Genetic Interactions Between TRPC6 and NPHS1 Variants Affect Posttransplant Risk of Recurrent Focal Segmental Glomerulosclerosis.

Individuals with TRPC6 mutations have variable phenotypes, ranging from healthy carrier to focal segmental glomerulosclerosis (FSGS) leading to renal failure. Here, we describe a family where six members had a novel TRPC6 p.R68W (c.202C>T) mutation, two of whom had renal failure from FSGS, and one had proteinuria. One healthy carrier donated a kidney to her sister. Both donor and recipient had no proteinuria at 20 years posttransplant. Two synonymous NPHS1 polymorphisms, rs2285450 (c.294C>T) and rs437168 (c.2289C>T) segregated with renal failure in this family. These variants had higher allele frequencies in 97 unrelated patients with nephrotic syndrome or FSGS compared to 224 controls. Using patch-clamp experiments in HEK293 and podocytes, we showed that the p.R68W mutation increased TRPC6 current amplitudes, which may be explained by enhanced TRPC6 surface expression. Additionally, while wild-type nephrin suppressed TRPC6 currents, this ability was lost in the presence of NPHS1 c.294C>T polymorphism. When cells were transfected according to combined TRPC6 and NPHS1 genotypes in the family, those representing the donor had lower TRPC6 currents than cells representing the recipient, suggesting that interactions between TRPC6 and NPHS1 variants could possibly account for the variable penetrance of TRPC6 mutations and the absence of recurrence in the graft.

A time-resolving spectrograph for free-flight ballistic range application.

Time-resolved spectra for some hypervelocity spheres and cones in a free-flight ballistic range are obtained using a large aperture, slitless spectrograph in conjunction with an image converter camera. For nonablating spheres, only emission from the shock cap can be observed with the present instrument. For ablating models at elevated speeds and range pressures, band systems for such molecular species as C(2), CH, and CN for some objects containing hydrocarbons and Cu(2), CuF, CuO, BeO, and AlO for metallic models have been observed in the near wake region of the flow. The feasibility of using a high gain image intensifier for the study of far wake emission is discussed.

Anamorphic condensing optics for a slitless spectrograph.

The use of a slitless spectrograph to obtain the spectra of wakes of hypervelocity projectiles launched in a free flight ballistic range has several advantages. The use of this instrument as a general spectroscopic tool is, however, especially limited for large objects. This is because resolution is determined by final trajectory image size as well as dispersion. The spectral resolution can be improved without altering the desirable properties of the instrument by using an anamorphic system to demagnify the wake image width only. Requirements are given for anamorphic optics used to focus the luminous wakes of hypervelocity projectiles onto the entrance focal plane of a slitless spectrograph. A system currently in use that meets these requirements is described. A comparison of spectra taken with anamorphic and spherical condensing systems is made.

A high gain, time-resolving spectrograph for the diagnosis of laboratory simulated reentry.

To increase the sensitivity of a time-resolving spectrograph, a four-stage, magnetically focused, cascade type image intensifier was coupled to an electron scanning image converter. A radiant intensity gain of more than 500, enough to permit the study of far wake radiation, has been achieved, along with sufficient spectral resolution for the determination of temperature and electron density profiles in the flow behind a hypervelocity object. An example of wake temperature results from the time-resolved vibrational bands of CN is presented.