bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synchronous 29-19 Ma arc hiatus, exhumation and subduction of forearc in southwestern Mexico
Authors: Keppie J. Duncan , Morán-Zenteno Dante J. , Martiny Barbara , González-Torres Enrique 
Published: December 2009

Abstract

The geology of southwestern Mexico (102–96°W) records several synchronous events in the Late Oligocene–Early Miocene (29–19 Ma): (1) a hiatus in arc magmatism; (2) removal of a wide (
c
. 210 km) Upper Eocene–Lower Oligocene forearc; (3) exhumation of 13–20 km of Upper Eocene–Lower Oligocene arc along the present day coast; and (4) breakup of the Farallon Plate. Events 2 and 3 have traditionally been related to eastward displacement of the Chortís Block from a position off southwestern Mexico between 105°W and 97°W; however at 30 Ma the Chortís Block would have lain east of 95°W. We suggest that the magmatic hiatus was caused by subduction of the forearc, which replaced the mantle wedge by relatively cool crust. Assuming that the subducted block separated along the forearc–arc boundary, a likely zone of weakness due to magmatism, the subducted forearc is estimated to be wedge-shaped varying from zero to
c
. 90 km in thickness; however such a wedge is not apparent in seismic data across central Mexico. Given the 121 km/Ma convergence rate between 20 and 10 Ma and 67 km/Ma since 10 Ma, it is probable that any forearc has been deeply subducted. Potential causes for subduction of the forearc include collision of an oceanic plateau with the trench, and a change in plate kinematics synchronous with breakup of the Farallon Plate and initiation of the Guadalupe–Nazca spreading ridge.
Analogue models of an Early Cenozoic transpressive regime in southern Mexico: implications on the evolution of the Xolapa complex and the North American-Caribbean Plate boundary
Authors: Cerca Mariano , Ferrari Luca , Tolson Gustavo , Corti Giacomo , Bonini Marco , Manetti Piero 
Published: December 2009

Abstract
We present analogue models that illustrate the tectonic evolution of the continental margin of southwestern Mexico and the Early Cenozoic deformation of the Xolapa complex. Together with geological data they suggest that oblique convergence caused distributed deformation and mountain building near the present-day margin of southern Mexico in a general left-lateral transpressional regime. A similar deformation is also observed north of the Xolapa complex in Maastrichtian to Paleocene sedimentary and volcanic rock units. Since post-Oligocene exhumation of middle crust does not significantly affect Late Eocene to Oligocene volcanic rocks, we infer that the evolution of the transform margin led to the formation of discrete boundaries that eventually decoupled exhumed mid-lower crust from the onshore upper-crust sequences since the Late Eocene.
A seismotectonic model for the Chortís Block
Authors: Guzmán-Speziale Marco 
Published: December 2009

Abstract

I propose a new seismotectonic model for the Chortís Block, at the northwestern corner of the Caribbean Plate. Shallow seismicity in the area clearly shows three zones of deformation: one along the North America–Caribbean Plate boundary and another along the Central America volcanic arc, and one in the area of the grabens of northern Central America. Analysis of Centroid moment–tensor solutions for shallow earthquakes in these three area show that
T
or tension axes are horizontal and trend away from the corner, and that
P
or compression axes for the plate boundary and the volcanic arc are also horizontal and trending towards the corner. Calculation of seismic moment release per unit volume reveals similar values for the volcanic arc and the plate boundary. The state of stress and similarity in seismic moment release suggest that the Chortís Block is being extruded towards the ESE. This is probably due to compression of the large North America and Cocos Plates that surround it.
Myeloid-Derived Suppressor Cells Inhibit T-Cell Activation by Depleting Cystine and Cysteine
Authors: Srivastava Minu K. , Sinha Pratima , Clements Virginia K. , Rodriguez Paulo , Ostrand-Rosenberg Suzanne 
Published: December 2009

