bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vorinostat enhances the radiosensitivity of a breast cancer brain metastatic cell line grown in vitro and as intracranial xenografts
Authors: Baschnagel Andrew , Russo Andrea , Burgan William E. , Carter Donna , Beam Katie , Palmieri Diane , Steeg Patricia S. , Tofilon Philip , Camphausen Kevin 
Published: June 2009

Abstract
Vorinostat (suberoylanilide hydroxamic acid), a histone deacetylase inhibitor, is currently undergoing clinical evaluation as therapy for cancer. We investigated the effects of vorinostat on tumor cell radiosensitivity in a breast cancer brain metastasis model using MDA-MB-231-BR cells. In vitro radiosensitivity was evaluated using clonogenic assay. Cell cycle distribution and apoptosis was measured using flow cytometry. DNA damage and repair was evaluated using γH2AX. Mitotic catastrophe was measured by immunostaining. Growth delay and intracranial xenograft models were used to evaluate the in vivo tumor radiosensitivity. Cells exposed to vorinostat for 16 hours before and maintained in the medium after irradiation had an increase in radiosensitivity with a dose enhancement factor of 1.57. γH2AX, as an indicator of double-strand breaks, had significantly more foci per cell in the vorinostat plus irradiation group. Mitotic catastrophe, measured at 72 hours, was significantly increased in cells receiving vorinostat plus irradiation. Irradiation of s.c. MDA-MB-231-BR tumors in mice treated with vorinostat resulted in an increase in radiation-induced tumor growth delay. Most importantly, animals with intracranial tumor implants lived the longest after combination treatment. These results indicate that vorinostat enhances tumor cell radiosensitivity in vitro and in vivo. There was a greater than additive improvement in survival in our intracranial model. Combining vorinostat with radiation may be a potential treatment option for patients with breast cancer who develop brain metastases. [Mol Cancer Ther 2009;8(6):1589–95]
Demonstration of the equivalent pharmacokinetic/pharmacodynamic dosing strategy in a multiple-dose study of gefitinib
Authors: Wang Shining , Zhou Qingyu , Gallo James M. 
Published: June 2009

Abstract
The goals of this investigation were to illustrate the use of pharmacokinetic (PK)/pharmacodynamic (PD) modeling strategies in drug development based on a multiple-dose study of gefitinib in a preclinical tumor model. Mice bearing s.c. LN229-wild-type epidermal growth factor receptor or LN229-EGFRvIII mutant (a sensitizing mutation) tumors were administered gefitinib at oral doses of either 55 mg/kg/d p.o. × 15 days or 30 mg/kg/d p.o. × 15 days, respectively, as dictated by the equivalent PK/PD dosing strategy. In each tumor group, gefitinib plasma and tumor concentrations were quantitated, as well as the tumoral amounts of phosphorylated-extracellular signal-regulated kinase 1/2 (pERK), a selected PD end point, and tumor size. The resultant data provided the basis to develop hybrid physiologically based PK/PD/tumor growth models for each tumor type. It was found that the 1.83-fold dose difference administered to the two tumor groups resulted in analogous pERK profiles on both days 1 and 15, and further induced similar antitumor efficacy based on tumor size. In addition, using brain tumor patient PK data linked to the pERK PD model, simulations were conducted to illustrate potential applications of a target tumor model to patients. The simulations provided insight on the relationships between blood-brain barrier penetration, brain tumor gefitinib concentrations, and the extent of inhibition of pERK. The implementation of the PK/PD equivalent dosing strategy offers a new approach to drug development. [Mol Cancer Ther 2009;8(6):1438–47]
Validation of the type 1 insulin-like growth factor receptor as a therapeutic target in renal cancer
Authors: Yuen John S.P. , Akkaya Erdem , Wang Yong , Takiguchi Megumi , Peak Sandra , Sullivan Mark , Protheroe Andrew S. , Macaulay Valentine M. 
Published: June 2009

