Search

The paper presents an iterative approach based on stochastic simulations and adaptive Kriging metamodels to perform reliability and safety assessments of soil slopes. Two new rules for adaptively selecting support points are proposed, considering an entropy learning function and the closeness to the failure domain defined by a limit state function. In addition, a stopping criterion is proposed based on root-mean-square and mean absolute percentage errors computed with cross-validation at the local level, focusing on regions where the uncertainties are relevant. Finally, the selection rules for support points and the error metrics are implemented in two benchmark problems with a low, moderate, and high probability of failure. Ultimately, the work leads to an adaptive Kriging strategy for slope stability assessment, offering: (1) a fair comparison with other strategies based on a significant number of realizations, (2) a stopping criteria based on a new local error metric, (3) an insight of the behavior across different magnitudes of the probability of failure, and (4) a new selection rule that reduces the total number of support points significantly. The proposed scheme is easily paired with commercial software to compute support points, resulting in an attractive tool for practitioners.

A systematic analysis of primary damage will follow for high-energy recoils, in order to get distribution of cascades and subcascades versus recoil energies. Considering Fe, simulations have been performed using new activation energies for diffusion of interstitial defects, and a new random 3D movement has been considered in modeling. New vacancy's migration energies for 3-4 vacancy clusters and last ab-initiodiffusion parameters for impurities were also implemented. Results will be compared to experiments, to quantify the defect concentration and the defect type. A new full scale of irradiation experiments of metals and diagnosis including resistivity analysis will also be presented. In addition, the plans to extend such defect dynamics simulation to the scale of defect-dislocation dynamics will be presented. Using defect energetic and cascade damage obtained from molecular dynamics, results will be presented on irradiation of hcp ${\rm \alpha} $-Zr under different conditions with a kinetic Monte Carlo model. Cascades of 25 keV will be considered in the evolution of the microstructure during irradiation under environment conditions of 600K, 10- 6dpa/s and 0.5 dpa. We will present preliminary comparisons with experimental data. Finally, our previous and present results on ${\rm \alpha} $-Zr will be extrapolated to Titanium that has very useful applications in nuclear fusion reactors. Defects in silica and carbon may be present in the material, in many cases associated to impurities, or generated by irradiation. A systematic identification of defect types in these materials, depending on its final potential energy and its morphology, calculating the co-ordination and neighbour type will be presented, and their concentration as a function of stoichiometric deviations is studied using classical molecular dynamic. To study the effects of different hydrogen isotopes in silica and their interaction with the defect concentration is considered as an important effect and a modelling analysis will be presented. A full-scale experimental program, using visible and infrared optical spectroscopy, for understanding those mechanisms and validate simulation results will also be presented.

Our aim was to assess short-term natural course of hypogonadism diagnosed during hospitalization for acute disease in aged male patients after discharge. A group of 43 hypogonadal males, aged 86.7 ± 5.7 year, was studied. Serum concentrations of testosterone (T) and gonadotropins (follicle-stimulating hormone, FSH, and luteinizing hormone, LH) were measured in every patient both at admission and one month after discharge. Mean serum T at entry was 115.4 ± 48.0 ng/dl. Hypogonadism was hyper-, hypo-, and normogonadotropic in 20 (46.5 %), 20 (46.5 %), and 3 (7.0 %) patients, respectively. One month after discharge serum T concentrations increased significantly (230.9 ± 135.6 ng/dl, p< 0.001). At this point, more than half of the patients (n= 27, 62.8 %) showed normal serum T concentrations. Both gonadotropins, FSH (p< 0.001), and LH (p= 0.04) also increased one month after discharge. Approximately, half of the patients (13, 48.1 %) who normalized serum T concentrations also showed normal serum gonadotropin concentrations. Patients who normalized their serum T concentrations one month after discharge showed significantly higher baseline values of T (134.7 ± 33.9 ng/dl) than those who persisted with hypogonadism (n= 16, 32.7 %; 82.8 ± 51.6 ng/dl, p< 0.001). Lastly, serum T was the only independent predictor for achieving eugonadal status (OR 1.030; CI 95 %, 1.010–1.050; p< 0.001). In conclusion, about 63 % of aged patients hospitalized for acute illness with hypogonadism discovered during hospitalization spontaneously normalize their serum T concentrations one month after discharge. Serum gonadotropin concentrations also increased after discharge. Serum T levels at admission was an independent predictor for the normalization of serum T concentrations.