AbstractMyeloid-derived suppressor cells (MDSC) are present in most cancer patients and are potent inhibitors of T-cell–mediated antitumor immunity. Their inhibitory activity is attributed to production of arginase, reactive oxygen species, inducible nitric oxide synthase, and interleukin-10. Here we show that MDSCs also block T-cell activation by sequestering cystine and limiting the availability of cysteine. Cysteine is an essential amino acid for T-cell activation because T cells lack cystathionase, which converts methionine to cysteine, and because they do not have an intact xc− transporter and therefore cannot import cystine and reduce it intracellularly to cysteine. T cells depend on antigen-presenting cells (APC), such as macrophages and dendritic cells, to export cysteine, which is imported by T cells via their ASC neutral amino acid transporter. MDSCs express the xc− transporter and import cystine; however, they do not express the ASC transporter and do not export cysteine. MDSCs compete with APC for extracellular cystine, and in the presence of MDSCs, APC release of cysteine is reduced, thereby limiting the extracellular pool of cysteine. In summary, MDSCs consume cystine and do not return cysteine to their microenvironment, thereby depriving T cells of the cysteine they require for activation and function. Cancer Res; 70(1); 68–77
Mining Tissue Microarray Data to Uncover Combinations of Biomarker Expression Patterns that Improve Intermediate Staging and Grading of Clear Cell Renal Cell Cancer
Authors: Dahinden Corinne , Ingold Barbara , Wild Peter , Boysen Gunther , Luu Van-Duc , Montani Matteo , Kristiansen Glen , Sulser Tullio , Bühlmann Peter , Moch Holger , Schraml Peter 
Published: December 2009

Abstract
Purpose: Tumor stage and nuclear grade are the most important prognostic parameters of clear cell renal cell carcinoma (ccRCC). The progression risk of ccRCC remains difficult to predict particularly for tumors with organ-confined stage and intermediate differentiation grade. Elucidating molecular pathways deregulated in ccRCC may point to novel prognostic parameters that facilitate planning of therapeutic approaches.
Experimental Design: Using tissue microarrays, expression patterns of 15 different proteins were evaluated in over 800 ccRCC patients to analyze pathways reported to be physiologically controlled by the tumor suppressors von Hippel-Lindau protein and phosphatase and tensin homologue (PTEN). Tumor staging and grading were improved by performing variable selection using Cox regression and a recursive bootstrap elimination scheme.
Results: Patients with pT2 and pT3 tumors that were p27 and CAIX positive had a better outcome than those with all remaining marker combinations. A prolonged survival among patients with intermediate grade (grade 2) correlated with both nuclear p27 and cytoplasmic PTEN expression, as well as with inactive, nonphosphorylated ribosomal protein S6. By applying graphical log-linear modeling for over 700 ccRCC for which the molecular parameters were available, only a weak conditional dependence existed between the expression of p27, PTEN, CAIX, and p-S6, suggesting that the dysregulation of several independent pathways are crucial for tumor progression.
Conclusions: The use of recursive bootstrap elimination, as well as graphical log-linear modeling for comprehensive tissue microarray (TMA) data analysis allows the unraveling of complex molecular contexts and may improve predictive evaluations for patients with advanced renal cancer. Clin Cancer Res; 16(1); 88–98
SPARC Is Associated with Gastric Cancer Progression and Poor Survival of Patients
Authors: Zhao Zhong-Sheng , Wang Yuan-Yu , Chu Yong-Quan , Ye Zai-Yuan , Tao Hou-Quan 
Published: December 2009

Abstract
Purpose: The present study investigated the clinical significance of secreted protein, acidic and rich in cysteine (SPARC), in the development and progression of gastric cancer.
Experimental Design: Immunohistochemistry was used to analyze SPARC, integrin β1, and matrix metalloproteinase (MMP)-2 expression in 436 clinicopathologically characterized gastric cancer cases.
Results: SPARC, integrin β1, and MMP-2 protein levels were upregulated in gastric cancer lesions compared with adjacent noncancerous tissues. SPARC protein was detected in 334 of 436 human gastric cancer cases and was highly expressed in 239 tumors. We also found a positive correlation between expression of SPARC and MMP2, and SPARC and integrin β1. In stages I, II, and III, the 5-year survival rate of patients with a high expression of SPARC was significantly lower than those in patients with low expression. In stage IV, SPARC expression did not correlate with the 5-year survival rate. Further multivariate analysis suggested that the depth of invasion; lymph node and distant metastasis; tumor-node-metastasis stage; and upregulation of SPARC, MMP-2, and integrin β1, were independent prognostic indicators for the disease.
Conclusions: Our study provided a basis for the development of a novel biomarker for diagnosis and prognosis of gastric cancer. Expression of SPARC in gastric cancer is significantly associated with lymph node and distant metastasis, high MMP2 expression, high intergrin β1 expression, and poor prognosis. SPARC, intergrin β1, and MMP-2 protein could be useful markers to predict tumor progression. Clin Cancer Res; 16(1); 260–8
Vorinostat Enhances the Activity of Temsirolimus in Renal Cell Carcinoma Through Suppression of Survivin Levels
Authors: Mahalingam Devalingam , Medina Ernest C. , Esquivel Juan A. , Espitia Claudia M. , Smith Sabrina , Oberheu Kelli , Swords Ronan , Kelly Kevin R. , Mita Monica M. , Mita Alain C. , Carew Jennifer S. , Giles Francis J. , Nawrocki Steffan T. 
Published: December 2009

