bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving power and robustness for detecting genetic association with extreme‐value sampling design
Authors: Chen Hua Yun , Li Mingyao 
Published: October 2011

AbstractExtreme‐value sampling design that samples subjects with extremely large or small quantitative trait values is commonly used in genetic association studies. Samples in such designs are often treated as “cases” and “controls” and analyzed using logistic regression. Such a case‐control analysis ignores the potential dose‐response relationship between the quantitative trait and the underlying trait locus and thus may lead to loss of power in detecting genetic association. An alternative approach to analyzing such data is to model the dose‐response relationship by a linear regression model. However, parameter estimation from this model can be biased, which may lead to inflated type I errors. We propose a robust and efficient approach that takes into consideration of both the biased sampling design and the potential dose‐response relationship. Extensive simulations demonstrate that the proposed method is more powerful than the traditional logistic regression analysis and is more robust than the linear regression analysis. We applied our method to the analysis of a candidate gene association study on high‐density lipoprotein cholesterol (HDL‐C) which includes study subjects with extremely high or low HDL‐C levels. Using our method, we identified several SNPs showing a stronger evidence of association with HDL‐C than the traditional case‐control logistic regression analysis. Our results suggest that it is important to appropriately model the quantitative traits and to adjust for the biased sampling when dose‐response relationship exists in extreme‐value sampling designs. Genet. Epidemiol. 2011.  © 2011 Wiley Periodicals, Inc.35:823‐830, 2011
Stereoselective synthesis of functional dehydrophenylalanine derivatives from novel β‐chloroamino esters
Authors: Ould Elemine Brahim , Ennigrou Mohamed Rached , Besbes Rafâa 
Published: October 2011

AbstractNew functional dehydrophenylalanines3were prepared from β‐amino alcohols1in a two‐step reaction sequence. The synthesis involved chlorination of the starting amino alcohols1to afford the intermediate erythro β‐chloroamines2. Treatment of the latter with an appropriate base led to a highly stereoselective elimination reaction, giving the corresponding (E)‐dehydrophenylalanine derivatives3in high yields. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:91–98, 2012; View this article online atwileyonlinelibrary.com. DOI 10.1002/hc.20756
Molecular biology of adenoid cystic carcinoma
Authors: Liu Jia , Shao Chunbo , Tan Marietta L. , Mu David , Ferris Robert L. , Ha Patrick K. 
Published: October 2011

AbstractBackgroundAdenoid cystic carcinoma (ACC) is an unusual salivary gland malignancy that remains poorly understood. Standard treatment, including surgery with postoperative radiation therapy, has attained reasonable local control rates, but the propensity for distant metastases has limited any improvement in survival over time. Our understanding of the molecular mechanisms driving ACC is quite rudimentary, due to the infrequent nature of its occurrence.MethodsAn extensive literature review was performed on salivary gland ACCs and basic science research findings.ResultsThis review highlights many findings that are emerging about the carcinogenesis of ACC including cytogenetics, tumor suppressor genes, oncogenes, epigenetic alterations, mitochondrial alterations, and biomarker studies.ConclusionAlthough there have been many discoveries, much still remains unknown about this rare malignancy. © 2011 Wiley Periodicals, Inc. Head Neck, 2011
Biochemical and Immunologic Effects of Rituximab in Patients With Primary Biliary Cirrhosis and an Incomplete Response to Ursodeoxycholic Acid
Authors: Tsuda Masanobu , Moritoki Yuki , Lian Zhe-Xiong , Zhang Weici , Yoshida Katsunori , Wakabayashi Kanji , Yang Guo-Xiang , Nakatani Toshio , Vierling John , Lindor Keith , Gershwin Eric M. , Bowlus Christopher L. 
Published: October 2011

