bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sp1-Mediated TRAIL Induction in Chemosensitization
Authors: Xu Jing , Zhou Jun-Ying , Wei Wei-Zen , Philipsen Sjaak , Wu Gen Sheng 
Published: August 2008

AbstractThe regulation of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) in cancer chemotherapy is not fully understood. Here, we show that the histone deacetylase (HDAC) inhibitors induce TRAIL in human breast cancer cells. Induction of TRAIL by the HDAC inhibitor MS275 can be enhanced by Adriamycin. Using different reporter constructs in conjunction with transcription activity assays and chromatin immunoprecipitation assays, we provide evidence that the transcription factor Sp1 is responsible for TRAIL induction by MS275 alone or in combination with Adriamycin. Further, we show that the combined treatment of breast cancer cells with MS275 and Adriamycin significantly increases apoptotic cell death via the activation of both death receptor and mitochondrial apoptotic pathways. Down-regulation of TRAIL by small interfering RNA silencing decreased MS275-mediated Adriamycin-induced caspase activation and apoptosis, thus conferring Adriamycin resistance. More importantly, breast cancer T47D cells in which Sp1 was knocked down or Sp1-knockout mouse embryonic stem cells were resistant to the combined treatments. Taken together, our results indicate that induction of TRAIL by the combined treatments with MS275 and Adriamycin is mediated by Sp1 and suggest that transcription factor Sp1 is an important target for the development of novel anticancer agents. [Cancer Res 2008;68(16):6718–26]
Stage-Specific Inhibitory Effects and Associated Mechanisms of Silibinin on Tumor Progression and Metastasis in Transgenic Adenocarcinoma of the Mouse Prostate Model
Authors: Raina Komal , Rajamanickam Subapriya , Singh Rana P. , Deep Gagan , Chittezhath Manesh , Agarwal Rajesh 
Published: August 2008

Abstract
Herein, using transgenic adenocarcinoma of the mouse prostate (TRAMP) model, we assessed the “stage-specific” efficacy of silibinin feeding against prostate cancer (PCa) initiation, progression, angiogenesis and metastasis, and associated molecular events involved in silibinin effects during these stages. Male TRAMP mice starting at ages 4, 12, 20, and 30 weeks of age were fed with control or 1% silibinin-supplemented diet for 8 to 15 weeks in stage-specific manners. At the end of studies, silibinin-fed mice showed less severe prostatic lesions compared with positive controls. During early stages of prostate tumor development, silibinin mediated its efficacy mostly via antiproliferative mechanisms. Feeding of silibinin to animals burdened with higher stages of prostate tumor significantly decreased tumor grade via antiproliferative effect, and inhibition of angiogenesis as evidenced by decreased expressions of platelet endothelial cell adhesion molecule-1/CD-31, vascular endothelial growth factor, and associated receptor, vascular endothelial growth factor R2, hypoxia-inducible factor-1α, and inducible nitric oxide synthase. Metastasis to distant organs was decreased in silibinin-fed mice, which was associated with a decreased expression of matrix metalloproteinases, mesenchymal markers snail-1, and fibronectin in the prostatic tissue and retention of epithelial characteristics. Together, these findings are both novel and highly significant in establishing the dual efficacy of silibinin where it inhibits progression of primary prostatic tumor and also shows protective efficacy against angiogenesis and late stage metastasis. These effects of silibinin could have potential implications to improve the morbidity and survival in PCa patients. [Cancer Res 2008;68(16):6822–30]
Aging and Cancer-Related Loss of Insulin-like Growth Factor 2 Imprinting in the Mouse and Human Prostate
Authors: Fu Vivian X. , Dobosy Joseph R. , Desotelle Joshua A. , Almassi Nima , Ewald Jonathan A. , Srinivasan Rajini , Berres Mark , Svaren John , Weindruch Richard , Jarrard David F. 
Published: August 2008