Abstract
Purpose: The mammalian target of rapamycin (mTOR) inhibitor temsirolimus has exhibited promising anticancer activity for the treatment of renal cell cancers (RCC). Survivin expression has been implicated in drug resistance and reducing its levels with the histone deacetylase (HDAC) inhibitor vorinostat may enhance the anticancer activity of temsirolimus.
Experimental Design: The sensitivity of RCC cell lines to the combination of temsirolimus and vorinostat was determined by measuring cell viability, clonogenic survival, and apoptosis. The effects of this combination on survivin levels were determined in vitro and in vivo. Survivin expression was silenced using small interfering RNA to evaluate its role in determining sensitivity to temsirolimus and vorinostat. The effect of the combination on angiogenesis was also determined in RCC xenograft models.
Results: Vorinostat synergistically improved the anticancer activity of temsirolimus in a panel of RCC cell lines in vitro and in two xenograft models in vivo. While each single agent led to a modest decrease in survivin levels, the combination dramatically reduced its expression, which correlated with an induction of apoptosis. Silencing survivin levels induced apoptosis and significantly improved the efficacy of temsirolimus and vorinostat. In addition, the temsirolimus/vorinostat combination led to a strong reduction in angiogenesis.
Conclusions: Vorinostat augmented the anticancer activity of temsirolimus in both in vitro and in vivo models of RCC. The effectiveness of the combination was due to a decrease in survivin levels and corresponding induction of apoptosis, and enhanced inhibition of angiogenesis. Targeting survivin may be a promising therapeutic strategy to improve RCC therapy. Clin Cancer Res; 16(1); 141–53
Aldehyde Dehydrogenase 1–Positive Cancer Stem Cells Mediate Metastasis and Poor Clinical Outcome in Inflammatory Breast Cancer
Authors: Charafe-Jauffret Emmanuelle , Ginestier Christophe , Iovino Flora , Tarpin Carole , Diebel Mark , Esterni Benjamin , Houvenaeghel Gilles , Extra Jean-Marc , Bertucci François , Jacquemier Jocelyne , Xerri Luc , Dontu Gabriela , Stassi Giorgio , Xiao Yi , Barsky Sanford H. , Birnbaum Daniel , Viens Patrice , Wicha Max S. 
Published: December 2009

Abstract
Purpose: To examine the role of cancer stem cells (CSC) in mediating metastasis in inflammatory breast cancer (IBC) and the association of these cells with patient outcome in this aggressive type of breast cancer.
Experimental Design: CSCs were isolated from SUM149 and MARY-X, an IBC cell line and primary xenograft, by virtue of increased aldehyde dehydrogenase (ALDH) activity as assessed by the ALDEFLUOR assay. Invasion and metastasis of CSC populations were assessed by in vitro and mouse xenograft assays. Expression of ALDH1 was determined on a retrospective series of 109 IBC patients and this was correlated with histoclinical data. All statistical tests were two sided. Log-rank tests using Kaplan-Meier analysis were used to determine the correlation of ALDH1 expression with development of metastasis and patient outcome.
Results: Both in vitro and xenograft assays showed that invasion and metastasis in IBC are mediated by a cellular component that displays ALDH activity. Furthermore, expression of ALDH1 in IBC was an independent predictive factor for early metastasis and decreased survival in this patient population.
Conclusions: These results suggest that the metastatic, aggressive behavior of IBC may be mediated by a CSC component that displays ALDH enzymatic activity. ALDH1 expression represents the first independent prognostic marker to predict metastasis and poor patient outcome in IBC. The results illustrate how stem cell research can translate into clinical practice in the IBC field. Clin Cancer Res; 16(1); 45–55
Immunotherapy of Malignant Disease with Tumor Antigen–Specific Monoclonal Antibodies
Authors: Campoli Michael , Ferris Robert , Ferrone Soldano , Wang Xinhui 
Published: December 2009

