Evaluation of a fluorocarbon plastic used in cryogenic valve seals

Effects of strain rate, temperature, crystallinity, and surface finish /smoothness/ on the tensile strength of a commercial chlorotrifluorethylene plastic /CTFE/ used for lipseals in very fast-acting liquid oxygen valves

Pulmonary arteriovenous malformations in children with hereditary hemorrhagic telangiectasia: A longitudinal study

Pulmonary arteriovenous malformations (PAVMs) often occur in children with hereditary hemorrhagic telangiectasia (HHT). A 14-year longitudinal study of PAVMs in children with HHT was undertaken to assess the prevalence, the clinical impact, and progression of these malformations. This was a retrospective, single-center study from May 2002 to December 2016 of 129 children with HHT diagnosed using Curacao criteria and/or confirmed by genetic testing. Transthoracic contrast echocardiography (TTCE) was the primary screening modality in all patients and PAVMs were diagnosed based on Barzilai criteria. Moderately positive TTCE (Barzilai criteria ≥ 2) was confirmed with subsequent contrast chest CT. New PAVMs were diagnosed with a positive TTCE after an initial negative TTCE. Embolization of PAVMs were performed according to HHT consensus guidelines. Of 129 children with HHT, 76 (59%) were found to have PAVMs. Sixty-seven (88%) were positive for PAVMs on initial screening. Of 63 children without PAVMs on initial screening, 31 were followed for \u3e1 year. Nine of the 31 (29%) developed new PAVMs after initial negative study. Thirty-eight (50%) of the total 76 children with PAVMs had or developed lesions large enough to be treated with embolization. Nine patients with PAVMs initially too small to be treated with embolization, developed progression of disease and ultimately were treated with embolization over time. The majority, 60% (23/38), of the children with large PAVMs had no related clinical symptoms. After embolization, 21% (8/38), of patients underwent repeat interventions. Genetic diagnosis, age, and gender were not associated with risk of having PAVM nor with need for repeat interventions. Nearly 60% of children with HHT develop PAVMs. The risk for new PAVMs to develop, small PAVMs to become large, and previously embolized PAVMs to require further intervention remains throughout childhood. Thus, children with HHT require continued follow-up until adulthood

A signalome screening approach in the autoinflammatory disease TNF Receptor Associated Periodic Syndrome (TRAPS) highlights the anti-inflammatory properties of drugs for repurposing

TNF Receptor Associated Periodic Syndrome (TRAPS) is an autoinflammatory disease caused by mutations in TNF Receptor 1 (TNFR1). Current therapies for TRAPS are limited and do not target the pro-inflammatory signalling pathways that are central to the disease mechanism. Our aim was to identify drugs for repurposing as anti-inflammatories based on their ability to down-regulate molecules associated with inflammatory signalling pathways that are activated in TRAPS. This was achieved using rigorously optimised, high through- put cell culture and reverse phase protein microarray systems to screen compounds for their effects on the TRAPS-associated inflammatory signalome. 1360 approved, publically available, pharmacologically active substances were investigated for their effects on 40 signalling molecules associated with pro-inflammatory signalling pathways that are constitutively upregulated in TRAPS. The drugs were screened at four ten-fold concentrations on cell lines expressing both wild-type (WT) TNFR1 and TRAPS-associated C33Y mutant TNFR1, or WT TNFR1 alone; signalling molecule levels were then determined in cell lysates by the reverse phase protein microarray. A novel mathematical methodology was developed to rank the compounds for their ability to reduce the expression of signalling molecules in the C33Y-TNFR1 transfectants towards the level seen in the WT-TNFR1 transfectants. Seven high-ranking drugs were selected and tested by RPPA for effects on the same 40 signalling molecules in lysates of peripheral blood mononuclear cells (PBMCs) from C33Y-TRAPS patients compared to PBMCs from normal controls. The fluoroquinolone antibiotic lomefloxacin, as well as others from this class of compounds, showed the most significant effects on multiple pro-inflammatory signalling pathways that are constitutively activated in TRAPS; lomefloxacin dose-dependently significantly reduced expression of 7/40 signalling molecules across the Jak/Stat, MAPK, NF-kB and PI3K/AKT pathways. This study demonstrates the power of signalome screening for identifying candidates for drug repurposing

Genetic Variance Estimates for Maize Yield, Grain Moisture, and Stalk Lodging for Doubled-Haploid and Conventional Selfed-Line Hybrids

An experiment was conducted to compare estimated genetic variance for maize doubled haploid (DH) with conventional twice-selfed (S2)-line hybrids. Starting with a 4-parent population, at least 160 lines were derived using both of these methods and crossed with two inbred testers. For both inbred testers, maize hybrid grain yield and stalk lodging had higher estimated genetic variances for DH than for S2. For one of the testers, estimated grain moisture genetic variance was higher for DH, but not for the other. The DH hybrid yield distributions on both testers were flatter and had more entries in tails compared with S2 distributions. With complete homozygosity of DH lines and the subsequent increased genetic variance among lines, the expected response to yield selection is higher for DH than for S2 line hybrids

Expression of trehalose-6-phosphate phosphatase in maize ears improves yield in well-watered and drought conditions

Maize, the highest-yielding cereal crop worldwide, is particularly susceptible to drought during its 2- to 3-week flowering period. Many genetic engineering strategies for drought tolerance impinge on plant development, reduce maximum yield potential or do not translate from laboratory conditions to the field. We overexpressed a gene encoding a rice trehalose-6-phosphate phosphatase (TPP) in developing maize ears using a floral promoter. This reduced the concentration of trehalose-6-phosphate (T6P), a sugar signal that regulates growth and development, and increased the concentration of sucrose in ear spikelets. Overexpression of TPP increased both kernel set and harvest index. Field data at several sites and over multiple seasons showed that the engineered trait improved yields from 9% to 49% under non-drought or mild drought conditions, and from 31% to 123% under more severe drought conditions, relative to yields from nontransgenic controls.&nbsp

Safety of anticoagulation with uninterrupted warfarin vs. interrupted dabigatran in patients requiring an implantable cardiac device

BACKGROUND: The optimal strategy of peri-procedural anticoagulation in patients undergoing permanent cardiac device implantation is controversial. Our objective was to compare the major bleeding and thromboembolic complications in patients managed with uninterrupted warfarin (UW) vs. interrupted dabigatran (ID) during permanent pacemaker (PPM) or implantable cardioverter defibrillators (ICD) implantation. METHODS: A retrospective cohort study of all eligible patients from July 2011 through January 2012 was performed. UW was defined as patients who had maintained a therapeutic international normalized ratio (INR) on the day of the procedure. ID was defined as stopping dabigatran \u3e /=12 hours prior to the procedure and then resuming after implantation. Major bleeding events included hemothorax, hemopericardium, intracranial hemorrhage, gastrointestinal bleed, epistaxis, or pocket hematoma requiring surgical intervention. Thromboembolic complications included stroke, transient ischemic attack, deep venous thrombosis, pulmonary embolism, or arterial embolism. RESULTS: Of the 133 patients (73.4+/-11.0 years; 91 males) in the study, 86 received UW and 47 received ID. One (1.2%) patient in the UW group sustained hemopericardium perioperatively and died. In comparison, the ID patients had no complications. As compared to the ID group, the UW group had a higher median CHADS2 score (2 vs. 3, P=0.04) and incidence of Grade 1 pocket hematoma (0% vs. 7%, P=0.09). Neither group developed any thromboembolic complications. CONCLUSIONS: Major bleeding rates were similar among UW and ID groups. Perioperative ID appears to be a safe anticoagulation strategy for patients undergoing PPM or ICD implantation