Recent experiments on DIII-D point to the importance of two factors in determining the rate at which deuterium particles can be pumped at the divertor target(s): (1) the divertor magnetic balance, ...i.e., the degree to which the divertor topology is single-null (SN) or double-null (DN), and (2) the direction of the of B×∇B ion drift with respect to the X-point(s). Changes in divertor magnetic balance near the DN shape have a much stronger effect on the pumping rate at the inner divertor target(s) than on the pumping rate at the outer divertor target(s). The behavior in the particle pumping observed at the inner and outer divertor target(s) in the DN and near-DN shapes suggests a redistribution of particles that would be expected in the presence of B×∇B and E×B ion particle drifts in the scrapeoff layer (SOL) and divertor(s).
Human myristoyl-CoA synthetase and myristoyl-CoA:protein N-myristoyltransferase (hNmt) have been partially purified from an erythroleukemia cell line. Their substrate specificities were examined ...using two in vitro assays of enzyme activity together with a panel of C7-C17 saturated fatty acids plus 72 myristic acid analogs containing oxygen, sulfur, ketocarbonyl, ester, amide, cis and trans double bonds, triple bonds, and para-substituted phenyl groups. There is an inverse relationship between the polarity and the activity of C14 fatty acid substrates of myristoyl-CoA synthetase. Surveys of tetradecenoic and tetradecynoic acids suggest that myristate is bound to the synthetase in a bent conformation with a principal bend occurring in the vicinity of C5-C6. The synthetase can tolerate a somewhat wider range of physical chemical properties in acyl chains than can the monomeric hNmt. However, like myristoyl-CoA synthetase, there is an inverse relationship between acyl chain polarity and the activities of hNmt's acyl-CoA substrates. Moreover, the acyl chain of myristoyl-CoA appears to be bound to hNmt in a bent conformation with bends located in the vicinity of C5 and C8. The acyl chain specificities of both enzymes make them well suited to utilize efficiently any cellular pools of 5Z-tetradecenoic and 5Z,8Z-tetradecadienoic acids and their CoA derivatives. This feature may account for the recent observation that in some mammalian cell lineages, certain N-myristoyl-proteins are heterogeneously acylated with these C14 fatty acids. Finally, the acyl-CoA binding sites of human and Saccharomyces cerevisiae Nmts appear to have been highly conserved. Given their overlapping yet distinct peptide substrate specificities, development of species-specific inhibitors of Nmts should probably focus on structural features recognized in the enzymes' peptide substrates rather than in the acyl chain of their acyl-CoA substrates.
This manuscript extends our previously published work (based on data from one clinic) on the association between three drinking water-treatment modalities (boiling, filtering, and bottling) and ...diarrhoeal disease in HIV-positive persons by incorporating data from two additional clinics collected in the following year. We conducted a cross-sectional survey of drinking water patterns, medication usage, and episodes of diarrhoea among HIV-positive persons attending clinics associated with the San Francisco Community Consortium. We present combined results from our previously published work in one clinic (n = 226) with data from these two additional clinics (n = 458). In this combined analysis we employed logistic regression and marginal structural modelling of the data. The relative risk of diarrhoea for ‘always’ vs. ‘never’ drinking boiled water was 0.68 (95% CI 0.45–1.04) and for ‘always’ vs. ‘never’ drinking bottled water was 1.22 (95% CI 0.82–1.82). Drinking filtered water was unrelated to diarrhoea 1.03 (95% CI 0.78, 1.35) for ‘always’ vs. ‘never’ drinking filtered water. Adjustment for confounding did not have any notable effect on the point estimates (0.61, 1.35 and 0.98 for boiled, bottled, and filtered water respectively, as defined above). The risk of diarrhoea was lower among those consuming boiled water but this finding was not statistically significant. Because of these findings, the importance of diarrhoea in immunocompromised individuals, and the limitations of cross-sectional data further prospective investigations of water consumption and diarrhoea among HIV-positive individuals are needed.
Two new bright Ae stars Monin, D. N.; Wade, G. A.; Fabrika, S. N.
Astronomy and astrophysics (Berlin),
11/2003, Volume:
411, Issue:
2
Journal Article
Peer reviewed
Open access
Two newly identified Ae stars, ν Cyg and κ UMa, were discovered in the course of the Magnetic Survey of Bright main sequence stars (Monin et al. 2002). We present their Hα profiles along with ...measurements of their equivalent width and parameters of emission features. Emission in the Hα line of ν Cyg is variable on a time scale of 3 years. κ UMa exhibits weak emission which is rather stable. The emission is thought to arise from a circumstellar disk, and we have estimated the size of that disk.Both new emission stars are IRAS sources. Their IR color excesses are consistent with those of classical Ae stars. Thus, ν Cyg and κ UMa appear not to belong to the class of Herbig Ae/Be stars. We argue that the frequency of Ae stars may be underestimated due to the difficulty of detection of weak emission in some A stars.
The prevalence of acne in adults 20 years and older Collier, Christin N., BS; Harper, Julie C., MD; Cantrell, Wendy C., CRNP ...
