Use of cohesive elements in fatigue analysis

Cohesive laws describe the resistance to incipient separation of material surfaces. A cohesive finite element is formulated on the basis of a particular cohesive law. Cohesive elements are placed at the boundary between adjacent standard volume finite elements to model fatigue damage that leads to fracture at the separation of the element boundaries per the cohesive law. In this work, a cohesive model for fatigue crack initiation is taken to be the irreversible loadingunloading hysteresis that represents fatigue damage occuring due to cyclic loads leading to the initiation of small cracks. Various cohesive laws are reviewed and one is selected that incorporates a hysteretic cyclic loading that accounts for energetic dissipative mechanisms. A mathematical representation is developed based on an exponential effective load-separation cohesive relationship. A three-dimensional cohesive element is defined using this compliance relationship integrated at four points on the mid-surface of the area element. Implementation into finite element software is discussed and particular attention is applied to numerical convergence issues as the inflection point between loading and 'unloading in the cohesive law is encountered. A simple example of a displacementcontrolled fatigue test is presented in a finite element simulation. Comments are made on applications of the method to prediction of fatigue life for engineering structures such as pressure vessels and piping

A Model of Investment Decision Making: How Adaptation to Losses Affects Investors' Selling Decisions

To provide more insight into investors' selling decisions, an integrated model of prospect theory, reference point adaptation and cognitive-experiential self-theory is proposed. We expect that the dynamically changing reference point, together with changing emotions and changing expectation for a stock's future performance, influence the decision to hold or sell losing investments. Experimental findings demonstrate a main effect of positive expectations on the decisions to hold. Also, larger total loss size and longer time in losing position are related to a more downwardly shifted reference point. This adapted reference point indirectly decreases the probability to hold the investment, via its impact on expectations

Optimal Control Strategies for Robust Certification

We present an optimal control methodology, which we refer to as concentration-of-measure optimal control (COMOC), that seeks to minimize a concentration-of-measure upper bound on the probability of failure of a system. The systems under consideration are characterized by a single performance measure that depends on random inputs through a known response function. For these systems, concentration-of-measure upper bound on the probability of failure of a system can be formulated in terms of the mean performance measure and a system diameter that measures the uncertainty in the operation of the system. COMOC then seeks to determine the optimal controls that maximize the confidence in the safe operation of the system, defined as the ratio of the design margin, which is measured by the difference between the mean performance and the design threshold, to the system uncertainty, which is measured by the system diameter. This strategy has been assessed in the case of a robot-arm maneuver for which the performance measure of interest is assumed to be the placement accuracy of the arm tip. The ability of COMOC to significantly increase the design confidence in that particular example of application is demonstrated

Wuchereria bancrofti infection is linked to systemic activation of CD4 and CD8 T cells

Background Susceptibility to HIV has been linked to systemic CD4+ T cell activation in cohorts of seronegative individuals with high HIV-exposure risk. We recently described an increased risk of HIV transmission in individuals infected with Wuchereria bancrofti, the causative agent for lymphatic filariasis, in a prospective cohort study. However, the reason for this phenomenon needs further investigation. Methodology/Principal findings Two-hundred and thirty-five HIV negative adults were tested using Trop Bio ELISA for detection of W. bancrofti infection and Kato Katz urine filtration and stool based RT-PCR for detection of soil transmitted helminths and schistosomiasis. FACS analysis of the fresh peripheral whole blood was used to measure T cell activation markers (HLA-DR, CD38), differentiation markers (CD45, CD27), markers for regulatory T cells (FoxP3, CD25) and the HIV entry receptor CCR5. Frequencies of activated HLA-DRpos CD4 T cells were significantly increased in subjects with W. bancrofti infection (n = 33 median: 10.71%) compared to subjects without any helminth infection (n = 42, median 6.97%, p = 0.011) or those with other helminths (Schistosoma haematobium, S. mansoni, Trichuris trichiura, Ascaris lumbricoides, hookworm) (n = 151, median 7.38%, p = 0.009). Similarly, a significant increase in HLA-DR(pos)CD38(pos) CD4 T cells and effector memory cells CD4 T cells (CD45RO(pos)CD27(neg)) was observed in filarial infected participants. Multivariable analyses further confirmed a link between W. bancrofti infection and systemic activation of CD4 T cells independent of age, fever, gender or other helminth infections. Conclusions/Significance W. bancrofti infection is linked to systemic CD4 T cell activation, which may contribute to the increased susceptibility of W. bancrofti infected individuals to HIV infection

