bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stream Execution on Embedded Wide-Issue Clustered VLIW Architectures
Authors: Yan Shan , Lin Bill 
Published: February 2009

AbstractVery long instruction word- (VLIW-) based processors have become widely adopted as a basic building block in modern System-on-Chip designs. Advances in clustered VLIW architectures have extended the scalability of the VLIW architecture paradigm to a large number of functional units and very-wide-issue widths. A central challenge with wide-issue clustered VLIW architecture is the availability of programming and automated compiler methods that can fully utilize the available computational resources. Existing compilation approaches for clustered-VLIW architectures are based on extensions of previously developed scheduling algorithms that primarily focus on the maximization of instruction-level parallelism (ILP). However, many applications do not have sufficient ILP to fully utilize a large number of functional units. On the other hand, many applications in digital communications and multimedia processing exhibit enormous amounts of data-level parallelism (DLP). For these applications, the streaming programming paradigm has been developed to explicitly expose coarse-grained data-level parallelism as well as the locality of communication between coarse-grained computation kernels. In this paper, we investigate the mapping of stream programs to wide-issue clustered VLIW processors. Our work enables designers to leverage their existing investments in VLIW-based architecture platforms to harness the advantages of the stream programming paradigm.
17β-Hydroxysteroid Dehydrogenase Type 12 in Human Breast Carcinoma: A Prognostic Factor via Potential Regulation of Fatty Acid Synthesis
Authors: Nagasaki Shuji , Suzuki Takashi , Miki Yasuhiro , Akahira Jun-ichi , Kitada Kunio , Ishida Takanori , Handa Hiroshi , Ohuchi Noriaki , Sasano Hironobu 
Published: February 2009

Abstract
17β-Hydroxysteroid dehydrogenase type 12 (17β-HSD12) has been shown to be involved in elongation of very long chain fatty acid (VLCFA) as well as in biosynthesis of estradiol (E2). 17β-HSD12 expression was also reported in breast carcinomas but its functions have remained unknown. In this study, we examined the correlation between mRNA expression profiles determined by microarray analysis and tissue E2 concentrations obtained from 16 postmenopausal breast carcinoma cases. No significant correlations were detected between 17β-HSD12 expression and E2 concentration. We then immunolocalized this enzyme in 110 cases of invasive ductal carcinoma. 17β-HSD12 immunoreactivity in breast carcinoma cells was significantly associated with poor prognosis of the patients. We further examined the biological significance of 17β-HSD12 using cell-based studies. Small interfering RNA–mediated knockdown of 17β-HSD12 in SK-BR-3 (estrogen receptor–negative breast carcinoma cell line) resulted in significant growth inhibition, which was recovered by the addition of VLCFAs such as arachidonic acid. The status of 17β-HSD12 immunoreactivity was also correlated with adverse clinical outcome in cyclooxygenase 2 (COX2)–positive breast cancer patients but not in COX2-negative patients. Therefore, these findings indicated that 17β-HSD12 was not necessarily related to intratumoral E2 biosynthesis, at least in human breast carcinoma, but was rather correlated with production of VLCFAs such as arachidonic acid, which may subsequently be metabolized to prostaglandins by COX2 and result in tumor progression of the patients. [Cancer Res 2009;69(4):1392–9]
Identification of SULF2 as a Novel Transcriptional Target of p53 by Use of Integrated Genomic Analyses
Authors: Chau B. Nelson , Diaz Robert L. , Saunders Matthew A. , Cheng Chun , Chang Aaron N. , Warrener Paul , Bradshaw Jeffrey , Linsley Peter S. , Cleary Michele A. 
Published: February 2009

Abstract
Microarray analysis has been useful for identifying the targets of many transcription factors. However, gene expression changes in response to transcription factor perturbation reveal both direct transcriptional targets and secondary gene regulation. By integrating RNA interference, gene expression profiling, and chromatin immunoprecipitation technologies, we identified a set of 32 direct transcriptional targets of the tumor suppressor p53. Of these 32 genes, 11 are not currently associated with the core p53 pathway. From among these novel pathway members, we focused on understanding the connection between p53 and SULF2, which encodes an extracellular heparan sulfate 6-O-endosulfatase that modulates the binding of growth factors to their cognate receptors and that has been shown to function as a tumor suppressor. Genetic and pharmacologic perturbation of p53 directly influences SULF2 expression, and similar to silencing of TP53, RNA interference–mediated suppression of SULF2 results in an impaired senescence response of cells to genotoxic stress. Thus, our integrated genomic approach has led to the identification of a novel mediator of p53 network biology. [Cancer Res 2009;69(4):1368–74]
Identification of a Novel Pathway That Selectively Modulates Apoptosis of Breast Cancer Cells
Authors: Tinnikov Alexander A. , Yeung Kay T. , Das Sharmistha , Samuels Herbert H. 
Published: February 2009

