bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bim Polymorphisms: Influence on Function and Response to Treatment in Children with Acute Lymphoblastic Leukemia
Authors: Gagné Vincent , Rousseau Julie , Labuda Malgorzata , Sharif-Askari Bahram , Brukner Ivan , Laverdière Caroline , Ceppi Francesco , Sallan Stephen E. , Silverman Lewis B. , Neuberg Donna , Kutok Jeffery L. , Sinnett Daniel , Krajinovic Maja 
Published: August 2013

Abstract
Purpose: Corticosteroids induce apoptosis in the malignant lymphoid cells and are critical component of combination therapy for acute lymphoblastic leukemia (ALL). Several genome-wide microarray studies showed major implication of proapoptotic Bim in mediating corticosteroid-related resistance in leukemia cells.
Experimental Design: We investigated Bim gene polymorphisms and their association with childhood ALL outcome, and the mechanism underlying the observed finding.
Results: Lower overall survival (OS) was associated with BimC29201T located in Bcl-2 homology 3 (BH3) domain (P = 0.01). An association remained significant in multivariate model (P = 0.007), was more apparent in high-risk patients (P = 0.004) and patients treated with dexamethasone (P = 0.009), and was subsequently confirmed in the replication patient cohort (P = 0.03). RNA analysis revealed that C29201T affects generation of γ isoforms (γ1) that lack proapoptotic BH3 domain. The phenotypic effect was minor suggesting the influence of additional factors that may act in conjunction with Bim genotype. Combined analysis with Mcl gene polymorphism (G-486T) revealed profound reduction in OS in individuals with both risk genotypes (P &lt; 0.0005 in discovery and P = 0.002 in replication cohort) and particularly in high-risk patients (P ≤ 0.008).
Conclusions: Increased expression of prosurvival Mcl1 and presence of Bim isoforms lacking proapoptotic function might explain marked reduction of OS in a disease and dose-dependent manner in ALL patients carrying Bim- and Mcl1-risk genotypes. Clin Cancer Res; 19(18); 5240–9. ©2013 AACR.
Natural Regulatory T Cells Limit Angiotensin II–Induced Aneurysm Formation and Rupture in Mice
Authors: Ait-Oufella Hafid , Wang Yu , Herbin Olivier , Bourcier Simon , Potteaux Stephane , Joffre Jeremie , Loyer Xavier , Ponnuswamy Padmapria , Esposito Bruno , Dalloz Marion , Laurans Ludivine , Tedgui Alain , Mallat Ziad 
Published: August 2013

Objective—
Abdominal aortic aneurysm is an inflammatory disease leading to destructive vascular remodeling and ultimately to lethal aortic rupture. Despite its frequent association with atherosclerosis, compelling studies have shown striking differences and potentially opposite roles of T-cell helper responses in aneurysm as compared with atherosclerosis, casting doubt on the relevance and suitability of T-cell–targeted therapies in this context.

Approach and Results—

Here, we show that selective depletion of T regulatory (Treg) cells using a CD25-specific monoclonal antibody significantly enhances the susceptibility of C57Bl/6 mice to angiotensin II–induced abdominal aortic aneurysm and promotes aortic rupture (n=25–44 mice/group). Similar results are observed in angiotensin II–treated
Cd80
−/−
/Cd86
−/−
or
Cd28
−/−
mice with impaired Treg cell homeostasis (n=18–23 mice/group). Treg cell depletion is associated with increased immune cell activation and a blunted interleukin (IL)-10 anti-inflammatory response, suggesting an immunoinflammatory imbalance. Interestingly,
Il-10
−/−
mice (n=20 mice/group) show increased susceptibility to angiotensin II–induced abdominal aortic aneurysm and aortic rupture and are insensitive to Treg cell depletion. Finally, reconstitution of
Cd28
−/−
Treg-deficient mice with Treg cells (n=22 mice/group) restores a balance in the immunoinflammatory response, rescues the animals from increased susceptibility to aneurysm, and prevents aortic dissection.

Conclusions—
These results identify a critical role for Treg cells and IL-10 in the control of aneurysm formation and its progression to rupture and suggest that therapies targeting Treg responses may be most suited to treat aneurysmal disease.
Reduction in Early Stroke Risk in Carotid Stenosis With Transient Ischemic Attack Associated With Statin Treatment
Authors: Merwick Áine , Albers Gregory W. , Arsava Ethem M. , Ay Hakan , Calvet David , Coutts Shelagh B. , Cucchiara Brett L. , Demchuk Andrew M. , Giles Matthew F. , Mas Jean-Louis , Olivot Jean Marc , Purroy Francisco , Rothwell Peter M. , Saver Jeffrey L. , Sharma Vijay K. , Tsivgoulis Georgios , Kelly Peter J. 
Published: August 2013

Background and Purpose—
Statins reduce stroke risk when initiated months after transient ischemic attack (TIA)/stroke and reduce early vascular events in acute coronary syndromes, possibly via pleiotropic plaque stabilization. Few data exist on acute statin use in TIA. We aimed to determine whether statin pretreatment at TIA onset modified early stroke risk in carotid stenosis.

