bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolation and characterization of a hydrogen- and ethanol-producing Clostridium sp. strain URNW
Authors: Ramachandran Umesh , Wrana Nathan , Cicek Nazim , Sparling Richard , Levin David B. 
Published: February 2011

Identification, characterization, and end-product synthesis patterns were analyzed in a newly identified mesophilic, anaerobic Clostridium sp. strain URNW, capable of producing hydrogen (H2) and ethanol. Metabolic profiling was used to characterize putative end-product synthesis pathways of the Clostridium sp. strain URNW, which was found to grow on cellobiose; on hexose sugars, such as glucose, sucrose, and mannose; and on sugar alcohols, like mannitol and sorbitol. When grown in batch cultures on 2 g cellobiose·L–1, Clostridium sp. strain URNW showed a cell generation time of 1.5 h, and the major end-products were H2, formate, carbon dioxide (CO2), lactate, butyrate, acetate, pyruvate, and ethanol. The total volumetric H2production was 14.2 mmol·(L culture)–1and the total production of ethanol was 0.4 mmol·(L culture)–1. The maximum yield of H2was 1.3 mol·(mol glucose equivalent)–1at a carbon recovery of 94%. The specific production rates of H2, CO2, and ethanol were 0.45, 0.13, and 0.003 mol·h–1·(g dry cell mass)–1, respectively. BLAST analyses of 16S rDNA and chaperonin 60 (cpn60) sequences from Clostridium sp. strain URNW revealed a 98% nucleotide sequence identity with the 16S rDNA and cpn60 sequences from Clostridium intestinale ATCC 49213. Phylogenetic analyses placed Clostridium sp. strain URNW within the butyrate-synthesizing clostridia.
社會工作的「社會」涵義：重拾社會工作中的社會本質
Authors: 甘 炳光 
Published: February 2011

本文旨在檢視爲何社會工作被稱爲社會工作，以及甚麽是社會工作中的「社會」涵義。回顧社會工作的發展，社會工作實務愈來愈走向個人輔導及治療模式的發展，而漸漸忘記了或忽略了關注社會改變、社會改革及社會公義的目標。本文嘗試討論若社會工作只強調個人轉變及個人治療，是否應該還被稱爲社會工作？社會工作理應也強調其「社會」本質及目標。社會工作專業應該重拾「社會」目標，重新理解及關注社會工作的真正「社會」涵義。本文首先討論社會工作邁向個人導向與治療化的趨勢及其原因，然後提出將社工專業回歸「社會」本質的重要，更列出社工所要包含的六點「社會」涵義或元素。最後建議在社工專業實踐、社工專業發展及社工教育中如何推動重新認識社會工作的「社會」本質及實踐其社會目標。 This article examines why social work is called by its name and what the "social" of social work is. The review of the development of social work has found that social work practice has put more emphasis on individual treatment and clinical therapies, and has increasingly neglected the aim of advancing social change, social reform and social justice. This article aims to discuss if social work only focuses on individual change and treatment, should it be still called by this name? Social work should also focus on its social goals. The social work profession needs to revive its social goals and identify the meaning of its social nature. This article begins with discussing the trend of therapeutisation of social work and the reasons behind, then examines the importance of realigning the profession with its social nature and identifies the six social dimensions of social work. It suggests how to promote the understanding of the social of social work and the achievement of its social goals with regard to the aspects of social work practice, the development of the social work profession and social work education.
OUTSOURCING OF NEW PRODUCT DEVELOPMENT AND THE OPENING OF INNOVATION IN MATURE INDUSTRIES: A LONGITUDINAL STUDY OF FIAT DURING CRISIS AND RECOVERY
Authors: CIRAVEGNA LUCIANO , MAIELLI GIULIANO 
Published: February 2011

