On the effects of friction modelling on small punch creep test responses: a numerical investigation

This paper shows the results of finite element (FE) analyses of Small Punch Creep Testing (SPCT) of a P91 steel at 600°C using two different approaches to model the friction between the specimen and the punch. The numerical results obtained by using the “classical” Coulomb friction model (i.e. constant friction coefficient) have been compared with those obtained by a more modern formulation, which takes into account the effects of local loading conditions, i.e. the contact pressure, between the contacting bodies (the small disc specimen and the punch) on the coefficient of friction. The aim of the work is to investigate the effects of the friction formulation used for the calculations on the numerical results representing the output of the test, i.e. the variation of the punch displacement versus time and the time to rupture. The calculations, carried out for various load levels, showed that the friction coefficient is not constant at all positions on the contacting surface between the punch and the specimen during the deformation process. The maximum value for the coefficient of friction is reached at the contact edge, which is a very important region in the specimen, because this is the position at which most of the creep deformation occurs. As expected, the displacement versus time curve (that is usually the only output obtained from experimental SPCTs) is affected by friction formulation which is used, as this directly influences the stress and strain fields in the specimen

Incidence and Outcome of Acute Phosphate Nephropathy in Iceland

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND: Oral sodium phosphate solutions (OSPS) are widely used for bowel cleansing prior to colonoscopy and other procedures. Cases of renal failure due to acute phosphate nephropathy following OSPS ingestion have been documented in recent years, questioning the safety of OSPS. However, the magnitude of the problem remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a population based, retrospective analysis of medical records and biopsies of all cases of acute phosphate nephropathy that were diagnosed in our country in the period from January 2005 to October 2008. Utilizing the complete official sales figures of OSPS, we calculated the incidence of acute phosphate nephropathy in our country. Fifteen cases of acute phosphate nephropathy were diagnosed per 17,651 sold doses of OSPS (0.085%). Nine (60%) were women and mean age 69 years (range 56-75 years). Thirteen patients had a history of hypertension (87%) all of whom were treated with either ACE-I or ARB and/or diuretics. One patient had underlying DM type I and an active colitis and one patient had no risk factor for the development of acute phosphate nephropathy. Average baseline creatinine was 81.7 µmol/L and 180.1 at the discovery of acute renal failure, mean 4.2 months after OSPS ingestion. No patient had a full recovery of renal function, and at the end of follow-up, 26.6 months after the OSPS ingestion, the average creatinine was 184.2 µmol/L. The average eGFR declined from 73.5 ml/min/1.73 m(2) at baseline to 37.3 ml/min/1.73 m(2) at the end of follow-up. One patient reached end-stage renal disease and one patient died with progressive renal failure. CONCLUSION/SIGNIFICANCE: Acute phosphate nephropathy developed in almost one out of thousand sold doses of OSPS. The consequences for kidney function were detrimental. This information can be used in other populations to estimate the impact of OSPS. Our data suggest that acute phosphate nephropathy may be greatly underreported worldwide

Fault Tolerance in Protein Interaction Networks: Stable Bipartite Subgraphs and Redundant Pathways

As increasing amounts of high-throughput data for the yeast interactome become available, more system-wide properties are uncovered. One interesting question concerns the fault tolerance of protein interaction networks: whether there exist alternative pathways that can perform some required function if a gene essential to the main mechanism is defective, absent or suppressed. A signature pattern for redundant pathways is the BPM (between-pathway model) motif, introduced by Kelley and Ideker. Past methods proposed to search the yeast interactome for BPM motifs have had several important limitations. First, they have been driven heuristically by local greedy searches, which can lead to the inclusion of extra genes that may not belong in the motif; second, they have been validated solely by functional coherence of the putative pathways using GO enrichment, making it difficult to evaluate putative BPMs in the absence of already known biological annotation. We introduce stable bipartite subgraphs, and show they form a clean and efficient way of generating meaningful BPMs which naturally discard extra genes included by local greedy methods. We show by GO enrichment measures that our BPM set outperforms previous work, covering more known complexes and functional pathways. Perhaps most importantly, since our BPMs are initially generated by examining the genetic-interaction network only, the location of edges in the protein-protein physical interaction network can then be used to statistically validate each candidate BPM, even with sparse GO annotation (or none at all). We uncover some interesting biological examples of previously unknown putative redundant pathways in such areas as vesicle-mediated transport and DNA repair

Genome-Wide Profiling of MicroRNAs in Adipose Mesenchymal Stem Cell Differentiation and Mouse Models of Obesity

In recent years, there has been accumulating evidence that microRNAs are key regulator molecules of gene expression. The cellular processes that are regulated by microRNAs include e.g. cell proliferation, programmed cell death and cell differentiation. Adipocyte differentiation is a highly regulated cellular process for which several important regulating factors have been discovered, but still not all are known to fully understand the underlying mechanisms. In the present study, we analyzed the expression of 597 microRNAs during the differentiation of mouse mesenchymal stem cells into terminally differentiated adipocytes by real-time RT-PCR. In total, 66 miRNAs were differentially expressed in mesenchymal stem cell-derived adipocytes compared to the undifferentiated progenitor cells. To further study the regulation of these 66 miRNAs in white adipose tissue in vivo and their dependence on PPARγ activity, mouse models of genetically or diet induced obesity as well as a mouse line expressing a dominant negative PPARγ mutant were employed

Effect of a Community Popular Opinion Leader HIV/STI Intervention on Stigma in Urban, Coastal Peru

