Aerothermal modeling program, Phase 2, Element C: Fuel injector-air swirl characterization

The main objectives of the NASA sponsored Aerothermal Modeling Program, Phase 2, Element C, are to collect benchmark quality data to quantify the fuel spray interaction with the turbulent swirling flows and to validate current and advanced two phase flow models. The technical tasks involved in this effort are discussed

The Treatment of Chronic Athletic Injuries of the Low Back and Lower Extremity Utilizing Manipulation

The purpose of this study was to determine whether spinal manipulation and/or lower extremity manipulation could be effective in a specific clinical situation -the treatment of chronically injured athletes. It was deemed important to set up a small pilot study that reflected exactly how a practitioner would deal with an injured athlete. Past trials of manipulation have been criticized because they did not resemble what actually occurs in a clinical situation. Participants were restricted to a few standard manipulations. They were not allowed to treat the participating patient as they normally would have(l)

Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytes

Feline immunodeficiency virus (FIV), the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection in peripheral blood CD4+ T-cells approximately eight months after experimental inoculation. In this study, cats experimentally infected with the FIV-C strain in the asymptomatic phase demonstrated an estimated viral load of 1 infected cell per approximately 103 CD4+ T-cells, with about 1 copy of viral DNA per cell. Approximately 1 in 10 proviral copies was capable of transcription in the asymptomatic phase. The latent FIV proviral promoter was associated with deacetylated, methylated histones, which is consistent with a condensed chromatin structure. In contrast, the transcriptionally active FIV promoter was associated with histone acetylation and demethylation. In addition, RNA polymerase II appeared to be paused on the latent viral promoter, and short promoter-proximal transcripts were detected. Our findings for the FIV promoter in infected cats are similar to results obtained in studies of human immunodeficiency virus (HIV)-1 latent proviruses in cell culture in vitro studies. Thus, the FIV/cat model may offer insights into in vivo mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus

Quality of life after infrainguinal bypass grafting surgery

AbstractPurpose: The purpose of this study was to compare quality of life in patients with and without various ischemic complications after infrainguinal bypass grafting surgery for occlusive vascular disease. Methods: A sample of patients (n = 746) randomized in the Dutch BOA study (n = 2645), a multicenter trial that compared the effectiveness of oral anticoagulant therapy with aspirin in the prevention of infrainguinal bypass graft occlusions, was entered in this study. On the basis of clinical outcomes of the trial, the patients were grouped as follows: patients with patent grafts (n = 409); patients with nontreated graft occlusions, subdivided into an asymptomatic group (n = 32) and a symptomatic group (n = 65); patients with subsequent revascularizations (n = 194); patients with amputations (n = 36); and patients with failed secondary revascularizations followed by secondary amputation (n = 38). In case an outcome event occurred, the patients were regrouped accordingly. Every half year, the patients completed a Short Form–36 and a EuroQol questionnaire. A multilevel model was used for repeated measure analysis. Results:The mean follow-up time was 21 months. The quality of life in patients with nontreated asymptomatic occlusions was roughly similar to the quality of life in patients with patent grafts. Patients with symptomatic nontreated occlusions had the lowest outcome with regard to pain as compared with the other groups. Furthermore, physical and social functioning was lower for these patients than for patients with patent grafts. Revascularizations, successful or not, negatively affected pain, social functioning, and physical and emotional role. After successful revascularization, some improvement was observed in pain, physical and social functioning, and general and mental health as compared with the group with nontreated symptomatic occlusions. Amputation deteriorated physical functioning strikingly, especially after failed secondary revascularization. These patients also had the lowest scores of all the groups in the dimensions of social functioning, physical and emotional role, and mental health. EuroQol score showed deterioration of quality of life after all events, except for asymptomatic occlusions. The same patterns emerged if we stratified our analysis according to the indication for the initial operation: claudication or limb salvage. Quality of life was constant over time in all the groups in the observed period. Conclusion: Quality of life in patients with asymptomatic occluded grafts is similar to quality of life in patients with patent grafts. Revascularization of symptomatic occluded grafts improves quality of life to a certain extent. Amputation, in particular after failed secondary revascularization, seemed to be the lowest possible outcome. The results of the Short Form-36 and EuroQol measurements were in line with the clinical expectations. The association of disease severity with scores on the instruments supports the construct validity of these outcome measures for an objective assessment of quality of life in controlled studies. (J Vasc Surg 1999;29:913-9.

Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer (OvCa) most often derives from ovarian surface epithelial (OSE) cells. Several lines of evidence strongly suggest that increased exposure to progesterone (P4) protects women against developing OvCa. However, the underlying mechanisms of this protection are incompletely understood.</p> <p>Methods</p> <p>To determine downstream gene targets of P4, we established short term <it>in vitro </it>cultures of non-neoplastic OSE cells from six subjects, exposed the cells to P4 (10^-6M) for five days and performed transcriptional profiling with oligonucleotide microarrays containing over 22,000 transcripts.</p> <p>Results</p> <p>We identified concordant but modest gene expression changes in cholesterol/lipid homeostasis genes in three of six samples (responders), whereas the other three samples (non-responders) showed no expressional response to P4. The most up-regulated gene was <it>TMEM97 </it>which encodes a transmembrane protein of unknown function (MAC30). Analyses of outlier transcripts, whose expression levels changed most significantly upon P4 exposure, uncovered coordinate up-regulation of 14 cholesterol biosynthesis enzymes, insulin-induced gene 1, low density lipoprotein receptor, <it>ABCG1</it>, endothelial lipase, stearoyl- CoA and fatty acid desaturases, long-chain fatty-acyl elongase, and down-regulation of steroidogenic acute regulatory protein and <it>ABCC6</it>. Highly correlated tissue-specific expression patterns of <it>TMEM97 </it>and the cholesterol biosynthesis genes were confirmed by analysis of the GNF Atlas 2 universal gene expression database. Real-time quantitative RT-PCR analyses revealed 2.4-fold suppression of the <it>TMEM97 </it>gene expression in short-term cultures of OvCa relative to the normal OSE cells.</p> <p>Conclusion</p> <p>These findings suggest that a co-regulated transcript network of cholesterol/lipid homeostasis genes and <it>TMEM97 </it>are downstream targets of P4 in normal OSE cells and that <it>TMEM97 </it>plays a role in cholesterol and lipid metabolism. The P4-induced alterations in cholesterol and lipid metabolism in OSE cells might play a role in conferring protection against OvCa.</p

Engaging rural preceptors in new longitudinal community clerkships during workforce shortage: a qualitative study

Background: In keeping with its mission to produce doctors for rural and regional Australia, the University of Wollongong, Graduate School of Medicine has established an innovative model of clinical education. This includes a 12-month integrated community-based clerkship in a regional or rural setting, offering senior students longitudinal participation in a \u27community of practice\u27 with access to continuity of patient care experiences, continuity of supervision and curriculum, and individualised personal and professional development. This required developing new teaching sites, based on attracting preceptors and providing them with educational and physical infrastructure. A major challenge was severe health workforce shortages. Methods: Before the new clerkship started, we interviewed 28 general practitioners to determine why they engaged as clerkship preceptors. Independent researchers conducted semi-structured interviews. Responses were transcribed for inductive qualitative content analysis. Results: The new model motivated preceptors to engage because it enhanced their opportunities to contribute to authentic learning when compared with the perceived limitations of short-term attachments. Preceptors appreciated the significant recognition of the value of general practice teaching and the honour of major involvement in the university. They predicted that the initiative would have positive effects on general practitioner morale and improve the quality of their practice. Other themes included the doctors\u27 commitment to their profession, \u27handing on\u27 to the next generation and helping their community to attract doctors in the future. Conclusions: Supervisors perceive that new models of clinical education offer alternative solutions to health care education, delivery and workforce. The longitudinal relationship between preceptor, student and community was seen as offering reciprocal benefits. General practitioners are committed to refining practice and ensuring generation of new members in their profession. They are motivated to engage in novel regional and rural longitudinal clinical clerkships as they perceive that they offer students an authentic learning experience and are a potential strategy to help address workforce shortages and maldistribution

Differential gene expression in human granulosa cells from recombinant FSH versus human menopausal gonadotropin ovarian stimulation protocols

<p>Abstract</p> <p>Background</p> <p>The study was designed to test the hypothesis that granulosa cell (GC) gene expression response differs between recombinant FSH and human menopausal gonadotropin (hMG) stimulation regimens.</p> <p>Methods</p> <p>Females < 35 years-old undergoing IVF for tubal or male factor infertility were prospectively randomized to one of two stimulation protocols, GnRH agonist long protocol plus individualized dosages of (1) recombinant (r)FSH (Gonal-F) or (2) purified human menopausal gonadotropin (hMG; Menopur). Oocytes were retrieved 35 h post-hCG, and GC were collected. Total RNA was extracted from each GC sample, biotinylated cRNA was synthesized, and each sample was run on Human Genome Bioarrays (Applied Microarrays). Unnamed genes and genes with <2-fold difference in expression were excluded.</p> <p>Results</p> <p>After exclusions, 1736 genes exhibited differential expression between groups. Over 400 were categorized as signal transduction genes, ~180 as transcriptional regulators, and ~175 as enzymes/metabolic genes. Expression of selected genes was confirmed by RT-PCR. Differentially expressed genes included A kinase anchor protein 11 (AKAP11), bone morphogenetic protein receptor II (BMPR2), epidermal growth factor (EGF), insulin-like growth factor binding protein (IGFBP)-4, IGFBP-5, and hypoxia-inducible factor (HIF)-1 alpha.</p> <p>Conclusions</p> <p>Results suggest that major differences exist in the mechanism by which pure FSH alone versus FSH/LH regulate gene expression in preovulatory GC that could impact oocyte maturity and developmental competence.</p

