Results of tests OA26 and IA16 in the NASA/ARC 3.5-foot hypersonic wind tunnel on an 0.015-scale model (36-OTS) of the space shuttle configuration 140A/B to obtain pressures for venting analysis

Tests were conducted, from November 15 to December 4, 1973, to obtain surface pressure data on an 0.015-scale replica of the Space Shuttle Vehicle 4. Data were obtained at Mach numbers of 5.3, 7.4, and 10.3, to support the venting analysis for both launch and entry conditions. These tests were the final tests in a series covering a Mach number range from 0.6 to 10.3. The model was instrumented with pressure orifices in the vicinity of the cargo bay door hinge and parting lines, and on the side of the fuselage at the crew compartment, and below the orbital maneuvering system pods at the aft compartment. The model was tested at angles of attack and sideslip consistent with expected divergencies from the nominal trajectory

The association between paternal and adolescent depressive symptoms: evidence from two population-based cohorts

BACKGROUND: Incidence of depression increases markedly around age 13 years, and nearly three-quarters of adults report that their mental health problems started in adolescence. Although maternal depression is a risk factor for adolescent depression, evidence about the association between paternal and adolescent depression is inconclusive, and many studies have methodological limitations. We aimed to assess the association between paternal and adolescent depressive symptoms in two large population-based cohort studies. METHODS: We used data for two-parent families from two representative prospective cohorts in Ireland (Growing up in Ireland [GUI]) and the UK (Millennium Cohort Study [MCS]). Parental depressive symptoms were measured with the Centre for Epidemiological Studies Depression Scale in the GUI cohort when children were 9 years old, and the Kessler six-item psychological distress scale in the MCS cohort when children were 7 years old. Adolescent depressive symptoms were measured with the Short Mood and Feelings Questionnaire (SMFQ) at age 13 years in the GUI cohort and age 14 years in the MCS cohort. We analysed data using linear regression models, before and after adjustment for confounders, in both multiply imputed and complete case samples. FINDINGS: There were 6070 families in GUI and 7768 in MCS. After all adjustments, a 1 SD (three-point) increase in paternal depressive symptoms was associated with an increase of 0·24 SMFQ points (95% CI 0·03-0·45; p=0·023) in the GUI cohort and 0·18 SMFQ points (0·01-0·36; p=0·041) in the MCS cohort. This association was independent of, and not different in magnitude to, the association between maternal and adolescent depressive symptoms (Wald test p=0·435 in the GUI cohort and 0·470 in the MCS cohort). INTERPRETATION: Our results show an association between depressive symptoms in fathers and depressive symptoms in their adolescent offspring. These findings support the involvement of fathers as well as mothers in early interventions to reduce the prevalence of adolescent depression, and highlight the importance of treating depression in both parents. FUNDING: Department of Children and Youth Affairs and Economic and Social Research Council

Values and identity process theory: theoretical integration and empirical interactions

Identity and values are important driving forces in human lives. Identity Process Theory (IPT; Breakwell, 1986, 2001b) and the Schwartz Value Theory (Schwartz, 1992) focus on distinct but related aspects of the self and have some overlapping propositions particularly with regards to human motivation. Hence, it is surprising that there has been no attempt so far to integrate them theoretically or empirically. This chapter provides the first attempt to address this gap in the literature. After presenting key elements of both theories, the chapter provides a theoretical integration that addresses the links between identity motives and outcomes and provides an empirical examination of the role of personal values as moderators of such links. Finally, we address identity and value change

Couples living with type 1 diabetes : an integrative review of the impacts on health and wellbeing

Impacts of type 1 diabetes and relationship factors on health and wellbeing of both persons with diabetes and partners (T1D partners) have not been investigated. Integrative review methods evaluated the evidence. From 323 titles, we included 24 studies involving 16,083 persons with diabetes and 1020 T1D partners. Studies were quantitative (n = 13), qualitative (n = 9) and mixed methods (n = 2). Maintaining resilient, good quality, intimate relationships optimises physical and psychological outcomes for persons with diabetes. Partners experience disturbed sleep and while general psychological health is maintained, distress surrounding hypoglycaemia is overwhelming for over a third of partners. Nurturing quality relationships could reap significant health benefits