Abstract
Expression of the nuclear receptor interacting factor 3 (NRIF3) coregulator in a wide variety of breast cancer cells selectively leads to rapid caspase-2–dependent apoptotic cell death. A novel death domain (DD1) was mapped to a 30–amino acid region of NRIF3. Because the cytotoxicity of NRIF3 and DD1 seems to be cell type–specific, these studies suggest that breast cancer cells contain a novel “death switch” that can be specifically modulated by NRIF3 or DD1. Using an MCF-7 cell cDNA library in a yeast two-hybrid screen, we cloned a factor that mediates apoptosis by DD1 and refer to this factor as DD1-interacting factor-1 (DIF-1). DIF-1 is a transcriptional repressor that mediates its effect through SirT1, and this repression is attenuated by the binding of NRIF3/DD1. DIF-1 expression rescues breast cancer cells from NRIF3/DD1-induced apoptosis. Small interfering RNA (siRNA) knockdown of DIF-1 selectively leads to apoptosis of breast cancer cells, further suggesting that DIF-1 plays a key role in NRIF3/DD1-mediated apoptosis. A protein kinase A inhibitor (H89) also elicits apoptosis of breast cancer cells but not of the other cell types examined, and DIF-1 also protects these cells from H89-mediated apoptosis. In addition, H89 incubation results in a rapid increase in NRIF3 levels and siRNA knockdown of NRIF3 protects breast cancer cells from H89-mediated apoptosis. Our results indicate that DIF-1 plays a key role in breast cancer cell survival and further characterizing this pathway may provide important insights into developing novel therapies to selectively target breast cancer cells for apoptosis. [Cancer Res 2009;69(4):1375–82]
An Activating β1 Integrin Mutation Increases the Conversion of Benign to Malignant Skin Tumors
Authors: Ferreira Manuela , Fujiwara Hironobu , Morita Kazumasa , Watt Fiona M. 
Published: February 2009

Abstract
Identifying the physiologic relevance of cancer-associated genetic polymorphisms is a major challenge. Several changes in the coding sequence of β integrin subunits have now been described in human tumors. One of these, T188Iβ1, was identified as a heterozygous mutation in a poorly differentiated squamous cell carcinoma (SCC) and shown to activate extracellular matrix adhesion and inhibit keratinocyte differentiation in vitro. To study its contribution to tumor development, we overexpressed the mutant or wild-type (WT) human β1 subunit in the basal layer of mouse epidermis using the keratin 14 promoter. The transgenic integrins were expressed at the cell surface and were functional, with the T188Iβ1 subunit promoting cell spreading to a greater extent than WTβ1. Epidermal proliferation and differentiation were unaffected and no expansion of the stem cell compartment was detected. During chemical carcinogenesis, both transgenes increased papilloma formation, but only the T188Iβ1 transgene stimulated the conversion of papillomas to SCCs. Papillomas bearing the mutation showed increased Erk activity and reduced differentiation. SCCs expressing T188Iβ1 were less well-differentiated than those expressing WTβ1. These observations establish that the expression of a genetic variant in the I-like domain of β1 integrins does not affect normal epidermal homeostasis, but increases tumor susceptibility and influences tumor type. [Cancer Res 2009;69(4):1334–42]
In vivo Off-Resonance Saturation Magnetic Resonance Imaging of αvβ3-Targeted Superparamagnetic Nanoparticles
Authors: Khemtong Chalermchai , Kessinger Chase W. , Ren Jimin , Bey Erik A. , Yang Su-Geun , Guthi Jagadeesh Setti , Boothman David A. , Sherry A. Dean , Gao Jinming 
Published: February 2009

