Technical and Economic Assessment of Span-Distributed Loading Cargo Aircraft Concepts

A 700,000 kg (1,540,000-lb) aircraft with a cruise Mach number of 0.75 was found to be optimum for the specified mission parameters of a 272 155-kg (600,000-lb) payload, a 5560-km (3000-n.mi.) range, and an annual productivity of 113 billion revenue-ton km (67 billion revenue-ton n. mi.). The optimum 1990 technology level spanloader aircraft exhibited the minimum 15-year life-cycle costs, direct operating costs, and fuel consumption of all candidate versions. Parametric variations of wing sweep angle, thickness ratio, rows of cargo, and cargo density were investigated. The optimum aircraft had two parallel rows of 2.44 x 2.44-m (8 x 8-ft) containerized cargo with a density of 160 kg/cu m (10 lb/ft 3) carried throughout the entire 101-m (331-ft) span of the constant chord, 22-percent thick, supercritical wing. Additional containers or outsized equipment were carried in the 24.4-m (80-ft) long fuselage compartment preceding the wing. Six 284,000-N (64,000-lb) thrust engines were mounted beneath the 0.7-rad (40-deg) swept wing. Flight control was provided by a 36.6-m (120-ft) span canard surface mounted atop the forward fuselage, by rudders on the wingtip verticals and by outboard wing flaperons

The influence of fear of falling on the control of upright stance across the lifespan

Background Standing at height, and subsequent changes in emotional state (e.g., fear of falling), lead to robust alterations in balance in adults. However, little is known about how height-induced postural threat affects balance performance in children. Children may lack the cognitive capability necessary to inhibit the processing of threatand fear-related stimuli, and as a result, may show more marked (and perhaps detrimental) changes in postural control compared to adults. This work explored the emotional and balance responses to standing at height in children and compared responses to young and older adults. Methods Children (age: 9.7 ± 0.8 years, n=38), young adults (age: 21.8 ± 4.0 years, n=45) and older adults (age: 73.3 ± 5.0 years, n=15) stood in bipedal stance in two conditions: on the floor and 80cm above ground. Centre of pressure (COP) amplitude (RMS), frequency (MPF) and complexity (sample entropy) were calculated to infer postural performance and strategy. Emotional responses were quantified by assessing balance confidence, fear of falling and perceived instability. Results Young and older adults demonstrated a postural adaptation characterised by increased frequency and decreased amplitude of the COP, in conjunction with increased COP complexity (sample entropy). In contrast, children demonstrated opposite patterns of changes: they exhibited an increase in COP amplitude and decrease in both frequency and complexity when standing in a hazardous situation. Significance Children and adults adopted different postural control strategies when standing at height. Whilst young and older adults exhibited a (potentially protective) “stiffening” response to a height-induced threat, children demonstrated a (potentially maladaptive) ineffective postural adaptation strategy. These observations expand upon existing postural threat related research in adults, providing important new insight into understanding how children respond to standing in a hazardous situation

A three-armed cognitive-motor exercise intervention to increase spatial orientation and life-space mobility in nursing home residents: study protocol of a randomized controlled trial in the PROfit project.