Abstract
Loss of imprinting (LOI) is an epigenetic alteration involving loss of parental origin-specific expression at normally imprinted genes. A LOI for Igf2, a paracrine growth factor, is important in cancer progression. Epigenetic modifications may be altered by environmental factors. However, is not known whether changes in imprinting occur with aging in prostate and other tissues susceptible to cancer development. We found a LOI for Igf2 occurs specifically in the mouse prostate associated with increased Igf2 expression during aging. In older animals, expression of the chromatin insulator protein CTCF and its binding to the Igf2-H19 imprint control region was reduced. Forced down-regulation of CTCF leads to Igf2 LOI. We further show that Igf2 LOI occurs with aging in histologically normal human prostate tissues and that this epigenetic alteration was more extensive in men with associated cancer. This finding may contribute to a postulated field of cancer susceptibility that occurs with aging. Moreover, Igf2 LOI may serve as a marker for the presence of prostate cancer. [Cancer Res 2008;68(16):6797–802]
Assimilation of GPS Radio Occultation Refractivity Data from CHAMP and SAC-C Missions over High Southern Latitudes with MM5 4DVAR
Authors: Wee Tae-Kwon , Kuo Ying-Hwa , Bromwich David H. , Monaghan Andrew J. 
Published: August 2008

Abstract
In this study, the GPS radio occultation (RO) data from the Challenging Minisatellite Payload (CHAMP) and Satellite de Aplicaciones Cientificas-C (SAC-C) missions are assimilated. An updated version of the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5) four-dimensional variational data assimilation system (4DVAR) is used to assess the impact of the GPS RO data on analyses and short-range forecasts over the Antarctic. The study was performed during the period of intense cyclonic activity in the Ross Sea, 9–19 December 2001. On average 66 GPS RO soundings were assimilated daily. For the assimilation over a single 12-h period, the impact of GPS RO data was only marginally positive or near neutral, and it varied markedly from one 12-h period to another. The large case-to-case variation was attributed to the low number of GPS RO soundings and a strong dependency of forecast impact on the location of the soundings relative to the rapidly developing cyclone. Despite the moderate general impact, noticeable reduction of temperature error in the upper troposphere and lower stratosphere was found, which demonstrates the value of GPS RO data in better characterizing the tropopause. Significant error reduction was also noted in geopotential height and wind fields in the stratosphere. Those improvements indicate that early detection of the upper-level precursors for storm development is a potential benefit of GPS RO data. When the assimilation period was extended to 48 h, a considerable positive impact of GPS RO data was found. All parameters that were investigated (i.e., temperature, pressure, and specific humidity) showed the positive impact throughout the entire model atmosphere for forecasts extending up to 5 days. The impact increased in proportion to the length of the assimilation period. Although the differences in the analyses as a result of GPS RO assimilation were relatively small initially, the subtle change and subsequent nonlinear growth led to noticeable forecast improvements at longer ranges. Consequently, the positive impact of GPS RO data was more evident in longer-range (e.g., greater than 2 days) forecasts. A correlation coefficient is introduced to quantify the linear relationship between the analysis errors without GPS RO assimilation and the analysis increments induced by GPS RO assimilation. This measure shows that the growth of GPS RO–induced modifications over time is related to the prominent error reduction observed in GPS RO experiments. The measure may also be useful for understanding how cycling analysis accumulates the positive impact of GPS RO data for an extended period of assimilation.
A Reanalysis of Ocean Climate Using Simple Ocean Data Assimilation (SODA)
Authors: Carton James A. , Giese Benjamin S. 
Published: August 2008

Abstract
This paper describes the Simple Ocean Data Assimilation (SODA) reanalysis of ocean climate variability. In the assimilation, a model forecast produced by an ocean general circulation model with an average resolution of 0.25° × 0.4° × 40 levels is continuously corrected by contemporaneous observations with corrections estimated every 10 days. The basic reanalysis, SODA 1.4.2, spans the 44-yr period from 1958 to 2001, which complements the span of the 40-yr European Centre for Medium-Range Weather Forecasts (ECMWF) atmospheric reanalysis (ERA-40). The observation set for this experiment includes the historical archive of hydrographic profiles supplemented by ship intake measurements, moored hydrographic observations, and remotely sensed SST. A parallel run, SODA 1.4.0, is forced with identical surface boundary conditions, but without data assimilation. The new reanalysis represents a significant improvement over a previously published version of the SODA algorithm. In particular, eddy kinetic energy and sea level variability are much larger than in previous versions and are more similar to estimates from independent observations. One issue addressed in this paper is the relative importance of the model forecast versus the observations for the analysis. The results show that at near-annual frequencies the forecast model has a strong influence, whereas at decadal frequencies the observations become increasingly dominant in the analysis. As a consequence, interannual variability in SODA 1.4.2 closely resembles interannual variability in SODA 1.4.0. However, decadal anomalies of the 0–700-m heat content from SODA 1.4.2 more closely resemble heat content anomalies based on observations.
A Multimoment Finite-Volume Shallow-Water Model on the Yin–Yang Overset Spherical Grid
Authors: Li Xingliang , Chen Dehui , Peng Xindong , Takahashi Keiko , Xiao Feng 
Published: August 2008