Abstract
Magnetic resonance imaging is a powerful clinical imaging technique that allows for noninvasive tomographic visualization of anatomic structures with high spatial resolution and soft tissue contrast. However, its application in molecular imaging of cancer has been limited by the lack of sensitivity and detection accuracy in depicting the biochemical expression of these diseases. Here, we combine an ultrasensitive design of superparamagnetic polymeric micelles (SPPM) and an off-resonance saturation (ORS) method to enhance the imaging efficacy of tumor biomarkers in vivo. SPPM nanoparticles encoded with cyclic(RGDfK) were able to target the αvβ3-expressing microvasculature in A549 non–small cell lung tumor xenografts in mice. ORS greatly improved tumor detection accuracy over the conventional T2*-weighted method by its ability to turn “ON” the contrast of SPPM. This combination of ORS imaging with a tumor vasculature–targeted, ultrasensitive SPPM design offers new opportunities in molecular imaging of cancer. [Cancer Res 2009;69(4):1651–8]
Breast Cancer Metastasis Suppressor 1 Up-regulates miR-146, Which Suppresses Breast Cancer Metastasis
Authors: Hurst Douglas R. , Edmonds Mick D. , Scott Gary K. , Benz Christopher C. , Vaidya Kedar S. , Welch Danny R. 
Published: February 2009

Abstract
Breast cancer metastasis suppressor 1 (BRMS1) is a predominantly nuclear protein that differentially regulates expression of multiple genes, leading to suppression of metastasis without blocking orthotopic tumor growth in multiple human and murine cancer cells of diverse origins. We hypothesized that miR-146 may be involved in the ability of BRMS1 to supress metastasis because miR-146 expression is altered by BRMS1 and because BRMS1 and miR-146 are both associated with decreased signaling through the nuclear factor-κB pathway. BRMS1 significantly up-regulates miR-146a by 6- to 60-fold in metastatic MDA-MB-231 and MDA-MB-435 cells, respectively, and miR-146b by 40-fold in MDA-MB-435 as measured by real-time quantitative reverse transcription-PCR. Transduction of miR-146a or miR-146b into MDA-MB-231 down-regulated expression of epidermal growth factor receptor, inhibited invasion and migration in vitro, and suppressed experimental lung metastasis by 69% and 84%, respectively (mean ± SE: empty vector = 39 ± 6, miR-146a = 12 ± 1, miR-146b = 6 ± 1). These results further support the recent notion that modulating the levels of miR-146a or miR-146b could have a therapeutic potential to suppress breast cancer metastasis. [Cancer Res 2009;69(4):1279–83]
Distinct BRAF (V600E) and KRAS Mutations in High Microsatellite Instability Sporadic Colorectal Cancer in African Americans
Authors: Kumar Krishan , Brim Hassan , Giardiello Francis , Smoot Duane T. , Nouraie Mehdi , Lee Edward L. , Ashktorab Hassan 
Published: February 2009

Abstract
Purpose: Colorectal cancer develops through genetic, epigenetic, and environmental events that result in uncontrolled cell proliferation. Colorectal cancer incidence and mortality is higher in African Americans (AA) than in the general population. Here, we carried out a molecular analysis of sporadic colorectal cancer tumors from AAs to investigate possible explanations for the observed disparities.
Experimental Design: A total of 222 AA colorectal cancer tumors were analyzed for microsatellite instability (MSI) for protein expression of two DNA mismatch repair genes, MLH1 and MSH2, by immunohistochemistry; for the methylation silencing of MLH1, p16, APC, and APC2 promoters by methylation-specific PCR; and for point mutations in two oncogenes, KRAS and BRAF, by sequencing.
Results: In our sample, 19.8% of the AAs colorectal cancer tumors were MSI high (MSI-H) and did not associate with any of the clinicopathologic features, except tumor differentiation. Higher levels of inactive DNA mismatch repair proteins MLH1 (41%) and MSH2 (33%) were found by immunohistochemistry. Methylation-specific PCR analysis revealed a high level of methylation for MLH1 (66%), APC (53%), and APC2 (90%), but not for p16 (26%). BRAF mutations were only within the MSI-H tumors, whereas most (64%) of KRAS mutations were found within the non–MSI-H group.
Conclusions:MLH1, MSH2, and BRAF alterations are significantly associated with MSI-H phenotype, unlike APC, APC2 and KRAS alterations. The prominent role of DNA mismatch repair gene suppression in MSI-H and a distinctive role of BRAF and KRAS mutations with respect to MSI status are supported by this study.
Establishment and Characterization of a Model of Acquired Resistance to Epidermal Growth Factor Receptor Targeting Agents in Human Cancer Cells
Authors: Benavente Sergio , Huang Shyhmin , Armstrong Eric A. , Chi Alexander , Hsu Kun-Tai , Wheeler Deric L. , Harari Paul M. 
Published: February 2009

