bluuebunny/crossref_metadata_2025 huggingface dataset:
Profiling neuroendocrine gene expression changes following fadrozole-induced estrogen decline in the female goldfish
Authors: Zhang Dapeng , Popesku Jason T. , Martyniuk Christopher J. , Xiong Huiling , Duarte-Guterman Paula , Yao Linhui , Xia Xuhua , Trudeau Vance L.
Published: June 2009

Teleost fish represent unique models to study the role of neuroestrogens because of the extremely high activity of brain aromatase (AroB; the product of cyp19a1b). Aromatase respectively converts androstenedione and testosterone to estrone and 17β-estradiol (E2). Specific inhibition of aromatase activity by fadrozole has been shown to impair estrogen production and influence neuroendocrine and reproductive functions in fish, amphibians, and rodents. However, very few studies have identified the global transcriptomic response to fadrozole-induced decline of estrogens in a physiological context. In our study, sexually mature prespawning female goldfish were exposed to fadrozole (50 μg/l) in March and April when goldfish have the highest AroB activity and maximal gonadal size. Fadrozole treatment significantly decreased serum E2 levels (4.7 times lower; P = 0.027) and depressed AroB mRNA expression threefold in both the telencephalon ( P = 0.021) and the hypothalamus ( P = 0.006). Microarray expression profiling of the telencephalon identified 98 differentially expressed genes after fadrozole treatment ( q value <0.05). Some of these genes have shown previously to be estrogen responsive in either fish or other species, including rat, mouse, and human. Gene ontology analysis together with functional annotations revealed several regulatory themes for physiological estrogen action in fish brain that include the regulation of calcium signaling pathway and autoregulation of estrogen receptor action. Real-time PCR verified microarray data for decreased (activin-βA) or increased (calmodulin, ornithine decarboxylase 1) mRNA expression. These data have implications for our understanding of estrogen actions in the adult vertebrate brain.
Malignant B Cells Skew the Balance of Regulatory T Cells and TH17 Cells in B-Cell Non-Hodgkin's Lymphoma
Authors: Yang Zhi-Zhang , Novak Anne J. , Ziesmer Steven C. , Witzig Thomas E. , Ansell Stephen M.
Published: June 2009

Using biopsy specimens from patients with B-cell non-Hodgkin's lymphoma, we observed a significantly low frequency of TH17 cells, including several samples with no detectable amount of interleukin (IL)-17–producing cells present in the tumor microenvironment. We found that, in the absence of lymphoma B cells, treatment with IL-1β/IL-6 or lipopolysaccharide (LPS) enhanced IL-17 expression in CD4+ T cells and this enhancement was attenuated when CD4+ T cells were cocultured with lymphoma B cells. Blockade of CD27-CD70 or CD28-CD80/86 interactions by anti-CD70 or anti-CD80/86 antibodies restored LPS-mediated induction of IL-17 expression in CD4+ T cells cocultured with lymphoma B cells. Because a subset of lymphoma B cells express IL-2 and given that IL-2 signaling is critically important in the development of regulatory T (Treg) cells, we tested the role of IL-2 signaling in TH17 cell development. We found that treatment with anti-IL-2 antibody to interrupt IL-2 signaling significantly inhibited Foxp3 expression in CD4+ T cells. In contrast, interruption of IL-2 signaling up-regulated IL-17 expression in CD4+ T cells and restored lymphoma-mediated down-regulation of IL-17–producing cells. Furthermore, the reversal of Treg cell activity by LPS or CpG-A resulted in an enhancement of IL-17–producing cells. Taken together, our study indicated that lymphoma B cells play an important role in skewing the balance between Treg and TH17 cells resulting in the establishment of a profoundly inhibitory tumor microenvironment. [Cancer Res 2009;69(13):5522–30]
The antiproliferative cytostatic effects of a self-activating viridin prodrug
Authors: Smith Adam , Blois Joseph , Yuan Hushan , Aikawa Elena , Ellson Christian , Figueiredo Jose-Luiz , Weissleder Ralph , Kohler Rainer , Yaffe Michael B. , Cantley Lewis C. , Josephson Lee
Published: June 2009

