bluuebunny/crossref_metadata_2025_split huggingface dataset:
Skp2 Directs Myc-Mediated Suppression of p27Kip1 yet Has Modest Effects on Myc-Driven Lymphomagenesis
Authors: Old Jennifer B. , Kratzat Susanne , Hoellein Alexander , Graf Steffi , Nilsson Jonas A. , Nilsson Lisa , Nakayama Keiichi I. , Peschel Christian , Cleveland John L. , Keller Ulrich B. 
Published: March 2010

Abstract
The universal cyclin-dependent kinase inhibitor p27Kip1 functions as a tumor suppressor, and reduced levels of p27Kip1 connote poor prognosis in several human malignancies. p27Kip1 levels are predominately regulated by ubiquitin-mediated turnover of the protein, which is marked for destruction by the E3 ubiquitin ligase SCFSkp2 complex following its phosphorylation by the cyclin E–cyclin-dependent kinase 2 complex. Binding of phospho-p27Kip1 is directed by the Skp2 F-box protein, and this is greatly augmented by its allosteric regulator Cks1. We have established that programmed expression of c-Myc in the B cells of Eμ-Myc transgenic mice triggers p27Kip1 destruction by inducing Cks1, that this response controls Myc-driven proliferation, and that loss of Cks1 markedly delays Myc-induced lymphomagenesis and cancels the dissemination of these tumors. Here, we report that elevated levels of Skp2 are a characteristic of Eμ-Myc lymphomas and of human Burkitt lymphoma that bear MYC/Immunoglobulin chromosomal translocations. As expected, Myc-mediated suppression of p27Kip1 was abolished in Skp2-null Eμ-Myc B cells. However, the effect of Skp2 loss on Myc-driven proliferation and lymphomagenesis was surprisingly modest compared with the effects of Cks1 loss. Collectively, these findings suggest that Cks1 targets, in addition to p27Kip1, are critical for Myc-driven proliferation and tumorigenesis. Mol Cancer Res; 8(3); 353–62
PAX5α Enhances the Epithelial Behavior of Human Mammary Carcinoma Cells
Authors: Vidal Laurent J-P , Perry Jo K. , Vouyovitch Cecile M. , Pandey Vijay , Brunet-Dunand Severine E. , Mertani Hichem C. , Liu Dong-Xu , Lobie Peter E. 
Published: March 2010

Abstract
Deregulated PAX5 expression has been associated with metastatic mammary carcinoma, although the precise role of PAX5 in cancer progression is unclear. Stable forced expression of PAX5α in the mammary carcinoma cell lines MCF-7 and MDA-MB-231 reduced cell cycle progression, cell survival, and anchorage-independent cell growth. In xenograft studies, forced expression of PAX5α was associated with a significant reduction in tumor volume. Furthermore, forced expression of PAX5α in mammary carcinoma cells resulted in altered cell morphology with resultant enhancement of epithelial cell characteristics. Morphologic changes were associated with localization of β-CATENIN at cell-cell junctions and with altered mRNA expression of mesenchymal markers in mammary carcinoma cells. In addition, forced expression of PAX5α in MCF-7 and MDA-MB-231 cells significantly reduced cell migration and invasion. Concomitantly, small interfering RNA–mediated depletion of PAX5α increased MCF-7 total cell number, cell motility, migration, and invasion. These studies show that PAX5α enhances the epithelial characteristics of mammary carcinoma cells, reminiscent of mesenchymal to epithelial transition. Mol Cancer Res; 8(3); 444–56
Greek “Variant Literary Editions” to the Hebrew Bible?
Authors: Debel Hans 
Published: March 2010

AbstractThe full publication of the scrolls from the Judaean Desert has given impetus to reflections on the history and development of the biblical text during the period of Second Temple Judaism. This study critically reviews the major contributions to the debate and finally makes a plea to extent Ulrich’s hermeneutical model to some Septuagint texts that are usually not included among his “variant literary editions.” Its major arguments in this regard are that these texts witness to the same dynamic process of the organic development of Scripture, and that relegating them to the interpretational tradition merely because they are not written in Hebrew reveals an unwarranted bias towards the Masoretic Text.
Tropical–Extratropical Interactions over Southern Africa: Three Cases of Heavy Summer Season Rainfall
Authors: Hart N. C. G. , Reason C. J. C. , Fauchereau N. 
Published: March 2010

