Study of flutter related computational procedures for minimum weight structural sizing of advanced aircraft

Results of a study of the development of flutter modules applicable to automated structural design of advanced aircraft configurations, such as a supersonic transport, are presented. Automated structural design is restricted to automated sizing of the elements of a given structural model. It includes a flutter optimization procedure; i.e., a procedure for arriving at a structure with minimum mass for satisfying flutter constraints. Methods of solving the flutter equation and computing the generalized aerodynamic force coefficients in the repetitive analysis environment of a flutter optimization procedure are studied, and recommended approaches are presented. Five approaches to flutter optimization are explained in detail and compared. An approach to flutter optimization incorporating some of the methods discussed is presented. Problems related to flutter optimization in a realistic design environment are discussed and an integrated approach to the entire flutter task is presented. Recommendations for further investigations are made. Results of numerical evaluations, applying the five methods of flutter optimization to the same design task, are presented

Study of flutter related computational procedures for minimum weight structural sizing of advanced aircraft, supplemental data

Computational aspects of (1) flutter optimization (minimization of structural mass subject to specified flutter requirements), (2) methods for solving the flutter equation, and (3) efficient methods for computing generalized aerodynamic force coefficients in the repetitive analysis environment of computer-aided structural design are discussed. Specific areas included: a two-dimensional Regula Falsi approach to solving the generalized flutter equation; method of incremented flutter analysis and its applications; the use of velocity potential influence coefficients in a five-matrix product formulation of the generalized aerodynamic force coefficients; options for computational operations required to generate generalized aerodynamic force coefficients; theoretical considerations related to optimization with one or more flutter constraints; and expressions for derivatives of flutter-related quantities with respect to design variables

Fiber-derived butyrate and the prevention of colon cancer

AbstractInhibition of the enzyme histone deacetylase by butyrate results in the direct transcriptional upregulation of the cyclin-dependent kinase inhibitor p21/Cip1/WAF1. We discuss a small-molecule-mediated signaling pathway to explain the suspected anti-colon-cancer properties of fiber-derived butyrate

A Framework for Evaluating Innovative Statistical and Risk Assessment Tools to Solve Environment Restoration Problems

Environmental restoration activities at the US Department of Energy (DOE) Hanford site face complex issues due to history of varied past contaminant disposal practices. Data collection and analysis required for site characterization, pathway modeling, and remediation selection decisions must deal with inherent uncertainties and unique problems associated with the restoration. A framework for working through the statistical aspects of the site characterization and remediation selection problems is needed. This framework would facilitate the selection of appropriate statistical tools for solving unique aspects of the environmental restoration problem. This paper presents a framework for selecting appropriate statistical and risk assessment methods. The following points will be made: (1) pathway modelers and risk assessors often recognize that some type'' of statistical methods are required but don't work with statisticians on tools development in the early planning phases of the project; (2) statistical tools selection and development are problem-specific and often site-specific, further indicating a need for up-front involvement of statisticians; and (3) the right tool, applied in the right way can minimize sampling costs, get as much information as possible out of the data that does exist, provide consistency and defensibility for the results, and given structure and quantitative measures to decision risks and uncertainties

Preclinical Evaluation of a Lentiviral Vector for Huntingtin Silencing.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder resulting from a polyglutamine expansion in the huntingtin (HTT) protein. There is currently no cure for this disease, but recent studies suggest that RNAi to downregulate the expression of both normal and mutant HTT is a promising therapeutic approach. We previously developed a small hairpin RNA (shRNA), vectorized in an HIV-1-derived lentiviral vector (LV), that reduced pathology in an HD rodent model. Here, we modified this vector for preclinical development by using a tat-independent third-generation LV (pCCL) backbone and removing the original reporter genes. We demonstrate that this novel vector efficiently downregulated HTT expression in vitro in striatal neurons derived from induced pluripotent stem cells (iPSCs) of HD patients. It reduced two major pathological HD hallmarks while triggering a minimal inflammatory response, up to 6 weeks after injection, when administered by stereotaxic surgery in the striatum of an in vivo rodent HD model. Further assessment of this shRNA vector in vitro showed proper processing by the endogenous silencing machinery, and we analyzed gene expression changes to identify potential off-targets. These preclinical data suggest that this new shRNA vector fulfills primary biosafety and efficiency requirements for further development in the clinic as a cure for HD

