bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Khanka Block, NE China, and its significance for the evolution of the Central Asian Orogenic Belt and continental accretion
Authors: Wilde Simon A. , Wu Fu-Yuan , Zhao Guochun 
Published: September 2010

Abstract

Sensitive high-resolution ion microprobe and inductively coupled plasma mass spectrometry U–Pb dating of zircons from granitoids and paragneiss in the Chinese segment of the Khanka Block reveals that granite magmatism occurred at 518±7 Ma and was followed shortly after by high-grade metamorphism at
c
. 500 Ma (timing ranging from 491±4 Ma in medium-grained granitoid, through 499±10 Ma in porphyritic granite, to 501±8 Ma in paragneiss). Such a scenario has previously been established on similar lithologies in the Jiamusi Block to the west, with identical ages. This suggests that the Khanka and Jiamusi blocks form part of a single terrane and that the Dunhua–Mishan Fault, which was previously considered to separate two unique terranes, cannot be a terrane boundary fault. Previous suggestions of a link between the Khanka Block and the Hida Block in Japan are not supported following a comparison of the new zircon data with published ages for the Japanese terranes. A granitoid with an age of 112±1 Ma in the Khanka Block probably records the effect of Pacific plate subduction, as such ages are common further south in the extreme eastern part of the North China Craton, where they have been related to post-collisional extension and lithospheric thinning in the Jiaodong Peninsula. The presence of such young granitoids, and the previous dating of blueschist-facies metamorphism as late Early Jurassic in the Heilongjiang Complex of the Jiamusi Block, supports the view that the current location of the Jiamusi–Khanka terrane is a product of circum-Pacific accretion rather than it being a microcontinental block that was trapped by the northward collision of the North China Craton with Siberia as part of the assembly of the main Central Asian Orogenic Belt.
Unified Tables for Exponential and Logarithm Families
Authors: Anand Christopher Kumar , Sharma Anuroop 
Published: September 2010

Accurate table methods allow for very accurate and efficient evaluation of elementary functions. We present new single-table approaches to logarithm and exponential evaluation, by which we mean that a single table of values works for both log(
x
) and log(1 +
x
), and a single table for
e
x
and
e
x
− 1. This approach eliminates special cases normally required to evaluate log(1 +
x
) and
e
x
− 1 accurately near zero, which will significantly improve performance on architectures which use SIMD parallelism, or on which data-dependent branching is expensive.

We have implemented it on the Cell/B.E. SPU (SIMD compute engine) and found the resulting functions to be up to twice as fast as the conventional implementations distributed in the IBM Mathematical Acceleration Subsystem (MASS). We include the literate code used to generate all the variants of exponential and log functions in the article, and discuss relevant language and hardware features.
Runtime Reconfiguration of Multiprocessors Based on Compile-Time Analysis
Authors: Purnaprajna Madhura , Porrmann Mario , Rueckert Ulrich , Hussmann Michael , Thies Michael , Kastens Uwe 
Published: September 2010

In multiprocessors, performance improvement is typically achieved by exploring parallelism with fixed granularities, such as instruction-level, task-level, or data-level parallelism. We introduce a new reconfiguration mechanism that facilitates variations in these granularities in order to optimize resource utilization in addition to performance improvements. Our reconfigurable multiprocessor QuadroCore combines the advantages of reconfigurability and parallel processing. In this article, a unified hardware-software approach for the design of our QuadroCore is presented. This design flow is enabled via compiler-driven reconfiguration which matches application-specific characteristics to a fixed set of architectural variations. A special reconfiguration mechanism has been developed that alters the architecture within a single clock cycle.
The QuadroCore has been implemented on Xilinx XC2V6000 for functional validation and on UMC’s 90nm standard cell technology for performance estimation. A diverse set of applications have been mapped onto the reconfigurable multiprocessor to meet orthogonal performance characteristics in terms of time and power. Speedup measurements show a 2--11 times performance increase in comparison to a single processor. Additionally, the reconfiguration scheme has been applied to save power in data-parallel applications. Gate-level simulations have been performed to measure the power-performance trade-offs for two computationally complex applications. The power reports confirm that introducing this scheme of reconfiguration results in power savings in the range of 15--24%.
What is majority/minority network synthesis?
Authors: Jha Niraj K. 
Published: September 2010

