bluuebunny/crossref_metadata_2025_split huggingface dataset:
Landslides in coastal areas of Italy
Authors: Iadanza C. , Trigila A. , Vittori E. , Serva L. 
Published: August 2009

Abstract
Of the more than 8000 km of coasts in Italy, about 35% consist of cliffs and rocky shores. On them many villages are located, some of them dating back to Roman or Greek times. Typical natural hazards along these coastal areas are rock falls, slides and debris flows. They induce locally extremely high levels of risk, as shown by the many disasters that have occurred in recent time. This paper provides a first portrait over the whole of Italy of (1) the number and distribution of coastal landslides; (2) their typologies; (3) their state of activity; (4) the most common damage and exposed elements; and (5) the most typical mitigation measures. This information has been largely derived from the IFFI archive (Italian Landslides Inventory). Geographic information system processing has allowed us to identify 4135 landslides affecting a large portion of the Italian cliffed coasts. The damage evaluation, based on the AVI archive (inventory of information on sites historically affected by landslides and floods in Italy for the period 1918–2000), has shown the extent of the problem: there have been 408 casualties in the 20th century and 713 significant disruptions of the rail and road networks. A more detailed analysis has been carried out in three sample areas to illustrate the basic factors controlling the genesis and evolution of slope instabilities in the various coastal settings.
Slope instability on rocky coast: a case study of Le Grazie landslides (eastern Liguria, northern Italy)
Authors: Brandolini P. , Faccini F. , Robbiano A. , Terranova R. 
Published: August 2009

Abstract
The stretch of rocky coast between Rapallo and Chiavari (Tigullio Gulf) is characterized by significant geomorphological instability phenomena, mainly contained between the shoreline and the Via Aurelia. Research was focused particularly on the geomorphological features and the states of activity of the landslides that are situated below the Santuario di N. S. delle Grazie. The dynamics can be partially attributed to natural causes, including the geological–tectonic layout, the geomechanical properties of the rock mass and wave undercutting, and partially to human activity related to the opening of limestone quarries and the construction of roadway, railway and communications networks. The recent evolution of the landslides, involving buildings, structures and infrastructure, requiring a variety of consolidation measures and work, has been observed. The latter were implemented following in-depth analysis of the subsoil geology and monitoring activity.
The use of documentary sources for reconstructing flood chronologies on the Amalfi rocky coast (southern Italy)
Authors: Porfido S. , Esposito E. , Alaia F. , Molisso F. , Sacchi M. 
Published: August 2009

Abstract
Documentary source materials are essential for retrospective reconstruction of flood events occurring in past centuries. This paper presents methods of research and archiving of historical data from the 16th century to the present. The quality and completeness of the various original sources were evaluated and carefully analysed in their historical context, to avoid serious mistakes. Systematic investigation of about 3000 documents, mainly found in national State Archives and libraries, allows us to identify and localize at least 106 flood events occurring along the Amalfi coast (southern Italy) for five centuries between the years 1500 and 2000. The collected data provide useful details on flood dynamics, size of flooded areas, flood duration, damage level, number of victims and induced geological effects. When available in sufficient quantity, the flood data allow determination of very useful parameters such as the severity class, to identify large floods and their recurrence interval.
Program locality analysis using reuse distance
Authors: Zhong Yutao , Shen Xipeng , Ding Chen 
Published: August 2009

On modern computer systems, the memory performance of an application depends on its locality. For a single execution, locality-correlated measures like average miss rate or working-set size have long been analyzed using
reuse distance
—the number of distinct locations accessed between consecutive accesses to a given location. This article addresses the analysis problem at the program level, where the size of data and the locality of execution may change significantly depending on the input.

