Prodynorphin and Proenkephalin in Cerebrospinal Fluid of Sporadic Creutzfeldt–Jakob Disease

Proenkephalin (PENK) and prodynorphin (PDYN) are endogenous opioid peptides mainly produced in the striatum and, to a lesser extent, in the cerebral cortex. Dysregulated metabolism and altered cerebrospinal fluid (CSF) levels of PENK and PDYN have been described in several neurodegenerative diseases. However, no study to date investigated these peptides in the CSF of sporadic Creutzfeldt–Jakob disease (sCJD). Using liquid chromatography-multiple reaction monitoring mass spectrometry, we evaluated the CSF PDYN- and PENK-derived peptide levels in 25 controls and 63 patients with sCJD belonging to the most prevalent molecular subtypes (MM(V)1, VV2 and MV2K). One of the PENK-derived peptides was significantly decreased in each sCJD subtype compared to the controls without a difference among subtypes. Conversely, PDYN-derived peptides were selectively decreased in the CSF of sCJD MV2K, a subtype with a more widespread overall pathology compared to the sCJD MM(V)1 and the VV2 subtypes, which we confirmed by semiquantitative analysis of cortical and striatal neuronal loss and astrocytosis. In sCJD CSF PENK and PDYN were associated with CSF biomarkers of neurodegeneration but not with clinical variables and showed a poor diagnostic performance. CSF PDYN and PENK-derived peptides had no significant diagnostic and prognostic values in sCJD; however, the distinct marker levels between molecular subtypes might help to better understand the basis of phenotypic heterogeneity determined by divergent neuronal targeting.     

A Novel Sprague-Dawley Rat Model Presents Improved NASH/NAFLD Symptoms with PEG Coated Vitexin Liposomes

Chronic liver disease (CLD) is a global threat to the human population, with manifestations resulting from alcohol-related liver disease (ALD) and non-alcohol fatty liver disease (NAFLD). NAFLD, if not treated, may progress to non-alcoholic steatohepatitis (NASH). Furthermore, inflammation leads to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Vitexin, a natural flavonoid, has been recently reported for inhibiting NAFLD. It is a lipogenesis inhibitor and activates lipolysis and fatty acid oxidation. In addition, owing to its antioxidant properties, it appeared as a hepatoprotective candidate. However, it exhibits low bioavailability and low efficacy due to its hydrophobic nature. A novel rat model for liver cirrhosis was developed by CCL4/Urethane co-administration. Vitexin encapsulated liposomes were synthesized by the ‘thin-film hydration’ method. Polyethylene glycol (PEG) was coated on liposomes to enhance stability and stealth effect. The diseased rats were then treated with vitexin and PEGylated vitexin liposomes, administered intravenously and orally. Results ascertained the liposomal encapsulation of vitexin and subsequent PEG coating to be a substantial strategy for treating liver cirrhosis through oral drug delivery.     

Discontinuous Precipitation and Phase Stability In Re- and Ru-Containing Nickel-Base Superalloys

The phase stability of nickel-base superalloys has been investigated using a new in-house-designed alloy series with stepwise increased additions of Re and Ru at otherwise fixed atomic fractions of alloying elements. Results presented in this study are focused on the lesser-known topologically closed packed (TCP) formation of columnar colonies or so-called discontinuous precipitation. A detailed investigation of these colonies allowed for identifying compositional changes during the growth process and for providing a three-dimensional (3-D) illustration of the TCP phases within these colonies. The results were used to compare the colony growth process with existing growth models. Furthermore, the influence of Re and Ru on the appearance of discontinuous precipitation has been investigated by means of colony width and the effect on creep properties. Larson-Miller plots are given to illustrate the creep strength of directionally solidified samples with and without TCP colonies compared with single crystalline samples free from TCP colonies.     

The processing element design for a large-scale spatio-temporal pattern clustering system

The clustering of spatio-temporal patterns are essential for many applications. Established from the biological analogy of the cortex, the parametrically coupled logistic map network (PCLMN) provides a viable solution to the clustering problem. To engineer for a single-chip spatio-temporal pattern clustering system, the highly modular PCLMN is designed in analog circuit. In this paper, the 0.6 μm 5 V CMOS design of the processing element is presented. The analog design employs self-calibration techniques to improve the accuracy and robustness of the nonlinear circuits. A fabricated element covers a die area of 0.55 mm², and consumes 240 mW power at 5 V supply. After calibration, simulation and testing results show that the element fulfills the system-level requirement of the Cort-X model for driving signals up to 1 MHz.     