Methods—
We analyzed data from 2770 patients with TIA from 11 centers, 387 with ipsilateral carotid stenosis. ABCD2 score, abnormal diffusion weighted imaging, medication pretreatment, and early stroke were recorded.

Results—

In patients with carotid stenosis, 7-day stroke risk was 8.3% (95% confidence interval [CI], 5.7–11.1) compared with 2.7% (CI, 2.0%–3.4%) without stenosis (
P
<0.0001; 90-day risks 17.8% and 5.7% [
P
<0.0001]). Among carotid stenosis patients, nonprocedural 7-day stroke risk was 3.8% (CI, 1.2%–9.7%) with statin treatment at TIA onset, compared with 13.2% (CI, 8.5%–19.8%) in those not statin pretreated (
P
=0.01; 90-day risks 8.9% versus 20.8% [
P
=0.01]). Statin pretreatment was associated with reduced stroke risk in patients with carotid stenosis (odds ratio for 90-day stroke, 0.37; CI, 0.17–0.82) but not nonstenosis patients (odds ratio, 1.3; CI, 0.8–2.24;
P
for interaction, 0.008). On multivariable logistic regression, the association remained after adjustment for ABCD2 score, smoking, antiplatelet treatment, recent TIA, and diffusion weighted imaging hyperintensity (adjusted
P
for interaction, 0.054).

Conclusions—
In acute symptomatic carotid stenosis, statin pretreatment was associated with reduced stroke risk, consistent with findings from randomized trials in acute coronary syndromes. These data support the hypothesis that statins started acutely after TIA symptom onset may also be beneficial to prevent early stroke. Randomized trials addressing this question are required.
Authenticity, Sincerity and Spontaneity: The Mutual Implication of Nature and Religion in China and the West
Authors: Miller James 
Published: August 2013

Abstract
Fundamental approaches to ethics and morality in both China and the West are bound up not only with conceptions of religion and ultimate truth, but also with conceptions of nature. One dominant theme in the West is to see nature in terms of an original goodness that precedes human manipulation. This theme is bound up with Biblical views of divine creation by a divine lawmaker. In contrast to this view, Chinese conceptions of sincerity (cheng) and spontaneity (ziran) mitigate against such an abstract conception of the original goodness or authenticity of nature.
Guillaume Postel and the Primordial Origins of the Middle East
Authors: Wheeler Brannon 
Published: August 2013

Abstract
Guillaume Postel is often credited as one of the founding fathers of the modern “orientalist” European study of the Middle East, and of Arabic, Islam, and the Quran in particular. He published his most influential work in 1544, calling on the French king to lead a Crusade against the Ottomans and usher in a new, apocalyptic age. Although usually credited as a pioneer in the comparative study of Semitic languages, an influential figure in French-Ottoman relations, and as one of the first Europeans to study the Quran in comparison with the Bible, it was the unique sixteenth-century renaissance combination of apocalyptism, European nationalism, and alchemy behind the specific formation of Postel’s universal linguistic theories that would most influence future scholarship. The following pages examine the historical context in which Postel produced his work with particular attention to the apocalyptism of his religious ideas and the kabbalistic sources of his linguistic scholarship.
A Dual-Polarization Radar Signature of Hydrometeor Refreezing in Winter Storms
Authors: Kumjian Matthew R. , Ryzhkov Alexander V. , Reeves Heather D. , Schuur Terry J. 
Published: August 2013

