Effect of Mechanical and Geometric Mismatching on Fatigue and Damage of Welded Joints

The future of high technology welded constructions will be characterised by higher strength materials and improved weld quality with respect to fatigue resistance. The expected implementation of high quality high strength steel welds will require that more attention be given to the issues of crack initiation and mechanical mismatching. Experiments and finite element analyses were performed within the framework of continuum damage mechanics to investigate the effect of mismatching of welded joints on void nucleation and coalescence during monotonic loading. It was found that the damage of undermatched joints mainly occurred in the sandwich layer and the damageresistance of the joints decreases with the decrease of the sandwich layer width. The damage of over-matched joints mainly occurred in the base metal adjacent to the sandwich layer and the damage resistance of the joints increases with thedecrease of the sandwich layer width. The mechanisms of the initiation of the micro voids/cracks were found to be cracking of the inclusions or the embrittled second phase, and the debonding of the inclusions from the matrix. Experimental fatigue crack growth rate testing showed that the fatigue life of under-matched central crack panel specimens is longer than that of over-matched and even-matched specimens. Further investigation by the elastic-plastic finite element analysis indicated that fatigue crack closure, which originated from the inhomogeneousyielding adjacent to the crack tip, played an important role in the fatigue crack propagation. The applicability of the J integral concept to the mismatched specimens with crack extension under cyclic loading was assessed. The concept of fatigue class used by the International Institute of Welding was introduced in the parametric numerical analysis of several welded joints. The effect of weld geometry and load condition on fatigue strength of ferrite-pearlite steel joints was systematically evaluated based on linear elastic fracture mechanics. Joint types included lap joints, angle joints and butt joints. Various combinations of the tensile and bending loads were considered during the evaluation with the emphasis focused on the existence of both root and toe cracks. For a lap joint with asmall lack-of-penetration, a reasonably large weld leg and smaller flank angle were recommended for engineering practice in order to achieve higher fatigue strength. It was found that the fatigue strength of the angle joint depended strongly on the location and orientation of the preexisting crack-like welding defects, even if the joint was welded with full penetration. It is commonly believed that the double sided butt welds can have significantly higher fatigue strength than that of a single sided welds, but fatigue crack initiation and propagation can originate from the weld root if the welding procedure results in a partial penetration. It is clearly shown that the fatigue strength of the butt joint could be improved remarkably by ensuring full penetration. Nevertheless, increasing the fatigue strength of a butt joint by increasing the size of the weld is an uneconomical alternative.

A mechanism of carbapenem resistance due to a new insertion element (ISPa133) in Pseudomonas aeruginosa

This study explored the evolutionary mechanism by which the clinical isolate PA110514 yields the imipenemresistant derivative PA116136. Both isolates were examined by PFGE and SDS-PAGE, which led to the identification of a new insertion sequence, ISPa133. This element was shown to have distinct chromosomal locations in each of the original isolates that appeared to explain the differences in imipenem susceptibilty. In strain PA110514, ISPa133 is located 56 nucleotides upstream of the translational start codon, which has no effect on expression of the porin OprD. However, in strain PA116136 ISPa133 it is located in front of nucleotide 696 and, by interrupting the coding region, causes a loss of OprD expression, thus conferring imipenem resistance. In vitro experiments mimicking the natural conditions of selective pressure yielded imipenem-resistant strains in which ISPa133 similarly interrupted oprD. A mechanism is proposed whereby ISPa133 acts as a mobile switch, with its position in oprD depending on the degree of selective pressure exerted by imipenem

A mechanism of carbapenem resistance due to a new insertion element (ISPa133) in Pseudomonas aeruginosa

This study explored the evolutionary mechanism by which the clinical isolate PA110514 yields the imipenemresistant derivative PA116136. Both isolates were examined by PFGE and SDS-PAGE, which led to the identification of a new insertion sequence, ISPa133. This element was shown to have distinct chromosomal locations in each of the original isolates that appeared to explain the differences in imipenem susceptibilty. In strain PA110514, ISPa133 is located 56 nucleotides upstream of the translational start codon, which has no effect on expression of the porin OprD. However, in strain PA116136 ISPa133 it is located in front of nucleotide 696 and, by interrupting the coding region, causes a loss of OprD expression, thus conferring imipenem resistance. In vitro experiments mimicking the natural conditions of selective pressure yielded imipenem-resistant strains in which ISPa133 similarly interrupted oprD. A mechanism is proposed whereby ISPa133 acts as a mobile switch, with its position in oprD depending on the degree of selective pressure exerted by imipenem

A mechanism of carbapenem resistance due to a new insertion element (ISPa133) in Pseudomonas aeruginosa

This study explored the evolutionary mechanism by which the clinical isolate PA110514 yields the imipenemresistant derivative PA116136. Both isolates were examined by PFGE and SDS-PAGE, which led to the identification of a new insertion sequence, ISPa133. This element was shown to have distinct chromosomal locations in each of the original isolates that appeared to explain the differences in imipenem susceptibilty. In strain PA110514, ISPa133 is located 56 nucleotides upstream of the translational start codon, which has no effect on expression of the porin OprD. However, in strain PA116136 ISPa133 it is located in front of nucleotide 696 and, by interrupting the coding region, causes a loss of OprD expression, thus conferring imipenem resistance. In vitro experiments mimicking the natural conditions of selective pressure yielded imipenem-resistant strains in which ISPa133 similarly interrupted oprD. A mechanism is proposed whereby ISPa133 acts as a mobile switch, with its position in oprD depending on the degree of selective pressure exerted by imipenem

Evaluating the Trabecular Micro-Bypass Stent Combined with Phacoemulsification Compared to Phacoemulsification Alone.