AbstractPurpose: The epidermal growth factor receptor (EGFR) is recognized as a key mediator of proliferation and progression in many human tumors. A series of EGFR-specific inhibitors have recently gained Food and Drug Administration approval in oncology. These strategies of EGFR inhibition have shown major tumor regressions in approximately 10% to 20% of advanced cancer patients. Many tumors, however, eventually manifest resistance to treatment. Efforts to better understand the underlying mechanisms of acquired resistance to EGFR inhibitors, and potential strategies to overcome resistance, are greatly needed.Experimental Design: To develop cell lines with acquired resistance to EGFR inhibitors we utilized the human head and neck squamous cell carcinoma tumor cell line SCC-1. Cells were treated with increasing concentrations of cetuximab, gefitinib, or erlotinib, and characterized for the molecular changes in the EGFR inhibitor–resistant lines relative to the EGFR inhibitor–sensitive lines.Results: EGFR inhibitor–resistant lines were able to maintain their resistant phenotype in both drug-free medium and in athymic nude mouse xenografts. In addition, EGFR inhibitor–resistant lines showed a markedly increased proliferation rate. EGFR inhibitor–resistant lines had elevated levels of phosphorylated EGFR, mitogen-activated protein kinase, AKT, and signal transducer and activator of transcription 3, which were associated with reduced apoptotic capacity. Subsequent in vivo experiments indicated enhanced angiogenic potential in EGFR inhibitor–resistant lines. Finally, EGFR inhibitor–resistant lines showed cross-resistance to ionizing radiation.Conclusions: We have developed EGFR inhibitor–resistant human head and neck squamous cell carcinoma cell lines. This model provides a valuable preclinical tool to investigate molecular mechanisms of acquired resistance to EGFR blockade.
The Expression of Three Genes in Primary Non–Small Cell Lung Cancer Is Associated with Metastatic Spread to the Brain
Authors: Grinberg-Rashi Helena , Ofek Efrat , Perelman Marina , Skarda Jozef , Yaron Pnina , Hajdúch Marián , Jacob-Hirsch Jasmin , Amariglio Ninette , Krupsky Meir , Simansky David A. , Ram Zvi , Pfeffer Raphael , Galernter Ilana , Steinberg David M. , Ben-Dov Issachar , Rechavi Gideon , Izraeli Shai 
Published: February 2009

AbstractPurpose: Brain metastases affect 25% of patients with non–small cell lung cancer (NSCLC). We hypothesized that the expression of genes in primary NSCLC tumors could predict brain metastasis and be used for identification of high-risk patients, who may benefit from prophylactic therapy.Experimental Design: The expression of 12 genes was measured by real-time quantitative reverse transcriptase PCR in 142 frozen NSCLC tissue samples. Univariate and multivariate Cox regression analysis was used to analyze the correlation between gene expression and the occurrence of brain metastasis. Immunohistochemistry on independent samples was used to verify the findings.Results: A score based on the expression levels of three genes, CDH2 (N-cadherin), KIFC1, and FALZ, was highly predictive of brain metastasis in early and advanced lung cancer. The probability of remaining brain metastasis–free at 2 years after diagnosis was 90.0 ± 9.5% for patients with stage I/stage II tumors and low score compared with 62.7 ± 12% for patients with high score (P &lt; 0.01). In patients with more advanced lung cancer, the brain metastasis–free survival at 24 months was 89% for patients with low score compared with only 37% in patients with high score (P &lt; 0.02). These results were confirmed by immunohistochemical detection of N-cadherin in independent cohort of primary NSCLC.Conclusions: The expression levels of three genes in primary NSCLC tumors may be used to identify patients at high risk for brain metastasis who may benefit from prophylactic therapy to the central nervous system.
The Effect of Speaking Rate onConsonant Vowel Coarticulation
Authors: Agwuele Augustine , Sussman Harvey M. , Lindblom Björn 
Published: February 2009