Abstract
A few tumor antigen (TA)–specific monoclonal antibodies (mAb) have been approved by the Food and Drug Administration for the treatment of several major malignant diseases and are commercially available. Once in the clinic, mAbs have an average success rate of ∼30% and are well tolerated. These results have changed the face of cancer therapy, bringing us closer to more specific and more effective biological therapy of cancer. The challenge facing tumor immunologists at present is represented by the identification of the mechanism(s) underlying the patients' differential clinical response to mAb-based immunotherapy. This information is expected to lead to the development of criteria to select patients to be treated with mAb-based immunotherapy. In the past, in vitro and in vivo evidence has shown that TA-specific mAbs can mediate their therapeutic effect by inducing tumor cell apoptosis, inhibiting the targeted antigen function, blocking tumor cell signaling, and/or mediating complement- or cell-dependent lysis of tumor cells. More recent evidence suggests that TA-specific mAb can induce TA-specific cytotoxic T-cell responses by enhancing TA uptake by dendritic cells and cross-priming of T cells. In this review, we briefly summarize the TA-specific mAbs that have received Food and Drug Administration approval. Next, we review the potential mechanisms underlying the therapeutic efficacy of TA-specific mAbs with emphasis on the induction of TA-specific cellular immune responses and their potential to contribute to the clinical efficacy of TA-specific mAb-based immunotherapy. Lastly, we discuss the potential negative effect of immune escape mechanisms on the clinical efficacy of TA-specific mAb-based immunotherapy. Clin Cancer Res; 16(1); 11–20
Influence of HLA-DRB1 alleles on the susceptibility and resistance to multiple sclerosis in Japanese patients with respect to anti-aquaporin 4 antibody status
Authors: Isobe N. , Matsushita T. , Yamasaki R. , Ramagopalan SV , Kawano Y. , Nishimura Y. , Ebers GC , Kira J. 
Published: December 2009

Background: Epistatic interactions between human leukocyte antigen (HLA)-DRB1 alleles alter multiple sclerosis (MS) risk in Caucasians. Such interactions have never been studied in Asian MS patients. Objective: To investigate the influence of HLA-DRB1 alleles, including epistatic interactions at this locus, in Japanese MS patients with and without the anti-aquaporin 4 (AQP4) antibody. Methods: The HLA-DRB1 locus was genotyped in 108 MS patients and 127 healthy controls. MS patients were further classified into two groups according to anti-AQP4 antibody status (27 positive and 81 negative). Results: HLA-DRB1*09 (adjusted odds ratio (OR) = 0.243, 95% confidence interval (CI) 0.099—0.533) and HLA-DRB1*01 (adjusted OR = 0.327, 95% CI 0.103—0.873) decreased the incidence of anti-AQP4 antibody-negative MS. By contrast, HLA-DRB1*12 increased the risk of anti-AQP4 antibody-positive MS (adjusted OR = 3.691, 95% CI 1.233—10.565). Individuals with HLA-DRB1*09/15 decreased the risk of anti-AQP4 antibody-negative MS (adjusted OR = 0.164, 95% CI 0.026—0.593), while those with HLA-DRB1*12/15 increased the risk of anti-AQP4 antibody-positive MS (adjusted OR = 10.870, 95% CI 2.004—81.752). Conclusions: The ability of HLA-DRB1*09 to reduce the risk of anti-AQP4 antibody-negative MS may arise from an interaction with HLA-DRB1*15. By contrast, HLA-DRB1*12 increases susceptibility to anti-AQP4 antibody-positive MS, possibly via an interaction with HLA-DRB1*15.
Identification of mammalian orthologs using local synteny
Authors: Jun Jin , Mandoiu Ion I , Nelson Craig E 
Published: December 2009

Abstract

Background
Accurate determination of orthology is central to comparative genomics. For vertebrates in particular, very large gene families, high rates of gene duplication and loss, multiple mechanisms of gene duplication, and high rates of retrotransposition all combine to make inference of orthology between genes difficult. Many methods have been developed to identify orthologous genes, mostly based upon analysis of the inferred protein sequence of the genes. More recently, methods have been proposed that use genomic context in addition to protein sequence to improve orthology assignment in vertebrates. Such methods have been most successfully implemented in fungal genomes and have long been used in prokaryotic genomes, where gene order is far less variable than in vertebrates. However, to our knowledge, no explicit comparison of synteny and sequence based definitions of orthology has been reported in vertebrates, or, more specifically, in mammals.

