Truss-like Discrete Element Method Applied to Damage Process Simulation in Quasi-Brittle Materials

This paper discusses the combined application of the lattice discrete element method (LDEM) and the acoustic emission (AE) technique to analyze damage in quasi-brittle materials. These methods were used to study the damage in a concrete slab under pure-shear stress and a pre-fissured sandstone beam subjected to three-point bending. The first test was restricted to simulation results, whereas the second included experimental data. The discrete element method was used to perform the simulations for both tests, whereas the corresponding results and the information from the experiments were assessed using AE analysis tools. It was shown that the synergistic use of these two methods led to a comprehensive understanding of the two analyzed cases and offered an effective, generalizable approach for assessing damage processes in quasi-brittle materials

Aquifex aeolicus 3-Deoxy- d - manno -2-Octulosonic Acid 8-Phosphate Synthase: A New Class of KDO 8-P Synthase?

The relationship between 3-deoxy- d - manno 2-octulosonic acid 8-phosphate (KDO 8-P) synthase and 3-deoxy- d - arabino -2-heptulosonic acid 7-phosphate (DAH 7-P) synthase has not been adequately addressed in the literature. Based on recent reports of a metal requiring KDO 8-P synthase and the newly solved X-ray crystal structures of both Escherichia coli KDO 8-P synthase and DAH 7-P synthase, we begin to address the evolutionary kinship between these catalytically similar enzymes. Using a maximum likelihood-based grouping of 29 KDO 8-P synthase sequences, we demonstrate the existence of a new class of KDO 8-P synthase, the members of which we propose to require a metal cofactor for catalysis. Similarly, we hypothesize a class of DAH 7-P synthase that does not have the metal requirement of the heretofore model E. coli enzyme. Based on this information and a careful investigation of the reported X-ray crystal structures, we also propose that KDO 8-P synthase and DAH 7-P synthase are the product of a divergent evolutionary process from a common ancestor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42370/1/239-52-2-205_10520205.pd

High fat, low carbohydrate diet limit fear and aggression in Göttingen minipigs

High fat, low carbohydrate diets have become popular, as short-term studies show that such diets are effective for reducing body weight, and lowering the risk of diabetes and cardiovascular disease. There is growing evidence from both humans and other animals that diet affects behaviour and intake of fat has been linked, positively and negatively, with traits such as exploration, social interaction, anxiety and fear. Animal models with high translational value can help provide relevant and important information in elucidating potential effects of high fat, low carbohydrate diets on human behaviour. Twenty four young, male Göttingen minipigs were fed either a high fat/cholesterol, low carbohydrate diet or a low fat, high carbohydrate/sucrose diet in contrast to a standard low fat, high carbohydrate minipig diet. Spontaneous behaviour was observed through video recordings of home pens and test-related behaviours were recorded during tests involving animal-human contact and reaction towards a novel object. We showed that the minipigs fed a high fat/cholesterol, low carbohydrate diet were less aggressive, showed more non-agonistic social contact and had fewer and less severe skin lesions and were less fearful of a novel object than minipigs fed low fat, high carbohydrate diets. These results found in a porcine model could have important implications for general health and wellbeing of humans and show the potential for using dietary manipulations to reduce aggression in human society

Nucleosynthetic osmium isotope anomalies in acid leachates of the Murchison meteorite

We present osmium isotopic results obtained by sequential leaching of the Murchison meteorite, which reveal the existence of very large internal anomalies of nucleosynthetic origin. The Os isotopic anomalies are correlated, and can be explained by the variable contributions of components derived from the s, r and p-processes of nucleosynthesis. Much of the s-process rich osmium is released by relatively mild leaching, suggesting the existence of an easily leachable s-process rich presolar phase, or alternatively, of a chemically resistant r-process rich phase. The s-process composition of Os released by mild leaching diverges slightly from that released by aggressive digestion techniques, perhaps suggesting that the presolar phases attacked by these differing procedures condensed in different stellar environments. The correlation between 190Os and 188Os can be used to constrain the s-process 190Os/188Os ratio to be 1.275 pm 0.043. Such a ratio can be reproduced in a nuclear reaction network for a MACS value for 190Os of ~200 pm 22 mbarn at 30 keV. We also present evidence for extensive internal variation of 184Os abundances in the Murchison meteorite. This suggests that p process rich presolar grains (e.g., supernova condensates) may be present in meteorites in sufficient quantities to influence the Os isotopic compositions of the leachates.Comment: 40 pages, 9 figures, 2 tables. Accepted for publication in Earth and Planetary Science Letter

