bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoscreening of the extracellular proteome of colorectal cancer cells
Authors: Klein-Scory Susanne , Kübler Salwa , Diehl Hanna , Eilert-Micus Christina , Reinacher-Schick Anke , Stühler Kai , Warscheid Bettina , Meyer Helmut E , Schmiegel Wolff , Schwarte-Waldhoff Irmgard 
Published: February 2010

Abstract

Background
The release of proteins from tumors can trigger an immune response in cancer patients involving T lymphocytes and B lymphocytes, which results in the generation of antibodies to tumor-derived proteins. Many studies aim to use humoral immune responses, namely autoantibody profiles, directly, as clinical biomarkers. Alternatively, the antibody immune response as an amplification system for tumor associated alterations may be used to indicate putative protein biomarkers with high sensitivity. Aiming at the latter approach we here have implemented an autoantibody profiling strategy which particularly focuses on proteins released by tumor cells in vitro: the so-called secretome.

Methods
For immunoscreening, the extracellular proteome of five colorectal cancer cell lines was resolved on 2D gels, immobilized on PVDF membranes and used for serological screening with individual sera from 21 colorectal cancer patients and 24 healthy controls. All of the signals from each blot were assigned to a master map, and autoantigen candidates were defined based of the pattern of immunoreactivities. The corresponding proteins were isolated from preparative gels, identified by MALDI-MS and/or by nano-HPLC/ESI-MS/MS and exemplarily confirmed by duplex Western blotting combining the human serum samples with antibodies directed against the protein(s) of interest.

Results
From 281 secretome proteins stained with autoantibodies in total we first defined the "background patterns" of frequently immunoreactive extracellular proteins in healthy and diseased people. An assignment of these proteins, among them many nominally intracellular proteins, to the subset of exosomal proteins within the secretomes revealed a large overlap. On this basis we defined and consequently confirmed novel biomarker candidates such as the extreme C-terminus of the extracellular matrix protein agrin within the set of cancer-enriched immunorectivities.

Conclusions
Our findings suggest, first, that autoantibody responses may be due, in large part, to cross-presentation of antigens to the immune system via exosomes, membrane vesicles released by tumor cells and constituting a significant fraction of the secretome. In addition, this immunosecretomics approach has revealed novel biomarker candidates, some of them secretome-specific, and thus serves as a promising complementary tool to the frequently reported immunoproteomic studies for biomarker discovery.
Microarray analysis of DNA damage repair gene expression profiles in cervical cancer cells radioresistant to 252Cf neutron and X-rays
Authors: Qing Yi , Yang Xue-Qin , Zhong Zhao-Yang , Lei Xin , Xie Jia-Yin , Li Meng-Xia , Xiang De-Bing , Li Zeng-Peng , Yang Zhen-Zhou , Wang Ge , Wang Dong 
Published: February 2010

Abstract

Background
The aim of the study was to obtain stable radioresistant sub-lines from the human cervical cancer cell line HeLa by prolonged exposure to 252Cf neutron and X-rays. Radioresistance mechanisms were investigated in the resulting cells using microarray analysis of DNA damage repair genes.

Methods
HeLa cells were treated with fractionated 252Cf neutron and X-rays, with a cumulative dose of 75 Gy each, over 8 months, yielding the sub-lines HeLaNR and HeLaXR. Radioresistant characteristics were detected by clone formation assay, ultrastructural observations, cell doubling time, cell cycle distribution, and apoptosis assay. Gene expression patterns of the radioresistant sub-lines were studied through microarray analysis and verified by Western blotting and real-time PCR.

Results
The radioresistant sub-lines HeLaNR and HeLaXR were more radioresisitant to 252Cf neutron and X-rays than parental HeLa cells by detecting their radioresistant characteristics, respectively. Compared to HeLa cells, the expression of 24 genes was significantly altered by at least 2-fold in HeLaNR cells. Of these, 19 genes were up-regulated and 5 down-regulated. In HeLaXR cells, 41 genes were significantly altered by at least 2-fold; 38 genes were up-regulated and 3 down-regulated.

