurdles from drug uptake to clinical trial design. We do not know yet how to select patients for this therapy and how to move it from life extension to cure. The epigenetic potential of DNA methylation inhibitors may be limited by other epigenetic mechanisms that are also worth exploring as therapeutic targets. But the idea of stably changing gene expression in vivo has transformative potential in cancer therapy and beyond.
Cancer DNA Methylation: Molecular Mechanisms and Clinical Implications
Authors: McCabe Michael T. , Brandes Johann C. , Vertino Paula M. 
Published: June 2009

AbstractDNA methylation plays a crucial role in the regulation of gene expression and chromatin organization within normal eukaryotic cells. In cancer, however, global patterns of DNA methylation are altered with global hypomethylation of repeat-rich intergenic regions and hypermethylation of a subset of CpG-dense gene-associated regions (CpG islands). Extensive research has revealed the cellular machinery that catalyzes DNA methylation, as well as several large protein complexes that mediate the transcriptional repression of hypermethylated genes. However, research is only just beginning to uncover the molecular mechanisms underlying the origins of cancer-specific DNA methylation. Herein, we present several recent advances regarding these mechanisms and discuss the relationship between histone modifications (i.e., H3K4me2/3, H4K16Ac, H3K9me2/3, H3K27me3, H4K20me3), chromatin-modifying enzymes (G9a, EZH2, hMOF, SUV4-20H), and aberrant DNA methylation. Additionally, the role played by inflammation, DNA damage, and miRNAs in the etiology of aberrant DNA methylation is considered. Finally, we discuss the clinical implications of aberrant DNA methylation and the utility of methylated biomarkers in cancer diagnosis and management.
Clinical Studies of Histone Deacetylase Inhibitors
Authors: Prince H. Miles , Bishton Mark J. , Harrison Simon J. 
Published: June 2009

Abstract
Over the last 5 years, a plethora of histone deacetylase inhibitors (HDACi) have been evaluated in clinical trials. These drugs have in common the ability to hyperacetylate both histone and nonhistone targets, resulting in a variety of effects on cancer cells, their microenvironment, and immune responses. To date, responses with single agent HDACi have been predominantly observed in advanced hematologic malignancies including T-cell lymphoma, Hodgkin lymphoma, and myeloid malignancies. Therefore, in this review we focus upon hematologic malignancies. Generally HDACi are well tolerated with the most common acute toxicities being fatigue, gastrointestinal, and transient cytopenias. Of note, few patients have been treated for prolonged periods of time and little is known about long-term toxicities. The use of the biomarker of histone hyperacetylation has been useful as a guide to target specificity, but generally does not predict for response and the search for more clinically relevant biomarkers must continue.
Rational Combinations Using HDAC Inhibitors
Authors: Bots Michael , Johnstone Ricky W. 
Published: June 2009

Abstract
In addition to well-characterized genetic abnormalities that lead to cancer onset and progression, it is now recognized that alterations to the epigenome may also play a significant role in oncogenesis. As a result, epigenetic-modulating agents such as histone deacetylase inhibitors (HDACi) have attracted enormous attention as anticancer drugs. In numerous in vitro and preclinical settings, these compounds have shown their vast potential as single agent anticancer therapies, but unfortunately equivalent responses have not always been observed in patients. Given the pleiotropic effects HDACi have on malignant cells, their true therapeutic potential most likely lies in combination with other anticancer drugs. In this review we will focus on the anticancer effects of HDACi when combined with other cancer therapeutics with an emphasis on those combinations based on a strong molecular rationale.
Epigenetic Modifiers: Basic Understanding and Clinical Development
Authors: Piekarz Richard L. , Bates Susan E. 
Published: June 2009

Abstract
More than 60 years after the first description of differentiation in cell culture and 40 years after the synthesis of 5-azacytidine, epigenetic therapies have been added to the anticancer armamentarium. DNA methyltransferase (DNMT) inhibitors such as 5-aza-2′-deoxycytidine or 5-azacytidine have been approved in myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML), whereas the histone deacetylase inhibitors (HDIs) including vorinostat, romidepsin, panobinostat, belinostat, and entinostat have been shown to be active in cutaneous and peripheral T-cell lymphoma. Although the range of malignancies in which monotherapy with DNMT inhibitors or HDIs are effective has been limited to date, the possibility remains that a broader spectrum of activity will be identified as combination studies are completed. Meanwhile, basic science has provided a steadily increasing understanding of the complexity of the epigenome, including the histone code and triggers for aberrant methylation, and their contribution to oncogenesis. As our basic understanding of the epigenetics of cancer increases, the number of potential therapeutic targets will also increase, offering more hope in the quest to treat cancer by normalizing the epigenome. This issue of CCR Focus is dedicated to understanding the clinical and translational aspects of epigenetics research.
Suppression of HER2/HER3-Mediated Growth of Breast Cancer Cells with Combinations of GDC-0941 PI3K Inhibitor, Trastuzumab, and Pertuzumab
Authors: Yao Evelyn , Zhou Wei , Lee-Hoeflich Si Tuen , Truong Tom , Haverty Peter M. , Eastham-Anderson Jeffrey , Lewin-Koh Nicholas , Gunter Bert , Belvin Marcia , Murray Lesley J. , Friedman Lori S. , Sliwkowski Mark X. , Hoeflich Klaus P. 
Published: June 2009

Abstract
Purpose: Oncogenic activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway is prevalent in breast cancer and has been associated with resistance to HER2 inhibitors in the clinic. We therefore investigated the combinatorial activity of GDC-0941, a novel class I PI3K inhibitor, with standard-of-care therapies for HER2-amplified breast cancer.
Experimental Design: Three-dimensional laminin-rich extracellular matrix cultures of human breast cancer cells were utilized to provide a physiologically relevant approach to analyze the efficacy and molecular mechanism of combination therapies ex vivo. Combination studies were done using GDC-0941 with trastuzumab (Herceptin), pertuzumab, lapatinib (Tykerb), and docetaxel, the principal therapeutic agents that are either approved or being evaluated for treatment of early HER2-positive breast cancer.
Results: Significant GDC-0941 activity (EC50 &lt;1 μmol/L) was observed for &gt;70% of breast cancer cell lines that were examined in three-dimensional laminin-rich extracellular matrix culture. Differential responsiveness to GDC-0941 as a single agent was observed for luminal breast cancer cells upon stimulation with the HER3 ligand, heregulin. Combined treatment of GDC-0941, trastuzumab, and pertuzumab resulted in growth inhibition, altered acinar morphology, and suppression of AKT mitogen-activated protein kinase (MAPK) / extracellular signed-regulated kinase (ERK) kinase and MEK effector signaling pathways for HER2-amplified cells in both normal and heregulin-supplemented media. The GDC-0941 and lapatinib combination further showed that inhibition of HER2 activity was essential for maximum combinatorial efficacy. PI3K inhibition also rendered HER2-amplified BT-474M1 cells and tumor xenografts more sensitive to docetaxel.
Conclusions: GDC-0941 is efficacious in preclinical models of breast cancer. The addition of GDC-0941 to HER2-directed treatment could augment clinical benefit in breast cancer patients.