Male hypogonadism is common in the elderly and has been associated with increased risk of mortality. Our objective has been to assess the prevalence of primary and central hypogonadism in elderly male patients admitted to the hospital because of acute illness. We also evaluated the relationships between gonadal dysfunction and in-hospital mortality. 150 patients, aged =65 years, admitted during 2010 and 2011 in our geriatric unit, were studied. Serum concentrations total, bioavailable and free testosterone, as well as of follicle-stimulating hormone and luteinizing hormone were quantified in every patient. Hypogonadism was defined by the presence of serum testosterone levels lower than 200 ng/dl. Hypogonadism was found in 80 patients (53.3 %). Serum gonadotropin concentrations were elevated in 43.7 % of these patients, whereas 41.3 % of hypogonadic patients showed normal and 15 % low gonadotropin concentrations. Respiratory tract infection and congestive heart failure were the main causes of hospitalization in hypogonadal men, whereas acute cerebrovascular disease was the main reason for admission in eugonadal patients. Of the 13 patients who died during hospitalization, 12 were hypogonadic. Patients who died showed significantly lower serum levels of total, free and bioavailable testosterone than those found in patients who survived. Our results show that about half of patients admitted for acute illness have hypogonadism, mainly of non-hypergonadotropic type. Gonadal hypofunction is significantly related with in-hospital mortality. A low value of serum testosterone may be a predictor for mortality in elderly male patients.

Objectives: To assess short-term spontaneous evolution of alterations in thyroid function tests in aged hospitalized patients after discharge. Methods: A group of 146 patients (mean age±SD 85.9±6.2 yr) was studied. Serum concentrations of TSH, free T4(FT4), and free T3(FT3) were evaluated in every patient both after admission and 1 month after discharge. Results: At entry, both serum TSH [median (interquartile range), 2.19 mU/l (0.89–2.31)] and FT4(mean±SD, 16.7±3.4 pmol/l) concentrations were into the normal range, whereas serum FT3concentrations were low (3.3±0.7 pmol/l). After discharge TSH and FT4concentrations remained normal and FT3low. However, both serum TSH [2.53 mU/l (1.24–3.33); p<0.01] and FT3(3.7±1.0 pmol/l; p*#x003C;0.001) concentrations significantly increased. Most patients (no.=124, 84.9%) showed the euthyroid sick syndrome (ESS). After discharge, ESS diminished to 76 (52.1%) subjects. Patients who normalized thyroid function tests showed significantly lower TSH values at entry compared with those who persisted with altered thyroid function tests [1.27 mU/l (0.69–1.89) vs1.69 mU/l (0.96–2.91), p<0.05]. Logistic regression analysis showed that serum levels of TSH at admission was the only variable negatively related to normalization of thyroid function [odds ratio 0.730; confidence interval 95%, 0.567–0.940; p=0.01). Conclusions: About 35% of aged patients hospitalized for acute illness spontaneously normalize their thyroid function tests 1 month after discharge, mainly due to the correction of ESS. Serum TSH levels at admission seem to be the only variable negatively related to normalization of thyroid function at this time.

Long term research in low activation materials is being pursued in fusion programs and the assessment of allowable elements and/or impurities from safety and repository reasons are being studied at Instituto Fusión Nuclear (DENIM), using ACAB code, for national ignition facility (NIF) and inertial fusion energy (IFE) reactors. Uncertainties in nuclear data are being considered, and experiments for validation of modeling will be presented. Multiscale simulation of radiation damage is now starting to be compared with experiments, and results on the simplest material can be reported as a function of impurities, temperature, and dose. Molecular dynamics (MD) allows us to identify stress-strain curve of FeCr ferritic steels under irradiation, and macroscopic conclusions can be advanced using simple models. However, a neutron source of enough intensity and adequate energy spectrum is needed which will be very peculiar in the case of pulsed IFE, as we claimed in past years. Development of international fusion materials irradiation facility (IFMIF) will be commented and compared with solutions such as spallation, and others using ultra-intense lasers for obtaining required irradiation magnitudes. Research on radiation damage in SiC composite is being pursued at macroscopic level, but basic knowledge is scarce. A systematic identification of type of stable defects is being presented with a new tight binding MD technique. Our research on simulation of silica irradiation damage will also be presented. The role of tritium, when elemental tritium (HT) and titrated water (HTO) derive in organically bound tritium (OBT) will be explained. The deposition and absorption processes are now being considered in our calculations giving more precision and accuracy to our conclusions of dosimetry effects. The role of HT versus HTO and the importance of re-emission process will be remarked, together with the long-term role of OBT.