Conclusions
Chronic exposure of cells to ionizing radiation induces adaptive responses that enhance tolerance of ionizing radiation and allow investigations of cellular radioresistance mechanisms. The insights gained into the molecular mechanisms activated by these "radioresistance" genes will lead to new therapeutic targets for cervical cancer.
Lipophilic aroylhydrazone chelator HNTMB and its multiple effects on ovarian cancer cells
Authors: Kim Kyu Kwang , Lange Thilo S , Singh Rakesh K , Brard Laurent 
Published: February 2010

AbstractBackgroundMetal chelators have gained much attention as potential anti-cancer agents. However, the effects of chelators are often linked solely to their capacity to bind iron while the potential complexation of other trace metals has not been fully investigated. In present study, we evaluated the effects of various lipophilic aroylhydrazone chelators (AHC), including novel compound HNTMB, on various ovarian cancer cell lines (SKOV-3, OVCAR-3, NUTU-19).MethodsCell viability was analyzed via MTS cytotoxicity assays and NCI60 cancer cell growth screens. Apoptotic events were monitored via Western Blot analysis, fluorescence microscopy and TUNEL assay. FACS analysis was carried out to study Cell Cycle regulation and detection of intracellular Reactive Oxygen Species (ROS)ResultsHNTMB displayed high cytotoxicity (IC50 200-400 nM) compared to previously developed AHC (oVtBBH, HNtBBH, StBBH/206, HNTh2H/315, HNI/311; IC50 0.8-6 μM) or cancer drug Deferoxamine, a hexadentate iron-chelator (IC50 12-25 μM). In a NCI60 cancer cell line screen HNTMB exhibited growth inhibitory effects with remarkable differences in specificity depending on the cell line studied (GI50 10 nM-2.4 μM). In SKOV-3 ovarian cancer cells HNTMB treatment led to chromatin fragmentation and activation of the extrinsic and intrinsic pathways of apoptosis with specific down-regulation of Bcl-2. HNTMB caused delayed cell cycle progression of SKOV-3 through G2/M phase arrest. HNTMB can chelate iron and copper of different oxidation states. Complexation with copper lead to high cytotoxicity via generation of reactive oxygen species (ROS) while treatment with iron complexes of the drug caused neither cytotoxicity nor increased ROS levels.ConclusionsThe present report suggests that both, non-complexed HNTMB as a chelator of intracellular trace-metals as well as a cytotoxic HNTMB/copper complex may be developed as potential therapeutic drugs in the treatment of ovarian and other solid tumors.
Hepatitis B and liver cancer knowledge and practices among healthcare and public health professionals in China: a cross-sectional study
Authors: Chao Jonathan , Chang Ellen T , So Samuel KS 
Published: February 2010

Abstract

Background
Chronic hepatitis B virus (HBV) infection is the leading cause of liver disease and liver cancer and a major source of health-related discrimination in China. To better target HBV detection and prevention programs, it is necessary to assess existing HBV knowledge, educational resources, reporting, and preventive practices, particularly among those health professionals who would be responsible for implementing such programs.

Methods
At the China National Conference on the Prevention and Control of Viral Hepatitis on April 26-29, 2004, the Asian Liver Center at Stanford University partnered with the China Foundation for Hepatitis Prevention and Control to distribute a voluntary written questionnaire to Chinese healthcare and public health professionals from regional and provincial Chinese Centers for Disease Control and Prevention, health departments, and medical centers. Correct responses to survey questions were summed into a total knowledge score, and multivariate linear regression was used to compare differences in the score by participant characteristics.

Results
Although the median score was 81% correct, knowledge about HBV was inadequate, even among such highly trained health professionals. Of the 250 participants who completed the survey, 34% did not know that chronic HBV infection is often asymptomatic and 29% did not know that chronic HBV infection confers a high risk of cirrhosis, liver cancer, and premature death. Furthermore, 34% failed to recognize all the modes of HBV transmission and 30% did not know the importance of the hepatitis B vaccine in preventing liver disease. Respondents who reported poorer preventive practices, such as not having personally been tested for HBV and not routinely disposing of used medical needles, scored significantly lower in HBV knowledge than those who reported sound preventive practices. Of note, 38% of respondents reported positive HBsAg results to patients' employers and 25% reported positive results to patients' schools, thereby subjecting those with positive results to potential discriminatory practices.