AbstractPolarimetric radar measurements in winter storms that produce ice pellets have revealed a unique signature that is indicative of ongoing hydrometeor refreezing. This refreezing signature is observed within the low-level subfreezing air as an enhancement of differential reflectivity ZDR and specific differential phase KDP and a decrease of radar reflectivity factor at horizontal polarization ZH and copolar correlation coefficient ρhv. It is distinct from the overlying melting-layer “brightband” signature and suggests that unique microphysical processes are occurring within the layer of hydrometeor refreezing. The signature is analyzed for four ice-pellet cases in central Oklahoma as observed by two polarimetric radars. A statistical analysis is performed on the characteristics of the refreezing signature for a case of particularly long duration. Several hypotheses are presented to explain the appearance of the signature, along with a summary of the pros and cons for each. It is suggested that preferential freezing of small drops and local ice generation are plausible mechanisms for the appearance of the ZDR and KDP enhancements. Polarimetric measurements and scattering calculations are used to retrieve microphysical information to explore the validity of the hypotheses. The persistence and repetitiveness of the signature suggest its potential use in operational settings to diagnose the transition between freezing rain and ice pellets.
An Observation-Based Investigation of Nudging in WRF for Downscaling Surface Climate Information to 12-km Grid Spacing
Authors: Bullock O. Russell , Alapaty Kiran , Herwehe Jerold A. , Mallard Megan S. , Otte Tanya L. , Gilliam Robert C. , Nolte Christopher G. 
Published: August 2013

AbstractPrevious research has demonstrated the ability to use the Weather Research and Forecasting model (WRF) and contemporary dynamical downscaling methods to refine global climate modeling results to a horizontal grid spacing of 36 km. Environmental managers and urban planners have expressed the need for even finer resolution in projections of surface-level weather to take into account local geophysical and urbanization patterns. In this study, WRF as previously applied at 36-km grid spacing is used with 12-km grid spacing with one-way nesting to simulate the year 2006 over the central and eastern United States. The results at both resolutions are compared with hourly observations of surface air temperature, humidity, and wind speed. The 12- and 36-km simulations are also compared with precipitation data from three separate observation and analysis systems. The results show some additional accuracy with the refinement to 12-km horizontal grid spacing, but only when some form of interior nudging is applied. A positive bias in precipitation found previously in the 36-km results becomes worse in the 12-km simulation, especially without the application of interior nudging. Model sensitivity testing shows that 12-km grid spacing can further improve accuracy for certain meteorological variables when alternate physics options are employed. However, the strong positive bias found for both surface-level water vapor and precipitation suggests that WRF as configured here may have an unbalanced hydrologic cycle that is returning moisture from land and/or water bodies to the atmosphere too quickly.
Observed Tropical Cyclone Eye Thermal Anomaly Profiles Extending above 300 hPa
Authors: Durden Stephen L. 
Published: August 2013

Abstract
As recently pointed out by Stern and Nolan, much of our knowledge of the warm core structure of the tropical cyclone eye has come from composites of in situ data taken from multiple aircraft studies of three storms in the late 1950s and 1960s. Further observational confirmation of eye thermal structure has been lacking, since much of the dropsonde data analyzed to date have been limited to pressure levels of 500 hPa or lower. However, there exist a number of dropsonde eye profiles extending to near 250 hPa; these profiles were acquired from NASA aircraft during various field campaigns. Here, the author uses these data to calculate eye temperature anomaly profiles. These data are supplemented by several surface-based radiosonde releases in tropical cyclone eyes over the period 1944–2003. The author finds that the pressure altitude of the maximum anomaly varies between 760 and 250 hPa. The author also finds positive correlations between the maximum anomaly level and storm intensity, size, upper-level divergence, and environmental instability.
Objective Tropical Cyclone Intensity Estimation Using Analogs of Spatial Features in Satellite Data
Authors: Fetanat Gholamreza , Homaifar Abdollah , Knapp Kenneth R. 
Published: August 2013

Abstract
An objective method for estimating tropical cyclone (TC) intensity using historical hurricane satellite data (HURSAT) is developed and tested. This new method, referred to as feature analogs in satellite imagery (FASI), requires a TC's center location to extract azimuthal brightness temperature (BT) profiles from current imagery as well as BT profiles from imagery 6, 12, and 24 h prior. Instead of using regression techniques, the estimated TC intensity is determined from the 10 closest analogs to this TC based on the BT profiles using a k-nearest-neighbor algorithm. The FASI technique was trained and validated using intensity data from aircraft reconnaissance in the North Atlantic Ocean, where the data were restricted to include storms that are over water and south of 45°N. This subset comprised 2016 observations from 165 storms during 1988–2006. Several tests were implemented to statistically justify the FASI algorithm using n-fold cross validation. The resulting average mean absolute intensity error was 10.9 kt (50% of estimates are within 10 kt, 1 kt = 0.51 m s−1) or 8.4 mb (50% of estimates are within 8 mb); its accuracy is on par with other objective techniques. This approach has the potential to provide global TC intensity estimates that could augment intensity estimates made by other objective techniques.
A survey of pharmacological and nonpharmacological treatment of functional gastrointestinal disorders
Authors: Lahner Edith , Bellentani Stefano , Bastiani Rudy De , Tosetti Cesare , Cicala Michele , Esposito Gianluca , Arullani Paolo , Annibale Bruno ,   Study Group Primary Care in Gastroenterology of the Italian Society of Gastroenterology
Published: August 2013

