A new aircraft architecture based on the ACHEON Coanda effect nozzle: flight model and energy evaluation

Purpose Aeronautic transport has an effective necessity of reducing fuel consumption and emissions to deliver efficiency and competitiveness driven by today commercial and legislative requirements. Actual aircraft configurations scenario allows envisaging the signs of a diffused technological maturity and they seem very near their limits. This scenario clearly shows the necessity of radical innovations with particular reference to propulsion systems and to aircraft architecture consequently. Methods This paper presents analyses and discusses a promising propulsive architecture based on an innovative nozzle, which allows realizing the selective adhesion of two impinging streams to two facing jets to two facing Coanda surfaces. This propulsion system is known with the acronym ACHEON (Aerial Coanda High Efficiency Orienting Nozzle). This paper investigates how the application of an all-electric ACHEONs propulsion system to a very traditional commuter aircraft can improve its relevant performances. This paper considers the constraints imposed by current state-of-the-art electric motors, drives, storage and conversion systems in terms of both power/energy density and performance and considers two different aircraft configurations: one using battery only and one adopting a more sophisticated hybrid cogeneration. The necessity of producing a very solid analysis has forced to limit the deflection of the jet in a very conservative range (±15°) with respect to the horizontal. This range can be surely produced also by not optimal configurations and allow minimizing the use of DBD. From the study of general flight dynamics equations of the aircraft in two-dimensional form it has been possible to determine with a high level of accuracy the advantages that ACHEON brings in terms of reduced stall speed and of reduced take-off and landing distances. Additionally, it includes an effective energy analysis focusing on the efficiency and environmental advantages of the electric ACHEON based propulsion by assuming the today industrial grade high capacity batteries with a power density of 207 Wh/kg. Results It has been clearly demonstrated that a short flight could be possible adopting battery energy storage, and longer duration could be possible by adopting a more sophisticated cogeneration system, which is based on cogeneration from a well-known turboprop, which is mostly used in helicopter propulsion. This electric generation system can be empowered by recovering the heat and using it to increase the temperature of the jet. It is possible to transfer this considerable amount of heat to the jet by convection and direct fluid mixing. In this way, it is possible to increase the energy of the jets of an amount that allows more than recover the pressure losses in the straitening section. In this case, it is then possible to demonstrate an adequate autonomy of flight and operative range of the aircraft. The proposed architecture, which is within the limits of the most conservative results obtained, demonstrates significant additional benefits for aircraft manoeuvrability. In conclusion, this paper has presented the implantation of ACHEON on well-known traditional aircraft, verifying the suitability and effectiveness of the proposed system both in terms of endurance with a cogeneration architecture and in terms of manoeuvrability. It has demonstrated the potential of the system in terms of both takeoff and landing space requirements. Conclusions This innovation opens interesting perspectives for the future implementation of this new vector and thrust propulsion system, especially in the area of greening the aeronautic sector. It has also demonstrated that ACHEON has the potential of renovating completely a classic old aircraft configuration such as the one of Cessna 402

Assessing the outcomes and experiences of care from the perspective of people living with chronic conditions, to support countries in developing people-centred policies and practices: study protocol of the International Survey of People Living with Chronic Conditions (PaRIS survey).

This is the final version. Available from BMJ Publishing via the DOI in this record. INTRODUCTION: In view of growing populations with chronic conditions, many countries are redesigning their health systems. However, little information is available about how health systems perform from the perspective of people living with chronic conditions. The Organisation for Economic Co-operation and Development (OECD) Member States therefore mandated the OECD to initiate the International Survey of People Living with Chronic Conditions (PaRIS survey), which aims to provide insight in outcomes and experiences of care as reported by people living with chronic conditions. The PaRIS-SUR consortium has been tasked by the OECD to support the development and implementation of the survey. METHODS AND ANALYSIS: As primary care services play a pivotal role in the management of chronic conditions, the PaRIS survey will be implemented in the primary care setting. Data will be collected with a survey among users of primary care services aged 45 years or older, of whom many have chronic conditions. An additional survey is conducted among their primary care providers. The nested study design will allow analysis of the patient-reported data in relation to characteristics of and care provided by primary care providers within and across countries. In 2022, the survey will be tested in a Field Trial in participating countries. Data for cross-country comparison will be collected by the Main Survey in 2023. ETHICS AND DISSEMINATION: Informed consent will be obtained from primary care providers and service users. National Project Managers search ethical approval of the survey in their country, if required. Reporting by the OECD will focus on questions for international comparison. A secured information technology platform will be developed for participants and stakeholders in countries to receive feedback and answer their own questions. Findings will also be disseminated through an international OECD flagship report, conferences, scientific papers and policy briefs, to inform strategies to improve care for people living with chronic conditions throughout the world.Organisation for Economic Co-operation and Development (OECD