Conclusions
These results indicate that there is a need for development of effective educational programs to improve HBV knowledge among health professionals and the general public to avoid missed vaccination opportunities, reduce misconceptions, and eliminate discrimination based on chronic hepatitis B in China.
Systems genetics analyses predict a transcription role for P2P-R: Molecular confirmation that P2P-R is a transcriptional co-repressor
Authors: Peidis Philippos , Giannakouros Thomas , Burow Matthew E , Williams Robert W , Scott Robert E 
Published: February 2010

Abstract

Background
The 250 kDa P2P-R protein (also known as PACT and Rbbp6) was cloned over a decade ago and was found to bind both the p53 and Rb1 tumor suppressor proteins. In addition, P2P-R has been associated with multiple biological functions, such as mitosis, mRNA processing, translation and ubiquitination. In the current studies, the online GeneNetwork system was employed to further probe P2P-R biological functions. Molecular studies were then performed to confirm the GeneNetwork evaluations.

Results
GeneNetwork and associated gene ontology links were used to investigate the coexpression of P2P-R with distinct functional sets of genes in an adipocyte genetic reference panel of HXB/BXH recombinant strains of rats and an eye genetic reference panel of BXD recombinant inbred strains of mice. The results establish that biological networks of 75 and 135 transcription-associated gene products that include P2P-R are co-expressed in a genetically-defined manner in rat adipocytes and in the mouse eye, respectively. Of this large set of transcription-associated genes, >10% are associated with hormone-mediated transcription. Since it has been previously reported that P2P-R can bind the SRC-1 transcription co-regulatory factor (steroid receptor co-activator 1, [Ncoa1]), the possible effects of P2P-R on estrogen-induced transcription were evaluated. Estrogen-induced transcription was repressed 50-70% by the transient transfection of P2P-R plasmid constructs into four different cell types. In addition, knockdown of P2P-R expression using an antisense oligonucleotide increased estrogen-mediated transcription. Co-immunoprecipitation assays confirmed that P2P-R interacts with SRC-1 and also demonstrated that P2P-R interacts with estrogen receptor α.

Conclusions
The findings presented in this study provide strong support for the value of systems genetics, especially GeneNetwork, in discovering new functions of genes that can be confirmed by molecular analysis. More specifically, these data provide evidence that the expression of P2P-R co-varies in a genetically-defined manner with large transcription networks and that P2P-R can function as a co-repressor of estrogen-dependent transcription.
Lacosamide
Authors: Cada Dennis J. , Levien Terri L. , Baker Danial E. 
Published: February 2010

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing inservices. A comprehensive target drug utilization evaluation (DUE) is also provided each month. With a subscription, the monographs are sent in print and are also available online. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The June 2009 monograph topics are everolimus; Japanese encephalitis vaccine, inactivated; inhaled insulin; pitavastatin; and dabigatran etexilate. The DUE is on plerixafor.
New distributional records from central-eastern Madagascar and patterns of morphological variation in the endangered shrew tenrec Microgale jobihely (Afrosoricida: Tenrecidae)
Authors: Soarimalala Voahangy , Raheriarisena Martin , Goodman Steven M. 
Published: February 2010

Abstract

Microgale jobihely (Afrosoricida: Tenrecidae) was described in 2006 based on 12 specimens from the southwestern flank of Tsaratanana Massif in northern Madagascar. This species is considered Endangered by the IUCN. During small mammal surveys conducted in central-eastern Madagascar within the Ambatovy Forest between June 2007 and February 2009, six specimens allocated to M. jobihely were collected. This site is 485 km southeast of the holotype locality and rests on ultrabasic soils associated with nickel and cobalt deposits. Morphological studies of the Ambatovy and Tsaratanana material provide insights into patterns of variation in this taxon. Notable size variation occurs between the northern and southern populations, as well as differences in craniodental morphology. A portion of the Ambatovy site will be cleared as a result of mineral exploitation and even with the discovery of a second population of this taxon, its conservation status remains Endangered.
Species limits and distribution of the Malagasy carnivoran genus Eupleres (Family Eupleridae)
Authors: Goodman Steven M. , Helgen Kristofer M. 
Published: February 2010

