bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating instruction cache vulnerability to transient errors
Authors: Yan Jun , Zhang Wei 
Published: December 2007

Recent research shows that microprocessors are increasingly susceptible to transient errors. In order to protect microprocessors cost-effectively, the first step is to accurately understand the impact of transient errors on the system reliability. While many research efforts have been focused on studying the vulnerability of data caches and other on-chip hardware components, instruction caches have received less attention. However, instructions are read every cycle, any undetected or uncorrected soft errors in instructions can lead to erroneous computation, wrong control flow or system crash.
This paper studies the instruction cache vulnerability by considering both the raw SRAM rate and the cache vulnerability factor. Based on the concept of cache vulnerability factor, we also investigate the impact of different cache configuration parameters on the reliability of instruction caches. We find that on average 67.5% of instruction cache soft errors can be masked by the I-cache itself without impacting other system components. While quantifying the instruction cache vulnerability itself does not solve the reliability problem of instruction cache against transient errors, we believe this work can provide useful insights for designers to develop cost-effective solutions to protect I-caches and to optimally balance the reliability of instruction caches with other system goals, such as cost, performance and energy.
Characterization of TMPRSS2:ETV5 and SLC45A3:ETV5 Gene Fusions in Prostate Cancer
Authors: Helgeson Beth E. , Tomlins Scott A. , Shah Nameeta , Laxman Bharathi , Cao Qi , Prensner John R. , Cao Xuhong , Singla Nirmish , Montie James E. , Varambally Sooryanarayana , Mehra Rohit , Chinnaiyan Arul M. 
Published: January 2008

Abstract
Recurrent gene fusions involving oncogenic ETS transcription factors (including ERG, ETV1, and ETV4) have been identified in a large fraction of prostate cancers. The most common fusions contain the 5′ untranslated region of TMPRSS2 fused to ERG. Recently, we identified additional 5′ partners in ETV1 fusions, including TMPRSS2, SLC45A3, HERV-K_22q11.23, C15ORF21, and HNRPA2B1. Here, we identify ETV5 as the fourth ETS family member involved in recurrent gene rearrangements in prostate cancer. Characterization of two cases with ETV5 outlier expression by RNA ligase–mediated rapid amplification of cDNA ends identified one case with a TMPRSS2:ETV5 fusion and one case with a SLC45A3:ETV5 fusion. We confirmed the presence of these fusions by quantitative PCR and fluorescence in situ hybridization. In vitro recapitulation of ETV5 overexpression induced invasion in RWPE cells, a benign immortalized prostatic epithelial cell line. Expression profiling and an integrative molecular concepts analysis of RWPE-ETV5 cells also revealed the induction of an invasive transcriptional program, consistent with ERG and ETV1 overexpression in RWPE cells, emphasizing the functional redundancy of ETS rearrangements. Together, our results suggest that the family of 5′ partners previously identified in ETV1 gene fusions can fuse with other ETS family members, suggesting numerous rare gene fusion permutations in prostate cancer. [Cancer Res 2008;68(1):73–80]
Clinical and Molecular Responses in Lung Cancer Patients Receiving Romidepsin
Authors: Schrump David S. , Fischette Maria R. , Nguyen Dao M. , Zhao Ming , Li Xinmin , Kunst Tricia F. , Hancox Ana , Hong Julie A. , Chen G. Aaron , Kruchin Evgeny , Wright John J. , Rosing Douglas R. , Sparreboom Alex , Figg William D. , Steinberg Seth M. 
Published: January 2008

