MANUFACTURING ASPECTS OF OFFSHORE FABRICATION AND INSTALLATION

The research presented in this paper aim at identifying research commonalities between shipbuilding, offshore fabrication practices and manufacturing. As part of an exploratory effort a literature review and a case study of two offshore structures projects were performed. Research concerning shipbuilding and offshore fabrication, together with literature from other industries in construction, larger engineering projects and traditional manufacturing was reviewed. The two offshore structures projects were analyzed by means of interviews and complemented by direct observations and document reviews. The study concludes that there are gaps in the research concerned with holistic perspectives on the fabrication and installation phases of shipbuilding and offshore projects. The number of actors involved in any project of this magnitude increase barriers and communication interfaces. The dynamic nature of these types of projects was also observed and the changeability should always be a accounted factor when dealing with projects of this sort. The interviews held as part of the verification of observed phenomena in literature was limited to two projects and a single company and actors perceptions. However the collected data served well in being complementary to the literature review. It could be the task of academia to patch the gaps for overall project success, in the cases where single industry actors simply cannot see the benefit or do not have the recourses to fill them themselves. This study combines findings from traditional manufacturing industries, shipbuilding, offshore structures fabrication and large engineering projects in general.</jats:p

The Structure of Murine <i>N</i>¹‑Acetylspermine Oxidase Reveals Molecular Details of Vertebrate Polyamine Catabolism

<i>N</i>¹-Acetylspermine oxidase (APAO) catalyzes the conversion of <i>N</i>¹-acetylspermine or <i>N</i>¹-acetylspermidine to spermidine or putrescine, respectively, with concomitant formation of <i>N</i>-acetyl-3-aminopropanal and hydrogen peroxide. Here we present the structure of murine APAO in its oxidized holo form and in complex with substrate. The structures provide a basis for understanding molecular details of substrate interaction in vertebrate APAO, highlighting a key role for an asparagine residue in coordinating the <i>N</i>¹-acetyl group of the substrate. We applied computational methods to the crystal structures to rationalize previous observations with regard to the substrate charge state. The analysis suggests that APAO features an active site ideally suited for binding of charged polyamines. We also reveal the structure of APAO in complex with the irreversible inhibitor MDL72527. In addition to the covalent adduct, a second MDL72527 molecule is bound in the active site. Binding of MDL72527 is accompanied by altered conformations in the APAO backbone. On the basis of structures of APAO, we discuss the potential for development of specific inhibitors

Detection of Growth Hormone Doping by Gene Expression Profiling of Peripheral Blood

Context: GH abuse is a significant problem in many sports, and there is currently no robust test that allows detection of doping beyond a short window after administration. Objective: Our objective was to evaluate gene expression profiling in peripheral blood leukocytes in-vivo as a test for GH doping in humans. Design: Seven men and thirteen women were administered GH, 2 mg/d sc for 8 wk. Blood was collected at baseline and at 8 wk. RNA was extracted from the white cell fraction. Microarray analysis was undertaken using Agilent 44K G4112F arrays using a two-color design. Quantitative RT-PCR using TaqMan gene expression assays was performed for validation of selected differentially expressed genes. Results: GH induced an approximately 2-fold increase in circulating IGF-I that was maintained throughout the 8 wk of the study. GH induced significant changes in gene expression with 353 in women and 41 in men detected with a false discovery rate of less than 5%. None of the differentially expressed genes were common between men and women. The maximal changes were a doubling for up-regulated or halving for down-regulated genes, similar in magnitude to the variation between individuals. Quantitative RT-PCR for seven target genes showed good concordance between microarray and quantitative PCR data in women but not in men. Conclusion: Gene expression analysis of peripheral blood leukocytes is unlikely to be a viable approach for the detection of GH doping

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines update 2023 on the pharmacological treatment of eating disorders

ObjectivesThis 2023 update of the WFSBP guidelines for the pharmacological treatment of eating disorders (EDs) reflects the latest diagnostic and psychopharmacological progress and the improved WFSBP recommendations for the assessment of the level of evidence (LoE) and the grade of recommendation (GoR).MethodsThe WFSBP Task Force EDs reviewed the relevant literature and provided a timely grading of the LoE and the GoR.ResultsIn anorexia nervosa (AN), only a limited recommendation (LoE: A; GoR: 2) for olanzapine can be given, because the available evidence is restricted to weight gain, and its effect on psychopathology is less clear. In bulimia nervosa (BN), the current literature prompts a recommendation for fluoxetine (LoE: A; GoR: 1) or topiramate (LoE: A; GoR: 1). In binge-eating disorder (BED), lisdexamfetamine (LDX; LoE: A; GoR: 1) or topiramate (LoE: A; GoR: 1) can be recommended. There is only sparse evidence for the drug treatment of avoidant restrictive food intake disorder (ARFID), pica, and rumination disorder (RD).ConclusionIn BN, fluoxetine, and topiramate, and in BED, LDX and topiramate can be recommended. Despite the published evidence, olanzapine and topiramate have not received marketing authorisation for use in EDs from any medicine regulatory agency

Regulation of Growth Hormone Signaling by Selective Estrogen Receptor Modulators Occurs through Suppression of Protein Tyrosine Phosphatases

Activation of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) pathway by GH is terminated by the suppressors of cytokine signaling (SOCSs) and protein tyrosine phosphatases, Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1 and SHP-2. Based on our recent report that estrogen inhibits GH signaling by stimulating SOCS-2 expression, we investigated the effects of selective estrogen receptor modulators (SERMs) on GH signaling in human embryonic kidney (HEK293) and breast cancer (MDA-MB-231) cells expressing human GH receptor and estrogen receptor-α. 17β-Estradiol (E) suppressed GH activation of a STAT5-responsive luciferase reporter and JAK2 phosphorylation in both cell models. 4-Hydroxytamoxifen and raloxifene augmented these actions of GH in HEK293 cells but not breast cancer cells. SOCS-2 expression in both cell types was stimulated by E but unaffected by SERMs. In HEK293 cells, SHP-1 was inhibited by raloxifene and 4-hydroxytamoxifen, whereas the latter additionally inhibited SHP-2. The phosphatases were unaffected by E. In breast cancer cells, phosphatase activity was not altered by SERMs or E . In summary, estrogen inhibited the JAK2/STAT5 signaling of GH and stimulated SOCS-2 expression in both HEK293 and breast cancer cells. By contrast, SERMs augmented GH signaling by reducing SHP activities in HEK293 cells and had no effect on both in breast cancer cells. We provide the first evidence for a novel mechanism regulating GH signaling, in which SERMs enhance GH activation of the JAK2/STAT5 pathway in a cell-type-dependent manner by attenuating protein tyrosine phosphatase activities