Abstract
A review was conducted of members of the endemic Malagasy carnivoran genus Eupleres (family Eupleridae) based on published and unpublished records and museum specimens. Classically, one species has been recognized in this poorly known genus – E. goudotii, divided into two geographical forms with non-overlapping distributions: E. g. goudotii distributed in the mesic forests of the east and E. g. major found in the dry areas of the northwest. Drawing on external and craniodental comparisons, we demonstrate that these two forms are highly distinctive morphologically and can be readily distinguished from each another. Furthermore, there is some evidence that they both can occur on the slopes of Montagne d'Ambre in the far north of the island. On this basis, we recognize these taxa as distinct species, E. goudotii and E. major.
Embrittlement Correlation Method for the Japanese Reactor Pressure Vessel Materials
Authors: Soneda Naoki , Dohi Kenji , Nomoto Akiyoshi , Nishida Kenji , Ishino Shiori 
Published: February 2010

Abstract
A new embrittlement correlation method developed for the Japanese reactor pressure vessel (RPV) steels is presented. The Central Research Institute of Electric Power Industry and the Japanese electric utilities conducted a project to develop a new embrittlement correlation method for the Japanese RPV steels based on the understandings on the mechanisms of the RPV embrittlement. In addition to the information from the literatures, we generated new information by characterizing the microstructural changes in the surveillance materials of the Japanese commercial reactors. We found that in low Cu materials, solute atom clusters containing little or no Cu atoms are formed at relatively low fluence of 3×1019 n/cm2, E&gt;1 MeV. The volume fraction of the solute atom clusters has a good correlation with the Charpy transition temperature shift regardless of the Cu content. We also found that the microstructure of the boiling water reactor surveillance material is different from that of the archive material irradiated in material testing reactor. The understandings on the RPV embrittlement mechanisms were formulated using a set of rate equations, and the coefficients of the equations were optimized using the ΔRTNDT values of the Japanese surveillance database. This method considers the effect of neutron flux. Only one set of coefficients was developed, and they are independent of the product form. Predictions of the new embrittlement correlation method were compared with those of the recent U.S. correlation method as well as the U.S. surveillance data. The comparison shows the characteristics of the present method.
Are ACL Injuries Related to Perceived Fatigue in Female Skiers?
Authors: Ruedl G. , Schranz A. , Fink C. , Pocecco E. , Nachbauer W. , Burtscher M. 
Published: February 2010

Abstract
In alpine skiing, knee injuries show marked sex differences, as female recreational skiers have a twofold greater incidence of knee injuries and a threefold higher anterior cruciate ligament (ACL) injury risk than male skiers. General preventive recommendations to reduce the incidence of ski injuries include avoiding fatigue. However, no study has yet examined to which extent ACL injuries in female recreational skiers are related to perceived fatigue. Therefore, 68 ACL injured female skiers and 136 matched controls were interviewed about skiing time and perception of fatigue in legs and the whole body at the time point of accident and questioning, respectively. In addition, skiing ability, self estimated fitness level, quantity and quality of breaks per run, sleeping quality, and group skiing and skill level of group members have been recorded. Patients and controls differ significantly regarding the duration of skiing as about 81 % of ACL injuries occurred within the first 3 h (odds ratio=4.4; P&lt;0.001). In patients about 71 % and in controls about 27 % felt no fatigue or a trace of fatigue in their legs at the time of injury and questioning, respectively (P&lt;0.001) . No other factors showed a significant difference. Therefore, fatigue seems no major risk factor for an ACL injury in female recreational skiing.
Simulation-Based Maximum Likelihood Median Pragmatic A-Basis and B-Basis Statistical Tolerance Limits Given Fatigue Datum Values with No Censoring or with Potential or Actual Type I Censoring
Authors: Little R. E. 
Published: February 2010