BackgroundTreatment of functional gastrointestinal disorders (FGIDs) is based on symptoms relieve by conventional drugs, but increasingly complementary and alternative medicine (CAM) is used.ObjectiveThis survey aimed to investigate the current treatments used by FGIDs patients.MethodsA total of 25 Italian gastroenterologists interviewed outpatients on gastrointestinal symptoms and treatments (pharmacological, CAM, diet/dietary supplements) used during the last year to relieve FGIDs. Consecutive adults with FGIDs according to Rome III were included.ResultsOf the 199 patients, 81% used conventional drugs, 64.3% diet/dietary supplements, and 48.7% CAM. Conventional drugs, diet/dietary supplements, or CAM as exclusive treatment were used by 24.6, 6, and 2.5% of patients, respectively. Two‐thirds used more than one treatment: 34.7% conventional drugs, CAM, and diet/dietary supplements, 17.1% conventional drugs and diet/dietary supplements, 10.1% diet and CAM, and 5% conventional drugs and CAM. Benefits and adverse effects were similar for conventional drugs and nonpharmacological treatments. Males (OR 2.4) without lower GI symptoms (OR 5.4) used more frequently exclusive pharmacological treatment of FGIDs.ConclusionsConventional drugs are the preferred treatment for FGID. CAM and dietary modifications are more likely used as an adjunct to rather than instead of conventional drugs. Adverse effects occurred in all treatments.
Distinct pathways regulated by menin and by MLL1 in hematopoietic stem cells and developing B cells
Authors: Li Bin E. , Gan Tao , Meyerson Matthew , Rabbitts Terence H. , Ernst Patricia 
Published: August 2013

Key Points
MLL1 does not require interaction with menin to maintain hematopoietic stem cell homeostasis. Menin and MLL1 are both critical during B-cell differentiation, but largely through distinct pathways.
Epidemiology of cancer-associated venous thrombosis
Authors: Timp Jasmijn F. , Braekkan Sigrid K. , Versteeg Henri H. , Cannegieter Suzanne C. 
Published: August 2013

Abstract
Cancer-associated venous thrombosis is a common condition, although the reported incidence varies widely between studies depending on patient population, start and duration of follow-up, and the method of detecting and reporting thrombotic events. Furthermore, as cancer is a heterogeneous disease, the risk of venous thrombosis depends on cancer types and stages, treatment measures, and patient-related factors. In general, cancer patients with venous thrombosis do not fare well and have an increased mortality compared with cancer patients without. This may be explained by the more aggressive type of malignancies associated with this condition. It is hypothesized that thromboprophylaxis in cancer patients might improve prognosis and quality of life by preventing thrombotic events. However, anticoagulant treatment leads to increased bleeding, particularly in this patient group, so in case of proven benefit of thromboprophylaxis, only patients with a high risk of venous thrombosis should be considered. This review describes the literature on incidence of and risk factors for cancer-associated venous thrombosis, with the aim to provide a basis for identification of high-risk patients and for further development and refinement of prediction models. Furthermore, knowledge on risk factors for cancer-related venous thrombosis may enhance the understanding of the pathophysiology of thrombosis in these patients.
Genetic loss of SH2B3 in acute lymphoblastic leukemia
Authors: Perez-Garcia Arianne , Ambesi-Impiombato Alberto , Hadler Michael , Rigo Isaura , LeDuc Charles A. , Kelly Kara , Jalas Chaim , Paietta Elisabeth , Racevskis Janis , Rowe Jacob M. , Tallman Martin S. , Paganin Maddalena , Basso Giuseppe , Tong Wei , Chung Wendy K. , Ferrando Adolfo A. 
Published: August 2013

Key PointsSH2B3 is a recessive tumor suppressor gene with germline and somatic mutations in ALL.
A note on complete convergence of weighted sums for array of rowwise AANA random variables
Authors: Wang Xinghui , Shen Aiting , Li Xiaoqin 
Published: August 2013

Abstract
In this paper, we consider complete convergence and complete moment convergence of weighted sums for an array of rowwise AANA random variables. The main result of the paper generalizes the Baum-Katz theorem on AANA random variables. Our results extend and improve the corresponding ones of Wang et al. (Abstr. Appl. Anal. 2012:315138, 2012).