Although viridins like wortmannin (Wm) have long been examined as anticancer agents, their ability to self-activate has only recently been recognized. Here, we describe the cytostatic effects of a self-activating viridin (SAV), which is an inactive, polymeric prodrug. SAV self-activates to generate a bioactive, fluorescent viridin NBD-Wm with a half-time of 9.2 hours. With cultured A549 cells, 10 μmol/L SAV caused growth arrest without inducing apoptosis or cell death, a cytostatic action markedly different from other chemotherapeutic agents (vinblastine, camptothecin, and paclitaxel). In vivo, a SAV dosing of 1 mg/kg once in 48 hours (i.p.) resulted in growth arrest of an A549 tumor xenograft, with growth resuming when dosing ceased. With a peak serum concentration of SAV of 2.36 μmol/L (at 2 hours post i.p. injection), the concentration of bioactive NBD-Wm was 41 nmol/L based on the partial inhibition of neutrophil respiratory burst. Therefore, SAV was present as an inactive prodrug in serum (peak = 2.36 μmol/L), which generated low concentrations of active viridin (41 nmol/L). SAV is a prodrug, the slow release and cytostatic activities of which suggest that it might be useful as a component of metronomic-based chemotherapeutic strategies. [Mol Cancer Ther 2009;8(6):1666–75]
Induction of programmed cell death in ErbB2/HER2-expressing cancer cells by targeted delivery of apoptosis-inducing factor
Authors: Mahmud Hayat , Dälken Benjamin , Wels Winfried S.
Published: June 2009

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein with NADH oxidase activity that has a vital function in healthy cells but is also an important mediator of caspase-independent programmed cell death in stressed and damaged cells. Here, we generated a truncated AIF derivative (AIFΔ100) that lacks the mitochondrial import signal of the protein. Bacterially expressed AIFΔ100 was functionally active and induced cell death on microinjection into Vero cells accompanied by clear signs of apoptosis. For specific targeting to tumor cells, AIFΔ100 was genetically fused to the scFv(FRP5) antibody fragment that recognizes the ErbB2 (HER2) receptor tyrosine kinase frequently overexpressed in many human cancers. Recombinant scFv(FRP5)-AIFΔ100 (5-AIFΔ100) protein and a similar scFv(FRP5)-ETA252-366-AIFΔ100 (5-E-AIFΔ100) molecule harboring in addition the nontoxic translocation domain of Pseudomonas exotoxin A as an endosome escape function displayed binding to ErbB2-expressing cells followed by protein internalization and accumulation in intracellular vesicles. In the presence of the endosomolytic reagent chloroquine 5-E-AIFΔ100 but not the similar 5-AIFΔ100 protein displayed potent cell killing activity, which was strictly dependent on the expression of ErbB2 on the target cell surface. Our results show that recombinant AIF specifically targeted to human cancer cells and delivered into the cytosol has potent cell killing activity, suggesting this molecule as an effector function suitable for the development of humanized immunotoxin-like molecules. [Mol Cancer Ther 2009;8(6):1526–35]
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

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

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

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

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)
Genome Scan, Fine-Mapping, and Candidate Gene Analysis of Non-Syndromic Cleft Lip with or without Cleft Palate Reveals Phenotype-Specific Differences in Linkage and Association Results
Authors: Marazita Mary L. , Lidral Andrew C. , Murray Jeffrey C. , Field L.Leigh , Maher Brion S. , Goldstein McHenry Toby , Cooper Margaret E. , Govil Manika , Daack-Hirsch Sandra , Riley Bridget , Jugessur Astanand , Felix Temis , Morene Lina , Mansilla M.Adela , Vieira Alexandre R. , Doheny Kim , Pugh Elizabeth , Valencia-Ramirez Consuelo , Arcos-Burgos Mauricio
Published: June 2009