Journal of the American Academy of Dermatology,
2008, 2008-Jan, 2008-01-00, 20080101, Volume:
58, Issue:
1
Journal Article
Peer reviewed
Background Acne, one of the most common skin diseases, is often mistakenly thought to affect exclusively the teenaged group. However, a significant number of patients either continue to experience ...acne or develop new-onset acne after the teenaged years. Objective A survey was designed to assess the prevalence of acne in the teenaged years, and aged 20 to 29 years, 30 to 39 years, 40 to 49 years, and 50 years and older. Methods Adults aged 20 years and older were asked to complete surveys distributed at various sites on our university campus and medical complex. Results Of 1013 participants aged 20 years and older, 73.3% (n = 744) reported ever having acne. After the teenaged years, women were more likely to report having acne than men, with the difference being statistically significant in all age groups. The prevalence of acne reported in women versus men was as follows: 20 to 29 years, 50.9% (n = 276) versus 42.5% (n = 201) ( P = .0073); 30 to 39 years, 35.2% (n = 152) versus 20.1% (n = 73) ( P < .0001); 40 to 49 years, 26.3% (n = 93) versus 12.0% (n = 36) ( P < .0001); and 50 years and older, 15.3% (n = 41) versus 7.3% (n = 18) ( P = .0046). Limitations Our results are based on the participant's own perception of the presence or absence of acne rather than a clinical evaluation. Conclusions Acne continues to be a common skin problem past the teenaged years, with women being affected at higher rates than men in all age groups 20 years or older.
Although immunocompromised persons may be at increased risk for gastrointestinal illnesses, no trials investigating drinking water treatment and gastrointestinal illness in such patients have been ...published. Earlier results from San Francisco suggested an association (OR 6.76) between tap water and cryptosporidiosis among HIV + persons. The authors conducted a randomized, triple-blinded intervention trial of home water treatment in San Francisco, California, from April 2000 to May 2001. Fifty HIV-positive patients were randomized to externally identical active (N = 24) or sham (N = 26) treatment devices. The active device contained a filter and UV light; the sham provided no treatment. Forty-five (90%) of the participants completed the study and were successfully blinded. Illness was measured using 'highly credible gastrointestinal illness' (HCGI), a previously published measure. There were 31 episodes of HCGI during 1,797 person-days in the sham group and 16 episodes during 1,478 person-days in the active group. The adjusted relative risk was 3.34 (95% CI: 0.99-11.21) times greater in those with the sham device. The magnitude of the point estimate of the risk, its consistency with recently published observational data, and its relevance for drinking water choices by immunocompromised individuals support the need for larger trials.
In a cross-sectional survey of 226 HIV-infected men, we examined the occurrence of diarrhoea and its relationship to drinking water consumption patterns, risk behaviours, immune status and medication ...use. Diarrhoea was reported by 47% of the respondents. Neither drinking boiled nor filtered water was significantly associated with diarrhoea (OR = 0·5 0·2, 1·6, 1·2 0·6, 2·5 respectively), whereas those that drank bottled water were at risk for diarrhoea (OR = 3·0 1·1, 7·8). Overall, 47% always or often used at least one water treatment. Of the 37% who were very concerned about drinking water, 62% had diarrhoea, 70% always or often used at least one water treatment. An increase in CD4 count was protective only for those with a low risk of diarrhoea associated with medication (OR = 0·6 0·5, 0·9). A 30% attributable risk to diarrhoea was estimated for those with high medication risk compared to those with low medication risk. The significant association between concern with drinking water and diarrhoea as well as between concern with drinking water and water treatment suggests awareness that drinking water is a potential transmission pathway for diarrhoeal disease. At the same time we found that a significant portion of diarrhoea was associated with other sources not related to drinking water such as medication usage.
The extracellular matrix (ECM) is a reservoir of cellular binding proteins and growth factors that are critical for normal cell behavior, and aberrations in the ECM invariably accompany malignancies ...such as prostate cancer. Carcinomas commonly overexpress macrophage inhibitory cytokine 1 (MIC-1), a proapoptotic and antitumorigenic transforming growth factor-beta superfamily cytokine. Here we show that MIC-1 is often secreted in an unprocessed propeptide containing form. It is variably processed intracellularly, with unprocessed forms being secreted from several tumor lines, including prostate carcinoma lines, PC-3 and LNCaP. Once secreted, only unprocessed proMIC-1 binds ECM, demonstrating for the first time the occurrence of extracellular stores of MIC-1. The propeptide mediates this association via its COOH-terminal 89 amino acids. Xenograft models bearing tumors secreting various engineered forms of MIC-1 show that the propeptide regulates the balance between ECM stores and circulating serum levels of mature MIC-1 in vivo. The absence of propeptide results in approximately 20-fold increase in serum MIC-1 levels. The significance of stromal MIC-1 stores was evaluated in prostate cancer tissue cores, which show major variation in stromal levels of MIC-1. Stromal MIC-1 levels are linked to prostate cancer outcome following radical prostatectomy, with decreasing stromal levels providing an important independent predictor of disease relapse. In low-grade localized prostate cancer (Gleason sum score < or = 6), the level of MIC-1 stromal stores was the best predictor of future relapse when compared with all other clinicopathologic variables. The secretion and ECM association of unprocessed proMIC-1 is likely to play a central role in modulating local bioavailability of MIC-1 which can affect patient outcome in prostate cancer and other epithelial tumors.