Abstract
Purpose: Our preclinical experiments indicated that Romidepsin (Depsipeptide FK228; DP) mediates growth arrest and apoptosis in cultured lung cancer cells. A phase II trial was done to examine clinical and molecular responses mediated by this histone deacetylase inhibitor in lung cancer patients.
Experimental Design: Nineteen patients with neoplasms refractory to standard therapy received 4-h DP infusions (17.8 mg/m2) on days 1 and 7 of a 21-day cycle. Each full course of therapy consisted of two identical 21-day cycles. Plasma DP levels were evaluated by liquid chromatography–mass spectrometry techniques. A variety of molecular end points were assessed in tumor biopsies via immunohistochemistry techniques. Long oligo arrays were used to examine gene expression profiles in laser-captured tumor cells before and after DP exposure, relative to lung cancer cells and adjacent normal bronchial epithelia from patients undergoing pulmonary resections.
Results: Nineteen patients were evaluable for toxicity assessment; 18 were evaluable for treatment response. Myelosuppression was dose limiting in one individual. No significant cardiac toxicities were observed. Maximum steady-state plasma DP concentrations ranged from 384 to 1,114 ng/mL. No objective responses were observed. Transient stabilization of disease was noted in nine patients. DP enhanced acetylation of histone H4, increased p21 expression in lung cancer cells, and seemed to shift global gene expression profiles in these cells toward those detected in normal bronchial epithelia.
Conclusion: Although exhibiting minimal clinical efficacy at this dose and schedule, DP mediates biological effects that may warrant further evaluation of this histone deacetylase inhibitor in combination with novel-targeted agents in lung cancer patients.
Can Inhibiting Dihydropyrimidine Dehydrogenase Limit Hand-Foot Syndrome Caused by Fluoropyrimidines?
Authors: Yen-Revollo Jane L. , Goldberg Richard M. , McLeod Howard L. 
Published: January 2008

AbstractHand-foot syndrome (HFS) is a cutaneous adverse event that occurs in some patients treated with fluoropyrimidines. Although it is not life threatening, HFS can severely disrupt the daily lives of patients. HFS appears more frequently with 5-fluorouracil (5-FU) delivered by continuous infusion or with the 5-FU oral derivative capecitabine than with bolus 5-FU therapy. HFS is a leading cause of treatment interruption, dosage reduction, or, even, therapy discontinuation for patients on a capecitabine regimen. Interestingly, addition of a dihydropyrimidine dehydrogenase (DPD) inhibitor, such as uracil, 5-chloro-2,4-dihydroxypyridine, or eniluracil, to the fluoropyrimidine treatment regimen significantly diminishes the incidence of HFS. DPD inhibitors were initially combined with fluoropyrimidines to increase the efficacy of the drugs by impairing the DPD-mediated catabolism of 5-FU. However, with the accumulating findings from clinical trials that show the benefits of DPD inhibition on decreasing the risk of HFS, consideration should be given to changing the recommendations for the treatment of cancer patients with fluoropyrimidines to include DPD inhibitor components as standard therapy.
Interleukin-13 Receptor α2, EphA2, and Fos-Related Antigen 1 as Molecular Denominators of High-Grade Astrocytomas and Specific Targets for Combinatorial Therapy
Authors: Wykosky Jill , Gibo Denise M. , Stanton Constance , Debinski Waldemar 
Published: January 2008

AbstractPurpose: We investigated the expression of interleukin-13 receptor α2 (IL-13Rα2), EphA2, and Fos-related antigen 1 (Fra-1) in astrocytomas and normal brain. We sought to document whether the expression of the three factors changed with progression to higher grade malignancy and whether two or three targets in combination might be sufficient to target all patients with high-grade astrocytomas.Experimental Design: Immunohistochemistry was done for IL-13Rα2, EphA2, and Fra-1 using human brain tumor tissue microarrays containing 30 specimens of WHO grades II and III astrocytomas, 46 glioblastoma multiformes (GBM), and 9 normal brain samples. Sections were scored based on frequency and intensity of expression. Western blotting was done for all three markers using GBM tumor specimens and xenograft cell lines. Two cytotoxins, IL-13.E13K.PE38QQR and ephrinA1-PE38QQR, which target IL-13Rα2 or EphA2, respectively, were tested for cytotoxicity against human GBM primary explant cells and established cells.Results: Expression of all three proteins was significantly higher in GBM compared with normal brain, low-grade, and anaplastic astrocytomas. Greater than 95% of GBM overexpressed at least two of the three markers. Importantly, every GBM overexpressed at least one marker. Human GBM primary explant cells and cell lines were potently killed by IL-13.E13K.PE38QQR and ephrinA1-PE38QQR, in accordance with their level of expression of IL-13Rα2 and EphA2, respectively.Conclusions: IL-13Rα2, EphA2, and Fra-1 are attractive therapeutic targets representing molecular denominators of high-grade astrocytomas. One hundred percent of GBM tumors overexpress at least one of these proteins, providing the basis for rational combinatorial targeted therapies/diagnostics suitable for all patients with this disease.
An In-Person Survey Investigating Public Perceptions of and Responses to Hurricane Rita Forecasts along the Texas Coast
Authors: Zhang Fuqing , Morss Rebecca E. , Sippel J. A. , Beckman T. K. , Clements N. C. , Hampshire N. L. , Harvey J. N. , Hernandez J. M. , Morgan Z. C. , Mosier R. M. , Wang S. , Winkley S. D. 
Published: January 2008