Abstract
The synoptic evolution of three tropical–extratropical (TE) interactions, each responsible for extreme rainfall events over southern Africa, is discussed in detail. Along with the consideration of previously studied events, common features of these heavy rainfall producing tropical temperate troughs (TTTs) over southern Africa are discussed. It is found that 2 days prior to an event, northeasterly moisture transports across Botswana, set up by the Angola low, are diverted farther south into the semiarid region of subtropical southern Africa. The TTTs reach full maturity as a TE cloud band, rooted in the central subcontinent, which is triggered by upper-level divergence along the leading edge of an upper-tropospheric westerly wave trough. Convection and rainfall within the cloud band is supported by poleward moisture transports with subtropical air rising as it leaves the continent and joins the midlatitude westerly flow. It is shown that these systems fit within a theoretical framework describing similar TE interactions found globally.
Uplift forcing for the extreme rainfall of each event is investigated. Unsurprisingly, quasigeostrophic uplift is found to dominate in the midlatitudes with convective processes strongest in the subtropics. Rainfall in the semiarid interior of South Africa appears to be a result of quasigeostrophically triggered convection.
Investigation of TTT formation in the context of planetary waves shows that early development is sometimes associated with previous anticyclonic wave breaking south of the subcontinent, with full maturity of TTTs occurring as a potential vorticity trough approaches the continent from the west. Sensitivity to upstream wave perturbations and effects on anticyclonic wave breaking in the South Indian Ocean are also observed.
On the Orthogonalization of Bred Vectors
Authors: Keller Jan D. , Hense Andreas , Kornblueh Luis , Rhodin Andreas 
Published: March 2010

Abstract
The key to the improvement of the quality of ensemble forecasts assessing the inherent flow uncertainties is the choice of the initial ensemble perturbations. To generate such perturbations, the breeding of growing modes approach has been used for the past two decades. Here, the fastest-growing error modes of the initial model state are estimated. However, the resulting bred vectors (BVs) mainly point in the phase space direction of the leading Lyapunov vector and therefore favor one direction of growing errors. To overcome this characteristic and obtain growing modes pointing to Lyapunov vectors different from the leading one, an orthogonalization implemented as a singular value decomposition based on the similarity between the BVs is applied. This transformation is similar to that used in the ensemble transform technique currently in operational use at NCEP but with certain differences in the metric used and in the implementation. In this study, results of this approach using BVs generated in the Ensemble Forecasting System (EFS) based on the global numerical weather prediction model GME of the German Meteorological Service are presented. The gain in forecast performance achieved with the orthogonalized BV initialization is shown by using different probabilistic forecast scores evaluating ensemble reliability, variance, and resolution. For a 3-month period in summer 2007, the results are compared to forecasts generated with simple BV initializations of the same ensemble prediction system as well as operational ensemble forecasts from ECMWF and NCEP. The orthogonalization vastly improves the GME–EFS scores and makes them competitive with the two other centers.
Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity
Authors: Liu Xiangdong , Shin Niu , Koblish Holly K. , Yang Gengjie , Wang Qian , Wang Kathy , Leffet Lynn , Hansbury Michael J. , Thomas Beth , Rupar Mark , Waeltz Paul , Bowman Kevin J. , Polam Padmaja , Sparks Richard B. , Yue Eddy W. , Li Yanlong , Wynn Richard , Fridman Jordan S. , Burn Timothy C. , Combs Andrew P. , Newton Robert C. , Scherle Peggy A. 
Published: March 2010