The article presents two techniques that predict how the locality of a program changes with its input. The first is approximate reuse-distance measurement, which is asymptotically faster than exact methods while providing a guaranteed precision. The second is statistical prediction of locality in all executions of a program based on the analysis of a few executions. The prediction process has three steps: dividing data accesses into groups, finding the access patterns in each group, and building parameterized models. The resulting prediction may be used on-line with the help of distance-based sampling. When evaluated on fifteen benchmark applications, the new techniques predicted program locality with good accuracy, even for test executions that are orders of magnitude larger than the training executions.
The two techniques are among the first to enable quantitative analysis of whole-program locality in general sequential code. These findings form the basis for a unified understanding of program locality and its many facets. Concluding sections of the article present a taxonomy of related literature along five dimensions of locality and discuss the role of reuse distance in performance modeling, program optimization, cache and virtual memory management, and network traffic analysis.
On Uniqueness of Conjugacy of Continuous and Piecewise Monotone Functions
Authors: Ciepliński Krzysztof , Zdun Marek Cezary 
Published: August 2009

AbstractWe investigate the existence and uniqueness of solutions "Equation missing" of the functional equation "Equation missing", "Equation missing", where "Equation missing" are closed intervals, and "Equation missing", "Equation missing" are some continuous piecewise monotone functions. A fixed point principle plays a crucial role in the proof of our main result.
Chemopreventive Effects of Gefitinib on Nonsmoking-Related Lung Tumorigenesis in Activating Epidermal Growth Factor Receptor Transgenic Mice
Authors: Ohashi Kadoaki , Takigawa Nagio , Osawa Masahiro , Ichihara Eiki , Takeda Hiromasa , Kubo Toshio , Hirano Seiki , Yoshino Tadashi , Takata Minoru , Tanimoto Mitsune , Kiura Katsuyuki 
Published: August 2009

AbstractTwenty-five percent of all lung cancer cases are not attributable to smoking. Epidermal growth factor receptor (EGFR) mutations, which are involved in ∼50% of nonsmoker lung cancer, are positively correlated with responsiveness to gefitinib, and inversely correlated with smoking history. Activating EGFR mutations play a critical role in the carcinogenesis of nonsmoking-related lung cancer. To investigate the chemopreventive effects of gefitinib on nonsmoking-related lung cancer, we generated transgenic mice expressing EGFR L858R in type II pneumocytes constitutively using the surfactant protein-C promoter. The transgenic mice invariably developed atypical adenomatous hyperplasia at age 4 weeks and multifocal adenocarcinoma of varying sizes at age 7 weeks. Notably, the expression levels of phosphorylated and total ErbB2, ErbB3, and thyroid transcription factor-1 were elevated in the transgenic mice compared with wild-type controls at age 3 weeks. Administration of gefitinib to 3-week-old transgenic mice for 1 week before carcinogenesis reduced the amount of phosphorylated EGFR in the lungs of the mice to the baseline level. Gefitinib (5 mg/kg/d; n = 5, 5, and 15) or vehicle (n = 5, 5, and 15) was administered to transgenic mice from age 3 to 8, 13, and 18 weeks, respectively. The numbers of lung tumors in the control and gefitinib-treated groups were 1.75, 5.8, 10.2, and 0 (P &lt; 0.05), respectively. No fatal toxic events occurred in either group, and gefitinib inhibited tumorigenesis completely in this mouse model. These results suggest the utility of molecular targeted chemoprevention against nonsmoking-related lung cancer. [Cancer Res 2009;69(17):7088–95]
TGFBR1 Haplotypes and Risk of Non–Small-Cell Lung Cancer
Authors: Lei Zhe , Liu Reng-Yun , Zhao Jun , Liu Zeyi , Jiang Xiefang , You Weiming , Chen Xiao-Feng , Liu Xia , Zhang Kui , Pasche Boris , Zhang Hong-Tao 
Published: August 2009

