bluuebunny/crossref_metadata_2025_split huggingface dataset:
Herbal Extract ofWedelia chinensisAttenuates Androgen Receptor Activity and Orthotopic Growth of Prostate Cancer in Nude Mice
Authors: Tsai Chin-Hsien , Lin Feng-Min , Yang Yu-Chih , Lee Ming-Ting , Cha Tai-Lung , Wu Guan-James , Hsieh Shih-Chuan , Hsiao Pei-Wen 
Published: August 2009

AbstractPurpose: Wedelia chinensis is a common ingredient of anti-inflammatory herbal medicines in Taiwan and southern China. Inflammation is involved in promoting tumor growth, invasion, and metastasis. This study aims to test the biological effects in vivo of W. chinensis extract on prostate cancer.Experimental Design: The in vivo efficacy and mechanisms of action of oral administration of a standardized extract of W. chinensis were analyzed in animals bearing a subcutaneous or orthotopic prostate cancer xenograft.Results: Exposure of prostate cancer cells to W. chinensis extract induced apoptosis selectively in androgen receptor (AR)–positive prostate cancer cells and shifted the proportion in each phase of cell cycle toward G2-M phase in AR-negative prostate cancer cells. Oral herbal extract (4 or 40 mg/kg/d for 24-28 days) attenuated the growth of prostate tumors in nude mice implanted at both subcutaneous (31% and 44%, respectively) and orthotopic (49% and 49%, respectively) sites. The tumor suppression effects were associated with increased apoptosis and lower proliferation in tumor cells as well as reduced tumor angiogenesis. The antitumor effect of W. chinensis extract was correlated with accumulation of the principle active compounds wedelolactone, luteolin, and apigenin in vivo.Conclusion: Anticancer action of W. chinensis extract was due to three active compounds that inhibit the AR signaling pathway. Oral administration of W. chinensis extract impeded prostate cancer tumorigenesis. Future studies of W. chinensis for chemoprevention or complementary medicine against prostate cancer in humans are thus warranted. (Clin Cancer Res 2009;15(17):5435–44)
mTOR Is a Promising Therapeutic Target Both in Cisplatin-Sensitive and Cisplatin-Resistant Clear Cell Carcinoma of the Ovary
Authors: Mabuchi Seiji , Kawase Chiaki , Altomare Deborah A. , Morishige Kenichirou , Sawada Kenjiro , Hayashi Masami , Tsujimoto Masahiko , Yamoto Mareo , Klein-Szanto Andres J. , Schilder Russell J. , Ohmichi Masahide , Testa Joseph R. , Kimura Tadashi 
Published: August 2009

Abstract
Purpose: Mammalian target of rapamycin (mTOR) plays a central role in cell proliferation and is regarded as a promising target in cancer therapy, including for ovarian cancer. This study aimed to examine the role of mTOR as a therapeutic target in clear cell carcinoma of the ovary, which is regarded as an aggressive, chemoresistant histologic subtype.
Experimental Design: Using tissue microarrays of 98 primary ovarian cancers (52 clear cell carcinomas and 46 serous adenocarcinomas), the expression of phospho-mTOR was assessed by immunohistochemistry. Then, the growth-inhibitory effect of mTOR inhibition by RAD001 (everolimus) was examined using two pairs of cisplatin-sensitive parental (RMG1 and KOC7C) and cisplatin-resistant human clear cell carcinoma cell lines (RMG1-CR and KOC7C-CR) both in vitro and in vivo.
Results: Immunohistochemical analysis showed that mTOR was more frequently activated in clear cell carcinomas than in serous adenocarcinomas (86.6% versus 50%). Treatment with RAD001 markedly inhibited the growth of both RMG1 and KOC7C cells both in vitro and in vivo. Increased expression of phospho-mTOR was observed in cisplatin-resistant RMG1-CR and KOC7C-CR cells, compared with the respective parental cells. This increased expression of phospho-mTOR in cisplatin-resistant cells was associated with increased activation of AKT. RMG1-CR and KOC7C-CR cells showed greater sensitivity to RAD001 than did parental RMG1 and KOC7C cells, respectively, in vitro and in vivo.
Conclusion: mTOR is frequently activated in clear cell carcinoma and can be a promising therapeutic target in the management of clear cell carcinoma. Moreover, mTOR inhibition by RAD001 may be efficacious as a second-line treatment of recurrent disease in patients previously treated with cisplatin. (Clin Cancer Res 2009;15(17):5404–13)
Mapatumumab, a Fully Human Agonistic Monoclonal Antibody That Targets TRAIL-R1, in Combination with Gemcitabine and Cisplatin: a Phase I Study
Authors: Mom Constantijne H. , Verweij Jaap , Oldenhuis Corina N.A.M. , Gietema Jourik A. , Fox Norma Lynn , Miceli Renée , Eskens Ferry A.L.M. , Loos Walter J. , de Vries Elisabeth G.E. , Sleijfer Stefan 
Published: August 2009

