Stress and Strain State Analysis of Defective Pipeline Portion

The paper presents computer simulation results of the pipeline having defects in a welded joint. Autodesk Inventor software is used for simulation of the stress and strain state of the pipeline. Places of the possible failure and stress concentrators are predicted on the defective portion of the pipeline

Stress and Strain State Analysis of Defective Pipeline Portion

The paper presents computer simulation results of the pipeline having defects in a welded joint. Autodesk Inventor software is used for simulation of the stress and strain state of the pipeline. Places of the possible failure and stress concentrators are predicted on the defective portion of the pipeline

Fibrinogen concentrate for treatment of bleeding and surgical prophylaxis in congenital fibrinogen deficiency patients

Background: Congenital fibrinogen deficiency is an ultra-rare disorder in which patients can experience severe and/or frequent bleeding episodes (BEs). Here, we present the largest prospective study to date on the treatment of this disorder. Methods: Hemostatic efficacy of human fibrinogen concentrate (HFC; FIBRYGA\uae, Octapharma AG) for treatment of bleeding or surgical prophylaxis was assessed by investigators and adjudicated by an independent data monitoring and endpoint adjudication committee (IDMEAC) according to a four-point scale, using objective criteria. Thromboelastometry maximum clot firmness (MCF) was also determined. Results: Twenty-five afibrinogenemia patients were treated with HFC: 24 for on-demand treatment of 89 BEs, and nine as prophylaxis for 12 surgeries. For BEs, treatment success (rating of excellent or good) evaluated by investigators was 96.6% (90% confidence interval [CI], 0.92-0.99; two missing ratings, classified as failures) and by the IDMEAC was 98.9% (90% CI, 0.95-0.999). Mean \ub1 standard deviation (SD) increase in MCF was 5.8 \ub1 2.5 mm one hour after the first HFC infusion (mean \ub1 SD dose, 61.88 \ub1 11.73 mg/kg). For the 12 surgeries (median [range] HFC dose/surgery, 85.80 mg/kg [34.09-225.36]), intraoperative and postoperative treatment success were both rated 100% (90% CI, 0.82-1.00) by investigators and the IDMEAC. Three adverse events were possibly treatment related, including a moderate case of thrombosis. There were no deaths, no severe allergic or hypersensitivity reactions, and no clinical evidence of neutralizing antifibrinogen antibodies. Conclusions: Human fibrinogen concentrate was efficacious for on-demand treatment of bleeding and as surgical prophylaxis, with a favorable safety profile, in patients with congenital afibrinogenemia

Pharmacokinetics, clot strength and safety of a new fibrinogen concentrate: randomized comparison with active control in congenital fibrinogen deficiency

Background: Human fibrinogen concentrate (HFC) corrects fibrinogen deficiency in congenital a-/hypofibrinogenemia. Objectives: To assess pharmacokinetics (PK), effects on thromboelastometry maximum clot firmness (MCF), and safety of a new double virusinactivated/eliminated, highly purified HFC vs. active control. Patients/Methods: In this multinational, randomized, phase II, open-label, crossover study in 22 congenital afibrinogenemia patients aged >= 12 years, 70 mg kg(-1) of new HFC (FIBRYGA, Octapharma AG) or control (Haemocomplettan (R) P/RiaSTAP (TM), CSL Behring GmbH) were administered, followed by crossover to the other concentrate. Fibrinogen activity, PK and MCF in plasma were assessed. Results: The concentrates were not bioequivalent for the primary endpoint, AUC(norm) (mean ratio, 1.196; 90% confidence interval [CI], 1.117, 1.281). Remaining PK parameters (C-maxnorm, IVR, t(1/2), MRT) reflected bioequivalence between concentrates, except for clearance (mean ratio, 0.836; 90% CI, 0.781, 0.895) and V-ss (mean ratio, 0.886; 90% CI, 0.791, 0.994). Mean AUC(norm) was significantly larger for the new HFC (1.62 +/- 0.45 vs. 1.38 +/- 0.47 h kg g L-1 mg(-1), P = 0.0001) and mean clearance was significantly slower (0.665 +/- 0.197 vs. 0.804 +/- 0.255 mL h(-1) kg(-1), P = 0.0002). Mean MCF increased from 0 mm to 9.68 mm (new HFC) and 10.00 mm (control) 1-hour post-infusion (mean difference, -0.32 mm; 95% CI, -1.70, 1.07, n.s.). No deaths, thromboses, viral seroconversions or serious related adverse events occurred. Conclusions: Bioequivalence was not demonstrated for AUC(norm), clearance and V-ss. Larger AUC(norm) and slower clearance were observed for the new HFC. Remaining pharmacokinetic parameters reflected bioequivalence to control. Safety profiles and increases in clot strength were comparable between concentrates

Skeletal Muscle–Specific Deletion of Lipoprotein Lipase Enhances Insulin Signaling in Skeletal Muscle but Causes Insulin Resistance in Liver and Other Tissues

OBJECTIVE—Skeletal muscle–specific LPL knockout mouse (SMLPL−/−) were created to study the systemic impact of reduced lipoprotein lipid delivery in skeletal muscle on insulin sensitivity, body weight, and composition

The role of networks to overcome large-scale challenges in tomography : the non-clinical tomography users research network