AbstractIndoleamine 2,3-dioxygenase-1 (IDO1; IDO) mediates oxidative cleavage of tryptophan, an amino acid essential for cell proliferation and survival. IDO1 inhibition is proposed to have therapeutic potential in immunodeficiency-associated abnormalities, including cancer. Here, we describe INCB024360, a novel IDO1 inhibitor, and investigate its roles in regulating various immune cells and therapeutic potential as an anticancer agent. In cellular assays, INCB024360 selectively inhibits human IDO1 with IC50 values of approximately 10nM, demonstrating little activity against other related enzymes such as IDO2 or tryptophan 2,3-dioxygenase (TDO). In coculture systems of human allogeneic lymphocytes with dendritic cells (DCs) or tumor cells, INCB024360 inhibition of IDO1 promotes T and natural killer (NK)–cell growth, increases IFN-γ production, and reduces conversion to regulatory T (Treg)–like cells. IDO1 induction triggers DC apoptosis, whereas INCB024360 reverses this and increases the number of CD86high DCs, potentially representing a novel mechanism by which IDO1 inhibition activates T cells. Furthermore, IDO1 regulation differs in DCs versus tumor cells. Consistent with its effects in vitro, administration of INCB024360 to tumor-bearing mice significantly inhibits tumor growth in a lymphocyte-dependent manner. Analysis of plasma kynurenine/tryptophan levels in patients with cancer affirms that the IDO pathway is activated in multiple tumor types. Collectively, the data suggest that selective inhibition of IDO1 may represent an attractive cancer therapeutic strategy via up-regulation of cellular immunity.
MyD88-dependent TLR4 signaling is selectively impaired in alveolar macrophages from asymptomatic HIV+ persons
Authors: Tachado Souvenir D. , Li Xin , Bole Medhavi , Swan Katharine , Anandaiah Asha , Patel Naimish R. , Koziel Henry 
Published: March 2010

AbstractAlveolar macrophages (AMs) are the predominant effector cell in the lungs and contribute to a critical first line of defense against bacterial pathogens through recognition by pattern recognition receptors such as Toll-like receptor 4 (TLR4). TLR4-mediated tumor necrosis factor α (TNFα) release is significantly impaired in HIV+ macrophages, but whether HIV impairs myeloid differentiation factor 88 (MyD88)–dependent and/or MyD-independent TLR4 signaling pathways in human macrophages is not known. Comparing human U937 macrophages with HIV+ U1 macrophages (HIV-infected U937 subclone), the current study shows that HIV infection is associated with impaired macrophage TLR4-mediated signaling, specifically targeting the MyD88-dependent TLR4-mediated signaling pathway (reduced MyD88–interleukin-1 receptor–associated kinase [IRAK] interaction, IRAK phosphorylation, nuclear factor [NF]–κB nuclear translocation, and TNFα release) while preserving the MyD88-independent TLR4-mediated signaling pathway (preserved STAT1 phosphorylation, interferon regulatory factor [IRF] nuclear translocation, and interleukin-10 [IL-10] and RANTES release). Extracellular TLR4 signaling complex was intact (similar levels of CD14 and MD2), and similar patterns of response were observed in clinically relevant AMs from healthy and asymptomatic HIV+ persons at high clinical risk of pneumonia. Taken together, these data support the concept that chronic HIV infection is associated with specific and targeted disruption of critical macrophage TLR4 signaling, which in turn may contribute to disease pathogenesis of bacterial pneumonia.
Development of O-antigen gene cluster-specific PCRs for rapid typing six epidemic serogroups of Leptospira in China
Authors: Cai Cheng-Song , Zhu Yong-Zhang , Zhong Yi , Xin Xiao-Fang , Jiang Xiu-Gao , Lou Xiao-Li , He Ping , Qin Jin-Hong , Zhao Guo-Ping , Wang Sheng-Yue , Guo Xiao-Kui 
Published: March 2010

Abstract

Background

Leptospira is the causative agent of leptospirosis. The O-antigen is the distal part of the lipopolysaccharide, which is a key component of outer membrane of Gram-negative bacteria and confers serological specificity. The epidemiology and clinical characteristics of leptospirosis are relative to the serology based taxonomic unit. Identification of Leptospira strains by serotyping is laborious and has several drawbacks.

Results
In this study, the O-antigen gene clusters of four epidemic Leptospira serogroups (serogroup Canicola, Autumnalis, Grippotyphosa and Hebdomadis) in China were sequenced and all genes were predicted in silico. Adding published sequences of two serogroups, Icterohaemorrhagiae (strain Lai and Fiocruz L1-130) and Sejroe (strain JB197 and L550), we identified six O-antigen-specific genes for six epidemic serogroups in China. PCR assays using these genes were developed and tested on 75 reference strains and 40 clinical isolates.