Majority (minority) network synthesis uses majority (minority) gates as logic elements. A majority (minority) gate has three inputs and one output and produces an output value 1 when a majority (minority) of input values are 1. Thus, the majority function, M, corresponding to a majority gate is given by
M(x1,x2,x3) = x1x2 + x2x3 + x1x3
The minority function, m, is simply given by M' (the complement of M).
Silencing of Thrombospondin-1 Is Critical for Myc-Induced Metastatic Phenotypes in Medulloblastoma
Authors: Zhou Limei , Picard Daniel , Ra Young-Shin , Li Meihua , Northcott Paul A. , Hu Yaqi , Stearns Duncan , Hawkins Cynthia , Taylor Michael D. , Rutka James , Der Sandy D. , Huang Annie 
Published: September 2010

Abstract
Mechanisms by which c-Myc (Myc) amplification confers aggressive medulloblastoma phenotypes are poorly defined. Here, we show using orthotopic models that high Myc expression promotes cell migration/invasion and induces metastatic tumors, which recapitulate aggressive histologic features of Myc-amplified primary human medulloblastoma. Using ChIP-chip analysis, we identified cell migration and adhesion genes, including Tsp-1/THBS1, ING4, PVRL3, and PPAP2B, as Myc-bound loci in medulloblastoma cells. Expression of Tsp-1 was most consistently and robustly diminished in medulloblastoma cell lines and primary human tumors with high Myc expression (n = 101, P = 0.032). Strikingly, stable Tsp-1 expression significantly attenuated in vitro transformation and invasive/migratory properties of high Myc-expressing medulloblastoma cells without altering cell proliferation, whereas RNA interference–mediated Myc knockdown was consistently accompanied by increased Tsp-1 levels and reduced cell migration and invasion in medulloblastoma cells. Chromatin immunoprecipitation (ChIP) assays revealed colocalization of Myc and obligate partner Max and correlated diminished RNA polymerase II occupancy (∼3-fold decrease, P &lt; 0.01) with increased Myc binding at a core Tsp-1 promoter. Reporter gene and/or gel shift assays confirmed direct repression of Tsp-1 transcription by Myc and also identified JPO2, a Myc interactor associated with metastatic medulloblastoma, as a cofactor in Myc-mediated Tsp-1 repression. These findings indicate the Myc-regulatory network targets Tsp-1 via multiple mechanisms in medulloblastoma transformation, and highlight a novel critical role for Tsp-1 in Myc-mediated aggressive medulloblastoma phenotypes. Cancer Res; 70(20); 8199–210. ©2010 AACR.
Apatinib (YN968D1) Reverses Multidrug Resistance by Inhibiting the Efflux Function of Multiple ATP-Binding Cassette Transporters
Authors: Mi Yan-jun , Liang Yong-ju , Huang Hong-bing , Zhao Hong-yun , Wu Chung-Pu , Wang Fang , Tao Li-yang , Zhang Chuan-zhao , Dai Chun-Ling , Tiwari Amit K. , Ma Xiao-xu , To Kenneth Kin Wah , Ambudkar Suresh V. , Chen Zhe-Sheng , Fu Li-wu 
Published: September 2010

