Vitamin A supplementation but not deworming improves growth of malnourished preschool children in eastern Zaire

14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (FTHA) has been recently introduced as a new tracer for fatty acid metabolism. Myocardial [18F]FTHA uptake is believed to reflect mainly beta-oxidation of the circulating free fatty acids (FFAs), since it is trapped in the mitochondria because subsequent steps of beta-oxidation are inhibited by sulfur heteroatom. We investigated [18F]FTHA kinetics in myocardial and skeletal muscle in vivo. METHODS: Two dynamic PET studies were performed in seven patients with stable coronary artery disease, once in the fasting state and once during euglycemic hyperinsulinemia (serum insulin approximately 60 mU/liter). The fractional [18F] FTHA uptake rates (Ki) were multiplied with serum FFA concentrations and were considered to represent FFA uptake. RESULTS: Serum FFA concentration decreased by 80% during insulin clamp. After tracer injection, rapid myocardial uptake was identified both in the fasting state and during insulin stimulation. The cardiac image quality was excellent in both occasions. In addition, femoral muscles were clearly visualized in both studies. The fractional myocardial [18F]FTHA uptake rates (Ki) in the normal myocardial regions were similar in the fasting state (0.11 +/- 0.04 ml/g/min (mean +/- s.d.) and during insulin clamp (0.12 +/- 0.03 ml/g/min; ns). The calculated myocardial FFA uptake was four times higher in the fasting state than during insulin clamp (5.8 +/- 1.7 versus 1.4 +/- 0.5 micromol/100 g/min, p < 0.005). The femoral muscle fractional [18F]FTHA uptake rates (Ki) were lower (0.0071 +/- 0.0014 ml/g/min) in the fasting state than during insulin clamp (0.0127 +/- 0.0036 ml/g/min; p = 0.03), but the estimated femoral muscle FFA uptake was three times higher in the fasting state (0.38 +/- 0.09 micromol/100 g/min) as compared to that during insulin clamp (0.12 +/- 0.05 micromol/100 g/min, p < 0.005). CONCLUSION: Fluorine-18-FTHA PET appears to be a feasible method to estimate fatty acid kinetics in myocardial and skeletal muscle. Physiologically reasonable rates of FFA uptake in myocardium and skeletal muscle were obtained. Furthermore, the uptake rates were suppressed in response to insulin both in the myocardial and femoral muscle as expected.     

A descriptive analysis of populations of three-dimensional structures calculated from primary sequences of proteins by OSIRIS

Among different ab initio approaches to calculate 3D-structures of proteins out of primary sequences, a few are using restricted dihedral spaces and empirical equations of energy as is OSIRIS. All those approaches were calibrated on a few proteins or fragments of proteins. To optimize the calculation over a larger diversity of structures, we need first to define for each sequence what are good conditions of calculations in order to choose a consensus procedure fitting most 3D-structures best. This requires objective classification of calculated 3D-structures. In this work, populations of avian and bovine pancreatic polypeptides (APP, BPP) and of calcium-binding protein (CaBP) are obtained by varying the rate of the angular dynamics of the second step of OSIRIS. Then, 3D-structures are clustered using a nonhierarchical method, SICLA, using rmsd as a distance parameter. A good clustering was obtained for four subpopulations of APP, BPP and CaBP. Each subpopulation was characterized by its barycenter, relative frequency and dispersion. For the three alpha-helix proteins, after the step 1 of OSIRIS, most secondary structures were correct but molecules have a few atomic contacts. Step 2, i.e., the angular dynamics, resolves those atomic contacts and clustering demonstrates that it generates subpopulations of topological conformers as the barycenter topologies show.     

Anwendungen kapazitiver Messtechnik

In this inangural lecture applications of capacitive measurement are focussed. First, the motivation for taking the chair of an institute of electrical measurement — having 20 years of experience in the field of industrial electronics, with emphasis on automotive electronics — shall be pointed out. Furthermore the integration of capacitive measurement into other research and development activities at the Institute of Electrical Measurement and Measurement Signal Processing at Graz University of Technology is shown.     

