Design definition study of a NASA/Navy lift/cruise fan technology V/STOL airplane: Risk assessment addendum to the final report

An assessment of risk, in terms of delivery delays, cost overrun, and performance achievement, associated with the V/STOL technology airplane is presented. The risk is discussed in terms of weight, structure, aerodynamics, propulsion, mechanical drive, and flight controls. The analysis ensures that risks associated with the design and development of the airplane will be eliminated in the course of the program and a useful technology airplane that meets the predicted cost, schedule, and performance can be produced

Aspectos epidemiológicos e ecológicos relacionados à malária na área de influência do lago da Represa de Porto Primavera, região oeste do Estado de São Paulo, Brasil

A study was carried out in the area of influence of the Porto Primavera Hydroelectric Power Station, in western São Paulo State, to investigate ecological and epidemiological aspects of malaria in the area and monitor the profile of the anopheline populations following the environmental changes brought about by the construction of the lake. Mosquitoes captured were analyzed by standardized indicator species analysis (ISA) before and during different flooding phases (253 m and 257 m elevations). The local human population was studied by means of parasitological (thin/thick blood smears), molecular (PCR) and serological tests. Serological tests consisted of Enzyme Linked Immunosorbent Assay (ELISA) with synthetic peptides of the circumsporozoite protein (CSP) from classic Plasmodium vivax, P. vivax variants (VK247 and "vivax-like"), P. malariae and P. falciparum and Indirect Immunofluorescence Assay (IFA) with asexual forms of P. vivax, P. malariae and P. falciparum. The results of the entomological survey indicated that, although the Anopheles darlingi population increased after the flooding, the population density remained very low. No malaria, parasite infection or DNA was detected in the inhabitants of the study area. However, there was a low frequency of antibodies against asexual forms and a significant prevalence of antibodies against P. vivax, P. vivax variants, P. falciparum and P. malariae; the presence of these antibodies may result from recent or less recent contact with human or simian Plasmodium (a parallel study in the same area revealed the existence of a sylvatic cycle). Nevertheless, these results suggest that, as in other places where malaria is present and potential vectors circulate, the local epidemiological conditions observed could potentially support the transmission of malaria in Porto Primavera Lake if infected individuals are introduced in sufficient numbers. Further studies are required to elucidate the phenomena described in this paper.Foi realizada pesquisa na área de influência do lago da Usina Hidrelétrica de Porto Primavera, região oeste do Estado de São Paulo, para estudar aspectos ecológicos e epidemiológicos da malária na localidade e acompanhar o perfil das populações de anofelinos frente às mudanças decorrentes do impacto ambiental pela formação do lago. Mosquitos capturados foram analisados pelo Índice de Abundância de Espécies Padronizado (IAEP), antes e durante o enchimento do reservatório (cotas 253 e 257 m). A população humana local foi estudada por meio de teste parasitológico (gota espessa e esfregaço sangüíneo), testes moleculares (PCR) e testes sorológicos. A sorologia consistiu na reação de ELISA com peptídeos sintéticos correspondentes à porção repetitiva da proteína circumsporozoíta (CSP) de Plasmodium vivax clássico, e suas variantes VK247 e "vivax-like", P. malariae e P. falciparum; e reação de Imunofluorescência Indireta (RIFI) com formas assexuadas de P. vivax, P. malariae e P. falciparum. Os resultados do estudo entomológico indicaram que, embora a população de Anopheles darlingi tenha aumentando após o enchimento, permaneceu em baixa densidade. Não foi detectada malária nem a presença de parasitos ou de DNA parasitário nos habitantes estudados. No entanto, foi observada baixa freqüência de anticorpos contra formas assexuadas e significativa prevalência de anticorpos contra esporozoítos de P. vivax e suas variantes, P. falciparum e P. malariae, que poderiam decorrer de contatos prévios, recentes ou não, com plasmódios humanos ou símios (o ciclo silvestre foi evidenciado em estudo paralelo realizado na mesma área). Por outro lado, estes resultados sugerem que, como em outros lugares onde existem vetores potenciais da malária, as condições epidemiológicas poderiam potencialmente permitir a transmissão da malária na área de influência do lago de Porto Primavera, se indivíduos infectados fossem introduzidos em número suficiente. Estudos adicionais deverão ser realizados para elucidar os fenômenos relatados neste artigo

SMARCB1 loss induces druggable cyclin D1 deficiency via upregulation of MIR17HG in atypical teratoid rhabdoid tumors

Atypical teratoid rhabdoid tumor (ATRT) is a fatal pediatric malignancy of the central neural system lacking effective treatment options. It belongs to the rhabdoid tumor family and is usually caused by biallelic inactivation of SMARCB1, encoding a key subunit of SWI/SNF chromatin remodeling complexes. Previous studies proposed that SMARCB1 loss drives rhabdoid tumor by promoting cell cycle through activating transcription of cyclin D1 while suppressing p16. However, low cyclin D1 protein expression is observed in most ATRT patient tumors. The underlying mechanism and therapeutic implication of this molecular trait remain unknown. Here, we show that SMARCB1 loss in ATRT leads to the reduction of cyclin D1 expression by upregulating MIR17HG, a microRNA (miRNA) cluster known to generate multiple miRNAs targeting CCND1. Furthermore, we find that this cyclin D1 deficiency in ATRT results in marked in vitro and in vivo sensitivity to the CDK4/6 inhibitor palbociclib as a single agent. Our study identifies a novel genetic interaction between SMARCB1 and MIR17HG in regulating cyclin D1 in ATRT and suggests a rationale to treat ATRT patients with FDA- approved CDK4/6 inhibitors. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156416/2/path5493.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156416/1/path5493_am.pd

Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer

The nuclease MRE11A is often included in genetic test panels for hereditary breast and ovarian cancer (HBOC) due to its BRCA1-related molecular function in the DNA repair pathway. However, whether MRE11A is a true predisposition gene for HBOC is still questionable. We determined to investigate this notion by dissecting the molecular genetics of the c.1516G > T;p.E506* truncating MRE11A variant, that we pinpointed in two unrelated French-Canadian (FC) HBOC patients. We performed a case-control study for the variant in ~ 2500 breast, ovarian, and endometrial cancer patients from the founder FC population of Quebec. Furthermore, we looked for the presence of second somatic alterations in the MRE11A gene in the tumors of the carriers. In summary, these investigations suggested that the identified variant is not associated with an increased risk of developing breast or ovarian cancer. We finally performed a systematic review for all the previously reported MRE11A variants in breast and ovarian cancer. We found that MRE11A germline variants annotated as pathogenic on ClinVar often lacked evidence for such classification, hence misleading the clinical management for affected patients. In summary, our report suggests the lack of clinical utility of MRE11A testing in HBOC, at least in the White/Caucasian populations

Measuring Health Related Quality of Life for Dengue Patients in Iquitos, Peru

Previous studies measuring the health-related quality of life (HRQoL) of individuals with dengue focused on treatment seeking populations. However, the vast majority of global dengue cases are unlikely to be detected by health systems. Representative measurements of HRQoL should therefore include patients with disease not likely to trigger treatment-seeking behavior. This study based in Iquitos, Peru used the Quality of Wellbeing Scale-Self Administered, a survey that enquires about not only physical health, but also psychological health, self-care, mobility, and usual social activities, and rates HRQoL between 0 (death) and 1 (optimum function), to evaluate the impact of dengue on HRQoL. In order to enroll treatment and non treatment-seeking participants, three modalities of participant recruitment were used. In addition to clinic and community-based febrile surveillance, a contact-cluster methodology was also employed to identify infected individuals less likely to seek treatment. We measured changes in HRQoL and identified common areas of health impairment in 73 virologically confirmed dengue cases at 3 time points during the participant\u27s illness; the early-acute (days 0-6 post symptom onset), late-acute (days 7-20), and convalescent illness phases (days 21 +). Participants reported HRQoL related impairments at significantly higher frequency during the early-acute versus convalescent illness phase (Fisher\u27s exact: P\u3c0.01). There was substantial heterogeneity in scores during each illness phase with median scores in the early-acute, late-acute and convalescent phases of 0.56 (IQR: 0.41-0.64), 0.70 (IQR: 0.57-0.94), and 1 (IQR: 0.80-1.00), respectively. In all illness phases participants recruited in clinics had on average the lowest HRQoL scores where as those recruited in the contact clusters had the highest. Only 1 individual who was recruited in the contact-clusters had no reduction in HRQoL score during their illness. These data illustrate that dengue should be considered as a disease that may have significant implications for not only physical health but also psychological health and social functioning. The impact of dengue on the HRQoL of non-treatment-seeking individuals, although lower than the impact among treatment-seeking individuals, is not necessarily trivial

A multimodal dataset for authoring and editing multimedia content:the MAMEM project

We present a dataset that combines multimodal biosignals and eye tracking information gathered under a human-computer interaction framework. The dataset was developed in the vein of the MAMEM project that aims to endow people with motor disabilities with the ability to edit and author multimedia content through mental commands and gaze activity. The dataset includes EEG, eye-tracking, and physiological (GSR and Heart rate) signals collected from 34 individuals (18 able-bodied and 16 motor-impaired). Data were collected during the interaction with specifically designed interface for web browsing and multimedia content manipulation and during imaginary movement tasks. The presented dataset will contribute towards the development and evaluation of modern human-computer interaction systems that would foster the integration of people with severe motor impairments back into society.</p

Contrasting patterns of turnover between plants, pollinators and their interactions

Aim: Biogeographers typically assess patterns of diversity across landscapes. As interacting groups often exhibit contrasting trends, this leads to variation in the structure of interaction networks and thereby influences ecosystem processes. Here we aim to disentangle how patterns of diversity differ between species (plants, pollinators) and their interactions across an agricultural landscape. The region is known for its irrigated gardens which appear as high-diversity islands in the mountainous habitat. We are interested in whether this local enhancement was (a) increasing landscape heterogeneity by supporting novel species or (b) increasing local diversity by supporting higher densities of species that also occur in the unmanaged habitat. Location: South Sinai, Egypt. Methods: We compared alpha diversity of plants, pollinators and interactions in agricultural gardens and plots of unmanaged habitat in two altitudinal categories, high and low mountains, with high and low habitat quality in the matrix respectively. We then used similarity analyses involving the CqN measure to compare levels of turnover across the landscape. Results: The impact of the gardens differed with respect to the landscape context; in the low mountains, gardens enhanced the abundance and diversity of plants, pollinators and interactions, but in the high mountains, they had no effect. Plants exhibited high levels of turnover, with gardens increasing heterogeneity by supporting novel crop species. In contrast, pollinators exhibited low levels of turnover, with gardens and unmanaged habitat supporting similar species. The diversity of interactions was influenced by the composition of the plant community and showed extremely high levels of turnover. Main conclusions: Plants, pollinators and their interactions can display contrasting patterns of turnover across a shared landscape. Although the enhancement of local habitat can boost pollinator diversity, the maintenance of habitat heterogeneity may also be required if you aim to conserve the diversity of interactions between plants and pollinators