Abstract
Purpose: To evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of mapatumumab, a fully human monoclonal antibody targeting tumor necrosis factor–related apoptosis–inducing ligand receptor 1 (TRAIL-R1), in combination with gemcitabine and cisplatin.
Experimental Design: Patients with advanced solid tumors received gemcitabine 1,250 mg/m2 i.v. on days 1 and 8 and cisplatin 80 mg/m2 i.v. on day 1 of each 21-day cycle. Escalating mapatumumab doses were administered i.v. every 21 days. Toxicity was evaluated and pharmacokinetic analysis of plasma mapatumumab, gemcitabine, 2-difluoro-2-deoxyuridine, and unbound and total platinum was done. TRAIL-R1 tumor expression was determined immunohistochemically.
Results: Forty-nine patients received mapatumumab (1 mg/kg, n = 4; 3 mg/kg, n = 7; 10 mg/kg, n = 12; 20 mg/kg, n = 13; or 30 mg/kg, n = 13). A median of six cycles (range, 1-48) was administered. The adverse events most commonly observed reflect the toxicity profile of gemcitabine and cisplatin. Dose-limiting toxicities were seen in 3 of 12 patients at 10 mg/kg, consisting of grade 3 transaminitis, neutropenic fever, and grade 4 thrombocytopenia. At 20 mg/kg, 2 of 12 patients had dose-limiting toxicities, including grade 4 thrombocytopenia and grade 4 fatigue. The maximum tolerated dose was not reached. Pharmacokinetic interactions have not been observed. Twelve patients had a partial response, and 25 patients showed stable disease with a median duration of 6 months.
Conclusions: Mapatumumab in combination with gemcitabine and cisplatin is safe and well tolerated at doses up to 30 mg/kg. Further studies on this combination are warranted. (Clin Cancer Res 2009;15(17):5584–90)
Shari'ah Courts and Shari'ah Records: The Application of Islamic Law in the Ottoman State
Authors: Akgündüz Ahmed 
Published: August 2009

AbstractThis essay addresses the Shari'ah courts and Shari'ah records within the broader framework of the application of Islamic law in the Ottoman state. We first explore historical developments before and after Tanzimat as well as a number of developments in the legal guidelines for the preservation of the Shari'ah records. A concise summary is given of the Shari'ah courts, qadis, and the judiciary, including the shaikhu islam and qadaskar. Section two reviews the Shari'ah records, with special attention to the sijil, mahdar, sakk, and hujjah deeds. This section also examines judicial decrees, including their definition, arrangement, qualities, types and models. Linked to this is a discussion of a number of interesting documents in the Shari'ah courts and the Shari'ah records, including ma'ruz and murasalah, as well as documents from other offices that are registered in the records.
Influence of Anomalous Warmer Winter on Statistics of Measured Winter Precipitation Data
Authors: Yamaguchi Satoru , Nakai Sento , Iwamoto Katsushi , Sato Atsushi 
Published: August 2009

Abstract
The winter of 2006/07 in Japan was the warmest in more than 100 years. To evaluate the effects of such an anomalous warmer winter on measured winter precipitation data, gauge-measured precipitation amounts from an area near the Japan Sea coast were compared with values corrected to account for undercatch errors due to the effect of wind. The measured data in this area of Japan are usually 60%–90% of the corrected winter precipitation because of large systematic errors in solid precipitation measurements. However, the measured precipitation for the winter of 2006/07 was much closer to the corrected precipitation because more precipitation than usual fell as rain rather than as snow. Series of precipitation data for 30 winters were corrected by accounting for undercatch errors, and the corrected data were compared with measured data. Both datasets showed the similar tendency that the warmer the winter is, the smaller the winter precipitation is. However, the ratio of the negative relationship between winter precipitation and mean winter temperature, which was calculated using corrected winter precipitation, is 2 times that calculated using measured winter precipitation data. These results suggest the possibility that measured winter precipitation data may show fictitious changes because of changes in the form of precipitation, even though the actual amount may not have changed. Moreover, statistical studies that fail to consider systematic errors in precipitation measurements may possibly result in misinterpretations of the tendency and fluctuation of winter precipitation.
Statistical Downscaling Forecasts for Winter Monsoon Precipitation in Malaysia Using Multimodel Output Variables
Authors: Juneng Liew , Tangang Fredolin T. , Kang Hongwen , Lee Woo-Jin , Seng Yap Kok 
Published: August 2009