PARP-1 regulates DNA repair factor availability.

PARP-1 holds major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context of cancer. Here, unbiased transcriptional profiling revealed the downstream transcriptional profile of PARP-1 enzymatic activity. Further investigation of the PARP-1-regulated transcriptome and secondary strategies for assessing PARP-1 activity in patient tissues revealed that PARP-1 activity was unexpectedly enriched as a function of disease progression and was associated with poor outcome independent of DNA double-strand breaks, suggesting that enhanced PARP-1 activity may promote aggressive phenotypes. Mechanistic investigation revealed that active PARP-1 served to enhance E2F1 transcription factor activity, and specifically promoted E2F1-mediated induction of DNA repair factors involved in homologous recombination (HR). Conversely, PARP-1 inhibition reduced HR factor availability and thus acted to induce or enhance BRCA-ness . These observations bring new understanding of PARP-1 function in cancer and have significant ramifications on predicting PARP-1 inhibitor function in the clinical setting

The effect of fluoride on enamel and dentin formation in the uremic rat incisor

Renal impairment in children is associated with tooth defects that include enamel pitting and hypoplasia. However, the specific effects of uremia on tooth formation are not known. In this study, we used rat mandibular incisors, which continuously erupt and contain all stages of tooth formation, to characterize the effects of uremia on tooth formation. We also tested the hypothesis that uremia aggravates the fluoride (F)-induced changes in developing teeth. Rats were subjected to a two-stage 5/6 nephrectomy or sham operation and then exposed to 0 (control) or 50 ppm NaF in drinking water for 14 days. The effects of these treatments on food intake, body growth rate, and biochemical serum parameters for renal function and calcium metabolism were monitored. Nephrectomy reduced food intake and weight gain. Intake of F by nephrectomized rats increased plasma F levels twofold and further decreased food intake and body weight gain. Uremia affected formation of dentin and enamel and was more extensive than the effect of F alone. Uremia also significantly increased predentin width and induced deposition of large amounts of osteodentin-like matrix-containing cells in the pulp chamber. In enamel formation, the cells most sensitive to uremia were the transitional-stage ameloblasts. These data demonstrate that intake of F by rats with reduced renal function impairs F clearance from the plasma and aggravates the already negative effects of uremia on incisor tooth development

The impact of intolerance of uncertainty and cognitive behavioural instructions on safety learning

Background Difficulty updating threat associations to safe associations has been observed in individuals who score high in self-reported Intolerance of Uncertainty (IU). Here we sought to determine whether an instruction based on fundamental principles of Cognitive Behavioural Therapy could promote safety learning in individuals with higher levels of IU, whilst controlling for self-reported trait anxiety (STICSA). Methods We measured skin conductance response, pupil dilation and expectancy ratings during an associative threat learning task in which participants either received a cognitive behavioural instruction or no instruction prior to threat extinction (n = 92). Results Analyses revealed that both self-reported IU and STICSA similarly predicted differences in skin conductance response. Only individuals with lower IU/STICSA in the cognitive behavioural instruction condition displayed successful safety learning via skin conductance response. Conclusions These initial results provide some insight into how simple cognitive behavioural instructions combined with exposure are applied differently in individuals with varying levels of self-reported anxiety. The results further our understanding of the role of basic cognitive behavioural principles and self-reported anxiety in safety learning