Abstract
Transforming growth factor β (TGF-β) receptors are centrally involved in TGF-β–mediated cell growth and differentiation and are frequently inactivated in non–small-cell lung cancer (NSCLC). Constitutively decreased type I TGF-β receptor (TGFBR1) expression is emerging as a novel tumor-predisposing phenotype. The association of TGFBR1 haplotypes with risk for NSCLC has not yet been studied. We tested the hypothesis that single-nucleotide polymorphisms (SNP) and/or TGFBR1 haplotypes are associated with risk of NSCLC. We genotyped six TGFBR1 haplotype-tagging SNPs (htSNP) by PCR-RFLP assays and one htSNP by PCR-single-strand conformation polymorphism assay in two case-control studies. Case-control study 1 included 102 NSCLC patients and 104 healthy controls from Suzhou. Case-control study 2 included 131 patients with NSCLC and 133 healthy controls from Wuxi. Individuals included in both case-control studies were Han Chinese. Haplotypes were reconstructed according to the genotyping data and linkage disequilibrium status of these seven htSNPs. None of the htSNP was associated with NSCLC risk in either study. However, a four-marker CTGC haplotype was significantly more common among controls than among cases in both studies (P = 0.014 and P = 0.010, respectively), indicating that this haplotype is associated with decreased NSCLC risk {adjusted odds ratio [OR], 0.09 [95% confidence interval (95% CI), 0.01–0.61] and 0.11 [95% CI, 0.02–0.59], respectively}. Combined analysis of both studies shows a strong association of this four-marker haplotype with decreased NSCLC risk (adjusted OR, 0.11; 95% CI, 0.03–0.39). This is the first evidence of an association between a TGFBR1 haplotype and risk for NSCLC. [Cancer Res 2009;69(17):7046–52]
Intracellular β-Tubulin/Chaperonin Containing TCP1-β Complex Serves as a Novel Chemotherapeutic Target against Drug-Resistant Tumors
Authors: Lin Yuan-Feng , Tsai Wen-Ping , Liu Hon-Ge , Liang Po-Huang 
Published: August 2009

Abstract
In the present study, treatment of HEK-293 cells with the synthetic small molecule N-iodoacetyl-tryptophan (I-Trp) at submicromolar concentrations efficiently induced cell apoptosis as judged from the accumulation of sub-G0 cells and intracellular DNA fragmentation. Activation of all intracellular caspases, except caspase-1, was detected in I-Trp–treated cells. Proteomic analysis revealed that β-tubulin acted as a specific intracellular target of I-Trp. Protein fingerprinting analysis indicated that the Cys354 residue in the peptide fragment TAVCDIPPR of β-tubulin, which is located at the binding interface with chaperonin containing TCP1-β (CCT-β), was alkylated by I-Trp. Moreover, site-directed mutagenesis of Cys354 (Cys-Ala) abolished the incorporation of I-Trp into β-tubulin, suggesting Cys354 is indeed the targeting site of I-Trp. Immunoprecipitation showed that the β-tubulin/CCT-β complex was constitutively formed but disrupted after treatment with I-Trp. Overexpression of the truncated β-tubulin (T351-S364) or treatment with I-Trp or the synthetic peptide Myr-TAVCDIPPRG caused more severe cell apoptosis in multidrug-resistant MES-SA/Dx5 cancer cells due to higher levels of CCT-β relative to wild-type MES-SA cancer cells. Silencing the expression of CCT-β rendered MES-SA/Dx5 cells less sensitive to I-Trp–induced apoptotic cell death. These findings suggest that the β-tubulin/CCT-β complex may serve as an effective chemotherapeutic target for treating clinical tubulin-binding agent-resistant or CCT-β–overexpressing tumors. [Cancer Res 2009;69(17):6879–88]
Comprehensive Molecular Analysis of Mismatch Repair Gene Defects in Suspected Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) Cases
Authors: Mueller James , Gazzoli Isabella , Bandipalliam Prathap , Garber Judy E. , Syngal Sapna , Kolodner Richard D. 
Published: August 2009

Abstract
An accurate algorithm is essential for effective molecular diagnosis of hereditary colorectal cancer (CRC). Here, we have extended the analysis of 71 CRC cases suspected to be Lynch syndrome cases for MSH2, MLH1, MSH6, and PMS2 gene defects. All cases were screened for mutations in MSH2, MLH1, and MSH6, and all cases where tumors were available were screened for microsatellite instability (MSI) and expression of MSH2 and MLH1. Subsequently, mutation-negative cases were screened for MLH1 methylation and mutations in PMS2. Of the MSI-high (MSI-H) cases, 96% had a mismatch repair (MMR) gene defect, mostly involving MSH2 or MLH1; one PMS2 mutation, one MLH1 epimutation, and no MSH6 mutations were found. Four of the 28 MSI-H cases, including one Amsterdam criteria case, had biallelic tumor MLH1 methylation, indicating that sporadic cases can be admixed in with Lynch syndrome cases, even those meeting the strongest criteria for Lynch syndrome. MMR gene defects were found in similar frequency in cases where tumors were and were not available. One MLH1 and one MSH2 deletion mutation were found in MSI–stable/low cases, indicating that MSI testing can exclude cases with pathogenic mutations. Our analysis supports a diagnostic algorithm where cases are selected for analysis based on clinical criteria or prediction models; isolated sporadic young-onset cases can be prescreened by tumor testing, whereas familial cases may be directly subjected to molecular analysis for mutations in MMR genes followed by MSI, protein expression, and DNA methylation analysis to aid in the resolution of mutation-negative cases. [Cancer Res 2009;69(17):7053–61]
Human Multiple Myeloma Cells Are Sensitized to Topoisomerase II Inhibitors by CRM1 Inhibition
Authors: Turner Joel G. , Marchion Douglas C. , Dawson Jana L. , Emmons Michael F. , Hazlehurst Lori A. , Washausen Peter , Sullivan Daniel M. 
Published: August 2009