CA125/MUC16 Is Dispensable for Mouse Development and Reproduction

Cancer antigen 125 (CA125) is a blood biomarker that is routinely used to monitor the progression of human epithelial ovarian cancer (EOC) and is encoded by MUC16, a member of the mucin gene family. The biological function of CA125/MUC16 and its potential role in EOC are poorly understood. Here we report the targeted disruption of the of the Muc16 gene in the mouse. To generate Muc16 knockout mice, 6.0 kb was deleted that included the majority of exon 3 and a portion of intron 3 and replaced with a lacZ reporter cassette. Loss of Muc16 protein expression suggests that Muc16 homozygous mutant mice are null mutants. Muc16 homozygous mutant mice are viable, fertile, and develop normally. Histological analysis shows that Muc16 homozygous mutant tissues are normal. By the age of 1 year, Muc16 homozygous mutant mice appear normal. Downregulation of transcripts from another mucin gene (Muc1) was detected in the Muc16 homozygous mutant uterus. Lack of any prominent abnormal phenotype in these Muc16 knockout mice suggests that CA125/MUC16 is not required for normal development or reproduction. These knockout mice provide a unique platform for future studies to identify the role of CA125/MUC16 in organ homeostasis and ovarian cancer

Fake hands in action: embodiment and control of supernumerary limbs

Demonstrations that the brain can incorporate a fake limb into our bodily representations when stroked in synchrony with our unseen real hand [(the rubber hand illusion (RHI)] are now commonplace. Such demonstrations highlight the dynamic flexibility of the perceptual body image, but evidence for comparable RHI-sensitive changes in the body schema used for action is less common. Recent evidence from the RHI supports a distinction between bodily representations for perception (body image) and for action (body schema) (Kammers et al. in Neuropsychologia 44:2430–2436, 2006). The current study challenges and extends these findings by demonstrating that active synchronous stroking of a brush not only elicits perceptual embodiment of a fake limb (body image) but also affects subsequent reaching error (body schema). Participants were presented with two moving fake left hands. When only one was synchronous during active touch, ownership was claimed for the synchronous hand only and the accuracy of reaching was consistent with control of the synchronous hand. When both fake hands were synchronous, ownership was claimed over both, but only one was controlled. Thus, it would appear that fake limbs can be incorporated into the body schema as well as the body image, but while multiple limbs can be incorporated into the body image, the body schema can accommodate only one

Inhibition of StearoylCoA Desaturase Activity Blocks Cell Cycle Progression and Induces Programmed Cell Death in Lung Cancer Cells

Lung cancer is the most frequent form of cancer. The survival rate for patients with metastatic lung cancer is ∼5%, hence alternative therapeutic strategies to treat this disease are critically needed. Recent studies suggest that lipid biosynthetic pathways, particularly fatty acid synthesis and desaturation, are promising molecular targets for cancer therapy. We have previously reported that inhibition of stearoylCoA desaturase-1 (SCD1), the enzyme that produces monounsaturated fatty acids (MUFA), impairs lung cancer cell proliferation, survival and invasiveness, and dramatically reduces tumor formation in mice. In this report, we show that inhibition of SCD activity in human lung cancer cells with the small molecule SCD inhibitor CVT-11127 reduced lipid synthesis and impaired proliferation by blocking the progression of cell cycle through the G1/S boundary and by triggering programmed cell death. These alterations resulting from SCD blockade were fully reversed by either oleic (18:1n-9), palmitoleic acid (16:1n-7) or cis-vaccenic acid (18:1n-7) demonstrating that cis-MUFA are key molecules for cancer cell proliferation. Additionally, co-treatment of cells with CVT-11127 and CP-640186, a specific acetylCoA carboxylase (ACC) inhibitor, did not potentiate the growth inhibitory effect of these compounds, suggesting that inhibition of ACC or SCD1 affects a similar target critical for cell proliferation, likely MUFA, the common fatty acid product in the pathway. This hypothesis was further reinforced by the observation that exogenous oleic acid reverses the anti-growth effect of SCD and ACC inhibitors. Finally, exogenous oleic acid restored the globally decreased levels of cell lipids in cells undergoing a blockade of SCD activity, indicating that active lipid synthesis is required for the fatty acid-mediated restoration of proliferation in SCD1-inhibited cells. Altogether, these observations suggest that SCD1 controls cell cycle progression and apoptosis and, consequently, the overall rate of proliferation in cancer cells through MUFA-mediated activation of lipid synthesis