Pathways to economic well-being among teenage mothers in Great Britain

The present study examines pathways to independence from social welfare among 738 teenage mothers, participants of the 1970 British Cohort Study, who were followed up at age 30 years. Using a longitudinal design, a pathway model is tested, examining linkages between family social background, cognitive ability, school motivation, and individual investments in education, as well as work- and family-related roles. The most important factors associated with financial independence by age 30 are continued attachment to the labor market as well as a stable relationship with a partner (not necessarily the father of the child). Pathways to financial independence, in turn, are predicted through own cognitive resources, school motivation, and family cohesion. Implications of findings for policy making are discussed.© 2010 Hogrefe Publishing

Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer:a nested case-control study

Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer

TWEAK Affects Keratinocyte G2/M Growth Arrest and Induces Apoptosis through the Translocation of the AIF Protein to the Nucleus

The soluble TNF-like weak inducer of apoptosis (TWEAK, TNFSF12) binds to the fibroblast growth factor-inducible 14 receptor (FN14, TNFRSF12A) on the cell membrane and induces multiple biological responses, such as proliferation, migration, differentiation, angiogenesis and apoptosis. Previous reports show that TWEAK, which does not contain a death domain in its cytoplasmic tail, induces the apoptosis of tumor cell lines through the induction of TNFα secretion. TWEAK induces apoptosis in human keratinocytes. Our experiments clearly demonstrate that TWEAK does not induce the secretion of TNFα or TRAIL proteins. The use of specific inhibitors and the absence of procaspase-3 cleavage suggest that the apoptosis of keratinocytes follows a caspase- and cathepsin B-independent pathway. Further investigation showed that TWEAK induces a decrease in the mitochondrial membrane potential of keratinocytes. Confocal microscopy showed that TWEAK induces the cleavage and the translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus, thus initiating caspase-independent apoptosis. Moreover, TWEAK induces FOXO3 and GADD45 expression, cdc2 phosphorylation and cdc2 and cyclinB1 degradation, resulting in the arrest of cell growth at the G2/M phase. Finally, we report that TWEAK and FN14 are normally expressed in the basal layer of the physiological epidermis and are greatly enhanced in benign (psoriasis) and malignant (squamous cell carcinoma) skin pathologies that are characterized by an inflammatory component. TWEAK might play an essential role in skin homeostasis and pathology

The cytokine tumor necrosis factor-like weak inducer of apoptosis and its receptor fibroblast growth factor-inducible 14 have a neuroprotective effect in the central nervous system

<p>Abstract</p> <p>Background</p> <p>Cerebral cortical neurons have a high vulnerability to the harmful effects of hypoxia. However, the brain has the ability to detect and accommodate to hypoxic conditions. This phenomenon, known as preconditioning, is a natural adaptive process highly preserved among species whereby exposure to sub-lethal hypoxia promotes the acquisition of tolerance to a subsequent lethal hypoxic injury. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are found in neurons and their expression is induced by exposure to sub-lethal hypoxia. Accordingly, in this work we tested the hypothesis that the interaction between TWEAK and Fn14 induces tolerance to lethal hypoxic and ischemic conditions.</p> <p>Methods</p> <p>Here we used <it>in vitro </it>and <it>in vivo </it>models of hypoxic and ischemic preconditioning, an animal model of transient middle cerebral artery occlusion and mice and neurons genetically deficient in TWEAK, Fn14, or tumor necrosis factor alpha (TNF-α) to investigate whether treatment with recombinant TWEAK or an increase in the expression of endogenous TWEAK renders neurons tolerant to lethal hypoxia. We used enzyme-linked immunosorbent assay to study the effect of TWEAK on the expression of neuronal TNF-α, Western blot analysis to investigate whether the effect of TWEAK was mediated by activation of mitogen-activated protein kinases and immunohistochemical techniques and quantitative real-time polymerase chain reaction analysis to study the effect of TWEAK on apoptotic cell death.</p> <p>Results</p> <p>We found that either treatment with recombinant TWEAK or an increase in the expression of TWEAK and Fn14 induce hypoxic and ischemic tolerance <it>in vivo </it>and <it>in vitro</it>. This protective effect is mediated by neuronal TNF-α and activation of the extracellular signal-regulated kinases 1 and 2 pathway via phosphorylation and inactivation of the B-cell lymphoma 2-associated death promoter protein.</p> <p>Conclusions</p> <p>Our work indicate that the interaction between TWEAK and Fn14 triggers the activation of a cell signaling pathway that results in the induction of tolerance to lethal hypoxia and ischemia. These data indicate that TWEAK may be a potential therapeutic strategy to protect the brain from the devastating effects of an ischemic injury.</p

TWEAK and Fn14 expression in the pathogenesis of joint inflammation and bone erosion in rheumatoid arthritis