Short-lived Nuclei in the Early Solar System: Possible AGB Sources

(Abridged) We review abundances of short-lived nuclides in the early solar system (ESS) and the methods used to determine them. We compare them to the inventory for a uniform galactic production model. Within a factor of two, observed abundances of several isotopes are compatible with this model. I-129 is an exception, with an ESS inventory much lower than expected. The isotopes Pd-107, Fe-60, Ca-41, Cl-36, Al-26, and Be-10 require late addition to the solar nebula. Be-10 is the product of particle irradiation of the solar system as probably is Cl-36. Late injection by a supernova (SN) cannot be responsible for most short-lived nuclei without excessively producing Mn-53; it can be the source of Mn-53 and maybe Fe-60. If a late SN is responsible for these two nuclei, it still cannot make Pd-107 and other isotopes. We emphasize an AGB star as a source of nuclei, including Fe-60 and explore this possibility with new stellar models. A dilution factor of about 4e-3 gives reasonable amounts of many nuclei. We discuss the role of irradiation for Al-26, Cl-36 and Ca-41. Conflict between scenarios is emphasized as well as the absence of a global interpretation for the existing data. Abundances of actinides indicate a quiescent interval of about 1e8 years for actinide group production in order to explain the data on Pu-244 and new bounds on Cm-247. This interval is not compatible with Hf-182 data, so a separate type of r-process is needed for at least the actinides, distinct from the two types previously identified. The apparent coincidence of the I-129 and trans-actinide time scales suggests that the last actinide contribution was from an r-process that produced actinides without fission recycling so that the yields at Ba and below were governed by fission.Comment: 92 pages, 14 figure files, in press at Nuclear Physics

Treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study

Introduction: As the immunosuppressive potency of 15-deoxyspergualin (DSG) has been shown in the therapy of renal transplant rejection and Wegener's granulomatosis, the intention of this study was to evaluate the safety of DSG in the therapy of lupus nephritis (LN). Methods: Patients with histologically proven active LN after prior treatment with at least one immunosuppressant were treated with 0.5 mg/kg normal body weight/day DSG, injected subcutaneously for 14 days, followed by a break of one week. These cycles were repeated to a maximum of 9 times. Doses of oral corticosteroids were gradually reduced to 7.5 mg/day or lower by cycle 4. Response was measured according to a predefined decision pattern. The dose of DSG was adjusted depending on the efficacy and side effects. Results: 21 patients were included in this phase-I/II study. After the first DSG injection, one patient was excluded from the study due to renal failure. 5 patients dropped out due to adverse events or serious adverse events including fever, leukopenia, oral candidiasis, herpes zoster or pneumonia. 11/20 patients achieved partial (4) or complete responses (7), 8 were judged as treatment failures and one patient was not assessable. 12 patients completed all 9 cycles; in those patients, proteinuria decreased from 5.88g/day to 3.37g/day (P = 0.028), Selena-SLEDAI decreased from 17.6 to 11.7. In 13/20 patients, proteinuria decreased by at least 50%; in 7 patients to less than 1g/day. Conclusions: Although the number of patients was small, we could demonstrate that DSG provides a tolerably safe treatment for LN. The improvement in proteinuria encourages larger controlled trials

The amyloid imaging for the prevention of Alzheimer's disease consortium: A European collaboration with global impact