Objectives: Non-syndromic orofacial clefts, i.e. cleft lip (CL) and cleft palate (CP), are among the most common birth defects. The goal of this study was to identify genomic regions and genes for CL with or without CP (CL/P). Methods: We performed linkage analyses of a 10 cM genome scan in 820 multiplex CL/P families (6,565 individuals). Significant linkage results were followed by association analyses of 1,476 SNPs in candidate genes and regions, utilizing a weighted false discovery rate (wFDR) approach to control for multiple testing and incorporate the genome scan results. Results: Significant (multipoint HLOD ≥3.2) or genome-wide-significant (HLOD ≥4.02) linkage results were found for regions 1q32, 2p13, 3q27-28, 9q21, 12p11, 14q21-24 and 16q24. SNPs in IRF6 (1q32) and in or near FOXE1 (9q21) reached formal genome-wide wFDR-adjusted significance. Further, results were phenotype dependent in that the IRF6 region results were most significant for families in which affected individuals have CL alone, and the FOXE1 region results were most significant in families in which some or all of the affected individuals have CL with CP. Conclusions: These results highlight the importance of careful phenotypic delineation in large samples of families for genetic analyses of complex, heterogeneous traits such as CL/P.
Methods for Assessing Familial Aggregation: Family History Measures and Confounding in the Standard Cohort, Reconstructed Cohort and Case-Control Designs
Authors: Zimmerman Regina , Pal Deb K. , Tin Adrienne , Ahsan Habibul , Greenberg David A.
Published: June 2009

Objectives: To test whether case-control-based familial aggregation studies produce estimates of risk to relatives that are inherently biased or confounded by age and family size, and to compare case-control-derived estimates with those from the reconstructed cohort method. In addition, we test if the definition of family history affects the accuracy of results obtained from either design. We use simulated data, which allows us to know the true data origin. Methods: We simulated populations of three generation families. Both a dominant genetic disease and a non-genetic disease were present in the population. We compared the effect estimates from different measures of family history with those derived from the actual genetic cause of disease. Results: Effect estimates from family history measures that used multiple family members were more accurate than those derived from measures based on a single relative. Neither family size nor age of family members defining family history were confounders in the case-control design. Conclusion: The case-control and reconstructed cohort designs are equally valid in assessing familial aggregation of disease.
Microtubules and Actin Cytoskeleton of Potentially Pathogenic Basidiomycetous Yeast as Targets for Antifungals
Authors: Kopecká Marie , Gabriel Miroslav
Published: June 2009

Background: The cytoskeleton was investigated as a potential target for the inhibition of cell division in Fellomyces fuzhouensis CBS 8243 related to Cryptococcus neoformans. Methods: Vincristine, vinblastine, paclitaxel, methyl benzimidazole-2-yl carbamate (BCM), thiabendazole, cytochalasins A, B and D and latrunculin A were added to yeast extract peptone dextrose medium containing cells, investigated by phase contrast and fluorescence microscopy, counted in a Bürker chamber and absorbance was measured. Results: Vincristine, vinblastine, paclitaxel, cytochalasins A, B and D transiently blocked proliferation. BCM disrupted microtubules and inhibited mitosis, but F-actin patches and cables persisted and neck-less conidia appeared without stalks. Latrunculin disrupted F-actin, cells became spherical, and stalks and necks degenerated; microtubules persisted, but mitosis, cytokinesis and conidiogenesis were blocked. The combined application of latrunculin and BCM disrupted F-actin and microtubules, and inhibited cells became spherical and did not divide. Conclusions: Microtubules and F-actin are effective targets for permanent inhibition of nuclear and cell division and conidiogenesis by BCM and latrunculin A.
Prevalence and Antimicrobial Resistance Patterns of Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Isolated from Blood Cultures in an Istanbul University Hospital
Authors: Koksal Fatma , Ak Kenan , Kucukbasmaci Omer , Samasti Mustafa
Published: June 2009

Between January 2001 and September 2006, a total of 459 Escherichia coli and 226 Klebsiella pneumoniae strains were isolated from blood samples of patients with bacteremia who were hospitalized at the Istanbul University Cerrahpasa Medical Faculty. Blood cultures were analyzed with the Bactec 9120 system (Becton Dickinson, USA). Antimicrobic resistance of the E. coli or K. pneumoniae strains was determined by the disk diffusion method according to the Clinical and Laboratory Standards Institute criteria. Extended spectrum β-lactamase (ESBL) production was examined with the double-disk synergy test. The percentage of ESBL was 40% (182/459) for E. coli and 49% (111/226) for K. pneumoniae. ESBL-producing E. coli and K. pneumoniae were highly resistant to trimethoprim/sulfamethoxazole (60 and 40.5%), amoxicillin/clavulanic acid (56.5 and 48.6%), ciprofloxacin (57.6 and 35%) and gentamicin (38 and 40.5%), respectively; however, lower resistance rates were found for amikacin (19.7 and 16%) and piperacillin/tazobactam (29.6 and 24%). None of the strains were resistant to imipenem. Our data indicated that prevalence of ESBL-producing E. coli and K. pneumoniae strains isolated from blood cultures is high and antimicrobial resistance increases. Considerable effort should be made to decrease the ESBL-positive organisms.
A Feasibility Study of Weekly Docetaxel with Capecitabine in Ovarian Cancer: A Promising Combination of Two Active Drugs with a Potential for Synergism
Authors: Safra T. , Bernstein Molho R. , Menzcher J. , Inbar M. , Grisaru D. , Levy T.
Published: June 2009

