24 research outputs found
Uncertainty in Calibration, Detection and Estimation of Metal Concentrations in Engine Plumes Using OPAD
Improvements in uncertainties in the values of radiant intensity (I) can be accomplished mainly by improvements in the calibration process and in minimizing the difference between the background and engine plume radiance. For engine tests in which the plume is extremely bright, the difference in luminance between the calibration lamp and the engine plume radiance can be so large as to cause relatively large uncertainties in the values of R. This is due to the small aperture necessary on the receiving optics to avoid saturating the instrument. However, this is not a problem with the SSME engine since the liquid oxygen/hydrogen combustion is not as bright as some other fuels. Applying the instrumentation to other type engine tests may require a much brighter calibration lamp
A functional variant in NEPH3 gene confers high risk of renal failure in primary hematuric glomerulopathies. Evidence for predisposition to microalbuminuria in the general population.
BACKGROUND: Recent data emphasize that thin basement membrane nephropathy (TBMN) should not be viewed as a form of benign familial hematuria since chronic renal failure (CRF) and even end-stage renal disease (ESRD), is a possible development for a subset of patients on long-term follow-up, through the onset of focal and segmental glomerulosclerosis (FSGS). We hypothesize that genetic modifiers may explain this variability of symptoms. METHODS: We looked in silico for potentially deleterious functional SNPs, using very strict criteria, in all the genes significantly expressed in the slit diaphragm (SD). Two variants were genotyped in a cohort of well-studied adult TBMN patients from 19 Greek-Cypriot families, with a homogeneous genetic background. Patients were categorized as "Severe" or "Mild", based on the presence or not of proteinuria, CRF and ESRD. A larger pooled cohort (HEMATURIA) of 524 patients, including IgA nephropathy patients, was used for verification. Additionally, three large general population cohorts [Framingham Heart Study (FHS), KORAF4 and SAPHIR] were used to investigate if the NEPH3-V353M variant has any renal effect in the general population. RESULTS AND CONCLUSIONS: Genotyping for two high-scored variants in 103 TBMN adult patients with founder mutations who were classified as mildly or severely affected, pointed to an association with variant NEPH3-V353M (filtrin). This promising result prompted testing in the larger pooled cohort (HEMATURIA), indicating an association of the 353M variant with disease severity under the dominant model (p = 3.0x10-3, OR = 6.64 adjusting for gender/age; allelic association: p = 4.2x10-3 adjusting for patients' kinships). Subsequently, genotyping 6,531 subjects of the Framingham Heart Study (FHS) revealed an association of the homozygous 353M/M genotype with microalbuminuria (p = 1.0x10-3). Two further general population cohorts, KORAF4 and SAPHIR confirmed the association, and a meta-analysis of all three cohorts (11,258 individuals) was highly significant (p = 1.3x10-5, OR = 7.46). Functional studies showed that Neph3 homodimerization and Neph3-Nephrin heterodimerization are disturbed by variant 353M. Additionally, 353M was associated with differential activation of the unfolded protein response pathway, when overexpressed in stressed cultured undifferentiated podocyte cells, thus attesting to its functional significance. Genetics and functional studies support a "rare variant-strong effect" role for NEPH3-V353M, by exerting a negative modifier effect on primary glomerular hematuria. Additionally, genetics studies provide evidence for a role in predisposing homozygous subjects of the general population to micro-albuminuria
Stress analysis of a fixed implant-supported denture by the finite element method (FEM) when varying the number of teeth used as abutments
Zirconium and Titanium Propylene Polymerization Precatalysts Supported by a Fluxional C
3d Early Transition Metal Complexes Supported by a New Sterically Demanding Aryloxide Ligand
Flowchart of the genotyping strategy followed to investigate the significance of the two SNPs in four genes that emerged to have functional significance based on the <i>in silico</i> assay (see material and methods).
<p>Black arrow symbolizes the <i>NEPH3</i>-V353M variant which initially derived indicative significant association and was investigated further (black not filled arrows symbolize the meta-analysis). Light grey arrows symbolize the three SNPs found not to be significantly associated in sub-cohort A and not tested further. Dot-lined arrows symbolize the two SNPs that were found to be non-polymorphic in this cohort and not tested further.</p
Frequencies and statistics of <i>NEPH3</i>-p.V353M in three general population cohorts including a meta-analysis.
<p>Frequencies and statistics of <i>NEPH3</i>-p.V353M in three general population cohorts including a meta-analysis.</p
Demographic data of the three general population cohorts genotyped for <i>NEPH3</i>-p.V353M.
<p>Demographic data of the three general population cohorts genotyped for <i>NEPH3</i>-p.V353M.</p
A functional variant in <i>NEPH3</i> gene confers high risk of renal failure in primary hematuric glomerulopathies. Evidence for predisposition to microalbuminuria in the general population
<div><p>Background</p><p>Recent data emphasize that thin basement membrane nephropathy (TBMN) should not be viewed as a form of benign familial hematuria since chronic renal failure (CRF) and even end-stage renal disease (ESRD), is a possible development for a subset of patients on long-term follow-up, through the onset of focal and segmental glomerulosclerosis (FSGS). We hypothesize that genetic modifiers may explain this variability of symptoms.</p><p>Methods</p><p>We looked <i>in silico</i> for potentially deleterious functional SNPs, using very strict criteria, in all the genes significantly expressed in the slit diaphragm (SD). Two variants were genotyped in a cohort of well-studied adult TBMN patients from 19 Greek-Cypriot families, with a homogeneous genetic background. Patients were categorized as “Severe” or “Mild”, based on the presence or not of proteinuria, CRF and ESRD. A larger pooled cohort (HEMATURIA) of 524 patients, including IgA nephropathy patients, was used for verification. Additionally, three large general population cohorts [Framingham Heart Study (FHS), KORAF4 and SAPHIR] were used to investigate if the <i>NEPH3</i>-V353M variant has any renal effect in the general population.</p><p>Results and conclusions</p><p>Genotyping for two high-scored variants in 103 TBMN adult patients with founder mutations who were classified as mildly or severely affected, pointed to an association with variant <i>NEPH3</i>-V353M (filtrin). This promising result prompted testing in the larger pooled cohort (HEMATURIA), indicating an association of the 353M variant with disease severity under the dominant model (p = 3.0x10<sup>-3</sup>, OR = 6.64 adjusting for gender/age; allelic association: p = 4.2x10<sup>-3</sup> adjusting for patients’ kinships). Subsequently, genotyping 6,531 subjects of the Framingham Heart Study (FHS) revealed an association of the homozygous 353M/M genotype with microalbuminuria (p = 1.0x10<sup>-3</sup>). Two further general population cohorts, KORAF4 and SAPHIR confirmed the association, and a meta-analysis of all three cohorts (11,258 individuals) was highly significant (p = 1.3x10<sup>-5</sup>, OR = 7.46). Functional studies showed that Neph3 homodimerization and Neph3-Nephrin heterodimerization are disturbed by variant 353M. Additionally, 353M was associated with differential activation of the unfolded protein response pathway, when overexpressed in stressed cultured undifferentiated podocyte cells, thus attesting to its functional significance. Genetics and functional studies support a “rare variant-strong effect” role for <i>NEPH3</i>-V353M, by exerting a negative modifier effect on primary glomerular hematuria. Additionally, genetics studies provide evidence for a role in predisposing homozygous subjects of the general population to micro-albuminuria.</p></div