Evaluation of outreach services for primary care and mental health; assessing the impact

Objectives: This paper reports an evaluation, carried out for London Health Libraries, of the impact of outreach services to primary care and mental health workers in thirteen different settings. The main aims of the project were to identify the impact being made by the service, and to produce best practice guidelines for outreach services in this kind of ‘difficult’ community setting. Methods: Methods used were: analysis of documents (all 13 services); analysis of any evaluation already performed by or for the service (all 13 services); interviews with outreach librarians (11 services); questionnaire survey of a representative sample of users (8 services, with 66 returned questionnaires, 35% response rate). The services evaluated were very diverse, in terms of setting, structure, functions and activities, and extent and nature of self-evaluation and reporting. The evaluation was therefore largely qualitative, in order to deal with the lack of a consistent ‘template’ for analysis. Emphasis was placed on trying to identify critical incidents , where it could be shown unambiguously that the outreach services made a difference to practice. Study limitations included the difficulty of summarising and comparing very different situations and diverse services, difficulty in identifying critical incidents, and an inability to study ‘non-users’. Findings: Service recipients felt better informed, more up- to-date, more aware of resources, more confident and supported in their work, and saved time. Services contributed to a richer information environment. Direct impacts, demonstrably improved patient care, cost savings etc., were more difficult to establish

Validation of Statistical Sampling Algorithms in Visual Sample Plan (VSP): Summary Report

The U.S. Department of Homeland Security, Office of Technology Development (OTD) contracted with a set of U.S. Department of Energy national laboratories, including the Pacific Northwest National Laboratory (PNNL), to write a Remediation Guidance for Major Airports After a Chemical Attack. The report identifies key activities and issues that should be considered by a typical major airport following an incident involving release of a toxic chemical agent. Four experimental tasks were identified that would require further research in order to supplement the Remediation Guidance. One of the tasks, Task 4, OTD Chemical Remediation Statistical Sampling Design Validation, dealt with statistical sampling algorithm validation. This report documents the results of the sampling design validation conducted for Task 4. In 2005, the Government Accountability Office (GAO) performed a review of the past U.S. responses to Anthrax terrorist cases. Part of the motivation for this PNNL report was a major GAO finding that there was a lack of validated sampling strategies in the U.S. response to Anthrax cases. The report (GAO 2005) recommended that probability-based methods be used for sampling design in order to address confidence in the results, particularly when all sample results showed no remaining contamination. The GAO also expressed a desire that the methods be validated, which is the main purpose of this PNNL report. The objective of this study was to validate probability-based statistical sampling designs and the algorithms pertinent to within-building sampling that allow the user to prescribe or evaluate confidence levels of conclusions based on data collected as guided by the statistical sampling designs. Specifically, the designs found in the Visual Sample Plan (VSP) software were evaluated. VSP was used to calculate the number of samples and the sample location for a variety of sampling plans applied to an actual release site. Most of the sampling designs validated are probability based, meaning samples are located randomly (or on a randomly placed grid) so no bias enters into the placement of samples, and the number of samples is calculated such that IF the amount and spatial extent of contamination exceeds levels of concern, at least one of the samples would be taken from a contaminated area, at least X% of the time. Hence, "validation" of the statistical sampling algorithms is defined herein to mean ensuring that the "X%" (confidence) is actually met

Inhibition of Inducible Nitric Oxide Synthase Expression by a Novel Small Molecule Activator of the Unfolded Protein Response