Abstract
Purpose: Expression of the type 1 insulin-like growth factor receptor (IGF1R) confers adverse prognosis in clear cell renal cell cancer (CC-RCC). We recently showed that IGF1R expression is inhibited by the von Hippel-Lindau (VHL) tumor suppressor, and the IGF1R is up-regulated in CC-RCC, in which VHL is frequently inactivated. We tested the hypothesis that IGF1R up-regulation mediates resistance to cancer therapeutics, evaluating the effects of IGF1R depletion on sensitivity to cytotoxic drugs, which are ineffective in RCC, and the mammalian target of rapamycin (mTOR) inhibitor rapamycin, analogues of which have clinical activity in this tumor.
Experimental Design: This study used CC-RCC cells harboring mutant VHL, and isogenic cells expressing functional VHL. Cells were transfected with nonsilencing control small interfering RNA (siRNA), or with one of two different IGF1R siRNAs. The more potent siRNA was modified by 2′-O-methyl derivatization for in vivo administration.
Results: CC-RCC cells expressing mutant VHL and higher IGF1R were more chemoresistant than cells expressing functional VHL. IGF1R depletion induced apoptosis, blocked cell survival, and sensitized to 5-fluorouracil and etoposide. These effects were significantly greater in CC-RCC cells expressing mutant VHL, supporting the hypothesis that IGF1R up-regulation makes a major contribution to the chemoresistance associated with VHL loss. IGF1R depletion also enhanced sensitivity to mTOR inhibition, at least in part due to suppression of rapamycin-induced Akt activation. Administration of stabilized IGF1R siRNA was shown to sensitize CC-RCC xenografts to rapamycin in vivo.
Conclusion: These data validate IGF1R as a therapeutic target in CC-RCC, and support the evaluation of IGF1R-inhibitory drugs in patients with renal cancer. [Mol Cancer Ther 2009;8(6):1448–59]
Epidermal Growth Factor Receptor–Mediated Membrane Type 1 Matrix Metalloproteinase Endocytosis Regulates the Transition between Invasive versus Expansive Growth of Ovarian Carcinoma Cells in Three-Dimensional Collagen
Authors: Moss Natalie M. , Liu Yueying , Johnson Jeff J. , Debiase Philip , Jones Jonathan , Hudson Laurie G. , Munshi Hidayatullah G. , Stack M. Sharon 
Published: June 2009

Abstract
The epidermal growth factor receptor (EGFR) is overexpressed in ovarian carcinomas and promotes cellular responses that contribute to ovarian cancer pathobiology. In addition to modulation of mitogenic and motogenic behavior, emerging data identify EGFR activation as a novel mechanism for rapid modification of the cell surface proteome. The transmembrane collagenase membrane type 1 matrix metalloproteinase (MT1-MMP, MMP-14) is a major contributor to pericelluar proteolysis in the ovarian carcinoma microenvironment and is subjected to extensive posttranslational regulation. In the present study, the contribution of EGFR activation to control of MT1-MMP cell surface dynamics was investigated. Unstimulated ovarian cancer cells display caveolar colocalization of EGFR and MT1-MMP, whereas EGFR activation prompts internalization via distinct endocytic pathways. EGF treatment results in phosphorylation of the MT1-MMP cytoplasmic tail, and cells expressing a tyrosine mutated form of MT1-MMP (MT1-MMP-Y573F) exhibit defective MT1-MMP internalization. As a result of sustained cell surface MT1-MMP activity, a phenotypic epithelial-mesenchymal transition is observed, characterized by enhanced migration and collagen invasion, whereas growth within three-dimensional collagen gels is inhibited. These data support an EGFR-dependent mechanism for regulation of the transition between invasive and expansive growth of ovarian carcinoma cells via modulation of MT1-MMP cell surface dynamics. (Mol Cancer Res 2009;7(6):809–20)
Sociology and Beyond: Towards A Deep Sociology
Authors: Clammer John 
Published: June 2009