Abstract
Apatinib, a small-molecule multitargeted tyrosine kinase inhibitor, is in phase III clinical trial for the treatment of patients with non–small-cell lung cancer and gastric cancer in China. In this study, we determined the effect of apatinib on the interaction of specific antineoplastic compounds with P-glycoprotein (ABCB1), multidrug resistance protein 1 (MRP1, ABCC1), and breast cancer resistance protein (BCRP, ABCG2). Our results showed that apatinib significantly enhanced the cytotoxicity of ABCB1 or ABCG2 substrate drugs in KBv200, MCF-7/adr, and HEK293/ABCB1 cells overexpressing ABCB1 and in S1-M1-80, MCF-7/FLV1000, and HEK293/ABCG2-R2 cells overexpressing ABCG2 (wild-type). In contrast, apatinib did not alter the cytotoxicity of specific substrates in the parental cells and cells overexpressing ABCC1. Apatinib significantly increased the intracellular accumulation of rhodamine 123 and doxorubicin in the multidrug resistance (MDR) cells. Furthermore, apatinib significantly inhibited the photoaffinity labeling of both ABCB1 and ABCG2 with [125I]iodoarylazidoprazosin in a concentration-dependent manner. The ATPase activity of both ABCB1 and ABCG2 was significantly increased by apatinib. However, apatinib, at a concentration that produced a reversal of MDR, did not significantly alter the ABCB1 or ABCG2 protein or mRNA expression levels or the phosphorylation of AKT and extracellular signal–regulated kinase 1/2 (ERK1/2). Importantly, apatinib significantly enhanced the effect of paclitaxel against the ABCB1-resistant KBv200 cancer cell xenografts in nude mice. In conclusion, apatinib reverses ABCB1- and ABCG2-mediated MDR by inhibiting their transport function, but not by blocking the AKT or ERK1/2 pathway or downregulating ABCB1 or ABCG2 expression. Apatinib may be useful in circumventing MDR to other conventional antineoplastic drugs. Cancer Res; 70(20); 7981–91. ©2010 AACR.
Hepatocyte Nuclear Factor 4α Suppresses the Development of Hepatocellular Carcinoma
Authors: Ning Bei-Fang , Ding Jin , Yin Chuan , Zhong Wei , Wu Kun , Zeng Xin , Yang Wen , Chen Yue-Xiang , Zhang Jun-Ping , Zhang Xin , Wang Hong-Yang , Xie Wei-Fen 
Published: September 2010

Abstract
Hepatocyte nuclear factor 4α (HNF4α) is a transcription factor that plays a key role in hepatocyte differentiation and the maintenance of hepatic function, but its role in hepatocarcinogenesis has yet to be examined. Here, we report evidence of a suppressor role for HNF4α in liver cancer. HNF4α expression was progressively decreased in the diethylinitrosamine-induced rat model of liver carcinogenesis. In human liver tissues, HNF4α expression was decreased in cirrhotic tissue and further decreased in hepatocarcinoma relative to healthy tissue. Notably, an inverse correlation existed with epithelial-mesenchymal transition (EMT). Enforced expression of HNF4α attenuated hepatocyte EMT during hepatocarcinogenesis, alleviated hepatic fibrosis, and blocked hepatocellular carcinoma (HCC) occurrence. In parallel, stem cell marker gene expression was inhibited along with cancer stem/progenitor cell generation. Further, enforced expression of HNF4α inhibited activation of β-catenin, which is closely associated with EMT and hepatocarcinogenesis. Taken together, our results suggest that the inhibitory effect of HNF4α on HCC development might be attributed to suppression of hepatocyte EMT and cancer stem cell generation through an inhibition of β-catenin signaling pathways. More generally, our findings broaden knowledge on the biological significance of HNF4α in HCC development, and they imply novel strategies for HCC prevention through the manipulation of differentiation-determining transcription factors in various types of carcinomas. Cancer Res; 70(19); 7640–51. ©2010 AACR.
Keratinocyte-Specific Stat3 Heterozygosity Impairs Development of Skin Tumors in Human Papillomavirus 8 Transgenic Mice
Authors: De Andrea Marco , Rittà Massimo , Landini Manuela M. , Borgogna Cinzia , Mondini Michele , Kern Florian , Ehrenreiter Karin , Baccarini Manuela , Marcuzzi Gian Paolo , Smola Sigrun , Pfister Herbert , Landolfo Santo , Gariglio Marisa 
Published: September 2010

