Cholesteryl ester transfer protein gene polymorphism is a determinant of HDL cholesterol and of the lipoprotein response to a lipid-lowering diet in type 1 diabetes

The TaqIB cholesteryl ester transfer protein (CETP) gene polymorphism (B1B2) is a determinant of HDL cholesterol in nondiabetic populations. Remarkably, this gene effect appears to be modified by environmental factors. We evaluated the effect of this polymorphism on HDL cholesterol levels and on the lipoprotein response to a linoleic acid-enriched, low-cholesterol diet in patients with type 1 diabetes. In 44 consecutive type 1 diabetic patients (35 men), CETP polymorphism, apolipoprotein (apo) E genotype, serum lipoproteins, serum CETP activity (measured with an exogenous substrate assay, n = 30), clinical variables, and a diet history were documented. The 1-year response to diet was assessed in 14 type 1 diabetic patients, including 6 B1B1 and 6 B1B2 individuals. HDL cholesterol was higher in 10 B2B2 than in 14 B1B1 homozygotes (1.63 +/- 0.38 vs. 1.24 +/- 0.23 mmol/l, P < 0.01). HDL cholesterol, adjusted for triglycerides and smoking, was 0.19 mmol/l higher for each B2 allele present. CETP activity levels were not significantly different between CETP genotypes. Multiple regression analysis showed that VLDL + LDL cholesterol was associated with dietary polyunsaturated:saturated fatty acids ratio (P < 0.02) and total fat intake (P < 0.05) in the B1B1 homozygotes only and tended to be related to the presence of the apo E4 allele (P < 0.10). In response to diet, VLDL + LDL cholesterol fell (P < 0.05) and HDL cholesterol remained unchanged in 6 B1B1 homozygotes. In contrast, VLDL + LDL cholesterol was unaltered and HDL cholesterol decreased (P < 0.05) in 6 B1B2 heterozygotes (P < 0.05 for difference in change in VLDL + LDL/HDL cholesterol ratio). This difference in response was unrelated to the apo E genotype. Thus, the TaqIB CETP gene polymorphism is a strong determinant of HDL cholesterol in type 1 diabetes. This gene effect is unlikely to be explained by a major influence on the serum level of CETP activity, as an indirect measure of CETP mass. Our preliminary data suggest that this polymorphism may be a marker of the lipoprotein response to dietary intervention.     

Contribution of the C-terminal amino acid to the stability of Bacillus subtilis neutral protease

The role of the C-terminal Leu300 in maintaining thermal stabilityof the neutral protease of Bacillus subtilis was investigated.From model building studies based on the three dimensional structureof thermolysin, the neutral protease of B.thermoproteolyticus,it was conduded that this residue is located in a hydrophobicpocket composed of residues located in the C-terminal and themiddle domain. To test the hypothesis that Leu300, by contributingto a stabilizing interaction between these domains, is importantfor enzyme stability, several neutral protease mutants wereconstructed and characterized. The thermostability of the enzymewas lowered by deleting Leu300 or by replacing this residueby a smaller (Ala), a polar (Asn) or a sterically unfavourable(He) amino acid. Thermostabiity was increased upon replacingLeu300 by Phe. These results are in agreement with model-buildingstudies. The effects on thermostability observed after mutatingthe corresponding Val318 in the thermostable neutral proteaseof B.stearothermophilus were less pronounced.     

Quenched phosphorescence detection in cyclodextrin-based electrokinetic chromatography

Quenched phosphorescence detection is a sensitive detection method recently introduced in capillary zone electrophoresis. It is based on the dynamic quenching interaction of the analytes (quenchers) with a phosphorophore, 1-bromo-4-naphthalenesulfonate (BrNS), present in the separation buffer. In this study, it is shown that this detection method can also be used in cyclodextrin-based electrokinetic chromatography (CD-EKC) despite the presence in the buffer solution of cyclodextrins, which are known to reduce the luminescence quenching rate constants. Experiments indicate that BrNS mainly resides in the aqueous phase, while the analytes are distributed between both phases. In principle, the observed quenching might arise from the interaction of BrNS with uncomplexed as well as complexed analytes. However, from the dependence of the fractional quenching on the capacity factor (the normalized fractional quenching was found to be equal to the fraction of analyte in the aqueous phase), it was concluded that only aqueous-phase quenching contributes significantly to the observed quenching. Nevertheless, separation and detection can be regarded as fully compatible, because the capacity factors encountered in CD-EKC are generally low (in this study they ranged from about 0.1 to 2.5). Indeed, with nitroaromatic compounds as the target analytes, limits of detection in the 10(-8) M range were achieved.     