Background: Amyloid-β (Aβ) accumulation is considered the earliest pathological change in Alzheimer's disease (AD). The Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) consortium is a collaborative European framework across European Federation of Pharmaceutical Industries Associations (EFPIA), academic, and ‘Small and Medium-sized enterprises’ (SME) partners aiming to provide evidence on the clinical utility and cost-effectiveness of Positron Emission Tomography (PET) imaging in diagnostic work-up of AD and to support clinical trial design by developing optimal quantitative methodology in an early AD population. The AMYPAD studies: In the Diagnostic and Patient Management Study (DPMS), 844 participants from eight centres across three clinical subgroups (245 subjective cognitive decline, 342 mild cognitive impairment, and 258 dementia) were included. The Prognostic and Natural History Study (PNHS) recruited pre-dementia subjects across 11 European parent cohorts (PCs). Approximately 1600 unique subjects with historical and prospective data were collected within this study. PET acquisition with [18F]flutemetamol or [18F]florbetaben radiotracers was performed and quantified using the Centiloid (CL) method. Results: AMYPAD has significantly contributed to the AD field by furthering our understanding of amyloid deposition in the brain and the optimal methodology to measure this process. Main contributions so far include the validation of the dual-time window acquisition protocol to derive the fully quantitative non-displaceable binding potential (BPND), assess the value of this metric in the context of clinical trials, improve PET-sensitivity to emerging Aβ burden and utilize its available regional information, establish the quantitative accuracy of the Centiloid method across tracers and support implementation of quantitative amyloid-PET measures in the clinical routine. Future steps: The AMYPAD consortium has succeeded in recruiting and following a large number of prospective subjects and setting up a collaborative framework to integrate data across European PCs. Efforts are currently ongoing in collaboration with ARIDHIA and ADDI to harmonize, integrate, and curate all available clinical data from the PNHS PCs, which will become openly accessible to the wider scientific community

N-acetylcysteine does not prevent contrast-induced nephropathy after cardiac catheterization in patients with diabetes mellitus and chronic kidney disease: a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) constitute to be a high-risk population for the development of contrast-induced nephropathy (CIN), in which the incidence of CIN is estimated to be as high as 50%. We performed this trial to assess the efficacy of <it>N</it>-acetylcysteine (NAC) in the prevention of this complication.</p> <p>Methods</p> <p>In a prospective, double-blind, placebo controlled, randomized clinical trial, we studied 90 patients undergoing elective diagnostic coronary angiography with DM and CKD (serum creatinine ≥ 1.5 mg/dL for men and ≥ 1.4 mg/dL for women). The patients were randomly assigned to receive either oral NAC (600 mg BID, starting 24 h before the procedure) or placebo, in adjunct to hydration. Serum creatinine was measured prior to and 48 h after coronary angiography. The primary end-point was the occurrence of CIN, defined as an increase in serum creatinine ≥ 0.5 mg/dL (44.2 μmol/L) or ≥ 25% above baseline at 48 h after exposure to contrast medium.</p> <p>Results</p> <p>Complete data on the outcomes were available on 87 patients, 45 of whom had received NAC. There were no significant differences between the NAC and placebo groups in baseline characteristics, amount of hydration, or type and volume of contrast used, except in gender (male/female, 20/25 and 34/11, respectively; P = 0.005) and the use of statins (62.2% and 37.8%, respectively; P = 0.034). CIN occurred in 5 out of 45 (11.1%) patients in the NAC group and 6 out of 42 (14.3%) patients in the placebo group (P = 0.656).</p> <p>Conclusion</p> <p>There was no detectable benefit for the prophylactic administration of oral NAC over an aggressive hydration protocol in patients with DM and CKD.</p> <p>Trial registration</p> <p>NCT00808795</p

Molecular biology of breast cancer metastasis Molecular expression of vascular markers by aggressive breast cancer cells

During embryogenesis, the formation of primary vascular networks occurs via the processes of vasculogenesis and angiogenesis. In uveal melanoma, vasculogenic mimicry describes the 'embryonic-like' ability of aggressive, but not nonaggressive, tumor cells to form networks surrounding spheroids of tumor cells in three-dimensional culture; these recapitulate the patterned networks seen in patients' aggressive tumors and correlates with poor prognosis. The molecular profile of these aggressive tumor cells suggests that they have a deregulated genotype, capable of expressing vascular phenotypes. Similarly, the embryonic-like phenotype expressed by the aggressive human breast cancer cells is associated with their ability to express a variety of vascular markers. These studies may offer new insights for consideration in breast cancer diagnosis and therapeutic intervention strategies