During the 1990s mature industries, such as car manufacturing, restructured their production and innovation processes, changing from vertical integration to high outsourcing. Open innovation is antithetic to vertical integration. Analyzing whether this restructuring influenced the emergence of open innovation is an important step towards improving our understanding of open innovation (Chesbrough and Crowther, 2006).During the 1990s, Fiat, one the largest European car producers, increased the extent to which it involved external firms in new product development (NPD). Unlike its competitors, Fiat outsourced the NPD of core products, resembling the opening of innovation that "radical innovators" implement in high technology industry (Laursen and Salter, 2006, 137). However, it failed to transition towards open innovation because its "opening" to external firms also entailed downsizing in-house NPD divisions, which caused a "hollowing out" of its knowledge (Becker and Zirpoli, 2003). The products developed through this system did not perform well. After a dramatic decline in market shares, Fiat changed its NPD system: it reduced outsourcing of NPD, whilst opening it to customers for the first time. This contributed to the development of highly successful models, which fuelled Fiat's recovery after 2004.The paper explains the Fiat case by looking at the drivers of its organizational changes from a historical perspective. It argues that Fiat's cost-cutting routines, developed because of its intangible specialization in small vehicles, explain why it opened NPD to suppliers but failed to adopt open innovation. The case study is relevant for the study of open innovation because it provides evidence of the relationships between outsourcing and open of innovation in a mature industry that went through a profound process of restructuring during the 1990s.
Cyclin D1 Inhibits Mitochondrial Activity in B Cells
Authors: Tchakarska Guergana , Roussel Mikel , Troussard Xavier , Sola Brigitte 
Published: February 2011

Abstract
Cyclin D1 is a cell cycle regulatory protein that acts at the G1-S transition, following its binding to and activation by the cyclin-dependent kinases 4 or 6. Cyclin D1 is absent from the entire B-cell lineage but is present in a large percentage of 2 types of malignant B-cell hemopathy—mantle cell lymphoma and multiple myeloma— suggesting a major role of this protein in the malignancy process. We show here, in an experimental model of cyclin D1 fusion protein transduction in mature B cells, that, cyclin D1 inhibits total mitochondrial activity. Cyclin D1 is localized at the outer mitochondrial membrane, bound to a voltage-dependent anion channel through its central domain, and it competes with hexokinase 2 for binding to this channel. The bound cyclin D1 decreases the supply of ADP, ATP, and metabolites, thereby reducing energy production. This function of cyclin D1 was also reported by others in normal and transformed mammary epithelial cells, suggesting that it may be ubiquitous. Cancer Res; 71(5); 1690–9. ©2011 AACR.
CNT1 Expression Influences Proliferation and Chemosensitivity in Drug-Resistant Pancreatic Cancer Cells
Authors: Bhutia Yangzom D. , Hung Sau Wai , Patel Bhavi , Lovin Dylan , Govindarajan Rajgopal 
Published: February 2011

Abstract
Overcoming the inherent chemoresistance of pancreatic cancers remains a major goal of therapeutic investigations in this disease. In this study, we discovered a role for the human concentrative nucleoside transporter-1 (hCNT1; SLC28A1), a high-affinity pyrimidine nucleoside transporter, in determining the chemosensitivity of human pancreatic cancer cells to gemcitabine, the drug used presently as a standard of care. Compared with normal pancreas and pancreatic ductal epithelial cells, hCNT1 expression was frequently reduced in pancreatic tumors and tumor cell lines. In addition, hCNT1-mediated 3H-gemcitabine transport was lower in pancreatic cancer cell lines and correlated with cytotoxic IC50 estimations of gemcitabine. In contrast to gemcitabine-sensitive pancreatic cancer cell lines, MIA PaCa-2, a gemcitabine-resistant pancreatic cancer cell line, exhibited relatively restrictive, cell cycle-dependent hCNT1 expression and transport. hCNT1 translation was suppressed in the late G1-enriched MIA PaCa-2 cell population possibly in an miRNA-dependent manner, which corresponded with the lowest hCNT1-mediated gemcitabine transport during this phase. Although hCNT1 protein was induced during G1/S transition, increased hCNT1 trafficking resulted in maximal cell surface recruitment and transport-overshoot in the G2/M phase-enriched cell population. hCNT1 protein was directed predominantly to proteasomal or lysosomal degradation in S or G2/M phase MIA PaCa-2 cells, respectively. Pharmacological inhibition of hCNT1 degradation moderately increased cell surface hCNT1 expression and cellular gemcitabine transport in MIA PaCa-2 cells. Constitutive hCNT1 expression reduced clonogenic survival of MIA PaCa-2 cells and steeply augmented gemcitabine transport and chemosensitization. In addition to supporting a putative tumor suppressor role for hCNT1, our findings identify hCNT1 as a potential candidate to render drug-resistant pancreatic cancer cells amenable to chemotherapy. Cancer Res; 71(5); 1825–35. ©2011 AACR.
Steroid Receptor Coactivator-1 Upregulates Integrin α5 Expression to Promote Breast Cancer Cell Adhesion and Migration
Authors: Qin Li , Chen Xian , Wu Yelin , Feng Zhen , He Tao , Wang Li , Liao Lan , Xu Jianming 
Published: February 2011