Abstract

The aim of this study was to determine the safety and potential efficacy of B-cell depletion with the anti-CD20 monoclonal antibody rituximab in patients with primary biliary cirrhosis (PBC) and an incomplete response to ursodeoxycholic acid (UDCA). This open-label study enrolled six patients with PBC and incomplete responses to UDCA to be treated with 2 doses of 1000 mg rituximab separated by 2 weeks and followed for 52 weeks. The primary endpoints were safety and changes in B-cell function. Two patients received only 1 dose of rituximab, one due to activation of latent varicella and the other due to a viral upper respiratory infection. Serum levels of total IgG, IgM, and IgA as well as anti-mitochondrial autoantibodies (AMAs) IgA and IgM decreased significantly from baseline by 16 weeks and returned to baseline levels by 36 weeks. Stimulation of B cells with CpG produced significantly less IgM at 52 weeks after treatment compared with B cells at baseline. In addition, transient decreases in memory B-cell and T-cell frequencies and an increase in CD25high CD4+ T cells were observed after treatment. These changes were associated with significant increases in mRNA levels of FoxP3 and transforming growth factor-β (TGF-β) and a decrease in tumor necrosis factor-α (TNF-α) in CD4+ T cells. Notably, serum alkaline phosphatase levels were significantly reduced up to 36 weeks following rituximab treatment.

Conclusion :

These data suggest that depletion of B cells influences the induction, maintenance, and activation of both B and T cells and provides a potential mechanism for treatment of patients with PBC with an incomplete response to UDCA. (Hepatology 2012)
Rapid and Facile Access to Indeno[1,2‐d]imidazoles via a Tandem AdditionCyclization Reaction
Authors: Alizadeh Abdolali , Zarei Ameneh , Rezvanian Atieh 
Published: October 2011

AbstractA novel and tandem synthesis of highly functionalized tetrahydroindeno[1,2‐d]imidazole is described. A one‐pot reaction between a primary amine, an aryl isothiocyanate, and ninhydrin leads to highly substituted indeno[1,2‐d]imidazoles under solvent‐free conditions in excellent yields (Scheme). Their structures were corroborated spectroscopically (IR, 1H‐ and 13C‐NMR, and EI‐MS) and by elemental analyses.
A New Germanium Complex Containing Chelating Pyridinecarboxylate Ligands: cis‐Dihydroxybis(pyridine‐2‐carboxylato‐κN1,κO2)germanium Hydrate (1 : 2) (cis‐[Ge(pyca)2(OH)2]⋅2 H2O)
Authors: Shestopalov Michael A. , Efremova Olga A. , Smolentsev Anton I. , Mironov Yuri V. , Fedorov Vladimir E. , Song Yong‐Won 
Published: October 2011

AbstractA new germanium complex, cis‐[Ge(pyca)2(OH)2]⋅2 H2O (1; pyca=pyridine‐2‐carboxylato), was synthesized by the reaction of [Ge(acac)2Cl2] (acac=acetylacetonato=pentane‐2,4‐dionato) with potassium pyridine‐2‐carboxylate (Kpyca) in H2O/THF. According to the single‐crystal X‐ray diffraction analysis, each Ge‐atom of 1 is coordinated by two pyca ligands and two OH− groups (Fig. 1). These molecules are bonded to each other via a system of H‐bonds resulting in a sheet‐like structure (Fig. 2). The complex is decomposed during heating with stepwise mass loss and formation of GeO2 as final product (Fig. 3).
Spatial variation in transient water table responses: differences between an upper and lower hillslope zone
Authors: Haught D. R. W. , van Meerveld H. J. 
Published: October 2011

AbstractTo better understand storage‐runoff dynamics, transient groundwater responses were examined in one of the steep watersheds in British Columbia's coastal mountains. Streamflow and piezometric data were collected for 1 year to determine the spatial and temporal relations between transient groundwater levels and discharge. Correlations between piezometer responses and lag‐time analysis were used to identify and better understand runoff generation mechanisms in this watershed. Results showed a large spatial and temporal variation in transient water table dynamics and indicated that two distinct zones existed: a lower hillslope zone and an upslope zone. Each zone was characterized by very different water table responses. The upper hillslope was disconnected from the stream for the majority of time, suggesting that during most events, it does not directly contribute to streamflow. Piezometers in the lower hillslope zone showed hydrologically limited responses, suggesting rapid subsurface flow, likely through the many macropores and soil pipes. The lag time between peak streamflow and peak groundwater level decreased with increasing antecedent moisture conditions and was more variable for piezometers further away from the stream than for piezometers close to the stream. The study results indicate that a single storage‐runoff model is not appropriate for this steep watershed and that a two‐ or three‐compartment model would be more suitable. Copyright © 2011 John Wiley & Sons, Ltd.
Assessment of the environmental fate and ecotoxicity of N,N-diethyl-m-toluamide (DEET)
Authors: Weeks JA , Guiney PD , Nikiforov AI 
Published: October 2011