Knock Down of Heat Shock Protein 27 (HspB1) Induces Degradation of Several Putative Client Proteins

Hsp27 belongs to the heat shock protein family and displays chaperone properties in stress conditions by holding unfolded polypeptides, hence avoiding their inclination to aggregate. Hsp27 is often referenced as an anti-cancer therapeutic target, but apart from its well-described ability to interfere with different stresses and apoptotic processes, its role in non-stressed conditions is still not well defined. In the present study we report that three polypeptides (histone deacetylase HDAC6, transcription factor STAT2 and procaspase-3) were degraded in human cancerous cells displaying genetically decreased levels of Hsp27. In addition, these proteins interacted with Hsp27 complexes of different native size. Altogether, these findings suggest that HDAC6, STAT2 and procaspase-3 are client proteins of Hsp27. Hence, in non stressed cancerous cells, the structural organization of Hsp27 appears to be a key parameter in the regulation by this chaperone of the level of specific polypeptides through client-chaperone type of interactions

Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.

We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification

Recurrent fusions in PLAGL1 define a distinct subset of pediatric-type supratentorial neuroepithelial tumors

Ependymomas encompass a heterogeneous group of central nervous system (CNS) neoplasms that occur along the entire neuroaxis. In recent years, extensive (epi-)genomic profiling efforts have identified several molecular groups of ependymoma that are characterized by distinct molecular alterations and/or patterns. Based on unsupervised visualization of a large cohort of genome-wide DNA methylation data, we identified a highly distinct group of pediatric-type tumors (n = 40) forming a cluster separate from all established CNS tumor types, of which a high proportion were histopathologically diagnosed as ependymoma. RNA sequencing revealed recurrent fusions involving the pleomorphic adenoma gene-like 1 (PLAGL1) gene in 19 of 20 of the samples analyzed, with the most common fusion being EWSR1:PLAGL1 (n = 13). Five tumors showed a PLAGL1:FOXO1 fusion and one a PLAGL1:EP300 fusion. High transcript levels of PLAGL1 were noted in these tumors, with concurrent overexpression of the imprinted genes H19 and IGF2, which are regulated by PLAGL1. Histopathological review of cases with sufficient material (n = 16) demonstrated a broad morphological spectrum of tumors with predominant ependymoma-like features. Immunohistochemically, tumors were GFAP positive and OLIG2- and SOX10 negative. In 3/16 of the cases, a dot-like positivity for EMA was detected. All tumors in our series were located in the supratentorial compartment. Median age of the patients at the time of diagnosis was 6.2 years. Median progression-free survival was 35 months (for 11 patients with data available). In summary, our findings suggest the existence of a novel group of supratentorial neuroepithelial tumors that are characterized by recurrent PLAGL1 fusions and enriched for pediatric patients

Functional diversity and co-operativity between subclonal populations of paediatric glioblastoma and diffuse intrinsic pontine glioma cells

The failure to develop effective therapies for pediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) is in part due to their intrinsic heterogeneity. We aimed to quantitatively assess the extent to which this was present in these tumors through subclonal genomic analyses and to determine whether distinct tumor subpopulations may interact to promote tumorigenesis by generating subclonal patient-derived models in vitro and in vivo. Analysis of 142 sequenced tumors revealed multiple tumor subclones, spatially and temporally coexisting in a stable manner as observed by multiple sampling strategies. We isolated genotypically and phenotypically distinct subpopulations that we propose cooperate to enhance tumorigenicity and resistance to therapy. Inactivating mutations in the H4K20 histone methyltransferase KMT5B (SUV420H1), present in <1% of cells, abrogate DNA repair and confer increased invasion and migration on neighboring cells, in vitro and in vivo, through chemokine signaling and modulation of integrins. These data indicate that even rare tumor subpopulations may exert profound effects on tumorigenesis as a whole and may represent a new avenue for therapeutic development. Unraveling the mechanisms of subclonal diversity and communication in pGBM and DIPG will be an important step toward overcoming barriers to effective treatments

Structural characterization of mechanically alloyed nanocrystalline Cu-Fe: Strain broadening due to dislocations

Nanocrystalline Cu(Fe) solid solution was successfully synthesized by using high-energy mechanical milling. The structural and morphological changes during mechanical milling were investigated by X-ray diffraction and scanning electron microscopy. The patterns so obtained were analyzed using the X’Pert High Score Plus program. The final product of the mechanical alloying process was nanocrystalline FCC Cu(Fe) solid solution with a mean crystallite size in the range of few nanometers. The final microstructure, especially the high levels of lattice strains was explained by the presence of dislocations, with a dislocation density of about 7.4×1016 m−2. The identified steady-state saturation values of these parameters can be related to accumulate strain hardening of the powder material during longer milling times