AbstractThis paper explores potential new directions for a sociology linked more to Asian social theory and to new forms of knowledge emerging from ecology and the new social movements than to its older foundations in Western philosophy and conceptions of society. It suggests that there is a route beyond the trajectory of modernist and postmodernist social thinking and it calls into question the anthropocentric, Cartesian and dualistic assumptions of most conventional sociology. It does so by exploring the possible relationships between sociology and the existential issues thrown up by Asian philosophical and religious traditions, and in particular Buddhism, and the in many ways parallel arguments of Deep Ecology. In doing so it calls into question the adequacy of current sociology as a vehicle for addressing fundamental existential questions and in particular the issues of social suffering, the emerging ecological crisis and the alternative conceptions of society generated by many of the new social movements, and suggests ways in which this inadequacy might potentially be resolved.
Sociology and Beyond: The Limits of Loyalty
Authors: Giri Ananta Kumar 
Published: June 2009

AbstractDebates and discussions in an intellectual field help us to come to terms with our existing condition and work towards its needed transformation. Debates and discussions have been very much part of traditions of sociological reflections in India. In the 1950s there was a debate about the 'book view' and 'field view' of studying Indian society in which the works of M. N. Srinivas and Louis Dumont were discussed. A recent debate has arisen on the need for Indian social sciences to overcome their entrenched parochial fixations and be simultaneously interested in fieldwork at home and the world. The article begins with this and discusses the need for Indian social sciences overcome their parochial fixation and simultaneously work with India and the world. This calls for overcoming the limits of loyalty such as uncritical loyalty to nation-state and cultivate a relationship of gratitude to both one's country and the world.
La maqāma – circulation d'un genre : d'al-Harīrī à al-Harizi, de l'arabe à l'hébreu, de l'Est à l'Ouest
Authors: Itzhaki Masha 
Published: June 2009

AbstractLa poésie hébraïque en Espagne, et la poésie profane en particulier, est le produit conjugué de deux sources culturelles extrêmement fortes : la poésie arabe classique d'une part, et, de l'autre, la langue de la Bible. Dans ce contexte particulier d'une ouverture culturelle sans équivoque, on trouve aussi la maqāma. Yehuda Al-Harizi (né en Espagne vers 1165) a ainsi produit un chef-d'œuvre en traduisant les Maqāmāt d'al-Harīrī, sous le titre hébreu de Mahbarot Ittiel (Les cahiers d'Ittiel). Poète, l'essentiel de son oeuvre littéraire se concentre dans le livre de maqāmāt hébraïques originales, intitulé Tahkemoni. L'article traite des questions liées au passage d'une langue à l'autre, d'une culture à l'autre, selon la conception médiévale de l'art de la traduction mais également à travers l'écriture « originale », directement en hébreu.
Characteristics of Precipitation, Cloud, and Latent Heating Associated with the Madden–Julian Oscillation
Authors: Lau K-M. , Wu H-T. 
Published: June 2009

Abstract
This study investigates the evolution of cloud and rainfall structures associated with Madden–Julian oscillation (MJO) using Tropical Rainfall Measuring Mission (TRMM) data. Two complementary indices are used to define MJO phases. Joint probability distribution functions (PDFs) of cloud-top temperature and radar echo-top height are constructed for each of the eight MJO phases. The genesis stage of MJO convection over the western Pacific (phases 1 and 2) features a bottom-heavy PDF, characterized by abundant warm rain, low clouds, suppressed deep convection, and higher sea surface temperature (SST). As MJO convection develops (phases 3 and 4), a transition from the bottom-heavy to top-heavy PDF occurs. The latter is associated with the development of mixed-phase rain and middle-to-high clouds, coupled with rapid SST cooling. At the MJO convection peak (phase 5), a top-heavy PDF contributed by deep convection with mixed-phase and ice-phase rain and high echo-top heights (&gt;5 km) dominates. The decaying stage (phases 6 and 7) is characterized by suppressed SST, reduced total rain, increased contribution from stratiform rain, and increased nonraining high clouds. Phase 7, in particular, signals the beginning of a return to higher SST and increased warm rain. Phase 8 completes the MJO cycle, returning to a bottom-heavy PDF and SST conditions similar to phase 1. The structural changes in rain and clouds at different phases of MJO are consistent with corresponding changes in derived latent heating profiles, suggesting the importance of a diverse mix of warm, mixed-phase, and ice-phase rain associated with low-level, congestus, and high clouds in constituting the life cycle and the time scales of MJO.
Influence of Rainfall Scenario Construction Methods on Runoff Projections
Authors: Mpelasoka Freddie S. , Chiew Francis H. S. 
Published: June 2009