On the Strategic Impact of the Degenerative Transfer of Xanthates on Synthetic Planning

The present brief account relates synthetic endeavours revolving around a novel chemistry of xanthates (dithiocarbonates) being developed in our group. The degenerative reversible transfer of xanthates has a unique ability to store reactive radicals in a dormant form, and thereby to enhance their lifetime in a concentrated medium, while at the same time, regulating their absolute and relative concentrations. It allows intermolecular radical additions even to unactivated alkenes, and can promote otherwise sluggish radical processes, such as 5-endo, 6-exo, 6-endo, 7-endo, and 8-endo cyclisations, as well as ring closures on (hetero)aromatic structures. This chemistry has proved remarkably versatile and powerful, both for solving synthetic problems and for the industrial production of block copolymers through the RAFT/MADIX technology.     

Thermomechanical material parameters characterization of the superalloy PN 3601669-7 under low-velocity impacts

This work concerns the characterization of the thermodynamic behavior of the superalloy Airsist 215 (PN 3601669-7) containing cobalt. Such superalloys are used in aeronautical construction, in the hot parts of the turbine. They are frequently used for the production of the paddles. The parts in service are subjected to dynamic solicitations and thermal fluctuations over the course of time. They are responsible for modification and degradation of material properties. This can lead to the appearance of cracks and, in the long term, to the rupture of these parts. In this paper, a preliminary physical study is made on the appearance of the cracks, followed by experiments using shocks at ambient temperature and under a heating situation which simulates combustion. It is found that these dynamic loads have a significant impact on the development of the cracks that appear on the segments of the turbine nozzle. The study is devoted to the elastic shock of Hertz-Boussinesq extended to viscoelastic bodies by direct convolution of Riemann-Stielges. The interest resides in the local convolution and the distribution of stresses in the contact zone. The shock excitation method includes a deduced force in the load and disload phases. This force is an impulse which approaches a Dirac function. The sample can be modeled approximately by a system of one degree of freedom for natural frequency, damping and transfer function. The spectral response of the specified shock allows calculation of the damping. Every point of this spectrum gives the response for the linear system of the transfer function. Then, viscoelastic shock parameters are deduced.     

Synthesis,Biological Evaluation of 1,1‐Diarylethylenes as a Novel Class of Antimitotic Agents

The cytotoxic activities of 23 new isocombretastatin A derivatives with modifications on the B‐ring were investigated. Several compounds exhibited excellent antiproliferative activity at nanomolar concentrations against a panel of human cancer cell lines. Compounds isoFCA‐4 ( 2 e ), isoCA‐4 ( 2 k ) and isoNH₂CA‐4 ( 2 s ) were the most cytotoxic, and strongly inhibited tubulin polymerization with IC₅₀ values of 4, 2 and 1.5 μM , respectively. These derivatives were found to be 10‐fold more active than phenstatin and colchicine with respect to growth inhibition but displayed similar activities as tubulin polymerization inhibitors. In addition, cell cycle arrest in the G₂/M phase and subsequent apoptosis was observed in three cancer cell lines when treated with these compounds. The disruptive effect of 2 e , 2 k and 2 s on the vessel‐like structures formed by human umbilical vein endothelial cells (HUVEC) suggest that these compounds may act as vascular disrupting agents. Both compounds 2 k and 2 s have the potential for further prodrug modification and development as vascular disrupting agents for treatment of solid tumors.     

A Concern-based Technique for Architecture Modelling Using the UML Package Merge

In this paper, we present a concern-based technique for software architecture modelling. We use the new UML 2 Package Merge relationship as a technique for the separation of concerns. We present the advantages of using the UML Package Merge relationship for software architecture modelling, and we propose a set of extensions for its limitations.     

On the Electromagnetic Interference Fringes Method in Geophysical Prospecting Applications

The method of electromagnetic interference fringes for the prospecting of conductive subsurfaces inside the earth is reviewed. The fields radiated by an electrically small horizontal loop situated on the earth's surface are derived and expressed in terms of different interfering wave components. The variable distance interference fringes (VDIF) method and the variable frequency interference (VFIF) method of prospecting are considered, and an interpretation procedure using the data obtained from both methods is suggested.