Extent: 10p.INTRODUCTION: TNF-like weak inducer of apoptosis (TWEAK) has been proposed as a mediator of inflammation and bone erosion in rheumatoid arthritis (RA). This study aimed to investigate TWEAK and TWEAK receptor (Fn14) expression in synovial tissue from patients with active and inactive rheumatoid arthritis (RA), osteoarthritis (OA) and normal controls and assess soluble (s)TWEAK levels in the synovial fluids from patients with active RA and OA. Effects of sTWEAK on osteoclasts and osteoblasts were investigated in vitro. METHODS: TWEAK and Fn14 expression were detected in synovial tissues by immunohistochemistry (IHC). Selected tissues were dual labelled with antibodies specific for TWEAK and lineage-selective cell surface markers CD68, Tryptase G, CD22 and CD38. TWEAK mRNA expression was examined in human peripheral blood mononuclear cells (PBMC) sorted on the basis of their expression of CD22. sTWEAK was detected in synovial fluid from OA and RA patients by ELISA. The effect of sTWEAK on PBMC and RAW 264.7 osteoclastogenesis was examined. The effect of sTWEAK on cell surface receptor activator of NF Kappa B Ligand (RANKL) expression by human osteoblasts was determined by flow cytometry. RESULTS: TWEAK and Fn14 expression were significantly higher in synovial tissue from all patient groups compared to the synovial tissue from control subjects (P < 0.05). TWEAK was significantly higher in active compared with inactive RA tissues (P < 0.05). TWEAK expression co-localised with a subset of CD38+ plasma cells and with CD22+ B-lymphocytes in RA tissues. Abundant TWEAK mRNA expression was detected in normal human CD22+ B cells. Higher levels of sTWEAK were observed in synovial fluids isolated from active RA compared with OA patients. sTWEAK did not stimulate osteoclast formation directly from PBMC, however, sTWEAK induced the surface expression of RANKL by human immature, STRO-1+ osteoblasts. CONCLUSIONS: The expression of TWEAK by CD22+ B cells and CD38+ plasma cells in RA synovium represents a novel potential pathogenic pathway. High levels of sTWEAK in active RA synovial fluid and of TWEAK and Fn14 in active RA tissue, together with the effect of TWEAK to induce osteoblastic RANKL expression, is consistent with TWEAK/Fn14 signalling being important in the pathogenesis of inflammation and bone erosion in RA.Anak A. S. S. K. Dharmapatni, Malcolm D. Smith, Tania N. Crotti, Christopher A. Holding, Cristina Vincent, Helen M. Weedon, Andrew C. W. Zannettino, Timothy S. Zheng, David M. Findlay, Gerald J. Atkins and David R. Hayne

Interleukin-32 Promotes Osteoclast Differentiation but Not Osteoclast Activation

Background: Interleukin-32 (IL-32) is a newly described cytokine produced after stimulation by IL-2 or IL-18 and IFN-γ. IL-32 has the typical properties of a pro-inflammatory mediator and although its role in rheumatoid arthritis has been recently reported its effect on the osteoclastogenesis process remains unclear. Methodology/principal findings: In the present study, we have shown that IL-32 was a potent modulator of osteoclastogenesis in vitro, whereby it promoted the differentiation of osteoclast precursors into TRAcP+ VNR+ multinucleated cells expressing specific osteoclast markers (up-regulation of NFATc1, OSCAR, Cathepsin K), but it was incapable of inducing the maturation of these multinucleated cells into bone-resorbing cells. The lack of bone resorption in IL-32-treated cultures could in part be explain by the lack of F-actin ring formation by the multinucleated cells generated. Moreover, when IL-32 was added to PBMC cultures maintained with soluble RANKL, although the number of newly generated osteoclast was increased, a significant decrease of the percentage of lacunar resorption was evident suggesting a possible inhibitory effect of this cytokine on osteoclast activation. To determine the mechanism by which IL-32 induces such response, we sought to determine the intracellular pathways activated and the release of soluble mediators in response to IL-32. Our results indicated that compared to RANKL, IL-32 induced a massive activation of ERK1/2 and Akt. Moreover, IL-32 was also capable of stimulating the release of IL-4 and IFN-γ, two known inhibitors of osteoclast formation and activation. Conclusions/significance: This is the first in vitro report on the complex role of IL-32 on osteoclast precursors. Further clarification on the exact role of IL-32 in vivo is required prior to the development of any potential therapeutic approach