Abstract
In 2007 Lindblom et al. introduced a methodological tool to disentangle consonant-vowel (CV) coarticulation attributable to emphatic stress apart from the vowel expansion effects known to accompany the prosodic overlay. After empirically accounting for the altered vowel positions, they reported small but consistent increases in F2 transition onsets in emphatically produced CVs that could not be attributed to vowel context influences, and that differed across stop place. At issue is whether the findings of these authors can be replicated, but in the opposite direction, for CVs produced at fast speaking rates. A modified locus equation regression metric was similarly used to account for rate-induced vowel reduction effects in predicting frequencies of F2 transition onsets in rapid speech. Six American-English speakers produced [V1.CV2] sequences embedded in a carrier sentence, at three speaking tempos: normal, fast, and fastest. Significant differences were found between ‘predicted’ and ‘observed’ F2 onsets across stops, with alveolars and velars showing greater decreases in F2 onsets during more rapid speech than labials. The complementary findings are discussed relative to a unified view of anticipatory coarticulation in CV production across a continuum of hyperarticulated spectral expansion to hypoarticulated spectral reduction.
Tonal Contrasts and Initial Consonants: A Case Study of Tamang, a ‘Missing Link’ in Tonogenesis
Authors: Mazaudon Martine , Michaud Alexis 
Published: February 2009

Abstract
Tamang (Bodic division of Tibeto-Burman) is spoken at the edge of the East Asian ‘tone-prone’ zone, next to the almost tone-free Indian linguistic area, and is, chronologically, at the late end of the tone multiplication wave which has swept through East Asia in the course of the last two millennia. It can be regarded as a ‘missing link’ in tonogenesis: following the loss of voicing contrasts on syllable-initial consonants, Tamang has four tonal categories instead of its earlier two-tone system; the present state of the prosodic system is typologically transitional, in that these four tonal categories are realised by several cues which include fundamental frequency (F0), phonation type, and allophonic variation in the realisation of consonants. Acoustic and electroglottographic recordings of 131 words in two carrier sentences by 5 speakers were conducted (total number of target syllables analysed: n = 1,651). They allow for a description in terms of F0, glottal open quotient, duration, and realisation of consonants. The results confirm the diversity of cues to the four tonal categories, and show evidence of laxness on tones 3 and 4, i.e. on the two tones which originate diachronically in voiced initials. The discussion hinges on the phonological definition of tone.
Modeling of Subgrid-Scale Mixing in Large-Eddy Simulation of Shallow Convection
Authors: Jarecka Dorota , Grabowski Wojciech W. , Pawlowska Hanna 
Published: February 2009

Abstract
This paper discusses an extension of the approach proposed previously to represent the delay of cloud water evaporation and buoyancy reversal due to the cloud–environment mixing in bulk microphysics large-eddy simulation of clouds. In the original approach, an additional equation for the mean spatial scale of cloudy filaments was introduced to represent the progress toward microscale homogenization of a volume undergoing turbulent cloud–environment mixing, with the evaporation of cloud water allowed only when the filament scale approached the Kolmogorov microscale. Here, it is shown through a posteriori analysis of model simulations that one should also predict the volume fraction of the cloudy air that was diagnosed in the original approach. The resulting model of turbulent mixing and homogenization, referred to as the λ–β model, is applied in a series of shallow convection simulations using various spatial resolutions and compared to the traditional bulk model. This work represents an intermediate step in the development of a modeling framework to simulate characteristics of microphysical transformations during entrainment and subgrid-scale turbulent mixing.
Loss of pleckstrin defines a novel pathway for PKC-mediated exocytosis
Authors: Lian Lurong , Wang Yanfeng , Flick Matthew , Choi John , Scott Edward W. , Degen Jay , Lemmon Mark A. , Abrams Charles S. 
Published: February 2009

AbstractPleckstrin, the platelet and leukocyte C kinase substrate, is a prominent substrate of PKC in platelets, monocytes, macrophages, lymphocytes, and granulocytes. Pleckstrin accounts for 1% of the total protein in these cells, but it is best known for containing the 2 prototypic Pleckstrin homology, or PH, domains. Overexpressed pleckstrin can affect polyphosphoinositide second messenger–based signaling events; however, its true in vivo role has been unknown. Here, we describe mice containing a null mutation within the pleckstrin gene. Platelets lacking pleckstrin exhibit a marked defect in exocytosis of δ and α granules, αIIbβ3 activation, actin assembly, and aggregation after exposure to the PKC stimulant, PMA. Pleckstrin-null platelets aggregate normally in response to thrombin, but they fail to aggregate in response to thrombin in the presence of PI3K inhibitors, suggesting that a PI3K-dependent signaling pathway compensates for the loss of pleckstrin. Although pleckstrin-null platelets merged their granules in response to stimulation of PKC, they failed to empty their contents into the open canalicular system. This might be attributable to impaired actin assembly present in cells lacking pleckstrin. These data show that pleckstrin regulates the fusion of granules to the cell membrane and is an essential component of PKC-mediated exocytosis.