Abstract
The future rainfall series used to drive hydrological models in most climate change impact studies is informed by global climate models (GCMs). This paper compares future runoff projections in ∼11 000 0.25° grid cells across Australia from a daily rainfall–runoff model driven with future daily rainfall series obtained using three simple scaling methods, informed by 14 GCMs. In the constant scaling and daily scaling methods, the historical daily rainfall series is scaled by the relative difference between GCM simulations for the future and historical climates. The constant scaling method scales all the daily rainfall by the same factor, and the daily scaling method takes into account changes in the daily rainfall distribution by scaling the different daily rainfall amounts differently. In the daily translation method, the GCM future daily rainfall series is translated to a 0.25° gridcell rainfall series using the relationship established between the historical GCM-scale rainfall and 0.25° gridcell rainfall data. The daily scaling and daily translation methods generally give higher extreme and annual runoff than the constant scaling method because they take into account the increase in extreme daily rainfall (which generates significant runoff) simulated by the large majority of the GCMs. However, the difference between the mean annual runoff simulated with future daily rainfall series obtained using the constant versus daily scaling methods is generally less than 5%, which is relatively smaller than the range of runoff results from the different GCMs of 30%–40%.
The Ability of the Small Ice Detector (SID-2) to Characterize Cloud Particle and Aerosol Morphologies Obtained during Flights of the FAAM BAe-146 Research Aircraft
Authors: Cotton Richard , Osborne S. , Ulanowski Z. , Hirst E. , Kaye P. H. , Greenaway R. S. 
Published: June 2009

Abstract
The Small Ice Detector mark 2 (SID-2), which was built by the University of Hertfordshire, has been operated by the Met Office on the Facility for Atmospheric Airborne Research (FAAM) BAe-146 aircraft during a large number of flights. The flights covered a wide range of atmospheric conditions, including stratocumulus, altocumulus lenticularis, cirrus, and mixed-phase cumulus clouds, as well as clear-sky flights over the sea and over desert surfaces. SID-2 is a laser scattering device that provides in situ data on cloud particle concentration and size. SID-2 also provides the spatial light scattering data from individual particles to give some information on the particle shape. The advantage of SID-2 is that it can characterize the cloud particle shape for particle sizes less than the resolutions of the more usual commercially available ice crystal imaging probes. The particle shape characteristics enable, for example, small just-nucleated ice particles to be discriminated from supercooled water drops. SID-2 also has an open-path inlet that reduces shattering of large cloud particles compared to other probes that use a tube inlet.
The aim of this paper is to illustrate the capability of SID-2 to count, size, and determine cloud particle and aerosol shape. This is done by comparing the response of SID-2 to water drops, ice particles, and aerosols with that from other standard aircraft-based probes.
Is Polymorphism within eNOS Gene Associated With the Late Onset of Myocardial Infarction? A Pilot Study
Authors: Gluba Anna , Banach Maciej , Rysz Jacek , Piotrowski Grzegorz , Fendler Wojciech , Pietrucha Tadeusz 
Published: June 2009

Introduction Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) is a potent vasodilator. Several polymorphisms in the eNOS gene have been described, some of them being linked with the increased risk of cardiovascular disease, coronary heart disease (CHD), and coronary spasm. Methods and Results We studied 3 polymorphisms within the gene of eNOS (-786T/C, G10T, and 894 G/T) in patients with their first myocardial infarction (MI) younger than 45 years and in healthy volunteers. We found the relation between the occurrence of eNOS 894G allele and the Gensini score, which describes the severity of CHD ( P = .020). Conclusions The fact that first clinical manifestation of MI occurred in G carriers when the atherosclerotic plaque was much more advanced than in T carriers may suggest that wild-type genotype provided a better compensatory mechanisms due to NO synthesis and/or release. The polymorphisms within eNOS gene G10T, 894G/T, and −786T/C were not associated with the increased risk of MI.
Inter-rater reliability of the Top Down Motor Milestone Test: a cross-sectional study
Authors: Jaya Shanker Tedla  , Ganesan Sailakshmi , Katragadda Srinadh 
Published: June 2009