Abstract
This paper compares the skills of four different forecasting approaches in predicting the 1-month lead time of the Malaysian winter season precipitation. Two of the approaches are based on statistical downscaling techniques of multimodel ensembles (MME). The third one is the ensemble of raw GCM forecast without any downscaling, whereas the fourth approach, which provides a baseline comparison, is a purely statistical forecast based solely on the preceding sea surface temperature anomaly. The first multimodel statistical downscaling method was developed by the Asia-Pacific Economic Cooperation (APEC) Climate Center (APCC) team, whereas the second is based on the canonical correlation analysis (CCA) technique using the same predictor variables. For the multimodel downscaling ensemble, eight variables from seven operational GCMs are used as predictors with the hindcast forecast data spanning a period of 21 yr from 1983/84 to 2003/04. The raw GCM forecast ensemble tends to have higher skills than the baseline skills of the purely statistical forecast that relates the dominant modes of observed sea surface temperature variability to precipitation. However, the downscaled MME forecasts have higher skills than the raw GCM products. In particular, the model developed by APCC showed significant improvement over the peninsular Malaysia region. This is attributed to the model’s ability to capture regional and large-scale predictor signatures from which the additional skills originated. Overall, the results showed that the appropriate downscaling technique and ensemble of various GCM forecasts could result in some skill enhancement, particularly over peninsular Malaysia, where other models tend to have lower or no skills.
The Maintenance of the Relative Humidity of the Subtropical Free Troposphere
Authors: Couhert Alexandre , Schneider Tapio , Li Juilin , Waliser Duane E. , Tompkins Adrian M. 
Published: August 2009

AbstractThe relative importance of different processes in the water vapor balance of the troposphere is assessed, using high-resolution hindcast data from the ECMWF Integrated Forecast System (IFS) for December–February 1998/99 interpolated to isentropic coordinates. The focus is on elucidating the processes that maintain the relative humidity of the subtropical free troposphere. The dominant drying process in the subtropical free troposphere is cross-isentropic subsidence driven by radiative cooling. In some subtropical regions [e.g., over continents in the Southern (summer) Hemisphere and over western portions of ocean basins in the Northern (winter) Hemisphere], drying by radiative subsidence is partially offset or overcompensated by moistening by cross-isentropic dynamic transport of water vapor from the surface upward (e.g., in convection). Any resultant net drying or moistening of the subtropical free troposphere by cross-isentropic motions is regionally primarily balanced by isentropic mean and eddy transport of water vapor from moister into drier regions. Isentropic transport redistributes water vapor within the subtropics and moderates relative humidity contrasts; however, it does not consistently lead to a substantial net import or export of water vapor into or out of the subtropics.
Changes in Climate at High Southern Latitudes: A Unique Daily Record at Orcadas Spanning 1903–2008
Authors: Zazulie Natalia , Rusticucci Matilde , Solomon Susan 
Published: August 2009

Abstract
The climate observations at Orcadas represent the only southern high-latitude site where data span more than a century, and its daily measurements are presented for the first time in this paper. Although limited to a single station, the observed warming trends are among the largest found anywhere on the earth, facilitating the study of changes in extreme temperatures as well as averages. Factors that may influence Antarctic climate include natural variability; changes in greenhouse gases; and, since about the mid-1970s, the development of the ozone hole. The seasonality of observed warming and its temporal evolution during the century are both key for interpretations of Antarctic climate change. No statistically significant climate trends are observed at Orcadas from 1903 to 1950. However, statistically significant warming is evident at Orcadas throughout all four seasons of the year since 1950. Particularly in austral fall and winter, the warming of the cold extremes (coldest 5% and 10% of days) substantially exceeds the warming of the mean or of the warmest days, providing a key indicator for cold season Antarctic climate change studies. Trends in the summer season means and extremes since 1970 are approximately twice as large as those observed earlier, supporting suggestions of additional regional warming in that season because of the effects of ozone depletion on the circulation. Further, in the spring and summer seasons, significant mean warming also occurred prior to the development of the Antarctic ozone hole (i.e., 1950–70), supporting an important role for processes other than ozone depletion, such as greenhouse gas increases, for the climate changes.
Characterizing Subdiurnal Extreme Precipitation in the Midwestern United States
Authors: Hitchens Nathan M. , Trapp Robert J. , Baldwin Michael E. , Gluhovsky Alexander 
Published: August 2009

