Discovery of Long Non-Coding RNA MALAT1 Amplification in Precancerous Colorectal Lesions

A colorectal adenoma, an aberrantly growing tissue, arises from the intestinal epithelium and is considered as precursor of colorectal cancer (CRC). In this study, we investigated structural and numerical chromosomal aberrations in adenomas, hypothesizing that chromosomal instability (CIN) occurs early in adenomas. We applied array comparative genomic hybridization (aCGH) to fresh frozen colorectal adenomas and their adjacent mucosa from 16 patients who underwent colonoscopy examination. In our study, histologically similar colorectal adenomas showed wide variability in chromosomal instability. Based on the obtained results, we further stratified patients into four distinct groups. The first group showed the gain of MALAT1 and TALAM1, long non-coding RNAs (lncRNAs). The second group involved patients with numerous microdeletions. The third group consisted of patients with a disrupted karyotype. The fourth group of patients did not show any CIN in adenomas. Overall, we identified frequent losses in genes, such as TSC2, COL1A1, NOTCH1, MIR4673, and GNAS, and gene gain containing MALAT1 and TALAM1. Since long non-coding RNA MALAT1 is associated with cancer cell metastasis and migration, its gene amplification represents an important event for adenoma development.     

Indoloazepinone‐Constrained Oligomers as Cell‐Penetrating and Blood–Brain‐Barrier‐Permeating Compounds

Non‐cationic and amphipathic indoloazepinone‐constrained (Aia) oligomers have been synthesized as new vectors for intracellular delivery. The conformational preferences of the [l ‐Aia‐Xxx]_n oligomers were investigated by circular dichroism (CD) and NMR spectroscopy. Whereas Boc‐[l ‐Aia‐Gly]_2,4‐OBn oligomers 12 and 13 and Boc‐[l ‐Aia‐β³‐h‐l ‐Ala]_2,4‐OBn oligomers 16 and 17 were totally or partially disordered, Boc‐[l ‐Aia‐l ‐Ala]₂‐OBn ( 14 ) induced a typical turn stabilized by C₅‐ and C₇‐membered H‐bond pseudo‐cycles and aromatic interactions. Boc‐[l ‐Aia‐l ‐Ala]₄‐OBn ( 15 ) exhibited a unique structure with remarkable T‐shaped π‐stacking interactions involving the indole rings of the four l ‐Aia residues forming a dense hydrophobic cluster. All of the proposed FITC‐6‐Ahx‐[l ‐Aia‐Xxx]₄‐NH₂ oligomers 19 – 23 , with the exception of FITC‐6‐Ahx‐[l ‐Aia‐Gly]₄‐NH₂ ( 18 ), were internalized by MDA‐MB‐231 cells with higher efficiency than the positive references penetratin and Arg₈. In parallel, the compounds of this series were successfully explored in an in vitro blood–brain barrier (BBB) permeation assay. Although no passive diffusion permeability was observed for any of the tested Ac‐[l ‐Aia‐Xxx]₄‐NH₂ oligomers in the PAMPA model, Ac‐[l ‐Aia‐l ‐Arg]₄‐NH₂ ( 26 ) showed significant permeation in the in vitro cell‐based human model of the BBB, suggesting an active mechanism of cell penetration.     

Crystallography and Morphology of Niobium Carbide in As-Cast HP-Niobium Reformer Tubes

The microstructures of two as-cast heats of niobium-modified HP stainless steels were characterized. Particular attention was paid to the interdendritic niobium-rich carbides formed during solidification of these alloys. At low magnifications, these precipitates are grouped in colonies of similar lamellae. Higher magnifications revealed that the lamellae actually obtain two distinct morphologies. The type I morphology exhibits broad planar interfaces with a smooth platelike shape. Type II lamellae have undulating interfaces and an overall reticulated shape. To provide further insight into the origin of these two different morphologies, the microstructure and crystallography of each have been studied in detail using high resolution scanning electron microscopy, transmission electron microscopy, various electron diffraction methods (electron backscatter diffraction (EBSD), selected area diffraction (SAD), and convergent beam electron diffraction (CBED)), and energy dispersive X-ray spectroscopy.     