A New Implementation of Automath

This paper presents aut, a modern Automath checker. It is a straightforward re-implementation of the Zandleven Automath checker from the seventies. It was implemented about five years ago, in the programming language C. It accepts both the AUT-68 and AUT-QE dialects of Automath. This program was written to restore a damaged version of Jutting's translation of Landau's Grundlagen. Some notable features: It is fast. On a 1 GHz machine it will check the full Jutting formalization (736 K of nonwhitespace Automath source) in 0.6 seconds. Its implementation of -terms does not use named variables or de Bruijn indices (the two common approaches) but instead uses a graph representation. In this representation variables are represented by pointers to a binder. The program can compile an Automath text into one big Automath single line-style -term. It outputs such a term using de Bruijn indices. (These -terms cannot be checked by modern systems like Coq or Agda, because the -typed -calculi of de Bruijn are different from the -typed -calculi of modern type theory.)The source of aut is freely available on the Web at the address .     

Developing a schematic petrogenetic transect for a contact aureole using field spectrometry; a case study in Los Santos,Salamanca Province,central-western Spain

Much work has been done in construction of petrogenetic grids for regional-scale metamorphic terrains, but low-pressure assemblages, such as contact aureoles, have been relatively ignored. This study has focused on developing a petrogenetic transect for a granitic aureole using a portable field spectrometer. Distribution of mineral assemblages, their modes, metamorphic zones, paragenetic sequences and isograds were mapped along a 4 km long transect. The transect starts at the fresh granite and cuts through the metamorphic contact aureole into the host rocks. Metamorphic reactions responsible for mineral changes were also defined. The method demonstrated potential in mineral mapping and the results could be used to support other methods like hyperspectral image analysis.     

Generality and legibility in mobile manipulation

This article investigates methods for achieving more general manipulation capabilities for mobile manipulation platforms, which produce legible behavior in human living environments. To achieve generality and legibility, we combine two control mechanisms. First of all, experience- and observation-based learning of skills is applied to routine tasks, so that the repetitive and stereotypical character of everyday activity is exploited. Second, we use planning, reasoning, and search for novel tasks which have no stereotypical solution. We apply these ideas to the learning and use of action-related places, to the model-based visual recognition and localization of objects, and the learning and application of reaching strategies and motions from humans. We demonstrate the integration of these mechanisms into a single low-level control system for autonomous manipulation platforms.     

Detection of pre-defined boundaries between hydrothermal alteration zones using rotation-variant template matching

A new method for the detection of pre-defined boundaries in single-band image data that uses a rotation-variant template matching (RTM) algorithm is presented. This algorithm matches a miniature image of a pre-defined boundary to image data at various orientations. The image pixels that match boundary criteria are reported in output imagery together with the rotation angle of the template. The method is applied to identify boundaries between hydrothermal alteration zones in processed airborne hyperspectral imagery, based on the presence of white mica minerals. Results show that boundaries identified with RTM are relatively free of noise and more coherent than those identified with, for instance, image slicing techniques. Identified boundaries can be used for image segmentation. The output of the RTM algorithm also provides information on the type of boundary, whether it is crisp or gradual. This information can be used to better characterize mineral variation in the alteration halo associated with fossil hydrothermal systems.     

Introduction of a stabilizing 10 residue {beta}-hairpin in Bacillus subtilis neutral protease

A 10 residue ß-hairpin, which is characteristic ofthermostable Bacillus neutral proteases, was engineered intothe thermolabile neutral protease of Bacillus subtilis. Therecipient enzyme remained fully active after introduction ofthe loop. However, the mutant protein exhibited autocatalyticnicking and a 0.4°C decrease in thermostability. Two additionalpoint mutations designed to improve the interactions betweenthe enzyme surface and the introduced ß-hairpin resultedin reduced nicking and increased thermostability. After theintroduction of both additional mutations in the loopcontainingmutant, nicking was largely prevented and an increase in thermostabilityof 1.1°C was achieved.     

Identification of inorganic pigments used in porcelain cards based on fusing Raman and X-ray fluorescence (XRF) data

Raman spectroscopy and X-ray fluorescence (XRF) spectroscopy are often used as complementary techniques that are well suited for the analysis of art objects because both techniques are fast, sensitive, and noninvasive and measurements can take place in situ. In most of these studies, both techniques are used separately, in the sense that the spectra are evaluated independently and single conclusions are obtained, considering both results. This paper presents a data fusion procedure for Raman and XRF data for the characterization of pigments used in porcelain cards. For the classification of the analyzed points of the porcelain cards principal component analysis (PCA) was used. A first attempt was made to develop a new procedure for the identification of the pigments using a database containing the fused Raman-XRF data of 24 reference pigments. The results show that the classification based on the fused Raman-XRF data is significantly better than the classifications based on the Raman data or the XRF data separately.