Abstract
A numerical model for shallow-water equations has been built and tested on the Yin–Yang overset spherical grid. A high-order multimoment finite-volume method is used for the spatial discretization in which two kinds of so-called moments of the physical field [i.e., the volume integrated average (VIA) and the point value (PV)] are treated as the model variables and updated separately in time. In the present model, the PV is computed by the semi-implicit semi-Lagrangian formulation, whereas the VIA is predicted in time via a flux-based finite-volume method and is numerically conserved on each component grid. The concept of including an extra moment (i.e., the volume-integrated value) to enforce the numerical conservativeness provides a general methodology and applies to the existing semi-implicit semi-Lagrangian formulations. Based on both VIA and PV, the high-order interpolation reconstruction can only be done over a single grid cell, which then minimizes the overlapping zone between the Yin and Yang components and effectively reduces the numerical errors introduced in the interpolation required to communicate the data between the two components. The present model completely gets around the singularity and grid convergence in the polar regions of the conventional longitude–latitude grid. Being an issue demanding further investigation, the high-order interpolation across the overlapping region of the Yin–Yang grid in the current model does not rigorously guarantee the numerical conservativeness. Nevertheless, these numerical tests show that the global conservation error in the present model is negligibly small. The model has competitive accuracy and efficiency.
Response of the Summer Marine Layer Flow to an Extreme California Coastal Bend
Authors: Dorman Clive E. , Koračin Darko 
Published: August 2008

Abstract
A summer wind speed maximum extending more than 200 km occurs over water around Point Conception, California, the most extreme bend along the U.S. West Coast. The following several causes were investigated for this wind speed maximum: 1) synoptic conditions, 2) marine layer hydraulic flow effects, 3) diurnal variations, 4) mountain leeside downslope flow, 5) sea surface temperature structure, and 6) island influence. Synoptic conditions set the general wind speed around Point Conception, and these winds are classified as strong, moderate, or weak. The strong wind condition extends about Point Conception, reaching well offshore toward the southwest, and the highest speeds are within 20 km to the south. Moderate wind cases do not extend as far offshore, and they have a moderate maximum wind speed that occurs over a smaller area in the western mouth of the Santa Barbara Channel. The weak wind speed case consists of light and variable winds about Point Conception. Each category occurs about one-third of the time. Atmospheric marine layer hydraulic dynamics dominate the situation after the synoptic condition is set. This includes an expansion fan on the south side of the point and a compression bulge on the north side. The expansion fan significantly increases the wind speeds over a large area that extends to the southwest, south, and east of Point Conception, and the maximum wind speed is increased for the strong and moderate synoptic cases as well. The horizontal sea surface temperature pattern contributes to the sea surface wind maximum through the Froude number, which links the potential temperature difference between the sea surface temperature and the capping inversion temperature with marine layer acceleration in an expansion fan. A greater potential temperature difference across the top of the marine layer also causes more energy to be trapped in the marine layer, instead of escaping upward. The thermally driven flow resulting from differential heating over land in the greater Los Angeles, California, coastal and elevated area to the east is not directly related to the wind speed maximum, either in the Santa Barbara Channel or in the open ocean extending farther offshore. The effects of the thermally driven flow extend only to the east of the Santa Barbara Channel. The downslope flow on the south side of the Santa Ynez Mountains that is generated by winds crossing the Santa Ynez Mountain ridge contributes neither to the high-speed wind maximum in the Santa Barbara channel nor to that extending farther offshore. Fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5) simulations do support a weak leeside flow in the upper portions of the Santa Ynez Mountains. The larger Channel Islands have a significant effect on the marine layer flow and the overwater wind structure. One major effect of the Santa Barbara Channel Islands is the extension of the zone of high-speed winds farther to the south than would otherwise be the case.
Plasmacytoid dendritic cells efficiently cross-prime naive T cells in vivo after TLR activation
Authors: Mouriès Juliette , Moron Gabriel , Schlecht Géraldine , Escriou Nicolas , Dadaglio Gilles , Leclerc Claude 
Published: August 2008

