The factor VII activating protease G511E (Marburg) variant and cardiovascular risk

A previous study had shown a strong relationship between a variant in factor VII activating protease (FSAP G511E) and advanced carotid atheroma. In-vitro, the variant has reduced fibrinolytic but normal pro-coagulant activity, which may constitute a prothrombotic state. The current study has addressed risk for coronary heart disease in a prospective study of cardio vascular disorders (Northwick Park Heart Study II). An interactive effect upon risk was found between the 511E allele and elevated levels of cholesterol and triglyceride. Fibrinogen could substitute for triglyceride levels in this risk-interaction analysis. The findings support the proposal that the FSAP 511E allele exacerbates atherosclerosis or its clinical sequelae

Increased plasma markers of oxidative stress are associated with coronary heart disease in males with diabetes mellitus and with 10-year risk in a prospective sample of males

Background: Increased oxidative stress is associated with coronary heart disease (CHD). We examined the association between plasma markers of oxidative stress and CHD in a cross-sectional sample of patients with diabetes and prospective CHD risk in a sample of men predominantly without diabetes. Methods: Plasma total antioxidant status (TAOS) and the ratio of oxidized LDL (Ox-LDL) to LDL-cholesterol (LDL-C) were determined in a cross-section of 761 Caucasian individuals with diabetes (UDACS study). Plasma TAOS was also determined in 310 baseline samples from a 10-year prospective cohort of 3012 healthy males (NPHSII). Results: Within UDACS, males with CHD had lower mean (SD) plasma TAOS [no CHD, 43.4 (13.2)%; CHD, 40.3 (13.8)%; P = 0.04]. The prevalence of CHD was higher in the lowest compared with the upper quartiles (32.7% vs 19.7%; P = 0.004). We observed a significant association between plasma Ox-LDL:LDL-C and CHD status [no CHD vs CHD, 16.9 (3.1) vs 19.3 (5.0) units/mmol; P = 0.04], with the prevalence of CHD being higher among men in the upper compared with lower quartiles (18.4% vs 35.1%; P = 0.003). No association was observed in females. In NPHSII, TAOS was lower in those who developed CHD [35.1 (8.0)% vs 37.1 (7.9)%; P = 0.04]. The odds ratio for CHD in the lowest compared with the upper quartile was 1.91 (95% confidence interval, 0.99–3.70; P = 0.04). This remained unchanged after adjustment for classic risk factors. Conclusions: A cross-sectional and prospective association exists between baseline plasma measures of oxidative stress and CHD risk. The association with prospective CHD risk remained after adjustment for "traditional" risk factors, implying an independent role for oxidative stress in CHD risk

Apolipoprotein AIV gene variant S347 is associated with increased risk of coronary heart disease and lower plasma apolipoprotein AIV levels

The impact of common variants in the apolipoprotein gene cluster (APOC3-A4-A5) on prospective coronary heart disease (CHD) risk was examined in healthy UK men. Of the 2808 men followed over 9 years, 187 had a clinically defined CHD event. Examination of 9 single nucleotide polymorphisms (SNPs) in this group revealed that homozygotes for APOA4 S347 had significantly increased risk of CHD [hazard ratio (HR) of 2.07 (95%CI 1.04 to 4.12)], whereas men homozygous for APOC3 1100T were protected [HR 0.28 (95%CI 0.09 to 0.87)]. In stepwise multiple regression analysis, after entering all the variants and adjusting for established risk factors APOA4 T347S alone remained in the model. Using all nine SNPs, the highest risk-estimate haplotypes carried APOA4 S347 and rare alleles of the two flanking intergenic markers. The protective effect of APOC3 1100T could be explained by negative linkage disequilibrium with these alleles. To determine the association of APOA4 T347S with apoAIV levels, the relationship was examined in 1600 healthy young European men and women. S347 homozygotes had significantly lower apoAIV plasma levels (13.64±0.59 mg/dL) compared with carriers of the T347 allele (14.90±0.12 mg/dL) (P=0.035). These results demonstrate that genetic variation in and around APOA4, independent of the effects of triglyceride, is associated with risk of CHD and apoAIV levels, supporting an antiatherogenic role for apoAIV

