Propulsion and airframe aerodynamic interactions of supersonic V/STOL configurations, phase 1

A wind tunnel model of a supersonic V/STOL fighter configuration has been tested to measure the aerodynamic interaction effects which can result from geometrically close-coupled propulsion system/airframe components. The approach was to configure the model to present two different test techniques. One was a coventional test technique composed of two test modes. In the Flow-Through mode, absolute configuration aerodynamics are measured, including inlet/airframe interactions. In the Jet-Effects mode, incremental nozzle/airframe interactions are measured. The other test technique is a propulsion simulator approach, where a subscale, externally powered engine is mounted in the model. This allows proper measurement of inlet/airframe and nozzle/airframe interactions simultaneously

The fracture behavior of Cr2AlC coatings

The erosion - and self-healing - behavior of Cr2AlC MAX phase coatings has been investigated [1]. It is well known that Cr2AlC coatings can be deposited at temperatures of around 450 °C [2], which is significantly lower than for other MAX phase systems, which often require growth temperatures around 900 °C [3]. To further explore the applicability of the Cr2AlC system in harsh environments, it is necessary to determine its mechanical response. Recent advances in micromechanical testing allow investigating the mechanical properties of hard coatings, especially the fracture behavior, which is of particular interest for several thin film applications. Furthermore, it is possible to deposit the Cr2AlC system with different microstructures, e.g. nanocrystalline or amorphous [2]. Preliminary results revealed a fracture toughness of ~2 MPam1/2 for a coating with columnar morphology. In this investigation, the effect of morphology and microstructure on the fracture toughness of Cr2AlC coatings will be presented. References [1] D. Eichner, A. Schlieter, C. Leyens, L. Shang, S. Shayestehaminzadeh, J.M. Schneider, Solid particle erosion behavior of nanolaminated Cr2AlC films, Wear. 402–403 (2018) 187–195. doi:10.1016/j.wear.2018.02.014. [2] C. Walter, D.P. Sigumonrong, T. El-Raghy, J.M. Schneider, Towards large area deposition of Cr2AlC on steel, Thin Solid Films. 515 (2006) 389–393. doi:10.1016/j.tsf.2005.12.219. [3] P. Eklund, M. Beckers, U. Jansson, H. Högberg, L. Hultman, The Mn+1AXn phases: Materials science and thin-film processing, Thin Solid Films. 518 (2010) 1851–1878. doi:10.1016/j.tsf.2009.07.184

Improving Upper Extremity Motor Skills in Girls with Rett Syndrome Using Virtual Reality

Introduction: Rett Syndrome is a genetic disorder that limits a girl's ability to use her upper extremities for daily activities, such as dressing and playing. One possible intervention to improve upper extremity function in this population is virtual reality, which can be used to increase activity demands during therapy sessions. Objectives: To determine the feasibility of using internet-based virtual reality intervention for Rett Syndrome (RTT-IVR), to decrease hand wringing/mouthing and increase hand and arm movements away from the midline by identifying attributes and limitations to the proposed intervention. Materials and Methods: Using FAAST Software and Microsoft Kinect sensor, RTT-IVR was trialed with 6 girls with RTT. Upper extremity movements were used to play free Internet games as means of increasing repetitions and purposeful arm movements. Data regarding attributes and limitations of the RTT-IVR intervention were collected via observation and post-session parent interviews. Results: Interviews and observation revealed successful game play when games were motivating, clearly established cause and effect, and matched level of cognitive ability of the participant. Limitations include technological glitches regarding Kinect sensor sensitivity and identifying appropriate games for each participant's interests and abilities. Conclusion: Internet based virtual reality interventions for girls with RTT should be highly individualized to increase motivation and success of intervention

Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts

Aims: Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia. Methods and Results: FGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (βKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-βKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast βKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-α (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased. Conclusion: In an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia

Long-term outcomes and response to treatment in diacylglycerol kinase epsilon nephropathy