AbstractCross-presentation is a crucial mechanism in tumoral and microbial immunity because it allows internalized cell associated or exogenous antigens (Ags) to be delivered into the major histocompatibility complex I pathway. This pathway is important for the development of CD8+ T-cell responses and for the induction of tolerance. In mice, cross-presentation is considered to be a unique property of CD8α+ conventional dendritic cells (DCs). Here we show that splenic plasmacytoid DCs (pDCs) efficiently capture exogenous Ags in vivo but are not able to cross-present these Ags at steady state. However, in vitro and in vivo stimulation by Toll-like receptor-7, or -9 or viruses licenses pDCs to cross-present soluble or particulate Ags by a transporter associated with antigen processing-dependent mechanism. Induction of cross-presentation confers to pDCs the ability to generate efficient effector CD8+ T-cell responses against exogenous Ags in vivo, showing that pDCs may play a crucial role in induction of adaptive immune responses against pathogens that do not infect tissues of hemopoietic origin. This study provides the first evidence for an in vivo role of splenic pDCs in Ag cross-presentation and T-cell cross-priming and suggests that pDCs may constitute an attractive target to boost the efficacy of vaccines based on cytotoxic T lymphocyte induction.
Rabaptin-5 regulates receptor expression and functional activation in mast cells
Authors: Rios Eon J. , Piliponsky Adrian M. , Ra Chisei , Kalesnikoff Janet , Galli Stephen J. 
Published: August 2008

AbstractRab5 is a small GTPase that regulates early endocytic events and is activated by RabGEF1/Rabex-5. Rabaptin-5, a Rab5 interacting protein, was identified as a protein critical for potentiating RabGEF1/Rabex-5's activation of Rab5. Using Rabaptin-5 shRNA knockdown, we show that Rabaptin-5 is dispensable for Rab5-dependent processes in intact mast cells, including high affinity IgE receptor (FcϵRI) internalization and endosome fusion. However, Rabaptin-5 deficiency markedly diminished expression of FcϵRI and β1 integrin on the mast cell surface by diminishing receptor surface stability. This in turn reduced the ability of mast cells to bind IgE and significantly diminished both mast cell sensitivity to antigen (Ag)-induced mediator release and Ag-induced mast cell adhesion and migration. These findings show that, although dispensable for canonical Rab5 processes in mast cells, Rabaptin-5 importantly contributes to mast cell IgE-dependent immunologic function by enhancing mast cell receptor surface stability.
CD11c+ antigen presenting cells from the alveolar space, lung parenchyma and spleen differ in their phenotype and capabilities to activate naïve and antigen-primed T cells
Authors: Kugathasan Kapilan , Roediger Elizabeth K , Small Cherrie-Lee , McCormick Sarah , Yang Pingchang , Xing Zhou 
Published: August 2008

AbstractBackgroundThe lung is divided into two major compartments: the alveolar space and the parenchyma. The alveolar macrophages are the first line of leukocytes in the lung taking up incoming microbes or microbial antigens whereas the parenchymal dendritic cells (DCs) are believed to be the sole potent antigen presenting cells (APCs) in the lung. Both resting alveolar macrophages and parenchymal DCs express CD11c. Several important questions remain to be elucidated: 1] to which extent the alveolar space and lung parenchymal CD11c+ APCs differ in their phenotype and ability to activate naïve T cells; 2] whether they differ in their ability to activate antigen-experienced or -primed T cells; and 3] whether these lung CD11c+ APC populations differ from the splenic CD11c+ APCs which have been commonly used for understanding APC biology.ResultsCD11c+ APCs from the alveolar space, lung parenchyma, and the spleen display differential co-stimulatory molecule expression and cytokine responsiveness upon stimulation. Alveolar space APCs are weak activators of naïve T cells compared to lung parenchymal and splenic CD11c+ APC populations. However, alveolar space APCs are able to potently activate the in vivo microbial antigen-primed T cells to a similar extent as lung parenchymal and splenic APCs.ConclusionTogether our findings indicate that alveolar CD11c+ APCs have a specialized T cell-activating function, capable of activating antigen-primed, but not naïve, T cells whereas lung CD11c+ APCs are capable of activating both the naïve and antigen-primed T cell populations.
Evolutional selection of a combinatorial phage library displaying randomly-rearranged various single domains of immunoglobulin (Ig)-binding proteins (IBPs) with four kinds of Ig molecules
Authors: Yang Hua , Cao Jie , Li Lian-Qing , Zhou Xia , Chen Qiu-Li , Liao Wen-Ting , Wen Zong-Mei , Jiang Shao-Hua , Xu Rong , Jia Jian-An , Pan Xin , Qi Zhong-Tian , Pan Wei 
Published: August 2008

