bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of lifestyle activities on alzheimer disease biomarkers and cognition
Authors: Vemuri Prashanthi , Lesnick Timothy G. , Przybelski Scott A. , Knopman David S. , Roberts Rosebud O. , Lowe Val J. , Kantarci Kejal , Senjem Mathew L. , Gunter Jeffrey L. , Boeve Bradley F. , Petersen Ronald C. , Jack Clifford R. 
Published: June 2012

AbstractObjective:A study was undertaken to investigate the association of intellectual and physical activity with biomarkers of Alzheimer disease (AD) pathophysiology and cognition in a nondemented elderly population. The biomarkers evaluated were brain Aβ load via Pittsburgh compound B (PiB)‐positron emission tomography (PET), neuronal dysfunction via 18F‐fluorodeoxyglucose (FDG)‐PET, and neurodegeneration via structural magnetic resonance imaging (MRI).Methods:We studied 515 nondemented (428 cognitively normal and 87 mild cognitive impairment) participants in the population‐based Mayo Clinic Study of Aging who completed a 3T MRI, PET scans, and APOE genotype, and had lifestyle activity measures and cognition data available. The imaging measures computed were global PiB‐PET uptake, and global FDG‐PET and MRI based hippocampal volume. We consolidated activity variables into lifetime intellectual, current intellectual, and current physical activities. We used a global cognitive z score as a measure of cognition. We applied 2 independent methods—partial correlation analysis adjusted for age and gender and path analysis using structural equations—to evaluate the associations between lifestyle activities, imaging biomarkers, and global cognition.Results:None of the lifestyle variables were correlated with the biomarkers, and the path associations between lifestyle variables and biomarkers were not significant (p > 0.05). Conversely, all the biomarkers were correlated with global cognitive z score (p < 0.05), and the path associations between (lifetime and current) intellectual activities and global z score were significant (p < 0.01).Interpretation:Intellectual and physical activity lifestyle factors were not associated with AD biomarkers, but intellectual lifestyle factors explained variability in the cognitive performance in this nondemented population. This study provides evidence that lifestyle activities may delay the onset of dementia but do not significantly influence the expression of AD pathophysiology. ANN NEUROL 2012;72:730–738
Assessment of environmental flow requirements
Authors: Jain Sharad K. 
Published: June 2012

AbstractFlow is considered to be the master variable for a river because the fluvial processes and health of its ecosystem critically depend upon flow. Increasing water withdrawals from many rivers of the world are leading to severe degradation in river ecosystems. Water is allocated for environmental needs so that a river can perform its natural functions. This article discusses the concept of environmental flow, methods to assess it, and issues in implementation. Copyright © 2012 John Wiley & Sons, Ltd.
Germline variants of base excision repair genes and breast cancer: A polymorphism in DNA polymerase gamma modifies gene expression and breast cancer risk
Authors: Popanda Odilia , Seibold Petra , Nikolov Ivaylo , Oakes Christopher C. , Burwinkel Barbara , Hausmann Sebastian , Flesch‐Janys Dieter , Plass Christoph , Chang‐Claude Jenny , Schmezer Peter 
Published: June 2012

AbstractBase excision repair (BER) removes DNA damage induced by endogenous reactive oxygen species or ionizing radiation, important breast cancer risk factors. Genetic variation associated with impaired BER might thus increase breast cancer risk. Therefore, we assessed risk associations of 123 common single nucleotide polymorphisms (SNPs) in 19 BER genes in 1,639 postmenopausal breast cancer cases and 1,967 controls from the German population‐based case‐control study MARIE. SNPs were tagging SNPs representing genetic variation across the gene together with potentially functional SNPs. Risk associations were assessed using conditional logistic regression, adjusted for potential breast cancer risk factors. Significant associations between polymorphisms and breast cancer risk were found for one SNP in PARP2 and three SNPs in the mitochondrial DNA polymerase gamma, POLG. A SNP in the promoter region of POLG (rs2856268, A>G) showed a protective effect for homozygous GG carriers (odds ratio 0.81, 95% confidence intervals 0.65–1.00). Joint analysis of an enlarged sample set and haplotype analysis supported the results for POLG. Quantification of POLG mRNA expression in lymphocytes of 148 breast cancer patients revealed higher mRNA levels for rs2856268 GG carriers (p value = 0.038). A luciferase promoter assay showed significant differences between constructs harboring the respective alleles. Taken together, our results suggest that genetic variation in the POLG promoter region affects DNA polymerase gamma levels in mitochondria. This could contribute to the reported increase in mitochondrial mutation frequency resulting in dysfunction and altered breast cancer risk. Risk effects and the functional impact of the POLG promoter variant require further confirmation.
Overcoming evasive resistance from vascular endothelial growth factor a inhibition in sarcomas by genetic or pharmacologic targeting of hypoxia‐inducible factor 1α
Authors: Kim Yeo‐Jung , Lee Hae‐June , Kim Tae‐Min , Eisinger‐Mathason T.S. Karin , Zhang Alexia Y. , Schmidt Benjamin , Karl Daniel L. , Nakazawa Michael S. , Park Peter J. , Simon M. Celeste , Yoon Sam S. 
Published: June 2012

