Current and future therapies for HCV infection: what should the end point for treatment be?

Based upon all of the available data relating to the natural history, chemical course, and response to therapy of HCV, the following recommendations are made: 1) The primary end point for HCV therapy should be HCV clearance from all tissue sites, eg plasma, liver and others 2) Therapy should be provided for patients with early infections as they have the best chance of achieving a virologic response 3) Therapy should be offered to patients with cirrhotic disease, as prevention of hepatic decompensation and degeneration to hepatic cancer is possible 4) End stage decompensated disease should be treated, particularly if liver transplantation is being considered, in an effort to either eliminate or ameliorate disease recurrence 5) Combination therapies are preferable to monotherapy as they enhance the likelihood of a therapeutic response. Some of these include agents that reduce the frequency of IFN-induced untoward events (NSAIDs) 6) The approach to HCV infection should be to view it as an infectious disease. In this way, multi-agent therapy could be used to prevent the emergence of drug resistant mutants as well as to obtain earlier clearance of the infection than is possible with monotherapy.     

Programmable CMOS switched-capacitor biquad using quasi-passivealgorithmic DAC's

This paper describes an electrically programmable switched-capacitor (SC) biquad using quasi-passive algorithmic digital-to-analog converters (DAC's). Since only two equal-valued capacitors are needed for programming each capacitance value, the proposed technique offers compact, cost-effective programmability when compared to traditional programming techniques employing binary-weighted capacitor-arrays (C-arrays). A demonstration prototype chip realized in a 1.2 μm CMOS double-metal double-poly technology, and which implements an 8 b programmable SC biquad giving a wide range of lowpass, bandpass and highpass filtering functions, occupies an active area of only 0.38 mm²     

Microstructure and domain configurations in ferroelectric PbTiO3 and Pb(Zr,Ti)O3 thin fims

Ferroelectric domain configurations in PbTiO₃ and Pb(Zr_xT_1−x)O₃ (PZT, x = 0.3 or 0.5) thin films have been studied by transmission electron microscopy. The PbTiOg and PZT thin films have been deposited by the ionized cluster beam technique and radio frequency sputtering, respectively. The grain size in these thin films is typically less than 0.5 μm. Lamellar 90°-domain features have been observed in both PbTiO₃ and PZT (30/70) samples. The domain walls correspond to the {011} twin boundaries. La-doping and Ca-modification are shown to affect the microstructure of the PZT films. No clear domain feature occurs in the PZT thin film that has composition near the morphotropic phase boundary. The effects of grain sizes are briefly discussed.     

Evidence against a direct role for the induction of c-jun expression in the mediation of drug-induced apoptosis in human acute leukemia cells

Previous reports have demonstrated that a variety of anticancer drugs, e.g., 1-beta-D-arabinofuranosylcytosine (ara-C), mitoxantrone, etoposide, camptothecin, and cisplatin, induce the expression of c-jun oncogene in leukemic cells prior to producing internucleosomal DNA fragmentation and the morphological features of apoptosis. This has led to the impression that the induction of c-jun expression may be directly involved in the molecular signaling of the final common pathway of programmed cell death or apoptosis. In the present study, we examined the role of c-jun expression in three different settings of anticancer drug-induced apoptosis in human leukemic cells. First, exposure of human myeloid leukemia HL-60 cells to high-dose ara-C for 4 h produced internucleosomal DNA fragmentation preceded by c-jun induction. However, pretreatment of HL-60 cells with staurosporine, a protein kinase C inhibitor, repressed c-jun yet enhanced DNA fragmentation and apoptosis due to ara-C. Second, in human pre-B leukemia 697/BCL-2 cells which are transfected with the cDNA of the bcl-2 oncogene and overexpress p26BCL-2, although ara-C or mitoxantrone treatment caused greater c-jun induction than in the 697/neo cells, significantly reduced endonucleolytic DNA fragmentation and apoptosis was observed in 697/BCL-2 cells. Finally, taxol-induced internucleosomal DNA fragmentation and morphological features of apoptosis in HL-60 cells were not associated with the induction of c-jun expression. These lines of evidence indicate that the induction of c-jun expression may not have a direct role in the molecular signaling of anticancer drug-induced apoptosis, and that the anticancer drug-induced apoptosis can occur by a mechanism that does not involve the induction of c-jun expression.     

On the exterior crack with contact zones

The paper discusses the exterior crack with possible contact zones, and shows by an example that contact between the crack faces exists for most combinations of the stress resultants applied at infinity.     

Engaging strangers in proximal interaction: Infants' social initiative.

Observed 72 infants aged 12, 18, and 24 mo in the presence of their mothers and 2 adult female strangers to assess their willingness to initiate proximal interaction (PI) with unfamiliar adults. Mothers and strangers were asked to be warmly responsive to infant overtures but not to invite interaction from the infant. A majority of the infants at the 3 ages initiated PI with one or both strangers, often repeatedly. For those who engaged in 2 or more PI bouts with the strangers, a significant upward trend in bout duration and intensity was noted. Older infants gave more toys to the strangers and initiated more mutual play. Stranger–mother distance affected amount of proximity, not PI. Mother–stranger conversation was associated with less PI with the conversing stranger. At all ages infants sought more PI with their mothers than with the strangers. Although infants initiated an appreciable amount of PI with the strangers during the 40-min observation, comparison with other studies indicates that a stranger who takes the initiative by inviting play can establish more rapport much sooner. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

1H-NMR of the amidation of syndiotactic poly(methacrylic acid) with carbodiimide

Summary The reaction of syndiotactic poly(methacrylic acid) with dicyclohexylcarbodiimide in the presence of benzylamine yields syndiotactic methacrylic acid-methacryloyl-N-benzylamide copolymers. A limiting conversion to amide of about 62% and a tendency of alternation for the monomer units is observed by¹H-NMR. The amidation is accompanied by the formation of a smaller amount of cyclic imide as a side reaction. The imide portion can also be transformed into amide by a consecutive hydrolysis step.     

In vitro incorporation of acetate-1-14C into the phospholipids of rabbit and human endometria

Endometria from nonpregnant and 6-day pregnant rabbits and from humans in the proliferative and secretory phases were incubated with 1-¹⁴C-acetate.¹⁴CO₂ was collected, and subsequently the amounts, specific radioactivities, and in some cases the fatty acid compositions of the isolated phospholipids were determined. Phosphatidyl choline was the phospholipid present in highest amount in endometria from both nonpregnant and pregnant rabbits, and in human endometria; this phospholipid also showed the highest degree of incorporation of¹⁴C-acetate. Pregnancy in the rabbit seemed to decrease the incorporation of¹⁴C-acetate into most of the endometrial phospholipid classes. In humans, the incorporation of acetate into phosphatidyl choline and phosphatidyl ethanolamine was lower in the secretory than the proliferative endometria. Of the fatty acids, linoleic acid in phosphatidyl choline and phosphatidyl ethanolamine of the rabbit endometria showed a significant relative increase during pregnancy and palmitoleic acid showed a decrease. This investigation was supported by a grant from the Ford Foundation.