AbstractHurricane Rita made landfall near the Texas–Louisiana border in September 2005, causing major damage and disruption. As Rita approached the Gulf Coast, uncertainties in the storm’s track and intensity forecasts, combined with the aftermath of Hurricane Katrina, led to major evacuations along the Texas coast and significant traffic jams in the broader Houston area. This study investigates the societal impacts of Hurricane Rita and its forecasts through a face-to-face survey with 120 Texas Gulf Coast residents. The survey explored respondents’ evacuation decisions prior to Hurricane Rita, their perceptions of hurricane risk, and their use of and opinions on Hurricane Rita forecasts. The vast majority of respondents evacuated from Hurricane Rita, and more than half stated that Hurricane Katrina affected their evacuation decision. Although some respondents said that their primary reason for evacuating was local officials’ evacuation order, many reported using information about the hurricane to evaluate the risk it posed to them and their families. Despite the major traffic jams and the minor damage in many evacuated regions, most evacuees interviewed do not regret their decision to evacuate. The majority of respondents stated that they intend to evacuate for a future category 3 hurricane, but the majority would stay for a category 2 hurricane. Most respondents obtained forecasts from multiple sources and reported checking forecasts frequently. Despite the forecast uncertainties, the respondents had high confidence in and satisfaction with the forecasts of Rita provided by the National Hurricane Center.
`Inclusive Education'
Authors: Clare Brenda , Mevik Kate 
Published: January 2008

• Summary: The article presents the findings of an exploratory study that considers the extent to which Australian and Norwegian social work education equips practitioners to work inclusively with children. It provides an analysis of details of curricula content found on universities' websites to provide a broad-brush map of teaching and learning priorities. It then presents the views of a number of Norwegian and Australian academics about what social work students are, and should be, taught about childhood and working with children. • Findings: The article reports a number of differences in emphasis in the teaching and learning models adopted in Australian and Norwegian social work programmes. Despite these differences, however, the tentative conclusion drawn from this study is that in both countries, equipping students to understand and work with children in their own right is a low priority. Reasons for this common outcome are discussed. • Applications : The scale of the study is small. However, the findings are of significance for social work educators, practitioners and policy-makers. If children are to be properly represented within the welfare arena, foundational professional education must equip students with knowledge, skills and attitudes that enable them to work with and for this population. The article argues that this may not be the case and highlights the need for further research.
Thinking through Sexuality
Authors: Hicks Stephen 
Published: January 2008

• Summary: This article is a discussion piece on the idea of `sexuality' within social work. The author discusses dominant models of sexuality — including those within anti-discriminatory practice theory — before going on to raise a number of problems with this perspective. The article draws upon queer, feminist and Foucaultian theories to suggest less restrictive ways of thinking through sexuality and social work. • Findings: Social work has a tendency to define `sexuality' as an essential identity with a fixed set of characteristics and social welfare `needs'. This article argues for a reflexive account of sexuality within social work, and for the investigation of the production and use of sexuality categories within everyday professional settings. • Applications : The author discusses the assessment of sexuality in cases of foster care or adoption applications by lesbians or gay men in order to highlight the practical application of these ideas. The article discusses why new ways of thinking through sexuality may be productive for social work.
Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis
Authors: Balgobind Brian V. , Van Vlierberghe Pieter , van den Ouweland Ans M. W. , Beverloo H. Berna , Terlouw-Kromosoeto Joan N. R. , van Wering Elisabeth R. , Reinhardt Dirk , Horstmann Martin , Kaspers Gertjan J. L. , Pieters Rob , Zwaan C. Michel , Van den Heuvel-Eibrink Marry M. , Meijerink Jules P. P. 
Published: January 2008

AbstractNeurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder caused by mutations in the NF1 gene. Patients with NF1 have a higher risk to develop juvenile myelomonocytic leukemia (JMML) with a possible progression toward acute myeloid leukemia (AML). In an oligo array comparative genomic hybridization–based screening of 103 patients with pediatric T-cell acute lymphoblastic leukemia (T-ALL) and 71 patients with MLL-rearranged AML, a recurrent cryptic deletion, del(17)(q11.2), was identified in 3 patients with T-ALL and 2 patients with MLL-rearranged AML. This deletion has previously been described as a microdeletion of the NF1 region in patients with NF1. However, our patients lacked clinical NF1 symptoms. Mutation analysis in 4 of these del(17)(q11.2)-positive patients revealed that mutations in the remaining NF1 allele were present in 3 patients, confirming its role as a tumor-suppressor gene in cancer. In addition, NF1 inactivation was confirmed at the RNA expression level in 3 patients tested. Since the NF1 protein is a negative regulator of the RAS pathway (RAS-GTPase activating protein), homozygous NF1 inactivation represent a novel type I mutation in pediatric MLL-rearranged AML and T-ALL with a predicted frequency that is less than 10%. NF1 inactivation may provide an additional proliferative signal toward the development of leukemia.
Cryptic diversity and deep divergence in an upper Amazonian leaflitter frog, Eleutherodactylus ockendeni
Authors: Elmer Kathryn R , Dávila José A , Lougheed Stephen C 
Published: December 2007

AbstractBackgroundThe forests of the upper Amazon basin harbour some of the world's highest anuran species richness, but to date we have only the sparsest understanding of the distribution of genetic diversity within and among species in this region. To quantify region-wide genealogical patterns and to test for the presence of deep intraspecific divergences that have been documented in some other neotropical anurans, we developed a molecular phylogeny of the wide-spread terrestrial leaflitter frogEleutherodactylus ockendeni(Leptodactylidae) from 13 localities throughout its range in Ecuador using data from two mitochondrial genes (16S and cyt b; 1246 base pairs). We examined the relation between divergence of mtDNA and the nuclear genome, as sampled by five species-specific microsatellite loci, to evaluate indirectly whether lineages are reproductively isolated where they co-occur. Our extensive phylogeographic survey thus assesses the spatial distribution ofE. ockendenigenetic diversity across eastern Ecuador.ResultsWe identified three distinct and well-supported clades within the Ecuadorean range ofE. ockendeni: an uplands clade spanning north to south, a northeastern and central lowlands clade, and a central and southeastern clade, which is basal. Clades are separated by 12% to 15% net corrected p-distance for cytochromeb, with comparatively low sequence divergence within clades. Clades marginally overlap in some geographic areas (e.g., Napo River basin) but are reproductively isolated, evidenced by diagnostic differences in microsatellite PCR amplification profiles or DNA repeat number and coalescent analyses (in MDIV) best modelled without migration. Using Bayesian (BEAST) and net phylogenetic estimates, the Southeastern Clade diverged from the Upland/Lowland clades in the mid-Miocene or late Oligocene. Lowland and Upland clades speciated more recently, in the early or late Miocene.ConclusionOur findings uncover previously unsuspected cryptic species diversity within the common leaflitter frogE. ockendeni, with at least three different species in Ecuador. While these clades are clearly geographically circumscribed, they do not coincide with any existing landscape barriers. Divergences are ancient, from the Miocene, before the most dramatic mountain building in the Ecuadorean Andes. Therefore, this diversity is not a product of Pleistocene refuges. Our research coupled with other studies suggests that species richness in the upper Amazon is drastically underestimated by current inventories based on morphospecies.
Predicting long-term response to strong opioids in patients with low back pain: findings from a randomized, controlled trial of transdermal fentanyl and morphine
Authors: Kalso Eija , Simpson Karen H , Slappendel Robert , Dejonckheere Joachim , Richarz Ute 
Published: December 2007

Abstract

Background
Some patients with long-standing low back pain will benefit from treatment with strong opioids. However, it would be helpful to predict which patients will have a good response. A fixed-term opioid trial has been recommended, but there is little evidence to suggest how long this trial should be. We assessed data from a large-scale randomized comparison of transdermal fentanyl (TDF) and sustained-release oral morphine (slow-release morphine; SRM) to determine characteristics of treatment responders.