Abstract
Metastatic breast cancer remains a lethal disease with poorly understood molecular mechanisms. Steroid receptor coactivator-1 (SRC-1 or NCOA1) is overexpressed in a subset of breast cancers with poor prognosis. It potentiates gene expression by serving as a coactivator for nuclear receptors and other transcription factors. We previously reported that SRC-1 promotes breast cancer metastasis without affecting primary mammary tumor formation. Herein, we found that SRC-1 deficiency in mouse and human breast cancer cells substantially reduced cell adhesion and migration capabilities on fibronectin and significantly extended the time of focal adhesion disassembly and reassembly. In agreement with this phenotype, SRC-1 expression positively correlated with integrin α5 (ITGA5) expression in estrogen receptor–negative breast tumors whereas SRC-1 deficiency decreased ITGA5 expression. Furthermore, ITGA5 reduction in SRC-1–deficient/insufficient breast cancer cells or knockdown of ITGA5 in SRC-1–expressing breast cancer cells was associated with a disturbed integrin-mediated signaling. Critical downstream changes included reduced phosphorylation and/or dampened activation of focal adhesion kinase, paxillin, Rac1, and Erk1/2 during cell adhesion. Finally, we found that SRC-1 enhanced ITGA5 promoter activity through an AP-1 (activator protein)–binding site proximal to the transcriptional initiation site; both SRC-1 and c-Jun were recruited to this promoter region in breast cancer cells. These results show that SRC-1 can promote breast cancer metastasis by directly enhancing ITGA5 expression and thus promoting ITGA5-mediated cell adhesion and migration. Therefore, targeting ITGA5 in SRC-1–positive breast cancers may result in inhibition of SRC-1–promoted breast cancer metastasis. Cancer Res; 71(5); 1742–51. ©2011 AACR.
Hypoxia Predicts Aggressive Growth and Spontaneous Metastasis Formation from Orthotopically Grown Primary Xenografts of Human Pancreatic Cancer
Authors: Chang Qing , Jurisica Igor , Do Trevor , Hedley David W. 
Published: February 2011

AbstractHypoxia in solid tumors is associated with treatment resistance and increased metastatic potential. Although hypoxia has been reported in pancreatic cancer patients, there is little direct evidence that this contributes to their overall poor prognosis. To address this, we examined the associations between hypoxia and biological aggression in a series of patient-derived xenografts grown orthotopically. Early passage xenografts were established from 16 patients undergoing surgery for pancreatic cancer and maintained in the pancreas of immune-deprived mice. Hypoxic cells were labeled using the 2-nitroimidazole probe EF5 and stained for immunofluorescence microscopy of tissue sections or as cell suspensions for flow cytometry. Bromodeoxyuridine (BrdUrd) uptake, microvessel density, cleaved caspase-3, and the differentiation markers E-cadherin, cytokeratin 19, and vimentin were analyzed in relation to hypoxia. Orthotopic implants closely resembled the histology of the original surgical samples. The 16 primary xenografts showed a wide range in their growth rates and metastatic potential, reminiscent of the spectrum of behavior seen in the clinic. EF5 labeling, tumor growth rates, and metastatic patterns were highly consistent within replicates, indicating a significant transmissible (genetic or epigenetic) component. Hypoxia was highly correlated with rapid tumor growth, increased BrdUrd uptake, and with spontaneous metastasis formation. mRNA expression analysis showed increased expression of genes involved in cell survival and proliferation in the hypoxic models. The results suggest that hypoxia is a major adverse prognostic factor in pancreatic cancer patients and support the introduction of techniques to measure hypoxia directly in patients and the development of treatment protocols to target hypoxia. Cancer Res; 71(8); 3110–20. ©2011 AACR.
Prostate Cancer Predisposition Loci and Risk of Metastatic Disease and Prostate Cancer Recurrence
Authors: Ahn Jiyoung , Kibel Adam S. , Park Jong Y. , Rebbeck Timothy R. , Rennert Hanna , Stanford Janet L. , Ostrander Elaine A. , Chanock Stephen , Wang Ming-Hsi , Mittal Rama D. , Isaacs William B. , Platz Elizabeth A. , Hayes Richard B. 
Published: February 2011