Objectives: To evaluate the safety and efficacy of weekly docetaxel with capecitabine in patients with recurrent/persistent epithelial ovarian cancer (EOC). Patients and Methods: Women treated for recurrent/persistent EOC in our department (January 2004 through December 2005) were recruited into this feasibility study. They received 35 mg/m2 docetaxel on days 1 and 8 and 1,000 mg/m2 capecitabine twice daily on days 1–14 in a 21-day cycle. Results: Nine patients were enrolled. The median age was 64 years (37–80). Time to progression ranged from 1.67 to 11.27 months: 1 had complete response, 3 had partial responses, 4 had stable disease and 1 had disease progression. There was no grade 3 or 4 bone marrow toxicity. Nonhematological toxicity included partial hair loss (n = 4), fatigue (n = 7), hand and foot syndrome (n = 2), diarrhea (n = 5) and fluid retention syndrome (n = 1). Conclusion: There was good antitumor activity but frequent moderate-to-severe nonhematological toxicities when weekly docetaxel and capecitabine were used as second-line therapy for recurrent EOC. Further investigation of this combination is warranted.
Sociology and Beyond: Towards A Deep Sociology
Authors: Clammer John
Published: June 2009

This 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

Debates 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

La 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

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 (>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

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

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.
The Moral Organization of the Professions
Authors: De Vries Raymond , Dingwall Robert , Orfali Kristina
Published: June 2009

Bioethics is a relatively new endeavor, emerging as a discourse distinct from considerations of moral responsibility occurring within the professions of medicine and science. This article uses the `de-centered comparative method' to examine how the emergence and development of bioethics varies across different social and cultural settings. In particular, the article looks at bioethical work in the US and France, exploring these different manifestations of the movement toward external oversight of those working in medicine and the life sciences. Our comparative data demonstrate how pathways of professionalization are shaped by contingent cultural and historical factors. We contrast `demand' and `supply' theories of professionalization and suggest that the increasing prominence of the bioethical occupation is the result of both the professional desires of bioethicists and a concern for the public good.
What Does “Highly Qualified” Mean for Urban Special Educators?
Authors: Williams Shealey Monika , Alvarez Mchatton Patricia , Farmer Jennie
Published: June 2009

In this article, the authors discuss the context of urban special education and the complexities of meeting the demands of standards-based reform in urban settings. The study presented highlights the voices of urban special educators in two large urban school districts as they navigate meeting the demands of teaching students with disabilities, and share their perceptions of their roles and responsibilities as a result of No Child Left Behind Act. Findings reveal several implications for educational policy and areas of future research in teacher quality and workplace conditions for urban special educators.
An Innovative Practitioner Research Model of Continuing Professional Development
Authors: Jindal-Snape D. , Hannah E. , Smith E. , Barrow W. , Kerr C.
Published: June 2009

This article presents an innovative model of Continuing Professional Development (CPD) that has been used in Scotland to encourage research and to develop research skills amongst applied educational (school) psychologists. 1 This is a process-based CPD model rather than the traditional `attendance at CPD workshops' model, leading to active learning and knowledge creation for the professional and the profession. Data collected from educational psychologists and stakeholders suggests that it is very effective but there is room for improvement. The lessons learnt over the 13 years of its operation and through a recently commissioned evaluation will hopefully be of interest to other applied educational psychologists internationally, as well as related professions.
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.
The Incorporation of Income and Leisure in Health State Valuations When the Measure Is Silent: An Empirical Inquiry into the Sound of Silence
Authors: Brouwer Werner B. F. , Grootenboer Saskia , Sendi Pedram
Published: June 2009