Recessive mutations in diacylglycerol kinase epsilon (DGKE) display genetic pleiotropy, with pathological features reported as either thrombotic microangiopathy or membranoproliferative glomerulonephritis (MPGN), and clinical features of atypical hemolytic uremic syndrome (aHUS), nephrotic syndrome or both. Pathophysiological mechanisms and optimal management strategies have not yet been defined. In prospective and retrospective studies of aHUS referred to the United Kingdom National aHUS service and prospective studies of MPGN referred to the National Registry of Rare Kidney Diseases for MPGN we defined the incidence of DGKE aHUS as 0.009/million/year and so-called DGKE MPGN as 0.006/million/year, giving a combined incidence of 0.015/million/year. Here, we describe a cohort of sixteen individuals with DGKE nephropathy. One presented with isolated nephrotic syndrome. Analysis of pathological features reveals that DGKE mutations give an MPGN-like appearance to different extents, with but more often without changes in arterioles or arteries. In 15 patients presenting with aHUS, ten had concurrent substantial proteinuria. Identified triggering events were rare but coexistent developmental disorders were seen in six. Nine with aHUS experienced at least one relapse, although in only one did a relapse of aHUS occur after age five years. Persistent proteinuria was seen in the majority of cases. Only two individuals have reached end stage renal disease, 20 years after the initial presentation, and in one, renal transplantation was successfully undertaken without relapse. Six individuals received eculizumab. Relapses on treatment occurred in one individual. In four individuals eculizumab was withdrawn, with one spontaneously resolving aHUS relapse occurring. Thus we suggest that DGKE-mediated aHUS is eculizumab non-responsive and that in individuals who currently receive eculizumab therapy it can be safely withdrawn. This has important patient safety and economic implications

Heat treatment significantly increases the sharpness of silcrete stone tools

Humans were regularly heat-treating stone tool raw materials as early as 130,000 years ago. The late Middle Stone Age (MSA) and Late Stone Age (LSA) of South Africa's Western Cape region provides some of the earliest and most pervasive archaeological evidence for this behaviour. While archaeologists are beginning to understand the flaking implications of raw material heat treatment, its potential functional benefits remain unanswered. Using silcrete from the Western Cape region, we investigate the impact of heat treatment on stone tool cutting performance. We quantify the sharpness of silcrete in its natural, unheated form, before comparing it with silcrete heated in three different conditions. Results show that heat-treated silcrete can be significantly sharper than unheated alternatives, with cutting forces halving and energy requirements reducing by approximately two-thirds. The data suggest that silcrete may have been heat treated during the South African MSA and LSA to increase the sharpness and performance of stone cutting edges. This early example of material engineering has implications for understanding Stone Age populations’ technological capabilities, inventiveness and raw material choices. We predict that heat-treatment behaviours in other prehistoric and ethnographic contexts may also be linked to increases in edge sharpness and concerns about functional performance

Allograft rejection is associated with development of functional IgE specific for donor MHC antigens.

BACKGROUND: Donor-specific antibodies of the IgG isotype are measured routinely for diagnostic purposes in renal transplant recipients and are associated with antibody-mediated rejection and long-term graft loss. OBJECTIVE: This study aimed to investigate whether MHC-specific antibodies of the IgE isotype are induced during allograft rejection. METHODS: Anti-MHC/HLA IgE levels were measured in sera of mice grafted with skin or heart transplants from various donor strains and in sera of kidney transplant patients with high levels of HLA IgG. Mediator release was triggered in vitro by stimulating basophils that were coated with murine or human IgE-positive serum, respectively, with specific recombinant MHC/HLA antigens. Kidney tissue samples obtained from organ donors were analyzed by using flow cytometry for cells expressing the high-affinity receptor for IgE (FcεRI). RESULTS: Donor MHC class I- and MHC class II-specific IgE was found on acute rejection of skin and heart grafts in several murine strain combinations, as well as during chronic antibody-mediated heart graft rejection. Anti-HLA IgE, including donor HLA class I and II specificities, was identified in a group of sensitized transplant recipients. Murine and human anti-MHC/HLA IgE triggered mediator release in coated basophils on stimulation with specific MHC/HLA antigens. HLA-specific IgE was not linked to atopy, and allergen-specific IgE present in allergic patients did not cross-react with HLA antigens. FcεRI+ cells were found in the human renal cortex and medulla and provide targets for HLA-specific IgE. CONCLUSION: These results demonstrate that MHC/HLA-specific IgE develops during an alloresponse and is functional in mediating effector mechanisms