Abstract
Purpose: Genome-wide association studies (GWAS) have identified multiple novel prostate cancer predisposition loci. Whether these common genetic variants are associated with incident metastatic prostate cancer or with recurrence after surgical treatment for clinically localized prostate cancer is uncertain.
Experimental Design: Twelve single nucleotide polymorphisms (SNPs) were selected for study in relation to prostate metastatic cancer and recurrence, based on their genome-wide association with prostate cancer in the Cancer Genetic Markers of Susceptibility (CGEMS). To assess risk for metastatic disease, we compared genotypes for the 12 SNPs by logistic regression of 470 incident metastatic prostate cancer cases and 1,945 controls in 3 case-control studies. To assess the relationship of these SNPs to risk for prostate cancer recurrence, we used Cox regression in a cohort of 1,412 men treated for localized prostate cancer, including 328 recurrences, and used logistic regression in a case-case study, comparing 450 recurrent versus 450 nonrecurrent prostate cancer cases. Study-specific relative risks (RRs) for risk of metastatic disease and recurrence were summarized using meta-analysis, with inverse variance weights.
Results:MSMB rs10993994 (per variant allele summary RR = 1.24, 95% CI = 1.05–1.48), 8q24 rs4242382 (RR = 1.40, 95% CI = 1.13–1.75), and 8q24 rs6983267 (RR = 0.67, 95% CI = 0.50–0.89) were associated with risk for metastatic prostate cancer. None of the 12 SNPs was associated with prostate cancer recurrence.
Conclusions: SNPs in MSMB and 8q24 which predispose to prostate cancer overall are associated with risk for metastatic prostate cancer, the most lethal form of this disease. SNPs predictive of prostate cancer recurrence were not identified, among the predisposition SNPs. GWAS specific to these 2 phenotypes may identify additional phenotype-specific genetic determinants. Clin Cancer Res; 17(5); 1075–81. ©2011 AACR.
Pancreatic Tumor Suppression by Benzyl Isothiocyanate Is Associated with Inhibition of PI3K/AKT/FOXO Pathway
Authors: Boreddy Srinivas Reddy , Pramanik Kartick C. , Srivastava Sanjay K. 
Published: February 2011

Abstract
Purpose: Our previous studies have shown that benzyl isothiocyanate (BITC) suppress pancreatic cancer growth by inducing apoptosis but the molecular mechanism was unclear. In this study we hypothesized the involvement of PI3K/AKT/FOXO pathway in BITC-induced apoptosis.
Experimental Design: Mice were implanted BxPC-3 tumor xenografts and orally gavaged with 12 μmol BITC. Plasma and tumor BITC concentration was estimated by liquid chromatography/tandem mass spectrometry. BxPC-3 and PanC-1 cells were used to elucidate PI3K/AKT/FOXO pathway. Electrophoretic mobility shift assay (EMSA), DNA binding activity, immunofluorescence, and gene transfection were used to delineate the mechanism.
Results: BITC-treated mice showed 43% less tumor growth as compared with control mice and correlated well with the therapeutic concentrations of 6.5 μmol/L BITC achieved in plasma and 7.5 μmol/g BITC in tumor tissue. Western blot analyses and immunohistochemistry revealed that tumors from BITC-treated mice showed reduced phosphorylation of PI3K, AKT, PDK1, mTOR, FOXO1, and FOXO3a and increased apoptosis. Complementing our in vivo results, we made similar observations in a dose- and time-dependent manner in BITC-treated BxPC-3 and Panc-1 cells. Binding of FOXO1 with 14-3-3 proteins was also reduced drastically by BITC treatment indicating nuclear retention of FOXO1 and this observation was further confirmed with EMSA, immunofluorescence, DNA binding, and upregulation of FOXO-responsive proteins Bim, p27, and p21 in BxPC-3 cells. Overexpression of AKT by transient transfection significantly blocked the modulation of FOXO proteins and protected the cells from BITC-mediated apoptosis and growth suppression.
Conclusions: Our results provide convincing evidence on the involvement of PI3K/AKT/FOXO pathway in BITC-mediated pancreatic tumor growth suppression. Clin Cancer Res; 17(7); 1784–95. ©2011 AACR.
A Novel HSP90 Inhibitor Delays Castrate-Resistant Prostate Cancer without Altering Serum PSA Levels and Inhibits Osteoclastogenesis
Authors: Lamoureux Francois , Thomas Christian , Yin Min-Jean , Kuruma Hidetoshi , Fazli Ladan , Gleave Martin E. , Zoubeidi Amina 
Published: February 2011