Abstract
This research establishes a methodology to quantify the characteristics of convective cloud systems that produce subdiurnal extreme precipitation. Subdiurnal extreme precipitation events are identified by examining hourly precipitation data from 48 rain gauges in the midwestern United States during the period 1956–2005. Time series of precipitation accumulations for 6-h periods are fitted to the generalized Pareto distribution to determine the 10-yr return levels for the stations. An extreme precipitation event is one in which precipitation exceeds the 10-yr return level over a 6-h period. Return levels in the Midwest vary between 54 and 93 mm for 6-h events. Most of the precipitation contributing to these events falls within 1–2 h. Characteristics of the precipitating systems responsible for the extremes are derived from the National Centers for Environmental Prediction stage II and stage IV multisensor precipitation data. The precipitating systems are treated as objects that are identified using an automated procedure. Characteristics considered include object size and the precipitation mean, variance, and maximum within each object. For example, object sizes vary between 96 and 34 480 km2, suggesting that a wide variety of convective precipitating systems can produce subdiurnal extreme precipitation.
Assessment of Drought due to Historic Climate Variability and Projected Future Climate Change in the Midwestern United States
Authors: Mishra Vimal , Cherkauer Keith A. , Shukla Shraddhanand 
Published: August 2009

Abstract
Understanding the occurrence and variability of drought events in historic and projected future climate is essential to managing natural resources and setting policy. The Midwest region is a key contributor in corn and soybean production, and the occurrence of droughts may affect both quantity and quality of these crops. Soil moisture observations play an essential role in understanding the severity and persistence of drought. Considering the scarcity of the long-term soil moisture datasets, soil moisture observations in Illinois have been one of the best datasets for studies of soil moisture. In the present study, the authors use the existing observational dataset and then reconstruct long-term historic time series (1916–2007) of soil moisture data using a land surface model to study the effects of historic climate variability and projected future climate change on regional-scale (Illinois and Indiana) drought. The objectives of this study are to (i) estimate changes and trends associated with climate variables in historic climate variability (1916–2007) and in projected future climate change (2009–99) and (ii) identify regional-scale droughts and associated severity, areal extent, and temporal extent under historic and projected future climate using reconstructed soil moisture data and gridded climatology for the period 1916–2007 using the Variable Infiltration Capacity (VIC) model. The authors reconstructed the soil moisture for a long-term (1916–2007) historic time series using the VIC model, which was calibrated for monthly streamflow and soil moisture at eight U.S. Geological Survey (USGS) gauge stations and Illinois Climate Network’s (ICN) soil moisture stations, respectively, and then it was evaluated for soil moisture, persistence of soil moisture, and soil temperature and heat fluxes. After calibration and evaluation, the VIC model was implemented for historic (1916–2007) and projected future climate (2009–99) periods across the study domain. The nonparametric Mann–Kendall test was used to estimate trends using the gridded climatology of precipitation and air temperature variables. Trends were also estimated for annual anomalies of soil moisture variables, snow water equivalent, and total runoff using a long-term time series of the historic period. Results indicate that precipitation, minimum air temperature, total column soil moisture, and runoff have experienced upward trends, whereas maximum air temperature, frozen soil moisture, and snow water equivalent experienced downward trends. Furthermore, the decreasing trends were significant for the frozen soil moisture in the study domain. The results demonstrate that retrospective drought periods and their severity were reconstructed using model-simulated data. Results also indicate that the study region is experiencing reduced extreme and exceptional droughts with lesser areal extent in recent decades.
Relation of Soluble Endothelial Protein C Receptor and Cytokines After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Azik Fatih Mehmet , Ertem Mehmet , Ileri Talia , Ince Elif Unal , Uysal Zumrut , Egin Yonca , Akar Nejat 
Published: August 2009