The transcription of inducible nitric oxide synthase (iNOS) is activated by a network of proinflammatory signaling pathways. Here we describe the identification of a small molecule that downregulates the expression of iNOS mRNA and protein in cytokine-activated cells and suppresses nitric oxide production in vivo. Mechanistic analysis suggests that this small molecule, erstressin, also activates the unfolded protein response (UPR), a signaling pathway triggered by endoplasmic reticulum stress. Erstressin induces rapid phosphorylation of eIF2α and the alternative splicing of XBP-1, hallmark initiating events of the UPR. Further, erstressin activates the transcription of multiple genes involved in the UPR. These data suggest an inverse relationship between UPR activation and iNOS mRNA and protein expression under proinflammatory conditions

Cigarette Smoke Exposure Alters mSin3a and Mi-2α/β Expression; implications in the control of pro-inflammatory gene transcription and glucocorticoid function

<p>Abstract</p> <p>Background</p> <p>The key co-repressor complex components HDAC-2, Mi-2α/β and mSin3a are all critical to the regulation of gene transcription. HDAC-2 function is impaired by oxidative stress in a PI3Kδ dependant manner which may be involved in the chronic glucocorticoid insensitive inflammation in the lungs of COPD patients. However, the impact of cigarette smoke exposure on the expression of mSin3a and Mi2α/β and their role in glucocorticoid responsiveness is unknown.</p> <p>Methods</p> <p>Wild type, PI3Kγ knock-out (PI3Kγ^-/-) and PI3K kinase dead knock-in (PI3Kδ^D910/A910) transgenic mice were exposed to cigarette smoke for 3 days and the expression levels of the co-repressor complex components HDAC-2, mSin3a, Mi-2α and Mi-2β and HDAC-2 activity in the lungs were assessed.</p> <p>Results</p> <p>Cigarette smoke exposure impaired glucocorticoid function and reduced HDAC-2 activity which was protected in the PI3Kδ^D910/A910mice. Both mSin3a and Mi-2α protein expression was reduced in smoke-exposed mice. Budesonide alone protected mSin3a protein expression with no additional effect seen with abrogation of PI3Kγ/δ activity, however Mi-2α, but not Mi-2β, expression was protected in both PI3Kδ^D910/A910and PI3Kγ^-/-budesonide-treated smoke-exposed mice. The restoration of glucocorticoid function coincided with the protection of both HDAC activity and mSin3a and Mi-2α protein expression.</p> <p>Conclusions</p> <p>Cigarette smoke exposure induced glucocorticoid insensitivity and alters co-repressor activity and expression which is prevented by blockade of PI3K signaling with glucocorticoid treatment. Inhibition of PI3Kδ signalling in combination with glucocorticoid treatment may therefore provide a therapeutic strategy for restoring oxidant-induced glucocortiocid unresponsiveness.</p

The composition of the protosolar disk and the formation conditions for comets

Conditions in the protosolar nebula have left their mark in the composition of cometary volatiles, thought to be some of the most pristine material in the solar system. Cometary compositions represent the end point of processing that began in the parent molecular cloud core and continued through the collapse of that core to form the protosun and the solar nebula, and finally during the evolution of the solar nebula itself as the cometary bodies were accreting. Disentangling the effects of the various epochs on the final composition of a comet is complicated. But comets are not the only source of information about the solar nebula. Protostellar disks around young stars similar to the protosun provide a way of investigating the evolution of disks similar to the solar nebula while they are in the process of evolving to form their own solar systems. In this way we can learn about the physical and chemical conditions under which comets formed, and about the types of dynamical processing that shaped the solar system we see today. This paper summarizes some recent contributions to our understanding of both cometary volatiles and the composition, structure and evolution of protostellar disks.Comment: To appear in Space Science Reviews. The final publication is available at Springer via http://dx.doi.org/10.1007/s11214-015-0167-