Prediction of epitopes and production of monoclonal antibodies against gastric H,K-ATPase

Monoclonal antibodies (mAbs) were produced against gastric H,K-ATPase usinga theoretical and experimental strategy based on prediction of linearepitopes by molecular modelling followed by production of anti- peptideantibodies. By analysing the alpha subunit sequence, we predicted severalepitopes corresponding to amino acids K519-L533, E543- Y553 and S786-L798and produced monoclonal antibodies HK519, HK543 and HK786. All three reactagainst gastric H,K-ATPase in RaLISA, immunohistochemistry and Westernblots demonstrating that they recognize the native and the SDS-denaturedionic pump and that the epitopes are located at the surface of the nativeATPase. Antibody Kd are in the range 6-10x10(-8) M. Monoclonal antibodyHK519 is a competitive inhibitor of ATP, in agreement with ATP binding toK519. Neither mAb 543, nor mAb 786 inhibit the ATPase activity. Monoclonalantibody 95111, whose epitope is mapped between residues C529 and E561,competes with mAb HK543 but not with the other two. We suggest that the95111 epitope is overlapping or very close to the HK543-553 sequence.Induction of E1 conformer by binding FITC to K519 increases the number ofmAb 95111 and mAb HK543 epitopes but not that of mAb 786, supporting thefact that the fragment E543-Y553 changes accessibility, maybe during theE1-E2 transconformation.     

Measurement of tumor vascular damage in mice with 99mTc-MIBI following photodynamic therapy

The clinical perfusion agent 99mTc-MIBI was used to monitor changes in tumor vascular perfusion (TVP) induced by Photofrin (PII)-mediated photodynamic therapy (PDT). BALB/c mice bearing an EMT-6 tumor on each hind thigh were given an intravenous injection of 1, 2 or 5 mg kg-1 PII. Twenty-four hours later, one tumor was illuminated (600-650 nm, 200 mW cm-2, 400 J cm-2) while the other served as a control. At various time intervals after PDT (0, 2 and 24 h) mice received an intravenous injection of 99mTc-hexakismethoxyisobutylisonitrile (MIBI) (0.18 MBq g-1) and were sacrificed 2 min later. The light-treated and the untreated tumors were then dissected, the radioactivity was counted and the percentage of the injected dose per gram of tumor (%ID g-1) was calculated as a measure of TVP. We observed that TVP is drug dose dependent, develops progressively with time post-PDT and is inversely related to PDT efficacy. Our data show that early tumor retention of 99mTc-MIBI is a simple method to assess TVP and vascular damage induced by PDT.     

Wind turbine main bearing rating lives as determined by IEC 61400-1 and ISO 281: A critical review and exploratory case study

This paper studies the rating lives of wind turbine main bearings, as determined by the IEC 61400-1 and ISO 281 standards. A critical review of relevant bearing life theory and turbine design requirements is provided, including discussion on possible shortcomings such as the existence (or not) of the bearing fatigue load limit and the validity of assuming linear damage accumulation. A detailed exploratory case study is then undertaken to determine rating lives for two models of main bearing in a 1.5 MW wind turbine. Rating life assessment is carried out under different conditions, including various combinations of main bearing temperature, wind field characteristics, lubricant viscosity, and contamination levels. Rating lives are found to be sufficiently above the desired 20-year design life for both bearing models under expected operating conditions. For the larger bearing, operational loads are shown to be below or close to the bearing fatigue load limit a vast majority of the time. Key sensitivities for rating life values are temperature and contamination. Overall, the results of this study suggest that an ISO 281 rating life assessment does not account for reported rates of main bearing failures in 1 to 3 MW wind turbines. It is recommended that a similar analysis be undertaken for ISO/TS 16281 rating lives, along with further efforts to identify principal root causes of main bearing failures in future work, possibly leading to a new application standard specific to this component. It is also recommended that the impacts of partial wake impingement on main bearing rating lives are investigated.     

Characterization of functional residues in the interfacial recognition domain of lecithin cholesterol acyltransferase (LCAT)

Lecithin cholesterol acyltransferase (LCAT) is an interfacialenzyme active on both high-density (HDL) and low-density lipoproteins(LDL). Threading alignments of LCAT with lipases suggest thatresidues 50–74 form an interfacial recognition site andthis hypothesis was tested by site-directed mutagenesis. The(56–68) deletion mutant had no activity on any substrate.Substitution of W61 with F, Y, L or G suggested that an aromaticresidue is required for full enzymatic activity. The activityof the W61F and W61Y mutants was retained on HDL but decreasedon LDL, possibly owing to impaired accessibility to the LDLlipid substrate. The decreased activity of the single R52A andK53A mutants on HDL and LDL and the severer effect of the doublemutation suggested that these conserved residues contributeto the folding of the LCAT lid. The membrane-destabilizing propertiesof the LCAT 56–68 helical segment were demonstrated usingthe corresponding synthetic peptide. An M65N–N66M substitutiondecreased both the fusogenic properties of the peptide and theactivity of the mutant enzyme on all substrates. These resultssuggest that the putative interfacial recognition domain ofLCAT plays an important role in regulating the interaction ofthe enzyme with its organized lipoprotein substrates.