BackgroundIn nursing home residents, the combination of decreasing mobility and declining cognitive abilities, including spatial orientation, often leads to reduced physical activity (PA) and life-space (LS) mobility. As a consequence of sedentary behavior, there is a lack of social interaction and cognitive stimulation, resulting in low quality of life. It has not yet been examined whether cognitive-motor training including spatial cognitive tasks is suitable to improve spatial orientation and, as a consequence, to enlarge LS mobility, and increase well-being and general cognitive-motor functioning. Therefore, the overall goal of this multicentric randomized controlled trial (RCT) is to compare the effect of three different intervention approaches including functional exercise and orientation tasks on PA, LS and spatial orientation in nursing home residents.MethodsA three-arm single-blinded multicenter RCT with a wait-list control group will be conducted in a sample of 513 individuals (needed according to power analysis) in three different regions in Germany. In each nursing home, one of three different intervention approaches will be delivered to participating residents for 12 weeks, twice a week for 45 min each: The PROfit basic group will perform functional strength, balance, flexibility, and walking exercises always at the same location, whereas the PROfit plus group changes the location three times while performing similar/the same exercises as the PROfit basic group. The PROfit orientation group receives navigation tasks in addition to the relocation during the intervention. Physical and cognitive functioning as well as psychological measures will be assessed in all study groups at baseline. Participants will then be randomized into either the intervention group or the wait-list control group. After 12 weeks, and after 24 weeks the measures will be repeated.DiscussionThis study evaluates whether the three different interventions are feasible to reduce the decline of or even improve PA, LS, and spatial orientation in nursing home residents. By adding different training locations in PROfit plus, the program is expected to be superior to PROfit basic in increasing physical and cognitive parameters. Moreover, we expect the PROfit orientation intervention to be most effective in terms of PA, LS, and spatial orientation due to two mechanisms: (1) increased physical and cognitive activity will enhance cognitive-motor capacity and (2) the spatial training will help to build up cognitive strategies to compensate for age-related loss of spatial orientation abilities and related limitations.Trial registrationThe trial was prospectively registered at DRKS.de with registration number DRKS00021423 on April 16, 2020 and was granted permission by the Technical University Berlin local ethics committee (No. GR_14_20191217)

Cessation of biomechanical stretch model of C2C12 cells models myocyte atrophy and anaplerotic changes in metabolism using non-targeted metabolomics analysis

Studies of skeletal muscle disuse, either in patients on bed rest or experimentally in animals (immobilization), have demonstrated that decreased protein synthesis is common, with transient parallel increases in protein degradation. Muscle disuse atrophy involves a process of transition from slow to fast myosin fiber types. A shift toward glycolysis, decreased capacity for fat oxidation, and substrate accumulation in atrophied muscles have been reported, as has accommodation of the liver with an increased gluconeogenic capacity. Recent studies have modeled skeletal muscle disuse by using cyclic stretch of differentiated myotubes (C2C12), which mimics the loading pattern of mature skeletal muscle, followed by cessation of stretch. We utilized this model to determine the metabolic changes using non-targeted metabolomics analysis of the media. We identified increases in amino acids resulting from protein degradation (largely sarcomere) that occurs with muscle atrophy that are involved in feeding the Kreb’s cycle through anaplerosis. Specifically, we identified increased alanine/proline metabolism (significantly elevated proline, alanine, glutamine, and asparagine) and increased α-ketoglutaric acid, the proposed Kreb’s cycle intermediate being fed by the alanine/proline metabolic anaplerotic mechanism. Additionally, several unique pathways not clearly delineated in previous studies of muscle unloading were seen, including: 1) elevated keto-acids derived from branched chain amino aicds (i.e. 2-ketoleucine and 2-keovaline), which feed into a metabolic pathway supplying acetyl-CoA and 2-hydroxybutyrate (also significantly increased); and 2) elevated guanine, an intermediate of purine metabolism, was seen at 12 hours unloading. Given the interest in targeting different aspects of the ubiquitin proteasome system to inhibit protein degradation, this C2C12 system may allow the identification of direct and indirect alterations in metabolism due to anaplerosis or through other yet to be identified mechanisms using a non-targeted metabolomics approach