Conclusion
The results show that the PCR-based assays can be reliable and alternative means for rapid typing of these six serogroups of Leptospira.
Polymorphisms in IL-1β, vitamin D receptor Fok1, and Toll-like receptor 2 are associated with extrapulmonary tuberculosis
Authors: Motsinger-Reif Alison A , Antas Paulo RZ , Oki Noffisat O , Levy Shawn , Holland Steven M , Sterling Timothy R 
Published: March 2010

Abstract

Background
Human genetic variants may affect tuberculosis susceptibility, but the immunologic correlates of the genetic variants identified are often unclear.

Methods
We conducted a pilot case-control study to identify genetic variants associated with extrapulmonary tuberculosis in patients with previously characterized immune defects: low CD4+ lymphocytes and low unstimulated cytokine production. Two genetic association approaches were used: 1) variants previously associated with tuberculosis risk; 2) single nucleotide polymorphisms (SNPs) in candidate genes involved in tuberculosis pathogenesis. Single locus association tests and multifactor dimensionality reduction (MDR) assessed main effects and multi-locus interactions.

Results
There were 24 extrapulmonary tuberculosis cases (18 black), 24 pulmonary tuberculosis controls (19 black) and 57 PPD+ controls (49 black). In approach 1, 22 SNPs and 3 microsatellites were assessed. In single locus association tests, interleukin (IL)-1β +3953 C/T was associated with extrapulmonary tuberculosis compared to PPD+ controls (P = 0.049). Among the sub-set of patients who were black, genotype frequencies of the vitamin D receptor (VDR) Fok1 A/G SNP were significantly different in extrapulmonary vs. pulmonary TB patients (P = 0.018). In MDR analysis, the toll-like receptor (TLR) 2 microsatellite had 76% prediction accuracy for extrapulmonary tuberculosis in blacks (P = 0.002). In approach 2, 613 SNPs in 26 genes were assessed. None were associated with extrapulmonary tuberculosis.

Conclusions
In this pilot study among extrapulmonary tuberculosis patients with well-characterized immune defects, genetic variants in IL-1β, VDR Fok1, and TLR2 were associated with an increased risk of extrapulmonary disease. Additional studies of the underlying mechanism of these genetic variants are warranted.
Construct validation of a non-exercise measure of cardiorespiratory fitness in older adults
Authors: Mailey Emily L , White Siobhan M , Wójcicki Thomas R , Szabo Amanda N , Kramer Arthur F , McAuley Edward 
Published: March 2010

Abstract

Background
Cardiorespiratory fitness (CRF) is associated with a decreased risk of all-cause mortality but is rarely assessed in medical settings due to burdens of time, cost, risk, and resources. The purpose of this study was to test the construct validity of a regression equation developed by Jurca and colleagues (2005) to estimate CRF without exercise testing in community dwelling older adults.

Methods
Participants (n = 172) aged 60 to 80 years with no contraindications to submaximal or maximal exercise testing completed a maximal graded exercise test (GXT) and the submaximal Rockport 1-mile walk test on separate occasions. Data included in the regression equation (age, sex, body mass index, resting heart rate, and physical activity) were obtained via measurement or self-report. Participants also reported presence of cardiovascular conditions.

Results
The multiple R for the regression equation was .72, p < .001 and CRF estimated from this equation was significantly correlated with the MET value from the GXT (r = 0.66) and with CRF estimated from submaximal field testing (r = 0.67). All three CRF indices were significantly and inversely associated with reporting more cardiovascular conditions.

Conclusions
This research provides preliminary evidence that a non-exercise estimate of CRF is at least as valid as field test estimates of CRF and represents a low-risk, low-cost, and expedient method for estimating fitness in older adults.
The development of a web- and a print-based decision aid for prostate cancer screening
Authors: Dorfman Caroline S , Williams Randi M , Kassan Elisabeth C , Red Sara N , Dawson David L , Tuong William , Parker Elizabeth R , Ohene-Frempong Janet , Davis Kimberly M , Krist Alexander H , Woolf Steven H , Schwartz Marc D , Fishman Mary B , Cole Carmella , Taylor Kathryn L 
Published: March 2010

Abstract

Background
Whether early detection and treatment of prostate cancer (PCa) will reduce disease-related mortality remains uncertain. As a result, tools are needed to facilitate informed decision making. While there have been several decision aids (DAs) developed and tested, very few have included an exercise to help men clarify their values and preferences about PCa screening. Further, only one DA has utilized an interactive web-based format, which allows for an expansion and customization of the material. We describe the development of two DAs, a booklet and an interactive website, each with a values clarification component and designed for use in diverse settings.

Methods
We conducted two feasibility studies to assess men's (45-70 years) Internet access and their willingness to use a web- vs. a print-based tool. The booklet was adapted from two previous versions evaluated in randomized controlled trials (RCTs) and the website was created to closely match the content of the revised booklet. Usability testing was conducted to obtain feedback regarding draft versions of the materials. The tools were also reviewed by a plain language expert and the interdisciplinary research team. Feedback on the content and presentation led to iterative modifications of the tools.

Results
The feasibility studies confirmed that the Internet was a viable medium, as the majority of men used a computer, had access to the Internet, and Internet use increased over time. Feedback from the usability testing on the length, presentation, and content of the materials was incorporated into the final versions of the booklet and website. Both the feasibility studies and the usability testing highlighted the need to address men's informed decision making regarding screening.

Conclusions
Informed decision making for PCa screening is crucial at present and may be important for some time, particularly if a definitive recommendation either for or against screening does not emerge from ongoing prostate cancer screening trials. We have detailed our efforts at developing print- and web-based DAs to assist men in determining how to best meet their PCa screening preferences. Following completion of our ongoing RCT designed to test these materials, our goal will be to develop a dissemination project for the more effective tool.

Trial Registration
NCT00623090
The disease management program for type 2 diabetes in Germany enhances process quality of diabetes care - a follow-up survey of patient's experiences
Authors: Schäfer Ingmar , Küver Claudia , Gedrose Benjamin , Hoffmann Falk , Ruß-Thiel Barbara , Brose Hans-Peter , van den Bussche Hendrik , Kaduszkiewicz Hanna 
Published: March 2010

Abstract

Background
In summer 2003 a disease management program (DMP) for type 2 diabetes was introduced on a nationwide basis in Germany. Patient participation and continuity of care within the DMP are important factors to achieve long-term improvements in clinical endpoints. Therefore it is of interest, if patients experience any positive or negative effects of the DMP on their treatment that would support or hamper further participation. The main objective of the study was to find out if the German Disease Management Program (DMP) for type 2 diabetes improves process and outcome quality of medical care for patients in the light of their subjective experiences over a period of one year.

Methods
Cohort study with a baseline interview and a follow-up after 10.4 ± 0.64 months. Data on process and outcome measures were collected by telephone interviews with 444 patients enrolled and 494 patients not enrolled in the German DMP for type 2 diabetes. Data were analyzed by multivariate logistic regression analyses.

Results
DMP enrolment was significantly associated with a higher process quality of care. At baseline enrolled patients more often reported that they had attended a diabetes education course (OR = 3.4), have ≥ 4 contacts/year with the attending physician (OR = 3.3), have at least one annual foot examination (OR = 3.1) and one referral to an ophthalmologist (OR = 3.4) and possess a diabetes passport (OR = 2.4). Except for the annual referral to an ophthalmologist these parameters were also statistically significant at follow-up. In contrast, no differences between enrolled and not enrolled patients were found concerning outcome quality indicators, e.g. self-rated health, Glycated hemoglobin (GHb) and blood pressure. However, 16-36% of the DMP participants reported improvements of body weight and/or GHb and/or blood pressure values due to enrolment - unchanged within one year of follow-up.

Conclusions
In the light of patient's experiences the DMP enhances the process quality of medical care for type 2 diabetes in Germany. The lack of significant differences in outcome quality between enrolled and not enrolled patients might be due to the short program duration. Our data suggest that the DMP for type 2 diabetes should not be withdrawn unless an evidently more promising approach is found.