AbstractIncreased levels of hypoxia and hypoxia‐inducible factor 1α (HIF‐1α) in human sarcomas correlate with tumor progression and radiation resistance. Prolonged antiangiogenic therapy of tumors not only delays tumor growth but may also increase hypoxia and HIF‐1α activity. In our recent clinical trial, treatment with the vascular endothelial growth factor A (VEGF‐A) antibody, bevacizumab, followed by a combination of bevacizumab and radiation led to near complete necrosis in nearly half of sarcomas. Gene Set Enrichment Analysis of microarrays from pretreatment biopsies found that the Gene Ontology category “Response to hypoxia” was upregulated in poor responders and that the hierarchical clustering based on 140 hypoxia‐responsive genes reliably separated poor responders from good responders. The most commonly used chemotherapeutic drug for sarcomas, doxorubicin (Dox), was recently found to block HIF‐1α binding to DNA at low metronomic doses. In four sarcoma cell lines, HIF‐1α shRNA or Dox at low concentrations blocked HIF‐1α induction of VEGF‐A by 84–97% and carbonic anhydrase 9 by 83–93%. HT1080 sarcoma xenografts had increased hypoxia and/or HIF‐1α activity with increasing tumor size and with anti‐VEGF receptor antibody (DC101) treatment. Combining DC101 with HIF‐1α shRNA or metronomic Dox had a synergistic effect in suppressing growth of HT1080 xenografts, at least in part via induction of tumor endothelial cell apoptosis. In conclusion, sarcomas respond to increased hypoxia by expressing HIF‐1α target genes that may promote resistance to antiangiogenic and other therapies. HIF‐1α inhibition blocks this evasive resistance and augments destruction of the tumor vasculature.
Tumor‐associated autoantibody signature for the early detection of gastric cancer
Authors: Zayakin Pawel , Ancāns Guntis , Siliņa Karīna , Meistere Irēna , Kalniņa Zane , Andrejeva Diāna , Endzeliņš Edgars , Ivanova Lāsma , Pismennaja Angelina , Ruskule Agnese , Doniņa Simona , Wex Thomas , Malfertheiner Peter , Leja Mārcis , Linē Aija 
Published: June 2012

AbstractAutoantibodies against tumor‐associated antigens are very attractive biomarkers for the development of noninvasive serological tests for the early detection of cancer because of their specificity and stability in the sera. In our study, we applied T7 phage display‐based serological analysis of recombinant cDNA expression libraries technique to identify a representative set of antigens eliciting humoral responses in patients with gastric cancer (GC), produced phage–antigen microarrays and exploited them for the survey of autoantibody repertoire in patients with GC and inflammatory diseases. We developed procedures for data normalization and cutoff determination to define sero‐positive signals and ranked them by the signal intensity and frequency of reactivity. To identify autoantibodies with the highest diagnostic value, a 1,150‐feature microarray was tested with sera from 100 patients with GC and 100 cancer‐free controls, and then the top‐ranked 86 antigens were used for the production of focused array that was tested with an independent validation set comprising serum samples from 235 patients with GC, 154 patients with peptic ulcer and gastritis and 213 healthy controls. The receiver operating characteristic curve analysis showed that 45‐autoantibody signature could discriminate GC and healthy controls with area under the curve (AUC) of 0.79 (59% sensitivity and 90% specificity), GC and peptic ulcer with AUC of 0.76 and GC and gastritis with AUC of 0.64. Moreover, it could detect early GC with equal sensitivity than advanced GC. Interestingly, the autoantibody production did not correlate with histological type, H. pylori status, grade, localization and size of the primary tumor, whereas it appeared to be associated with the metastatic disease.
Ikaros is a critical target during simultaneous exposure to X‐rays and N‐ethyl‐N‐nitrosourea in mouse T‐cell lymphomagenesis
Authors: Hirano Shinobu , Kakinuma Shizuko , Amasaki Yoshiko , Nishimura Mayumi , Imaoka Tatsuhiko , Fujimoto Shinji , Hino Okio , Shimada Yoshiya 
Published: June 2012

AbstractCancer risk associated with radiation exposure is considered the result of concurrent exposure to other natural and manmade carcinogens. Available data on the molecular characteristics of cancer after simultaneous exposure to radiation and chemicals are insufficient. In our study, we used a mouse thymic lymphoma (TL) model that was synergistically induced by simultaneous exposure to X‐rays and N‐ethyl‐N‐nitrosourea (ENU) at subcarcinogenic doses and analyzed the mutation frequency and spectrum of the TL‐associated genes Ikaros, Notch1, p53 and Kras. We found that the point mutation frequency in Ikaros was significantly increased to 47% for simultaneous exposure compared to 13 and 0% for X‐ray and ENU exposure alone, respectively. These mutations were mostly G:C > A:T at non‐CpG sites and T:A > C:G, both of which are characteristic of ENU mutagenesis. About half of the point mutations were accompanied by loss of heterozygosity (LOH), typical of X‐irradiation. The remaining half did not include LOH, which suggests that they were dominant‐negative mutations. In Notch1, the frequency of abnormalities was high (>58%) regardless of the treatment, suggesting that Notch1 aberration may be important for T‐cell lymphomagenesis. The p53 and Kras mutation frequencies were low for all treatments (<23%). Importantly, the frequency of TLs containing mutations in multiple genes, especially both Ikaros and Notch1, increased after simultaneous exposure. Thus, after simultaneous exposure, Ikaros is a critical target and is inactivated by ENU‐induced point mutations and/or X‐ray‐induced LOH in T‐cell lymphomagenesis. Furthermore, concomitant alterations of multiple tumor‐associated genes may contribute to enhanced lymphomagenesis after simultaneous exposure.
Three‐dimensional finite elements with embedded strong discontinuities to model material failure in the infinitesimal range
Authors: Armero F. , Kim J. 
Published: June 2012

SUMMARYThis paper presents new three‐dimensional finite elements with embedded strong discontinuities in the small strain infinitesimal range. The goal is to model localized surfaces of failure in solids, such as cracks at fracture, through enhancements of the finite elements that capture the propagating discontinuities of the displacement field in the element interiors. In this way, such surfaces of discontinuity can be sharply resolved in general meshes not necessarily related to the detailed geometry of the surface, unknown a priori. An important issue is also the consideration of general finite element formulations in the developments (e.g., basic displacement‐based, mixed or enhanced assumed strain finite element formulations), as needed to optimally resolve the continuum problem in the bulk. The actual modeling of the discontinuity effects, including the incorporation of the cohesive law defining the discontinuity constitutive response, is carried out at the element level with the proper enhancement of the discrete strain field of the element. The added elemental degrees of freedom approximate the displacement jumps associated with the discontinuity and are defined independently from element to element, thus allowing their static condensation at the element level without affecting the global mechanical problem in terms of the number and topology of the global degrees of freedom. In fact, this global‐local structure of the finite element methods developed in this work arises naturally from a multi‐scale characterization of these localized solutions, with the discontinuities understood to appear in the small scales, thus leading directly to these computationally efficient numerical methods for their numerical resolution, easily incorporated to an existing finite element code. The focus in this paper is on the development of finite elements incorporating a linear interpolation of the displacement jumps in the general three‐dimensional setting. These interpolations are shown to be necessary for hexahedral elements to avoid the so‐called stress locking that occurs with simpler constant approximations of the jumps (namely, a spurious transfer of stresses across the discontinuity not allowing its full release and, hence, resulting in an overstiff or locked numerical solution). The design of the new finite elements is accomplished in this work by a direct identification of the separation modes to be incorporated in the discrete strain field of the element, rather than from an assumed discontinuous interpolation of the displacements, assuring with this approach their locking‐free response by design. An additional issue addressed in the paper is the geometric characterization and propagation of the discontinuity surfaces in the general three‐dimensional setting of interest here. The paper includes a series of numerical simulations illustrating and evaluating the properties of the new finite elements. Copyright © 2012 John Wiley & Sons, Ltd.
An XFEM‐based numerical strategy to model mechanical interactions between biological cells and a deformable substrate
Authors: Farsad Mehdi , Vernerey Franck J. 
Published: June 2012