Our ability to visualize and quantify the internal structures of objects via computed tomography (CT) has fundamentally transformed science. As tomographic tools have become more broadly accessible, researchers across diverse disciplines have embraced the ability to investigate the 3D structure-function relationships of an enormous array of items. Whether studying organismal biology, animal models for human health, iterative manufacturing techniques, experimental medical devices, engineering structures, geological and planetary samples, prehistoric artifacts, or fossilized organisms, computed tomography has led to extensive methodological and basic sciences advances and is now a core element in science, technology, engineering, and mathematics (STEM) research and outreach toolkits. Tomorrow's scientific progress is built upon today's innovations. In our data-rich world, this requires access not only to publications but also to supporting data. Reliance on proprietary technologies, combined with the varied objectives of diverse research groups, has resulted in a fragmented tomography-imaging landscape, one that is functional at the individual lab level yet lacks the standardization needed to support efficient and equitable exchange and reuse of data. Developing standards and pipelines for the creation of new and future data, which can also be applied to existing datasets is a challenge that becomes increasingly difficult as the amount and diversity of legacy data grows. Global networks of CT users have proved an effective approach to addressing this kind of multifaceted challenge across a range of fields. Here we describe ongoing efforts to address barriers to recently proposed FAIR (Findability, Accessibility, Interoperability, Reuse) and open science principles by assembling interested parties from research and education communities, industry, publishers, and data repositories to approach these issues jointly in a focused, efficient, and practical way. By outlining the benefits of networks, generally, and drawing on examples from efforts by the Non-Clinical Tomography Users Research Network (NoCTURN), specifically, we illustrate how standardization of data and metadata for reuse can foster interdisciplinary collaborations and create new opportunities for future-looking, large-scale data initiatives

Conserved elements in the transcription initiation regions preceding highly expressed structural genes of methanogenic archaebacteria.

The sequences of the intergenic regions of the strongly expressed genes encoding methyl CoM reductase in three different methanogenic archaebacteria were determined and the 5'-ends of the transcripts were mapped. After alignment, consensus sequences were found which are located both upstream and downstream of the transcription starts. They correspond, in part, to those previously characterized as putative elements of archaebacterial promoter sequences. In addition, bending of the DNA in front of the transcription start sites was shown in two cases and a characteristic common DNA structure immediately downstream of the 5'-end of the transcript was discovered. This structure was also found in the corresponding regions of previously described genes in methanogens. Our results suggest that both sequence and structural information may have roles in the initiation of transcription of protein encoding genes of these archaebacteria

Comparison of bioactive aldehydes modifying action on human albumin

Protein’s postsynthetic modifications are a cause and a consequence of many diseases. Endogenous aldehydes are one of the main factors of these modifications formation. The human albumin’s modification under some aldehydes influence in in vitro experiment has been investigated. Human albumin (20 mM) was incubated with following aldehydes: ribose, glyoxal, methylglyoxal and formaldehyde (20 mM each) and their combinations in 0.1 M Na-phosphate buffer (pH 7.4) with 0.02% sodium azide at 37 °C in the dark for up to 30 days. We have determined the fluorescent properties of the samples, the content of protein’s carbonyl groups and the redistribution of protein’s molecular weight. The following ratings of aldehydes from the lowest to the highest effect have been obtained. Fluo­rescent albumin adducts formation: formaldehyde, methylglyoxal, ribose, glyoxal; carbonylation of the protein: ribose, formaldehyde, glyoxal, methyl­glyoxal; polymerization of albumin – the formation of intermolecular crosslinks: ribose, methylglyoxal, glyoxal, formaldehyde. The results indicate that these aldehydes have different capability for protein’s modifications. For example, formaldehyde, having the lowest ability to form fluorescent adducts, shows the highest ability to form protein’s intermolecular crosslinks. Therefore, methods and parame­ters in order to evaluate the protein postsynthetic modification intensity have to be chosen correctly according to carbonyl stress peculiarity in order to evaluate the protein’s postsynthetic modification intensity

Sepiapterin Improves Vascular Reactivity and Insulin-Stimulated Glucose in Wistar Rats

In the vasculature, sedentary behavior leads to endothelial abnormalities, resulting in elevated cardiovascular disease risk. Endothelial nitric oxide synthase (eNOS) aberrations characterize endothelial dysfunction; eNOS also regulates mitochondrial function. We hypothesized that sepiapterin (a precursor to eNOS cofactor tetrahydrobiopterin (BH4)) supplementation would improve endothelium-dependent vascular relaxation in sedentary animals via modulation of NOS function and mitochondrial activity. Sedentary male Wistar rats were fed ad libitum for a total of 10 weeks. Sepiapterin was administered in diet during the final 5 weeks. Intraperitoneal insulin and glucose tolerance tests (IP-ITT/IP-GTT) were conducted at baseline and endpoint. Aorta was assessed for vasoreactivity and mitochondrial respiration. Insulin tolerance, determined by IP-ITT, significantly improved in rats treated with sepiapterin (p<0.05, interaction of time and treatment). Acetylcholine- (ACh-) driven vasodilation was significantly greater in aorta from sepiapterin-treated rats as compared with control (76.4% versus 54.9% of phenylephrine contraction at 20 μM ACh, p<0.05). Sepiapterin treatment resulted in significantly elevated state 3 (9.00 oxygen pmol/sec∗mg versus 8.17 oxygen pmol/sec∗mg, p<0.05) and 4 (7.28 oxygen pmol/sec∗mg versus 5.86 oxygen pmol/sec∗mg, p<0.05) aortic mitochondrial respiration with significantly lower respiratory control ratio (p<0.05) during octanoylcarnitine-driven respiration. Vasodilation and insulin sensitivity were improved through targeting NOS via sepiapterin supplementation