Test Data of Flow Field of Shuttle SRM Nozzle Joint with Bond Defects, Using Unheated Air

The nozzle-to-case joint on the Shuttle SRM (as redesigned after the Challenger accident) features an adhesive sealant filling and bonding the joint, with a wiper O-ring to prevent the adhesive from reaching and disabling the closure O-ring. Flawless implementation of that joint design would ensure that hot, corrosive propellant combustion gases never reach the closure O-ring. However, understanding the flow field related to bonding defects is prudent. A comprehensive test program was conducted to quantify such flow fields and associated heating environments. A two-dimensional, full-scale model represented 65 inches of the nozzle joint, using unheated air as the test medium, in a blowdown mode. Geometry variations modeled RSRM assembly tolerances, and two types of bonding defects: pullaways and blowholes. A range of the magnitude of each type defect was tested. Also a range of operational parameters was tested, representative of the RSRM flow environment, including duplication of RSRM Mach and Reynolds numbers. Extensive instrumentation was provided to quantify pressures, heat rates, and velocities. The resulting data established that larger geometric defects cause larger pressure and larger heating, at the closure O-ring region. Velocity trends were not so straight-forward. Variations in assembly tolerances did not generally affect flow fields or heating. Operational parameters affected flow fields and heating as might be expected, increasing density or velocity increased heating. Complete details of this test effort are presented

A mouse model for adult cardiac-specific gene deletion with CRISPR/Cas9

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) 9 genomic editing has revolutionized the generation of mutant animals by simplifying the creation of null alleles in virtually any organism. However, most current approaches with this method require zygote injection, making it difficult to assess the adult, tissue-specific functions of genes that are widely expressed or which cause embryonic lethality when mutated. Here, we describe the generation of cardiac-specific Cas9 transgenic mice, which express high levels of Cas9 in the heart, but display no overt defects. In proof-of-concept experiments, we used Adeno-Associated Virus 9 (AAV9) to deliver single-guide RNA (sgRNA) that targets the Myh6 locus exclusively in cardiomyocytes. Intraperitoneal injection of postnatal cardiac-Cas9 transgenic mice with AAV9 encoding sgRNA against Myh6 resulted in robust editing of the Myh6 locus. These mice displayed severe cardiomyopathy and loss of cardiac function, with elevation of several markers of heart failure, confirming the effectiveness of this method of adult cardiac gene deletion. Mice with cardiac-specific expression of Cas9 provide a tool that will allow rapid and accurate deletion of genes following a single injection of AAV9-sgRNAs, thereby circumventing embryonic lethality. This method will be useful for disease modeling and provides a means of rapidly editing genes of interest in the heart

The Endothelial-Specific MicroRNA miR-126 Governs Vascular Integrity and Angiogenesis

SummaryEndothelial cells play essential roles in maintenance of vascular integrity, angiogenesis, and wound repair. We show that an endothelial cell-restricted microRNA (miR-126) mediates developmental angiogenesis in vivo. Targeted deletion of miR-126 in mice causes leaky vessels, hemorrhaging, and partial embryonic lethality, due to a loss of vascular integrity and defects in endothelial cell proliferation, migration, and angiogenesis. The subset of mutant animals that survives displays defective cardiac neovascularization following myocardial infarction. The vascular abnormalities of miR-126 mutant mice resemble the consequences of diminished signaling by angiogenic growth factors, such as VEGF and FGF. Accordingly, miR-126 enhances the proangiogenic actions of VEGF and FGF and promotes blood vessel formation by repressing the expression of Spred-1, an intracellular inhibitor of angiogenic signaling. These findings have important therapeutic implications for a variety of disorders involving abnormal angiogenesis and vascular leakage

Impaired activity of the fusogenic micropeptide Myomixer causes myopathy resembling Carey-Fineman-Ziter syndrome

Skeletal muscle fibers contain hundreds of nuclei, which increase the overall transcriptional activity of the tissue and perform specialized functions. Multinucleation occurs through myoblast fusion, mediated by the muscle fusogens Myomaker (MYMK) and Myomixer (MYMX). We describe a human pedigree harboring a recessive truncating variant of the MYMX gene that eliminates an evolutionarily conserved extracellular hydrophobic domain of MYMX, thereby impairing fusogenic activity. Homozygosity of this human variant resulted in a spectrum of abnormalities that mimicked the clinical presentation of Carey-Fineman-Ziter syndrome (CFZS), caused by hypomorphic MYMK variants. Myoblasts generated from patient-derived induced pluripotent stem cells displayed defective fusion, and mice bearing the human MYMX variant died perinatally due to muscle abnormalities. In vitro assays showed that the human MYMX variant conferred minimal cell-cell fusogenicity, which could be restored with CRISPR/Cas9-mediated base editing, thus providing therapeutic potential for this disorder. Our findings identify MYMX as a recessive, monogenic human disease gene involved in CFZS, and provide new insights into the contribution of myoblast fusion to neuromuscular diseases

Jupiter and How to Observe It

Jupiter is one of the most spectacular observing targets for amateur astronomers. There are various books about observing the planets, and several about Jupiter itself, but this is the only book to deal with the giant planet - its formation, structure, and incredible physics - as well as with the practical aspects of observation of the planet and its moons. The concept of the book - and of the series - is to present an up-to-date detailed physical and astrophysical description (part one); and then (part two) to consider how best to observe and image the giant planet. Jupiter and How to Observe It is a mine of information for all levels of amateur observers, from the beginning to the experienced, and will be fascinating reading for all practical amateur astronomers

Scalp potentials evoked by amplitude-modulated tones in dyslexia

We recorded the far-field EEG potential evoked by amplitude modulation of acoustic stimuli (the amplitude modulation following response, AMFR) in adults with developmental dyslexia and in a matched control group of adults with no history of reading problems. The mean AMFR recorded from participants with dyslexia was significantly smaller than that recorded from members of the control group. In contrast, the amplitude of the click-evoked auditory brainstem response [ABR) was not significantly different between participant groups. Also, there was no difference between participant groups in the latency of the AMFR or ABR. The reduced AMFR in listeners with dyslexia may reflect impaired ability of the auditory system to follow rapid changes in stimulus energy, a cue believed to be important in the perception of speech

Psychophysical sensitivity and physiological response to amplitude modulation in adult dyslexic listeners

This study reports two experiments conducted to assess the sensitivity of dyslexic listeners to amplitude modulation (AM) of acoustic stimuli. The smallest detectable depth of AM of white noise was measured as a function of modulation frequency. Dyslexic listeners had significantly higher thresholds of AM depth than did matched control listeners. We also recorded the scalp potential evoked by AM of white noise (the amplitude modulation following response, AMFR). Dyslexic listeners had significantly smaller AMFRs than did matched control listeners. The reduced AMFR is consistent with reduced sensitivity to AM, and there was a strong association between these psychophysical and physiological measures. This deficit in AM sensitivity may result in impaired perception of the AM present in speech