Objective . The objective of the present study is to evaluate whether people 1) expect income and leisure to be affected by certain health states, 2) include the effects of ill-health on income and leisure in health state valuations when the measure is silent on both, and 3) what effect this has on these valuations. Data and Methods . A convenience sample of 75 individuals from the general public rated 3 different health states on a visual analogue scale without instruction on the incorporation of income and leisure. Different subgroups were created on the basis of expecting income and leisure to be affected and the indicated incorporation of these effects. Comparative and multivariate analyses were used to analyze the data. Results . The results show that most respondents (69%) did not consider income effects, whereas 61% did consider the effects on leisure. The expected influence of health states on income and leisure differed substantially between respondents. Only the incorporation of leisure proved to be influential in health state valuations. Conclusions . Health state valuation methods that are silent and noninformative regarding leisure and income lead to interrespondent differences regarding how they expect leisure and income to be affected and regarding the inclusion of these effects. This may be especially problematic for leisure if productivity costs are captured at the cost side of the cost-effectiveness ratio.
Engaging China's Nuclear and Missile Threat
Authors: Kumar Neha
Published: June 2009

The relationship between India and China is guided by mistrust and competition, despite their trade dependence and geographical proximity. India is more conscious of China's nuclear and missile modernization because India's forces lack strategic depth against China. China has strategic doctrine, planning and resources, while India lacks in all these. China also helped Pakistan, which is a crucial point for India to note. This article tries to find out how to deal with these gaps at the strategic, military, diplomatic and economic level.
Features of Success in Engineering Design Presentations
Authors: Dannels Deanna P.
Published: June 2009

This study explores design presentations that were graded by engineering faculty in order to assess the distinguishing features of those that were successful. Using a thematic analysis of 17 videotaped, final presentations from a capstone chemical engineering (CHE) course, it explores the rhetorical strategies, oral styles, and organizational structures that differentiate successful and unsuccessful team presentations. The results suggest that successful presenters used rhetorical strategies, oral styles, and organizational structures that illustrated students’ ability to negotiate the real and simulated relational and identity nuances of the design presentation genre—in short, they illustrated students’ relational genre knowledge.
Differences between White Americans and Asian Americans for Social Responsibility, Individual Right and Intentions Regarding Organ Donation
Authors: Hee Sun Park  , Yoon Sook Shin  , Yun Doshik
Published: June 2009

This study examined factors affecting intention to enroll in an organ donor registry and intention to talk to family about organ donation. Participants indicated their views about maintaining body integrity as an individual right and donating organs as a social responsibility. Results showed that the influence of social responsibility on intention to enroll was stronger for white Americans than for Asian Americans. Individual right was negatively associated with intention to enroll among Asian Americans, but not among white Americans. Social responsibility was significant for intention to talk among both white Americans and Asian Americans, but individual right was not significant.
Response Coefficient: A New Concept to Evaluate Ventilation Performance with ''Pulse'' Boundary Conditions
Authors: Xianting Li  , Fenfei Zhu
Published: June 2009

Releasing a ''pulse'' tracer contaminant at a given point, either in the air supply or in the indoor space, and monitoring its transient distribution in a steady-state flow field, allows the performance of the air distribution to be evaluated. Two nondimensional indices have been defined, Response Coefficient to Supply Air (RCSA) and Response Coefficient to Contaminant Source (RCCS), to characterize spatial and temporal distribution under different air distribution patterns. To demonstrate their characteristics a 2D ventilated room was numerically analyzed. The results show that RCSA at each location (except the inlet) and RCCS at each location in the room (except the contaminant source) initially increase, then decrease, and become zero when time is long enough; RCSA ``records'' the characteristics of the flow field. There will be only one maximum response coefficient value under a piston flow field, while under a flow field with recirculation, there will be several, which may be used to evaluate the airflow pattern; RCCS contains information on the contaminant source position under a specific flow field. The relative positions of the contaminant source and the monitoring points determine response curves, which may be used to judge the position of a contaminant source; accumulation of RCSA and RCCS will become constant when time is long enough. The accumulation value of RCSA at any location indoors is 1, while accumulation values of RCCS at different locations differ from each other, but are determined by the relative position of the contaminant source and the location.
A Study on the Application of a Ceiling Plenum Ventilation System in an Apartment House
Authors: Yang Jeong-Hoon , Seok Ho-Tae , Lee Sueng-Jae
Published: June 2009