Aim: The aim of this study was to assess the effect of iStent (trabecular micro-bypass stent) implantation in combination with phacoemulsification on IOP and glaucoma medications and to compare this to the outcome of phacoemulsification alone. Patients and Methods: A retrospective consecutive comparative review was undertaken. 131 eyes with ocular hypertension and medically controlled glaucoma underwent phacoemulsification alone (n = 78 group I) or combined with gonioscopic-guided implantation of one iStent (n = 31, group II) or two iStents (n = 22, group III). Patients were assessed at postoperative weeks 1, 3 and 6, and months 3 and 6. Pre- and post-operative measures included visual acuity, IOP and glaucoma medications. Results: Post-operatively at 6 months, mean IOP decreased from 16.3 mmHg to 14.2 mmHg in group I (p < 0.01), from 16.7 mmHg to 15.1 mmHg in group II (p < 0.16) and from 17.0 to 13.8 in group III (p = 0.05). Mean glaucoma medication decreased from 1.9 to 1.6 in group I (8 %, p = 0.12), from 2.5 to 0.8 in group II (27 %, p = 0.04), and from 2.1 to 1.0 in group III (45 %, p < 0.01). Conclusions: iStent implantation resulted in similar IOP reduction to phacoemulsification alone but achieved a significantly greater reduction in glaucoma medications. This may improve compliance and quality of life, and reduce health care costs in patients with early to moderate glaucoma.

Hepatocyte nuclear factor-4 alpha regulates the human apolipoprotein AV gene: Identification of a novel response element and involvement in the control by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, AMP-activated protein kinase, and mitogen-activated protein kinase pathway

The recently discovered apolipoprotein AV (apoAV) gene has been reported to be a key player in modulating plasma triglyceride levels. Here we identify the hepatocyte nuclear factor-4 (HNF-4 ) as a novel regulator of human apoAV gene. Inhibition of HNF-4 expression by small interfering RNA resulted in down-regulation of apoAV. Deletion, mutagenesis, and binding assays revealed that HNF-4 directly regulates human apoAV promoter through DR1 [a direct repeat separated by one nucleotide (nt)], and via a novel element for HNF-4 consisting of an inverted repeat separated by 8 nt (IR8). In addition, we show that the coactivator peroxisome proliferator-activated receptor- coactivator-1 was capable of stimulating the HNF-4 -dependent transactivation of apoAV promoter. Furthermore, analyses in human hepatic cells demonstrated that AMP-activated protein kinase (AMPK) and the MAPK signaling pathway regulate human apoAV expression and suggested that this regulation may be mediated, at least in part, by changes in HNF-4 . Intriguingly, EMSAs and mice with a liver-specific disruption of the HNF-4 gene revealed a species-distinct regulation of apoAV by HNF-4 , which resembles that of a subset of HNF-4 target genes. Taken together, our data provide new insights into the binding properties and the modulation of HNF-4 and underscore the role of HNF-4 in regulating triglyceride metabolism.

Is syndecan-2 a key angiogenic element?

Angiogenesis is a tightly regulated process in vertebrates that leads to the formation of new blood vessels from pre-existing vessels or by the recruitment of bone marrow-derived endothelial precursor cells[1]. During embryogenesis, after stimulation by proangiogenic factors, such as VEGF or FGF, it contributes to the maturation of the vascular plexus. In adults, it is important in some physiologic conditions, such as wound healing or the reproductive cycle in females, although most of the time it is"switched off" by endogenous inhibitors, such as endostatin or angiostatin. Furthermore, its misregulation is the cause of many pathological situations, as it contributes to tumor development[2], diabetic retinopathy[3], rheumatoid arthritis[4], psoriasis[5], but also cardiovascular disorders[6] and obesity[7]

Trace element monitoring in the ICU: quality and economic impact of a change in sampling practice.