Covalent attachment of myristic acid (C14:0) to the amino-terminal glycine residue of a variety of eukaryotic cellular and viral proteins can have a profound influence on their biological properties. ...The enzyme that catalyzes this modification, myristoyl-CoA-protein N-myristoyltransferase (NMT), has been identified as a potential target for antiviral and antifungal therapy. Its reaction mechanism is ordered Bi Bi with myristoyl-CoA binding occurring before binding of peptide and CoA release preceding release of myristoylpeptide. Perturbations in the binding of its acyl-CoA substrate would therefore be expected to have an important influence on catalysis. We have synthesized 56 analogs of myristic acid (C14:0) to further characterize the acyl-CoA binding site of Saccharomyces cerevisiae NMT. The activity of fatty acid analogs was assessed using a coupled in vitro assay system that employed the reportedly nonspecific Pseudomonas acyl-CoA synthetase, purified S. cerevisiae NMT, and octapeptide substrates derived from residues 2-9 of the catalytic subunit of cyclic AMP-dependent protein kinase and the Pr55gag polyprotein precursor of human immunodeficiency virus I (HIV-I). Analysis of ketocarbonyl-, ester-, and amide-containing myristic acid analogs (the latter in two isomeric arrangements, the acylamino acid (-CO-NH-) and the amide (-NH-CO)) indicated that the enzyme's binding site is able to accommodate a dipolar protrusion from C4 through C13. This includes the region of the acyl chain occurring near C5-C6 (numbered from carboxyl) that appears to be bound in a bent conformation of 140-150 degrees. The activities of NMT's acyl-CoA substrates decrease with increasing polarity. This relationship was particularly apparent from an analysis of a series of analogs in which the hydrocarbon chain was terminated by (i) an azido group or (ii) one of three nitrogen heterocycles (imidazole, triazole, and tetrazole) alkylated at either nitrogen or carbon. This inverse relationship between polarity and activity was confirmed after comparison of the activities of the closely related ester- or amide-containing tetradecanoyl-CoA derivatives. Members from all of the analog series were surveyed to determine whether they could inhibit replication of human immunodeficiency virus I (HIV-I), a retrovirus that depends upon N-myristoylation of its Pr55gag for propagation. 12-Azidododecanoic acid was the most active analog tested, producing a 60-90% inhibition of viral production in both acutely and chronically infected T-lymphocyte cell lines at a concentration of 10-50 microM without associated cellular toxicity.
OBJECTIVE: Our objective was to compare the ability of two methods of amniotic fluid assessment (two-diameter amniotic fluid pocket versus the amniotic fluid index) to predict oligohydramnios (actual ...amniotic fluid volume <500 ml) or polyhydramnios (actual amniotic fluid volume >1500 ml).
STUDY DESIGN: The amniotic fluid index and the two-diameter amniotic fluid pocket were assessed before amniocentesis and determination of amniotic fluid volume with the dye (aminohippurate sodium)–dilution technique. To assess the detection of either oligohydramnios or polyhydramnios, the areas under the receiver-operator characteristic curves (±SE) were estimated by the point-to-point trapezoidal method of integration. Prediction limits were calculated by regression analysis of amniotic fluid index or two-diameter amniotic fluid pocket versus actual amniotic fluid volume and determination of 95th percentile ranges for amniotic fluid volume.
RESULTS: We studied 144 patients with a mean (±SD) gestational age of 31.7 ± 5.5 weeks; mean (±SD) amniotic flluid index and two-diameter amniotic fluid pocket were 12.6 ± 6.1 cm and 21.2 ± 18.4 cm
2, respectively. Mean (±SD) actual amniotic fluid volume was 722 ± 735 ml (range 101 to 4318 ml). The areas under the four receiver-operator characteristic curves were not significantly different from the nondiagnostic line (
p < 0.05). Regression slopes (
r values) for amniotic fluid index and two-diameter amniotic fluid pocket versus actual amniotic fluid volume were 0.34 and 0.23, respectively. Calculation of the prediction limit for 95% confidence that oligohydramnios is absent requires that the amniotic fluid index be 30 cm and the two-dimension amniotic fluid pocket be 90 cm
2
, both thresholds of which are currently considered to represent clinical polyhydramnios.
CONCLUSIONS: Both amniotic fluid index and two-dimension amniotic fluid pocket appear to be inaccurate predictors of actual oligohydramnios or polyhydramnios when compared with dye-dilution calculations of actual amniotic fluid volume. (Am J Obstet Gynecol 1997;177:291-7.)
PDF