Determining the Positive Definiteness Margin of Interval Matrices

A method for determining the positive definiteness margin of interval matrices is suggested. It is based on the use of outer interval bounds on the solution set of an interval eigenvalue problem. Three algorithms of the method are developed. It is shown that their numerical complexity is polynomial. Numerical examples illustrating the applicability of the method suggested are provided.     

Impact of a satellite-derived leaf area index monthly climatology in a global numerical weather prediction model

The leaf area index (LAI), defined as the one-sided green leaf area per unit ground area, is used in many numerical weather prediction (NWP) models as an indicator of the vegetation development state, which is of paramount importance to characterize land evaporation, photosynthesis, and carbon-uptake processes. LAI is often simply represented by lookup tables, dependent on the vegetation type and seasons. However, global LAI datasets derived from remote sensing observations have more recently become available. These products are based on sensors such as the Advanced Very High Resolution Radiometer (AVHRR) or the Moderate Resolution Imaging Spectroradiometer (MODIS), onboard polar orbiting satellites that can cover the entire globe within typically 3 days and with a spatial resolution of the order of 1 km.

We examine the meteorological impact of satellite-derived LAI products on near-surface air temperature and humidity, which comes both from the stomatal transpiration of leaves and from the intercepted water on the surface of leaves, re-evaporating into the atmosphere.

Two distinct monthly LAI climatology datasets derived respectively from AVHRR and MODIS sensors are tested. A set of forecasts and data assimilation experiments with the integrated forecasting system of the European Centre for Medium-range Weather Forecasts is performed with the monthly LAI climatology datasets as opposed to a vegetation-dependent constant LAI. The monthly LAI is shown to improve the forecasts of near-surface (screen-level) air temperature and relative humidity through its effect on evapotranspiration, with the largest impact obtained over needleleaf forests, crops, and grassland. At longer time-scales, the introduction of the monthly LAI is shown to have a positive impact on the model climate particularly during the boreal spring, where the LAI climatology has a large seasonal cycle.     

Solutions to a class of non-standard non-linear H infinity control problems

This paper presents new solutions to certain non-standard non-linear H infinity control problems. We consider non-linear affine plants whose measurement output is of dimension larger than the dimension of the external input. This problem is, under proper assumptions, transformed to the problem of stabilization by means of output injection and solution of a Hamilton-Jacobi partial differential inequality arising in singular H infinity state-feedback control. General sufficient solvability conditions are given. Explicit solutions are available in the local and semilocal cases. The former concerns a certain neighbourhood of the origin in the closed loop state-space, whereas the latter assumes that the trajectories are restricted to a neighbourhood of an invariant manifold. The issue of the controller order is addressed and a reducedorder controller is obtained in the local case. A new generalization of the chain-scattering formalism provides a very useful framework for solving this problem.     

The effects of castration on body composition, adipose tissue cellularity and lipid and carbohydrate metabolism in adult male rats

Gonadal hormones affect body composition, food intake, weight gain and serum lipids in numerous species including man. In this study, mature male Sprague-Dawley rats were castrated or sham-operated at 16 weeks of age. During the 6-week observation period with weekly records of food intake and weight gain, these parameters were significantly lower in the castrated group. The decrease in food intake in this group could not account for the difference in body weight between the groups, indicating a lower feed utilisation in the castrates. At sacrifice accessory reproductive organs, the levator ani muscle, thymus and adrenals were dissected for determination of organ weight and histology, revealing significant reductions in the accessory reproductive organs and levator ani of the castrates. The thymus was significantly heavier in the castrated animals. No differences were found in the adrenals. Two of the sham-operated animals had signs of accidental functional castration. The proportion of body cell mass and total lipid of the carcass was the same in both groups. Significant reductions in adipocyte weights were found in the epididymal depots of the castrated rats. Blood samples taken at sacrifice in pentobarbital anaesthesia were analysed for glucose, insulin, triglycerides, cholesterol, FFA, glycerol and protein. Statistically significant reductions in triglycerides and protein were recorded in the castrated animals without any significant changes in the other parameters studied. The results are discussed with reference to the age of castration and the importance of the reduced food intake in castrated animals.