Abstract
Purpose: Prostate cancer responds initially to antiandrogen therapies; however, progression to castration-resistant disease frequently occurs. Therefore, there is an urgent need for novel therapeutic agents that can prevent the emergence of castrate-resistant prostate cancer (CRPC). HSP90 is a molecular chaperone involved in the stability of many client proteins including Akt and androgen receptor (AR). 17-Allylamino-17-demethoxy-geldanamycin (17-AAG) has been reported to inhibit tumor growth in various cancers; however, it induces tumor progression in the bone microenvironment.
Methods: Cell growth, apoptosis, and AR transactivation were examined by crystal violet assay, flow cytometric, and luciferase assays, respectively. The consequence of HSP90 therapy in vivo was evaluated in LNCaP xenograft model. The consequence of PF-04928473 therapy on bone metastasis was studied using an osteoclastogenesis in vitro assay.
Results: PF-04928473 inhibits cell growth in a panel of prostate cancer cells, induces cell-cycle arrest at sub-G1, and leads to apoptosis and increased caspase-3 activity. These biological events were accompanied by decreased activation of Akt and Erk as well as decreased expression of Her2, and decreased AR expression and activation in vitro. In contrast to 17-AAG, PF-04928473 abrogates RANKL-induced osteoclast differentiation by affecting NF-κB activation and Src phosphorylation. Finally, PF-04929113 inhibited tumor growth and prolonged survival compared with controls. Surprisingly, PF-04929113 did not reduce serum prostate-specific antigen (PSA) levels in vivo; in parallel, these decrease in tumor volume.
Conclusion: These data identify significant anticancer activity of PF-04929113 in CRPC but suggest that serum PSA may not prove useful as pharmacodynamic tool for this drug. Clin Cancer Res; 17(8); 2301–13. ©2011 AACR.
Abstract 1001: Effects of matrix compositions on the development of breast acini and ducts in a 3D in-vitro culture model
Authors: Swamydas Muthulekha , Eddy Jill , Burg Karen L. , Dréau Didier 
Published: February 2011

Abstract
Background: Epithelial cells of the breast respond to cues from the stromal components and develop into polarized and highly organized functional acinar and ductal structures. Extracellular matrix components and increased stiffness in particular have been shown to promote breast cancer. The stroma - cell interactions that determine the cellular organization and differentiation are in part reproduced in a 3D environment. Whether alterations of the microenvironment in 3D cultures could mimic phenotypic alterations observed during breast cancer progression remain to be fully determined. Here we present the effects of various stroma physical compositions on the ability of heterotypic 3D cultures of epithelial and mesenchymal stem cells to organize into acinar and tubular structures.
Material & Methods: The normal murine mammary gland (NMuMG) cells were cultured either alone or in combination (30:70) with mouse mesenchymal stem cells (D1), in 3D cell culture conditions generated by agarose, collagen and Matrigel® alone or a combination thereof. After 3-5 days in culture, cell distribution, organization and the presence of acinus-like and tubule-like structures were determined.
Results: By immunohistochemistry, NMuMG cells co-cultured with D1 cells were shown to form acinar structures with the NMuMG epithelial cells surrounding a lumen composed of dead cells whereas the D1 cells were mostly peripheral. Immuno-staining for laminin indicated the presence of basement membrane when NMuMG cells were grown in Matrigel® alone or co-cultured with D1 cells in a combination of Matrigel® and collagen I. The number of acinar structures was significantly higher in cultures grown in combination of agarose with Matrigel® or collagen I when compared to the cultures grown in Matrigel® or collagen I alone (P&lt;0.05). No tubular structures were formed when agarose was included in the matrix, regardless of the combination. In Matrigel® but not in collagen I/ Matrigel® microenvironment the number of tubular structures was significantly increased in NMuMG /D1 co-culture when compared to culture of NMuMG cells alone (P&lt;0.05).
Conclusion: These results indicate that the physical and biochemical properties of the matrix and cellular composition alter the organization of the mammary gland. Furthermore, they underline the likely critical role of the extracellular matrix in breast cancer progression.
Supported by grants from the Department of Defense Era of Hope Program and the National Science Foundation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1001.