Methods
This was a secondary analysis of a previously published 13-month randomized trial involving 680 patients with long-standing low back pain (median age 52 years, 61% women, median duration of back pain 87 months). Pain relief was recorded using visual analogue scales (VAS). Treatment response was defined as pain relief of at least 30% from baseline to any point during the trial. We used a step-wise logistic regression to identify variables that might predict response to treatment. Covariates included treatment group, sex, age, duration of pain, presence of neuropathic pain, baseline pain scores, educational/employment status, use of high doses of opioids, and social functioning (SF)-36 scores.

Results
Over half the patients in both groups (n = 370; 54% TDF, 55% SRM) were treatment responders. There were no differences between the TDF and SRM responders in terms of age, sex, type or duration of pain between responders and non-responders. The difference in response to treatment between responders and non-responders could be detected at 3 weeks. Lack of response after 1 month had a stronger negative predictive value (i.e., ability to detect non-responders) than the presence of response after 1 month. The most influential factors for predicting a response were employment status (χ2 = 11.06, p = 0.0259) and use of high doses of opioids (χ2 = 3.04, p = 0.0811).

Conclusion
No clear pattern of baseline pain (type or severity) or patient characteristics emerged that could be used to predict responders before the start of opioid treatment. However, a 1-month trial period appears sufficient to determine response and tolerability in most cases.
Consistent dissection of the protein interaction network by combining global and local metrics
Authors: Wang Chunlin , Ding Chris , Yang Qiaofeng , Holbrook Stephen R 
Published: December 2007

AbstractWe propose a new network decomposition method to systematically identify protein interaction modules in the protein interaction network. Our method incorporates both a global metric and a local metric for balance and consistency. We have compared the performance of our method with several earlier approaches on both simulated and real datasets using different criteria, and show that our method is more robust to network alterations and more effective at discovering functional protein modules.
CHEK2*1100delC Genotyping for Clinical Assessment of Breast Cancer Risk: Meta-Analyses of 26,000 Patient Cases and 27,000 Controls
Authors: Weischer Maren , Bojesen Stig Egil , Ellervik Christina , Tybjærg-Hansen Anne , Nordestgaard Børge Grønne 
Published: January 2008

Purpose CHEK2*1100delC heterozygosity may be associated with an increased risk of breast cancer; however, it is unclear whether the evidence is sufficient to recommend genotyping in clinical practice. Patients and Methods We identified studies on CHEK2*1100delC heterozygosity and the risk of unselected, early-onset, and familial breast cancer through comprehensive, computer-based searches of PubMed, EMBASE, and Web of Science. Aggregated risk estimates were compared with previous estimates for BRCA1 and BRCA2 mutation heterozygotes. Results By using fixed-effect models for CHEK2*1100delC heterozygotes versus noncarriers, we found aggregated odds ratios of 2.7 (95% CI, 2.1 to 3.4) for unselected breast cancer, 2.6 (95% CI, 1.3 to 5.5) for early-onset breast cancer, and 4.8 (95% CI, 3.3 to 7.2) for familial breast cancer. For familial breast cancer, this corresponds to a cumulative risk of breast cancer at age 70 years in CHEK2*1100delC heterozygotes of 37% (95% CI, 26% to 56%), which compares with similar previous estimates of 57% (95% CI, 47% to 66%) for BRCA1 mutation heterozygotes and 49% (95% CI, 40% to 57%) for BRCA2 mutation heterozygotes. Conclusion These meta-analyses emphasize that CHEK2*1100delC is an important breast cancer–predisposing gene, which increases the risk three- to five-fold. Because the cumulative risk of breast cancer at age 70 years among familial patient cases for CHEK2*1100delC heterozygotes is almost as high as that for BRCA1 and BRCA2 mutation heterozygotes, genotyping for CHEK2*1100delC should be considered together with BRCA1 and BRCA2 mutation screening in women with a family history of breast cancer.