Abstract
This technical note introduces the author’s simulation-based maximum likelihood median pragmatic A-basis or B-basis statistical tolerance limit calculation methodology. It presents websites that provide exemplar outputs of microcomputer programs that employ this methodology to compute these statistical tolerance limits given (i) replicate Weibull and loge-normal fatigue life datum values pertaining to a material without an endurance limit and (ii) s-N data with either linear and quadratic models pertaining to a material without an endurance limit or with a two-segment straight-line model pertaining to a material with an endurance limit.
A systematic approach for model verification: application on seven published activated sludge models
Authors: Hauduc H. , Rieger L. , Takács I. , Héduit A. , Vanrolleghem P. A. , Gillot S. 
Published: February 2010

Abstract
The quality of simulation results can be significantly affected by errors in the published model (typing, inconsistencies, gaps or conceptual errors) and/or in the underlying numerical model description. Seven of the most commonly used activated sludge models have been investigated to point out the typing errors, inconsistencies and gaps in the model publications: ASM1; ASM2d; ASM3; ASM3 + Bio-P; ASM2d + TUD; New General; UCTPHO+. A systematic approach to verify models by tracking typing errors and inconsistencies in model development and software implementation is proposed. Then, stoichiometry and kinetic rate expressions are checked for each model and the errors found are reported in detail. An attached spreadsheet (see http://www.iwaponline.com/wst/06104/0898.pdf) provides corrected matrices with the calculations of all stoichiometric coefficients for the discussed biokinetic models and gives an example of proper continuity checks.
Circulating nucleic acids as a new diagnostic tool
Authors: Urbanova Marketa , Plzak Jan , Strnad Hynek , Betka Jan 
Published: February 2010

AbstractThe discovery of circulating nucleic acids in the 1940s opened up new possibilities for the non-invasive detection, monitoring and screening of various human disorders. Several tumour markers that enable early cancer detection or tumour behaviour prediction have been detected in the plasma of cancer patients. Maternal plasma analysis can be used to detect certain fetal abnormalities, with the quantification of cell-free nucleic acids used to screen for several pregnancy-associated disorders. Some other applications are in transplant monitoring and graft rejection assessment, and in certain medical emergencies such as trauma and burn severity stratification. Many studies have yielded promising results in this field, but the techniques have yet to be applied in routine clinical practice. Large-scale studies using similar technologies and a broad spectrum of patients are still needed to verify the results of the various studies.
Inhibitor of differentiation 1 (Id1) promotes cell survival and proliferation of prostate epithelial cells
Authors: Schmidt Michelle , Asirvatham Ananthi , Chaudhary Jaideep 
Published: February 2010

AbstractId1 (inhibitor of differentiation 1) is a member of the bHLH protein family. Consistent with its role in promoting proliferation and inhibiting differentiation, Id1 expression is low or negligible in normal prostate epithelial cells but is high in prostate cancer. Ectopic expression of Id1 in normal prostate epithelial cells could therefore provide a model for understanding early events involved in initiation of prostate cancer. Over-expression of Id1 immortalized but did not transform ventral prostate epithelial cells (Id1-RPE). Immortalization was associated with decreased Cdkn2a, Cdkn1a, androgen receptor and increased Tert expression. Gene expression profiling over successive doublings was used to identify transcriptomic changes involved during immortalization (Tieg, Jun, alpha actin, Klf10, Id2) and in maintaining the immortalized phenotype (Igfbp3, Igfbp5, Mmp2, Tgfb3). Network analysis indicated that Id1 promotes cancer/tumor morphology, cell cycle and epithelial to mesenchymal transition by influencing AP1, tnf, tgfβ, PdgfBB and estradiol pathways. During immortalization, the expression of majority of differentially expressed genes reduced over progressive doublings suggesting a decline in transcriptional regulatory mechanisms. The associated molecular/gene expression profile of Id1-RPE cells provides an opportunity to understand the molecular pathways associated with prostate epithelial cell survival and proliferation.