Abstract
Topoisomerase IIα (topo IIα) is exported from the nucleus of human myeloma cells by a CRM1-dependent mechanism at cellular densities similar to those found in patient bone marrow. When topo IIα is trafficked to the cytoplasm, it is not in contact with the DNA; thus, topo IIα inhibitors are unable to induce DNA-cleavable complexes and cell death. Using a CRM1 inhibitor or a CRM1-specific small interfering RNA (siRNA), we were able to block nuclear export of topo IIα as shown by immunofluorescence microscopy. Human myeloma cell lines and patient myeloma cells isolated from bone marrow were treated with a CRM1 inhibitor or CRM1-specific siRNA and exposed to doxorubicin or etoposide at high cell densities. CRM1-treated cell lines or myeloma patient cells were 4-fold more sensitive to topo II poisons as determined by an activated caspase assay. Normal cells were not significantly affected by CRM1-topo II inhibitor combination treatment. Cell death was correlated with increased DNA double-strand breaks as shown by the comet assay. Band depletion assays of CRM1 inhibitor–exposed myeloma cells showed increased topo IIα covalently bound to DNA. Topo IIα knockdown by a topo IIα–specific siRNA abrogated the CRM1-topo II therapy synergistic effect. These results suggest that blocking topo IIα nuclear export sensitizes myeloma cells to topo II inhibitors. This method of sensitizing myeloma cells suggests a new therapeutic approach to multiple myeloma. [Cancer Res 2009;69(17):6899–905]
MicroRNA Expression, Chromosomal Alterations, and Immunoglobulin Variable Heavy Chain Hypermutations in Mantle Cell Lymphomas
Authors: Navarro Alba , Beà Sílvia , Fernández Verónica , Prieto Miriam , Salaverria Itziar , Jares Pedro , Hartmann Elena , Mozos Anna , López-Guillermo Armando , Villamor Neus , Colomer Dolors , Puig Xavier , Ott German , Solé Francesc , Serrano Sergi , Rosenwald Andreas , Campo Elías , Hernández Luis 
Published: August 2009

Abstract
The contribution of microRNAs (miR) to the pathogenesis of mantle cell lymphoma (MCL) is not well known. We investigated the expression of 86 mature miRs mapped to frequently altered genomic regions in MCL in CD5+/CD5− normal B cells, reactive lymph nodes, and purified tumor cells of 17 leukemic MCL, 12 nodal MCL, and 8 MCL cell lines. Genomic alterations of the tumors were studied by single nucleotide polymorphism arrays and comparative genomic hybridization. Leukemic and nodal tumors showed a high number of differentially expressed miRs compared with purified normal B cells, but only some of them were commonly deregulated in both tumor types. An unsupervised analysis of miR expression profile in purified leukemic MCL cells revealed two clusters of tumors characterized by different mutational status of the immunoglobulin genes, proliferation signature, and number of genomic alterations. The expression of most miRs was not related to copy number changes in their respective chromosomal loci. Only the levels of miRs included in the miR-17-92 cluster were significantly related to genetic alterations at 13q31. Moreover, overexpression of miR-17-5p/miR-20a from this cluster was associated with high MYC mRNA levels in tumors with a more aggressive behavior. In conclusion, the miR expression pattern of MCL is deregulated in comparison with normal lymphoid cells and distinguishes two subgroups of tumors with different biological features. [Cancer Res 2009;69(17):7071–8]
Circulating Galectin-3 Promotes Metastasis by Modifying MUC1 Localization on Cancer Cell Surface
Authors: Zhao Qicheng , Guo Xiuli , Nash Gerard B. , Stone Philip C. , Hilkens John , Rhodes Jonathan M. , Yu Lu-Gang 
Published: August 2009

