Neurofibromin knockdown in glioma cell lines is associated with changes in cytokine and chemokine secretion in vitro.

The neurofibromin-1 tumor suppressor gene (NF1) is altered in approximately 20% of sporadic glioblastoma (GBM) cases. NF1 deficient GBM frequently shows a mesenchymal gene expression signature, suggesting a relationship between NF1 status and the tumor microenvironment. To identify changes in the production of secreted cytokines/chemokines in NF1 deficient glioma, we applied cytokine arrays to conditioned media from a panel of three GBM cell lines after siRNA-mediated NF1 knockdown. We identified increased secretion of platelet-derived growth factor AA (PDGF-AA), chitinase-3-like protein 1 (CHI3L1), interleukin-8 (IL-8), and endoglin (ENG) in different subsets of these cell lines. Secretion was associated with induction of the corresponding messenger RNA, suggesting a mechanism involving transcriptional upregulation. By contrast, in non-transformed immortalized normal human astrocytes, PDGF-AA secretion was increased upon NF1 knockdown, while secreted CHI3L1, ENG, and IL-8 were reduced or unchanged. Analysis of The Cancer Genome Atlas confirmed a relationship between glioma NF1 status and ENG and CHI3L1 in tumor samples. Overall, this study identifies candidate changes in secreted proteins from NF1 deficient glioma cells that could influence the tumor microenvironment, and suggests a direct link between NF1 loss and increased tumor cell production of CHI3L1 and endoglin, two factors implicated in mesenchymal identity in glioblastoma

Combustor design and analysis using the Rocket Combustor Interactive Design (ROCCID) methodology

The ROCket Combustor Interactive Design (ROCCID) Methodology is a newly developed, interactive computer code for the design and analysis of a liquid propellant rocket combustion chamber. The application of ROCCID to design a liquid rocket combustion chamber is illustrated. Designs for a 50,000 lbf thrust and 1250 psi chamber pressure combustor using liquid oxygen (LOX)RP-1 propellants are developed and evaluated. Tradeoffs between key design parameters affecting combustor performance and stability are examined. Predicted performance and combustion stability margin for these designs are provided as a function of the combustor operating mixture ratio and chamber pressure

Land vehicle antennas for satellite mobile communications

The RF performance, size, pointing system, and cost were investigated concepts are: for a mechanically steered 1 x 4 tilted microstrip array, a mechanically steered fixed-beam conformal array, and an electronically steered conformal phased array. Emphasis is on the RF performance of the tilted 1 x 4 antenna array and methods for pointing the various antennas studied to a geosynchronous satellite. An updated version of satellite isolations in a two-satellite system is presented. Cost estimates for the antennas in quantities of 10,000 and 100,000 unites are summarized

Center-of-mass effects on the quasi-hole spectroscopic factors in the 16O(e,e'p) reaction

The spectroscopic factors for the low-lying quasi-hole states observed in the 16O(e,e'p)15N reaction are reinvestigated with a variational Monte Carlo calculation for the structure of the initial and final nucleus. A computational error in a previous report is rectified. It is shown that a proper treatment of center-of-mass motion does not lead to a reduction of the spectroscopic factor for $p$-shell quasi-hole states, but rather to a 7% enhancement. This is in agreement with analytical results obtained in the harmonic oscillator model. The center-of-mass effect worsens the discrepancy between present theoretical models and the experimentally observed single-particle strength. We discuss the present status of this problem, including some other mechanisms that may be relevant in this respect.Comment: 14 pages, no figures, uses Revtex, to be published in Phys. Rev. C 58 (1998

Neutron Drops and Skyrme Energy-Density Functionals

The J$^{\pi}$=0$^+$ ground state of a drop of 8 neutrons and the lowest 1/2$^-$ and 3/2$^-$ states of 7-neutron drops, all in an external well, are computed accurately with variational and Green's function Monte Carlo methods for a Hamiltonian containing the Argonne $v_{18}$ two-nucleon and Urbana IX three-nucleon potentials. These states are also calculated using Skyrme-type energy-density functionals. Commonly used functionals overestimate the central density of these drops and the spin-orbit splitting of 7-neutron drops. Improvements in the functionals are suggested

Selecting and implementing overview methods: implications from five exemplar overviews

