Nonalcoholic fatty liver disease is closely associated with metabolic disorders, even in nonobese, nondiabetic subjects. Nonalcoholic fatty liver disease can be considered an early predictor of metabolic disorders, particularly in the normal-weight population.

These results revealed that fasting and 2-hr plasma glucose levels, as well as the proinsulin/insulin ratio before transplantation, are both possible indicators of beta-cell dysfunction and may be predictors for the development of PTDM. Furthermore, beta-cell dysfunction, rather than insulin resistance, was proven to be the main factor for the pathogenesis of PTDM.

Conventional CMOS charge pump circuits have some current mismatching characteristics. The current mismatch of the charge pump in the PLLs generates a phase offset, which increases spurs in the PLL output signals. In particular, it reduces the locking range in wide range PLLs with a dual loop scheme. A new charge pump circuit with perfect current matching characteristics is proposed. By using an error amplifier and reference current sources, one can acheve a charge pump with good current matching characteristics. It shows nearly perfect current matching characteristics over the whole VCO input range, and the amount of the reference spur is < -75dBc in the PLL output signal. The charge pump circuit is implemented in a 0 . 2 5~ CMOS process.Introduction: A charge pump is widely used in modem phaselocked loops (PLL) for a low cost IC solution. Having a neutral state, an ideal charge pump combined with a phase/frequency detector (PIFD) provides an infinite DC gain with passive filters, which results in the unbounded pull-in range for second and higher order PLLs if not limited by the voltage controlled oscillator (VCO) input range [l]. As long as the P E D and the charge pump are ideal, zero static phase error can be obtained. The charge pump, in general, shows nonideal characteristics when implemented in a circuit and its practical issues need to be considered in the design of the PLLs. One of the issues in the charge pump design is the current mismatch. In this Letter we consider the effects of the phase offset caused by the current mismatch and propose a new charge pump circuit with nearly perfect current matching characteristics. VDD M I up-ri M2 l l e c 1 12 'I REF 1 I' 0 VDD CPOUT p J

A preproparathyroid hormone allele from a patient with familial isolated hypoparathyroidism was shown to have a single point mutation in the hydrophobic core of the signal sequence. This mutation, changing a cysteine to an arginine codon at the -8 position of the signal peptide, was associated with deleterious effects on the processing of preproparathyroid hormone to proparathyroid hormone in vitro. To examine the biochemical consequence(s) of this mutation, proteins produced by cell-free translation of wild-type and mutant cRNAs were used in assays that reconstitute the early steps of the secretory pathway. We find that the mutation impairs interaction of the nascent protein with signal recognition particle and the translocation machinery. Moreover, cleavage of the mutant signal sequence by solubilized signal peptidase is ineffective. The consequence of this mutation on processing and secretion of parathyroid hormone is confirmed in intact cells by pulse-chase experiments following transient expression of the mutant protein in COS-7 cells. The inability of the mutant signal sequence, however, to interfere with the targeting and processing of other secreted proteins does not support obstruction of the translocation apparatus as the mechanism underlying the dominant mode of inheritance of hypoparathyroidism in this family.

To study the peripheral effects of melanocortin on fuel homeostasis in skeletal muscle, we assessed palmitate oxidation and AMP kinase activity in ␣-melanocyte-stimulating hormone