Abstract
Human papillomaviruses (HPV) of the genus β are thought to play a role in human skin cancers, but this has been difficult to establish using epidemiologic approaches. To gain insight into the transforming activities of β-HPV, transgenic mouse models have been generated that develop skin tumors. Recent evidence suggests a central role of signal transducer and activator of transcription 3 (Stat3) as a transcriptional node for cancer cell–autonomous initiation of a tumor-promoting gene signature associated with cell proliferation, cell survival, and angiogenesis. Moreover, high levels of phospho-Stat3 have been detected in tumors arising in HPV8-CER transgenic mice. In this study, we investigate the in vivo role of Stat3 in HPV8-induced skin carcinogenesis by combining our established experimental model of HPV8-induced skin cancer with epidermis-restricted Stat3 ablation. Stat3 heterozygous epidermis was less prone to tumorigenesis than wild-type epidermis. Three of the 23 (13%) Stat3+/−:HPV8 animals developed tumors within 12 weeks of life, whereas 54.3% of Stat3+/+:HPV8 mice already exhibited tumors in the same observation period (median age for tumor appearance, 10 weeks). The few tumors that arose in the Stat3+/−:HPV8 mice were benign and never progressed to a more malignant phenotype. Collectively, these results offer direct evidence of a critical role for Stat3 in HPV8-driven epithelial carcinogenesis. Our findings imply that targeting Stat3 activity in keratinocytes may be a viable strategy to prevent and treat HPV-induced skin cancer. Cancer Res; 70(20); 7938–48. ©2010 AACR.
A Bispecific Antibody-IFNα2b Immunocytokine Targeting CD20 and HLA-DR Is Highly Toxic to Human Lymphoma and Multiple Myeloma Cells
Authors: Rossi Edmund A. , Rossi Diane L. , Stein Rhona , Goldenberg David M. , Chang Chien-Hsing 
Published: September 2010

Abstract
The short circulating half-life and side effects of IFNα affect its dosing schedule and efficacy. Fusion of IFNα to a tumor-targeting monoclonal antibody (MAb-IFNα) can enhance potency due to increased tumor localization and improved pharmacokinetics. We report the generation and characterization of the first bispecific MAb-IFNα, designated 20-C2-2b, which comprises two copies of IFNα2b and a stabilized F(ab)2 of hL243 (humanized anti–HLA-DR; IMMU-114) site-specifically linked to veltuzumab (humanized anti-CD20). In vitro, 20-C2-2b inhibited each of four lymphoma and eight myeloma cell lines, and was more effective than monospecific CD20-targeted MAb-IFNα or a mixture comprising the parental antibodies and IFNα in all but one (HLA-DR−/CD20−) myeloma line, suggesting that 20-C2-2b should be useful in the treatment of various hematopoietic malignancies. 20-C2-2b displayed greater cytotoxicity against KMS12-BM (CD20+/HLA-DR+ myeloma) compared with monospecific MAb-IFNα, which targets only HLA-DR or CD20, indicating that all three components in 20-C2-2b could contribute to toxicity. Our findings indicate that a given cell's responsiveness to MAb-IFNα depends on its sensitivity to IFNα and the specific antibodies, as well as the expression and density of the targeted antigens. Cancer Res; 70(19); 7600–9. ©2010 AACR.
Key Role of Phosphoinositide 3-Kinase Class IB in Pancreatic Cancer
Authors: Edling Charlotte E. , Selvaggi Federico , Buus Richard , Maffucci Tania , Di Sebastiano Pierluigi , Friess Helmut , Innocenti Paolo , Kocher Hemant M. , Falasca Marco 
Published: September 2010

