Biaxial Braided Flared Cone Structural Analysis

Computed Tomography (CT) is a useful tool for performing structural analysis on polymer based materials due to its high precision and accuracy. CT data was taken of two flared cones made from carbon fiber and fiberglass. One of the flared cones is pictured below. The variation in braid angle throughout the part was measured using Avizo 3D modelling software while the variation in thickness throughout the part was determined using MATLAB. Samples of pictures from the process of each of these analyses are shown below. The overall goal of this analysis was to collect structural data relevant to future testing of the parts

Roller Testing to Mimic Damage of the ISS SARJ Ring and Durability Test to Simulate Fifteen Years of SARJ Operation Using the Damaged Surface

The International Space Station's starboard Solar Alpha Rotary Joint (SARJ) experienced a breakdown of the joint's race ring surface. The starboard SARJ mechanism was cleaned and lubricated with grease. To provide some guidance on the expected behavior of the damaged SARJ ring with continued operations, experiments were conducted using rollers and a vacuum roller test rig. The approach of the experimental work involved three main steps: (1) initiate damage using conditions representative of the SARJ with inadequate lubrication; (2) propagate the damage by operating the test rollers without lubrication; and (3) assess the durability of the roller by testing to simulate the equivalent of 15 years of SARJ operation on the damaged surface assuming adequate grease lubrication. During the rig testing, additional and/or replacement grease was introduced at regular intervals to maintain good lubrication in the rig. The damage to the nitride layer continued even after application of grease. The grease lubrication proved to be effective for limiting the value of the axial force that can be developed. Limiting the axial force on the SARJ mechanism is important since the larger the axial force the more concentrated the load pressure becomes on the blend-radius location on the SARJ roller. After the testing simulating 15 years of SARJ operations, the wear depths were the order of 0.2 mm for the nitrided 15-5 roller and the order of 0.06 mm for the mating 440C roller. Metallographic inspections were done to search for indications of impending fatigue or other fracture indications that might eventually propagate and cause structural failure. There were no indications or features found that could eventually compromise structural integrity

Laser Induced Breakdown Spectroscopy for In-Situ Monitoring of Laser Powder Bed Fusion Processing

A major challenge for laser powder bed fusion processes is identifying and addressing flaws in the as-built part. In-situ monitoring of the magnitude of radiation emitted from the vicinity of the melt pool largely corresponds to the temperature field. This has been correlated with the local porosity and microstructure of the part. However, the composition of the part can also vary, either because of processing conditions or differences in the powder. Spectroscopy has the potential to resolve material composition because spectral lines corresponding to atomic species present in the metal can be clearly observed. The line emission phenomena from ionization and excitation in the vapor plume is limited under standard LPBF conditions. Laser induced breakdown spectroscopy (LIBS) uses a pulsed laser to produce a localized plasma. This is demonstrated in LPBF using an ultrashort pulsed (USP) laser coaligned to the continuous wave (CW) process laser. The USP laser can be used to probe the melt pool and plume in-process, creating a plasma that is independent of the process conditions. This probing process has minimal adverse effects on the melt pool. LIBS can provide feedback about the local species content through time resolved spectroscopy and provides the potential for voxelwise composition information to be obtained from the material.Mechanical Engineerin

Dobutamine “Stress” Test and Latent Cardiac Susceptibility to Inhaled Diesel Exhaust in Normal and Hypertensive Rats

Background: Exercise “stress” testing is a screening tool used to determine the amount of stress for which the heart can compensate before developing abnormal rhythm or ischemia, particularly in susceptible persons. Although this approach has been used to assess risk in humans exposed to air pollution, it has never been applied to rodent studies

A Zebrafish Model of Roberts Syndrome Reveals That Esco2 Depletion Interferes with Development by Disrupting the Cell Cycle