SUMMARYContractile cells are known to constantly probe and respond to their mechanical environment through mechanosensing. Although the very mechanisms responsible for this behavior are still obscure, it is now clear that cells make full use of cross‐talks between mechanics, chemistry, and transport to organize their structure and generate forces. To investigate these processes, it is important to derive mathematical and numerical models that can accurately capture the interactions between cells and an underlying deformable substrate. The present paper therefore introduces a computational framework, based on the extended FEM (XFEM) and the level set method, to model the evolution of two‐dimensional (plane stress) cells lying on an elastic substrate whose properties can be varied. Cells are modeled with a continuum mixture approach previously developed by the authors to describe key phenomena of cell sensing, such as stress fiber formation, mechanosensitive contraction, and molecular transport whereas cell–substrate adhesion is formulated with a linear elastic cohesive model. From a numerical viewpoint, cell and substrate are discretized on a single, regular finite element mesh, whereas the potentially complex cell geometry is defined in terms of a level set function that is independent of discretization. Field discontinuities across the cell membrane are then naturally enforced using enriched shape functions traditionally used in the XFEM formulation. The resulting method provides a flexible platform that can handle complex cell geometries, can avoid expensive meshing techniques, and can potentially be extended to study cell growth and migration on an elastic substrate. In addition, the XFEM formalism facilitates the consideration of the cell's cortical elasticity, a feature that is known to be important during cell deformation. The proposed method is illustrated with a few biologically relevant examples of cell–substrate interactions. Generally, the method is able to capture some key phenomena observed in biological systems and displays numerical versatility and accuracy at a moderate computational cost.Copyright © 2012 John Wiley & Sons, Ltd.
Finite element modeling of cerebral angioplasty using a structural multi‐mechanism anisotropic damage model
Authors: Li Dalong , Robertson Anne M. , Lin Guoyu , Lovell Michael 
Published: June 2012

SUMMARYArterial progressive damage, softening and non‐recoverable deformation are typical effects of percutaneous transluminal angioplasty (PTA), induced mechanically by the overstretching and widening of arterial walls during balloon dilatation. In this paper, we model this ‘controlled vessel injury’ in cerebral balloon angioplasty by extending a recently developed structural multi‐mechanism damage model for cerebral arterial tissue in early stage aneurysms. The current constitutive model focuses on arterial mechanical damage and can characterize the wall anisotropy and subfailure damage of the elastin, ground matrix and collagen, represented by the recruitment of collagen fibers, gradual degeneration, failure of arterial components and changes in the tissue mechanical properties. Cyclic uniaxial response of homogeneous artery models is used to validate the numerical implementation of the constitutive model. Cerebral arteries are modeled as a multi‐layer heterogeneous wall model composed of the internal elastic lamina, media and adventitia. Cerebral angioplasty is simulated by contact between the heterogeneous artery model and a simplified balloon model. The states of arterial deformation, tissue damage and wall stress during angioplasty are analyzed, which reproduces the qualitative features of cerebral PTA observed experimentally. The constitutive model and computational methods are demonstrated to be robust in simulating complex tissue response caused by the mechanical intervention of angioplasty, and are applied in more realistic artery‐plaque‐balloon‐stent models. Copyright © 2012 John Wiley & Sons, Ltd.
Theoretical study on angular momentum polarization parameters, branching ratios, and anisotropy parameters of chlorine atoms from Photodissociation of Iodine Monochloride
Authors: Matsuoka Takahide , Oonishi Sayo , Yabushita Satoshi 
Published: June 2012