Objective: To assess the inter-rater reliability of the Top Down Motor Milestone Test, which is the first step of the Mobility Opportunities Via Education programme in children with motor disabilities. Design: A cross-sectional study. Setting: Neurosensory Developmental Unit of a tertiary hospital. Subjects: Parents of 21 children with motor disabilities were interviewed and scored on the Top Down Motor Milestone Test. Methods: The subjects were interviewed by one therapist while two other therapists observed the interview procedure. All three therapists were blinded to each other's scores. Results: Inter-rater reliability was analysed for all the 16 subtests using the inter-rater kappa. The pooled kappa was done for the three raters. The standard error and the P-value were also calculated. The value of inter-rater kappa for individual subtests ranged from 0.74 to 0.96. Pooled kappa for the Top Down Motor Milestone Test was 0.88 with standard error 0.06 and P-value50.01. Conclusion: The inter-rater reliability of the Top Down Motor Milestone Test proved to be good for each subtest and for the whole test.
A superior drug carrier – aponeocarzinostatin in partially unfolded state fully protects the labile antitumor enediyne
Authors: Shanmuganathan Aranganathan , Kumar Thallapuranam Krishnaswamy Suresh , Huang Chiy-Mey , Yu Chin , Chin Der-Hang 
Published: June 2009

Abstract

Background
Neocarzinostatin is a potent antitumor drug consisting of an enediyne chromophore and a protein carrier.

Methods
We characterized an intermediate in the equilibrium unfolding pathway of aponeocarzinostatin, using a variety of biophysical techniques including 1-anilino-8-napthalene sulfonate binding studies, size-exclusion fast protein liquid chromatography, intrinsic tryptophan fluorescence, circular dichroism, and 1H-15N heteronuclear single quantum coherence spectroscopy.

Results
The partially unfolded protein is in molten globule-like state, in which ~60% and ~20% tertiary and secondary structure is disrupted respectively. Despite lacking a fully coordinated tertiary structure for assembling a functional binding cleft, the protein in molten globule-like state is still able to fully protect the labile chromophore. Titration of chromophore leads the partially denatured apoprotein to fold into its native state.

Conclusion
These findings bring insight into conserving mechanism of neocarzinostatin under harsh environment, where even the partially denatured apoprotein exhibits protective effect, confirming the superiority of the drug carrier.
The High Throughput Sequence Annotation Service (HT-SAS) – the shortcut from sequence to true Medline words
Authors: Kaczanowski Szymon , Siedlecki Pawel , Zielenkiewicz Piotr 
Published: June 2009

Abstract

Background
Advances in high-throughput technologies available to modern biology have created an increasing flood of experimentally determined facts. Ordering, managing and describing these raw results is the first step which allows facts to become knowledge. Currently there are limited ways to automatically annotate such data, especially utilizing information deposited in published literature.

Results
To aid researchers in describing results from high-throughput experiments we developed HT-SAS, a web service for automatic annotation of proteins using general English words. For each protein a poll of Medline abstracts connected to homologous proteins is gathered using the UniProt-Medline link. Overrepresented words are detected using binomial statistics approximation. We tested our automatic approach with a protein test set from SGD to determine the accuracy and usefulness of our approach. We also applied the automatic annotation service to improve annotations of proteins from Plasmodium bergei expressed exclusively during the blood stage.

Conclusion
Using HT-SAS we created new, or enriched already established annotations for over 20% of proteins from Plasmodium bergei expressed in the blood stage, deposited in PlasmoDB. Our tests show this approach to information extraction provides highly specific keywords, often also when the number of abstracts is limited. Our service should be useful for manual curators, as a complement to manually curated information sources and for researchers working with protein datasets, especially from poorly characterized organisms.