Automated phenotyping of mosquito larvae enables high-throughput screening for novel larvicides and offers potential for smartphone-based detection of larval insecticide resistance

Pyrethroid-impregnated nets have contributed significantly to halving the burden of malaria but resistance threatens their future efficacy and the pipeline of new insecticides is short. Here we report that an invertebrate automated phenotyping platform (INVAPP), combined with the algorithm Paragon, provides a robust system for measuring larval motility in Anopheles gambiae (and An. coluzzi) as well as Aedes aegypti with the capacity for high-throughput screening for new larvicides. By this means, we reliably quantified both time- and concentration-dependent actions of chemical insecticides faster than using the WHO standard larval assay. We illustrate the effectiveness of the system using an established larvicide (temephos) and demonstrate its capacity for library-scale chemical screening using the Medicines for Malaria Venture (MMV) Pathogen Box library. As a proof-of-principle, this library screen identified a compound, subsequently confirmed to be tolfenpyrad, as an effective larvicide. We have also used the INVAPP / Paragon system to compare responses in larvae derived from WHO classified deltamethrin resistant and sensitive mosquitoes. We show how this approach to monitoring larval response to insecticides can be adapted for use with a smartphone camera application and therefore has potential for further development as a simple portable field-assay with associated real-time, geo-located information to identify hotspots

Effects of genuine dimension-six Higgs operators

We systematically discuss the consequences of genuine dimension-six Higgs operators. These operators are not subject to stringent constraints from electroweak precision data. However, they can modify the couplings of the Higgs boson to electroweak gauge bosons and, in particular, the Higgs self-interactions. We study the sensitivity to which those couplings can be probed at future \ee linear colliders in the sub-TeV and in the multi-TeV range. We find that for $\sqrt s=500$ GeV with a luminosity of 1 ab$^{-1}$ the anomalous $WWH$ and $ZZH$ couplings may be probed to about the 0.01 level, and the anomalous $HHH$ coupling to about the 0.1 level.Comment: 21 pages, 17 figures; typos corrected and references adde

Bridging the gap between stellar-mass black holes and ultraluminous X-ray sources

The X-ray spectral and timing properties of ultraluminous X-ray sources (ULXs) have many similarities with the very high state of stellar-mass black holes (power-law dominated, at accretion rates greater than the Eddington rate). On the other hand, their cool disk components, large characteristic inner-disk radii and low characteristic timescales have been interpreted as evidence of black hole masses ~ 1000 Msun (intermediate-mass black holes). Here we re-examine the physical interpretation of the cool disk model, in the context of accretion states of stellar-mass black holes. In particular, XTE J1550-564 can be considered the missing link between ULXs and stellar-mass black holes, because it exhibits a high-accretion-rate, low-disk-temperature state (ultraluminous branch). On the ultraluminous branch, the accretion rate is positively correlated with the disk truncation radius and the bolometric disk luminosity, while it is anti-correlated with the peak temperature and the frequency of quasi-periodic-oscillations. Two prototypical ULXs (NGC1313 X-1 and X-2) also seem to move along that branch. We use a phenomenological model to show how the different range of spectral and timing parameters found in the two classes of accreting black holes depends on both their masses and accretion rates. We suggest that ULXs are consistent with black hole masses ~ 50-100 Msun, moderately inefficiently accreting at ~20 times Eddington.Comment: 11 pages, accepted for publication in Astrophysics and Space Science. Based on work presented at the Fifth Stromlo Symposium, Australian National University, Dec 200

Excitation of High-Spin States by Inelastic Proton Scattering

This work was supported by National Science Foundation Grant PHY 76-84033 and Indiana Universit

Shell Structure Studies in the Pb-Region

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

Search for 3S(1/2) Hole-Strength Fragments via the 208-Pb(d,3-He)207-Tl Reaction

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

Shell Structure Studies in the Pb-Region

This research was sponsored by the National Science Foundation Grant NSF PHY-931478