AbstractLow‐lying excited state potential energy curves (PECs), nonadiabatic coupling terms, and transition dipole moments of ICl have been obtained by a spin‐orbit configuration interaction method. The angular momentum polarization parameters of photofragments can be calculated from these properties of the molecule. The first‐rank parameter Im[a1(1)(//,⟂)] of the ground state photofragment Cl(2P3/2) in the first absorption band (490–560 nm) is very sensitive to the PECs of the low‐lying excited states, especially the A(1) and B(0+) states. The phase part of the calculated parameter Im[a1(1)(//,⟂)] agrees well with experiment. We further clarify the characteristics of avoided crossing between the X(0+) and B(0+) states. We calculated the product fraction of Cl*(2P1/2) and the anisotropy parameter β to demonstrate the effect of photoabsorption caused by the z(1) state, which supports a recent experimental analysis. © 2012 Wiley Periodicals, Inc.
Theoretical estimation of the acidities of alcohols and azoles in gas phase, DMSO, and water
Authors: Seybold Paul G. , Kreye W. C. 
Published: June 2012

AbstractMost acidities and basicities of chemical compounds are measured in aqueous solution since this solvent is most important for biochemical and environmental applications, but the acidities of compounds in the gas phase and in other solvents can also be of interest. As a polar, aprotic solvent, dimethyl sulfoxide (DMSO) presents a unique environment for acid dissociation, and this solvent offers informative comparisons with both the vacuum and aqueous environments. Here, quantum chemical approaches previously used for the estimation of aqueous pKa values are applied to the estimation of DMSO, aqueous, and gas‐phase acidities for two representative series of compounds: alcohols/phenols and azoles. Calculations were performed using both the semiempirical RM1 method and density functional theory (B3LYP/6‐31+G**). The effectiveness of the SM5.4 and SM8 solvent models in estimating the solution‐phase acidities was also examined. © 2012 Wiley Periodicals, Inc.
Increased Glyceride–Glycerol Synthesis in Liver and Brown Adipose Tissue of Rat: In‐Vivo Contribution of Glycolysis and Glyceroneogenesis
Authors: Chaves Valéria E. , Frasson Danúbia , Garófalo Maria A. R. , Navegantes Luiz C. C. , Migliorini Renato H. , Kettelhut Isis C. 
Published: June 2012

AbstractWe have previously shown that a high‐protein, carbohydrate‐free diet can decrease the production of glycerol‐3‐phosphate (G3P) from glucose and increase glyceroneogenesis in both brown (BAT) and epididymal (EAT) adipose tissue. Here, we utilized an in‐vivo approach to examine the hypothesis that there is reciprocal regulation in the G3P synthesis from glucose (via glycolysis) and glyceroneogenesis in BAT, EAT and liver of fasted rats and cafeteria diet‐fed rats. Glyceroneogenesis played a prominent role in the generation of G3P in the liver (~70 %) as well as in BAT and EAT (~80 %) in controls rats. The cafeteria diet induced an increase in the total glyceride‐glycerol synthesis and G3P synthesis from glucose and a decrease in glyceroneogenesis in BAT; this diet did not affect either the total glyceride‐glycerol synthesis or G3P generation from glyceroneogenesis or glycolysis in the liver or EAT. Fasting induced an increase in total glyceride‐glycerol synthesis and glyceroneogenesis and a decrease in G3P synthesis from glucose in the liver but did not affect either the total glyceride‐glycerol synthesis or G3P synthesis from glyceroneogenesis in BAT and EAT, despite a reduction in glycolysis in these tissues. These data demonstrate that reciprocal changes in the G3P generation from glucose and from glyceroneogenesis in the rat liver and BAT occur only when the synthesis of glycerides–glycerol is increased. Further, our data suggest that this increase may be essential for the systemic recycling of fatty acids by the liver from fasted rats and for the maintenance of the thermogenic capacity of BAT from cafeteria diet‐fed rats.