Abstract
N,N-diethyl-m-toluamide (DEET) is a key active ingredient in many insect repellents available commercially throughout the world. Owing to its popularity among consumers for nearly 30 years, considerable work conducted in the past has demonstrated—and continues to demonstrate—that human exposure to DEET poses no significant health risk to the general population. The results of several studies reported in this paper describe more recent work to understand the environmental fate of DEET, particularly in surface waters and soil, and the potential hazards to aquatic and terrestrial organisms. In summary, DEET enters the environment through several pathways: directly into air during spray application; to surface water from overspray and indirectly via wastewater treatment plant (WTTP) discharges (as a result of washing of skin and laundering of clothing); or to soil via overspray and application of treated sewage as an amendment. Multimedia environmental fate modeling predicts that DEET entering the environment is retained either in receiving waters (∼79%) or in soil (∼21%). Based on its physicochemical properties, DEET is expected to be moderately mobile in the soil column. In surface waters and soil, DEET degrades at a moderate to rapid rate (its half-life is measured in days to weeks). The small amounts of DEET retained in air are subject to rapid photo-oxidation via hydroxyl radical–mediated degradation or, if in droplet form, gravitational settling to soil or water. DEET does not interfere with ozone formation in the upper atmosphere. The bioaccumulation potential of DEET is low; it is neither a persistent, bioaccumulative toxicant nor a persistent organic pollutant. Among aquatic species, acute effect concentrations range between 4 and 388 mg/L. The chronic no-observed effect concentrations (NOEC) for daphnids and green algae range from approximately 0.5 to 24 mg/L. Measured concentrations of DEET in surface waters are several hundreds to thousands of times lower than the lowest NOEC measured, and thus the probability for adverse effects to environmental species is low. A separate paper by Aronson et al. (this issue) supports this conclusion by quantitatively exploring the risks to the aquatic environment using a combination of monitoring data and exposure modeling. Integr Environ Assess Manag 2012;8:120–134. © 2011 SETAC
Links between mutant p53 and genomic instability
Authors: Hanel Walter , Moll Ute M. 
Published: October 2011

AbstractThe tumor suppressor p53 has long been known to play a central role in maintaining a stable genome in the face of toxic insults through its role in promoting cell‐cycle checkpoints, DNA repair, and apoptosis. However, p53 null cells still retain some function of certain checkpoint and repair processes, reducing the genomic changes that otherwise would occur if these mechanisms were absent. Accumulating evidence suggests that mutant forms of p53 proteins may drastically perturb these residual genome‐stabilizing mechanisms through gain‐of‐function interactions with multiple proteins leading to a higher level of genomic instability than in p53 null cells. This review summarizes the current body of evidence that mutp53 plays a role in promoting various forms of genomic instability and provides an overview of current mechanistic proposals. J. Cell. Biochem. 113: 433–439, 2012. © 2011 Wiley Periodicals, Inc.
Mechanical forces‐induced human osteoblasts differentiation involves MMP‐2/MMP‐13/MT1‐MMP proteolytic cascade
Authors: Barthelemi Stéphane , Robinet Julien , Garnotel Roselyne , Antonicelli Frank , Schittly Estelle , Hornebeck William , Lorimier Sandrine 
Published: October 2011

AbstractMatrix metalloproteinase (MMP) family proteins play diverse roles in many aspects of cellular processes such as osteoblastic differentiation. Besides, mechanical forces that occur in 3D collagen gel promote the osteoblastic phenotype and accelerate matrix mineralization. Although MMPs have been involved in bone differentiation, the proteolytic cascades triggered by mechanical forces are still not well characterized. In this study, we have investigated the contribution of both proteolytic cascades, MMP‐3/MMP‐1 and MMP‐2/MMP‐13/MT1‐MMP in the differentiation of human osteoblasts cultured in a floating type I collagen lattice (FL) versus an attached collagen lattice (AL). Compared to AL, contraction of human osteoblasts‐populated FL led to a fast (1 day) induction of alkaline phosphatase (ALP), bone sialoprotein (BSP), osteoprotegerin (OPG), and Runx‐2 expression. At day 4, osteocalcin (OC) overexpression preceded the formation of calcium‐containing nodule formation as assessed by X‐ray analyses. MMP‐1 and MMP‐3 were produced to similar extent by cells cultured in FL and AL, whereas contraction of collagen lattices triggered both mRNA overexpression of MMP‐2, MMP‐13, and MT1‐MMP (i.e., MMP‐14), and their activation as evidenced by Western blotting or zymographic analyses. Down‐regulating MT1‐MMP expression or activity either by siRNA transfection or supplementation of culture medium with TIMP‐1 or TIMP‐2 highlighted the contribution of that enzyme in OC, ALP, and OPG expression. MMP‐2 and MMP‐13 were more directly involved in BSP expression. So, these results suggest that the main proteolytic cascade, MMP‐2/MMP‐13/MT1‐MMP, and more particularly, its initial regulator MT1‐MMP is involved in osteoblast differentiation through mechanical forces. J. Cell. Biochem. 113: 760–772, 2012. © 2011 Wiley Periodicals, Inc.
Immunotherapy for metastatic melanoma
Authors: Zito Christopher R. , Kluger Harriet M. 
Published: October 2011