AbstractBackgroundProtein A, protein G and protein L are three well-defined immunoglobulin (Ig)-binding proteins (IBPs), which show affinity for specific sites on Ig of mammalian hosts. Although the precise functions of these molecules are not fully understood, it is thought that they play an important role in pathogenicity of bacteria. The single domains of protein A, protein G and protein L were all demonstrated to have function to bind to Ig. Whether combinations of Ig-binding domains of various IBPs could exhibit useful novel binding is interesting.ResultsWe used a combinatorial phage library which displayed randomly-rearranged various-peptide-linked molecules of D and A domains of protein A, designated PA(D) and PA(A) respectively, B2 domain of protein G (PG) and B3 domain of protein L (PL) for affinity selection with human IgG (hIgG), human IgM (hIgM), human IgA (hIgA) and recombinant hIgG1-Fc as bait respectively. Two kinds of novel combinatorial molecules with characteristic structure of PA(A)-PG and PA(A)-PL were obtained in hIgG (hIgG1-Fc) and hIgM (hIgA) post-selection populations respectively. In addition, the linking peptides among all PA(A)-PG and PA(A)-PL structures was strongly selected, and showed interestingly divergent and convergent distribution. The phage binding assays and competitive inhibition experiments demonstrated that PA(A)-PG and PA(A)-PL combinations possess comparable binding advantages with hIgG/hIgG1-Fc and hIgM/hIgA respectively.ConclusionIn this work, a combinatorial phage library displaying Ig-binding domains of protein A, protein G, or protein L joined by various random linking peptides was used to conducted evolutional selectionin vitrowith four kinds of Ig molecules. Two kinds of novel combinations of Ig-binding domains, PA(A)-PG and PA(A)-PL, were obtained, and demonstrate the novel Ig binding properties.
Prognostic relevance of Centromere protein H expression in esophageal carcinoma
Authors: Guo Xian-Zhi , Zhang Ge , Wang Jun-Ye , Liu Wan-Li , Wang Fang , Dong Ju-Qin , Xu Li-Hua , Cao Jing-Yan , Song Li-Bing , Zeng Mu-Sheng 
Published: August 2008

Abstract

Background
Many kinetochore proteins have been shown to be associated with human cancers. The aim of the present study was to clarify the expression of Centromere protein H (CENP-H), one of the fundamental components of the human active kinetochore, in esophageal carcinoma and its correlation with clinicopathological features.

Methods
We examined the expression of CENP-H in immortalized esophageal epithelial cells as well as in esophageal carcinoma cells, and in 12 cases of esophageal carcinoma tissues and the paired normal esophageal tissues by RT-PCR and Western blot analysis. In addition, we analyzed CENP-H protein expression in 177 clinicopathologically characterized esophageal carcinoma cases by immunohistochemistry. Statistical analyses were applied to test for prognostic and diagnostic associations.

Results
The level of CENP-H mRNA and protein were higher in the immortalized cells, cancer cell lines and most cancer tissues than in normal control tissues. Immunohistochemistry showed that CENP-H was expressed in 127 of 171 ESCC cases (74.3%) and in 3 of 6 esophageal adenocarcinoma cases (50%). Statistical analysis of ESCC cases showed that there was a significant difference of CENP-H expression in patients categorized according to gender (P = 0.013), stage (P = 0.023) and T classification (P = 0.019). Patients with lower CENP-H expression had longer overall survival time than those with higher CENP-H expression. Multivariate analysis suggested that CENP-H expression was an independent prognostic marker for esophageal carcinoma patients. A prognostic value of CENP-H was also found in the subgroup of T3~T4 and N0 tumor classification.

Conclusion
Our results suggest that CENP-H protein is a valuable marker of esophageal carcinoma progression. CENP-H might be used as a valuable prognostic marker for esophageal carcinoma patients.