Abstract
Purpose: Phosphoinositide 3-kinase (PI3K) signaling is well established as important in cancer. To date most studies have been focused on the PI3K/p110α isoform, which has been found to be mutated in several different cancers. The aim of our study was to determine which specific PI3K isoforms are involved in pancreatic ductal adenocarcinoma (PDAC) and investigate the effects of these isoforms on proliferation, survival, and induction of Akt activation in pancreatic cancer cells.
Experimental Design: The expression of all PI3K isoforms and downstream targets was analyzed by immunohistochemistry in human pancreatic cancer tissue and normal counterparts. Isoform selective inhibitors and short interfering RNA (siRNA) were employed to investigate the effects of the different PI3Ks on proliferation, survival, and intracellular signaling in PDAC cell lines.
Results: Immunohistochemical screening revealed high specific expression of the PI3K/p110γ isoform. Scoring indicated that 72% of the PDAC tissue stained positive for PI3K/p110γ, whereas no stain was detected in normal pancreatic ducts. Proliferation analyses after selective inhibition and siRNA downregulation of PI3K/p110γ showed that PI3K/p110γ, but not other PI3K isoforms, was required for cell proliferation. Overexpression of PI3K/p110γ indeed increased cell numbers and mediated activation of Akt in PDAC cell lines. Moreover, PI3K/p110γ was required for Akt activation via lysophosphatidic acid receptors.
Conclusions: These data represent the first identification of a tumor-specific accumulation of the PI3K isoform p110γ in human cancer. Further, our results signify a critical role for PI3K/p110γ in pancreatic cancer, and we hypothesize that PI3K/p110γ overexpression is a key event in the disease progression. Clin Cancer Res; 16(20); 4928–37. ©2010 AACR.
Preclinical Characterization of Mitochondria-Targeted Small Molecule Hsp90 Inhibitors, Gamitrinibs, in Advanced Prostate Cancer
Authors: Kang Byoung Heon , Siegelin Markus D. , Plescia Janet , Raskett Christopher M. , Garlick David S. , Dohi Takehiko , Lian Jane B. , Stein Gary S. , Languino Lucia R. , Altieri Dario C. 
Published: September 2010

Abstract
Purpose: This study aimed to characterize the preclinical activity of the first class of combinatorial, mitochondria-targeted, small molecule heat shock protein-90 (Hsp90) inhibitors, gamitrinibs, in models of hormone-refractory, drug-resistant, localized, and bone metastatic prostate cancer in vivo.
Experimental Design: Mitochondrial permeability transition, apoptosis, and changes in metabolic activity were examined by time-lapse videomicroscopy, multiparametric flow cytometry, MTT, and analysis of isolated mitochondria. Drug-resistant prostate cancer cells were generated by chronic exposure of hormone-refractory PC3 cells to the Hsp90 inhibitor 17-allylaminogeldanamycin (17-AAG). The effect of gamitrinibs on s.c. or intratibial prostate cancer growth was studied in xenograft models. Bone metastatic tumor growth and bone parameters were quantified by micro–computed tomography imaging.
Results: In the NCI 60-cell line screening, gamitrinibs were active against all tumor cell types tested, and efficiently killed metastatic, hormone-refractory, and multidrug-resistant prostate cancer cells characterized by overexpression of the ATP binding cassette transporter P-glycoprotein. Mechanistically, gamitrinibs, but not 17-AAG, induced acute mitochondrial dysfunction in prostate cancer cells with loss of organelle membrane potential, release of cytochrome c, and caspase activity, independently of proapoptotic Bcl-2 proteins Bax and Bak. Systemic administration of gamitrinibs to mice was well tolerated, and inhibited s.c. or bone metastatic prostate cancer growth in vivo.
Conclusions: Gamitrinibs have preclinical activity and favorable safety in models of drug-resistant and bone metastatic prostate cancer in vivo. Clin Cancer Res; 16(19); 4779–88. ©2010 AACR.
Wheel Running–Induced Changes in Plasma Biomarkers and Carcinogenic Response in the 1-Methyl-1-Nitrosourea–Induced Rat Model for Breast Cancer
Authors: Thompson Henry J. , Wolfe Pamela , McTiernan Anne , Jiang Weiqin , Zhu Zongjian 
Published: September 2010