BACKGROUND & AIMS: Trace elements (TE) are involved in the immune and antioxidant defences which are of particular importance during critical illness. Determining plasma TE levels is costly. The present quality control study aimed at assessing the economic impact of a computer reminded blood sampling versus a risk guided on-demand monitoring of plasma concentrations of selenium, copper, and zinc. METHODS: Retrospective analysis of 2 cohorts of patients admitted during 6 months periods in 2006 and 2009 to the ICU of a University hospital. INCLUSION CRITERIA: to receive intravenous micronutrient supplements and/or to have a TE sampling during ICU stay. The TE samplings were triggered by computerized reminder in 2006 versus guided by nutritionists in 2009. RESULTS: During the 2 periods 636 patients met the inclusion criteria out of 2406 consecutive admissions, representing 29.7% and 24.9% respectively of the periods' admissions. The 2009 patients had higher SAPS2 scores (p = 0.02) and lower BMI compared to 2006 (p = 0.007). The number of laboratory determinations was drastically reduced in 2009, particularly during the first week, despite the higher severity of the cohort, resulting in à 55% cost reduction. CONCLUSIONS: The monitoring of TE concentrations guided by a nutritionist resulted in a reduction of the sampling frequency, and targeting on the sickest high risk patients, requiring a nutritional prescription adaptation. This control leads to cost reduction compared to an automated sampling prescription.

A survey of transposable element classification systems--a call for a fundamental update to meet the challenge of their diversity and complexity.

The increase of publicly available sequencing data has allowed for rapid progress in our understanding of genome composition. As new information becomes available we should constantly be updating and reanalyzing existing and newly acquired data. In this report we focus on transposable elements (TEs) which make up a significant portion of nearly all sequenced genomes. Our ability to accurately identify and classify these sequences is critical to understanding their impact on host genomes. At the same time, as we demonstrate in this report, problems with existing classification schemes have led to significant misunderstandings of the evolution of both TE sequences and their host genomes. In a pioneering publication Finnegan (1989) proposed classifying all TE sequences into two classes based on transposition mechanisms and structural features: the retrotransposons (class I) and the DNA transposons (class II). We have retraced how ideas regarding TE classification and annotation in both prokaryotic and eukaryotic scientific communities have changed over time. This has led us to observe that: (1) a number of TEs have convergent structural features and/or transposition mechanisms that have led to misleading conclusions regarding their classification, (2) the evolution of TEs is similar to that of viruses by having several unrelated origins, (3) there might be at least 8 classes and 12 orders of TEs including 10 novel orders. In an effort to address these classification issues we propose: (1) the outline of a universal TE classification, (2) a set of methods and classification rules that could be used by all scientific communities involved in the study of TEs, and (3) a 5-year schedule for the establishment of an International Committee for Taxonomy of Transposable Elements (ICTTE).

Sterol regulatory element binding protein-1a transactivates 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene promoter

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB)catalyzes the synthesis and degradation of fructose-2,6-bisphosphate, a key modulator of glycolysis-gluconeogenesis. To gain insight into the molecular mechanism behind hormonal and nutritional regulation of PFKFB expression, we have cloned and characterized the proximal promoter region of the liver isoform of PFKFB (PFKFB1) from gilthead sea bream (Sparus aurata). Transient transfection of HepG2 cells with deleted gene promoter constructs and electrophoretic mobility shift assays allowed us to identify a sterol regulatory element (SRE) to which SRE binding protein-1a (SREBP-1a)binds and transactivates PFKFB1 gene transcription. Mutating the SRE box abolished SREBP-1a binding and transactivation. The in vivo binding of SREBP-1a to the SRE box in the S. aurata PFKFB1 promoter was confirmed by chromatin immunoprecipitation assays. There is a great deal of evidence for a postprandial rise of PFKB1 mRNA levels in fish and rats. Consistently, starved-to-fed transition and treatment with glucose or insulin increased SREBP-1 immunodetectable levels, SREBP-1 association to PFKFB1 promoter, and PFKFB1 mRNA levels in the piscine liver. Our findings demonstrate involvement of SREBP-1a in the transcriptional activation of PFKFB1, and we conclude that SREBP-1a may exert a key role mediating postprandial activation of PFKFB1 transcription.

Sterol regulatory element binding protein-1a transactivates 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene promoter

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB)catalyzes the synthesis and degradation of fructose-2,6-bisphosphate, a key modulator of glycolysis-gluconeogenesis. To gain insight into the molecular mechanism behind hormonal and nutritional regulation of PFKFB expression, we have cloned and characterized the proximal promoter region of the liver isoform of PFKFB (PFKFB1) from gilthead sea bream (Sparus aurata). Transient transfection of HepG2 cells with deleted gene promoter constructs and electrophoretic mobility shift assays allowed us to identify a sterol regulatory element (SRE) to which SRE binding protein-1a (SREBP-1a)binds and transactivates PFKFB1 gene transcription. Mutating the SRE box abolished SREBP-1a binding and transactivation. The in vivo binding of SREBP-1a to the SRE box in the S. aurata PFKFB1 promoter was confirmed by chromatin immunoprecipitation assays. There is a great deal of evidence for a postprandial rise of PFKB1 mRNA levels in fish and rats. Consistently, starved-to-fed transition and treatment with glucose or insulin increased SREBP-1 immunodetectable levels, SREBP-1 association to PFKFB1 promoter, and PFKFB1 mRNA levels in the piscine liver. Our findings demonstrate involvement of SREBP-1a in the transcriptional activation of PFKFB1, and we conclude that SREBP-1a may exert a key role mediating postprandial activation of PFKFB1 transcription.