Currently, an air change rate (0.7 h-1) and spring cooler installation must be considered when building an apartment house in Korea, in order to comply with the Building Standards and the Fire Service Act. In accordance with a series of legal requirements for Korean apartment houses, the improvement of the availability of ceiling space and space for working ease is required in apartments by installing a new ventilation system in the ceiling space to accommodate a spring cooler. In this study, a new ventilation system is suggested, called the ceiling plenum ventilation system. To introduce this system in the residential section of a residential-commercial complex building, a constant air volume system or combination air volume system with a 150 mm supply opening and branch duct must be used. For residential-commercial complex buildings with lower ceilings or for general apartment houses, the effective area of the supply opening of the rooms and the air supply duct at the total heat exchanger side must be increased and a combination air volume system must be used.
Influence of the Convective Surface Transfer Coefficients on the Heat, Air, and Moisture (HAM) Building Performance
Authors: Steskens Paul W.M.H. , Janssen Hans , Rode Carsten
Published: June 2009

Current models to predict heat, air, and moisture (HAM) conditions in buildings assume constant boundary conditions for the temperature and relative humidity of the neighboring air and for the surface heat and moisture transfer coefficients. These assumptions may introduce errors in the predicted HAM conditions. The paper focuses on the influence of the interior surface heat and moisture transfer coefficients, and investigates its effect on the hygrothermal performance. The parameter study showed that the magnitude of the convective surface transfer coefficients has a relatively large influence on the predicted hygrothermal conditions at the surface of a building component and on the heat and vapor exchange with the indoor environment.
A Validation Methodology for Human Behavior Representation Models
Authors: Goerger Simon R. , McGinnis Michael L. , Darken Rudolph P.
Published: June 2009

The Department of Defense (DoD) relies heavily on mathematical models and computer simulations to analyze and acquire new weapon systems. Models and simulations help decision makers understand the differences between systems and provide insights into the implications of weapon system tradeoffs. Given this key role, the credibility of simulations is paramount. For combat models, this is gained through the verification, validation, and accreditation process required of DoD analytical models prior to their use in weapon systems acquisition and other studies. The nature of nondeterministic human behavior makes validation of models of human behavior representation contingent on the judgments of subject matter experts that are routinely acquired using a face validation methodology. In an attempt to better understand the strengths and weaknesses of assessing human behavior representation using experts and the face validation methodology, the authors conducted experiments to identify issues critical to utilizing human experts for the purpose of ascertaining ways to enrich the validation process for models relying on human behavior representation. The research was limited to the behaviors of individuals engaged in close combat in an urban environment. This paper presents the study methodology, data analysis, and recommendations for mitigating attendant problems with validation of human behavior representation models.
Mission Effectiveness and European Airspace: U.S. Air Force CNS/ATM Planning for Future Years
Authors: Wigfield Edward , Connolly Kelly , Morris John , Alshtein Alexander , DeArmon James , Flournoy Richard , Hershey William , James John , Mahoney Paula , Mathieu Jennifer , Maurer John , Ostwald Paul
Published: June 2009

The U.S. Air Force (USAF) uses the term Communication Navigation Surveillance/Air Traffic Management (CNS/ATM) for capabilities that allow its aircraft to use civil airspace and air traffic control services. The resulting ability to interoperate with air traffic control systems around the world supports the USAF's global, multi-faceted mission, but entails great expense in on-board equipage and training. It is important to understand the trade-offs that the USAF must make in assessing the value of specific CNS/ATM capabilities. In this paper, we describe a model-driven analysis to assess mission effectiveness. The analysis is accomplished via a five-step process involving military route generation, simulation of the civilian airspace activity, simulation of delay events for military flights, and evaluation of several figures of merit. The software modules used for these activities were a combination of existing packages and some newly-developed programs. The analysis accounts for planned USAF CNS/ATM capabilities by aircraft type, as well as any airspace and operational restrictions that might be encountered in specific geographic regions when the aircraft does not have the required capabilities. Two layers of interactions are investigated: first, within the USAF enterprise, specifically, between the fighter and tankers assets and, second, between the USAF and civilian ATM.