Uncertainty Analysis of Experimental Discharge Coefficients in Additively Manufactured Liquid Injector Elements

Screening of two additively manufactured liquid injector designs was conducted in the UAH high pressure spray facility. Four variants of each geometry with slightly different dimensions were obtained from eleven separate commercial additive manufacturing services. The devices were manufactured from Inconel 625 using the selective laser melting (SLM) powder bed process. The devices were cold flowed with water over a range of relevant pressure drops (75 psi to 1500 psi) to produce water flow rates from 0.037 to 1.75 lbm/s into ambient back pressure. Discharge coefficients determined from the testing along with the associated uncertainties provide insight into characteristic flow performance variabilities that can be expected from the SLM process for similar geometries

Trial of Amiloride in Type 2 Diabetes With Proteinuria

Renal sodium (Na+) retention and extracellular fluid volume expansion are hallmarks of nephrotic syndrome, which occurs even in the absence of activation of hormones that stimulate renal Na+ transporters. Plasmin-dependent activation of the epithelial Na+ channel has been proposed to have a role in renal Na+ retention in the setting of nephrotic syndrome. We hypothesized that the epithelial Na+ channel inhibitor amiloride would be an effective therapeutic agent in inducing a natriuresis and lowering blood pressure in individuals with macroscopic proteinuria. Methods: We conducted a pilot double-blind randomized cross-over study comparing the effects of daily administration of either oral amiloride or hydrochlorothiazide to patients with type 2 diabetes and macroscopic proteinuria. Safety and efficacy were assessed by monitoring systolic blood pressure, kidney function, adherence, weight, urinary Na+ excretion, and serum electrolytes. Nine subjects were enrolled in the trial. Results: No significant difference in systolic blood pressure or weight was seen between subjects receiving hydrochlorothiazide and those receiving amiloride (P ≥ 0.15). Amiloride induced differences in serum potassium (P < 0.001), with a 0.88 ± 0.30 mmol/l greater acute increase observed. Two subjects developed acute kidney injury and hyperkalemia when treated with amiloride. Four subjects had readily detectable levels of urinary plasminogen plus plasmin, and 5 did not. Changes in systolic blood pressure in response to amiloride did not differ between individuals with versus those without detectable urinary plasminogen plus plasmin. Discussion: In summary, among patients with type 2 diabetes, normal renal function, and proteinuria, there were reductions in systolic blood pressure in groups treated with hydrochlorothiazide or amiloride. Acute kidney injury and severe hyperkalemia were safety concerns with amiloride

Urinary Plasmin(ogen) as a Prognostic Factor for Hypertension

IntroductionPlasmin and its precursor, plasminogen, are detectable in urine from patients with glomerular disease. Urinary plasmin(ogen) levels correlate with blood pressure (BP) and may contribute to renal Na+ retention by activating the epithelial Na+ channel (ENaC). In a longitudinal nested-cohort study, we asked whether urinary plasmin(ogen) levels predict subsequent increase in BP, incident hypertension, or mortality in subjects with type I diabetes, who often develop proteinuria.MethodsThe Pittsburgh Epidemiology of Diabetes Complications (EDC) study followed up type I diabetic subjects for 25 years. Urine specimens from 70 subjects with a spectrum of baseline urinary albumin levels were examined. Outcomes included increased BP after 2 years (≥1 SD over baseline systolic or diastolic BP, examined via logistic regression), 25-year incident hypertension (≥140/90 mm&nbsp;Hg or initiating BP-lowering medications), and all-cause or cardiovascular mortality, examined using Cox regression.ResultsSubjects experiencing a 2-year increase in BP had higher baseline urinary plasmin(ogen)/creatinine levels (uPl/Cr) than other subjects (P&nbsp;= 0.04); the difference in baseline urinary albumin/creatinine levels (uAlb/Cr) was similar (P&nbsp;= 0.07). Baseline uPl/Cr was associated with increased 25-year hypertension incidence (hazard ratio&nbsp;= 2.05, P&nbsp;= 0.001), all-cause mortality (HR&nbsp;= 2.05, P&nbsp;= 0.01) and cardiovascular mortality (HR&nbsp;= 3.30, P&nbsp;= 0.005), although not independent of uAlb/Cr.ConclusionThis is the first long-term prospective study addressing clinical outcomes associated with increased urinary plasmin(ogen). Findings are consistent with a role for plasmin(ogen) in promoting increased BP, but also demonstrate the difficulty in distinguishing effects due to plasmin(ogen) from those of albuminuria

\u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu