A 1-V programmable DSP for wireless communications [CMOS]

In an effort to extend battery life, the manufacturers of portable consumer electronics are continually driving down the supply voltages of their systems. For example, next-generation cellular phones are expected to utilize a 1-V power supply for their digital component. To address this market, an energy-efficient, programmable digital signal processing (DSP) chip that operates from a 1-V supply has been designed, fabricated, and tested. The DSP features an instruction set and micro-architecture that are specifically targeted at wireless communication applications and that have been carefully optimized to minimize power consumption without sacrificing performance. The design utilizes a 0.35-μm dual-V_t technology with 0.25-μm minimum gate lengths that enables good performance at 1 V. Specifically, the chip dissipates 17 mW at 1 V, achieving 63-MHz operation with a power-performance metric of 0.21 mW/MHz     

Polyphenolic compositions of Basque natural ciders: A chemometric study

Polyphenolic compositions of Basque natural ciders were determined by high-performance liquid chromatography, with diode array detection following thiolysis, in order to differentiate ciders according to the geographical origin of the main raw material used for their elaboration. Fifty percent of the apples used for cidermaking in the Basque Country are imported from France or Galicia (N.W. Spain); this gives beverages of different chemical compositions and sensory qualities. A data set, consisting of 64 cider samples and 33 measured variables, was evaluated using multivariate chemometric techniques. A preliminary study of data structure was performed by cluster analysis and principal component analysis. Different classification systems for the two categories were obtained on the basis of the chemical data by applying several supervised pattern recognition procedures, such as linear discriminant analysis (LDA), K-nearest neighbours (KNN), soft independent modelling of class analogy (SIMCA), and multilayer feed-forward artificial neural networks (MLF-ANN). KNN, SIMCA and the MLF neural network provided complementary results: KNN allowed the correct classification of almost all the ciders of the Galician category, SIMCA provided a model for the ciders of the French category that excluded all ciders made with Galician apples (50% of raw material), and the neural network achieved a level of hits for the classification of the ciders obtained from French apples (50% of raw material) above 95%. Polyphenolic profiles of the ciders provide enough information to develop classification rules for identifying ciders according to the geographical origin of the raw material used for cidermaking.     

Choline kinase inhibitors as a novel approach for antiproliferative drug design

Recent progress in deciphering the molecular basis of carcinogenesis is of utmost importance to the development of new anticancer strategies. To this end, it is essential to understand the regulation of both normal cell proliferation and its alterations in cancer cells. We have previously demonstrated that in ras-transformed cells there is an increased level of phosphorylcholine (PCho) resulting from a constitutive activation on choiline kinase (ChoK). The importance of ChoK for the regulation of cell proliferation has also been proposed since an inhibitor for this enzyme, hemicholinium-3 (HC-3), drastically reduces entry into the S phase after stimulation with growth factors. Here we report the synthesis of several new compounds which are highly specific inhibitors for ChoK, with up to 1000-fold or 600-fold increased inhibitory activity, compared to HC-3 under ex vivo or in vitro conditions respectively. These novel compounds also drastically reduce entry into the S phase after stimulation with specific growth factors. A more profound inhibition of cell proliferation was observed in ras-, src- and mos-transformed cells in the presence of ChoK inhibitors, compared to their parental, untransformed NIH3T3 cells. By contrast, this effect was not observed in fos-transformed cells. While ras, src and mos transformation is associated with elevated levels of ChoK activity, fos-induced transformation does not affect ChoK activity. The inhibitory effect on proliferation of the new compounds correlates with their ability to inhibit the production of phosphorylcholine in whole cells, a proposed novel second messenger for cell proliferation. These results strongly support a critical role of choline kinase in the regulation of cell growth and makes this enzyme a novel target for the design of new antiproliferative and anticancer drugs.     

Nicotine dependence criteria of the DIS and DSM-III-R: a factor analysis.

This paper reports a factor analysis of the symptoms of nicotine dependence that were determined in an assessment of 821 current cigarette-smoking research volunteers, according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised (DSM-III-R) of the American Psychiatric Association as well as an analysis of a subset who unsuccessfully attempted to quit (n=636). In the total sample, two factors with eigenvalues greater than 1 accounted for 62.7% of the variance. When the factor analysis was repeated with the subset of research volunteers who unsuccessfully attempted to quit, only one DSM-III-R nicotine dependence symptom loaded on the second factor. This finding suggests that the two-factor structure found in this and a previous factor analysis study of the nicotine dependence segment of the DSM-III-R may be an artifact of the skipout pattern of the DSM-III-R, which assumes that smokers who have not attempted to quit have not experienced withdrawal symptoms or used tobacco to avoid these symptoms. Goodness-of-fit measures suggested that the two-factor structure is a better fit than the one-factor structure for both the total population and the subset who unsuccessfully attempted to quit or cut down. Our sample of current smokers who had not attempted to quit (n=185) was too small to permit factor analyses. Further work with other large samples from the general population of current smokers who have unsuccessfully attempted to quit as well as those who have not attempted to quit will enhance our understanding of the factor structure of the nicotine dependence segment of the DSM-III-R and clarify the effect of the skipout pattern on its factor structure.     

C-C chemokines, pivotal in protection against HIV type 1 infection

Exposure to HIV type 1 (HIV-1) does not usually lead to infection. Although this could be because of insufficient virus titer, there is now abundant evidence that some individuals resist infection even when directly exposed to a high titer of HIV. This protection recently has been correlated with homozygous mutations of an HIV-1 coreceptor, namely CCR5, the receptor for the beta-chemokines. Moreover, earlier results already had shown that the same chemokines markedly suppress the nonsyncitial inducing variants of HIV-1, the chief virus type transmitted from person to person. CCR5 mutation, as a unique mechanism of protection, is, however, suspect because HIV-1 variants can use other chemokine receptors as their coreceptor. Moreover, recent results have established that infection can indeed sometimes occur with such mutations. Here, we report on transient natural resistance over time of most of 128 hemophiliacs who were inoculated repeatedly with HIV-1-contaminated Factor VIII concentrate from plasma during 1980-1985 before the development of the HIV blood test. Furthermore, and remarkably, 14 subjects remain uninfected to this date, and in these subjects we found homozygous CCR5 mutations in none but in most of them overproduction of beta chemokines. In vitro experiments confirmed the potent anti-HIV suppressive effect of these chemokines.     

Efficacy of antitat gene therapy in the presence of high multiplicity infection and inflammatory cytokines

Because human immunodeficiency virus type 1 (HIV-1) infection is characterized by a large number of viral replication cycles and rapid cell turnover in vivo, successful gene therapy requires an approach effective under these conditions. The antitat gene has been proposed for gene therapy because it effectively blocks Tat function and the replication of HIV-1. However, neither antitat nor any other antiviral gene has been shown to inhibit HIV in the presence of high viral load and inflammatory cytokines, a condition closer to the in vivo situation. We show that cells transduced with antitat retrovirus vector are resistant to high multiplicity of HIV infection. In the presence of inflammatory cytokines, including interleukin-1 and tumor necrosis factor, both known to activate viral gene expression independently of Tat, antitat suppressed virus replication. HIV-1 inhibition was observed when cell were treated with a mixture of inflammatory cytokines able to induce acquired immunodeficiency syndrome (AIDS) Kaposi's sarcoma cell growth. These molecules have been shown to be increased in HIV-1-infected individuals, and it is suggested they play a role in the pathogenesis of AIDS. Our results suggest that antitat is effective under conditions present in vivo and therefore a primary candidate for HIV-1 gene therapy.     

Bacteria-hemocyte interactions and phagocytosis in marine bivalves

Marine bivalves (such as mussels, oysters, and clams) are widespread mollusks in coastal waters at different latitudes; due to their filter-feeding habits, they accumulate large numbers of bacteria from the harvesting waters and may act as passive carriers of human pathogens. To cope with this challenge, bivalves possess both humoral and cellular defense mechanisms with remarkably effective capabilities. The circulating cells, or hemocytes, are primarily responsible for defense against parasites and pathogens; microbial killing results from the combined action of the phagocytic process with humoral defense factors such as agglutinins (e.g., lectins), lysosomal enzymes (e.g., acid phosphatase, lysozyme), toxic oxygen intermediates, and various antimicrobial peptides. In this work, current knowledge of the mechanisms underlying the interactions between bacteria and the hemolymph components of marine bivalves is summarized. Bacterial susceptibility to hemolymph killing in different bivalve species may be a consequence of the different ability of bacterial products to attract phagocytes, the presence or absence of specific opsonizing molecules, the hemocyte capability to bind and engulf different bacteria, and the different bacterial sensitivity to intracellular killing. The role of soluble (e.g., agglutinins and opsonins) and surface-bound factors in bacterial phagocytosis by hemocytes of the most common marine bivalve species is described and the possibility that environmental temperatures and other seasonal factors may influence this process is considered. Moreover, the potential strategies used by bacteria to evade phagocytic killing by hemocytes are discussed. From the available data it is clear that several questions need further investigation; the elucidation of the factors influencing phagocytosis in bivalves and the fundamental strategies used by bacteria to escape hemolymph killing are important not only to understand bivalve immune defenses but also to explain the persistence of pathogenic bacteria in bivalve tissues and to predict the consequent impact on human health.     

Depression without sadness: functional outcomes of nondysphoric depression in later life

OBJECTIVES: We hypothesized that depressive symptoms not meeting full standard criteria for Major Depression would be associated with significant functional impairment among older adults over the course of a 13-year follow-up interval. Specifically, we developed criteria for a form of depression whose core symptoms did not include sadness or dysphoria. DESIGN: Population-based 13-year follow-up survey. SETTING: Community-dwelling adults living in East Baltimore in 1981. PARTICIPANTS: Subjects were the 1612 participants of the Baltimore sample of the Epidemiologic Catchment Area Program aged 50 years and older at the initial interview in 1981. MEASUREMENTS: The subjects were sorted into four categories based on their responses at baseline: (1) persons meeting standard criteria for Major Depression; (2) persons meeting alternative criteria for depression with dysphoria or (3) without dysphoria; and (4) a comparison category of persons not meeting any criteria for depression ("noncases"). The mortality and functional status of each group were compared after a 13-year follow-up interval. RESULTS: Compared with non-cases, participants aged 50 years and older who reported depressive symptoms but who denied sadness or dysphoria (nondysphoric depression) were at increased risk for death (relative risk (RR) = 1.70; 95% confidence interval (CI) (1.09, 2.67)), impairment in activities of daily living (RR = 3.76; 95% CI (1.73, 8.14)), impairment in instrumental activities of daily living (RR = 5.07; 95% CI (2.24, 11.44)), psychologic distress (RR = 3.68; 95% CI (1.47, 9.21)), and cognitive impairment (RR = 3.00; 95% CI (1.31, 6.89)) after a 13-year follow-up interval. The findings were not wholly explained by potentially influential baseline characteristics such as age, education, selected comorbid medical conditions, and functional status. CONCLUSION: Among adults aged 50 years and older, nondysphoric depression may be as important as Major Depression in relation to the development of functional disability and other long-term outcomes.