This is the final version of the article. Available from BioMed Central via the DOI in this record.Background Overviews of systematic reviews are an increasingly popular method of evidence synthesis; there is a lack of clear guidance for completing overviews and a number of methodological challenges. At the UK Cochrane Symposium 2016, methodological challenges of five overviews were explored. Using data from these five overviews, practical implications to support methodological decision making of authors writing protocols for future overviews are proposed. Methods Methods, and their justification, from the five exemplar overviews were tabulated and compared with areas of debate identified within current literature. Key methodological challenges and implications for development of overview protocols were generated and synthesised into a list, discussed and refined until there was consensus. Results Methodological features of three Cochrane overviews, one overview of diagnostic test accuracy and one mixed methods overview have been summarised. Methods of selection of reviews and data extraction were similar. Either the AMSTAR or ROBIS tool was used to assess quality of included reviews. The GRADE approach was most commonly used to assess quality of evidence within the reviews. Eight key methodological challenges were identified from the exemplar overviews. There was good agreement between our findings and emerging areas of debate within a recent published synthesis. Implications for development of protocols for future overviews were identified. Conclusions Overviews are a relatively new methodological innovation, and there are currently substantial variations in the methodological approaches used within different overviews. There are considerable methodological challenges for which optimal solutions are not necessarily yet known. Lessons learnt from five exemplar overviews highlight a number of methodological decisions which may be beneficial to consider during the development of an overview protocol.The overview conducted by Pollock [19] was supported by a project grant from the Chief Scientist Office of the Scottish Government. The overview conducted by McClurg [21] was supported by a project grant by the Physiotherapy Research Foundation. The overview by Hunt [22] was supported as part of doctoral programme funding by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula (PenCLAHRC). The overview conducted by Estcourt [20] was supported by an NIHR Cochrane Programme Grant for the Safe and Appropriate Use of Blood Components. The overview conducted by Brunton [23] was commissioned by the Department of Health as part of an ongoing programme of work on health policy research synthesis. Alex Pollock is employed by the Nursing, Midwifery and Allied Health Professions (NMAHP) Research Unit, which is supported by the Chief Scientist Office of the Scottish Government. Pauline Campbell is supported by the Chief Nurses Office of the Scottish Government

Analysis of Cognitive Abilities of Adolescents Learning Disabled Specifically in Arithmetic Computation

This research was published by the KU Center for Research on Learning, formerly known as the University of Kansas Institute for Research in Learning Disabilities.This investigation identified a group of adolescents homogeneously defined as specifically learning disabled in arithmetic and examined whether cognitive processes measured by visual-spatial, visual-reasoning, and visual-memory tasks are related to this task failure. The results indicate that a relationship exists between two major components in the LD definition --academic task failure and specific cognitive abilities. There is validity to these two components when a very specific population of students disabled in arithmetic have been identified

International variation in outcomes among people with cardiovascular disease or cardiovascular risk factors and impaired glucose tolerance: insights from the NAVIGATOR Trial

Background: Regional differences in risk of diabetes mellitus and cardiovascular outcomes in people with impaired glucose tolerance are poorly characterized. Our objective was to evaluate regional variation in risk of new‐onset diabetes mellitus, cardiovascular outcomes, and treatment effects in participants from the NAVIGATOR (Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research) trial. Methods and Results: NAVIGATOR randomized people with impaired glucose tolerance and cardiovascular risk factors or with established cardiovascular disease to valsartan (or placebo) and to nateglinide (or placebo) with a median 5‐year follow‐up. Data from the 9306 participants were categorized by 5 regions: Asia (n=552); Europe (n=4909); Latin America (n=1406); North America (n=2146); and Australia, New Zealand, and South Africa (n=293). Analyzed outcomes included new‐onset diabetes mellitus; cardiovascular death; a composite cardiovascular outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke; and treatment effects of valsartan and nateglinide. Respective unadjusted 5‐year risks for new‐onset diabetes mellitus, cardiovascular death, and the composite cardiovascular outcome were 33%, 0.4%, and 4% for Asia; 34%, 2%, and 6% for Europe; 37%, 4%, and 8% for Latin America; 38%, 2%, and 6% for North America; and 32%, 4%, and 8% for Australia, New Zealand, and South Africa. After adjustment, compared with North America, European participants had a lower risk of new‐onset diabetes mellitus (hazard ratio 0.86, 95% CI 0.78–0.94; P=0.001), whereas Latin American participants had a higher risk of cardiovascular death (hazard ratio 2.68, 95% CI 1.82–3.96; P<0.0001) and the composite cardiovascular outcome (hazard ratio 1.48, 95% CI 1.15–1.92; P=0.003). No differential interactions between treatment and geographic location were identified. Conclusions: Major regional differences regarding the risk of new‐onset diabetes mellitus and cardiovascular outcomes in NAVIGATOR participants were identified. These differences should be taken into account when planning global trials