AbstractThe purpose of this investigation was to identify pathways by which physical activity, implemented as running in an activity wheel, inhibits carcinogenesis. The focus of this analysis was on 20 plasma biomarkers for glucose homeostasis, inflammation, cytokine function, and endocrine activity, known to be affected by a physically active lifestyle. Plasma for analysis was obtained from previously reported carcinogenesis experiments in which the effects on mammary carcinogenesis, induced by i.p. injection of 1-methyl-1-nitrosurea, of running on a motorized activity wheel or a nonmotorized free wheel were compared with sedentary controls. Wheel running reduced cancer incidence (P = 0.0004) and the number of cancers per animal (P = 0.005). Principal components analysis was used to reduce the 20 plasma biomarkers to a concise index that was significantly different by treatment group assignment (P &lt; 0.0001). Statistical analyses provided evidence that supported the hypothesis of a mediational role of these molecules in accounting for the protective effect of wheel running on the carcinogenic process. In addition, the plasma biomarker index derived from principal components analysis was a good discriminator of treatment group assignment (only 4.5% of animals were misclassified). These findings suggest that the plasma biomarkers evaluated have utility in assessing the breast cancer response to a physical activity intervention. Identification of such biomarkers is critical in clinical studies for which evaluating the effects of physical activity on cancer outcomes (diagnosis, recurrence, or mortality) is not possible. Cancer Prev Res; 3(11); 1484–92. ©2010 AACR.
Pathophysiology of Tricuspid Regurgitation
Authors: Topilsky Yan , Tribouilloy Christophe , Michelena Hector I. , Pislaru Sorin , Mahoney Douglas W. , Enriquez-Sarano Maurice 
Published: September 2010

Background—
Respiratory dependence of tricuspid regurgitation (TR), a long-held concept suggested by murmur variation, remains unproven and of unclear mechanisms.

Methods and Results—

In 41 patients with mild or greater TR (median age, 67 years), we performed triple Doppler echocardiographic quantification (TR severity, right ventricular, and right atrial quantification) with simultaneous respirometer recording of respiratory phases. Expiration to inspiration changes (median) affected TR peak velocity (−40 cm/s; 25th to 75th percentile, −60 to −30 cm/s), duration (−12 milliseconds; 25th to 75th percentile, −45 to 2 milliseconds), and time-velocity integral (−17 cm; 25th to 75th percentile, −23.4 to −10 cm; all
P
<0.001), consistent with decreased TR driving force. Nevertheless, inspiratory TR augmentation was demonstrated by increased effective regurgitant orifice (0.21 cm
2
; 25th to 75th percentile, 0.09 to 0.34 cm
2
) and volume (18 mL per beat; 25th to 75th percentile, 10 to 25 mL per beat; all
P
<0.001) infrequently detected clinically (2 of 41, 5). As a result of reduced TR driving force, regurgitant volume increased less than effective regurgitant orifice (120 [25th to 75th percentile, 78.6 to 169] versus 169 [ 25th to 75th percentile, 12.9 to 226.1];
P
<0.001). During inspiration, right ventricular area increased (diastolic, 27.8 [25th to 75th percentile, 22.6 to 36.3] versus 26.5 [21.1 to 31.9];
P
<0.0001) with widening of right ventricular shape (length-to-width ratio, 1.6 [ 25th to 75th percentile, 1.37 to 1.95] versus 1.7 [1.46 to 2.1];
P
<0.0001), increased systolic annular diameter (
P
=0.003), valve tenting height (
P
<0.0001) and area (
P
<0.0001), and reduced valvular-to-annular ratio (
P
=0.006). Effective regurgitant orifice during inspiration was independently determined by inspiratory valvular-to-annular ratio (
P
=0.026) and inspiratory change in right ventricular length-to-width ratio (
P
=0.008) and valve tenting area (
P
=0.015).

Conclusions—
TR is dynamic with almost universal respiratory changes of large magnitude and complex pathophysiology. During inspiration, a large increase in effective regurgitant orifice causes, despite a decline in regurgitant gradient, a notable increase in regurgitant volume. Effective regurgitant orifice changes are independently linked to inspiratory annular enlargement (decreased valvular coverage) and to inspiratory right ventricular shape widening with increased valvular tenting. These novel physiological insights into TR respiratory dependence underscore right-side heart plasticity and are important for clinical TR severity evaluation.