Subsidence over Hampton Roads: SqueeSAR Cosmo-SkyMed Analysis

Presentation by Jessica Morgan of TRE Altamira Inc., Mike Aslaksen of NOAA\u27s National Geodetic Survey, and Dave Maune of Dewberry, for the Hampton Roads Adaptation Forum, October 13, 2017

Passive immunotherapy against Aβ in aged APP-transgenic mice reverses cognitive deficits and depletes parenchymal amyloid deposits in spite of increased vascular amyloid and microhemorrhage

BACKGROUND: Anti-Aβ immunotherapy in transgenic mice reduces both diffuse and compact amyloid deposits, improves memory function and clears early-stage phospho-tau aggregates. As most Alzheimer disease cases occur well past midlife, the current study examined adoptive transfer of anti-Aβ antibodies to 19- and 23-month old APP-transgenic mice. METHODS: We investigated the effects of weekly anti-Aβ antibody treatment on radial-arm water-maze performance, parenchymal and vascular amyloid loads, and the presence of microhemorrhage in the brain. 19-month-old mice were treated for 1, 2 or 3 months while 23-month-old mice were treated for 5 months. Only the 23-month-old mice were subject to radial-arm water-maze testing. RESULTS: After 3 months of weekly injections, this passive immunization protocol completely reversed learning and memory deficits in these mice, a benefit that was undiminished after 5 months of treatment. Dramatic reductions of diffuse Aβ immunostaining and parenchymal Congophilic amyloid deposits were observed after five months, indicating that even well-established amyloid deposits are susceptible to immunotherapy. However, cerebral amyloid angiopathy increased substantially with immunotherapy, and some deposits were associated with microhemorrhage. Reanalysis of results collected from an earlier time-course study demonstrated that these increases in vascular deposits were dependent on the duration of immunotherapy. CONCLUSIONS: The cognitive benefits of passive immunotherapy persist in spite of the presence of vascular amyloid and small hemorrhages. These data suggest that clinical trials evaluating such treatments will require precautions to minimize potential adverse events associated with microhemorrhage

Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice

BACKGROUND: The pathology of Alzheimer's disease (AD) is comprised of extracellular amyloid plaques, intracellular tau tangles, dystrophic neurites and neurodegeneration. The mechanisms by which these various pathological features arise are under intense investigation. Here, expanding upon pilot gene expression studies, we have further analyzed the relationship between Na+/K+ ATPase and amyloid using APP+PS1 transgenic mice, a model that develops amyloid plaques and memory deficits in the absence of tangle formation and neuronal or synaptic loss. RESULTS: We report that in addition to decreased mRNA expression, there was decreased overall Na+/K+ ATPase enzyme activity in the amyloid-containing hippocampi of the APP+PS1 mice (although not in the amyloid-free cerebellum). In addition, dual immunolabeling revealed an absence of Na+/K+ ATPase staining in a zone surrounding congophilic plaques that was occupied by dystrophic neurites. We also demonstrate that cerebral Na+/K+ ATPase activity can be directly inhibited by high concentrations of soluble Aβ. CONCLUSIONS: The data suggest that the reductions in Na+/K+ ATPase activity in Alzheimer tissue may not be purely secondary to neuronal loss, but may results from direct effects of amyloid on this enzyme. This disruption of ion homeostasis and osmotic balance may interfere with normal electrotonic properties of dendrites, blocking intraneuronal signal processing, and contribute to neuritic dystrophia. These results suggest that therapies aimed at enhancing Na+/K+ ATPase activity in AD may improve symptoms and/or delay disease progression

Portfolio management in the Air Force : current status and opportunities

Thesis (S.M. in Engineering and Management)--Massachusetts Institute of Technology, Engineering Systems Division, System Design and Management Program, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 65-68).There are hundreds of weapons programs, under the management of the United States Air Force worth billions of dollars. These programs are being developed to fulfill a need in the U.S. defense strategy. Bringing these weapon systems to operational status is not an easy process. It takes communication and coordination of many stakeholders and development of state-of the-art technology. More often than not, weapons programs are developed with the final cost and schedule being much higher that forecasted. Inherently weapons systems are expensive, however the costs of these systems continue to rise with no apparent end in sight. The Government Accountability Office, RAND, Congressional studies and the Defense Acquisition Performance Assessment have has criticized the Department of Defense for escalating costs. These studies point to poor requirement definition, errors in cost and scheduling forecasts, poor oversight, bad decisions by the government, and failure to adopt recommendations from reform policies as the main causes. One way ameliorate cost escalation is to employ portfolio management technique. The Air Force groups their weapon systems into 20 portfolios. Some form of portfolio management has been employed for the last decade. Portfolio management cannot solve the issues above but it can offer a solution that can potentially save millions and perhaps billions of dollars This thesis examines the Air Force's current use of Portfolio Management theory and what opportunities we can do to improve it in the acquisition community. The thesis poses three research questions: 1) How can the Air Force better employ portfolio management to curb cost overruns and schedule delays in their weapon acquisition programs? 2) What can the Air Force do to empower portfolio managers for success? 3) What barriers can the Air Force eliminate or streamline to help portfolio managers execute their portfolios more effectively and efficiently. Acquisition professionals were interviewed to glean their perspectives and opinions. More specifically acquisition personnel were asked how portfolio management was being executed and how can the Air Force improve this technique to better execute weapon systems programs. From these interviews and the research conducted, the following recommendations were made: 1) Program Executive Officers should be given more authority with respect to utilizing funds and hiring of specialized personnel 2) The Air Force needs to streamline the process for reallocating funds and, 3) The Air Force needs to modify number of reporting requirements and policy changes to make the process more efficient and effective.by Dave B. Morgan.S.M.in Engineering and Managemen