Abstract
Adhesion of circulating tumor cells to the blood vessel endothelium is a critical step in cancer metastasis. We show in this study that galectin-3, the concentration of which is greatly increased in the circulation of cancer patients, increases cancer cell adhesion to macrovascular and microvascular endothelial cells under static and flow conditions, increases transendothelial invasion, and decreases the latency of experimental metastasis in athymic mice. These effects of galectin-3 are shown to be a consequence of its interaction with cancer-associated MUC1, which breaks the “protective shield” of the cell-surface MUC1 by causing MUC1 polarization, leading to exposure of smaller cell-surface adhesion molecules/ligands including CD44 and ligand(s) for E-selectin. Thus, the interaction in the bloodstream of cancer patients between circulating galectin-3 and cancer cells expressing MUC1 bearing the galectin-3 ligand TF (Galβ1,3GalNAc-) promotes metastasis. This provides insight into the molecular regulation of metastasis and has important implications for the development of novel therapeutic strategies for prevention of metastasis. [Cancer Res 2009;69(17):6799–806]
Ectopic Runx2 Expression in Mammary Epithelial Cells Disrupts Formation of Normal Acini Structure: Implications for Breast Cancer Progression
Authors: Pratap Jitesh , Imbalzano Karen M. , Underwood Jean M. , Cohet Nathalie , Gokul Karthiga , Akech Jacqueline , van Wijnen Andre J. , Stein Janet L. , Imbalzano Anthony N. , Nickerson Jeffrey A. , Lian Jane B. , Stein Gary S. 
Published: August 2009

Abstract
The transcription factor Runx2 is highly expressed in breast cancer cells compared with mammary epithelial cells and contributes to metastasis. Here we directly show that Runx2 expression promotes a tumor cell phenotype of mammary acini in three-dimensional culture. Human mammary epithelial cells (MCF-10A) form polarized, growth-arrested, acini-like structures with glandular architecture. The ectopic expression of Runx2 disrupts acini formation, and electron microscopic ultrastructural analysis revealed the absence of lumens. Characterization of the disrupted acini structures showed increased cell proliferation (Ki-67 positive cells), decreased apoptosis (Bcl-2 induction), and loss of basement membrane formation (absence of β4 integrin expression). In complementary experiments, inhibition of Runx2 function in metastatic MDA-MB-231 breast cancer cells by stable expression of either short hairpin RNA-Runx2 or a mutant Runx2 deficient in subnuclear targeting resulted in reversion of acini to more normal structures and reduced tumor growth in vivo. These novel findings provide direct mechanistic evidence for the biological activity of Runx2, dependent on its subnuclear localization, in promoting early events of breast cancer progression and suggest a molecular therapeutic target. [Cancer Res 2009;69(17):6807–14]
Identification of a Stat3-Dependent Transcription Regulatory Network Involved in Metastatic Progression
Authors: Ranger Jill J. , Levy David E. , Shahalizadeh Solmaz , Hallett Michael , Muller William J. 
Published: August 2009

AbstractHigh levels of activated Stat3 are often found in human breast cancers and can correlate with poor patient outcome. We employed an activated ErbB2 mouse model of breast cancer to investigate the in vivo role of Stat3 in mammary tumor progression and found that Stat3 does not alter mammary tumor initiation but dramatically affects metastatic progression. Four-fold fewer animals exhibited lung metastases in the absence of Stat3 and a 12-fold reduction in the number of lung lesions was observed in animals bearing Stat3-null tumors when compared with the wild-type cohort. The decreased malignancy in Stat3-deficient tumors is attributed to a reduction in both angiogenic and inflammatory responses associated with a Stat3-dependent transcriptional cascade involving CCAAT/enhancer binding protein δ. [Cancer Res 2009;69(17):6823–30]