Evaluating interventions that reduce HIV stigma may help to craft effective stigma-reduction programs. This study evaluates the effects of a community popular opinion leader HIV/STI intervention on stigma in urban, coastal Peru. Mixed effects modeling was used to analyze data on 3,049 participants from the Peru site of the NIHM collaborative trial. Analyses looked at differences between the comparison and intervention groups on a stigma index from baseline to 12- and 24-month follow-up. Sub-analyses were conducted on heterosexual-identified men (esquineros), homosexual-identified men (homosexuales), and socially marginalized women (movidas). Compared to participants in the comparison group, intervention participants reported lower levels of stigma at 12- and 24-month follow-up. Similar results were found within esquineros and homosexuales. No significant differences were found within movidas. Findings suggest that interventions designed to normalize HIV prevention behaviors and HIV communication can reduce HIV-related stigma and change community norms

Abilities to explicitly and implicitly infer intentions from actions in adults with autism spectrum disorder

Previous research suggests that Autism Spectrum Disorder (ASD) might be associated with impairments on implicit but not explicit mentalizing tasks. However, such comparisons are made difficult by the heterogeneity of stimuli and the techniques used to measure mentalizing capabilities. We tested the abilities of 34 individuals (17 with ASD) to derive intentions from others’ actions during both explicit and implicit tasks and tracked their eye-movements. Adults with ASD displayed explicit but not implicit mentalizing deficits. Adults with ASD displayed typical fixation patterns during both implicit and explicit tasks. These results illustrate an explicit mentalizing deficit in adults with ASD, which cannot be attributed to differences in fixation patterns

Risk of chronic kidney disease after cancer nephrectomy.

The incidence of early stage renal cell carcinoma (RCC) is increasing and observational studies have shown equivalent oncological outcomes of partial versus radical nephrectomy for stage I tumours. Population studies suggest that compared with radical nephrectomy, partial nephrectomy is associated with decreased mortality and a lower rate of postoperative decline in kidney function. However, rates of chronic kidney disease (CKD) in patients who have undergone nephrectomy might be higher than in the general population. The risks of new-onset or accelerated CKD and worsened survival after nephrectomy might be linked, as kidney insufficiency is a risk factor for cardiovascular disease and mortality. Nephron-sparing approaches have, therefore, been proposed as the standard of care for patients with type 1a tumours and as a viable option for those with type 1b tumours. However, prospective data on the incidence of de novo and accelerated CKD after cancer nephrectomy is lacking, and the only randomized trial to date was closed prematurely. Intrinsic abnormalities in non-neoplastic kidney parenchyma and comorbid conditions (including diabetes mellitus and hypertension) might increase the risks of CKD and RCC. More research is needed to better understand the risk of CKD post-nephrectomy, to develop and validate predictive scores for risk-stratification, and to optimize patient management

Biology of urothelial tumorigenesis: insights from genetically engineered mice

Urothelium, one of the slowest cycling epithelia in the body, embodies a unique biological context for cellular transformation. Introduction of oncogenes into or removing tumor suppressor genes from the urothelial cells or a combination of both using the transgenic and/or knockout mouse approaches has provided useful insights into the molecular mechanisms of urothelial transformation and tumorigenesis. It is becoming increasingly clear that over-activation of the receptor tyrosine kinase (RTK) pathway, as exemplified by the constitutively activated Ha-ras oncogene, is both necessary and sufficient to initiate the low-grade, non-invasive urothelial carcinomas. Dosage of the mutated Ha-ras, but not concurrent inactivation of pro-senescence molecules p16Ink4a and p19Arf, dictates whether and when the low-grade urothelial carcinomas arise. Inactivation of both p53 and pRb, a prevailing paradigm previously proposed for muscle-invasive urothelial tumorigenesis, is found to be necessary but insufficient to initiate this urothelial carcinoma variant. Instead, downregulation in p53/pRb co-deficient urothelial cells of p107, a pRb family member, is associated with the genesis of the muscle-invasive bladder cancers. p53 deficiency also seems to be capable of cooperating with that of PTEN in eliciting invasive urothelial carcinomas. The genetically engineered mice have improved the molecular definition of the divergent pathways of urothelial tumorigenesis and progression, helped delineate the intricate crosstalk among different genetic alterations within a urothelium-specific context, identified new prognostic markers and novel therapeutic targets potentially applicable for clinical intervention, and provided in vivo platforms for testing preventive strategies of bladder cancer

The rate of facultative sex governs the number of expected mating types in isogamous species

It is unclear why sexually reproducing isogamous species frequently contain just two self-incompatible mating types. Deterministic theory suggests that since rare novel mating types experience a selective advantage (by virtue of their many potential partners), the number of mating types should consistently grow. However, in nature, species with thousands of mating types are exceedingly rare. Several competing theories for the predominance of species with two mating types exist, yet they lack an explanation for how many are possible and in which species to expect high numbers. Here, we present a theoretical null model that explains the distribution of mating type numbers using just three biological parameters: mutation rate, population size and the rate of sex. If the number of mating types results from a mutation–extinction balance, the rate of sexual reproduction plays a crucial role. If sex is facultative and rare (a very common combination in isogamous species), mating type diversity will remain low. In this rare sex regime, small fitness differences between the mating types lead to more frequent extinctions, further lowering mating type diversity. We also show that the empirical literature supports the role of drift and facultativeness of sex as a determinant of mating type dynamics