MSC:60B10, 60F15.
Antioxidants cause rapid expansion of human adipose-derived mesenchymal stem cells via CDK and CDK inhibitor regulation
Authors: Sun Li-Yi , Pang Cheng-Yoong , Li Dian-Kun , Liao Chia-Hsin , Huang Wei-Chao , Wu Chao-Chuan , Chou Yi-Yo , Li Wei Wu , Chen Shin-Yuan , Liu Hwan-Wun , Chang Yao-Jen , Cheng Ching-Feng 
Published: August 2013

AbstractBackgroundAntioxidants have been shown to enhance the proliferation of adipose-derived mesenchymal stem cells (ADMSCs)in vitro, although the detailed mechanism(s) and potential side effects are not fully understood.In this study, human ADMSCs cultured in ImF-A medium supplemented with antioxidants (N-acetyl-l-cysteine and ascorbic acid-2-phosphate) and fibroblast growth factor 2 (FGF-2) were compared with ADMSCs cultured with FGF-2 alone (ImF) or with FGF-2 under 5% pO2conditions (ImF-H).ResultsDuring log-phase growth, exposure to ImF-A resulted in a higher percentage of ADMSCs in the S phase of the cell cycle and a smaller percentage in G0/G1 phase. This resulted in a significantly reduced cell-doubling time and increased number of cells in the antioxidant-supplemented cultures compared with those supplemented with FGF-2 alone, an approximately 225% higher cell density after 7 days. Western blotting showed that the levels of the CDK inhibitors p21 and p27 decreased after ImF-A treatment, whereas CDK2, CDK4, and CDC2 levels clearly increased. In addition, ImF-A resulted in significant reduction in the expression of CD29, CD90, and CD105, whereas relative telomere length, osteogenesis, adipogenesis, and chondrogenesis were enhanced. The results were similar for ADMSCs treated with antioxidants and those under hypoxic conditions.ConclusionAntioxidant treatment promotes entry of ADMSCs into the S phase by suppressing cyclin-dependent kinase inhibitors and results in rapid cell proliferation similar to that observed under hypoxic conditions.
Cysteine-rich domain of scavenger receptor AI modulates the efficacy of surface targeting and mediates oligomeric Aβ internalization
Authors: Huang Fong-Lee , Shiao Young-Ji , Hou Sheue-Jane , Yang Cheng-Ning , Chen Yi-Jen , Lin Chao-Hsiung , Shie Feng-Shiun , Tsay Huey-Jen 
Published: August 2013

Abstract

Background
Insufficient clearance of soluble oligomeric amyloid-β peptide (oAβ) in the central nervous system leads to the synaptic and memory deficits in Alzheimer's disease (AD). Previously we have identified scavenger receptor class A (SR-A) of microglia mediates oligomeric amyloid-β peptide (oAβ) internalization by siRNA approach. SR-A is a member of cysteine-rich domain (SRCR) superfamily which contains proteins actively modulating the innate immunity and host defense, however the functions of the SRCR domain remain unclear. Whether the SRCR domain of SR-AI modulates the receptor surface targeting and ligand internalization was investigated by expressing truncated SR-A variants in COS-7 cells. Surface targeting of SR-A variants was examined by live immunostaining and surface biotinylation assays. Transfected COS-7 cells were incubated with fluorescent oAβ and acetylated LDL (AcLDL) to assess their ligand-internalization capabilities.

Result
Genetic ablation of SR-A attenuated the internalization of oAβ and AcLDL by microglia. Half of oAβ-containing endocytic vesicles was SR-A positive in both microglia and macrophages. Clathrin and dynamin in SR-AI-mediated oAβ internalization were involved. The SRCR domain of SR-AI is encoded by exons 10 and 11. SR-A variants with truncated exon 11 were intracellularly retained, whereas SR-A variants with further truncations into exon 10 were surface-targeted. The fusion of exon 11 to the surface-targeted SR-A variant lacking the SRCR domain resulted in the intracellular retention and the co-immunoprecipitation of Bip chaperon of the endoplasmic reticulum. Surface-targeted variants were N-glycosylated, whereas intracellularly-retained variants retained in high-mannose states. In addition to the collagenous domain, the SRCR domain is a functional binding domain for oAβ and AcLDL. Our data suggest that inefficient folding of SR-AI variants with truncated SRCR domain was recognized by the endoplasmic reticulum associated degradation which leads to the immature N- glycosylation and intracellular retention.

Conclusion
The novel functions of the SRCR domain on regulating the efficacy of receptor trafficking and ligand binding may lead to possible approaches on modulating the innate immunity in Alzheimer’s disease and atherosclerosis.