Aim: The objective of this study was to elucidate the effects of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), interleukin 2 (IL-2), interleukin 6 (IL-6), and interleukin 8 (IL-8) on the expression of soluble endothelial protein C receptor (sEPCR) in the pathogenesis of thrombotic complications after hematopoietic stem cell transplantation (HSCT). Methods: The relationship between plasma concentrations of proinflammatory cytokines (TNF-α, IL-1β, IL-2, IL-6, and IL-8) and sEPCR was evaluated in 32 consecutive allogeneic hematopoietic stem cell—transplanted patients prior to conditioning regimen and randomly once between +5 and +30 days after transplantation and compared these results with 20 healthy controls. Results: Soluble endothelial protein C receptor levels did not indicate any significant difference between pre- and posttransplantation period, and sEPCR levels showed a significantly negative correlation between IL-6 and IL-8 (sEPCR and IL-6, r = —.43, P < .01; sEPCR and IL-8, r = —.57, P < .01). There was no correlation between sEPCR levels and TNF-α, IL-1β, or IL-2 (sEPCR and TNF-α, r = —.13, P > .05; sEPCR and IL-1β, r = —.1, P ≥ .05; sEPCR and IL-2, r = —.07, P > .05). Conclusions: Our results suggest that the production of sEPCR was not affected by allogeneic HSCT. Soluble endothelial protein C receptor did not show any positive correlation between these proinflammatory cytokines (TNF-α, IL-1β, IL-2, IL-6, and IL-8), on the contrary a significantly negative correlation was determined between sEPCR and either IL-6 or IL-8. This negative correlation may be a protective mechanism in the pathway of protein C activation.
Multiple sclerosis, immunomodulators, and pregnancy outcome: a prospective observational study
Authors: Weber-Schoendorfer C , Schaefer C 
Published: August 2009

Background There is still uncertainty about the management of pregnant women exposed to immunomodulatory therapy for treatment of multiple sclerosis (MS) in pregnancy. Objective To assess the safety of interferon (IFN)-β1a, IFN-β1b, and glatiramer acetate (GA) for treatment of MS during pregnancy. Methods A prospective observational cohort study was performed with patients enrolled through a drug risk assessment by the Teratology Information Service (TIS), Berlin, from 1996 to 2007. Pregnancy outcomes for four groups of women were compared: two exposed groups (IFN, n = 69; GA, n = 31), MS patients without exposure to IFN or GA ( n = 64) and a healthy comparative group ( n = 1556). Results Spontaneous abortion rates were in normal range for all groups except the small subgroup of IFN-β1b exposed ( n = 21), where 28% aborted spontaneously. There were two major birth defects in the GA group (club feet and atrioventricular canal) and none in the IFN cohort. Preterm delivery was not significantly different between exposed cohorts and healthy controls. The adjusted mean birth weight was in normal range in all groups (>3200 g), but newborns exposed to IFN had a significantly lower birth weight. Conclusion Our findings suggest that neither GA nor IFN constitutes a major risk for prenatal developmental toxicity.
Plasmacytoid dendritic cells express TRAIL and induce CD4+ T-cell apoptosis in HIV-1 viremic patients
Authors: Stary Georg , Klein Irene , Kohlhofer Sabine , Koszik Frieder , Scherzer Thomas , Müllauer Leonhard , Quendler Heribert , Kohrgruber Norbert , Stingl Georg 
Published: August 2009

AbstractArtificial Toll-like receptor 7/8 (TLR7/8) ligands can endow plasmacytoid dendritic cells (pDCs) with tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–dependent lytic properties. Keeping in mind that ssRNA serves as natural TLR7/8 ligand, we searched for TRAIL-expressing cells in persons infected with HIV and identified TRAIL+ pDCs in HIV-1 viremic persons, but not in nonviremic and healthy persons. TRAIL expression on pDCs was directly correlated with individual viral loads. Conversely, HIV-1 viremia was found to be associated with the up-regulation of the apoptosis-transmitting receptor TRAIL R1 on activated CD4+ T cells. As a consequence, the latter became susceptible to TRAIL-dependent pDC-mediated killing. In contrast, initiation of antiretroviral therapy led to the up-regulation of apoptosis-inhibiting TRAIL R4 on CD4+ T cells, which subsequently became resistant against pDC-mediated cellular injury. Definition of pDCs as killers of CD4+ T cells implies a new mechanism of disease progression in HIV infection.