Excitation-contraction coupling in skeletal muscle is believed to be triggered by direct protein-protein interactions between the sarcolemmal dihydropyridine-sensitive Ca2+ channel and the Ca2+ release channel/ryanodine receptor (RyR) of sarcoplasmic reticulum. A 138-amino acid cytoplasmic loop between repeats II and III of the alpha1 subunit of the skeletal dihydropyridine receptor (the II-III loop) interacts with a region of the RyR to elicit Ca2+ release. In addition, small segments (10-20 amino acid residues) of the II-III loop retain the capacity to activate Ca2+ release. Imperatoxin A, a 33-amino acid peptide from the scorpion Pandinus imperator, binds directly to the RyR and displays structural and functional homology with an activating segment of the II-III loop (Glu666-Leu690). Mutations in a structural motif composed of a cluster of basic amino acids followed by Ser or Thr dramatically reduce or completely abolish the capacity of the peptides to activate RyRs. Thus, the Imperatoxin A-RyR interaction mimics critical molecular characteristics of the II-III loop-RyR interaction and may be a useful tool to elucidate the molecular mechanism that couples membrane depolarization to sarcoplasmic reticulum Ca2+ release in vivo.

We consider multistep discretizations, stabilized by ß-blocking, for Euler-Lagrange DAEs of index 2. Thus we may use “nonstiff” multistep methods with an appropriate stabilizing difference correction applied to the Lagrangian multiplier term. We show that orderp =k + 1 can be achieved for the differential variables with orderp =k for the Lagrangian multiplier fork-step difference corrected BDF methods as well as for low orderk-step Adams-Moulton methods. This approach is related to the recently proposed “half-explicit” Runge-Kutta methods.

We present an in-depth analysis of the structural and functional properties of Imperatoxin I (IpTxi), an approximately 15-kDa protein from the venom of the scorpion Pandinus imperator that inhibits Ca2+ release channel/ryanodine receptor (RyR) activity (Valdivia, H. H., Kirby, M. S., Lederer, W. J., and Coronado, R. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 12185-12189). A cDNA library was prepared from the venomous glands of this scorpion and used to clone the gene encoding IpTxi. From a single continuous messenger RNA, the information coding for the toxin is translated into two mature polypeptide subunits after elimination of a basic pentapeptide. The IpTxi dimer consists of a large subunit (104-amino acid residues) with phospholipase A2 (PLA2) activity covalently linked by a disulfide bond to a smaller (27 amino acid residues), structurally unrelated subunit. Thus, IpTxi is a heterodimeric protein with lipolytic action, a property that is only shared with beta-bungarotoxins, a group of neurotoxins from snake venoms. The enzymatic subunit of IpTxi is highly homologous to PLA2 from bee (Apis mellifera) and lizard (Heloderma horridum) venoms. The small subunit has no significant similarity to any other known peptide, including members of the Kunitz protease inhibitors superfamily that target the lipolytic effect of beta-bungarotoxins. A synthetic peptide with amino acid sequence identical to that of the small subunit failed to inhibit RyR. On the other hand, treatment of IpTxi with p-bromophenacylbromide, a specific inhibitor of PLA2 activity, greatly reduced the capacity of IpTxi to inhibit RyRs. These results suggested that a lipid product of PLA2 activity, more than a direct IpTxi-RyR interaction, was responsible for RyR inhibition.

We have used [3H]ryanodine binding experiments and single channel recordings to provide convergent descriptions of the effect of imperatoxin A (IpTxa), a approximately 5-kDa peptide from the venom of the scorpion Pandinus imperator (Valdivia, H. H., Kirby, M. S., Lederer, W. J., and Coronado, R. (1992) Proc. Ntl. Acad. Sc. U.S.A. 89, 12185-12189) on Ca2+ release channels/ryanodine receptors (RyR) of sarcoplasmic reticulum (SR). At nanomolar concentrations, IpTxa increased the binding of [3H]ryanodine to skeletal SR and, to a lesser extent, to cerebellum microsomes. The activating effect of IpTxa on skeletal SR was Ca(2+)-dependent, synergized by caffeine, and independent of other modulators of RyRs. However, IpTxa had negligible effects on tissues where the expression of skeletal-type RyR isoforms (RyR1) is small or altogether absent, i.e. cardiac, cerebrum, and liver microsomes. Thus, IpTxa may be used as a ligand capable of discriminating between RyR isoforms with nanomolar affinity. IpTxa increased the open probability (Po) of rabbit skeletal muscle RyRs by increasing the frequency of open events and decreasing the duration of the closed lifetimes. This activating effect was dose-dependent (ED50 = 10 nM), had a fast onset, and was fully reversible. Purified RyR from solubilized skeletal SR displayed high affinity for [3H]ryanodine with a KD of 6.1 nM and Bmax of approximately 30 pmol/mg of protein. IpTxa increased [3H]ryanodine binding noncompetitively by increasing Bmax to approximately 60 pmol/mg of protein. These results suggested the presence of an IpTxa-binding site on the RyR or a closely associated regulatory protein. This site appears to be distinct from the caffeine- and adenine nucleotide-regulatory sites. IpTxa may prove a useful tool to identify regulatory domains critical for channel gating and to dissect the contribution of skeletal-type RyRs to intracellular Ca2+ waveforms generated by stimulation of different RyR isoforms.