The human developmental diseases Cornelia de Lange Syndrome (CdLS) and Roberts Syndrome (RBS) are both caused by mutations in proteins responsible for sister chromatid cohesion. Cohesion is mediated by a multi-subunit complex called cohesin, which is loaded onto chromosomes by NIPBL. Once on chromosomes, cohesin binding is stabilized in S phase upon acetylation by ESCO2. CdLS is caused by heterozygous mutations in NIPBL or cohesin subunits SMC1A and SMC3, and RBS is caused by homozygous mutations in ESCO2. The genetic cause of both CdLS and RBS reside within the chromosome cohesion apparatus, and therefore they are collectively known as “cohesinopathies”. However, the two syndromes have distinct phenotypes, with differences not explained by their shared ontology. In this study, we have used the zebrafish model to distinguish between developmental pathways downstream of cohesin itself, or its acetylase ESCO2. Esco2 depleted zebrafish embryos exhibit features that resemble RBS, including mitotic defects, craniofacial abnormalities and limb truncations. A microarray analysis of Esco2-depleted embryos revealed that different subsets of genes are regulated downstream of Esco2 when compared with cohesin subunit Rad21. Genes downstream of Rad21 showed significant enrichment for transcriptional regulators, while Esco2-regulated genes were more likely to be involved the cell cycle or apoptosis. RNA in situ hybridization showed that runx1, which is spatiotemporally regulated by cohesin, is expressed normally in Esco2-depleted embryos. Furthermore, myca, which is downregulated in rad21 mutants, is upregulated in Esco2-depleted embryos. High levels of cell death contributed to the morphology of Esco2-depleted embryos without affecting specific developmental pathways. We propose that cell proliferation defects and apoptosis could be the primary cause of the features of RBS. Our results show that mutations in different elements of the cohesion apparatus have distinct developmental outcomes, and provide insight into why CdLS and RBS are distinct diseases

Genomic analyses in Cornelia de Lange Syndrome and related diagnoses: Novel candidate genes, <scp>genotype–phenotype</scp> correlations and common mechanisms

Cornelia de Lange Syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder characterized by highly variable manifestations of growth and developmental delays, upper limb involvement, hypertrichosis, cardiac, gastrointestinal, craniofacial, and other systemic features. Pathogenic variants in genes encoding cohesin complex structural subunits and regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the major pathogenic contributors to CdLS. Heterozygous or hemizygous variants in the genes encoding these five proteins have been found to be contributory to CdLS, with variants in NIPBL accounting for the majority (&gt;60%) of cases, and the only gene identified to date that results in the severe or classic form of CdLS when mutated. Pathogenic variants in cohesin genes other than NIPBL tend to result in a less severe phenotype. Causative variants in additional genes, such as ANKRD11, EP300, AFF4, TAF1, and BRD4, can cause a CdLS‐like phenotype. The common role that these genes, and others, play as critical regulators of developmental transcriptional control has led to the conditions they cause being referred to as disorders of transcriptional regulation (or “DTRs”). Here, we report the results of a comprehensive molecular analysis in a cohort of 716 probands with typical and atypical CdLS in order to delineate the genetic contribution of causative variants in cohesin complex genes as well as novel candidate genes, genotype–phenotype correlations, and the utility of genome sequencing in understanding the mutational landscape in this population

Microduplications of 16p11.2 are associated with schizophrenia

Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders1,2,3. We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 × 10−5, OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 × 10−7), bipolar disorder (P = 0.017) and autism (P = 1.9 × 10−7). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 × 10−13). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007)

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Electrocardiogram characteristics of methadone and buprenorphine maintained subjects

Copyright © 2008 Haworth Press, Inc.There has been recent concern about the association between high dose methadone and prolongation of QTc in the electrocardiogram. QTc is the time from the beginning of the QRS complex to the end of the T have as measured on an electrocardiogram and corrected for heart rate. To date, no association has been made between methadone and buprenorphine in commonly used doses and prolonged QTc. Electrocardiograms were performed on groups of methadone (n = 35, mean daily dose +/- standard deviation, 69 +/- 29 mg) and buprenorphine (n = 19, mean daily dose 11 +/- 5 mg) subjects and a group of non-opioid dependent controls (n = 17). Mean QTc did not differ (p = 0.45) between methadone, buprenorphine, or controls. Methadone subjects were significantly (odds ratio of 7.8) more likely to have U waves than buprenorphine and controls combined. Methadone subjects with U waves were maintained on higher (p = 0.004) doses (89 +/- 29 mg/day) than methadone subjects without U waves (60 +/- 24 mg/day). Methadone subjects taking 60 mg and above had higher (p = 0.02) QTc (405 +/- 29 milliseconds) than methadone subjects taking less than 60 mg per day (381 +/- 27 milliseconds). Although an association is thought to exist between high methadone doses and elongated QTc, methadone and buprenorphine, at commonly used daily doses, remain safe agents for opioid substitution therapy.Peter Athanasos; Aaron L. Farquharson; Peggy Compton; Peter Psaltis and Justin Ha