196 research outputs found

    A Damage Mechanics Approach to Life Prediction for a Salt Structure

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    Excavated rooms in natural bedded salt formations are being considered for use as repositories for nuclear waste. It is presumed that deformation of the rooms by creep will lead to loss of structural integrity and affect room life history and seal efficiency. At projected repository temperatures, two possible fracture mechanisms in salt are creep-induced microcracking in triaxial compression and cleavage in tension. Thus, an accurate prediction of room life and seal degradation requires a reliable description of the creep and damage processes. While several constitutive models that treat either creep or fracture in salt are available in the literature, very few models have considered creep and damage in a coupled manner. Previously, Munson and Dawson formulated a set of creep equations for salt based on the consideration of dislocation mechanisms in the creep process. This set of creep equations has been generalized to include continuum, isotropic damage as a fully coupled variable in the response equation. The extended model has been referred to as the Multimechanism Deformation Coupled Fracture (MDCF) model. A set of material constants for the creep and damage terms was deduced based on test data for both clean and argillaceous salt. In this paper, the use of the MDCF model for establishing the failure criteria and for analyzing the creep response of a salt structure is demonstrated. The paper is divided into three parts. A summary of the MDCF model is presented first, which is followed by an evaluation of the MDCF model against laboratory data. Finally, finite-element calculations of the creep and damage response of a salt structure are presented and compared against in-situ field measurements

    A mouse model for Luminal epithelial like ER positive subtype of human breast cancer

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    <p>Abstract</p> <p>Background</p> <p>Generation of novel spontaneous ER positive mammary tumor animal model from heterozygous NIH nude mice.</p> <p>Methods</p> <p>Using brother-sister mating with pedigree expansion system, we derived a colony of heterozygous breeding females showing ER-Positive tumors around the age of 6 months. Complete blood picture, differential leukocyte count, and serum levels of Estrogen, Alanine amino transferase (SGPT), Aspartate amino transferase (SGOT), total protein and albumin were estimated. Aspiration biopsies and microbiology were carried out. Gross pathology of the tumors and their metastatic potential were assessed. The tumors were excised and further characterized using histopathology, cytology, electron microscopy (EM), molecular markers and Mouse mammary Tumor Virus – Long Terminal Repeats (MMTV LTR) specific RT-PCR.</p> <p>Results</p> <p>The tumors originated from 2<sup>nd</sup>or 5<sup>th</sup>or both the mammary glands and were multi-nodulated with variable central necrosis accompanied with an accumulation of inflammatory exudate. Significant increases in estrogen, SGPT, SGOT and neutrophils levels were noticed. Histopathologically, invasive nodular masses of pleomorphic tubular neoplastic epithelial cells invaded fibro-vascular stroma, adjacent dermis and subcutaneous tissue. Metastatic spread through hematogenous and regional lymph nodes, into liver, lungs, spleen, heart and dermal lymphatics was observed. EM picture revealed no viral particles and MMTV-negativity was confirmed through MMTV LTR-specific RT-PCR. High expression of ER α, moderate to high expression of proliferating cell nuclear antigen (PCNA), moderate expression of vimentin and Cytokeratin 19 (K19) and low expression of p53 were observed in tumor sections, when compared with that of the normal mammary gland.</p> <p>Conclusion</p> <p>Since 75% of human breast cancer were classified ER-positive and as our model mimics (in most of the characteristics, such as histopathology, metastasis, high estrogen levels) the ER-positive luminal epithelial-like human breast cancer, this model will be an attractive tool to understand the biology of estrogen-dependant breast cancer in women. To our knowledge, this is the first report of a spontaneous mammary model displaying regional lymph node involvement with both hematogenous and lymphatic spread to liver, lung, heart, spleen and lymph nodes.</p

    Psychosocial stressors and depression at a Swedish primary health care centre. A gender perspective study

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    <p>Abstract</p> <p>Background</p> <p>Psychosocial stress may account for the higher prevalence of depression in women and in individuals with a low educational background. The aim of this study was to analyse the association between depression and socio-demographic data, psychosocial stressors and lifestyle circumstances from a gender perspective in a relatively affluent primary care setting.</p> <p>Methods</p> <p>Patients, aged 18- 75 years, visiting a drop-in clinic at a primary care health centre were screened with Beck's Depression Inventory (BDI). The physicians used also targeted screening with BDI. A questionnaire on socio-demographic data, psychosocial stressors and use of alcohol and tobacco was distributed. Among patients, who scored BDI ≥10, DSM-IV-criteria were used to diagnose depression. Of the 404 participants, 48 men and 76 women were diagnosed with depression. The reference group consisted of patients with BDI score <10, 187 men and 93 women. Age-adjusted odds ratios (ORs) with 95% confidence intervals (CI) as being depressed were calculated for the psychosocial stressors and lifestyle circumstances, separately for men and women. Multiple logistic regression analyses were used to determine the age-adjusted main effect models for men and women.</p> <p>Results</p> <p>The same three psychosocial stressors: feeling very stressed, perceived poor physical health and being dissatisfied with one's family situation were associated with depression equally in men and women. The negative predictive values of the main effect models in men and women were 90.7% and 76.5%, respectively. Being dissatisfied with one's work situation had high ORs in both men and women. Unemployment and smoking were associated with depression in men only.</p> <p>Conclusions</p> <p>Three questions, frequently asked by physicians, which involve patient's family and working situation as well as perceived stress and physical health, could be used as depression indicators in early detection of depression in men and women in primary health care.</p

    Alterations of brain and cerebellar proteomes linked to Aβ and tau pathology in a female triple-transgenic murine model of Alzheimer's disease

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    The triple-transgenic Alzheimer (3 × Tg-AD) mouse expresses mutant PS1M146V, APPswe, and tauP301L transgenes and progressively develops plaques and neurofibrillary tangles with a temporal- and region-specific profile that resembles the neuropathological progression of Alzheimer's disease (AD). In this study, we used proteomic approaches such as two-dimensional gel electrophoresis and mass spectrometry to investigate the alterations in protein expression occurring in the brain and cerebellum of 3 × Tg-AD and presenilin-1 (PS1) knock-in mice (animals that do not develop Aβ- or tau-dependent pathology nor cognitive decline and were used as control). Finally, using the Ingenuity Pathway Analysis we evaluated novel networks and molecular pathways involved in this AD model. We identified several differentially expressed spots and analysis of 3 × Tg-AD brains showed a significant downregulation of synaptic proteins that are involved in neurotransmitter synthesis, storage and release, as well as a set of proteins that are associated with cytoskeleton assembly and energy metabolism. Interestingly, in the cerebellum, a structure not affected by AD, we found an upregulation of proteins involved in carbohydrate metabolism and protein catabolism. Our findings help to unravel the pathogenic brain mechanisms set in motion by mutant amyloid precursor protein (APP) and hyperphosphorylated tau. These data also reveal cerebellar pathways that may be important to counteract the pathogenic actions of Aβ and tau, and ultimately offer novel targets for therapeutic intervention
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