AbstractMelanoma has traditionally been considered an immunogenic tumor. A number of approaches have been studied for enhancement of antitumor immunity. The first cytokine approved for the treatment of metastatic melanoma, interleukin‐2, has resulted in prolonged responses in a small subset of patients, providing hope that immunotherapy might be useful for this disease. Ipilimumab, a monoclonal antibody to CTLA‐4, was recently approved and a number of other promising investigational approaches are currently being pursued. This manuscript discusses more recent advances in the treatment of melanoma employing a variety of immune‐enhancing approaches. J. Cell. Biochem. 113: 725–734, 2012. © 2011 Wiley Periodicals, Inc.
Efficient transgene expression from naked DNA delivered into an arterio‐venous fistula model for kidney dialysis
Authors: Globerman Anat S. , Chaouat Malka , Shlomai Zippora , Galun Eithan , Zeira Evelyn , Zamir Gideon 
Published: October 2011

AbstractBackgroundPatients with kidney failure frequently require the formation of an arterio‐venous fistula (AVF) in which a vein is connected to an artery resulting in arterialization of the vein to allow adequate blood flow into an external ‘artificial kidney’. In most patients, neo‐intimal hyperplasia (NIH) ensues, causing narrowing and subsequent occlusion of the vein, leading to significant morbidity. The cellular events causing venous NIH may serve as ideal targets for molecular‐based therapies. However, therapeutic gene delivery into the vascular system is seriously impeded by problems related to the low efficacy and toxicity of targeted viral vector delivery.Materials and methodsTo explore the feasibility of a plasmid‐based vascular gene delivery system, we established a rat AVF model that develops NIH. Plasmids encoding for reporter or therapeutic genes were delivered into the blood vessels at the time or after AVF formation.ResultsIntra‐luminal injection of plasmid into the AVF resulted in extensive and long‐term reporter gene expression at the venous limb mainly at the site of NIH formation. Transgene expression was confined to endothelial cells and myofibroblasts that migrate inwards from the adventitia and form the NIH lesion. There was no detrimental tissue reaction to plasmid delivery, contrasting with the severe inflammatory response observed after adenovirus infection. Intra‐vascular delivery of a plasmid carrying the endothelial nitric oxide synthase gene resulted in sustained production of nitric oxide, previously shown to mitigate NIH formation.ConclusionsThese findings open the possibility of vascular transduction with naked DNA bearing therapeutic genes in areas prone to NIH to ameliorate vein graft pathologies using simple and clinically applicable vector delivery methods. Copyright © 2011 John Wiley & Sons, Ltd.
MR in hypertension
Authors: Roditi Giles 
Published: October 2011

AbstractHypertension is a common systemic disorder affecting the cardiovascular system and kidneys with important morbidity and mortality. However, hypertension is often thought of by radiologists as an “invisible” disease. The aim of this article is to first review hypertension first in terms of its diagnosis, epidemiology and clinical importance. Second, those causes of secondary hypertension that may be diagnosed with MRI techniques are described along with the effects of hypertension on the cardiovascular system and kidneys that are demonstrable with MRI with particular emphasis on renovascular disease. Lastly the use of integrated MRI protocols to evaluate the hypertensive patient and areas for future research are considered. J. Magn. Reson. Imaging 2011. © 2011 Wiley Periodicals, Inc.
Physiological oxygen level is critical for modeling neuronal metabolism in vitro
Authors: Zhu Jing , Aja Susan , Kim Eun‐Kyoung , Park Min Jung , Ramamurthy Santosh , Jia Junling , Hu Xueying , Geng Ping , Ronnett Gabriele V. 
Published: October 2011

