Hyperinsulinemic Hypoglycemia Associated with a CaV1.2 Variant with Mixed Gain- and Loss-of-Function Effects

The voltage-dependent L-type calcium channel isoform Ca_V1.2 is critically involved in many physiological processes, e.g., in cardiac action potential formation, electromechanical coupling and regulation of insulin secretion by beta cells. Gain-of-function mutations in the calcium voltage-gated channel subunit alpha 1 C (CACNA1C) gene, encoding the Ca_V1.2 α₁-subunit, cause Timothy syndrome (TS), a multisystemic disorder that includes autism spectrum disorders and long QT (LQT) syndrome. Strikingly, TS patients frequently suffer from hypoglycemia of yet unproven origin. Using next-generation sequencing, we identified a novel heterozygous CACNA1C mutation in a patient with congenital hyperinsulinism (CHI) and associated hypoglycemic episodes. We characterized the electrophysiological phenotype of the mutated channel using voltage-clamp recordings and in silico action potential modeling experiments. The identified Ca_V1.2^L566P mutation causes a mixed electrophysiological phenotype of gain- and loss-of-function effects. In silico action potential modeling supports that this mixed electrophysiological phenotype leads to a tissue-specific impact on beta cells compared to cardiomyocytes. Thus, CACNA1C variants may be associated with non-syndromic hyperinsulinemic hypoglycemia without long-QT syndrome, explained by very specific electrophysiological properties of the mutated channel. We discuss different biochemical characteristics and clinical impacts of hypoglycemia in the context of CACNA1C variants and show that these may be associated with significant morbidity for Timothy Syndrome patients. Our findings underline that the potential of hypoglycemia warrants careful attention in patients with CACNA1C variants, and such variants should be included in the differential diagnosis of non-syndromic congenital hyperinsulinism.     

Additive bit-serial algorithm for discrete logarithm modulo 2/sup k/

A novel algorithm for computing the discrete logarithm modulo 2/sup k/ that is suitable for fast software or hardware implementation is described. The chosen preferred implementation is based on a linear-time multiplier-less method and has a critical path of less than k modulo 2/sup k/ shift-and-add operations.     

Frequency selective lens antenna

A variant of the hemispherical microwave lens antenna is reported where the ground plane region is modified through use of a frequency selective surface. This allows discrimination of frequencies by two closely spaced primary feeds. A scale model is reported operating at 12 and 30 GHz     

Magnetotransport of two-dimensional electron gas in Si/SiGe modulation doped structures grown by gas source molecular beam epitaxy

We have characterized two-dimensional electron gases (2DEGs) in Si/SiGe modulation doped structures grown by gas source molecular beam epitaxy. Hall bar structures were fabricated to characterize the structures and magnetotransport measurements were carried out at temperatures down to 0.4 K. Pronounced Shubnikov-de Haas oscillations were observed in the longitudinal magnetoresistance, indicative of high quality 2DEG in the channel. Electron mobilities up to 87,000 cm² V⁻¹ s⁻¹ with sheet densities about 7 × 10¹¹ cm⁻² were obtained at low temperature. Dingle plots of the magnetoresistance vs reciprocal magnetic field were utilized to determine the single-particle relaxation times in order to investigate scattering mechanisms in these structure. The ratio of the transport scattering time derived from electron mobility to the single-particle relaxation time is of the order of 10, indicating that remote impurity scattering is a dominant factor limiting the mobility of our structures. The behaviour of the magnetotransport data is discussed using a model for parallel conduction.     

Independently addressable VCSEL arrays on 3-μm pitch

We present an exceedingly dense linear vertical-cavity surface-emitting laser (VCSEL) array with independently addressable elements on a staggered 3-μm pitch. Our devices utilize an all-epitaxial structure and operate at a wavelength of 813 mm with threshold currents below 400 μA. The high-packing density is enabled by combining transparent contact technology with a planar laterally oxidized device architecture. The array exhibits low interelement thermal crosstalk and has electrical resistances of 3 MΩ between adjacent array elements     

Two-phase micropipeline control wrapper with early evaluation

A two-phase control wrapper for a micropipeline is presented. The wrapper is implemented in an Artisan 0.13/spl mu/ standard cell library that has not been augmented with any special cells for asynchronous design. The wrapper supports early evaluation allowing the output to be updated after a subset of the inputs have arrived, thus improving the throughput of the micropipeline.     

The Free Fatty Acid Content of Fish Oil,Part II: The Effect of Anchovy Quality on the Free Fatty Acid Content of the Resulting Anchovy Oil and Meal

The free fatty acid (FFA) content of anchovy oil and the residual lipids in anchovy meal were studied as a function of the length and temperature of the delay between catching and processing the fish. It was found that there was a marked increase in the FFA content of the press oil and the residual meal lipids as a result of increased-delay between catching and processing. It was also found that — other things being equal — lean anchovy yielded oils with higher FFA values than fatty anchovy. Calculation showed that the phospholipid level of an anchovy meal may serve as a useful quality index.     

Intellectual deficits after transient tyrosinemia in the term neonate

An analysis was made of the obstetric history of 1,360 patients who were delivered in 1971. It involved 3,185 pregnancies. The aim of the study was to evaluate the risk of spontaneous termination of the pregnancy, worked out from its demographic aspect. Several ideas are worthy of consideration. The risk of spontaneous intra-uterine death is cumulative, sharply increased by a repetition of such cessation of pregnancy. The same patients often undergo intentional abortion repeatedly. The respective risks of spontaneous and provoked interruption of pregnancy have been studied in greater detail as a function of parity.