Improving Mean Time Between Pump Failures

Discussion Grou

Improvement of a low pH antigen-antibody dissociation procedure for ELISA measurement of circulating anti-Aβ antibodies

BACKGROUND: Prior work from our group found that acid dissociation (pH 2.5 incubation) of serum from APP transgenic mice vaccinated against Aβ increased the apparent anti-Aβ titers, suggesting antibody masking by antigen in the ELISA assay. Subsequently, we found that pH 2.5 incubation of serum from unvaccinated non-transgenic mice showed antibody binding to Aβ1–42, but no increase when other proteins, including shorter Aβ peptides, coated the ELISA plate. To investigate further the effects of low pH incubation on apparent anti-Aβ1–42 signals, we examined normal sera from nonTg unvaccinated mice, nonTg mice vaccinated with Aβ peptide (to produce authentic anti-Aβ antibodies) or a monoclonal antibody against Aβ (6E10) using competitive-inhibition ELISA and Aβ epitope mapping assays. In addition, we examined use of a less stringent low pH procedure at pH 3.5, to ascertain if it had the same effects as the pH 2.5 procedure. RESULTS: We believe there are three distinct effects of pH 2.5 incubation.; A) an artifactual increase in binding to full length Aβ by mouse immunoglobulin which has low affinity for Aβ, B) an inactivation of anti-Aβ antibodies that is time dependent and C) unmasking of high affinity anti-Aβ antibodies when high levels of circulating Aβ is present in APP transgenic mice. All three reactions can interact to produce the final ELISA signal. Incubation of sera from unvaccinated nonTg mice at pH 2.5 enhanced ELISA signals by process A. Conversely, pH 2.5 incubation of sera from vaccinated nonTg mice with caused a time dependent reduction of antibody signal by process B (overcoming the increase caused by A). The artifactual anti-Aβ ELISA signal enhanced by pH 2.5 incubation of normal mouse sera could not be effectively competed by low to moderate concentrations of Aβ, nor bind to shorter Aβ peptides in a manner similar to authentic anti-Aβ antibodies. Incubation of mouse sera at pH 3.5 caused neither an apparent increase in anti-Aβ ELISA signal, nor an inactivation of the ELISA signals resulting from either vaccination or monoclonal antibodies. However, incubation at pH 3.5 was able to completely reverse the reduction in ELISA signal caused by Aβ complexing with antibodies in sera from vaccinated mice or monoclonal anti-Aβ antibodies. CONCLUSION: Incubation at pH 3.5 is sufficient to dissociate Aβ bound to anti-Aβ antibodies without producing artifactual increases in the signal, or inactivating authentic antibody binding. Thus, use of pH 3.5 is a considerable improvement over pH 2.5 incubation for unmasking anti-Aβ antibodies in ELISA assays to measure antibodies in APP transgenic mouse sera

Local Authority responses to people with NRPF during the pandemic: Interim project findings briefing

This interim briefing presents initial findings from a project exploring the support available to migrants with no recourse to public funds during the COVID-19 pandemic. The research included a survey of local authorities in England, and a call for evidence from migrant support organisations in England, Scotland and Wales. More than 90 percent of local authorities had not shared information about support for people with NRPF during the pandemic, and support organisations reported that service users had struggled to access food, shelter and subsistence support during the pandemic.Paul Hamlyn Foundatio

COMBAR COST EU. A mobile application proposal

Diagnosis and treatment options/strategies for helminth parasitic diseases are not standardized globally, or even across Europe, due to factors such as epidemiology, resources availability, socio-economics, and the lack of adequate information. Good communication of options can help to overcome some of these problems. In this sense, it is proposed to develop a mobile application (Abozeid et al., 2021) that allows the tailoring, and sharing, of knowledge (Abu-El-Noor et al., 2021; Kunkel et al., 2021) related to the various diagnoses and treatments in a format appropriate for all stakeholders (e.g. farmers, veterinarians, universities, researchers, laboratories, industries). The proposal aims to present the theoretical functionalities for the creation of a mobile application (Muashekele et al., 2021), the application should have a sequence of options that must be grounded in theoretical requirements. First of all, there is a necessity to have inputs standardized by the application (e.g. country/region, applicable legislation, animal typology, disease characteristics, symptoms) that should be entered into the application. The aim is to provide a range of tailored options to the end-user. Second, given the user's choices, the application can offer information and guidelines (including veterinarians available, laboratories, diagnosis, treatments, stores, among others). It is highlighted that the main gain may be the collection of information, whenever the user allows it. Finally, considering that most farmers use the language of their country, it is crucial to have the application in different European languages.info:eu-repo/semantics/publishedVersio