AbstractIn vitro models are important tools for studying the mechanisms that govern neuronal responses to injury. Most neuronal culture methods employ nonphysiological conditions with regard to metabolic parameters. Standard neuronal cell culture is performed at ambient (21%) oxygen levels, whereas actual tissue oxygen levels in the mammalian brain range from 1% to 5%. In this study, we examined the consequences of oxygen level on the viability and metabolism of primary cultures of cortical neurons. Our results indicate that physiological oxygen level (5% O2) has a beneficial effect on cortical neuronal survival and mitochondrial function in vitro. Moreover, oxygen level affects metabolic fluxes: glucose uptake and glycolysis was enhanced at physiological oxygen level, whereas glucose oxidation and fatty acid oxidation were reduced. Adenosine monophosphate‐activated protein kinase (AMPK) was more activated in 5% O2 and appears to play a role in these metabolic effects. Inhibiting AMPK activity with compound C decreased glucose uptake, intracellular ATP level, and viability in neurons cultured in 5% O2. These data indicate that oxygen level is an important parameter to consider when modeling neuronal responses to stress in vitro. © 2011 Wiley Periodicals, Inc.
Growth and development of pepper are affected by humic substances derived from composted sludge
Authors: Azcona Iñaki , Pascual Inmaculada , Aguirreolea Jone , Fuentes Marta , García‐Mina José María , Sánchez‐Díaz Manuel 
Published: October 2011

AbstractA greenhouse experiment was conducted to evaluate the effects of humic substances extracted from composted sewage sludge on growth, phenological development, and photosynthetic activity of pepper (Capsicum annuum L. cv. Piquillo) plants. Humic substances derived from composted sludge (HSS) were compared with those derived from leonardite (HSL). Two doses of both humic substances were assayed (200 and 500 mg C [L substrate]–1) and compared with a control (C). HSS showed higher nitrogen content and a higher percentage of aliphatic carbon, as well as a lower content of aromatic and phenolic carbon than HSL. HSS significantly increased plant dry‐matter production (up to 560%), plant height (86%–151%), and leaf area (436%–1397%) during the early stages of pepper development. Net photosynthesis and stomatal conductance increased in the treatments with HSS (up to 48% and 63%, respectively) at the vegetative stage. In addition, HSS accelerated the phenological development of pepper plants, reducing significantly the number of days to flowering and ripening, which occurred 12 and 14 d earlier than in control plants, respectively. In general, the treatments with HSS and HSL did not markedly affect chlorophyll and nutrient concentrations in the leaves. At maturity, only small differences in total fruit yield, number of fruits per plant, and fruit size were observed between amended and control plants. The results suggest that the mechanisms through which HSS affected plant growth and development were not associated with an improved nutrient uptake. Although the identity of the growth‐promoting factors remains to be found, the results suggest that they may be linked to the chemical structure of the humic substances.
Compost and phosphorus amendments for stimulating microorganisms and growth of ryegrass in a Ferralsol and a Luvisol
Authors: Khan Khalid Saifullah , Joergensen Rainer Georg 
Published: October 2011

AbstractA greenhouse pot experiment was carried out to investigate the effects of different P‐fertilizer application forms (triple superphosphate [TSP], compost + TSP, TSP‐enriched compost) on the growth of ryegrass and the soil microbial biomass. The fertilizers were applied at equivalent doses for all nutrients to a neutral Luvisol in comparison with an acidic Ferralsol. Fertilizer application led to significantly increased contents of microbial biomass C, N, and P. Furthermore, yields of shoot C and root C, and concentrations of P, Ca, Mg, K, Fe, and Mn in shoots and roots were significantly increased. These increases always followed the order TSP < compost + TSP < TSP‐enriched compost. Sole TSP application led only to maximum concentrations of N and S. In the Ferralsol, TSP had only minimal positive effect on the P concentration of the grass shoots. The positive effect of TSP‐enriched compost, i.e., incubating TSP together with compost for 24 h, did not differ between the neutral Luvisol and the acidic Ferralsol, i.e., the effect is independent of the soil type. Consequently, soluble inorganic P fertilizer should generally be mixed into an organic fertilizer before application to soil.