Summary of NASA landing-gear research

Research relative to tire tread, powered-wheel taxiing, air cushion landing systems, and crosswind landing gear is discussed

Summary of NASA landing-gear research

This paper presents a brief summary of the airplane landing gear research underway at NASA. The technology areas include: ground handling simulator, antiskid braking systems, space shuttle nose-gear shimmy, active control landing gear, wire brush skid landing gear, air cushion landing systems, tire/surface friction characteristics, tire mechanical properties, tire-tread materials, powered wheels for taxiing, and crosswind landing gear. This paper deals mainly with the programs on tire-tread materials, powered wheel taxiing, air cushion landing systems, and crosswind landing gear research with particular emphasis on previously unreported results of recently completed flight tests. Work in the remaining areas is only mentioned

Familial Dilated Cardiomyopathy of Young Portuguese Water Dogs

A novel dilated cardiomyopathy (DCM) in 12 related Portuguese Water Dogs was identified by retrospective analysis of postmortem and biopsy case records. Male and female puppies born to clinically healthy parents typically died at 13 (± 7.3) weeks of age (range, 2–32 weeks) because of congestive heart failure. Puppies died suddenly without previous signs or with mild depression followed by clinical signs of congestive heart failure 1–5 days before death. There was no sex predilection. The hearts were enlarged and rounded, with marked left ventricular and atrial dilation. No other significant structural cardiac defects were noted. The histologic changes in the myocardium were diffuse and characterized by myofibers of irregular sizes separated by an edematous interstitium. The myofibers had multifocal swollen, cleared segments often involving perinuclear areas that contained granular, phosphotungstic-acid-hematoxylin-positive material consistent with mitochondria. There was loss of the cross-striation pattern, and intercalated discs were difficult to identify. There was no evidence of concurrent myocardial fibrosis; rare chronic inflammatory infiltrates were noted in one dog. Noncardiac skeletal muscles were not affected. The underlying cause is unknown. From the pedigree analysis, an autosomal recessive pattern of inheritance is suspected. Based on the histologic findings, this DCM is most likely due to an underlying molecular (biochemical or structural) defect. The early onset and rapid progression of the disease makes this a clinically distinctive form of canine DCM

An experimental simulation study of four crosswind landing gear concepts

An experimental investigation was conducted in order to evaluate several crosswind landing-gear concepts which have a potential application to tricycle-gear-configured, short take-off and landing (STOL) aircraft landing at crab or heading angles up to 30 deg. In this investigation, the landing gears were installed on a dynamic model which had a scaled mass distribution and gear spacing but no aerodynamic similarities when compared with a typical STOL aircraft. The model was operated as a free body with radio-control steering and was launched onto a runway sloped laterally in order to provide a simulated crosswind side force. During the landing rollout, the gear forces and the model trajectory were measured and the various concepts were compared with each other. Within the test limitations, the landing gear system, in which the gears were alined by the pilot and locked in the direction of motion prior to touchdown, gave the smoothest runout behavior with the vehicle maintaining its crab angle throughout the landing runout

Overexpression of SERCA1a in the \u3cem\u3emdx\u3c/em\u3e Diaphragm Reduces Susceptibility to Contraction-Induced Damage

Although the precise pathophysiological mechanism of muscle damage in dystrophin-deficient muscle remains disputed, calcium appears to be a critical mediator of the dystrophic process. Duchenne muscular dystrophy patients and mouse models of dystrophin deficiency exhibit extensive abnormalities of calcium homeostasis, which we hypothesized would be mitigated by increased expression of the sarcoplasmic reticulum calcium pump. Neonatal adeno-associated virus gene transfer of sarcoplasmic reticulum ATPase 1a to the mdx diaphragm decreased centrally located nuclei and resulted in reduced susceptibility to eccentric contraction-induced damage at 6 months of age. As the diaphragm is the mouse muscle most representative of human disease, these results provide impetus for further investigation of therapeutic strategies aimed at enhanced cytosolic calcium removal

Inheritance, Biochemical Abnormalities, and Clinical Features of Feline Mucolipidosis II: The First Animal Model of Human I-Cell Disease

Mucolipidosis II (ML II), also called I-cell disease, is a unique lysosomal storage disease caused by deficient activity of the enzyme N-acetylglucosamine-1-phosphotransferase, which leads to a failure to internalize enzymes into lysosomes. We report on a colony of domestic shorthair cats with ML II that was established from a half-sibling male of an affected cat. Ten male and 9 female kittens out of 89 kittens in 26 litters born to clinically normal parents were affected; this is consistent with an autosomal recessive mode of inheritance. The activities of three lysosomal enzymes from affected kittens, compared to normal adult control cats, were high in serum (11-73 times normal) but low in cultured fibroblasts (9-56% of normal range) that contained inclusion bodies (I-cells), reflecting the unique enzyme defect in ML II. Serum lysosomal enzyme activities of adult obligate carriers were intermediate between normal and affected values. Clinical features in affected kittens were observed from birth and included failure to thrive, behavioral dullness, facial dysmorphia, and ataxia. Radiographic lesions included metaphyseal flaring, radial bowing, joint laxity, and vertebral fusion. In contrast to human ML II, diffuse retinal degeneration leading to blindness by 4 months of age was seen in affected kittens. All clinical signs were progressive and euthanasia or death invariably occurred within the first few days to 7 months of life, often due to upper respiratory disease or cardiac failure. The clinical and radiographic features, lysosomal enzyme activities, and mode of inheritance are homologous with ML II in humans. Feline ML II is currently the only animal model in which to study the pathogenesis of and therapeutic interventions for this unique storage diseas