Results
We test a simple method for the measurement and utilization of gene order (local synteny) in the identification of mammalian orthologs by investigating the agreement between coding sequence based orthology (Inparanoid) and local synteny based orthology. In the 5 mammalian genomes studied, 93% of the sampled inter-species pairs were found to be concordant between the two orthology methods, illustrating that local synteny is a robust substitute to coding sequence for identifying orthologs. However, 7% of pairs were found to be discordant between local synteny and Inparanoid. These cases of discordance result from evolutionary events including retrotransposition and genome rearrangements.

Conclusions
By analyzing cases of discordance between local synteny and Inparanoid we show that local synteny can distinguish between true orthologs and recent retrogenes, can resolve ambiguous many-to-many orthology relationships into one-to-one ortholog pairs, and might be used to identify cases of non-orthologous gene displacement by retroduplicated paralogs.
Are there geographic and socio-economic differences in incidence, burden and prevention of malaria? A study in southeast Nigeria
Authors: Onwujekwe Obinna , Uzochukwu Benjamin , Dike Nkem , Okoli Chijioke , Eze Soludo , Chukwuogo Ogoamaka 
Published: December 2009

Abstract

Rationale
It is not clearly evident whether malaria affects the poor more although it has been argued that the poor bear a very high burden of the disease. This study explored the socioeconomic and geographic differences in incidence and burden of malaria as well as ownership of mosquito nets.

Methods
Structured questionnaires were used to collect information from 1657 respondents from rural and urban communities in southeast Nigeria on: incidence of malaria, number of days lost to malaria; actions to treat malaria and household ownership of insecticide treated and untreated mosquito nets. Data was compared across socio-economic status (SES) quartiles and between urban and rural dwellers.

Results
There was statistically significant urban-rural difference in malaria occurrence with malaria occurring more amongst urban dwellers. There was more reported occurrence of malaria amongst children and other adult household members in better-off SES groups compared to worse-off SES groups, but not amongst respondents. The average number of days that people delayed before seeking treatment was two days, and both adults and children were ill with malaria for about six days. Better-off SES quartile and urban dwellers owned more mosquito nets (p < 0.05) (treated and untreated).

Conclusion
Malaria occurs more amongst better-off SES groups and urban dwellers in southeast Nigeria. Deployment of malaria control interventions should ensure universal access since targeting the poor and other supposedly vulnerable groups may exclude people that really require malaria control services.
Systematic review of epidemiological studies on health effects associated with management of solid waste
Authors: Porta Daniela , Milani Simona , Lazzarino Antonio I , Perucci Carlo A , Forastiere Francesco 
Published: December 2009

Abstract

Background
Management of solid waste (mainly landfills and incineration) releases a number of toxic substances, most in small quantities and at extremely low levels. Because of the wide range of pollutants, the different pathways of exposure, long-term low-level exposure, and the potential for synergism among the pollutants, concerns remain about potential health effects but there are many uncertainties involved in the assessment. Our aim was to systematically review the available epidemiological literature on the health effects in the vicinity of landfills and incinerators and among workers at waste processing plants to derive usable excess risk estimates for health impact assessment.

Methods
We examined the published, peer-reviewed literature addressing health effects of waste management between 1983 and 2008. For each paper, we examined the study design and assessed potential biases in the effect estimates. We evaluated the overall evidence and graded the associated uncertainties.

Results
In most cases the overall evidence was inadequate to establish a relationship between a specific waste process and health effects; the evidence from occupational studies was not sufficient to make an overall assessment. For community studies, at least for some processes, there was limited evidence of a causal relationship and a few studies were selected for a quantitative evaluation. In particular, for populations living within two kilometres of landfills there was limited evidence of congenital anomalies and low birth weight with excess risk of 2 percent and 6 percent, respectively. The excess risk tended to be higher when sites dealing with toxic wastes were considered. For populations living within three kilometres of old incinerators, there was limited evidence of an increased risk of cancer, with an estimated excess risk of 3.5 percent. The confidence in the evaluation and in the estimated excess risk tended to be higher for specific cancer forms such as non-Hodgkin's lymphoma and soft tissue sarcoma than for other cancers.

Conclusions
The studies we have reviewed suffer from many limitations due to poor exposure assessment, ecological level of analysis, and lack of information on relevant confounders. With a moderate level confidence, however, we have derived some effect estimates that could be used for health impact assessment of old landfill and incineration plants. The uncertainties surrounding these numbers should be considered carefully when health effects are estimated. It is clear that future research into the health risks of waste management needs to overcome current limitations.