Positional cloning of the barley tillering gene uniculme4

Manipulation of plant architectural traits such as the number of tillers can effectively increase grain yield in cereals. Within the frame of the TriticeaeGenome project (www.triticeaegenome.eu), the objective of our group was the fine mapping and positional cloning of uniculme4 (cul4), a gene required for tillering in barley. Based on initial medium resolution mapping of the locus, a segregating population including 4900 F3 plants was developed and genotyped with three tightly linked SNP markers (Tavakol et al., abstract P321, PAG XIX). The locus was further resolved through mapping of 8 synteny-derived markers allowing the identification of a candidate gene that co-segregates with the cul4 phenotype. The two genes that flank the candidate gene in Brachypodium and rice were positioned 0.11 cM and 0.12 cM from cul4, respectively: development of new markers is underway using sequence information from two BACs anchored to the physical map and spanning this region. The intron-exon structure of the candidate gene was determined from a cDNA isolated from wild-type plants. Resequencing of independent cul4 stocks identified three distinct mutations within the candidate gene, including a deletion of the 5\u2019 region. Comparison of expression levels and patterns in mutant and wild-type plants is underway

Modelling mutational landscapes of human cancers in vitro

Experimental models that recapitulate mutational landscapes of human cancers are needed to decipher the rapidly expanding data on human somatic mutations. We demonstrate that mutation patterns in immortalised cell lines derived from primary murine embryonic fibroblasts (MEFs) exposed in vitro to carcinogens recapitulate key features of mutational signatures observed in human cancers. In experiments with several cancer-causing agents we obtained high genome-wide concordance between human tumour mutation data and in vitro data with respect to predominant substitution types, strand bias and sequence context. Moreover, we found signature mutations in well-studied human cancer driver genes. To explore endogenous mutagenesis, we used MEFs ectopically expressing activation-induced cytidine deaminase (AID) and observed an excess of AID signature mutations in immortalised cell lines compared to their non-transgenic counterparts. MEF immortalisation is thus a simple and powerful strategy for modelling cancer mutation landscapes that facilitates the interpretation of human tumour genome-wide sequencing data

Cardiomyocyte-Specific Human Bcl2-Associated Anthanogene 3 P209L Expression Induces Mitochondrial Fragmentation, Bcl2-Associated Anthanogene 3 Haploinsufficiency, and Activates p38 Signaling

Supplemental Data Supplemental Table S1 Download Supplemental Table S2 Download Supplemental Table S3 Download Supplemental Table S4 Download Supplemental Data Supplemental material for this article can be found at . The Bcl2-associated anthanogene (BAG) 3 protein is a member of the BAG family of cochaperones, which supports multiple critical cellular processes, including critical structural roles supporting desmin and interactions with heat shock proteins and ubiquitin ligases intimately involved in protein quality control. The missense mutation P209L in exon 3 results in a primarily cardiac phenotype leading to skeletal muscle and cardiac complications. At least 10 other Bag3 mutations have been reported, nine resulting in a dilated cardiomyopathy for which no specific therapy is available. We generated αMHC-human Bag3 P209L transgenic mice and characterized the progressive cardiac phenotype in vivo to investigate its utility in modeling human disease, understand the underlying molecular mechanisms, and identify potential therapeutic targets. We identified a progressive heart failure by echocardiography and Doppler analysis and the presence of pre-amyloid oligomers at 1 year. Paralleling the pathogenesis of neurodegenerative diseases (eg, Parkinson disease), pre-amyloid oligomers–associated alterations in cardiac mitochondrial dynamics, haploinsufficiency of wild-type BAG3, and activation of p38 signaling were identified. Unexpectedly, increased numbers of activated cardiac fibroblasts were identified in Bag3 P209L Tg+ hearts without increased fibrosis. Together, these findings point to a previously undescribed therapeutic target that may have application to mutation-induced myofibrillar myopathies as well as other common causes of heart failure that commonly harbor misfolded proteins

A Precision Measurement of Nuclear Muon Capture on 3He

The muon capture rate in the reaction mu- 3He -> nu + 3H has been measured at PSI using a modular high pressure ionization chamber. The rate corresponding to statistical hyperfine population of the mu-3He atom is (1496.0 +- 4.0) s^-1. This result confirms the PCAC prediction for the pseudoscalar form factors of the 3He-3H system and the nucleon.Comment: 13 pages, 6 PostScript figure