Adeno-Assocated Virus (AAV) Serotype 9 Provides Global Cardiac Gene Transfer Superior to AAV1, AAV6, AAV7, and AAV8 in the Mouse and Rat

Heart disease is the leading cause of morbidity and mortality. Cardiac gene transfer may serve as a novel therapeutic approach. This investigation was undertaken to compare cardiac tropisms of adeno-associated virus (AAV) serotypes 1, 6, 7, 8, and 9. Neonatal mice were injected with 2.5 × 1011 genome copies (GC) of AAV serotype 1, 6, 7, 8, or 9 expressing LacZ under the control of the constitutive chicken β-actin promoter with cytomegalovirus enhancer promoter via intrapericardial injection and monitored for up to 1 year. Adult rats were injected with 5 × 1011 GC of the AAV vectors via direct cardiac injection and monitored for 1 month. Cardiac distribution of LacZ expression was assessed by X-Gal histochemistry, and β-galactosidase activity was quantified in a chemiluminescence assay. Cardiac functional data and biodistribution data were also collected in the rat. AAV9 provided global cardiac gene transfer stable for up to 1 year that was superior to other serotypes. LacZ expression was relatively cardiac specific, and cardiac function was unaffected by gene transfer. AAV9 provides high-level, stable expression in the mouse and rat heart and may provide a simple alternative to the creation of cardiac-specific transgenic mice. AAV9 should be used in rodent cardiac studies and may be the vector of choice for clinical trials of cardiac gene transfer

Acute Vascular Occlusion in Horses: Effects on Skeletal Muscle Size and Blood Flow

The purpose of this study was to demonstrate whether acute vascular occlusion was safe and if it would result in changes to limb muscle size in horses. Six healthy, unfit Standardbred mares were used. Horses (standing at rest) wore an occlusion cuff at the most proximal position of the left forelimb. The right forelimb was used as control. An occlusion pressure of 200 mmHg was set for 5 min followed by a 2 min recovery. Three sets of occlusions were given to each horse. Muscle thickness was measured using B-mode ultrasound. The circumference of the forelimb and first phalanx was measured using a flexible tape measure. Pulsed-wave Doppler was performed on the radialis artery with a 5–10 MHz mechanical transducer at baseline and at each occlusion. Peak flow velocity (PFV) and the flow velocity integral (FVI) were measured each time. Mid-forelimb, but not first phalanx, girth was increased (P \u3c 0.05) in the occluded but not in the control leg following occlusion. Extensor and flexor muscle thickness was increased (P \u3c 0.05) in the occluded but not in the control leg. There were no changes (P \u3e 0.05) in PFV or FVI at any measurement time point. Acute vascular occlusion may be a suitable and safe model for studying muscle hypertrophy in horses

Systemic Myostatin Inhibition via Liver-Targeted Gene Transfer in Normal and Dystrophic Mice

Background: Myostatin inhibition is a promising therapeutic strategy to maintain muscle mass in a variety of disorders, including the muscular dystrophies, cachexia, and sarcopenia. Previously described approaches to blocking myostatin signaling include injection delivery of inhibitory propeptide domain or neutralizing antibodies. Methodology/Principal Findings: Here we describe a unique method of myostatin inhibition utilizing recombinant adenoassociated virus to overexpress a secretable dominant negative myostatin exclusively in the liver of mice. Systemic myostatin inhibition led to increased skeletal muscle mass and strength in control C57 Bl/6 mice and in the dystrophindeficient mdx model of Duchenne muscular dystrophy. The mdx soleus, a mouse muscle more representative of human fiber type composition, demonstrated the most profound improvement in force production and a shift toward faster myosin-heavy chain isoforms. Unexpectedly, the 11-month-old mdx diaphragm was not rescued by long-term myostatin inhibition. Further, mdx mice treated for 11 months exhibited cardiac hypertrophy and impaired function in an inhibitor dose–dependent manner. Conclusions/Significance: Liver-targeted gene transfer of a myostatin inhibitor is a valuable tool for preclinical investigation of myostatin blockade and provides novel insights into the long-term effects and shortcomings of myostatin inhibition o

Emergency revascularization in patients with cardiogenic shock on admission: a report from the SHOCK trial and registry

Aims To determine clinical correlates and optimal treatment strategy in patients with cardiogenic shock (CS) on admission. Methods and results In SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK? (SHOCK) trial and registry patients with left ventricular (LV) dysfunction (n=1053), CS on admission occurred in 26% of directly admitted patients (n=166/627). Time from myocardial infarction to CS was shorter, initial haemodynamic profile poorer, and aggressive treatment less frequent in CS on admission than in delayed CS patients. CS on admission patients constituted a smaller relative proportion (11%) of the transferred (n=48/426) when compared with the directly admitted cohort (P<0.001). In-hospital mortality was higher (75 vs. 56%; P<0.001) with more rapid death (24-h mortality 40 vs. 17%; P<0.001) in CS on admission than in delayed CS patients. Emergency revascularization reduced in-hospital mortality in CS on admission (60 vs. 82%; P=0.001) and in delayed CS patients similarly (46 vs. 62%; P<0.001; interaction P=0.25). After adjustment for clinical differences, CS on admission was an independent predictor of in-hospital mortality (P=0.008). Conclusion CS on admission patients have a worse outcome but benefit equally from emergency revascularization as delayed CS patients, emphasizing the need for rapid and direct access of CS on admission patients to facilities providing this car