Long-term treatment of psychotic (delusional) depression with fluvoxamine: an open pilot study

The aim of this open pilot study was to evaluate the efficacy of fluvoxamine in the continuation as well as in the maintenance therapy of delusional depression. Thirty patients with recurrent, unipolar depression (DSM-IV criteria) were selected who had at least one depressive episode during the 18 months preceding the delusional depressive index episode and were treated with fluvoxamine 300 mg/day. Twenty-five of them had a sustained response to this short-term treatment and agreed to enter into the 30-month follow up study. All participants completed the follow up period. No relapse was observed during the 6 months of continuation therapy. During the further 24 months of maintenance therapy, 80% of the patients remained well, whereas 20% (five out of 25) had a single recurrence. Based on these observations, fluvoxamine might be a promising drug for long-term therapy of delusional depression. Further controlled studies are required to confirm this finding.     

Rationally designed inhibitors as tools for comparing the mechanism of squalene-hopene cyclase with oxidosqualene cyclase

The inhibition of squalene-hopene cyclase (SHC) (E.C. 5.4.99.-), an enzyme of bacterial membranes catalyzing the formation of pentacyclic sterol-like triterpenes, was studied by using different classes of compounds originally developed as inhibitors of oxidosqualene cyclase (OCS) (E.C. 5.4.99.7), the enzyme of eukaryotes responsible for the formation of tetracyclic precursors of sterols. The mechanism of cyclization of squalene by SHC, beginning with a protonation of the 2,3 double bond by an acidic residue of the enzyme, followed by a series of electrophilic additions of the carbocationic intermediates to the double bonds, is similar to the mechanism of cyclization of 2,3-oxidosqualene by OSC. The inhibitors studied included: (i) analogs of the carbocationic intermediates formed during cyclization, such as aza-analogs of squalene and 2,3-oxidosqualene; (ii) affinity-labeling inhibitors bearing a methylidene reactive group; and (iii) vinyldioxidosqualenes and vinylsulfide derivatives of the substrates. Comparison of the results obtained with the two enzymes, SHC and OSC, showed that many of the most effective inhibitors of OSC were also able to inhibit SHC, while some derivatives acted as specific inhibitors. Differences could be easily explained on the basis of the different substrate specificity of the two enzymes.     

Access of the substrate to the active site of yeast oxidosqualene cyclase: an inhibition and site-directed mutagenesis approach

A structural model of Saccharomyces cerevisiae oxidosqualene cyclase (SceOSC) suggests that some residues of the conserved sequence Pro-Ala-Glu-Val-Phe-Gly (residues 524-529) belong to a channel constriction that gives access to the active-site cavity. Starting from the SceOSC C457D mutant, which lacks the cysteine residue next to the catalytic Asp456 residue Cys457 has been replaced but Asp456 is still there, we prepared two further mutants where the wild-type residues Ala525 and Glu526 were individually replaced by cysteine. These mutants, especially E526C, were very sensitive to the thiol-reacting agent dodecyl-maleimide. Moreover, both the specific activity and the thermal stability of E526C were severely reduced. A similar decrease of the enzyme functionality was obtained by replacing Glu526 with alanine, while substitution with the conservative residues aspartate or glutamine did not alter catalytic activity. Molecular modeling of the yeast wild-type OSC and mutants on the template structure of human OSC confirms that the channel constriction is an important aspect of the protein structure and suggests a critical structural role for Glu526.     

P2P multicast for pervasive ad hoc networks

During the last few years, the proliferation of miniaturised devices with networking capabilities has provided the technological grounds for pervasive networking environments. It is not visionary to foresee a world of pervasive devices embedded in the environment interacting between them, and with those carried by users, via wireless communications. In addition, fostered by the diffusion of small-size, computational-rich mobile devices, the way content is generated, and accessed is changing with respect to the legacy-Internet paradigm. An ever-increasing share of the Internet content is generated directly by the users, and shared on the network (following the User-Generated Content model). While today the legacy Internet is still used to share user-generated content, it is reasonable to envision that pervasive networking technologies will represent the natural platform to support this new model. This will result in content being distributed on users’ devices rather than on centralised servers on the Internet, and in users creating ad hoc networks to share content. The p2p paradigm is particularly suitable for this scenario, because communications will occur directly among users, instead of being necessarily mediated by centralised servers. Motivated by these remarks, in this work we focus on p2p multicast services over ad hoc networks aimed at sharing content among groups of users interested in the same topics. Specifically, starting from a reference solution in legacy wired networks (Scribe), we design a cross-layer optimised protocol (XScribe) that addresses most of the Scribe problems on ad hoc networks. XScribe exploits cross-layer interactions with a proactive routing protocol to manage group membership. Furthermore, it uses a lightweight, structureless approach to deliver data to group members. By jointly using experimental results and analytical models, we show that, with respect to Scribe, XScribe significantly reduces the packet loss and the delay experienced by multicast receivers, and increases the maximum throughput that can be delivered to multicast groups.     

Simulated annealing-based fitting of CAD models to point clouds of mechanical parts’ assemblies

Engineering with Computers - This paper introduces a new fitting approach to allow an efficient part-by-part reconstruction or update of editable CAD models fitting the point cloud of a digitized...     

MOSFET threshold voltage: Definition,extraction, and some applications

This paper exploits a universal current-based definition of the threshold voltage (V_T) and discusses some direct methods to measure it. The consistency, accuracy, and sensitivity of the extraction procedures to second-order effects are examined through numerical simulations and experimental measurements. In addition to three procedures based on dc current measurements we propose an automatic V_T-extractor circuit which allows the direct determination of the threshold voltage with minimum influence of second-order effects.     

Oxidative stability and dietary treatment with vitamin E, oleic acid and copper of fresh and cooked pork chops

Research has been conducted on the effects of feed supplementation with vitamin E, oleic acid (sunflower oil) and copper on some quality characteristics of pork chops. The study was based on the measurement of pH 45' and 24 hr post mortem, proximate composition, colour both objective and sensory, colour stability after packing in oxygen permeable film and protective atmosphere, copper and iron contents, vitamin E content in fresh and cooked chops, peroxide and TBARS value in raw and cooked meat, total cholesterol, cholesterol oxides and aldehydes in cooked meat, sensory evaluation of the eating quality of cooked chops and iodine number of subcutaneous fat. Vitamin E content was significantly higher with oil and vitamin supplementation. No variation has been observed in copper and iron contents. A higher stability of the colour of meat packed under modified atmosphere has been observed with increasing vitamin E content, but the same did not apply with meat packed in oxygen permeable film. No differences have been observed on fatty acid oxidative stability of fresh m. longissimus dorsi and cooked chops (peroxide and TBARS values), on cholesterol oxidation and aldehydes production of cooked chops with increasing vitamin E content. Iodine number in supplemented animals reached levels normally considered at risk for fat firmness.     

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