Character sets of today and tomorrow

This paper reviews the character sets used in today's computer systems and discusses character sets for future computer systems. Some newer Latin-based character sets are introduced and compared in terms of their suitability for information interchange and information processing. Finally, the character set most appropriate for use in future computer systems is suggested.     

Structure–Activity Relationship Studies on (R)‐PFI‐2 Analogues as Inhibitors of Histone Lysine Methyltransferase SETD7

SETD7 is a histone H3K4 lysine methyltransferase involved in human gene regulation. Aberrant expression of SETD7 has been associated with various diseases, including cancer. Therefore, SETD7 is considered a good target for the development of new epigenetic drugs. To date, few selective small‐molecule inhibitors have been reported that target SETD7, the most potent being (R)‐PFI‐2. Herein we report structure–activity relationship studies on (R)‐PFI‐2 and its analogues. A library of 29 structural analogues of (R)‐PFI‐2 was synthesized and evaluated for inhibition of recombinantly expressed human SETD7. The key interactions were found to be a salt bridge and a hydrogen bond formed between (R)‐PFI‐2′s NH₂⁺ group and SETD7′s Asp256 and His252 residue, respectively.     

Synthesis of Nanowire TiO2 Thin Films by Hydrothermal Treatment and their Photoelectrochemical Properties

Nanowire TiO₂ thin films were successfully prepared on Ti metal substrates by hydrothermal treatment of calcined Ti foils in 10 M NaOH. The nanowire TiO₂ thin films exhibited much larger surface area and higher photoelectrochemical performance than the TiO₂ thin films prepared on Ti metal substrates by the calcination of Ti foil. These nanowire films were shown to act as an efficient photoanodes for the photoelectrochemical water splitting reaction.     

Intrathecal Actions of the Cannabis Constituents Δ(9)-Tetrahydrocannabinol and Cannabidiol in a Mouse Neuropathic Pain Model

(1) Background: The psychoactive and non-psychoactive constituents of cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), synergistically reduce allodynia in various animal models of neuropathic pain. Unfortunately, THC-containing drugs also produce substantial side-effects when administered systemically. We examined the effectiveness of targeted spinal delivery of these cannabis constituents, alone and in combination. (2) Methods: The effect of acute intrathecal drug delivery on allodynia and common cannabinoid-like side-effects was examined in a mouse chronic constriction injury (CCI) model of neuropathic pain. (3) Results: intrathecal THC and CBD produced dose-dependent reductions in mechanical and cold allodynia. In a 1:1 combination, they synergistically reduced mechanical and cold allodynia, with a two-fold increase in potency compared to their predicted additive effect. Neither THC, CBD nor combination THC:CBD produced any cannabis-like side-effects at equivalent doses. The anti-allodynic effects of THC were abolished and partly reduced by cannabinoid CB1 and CB2 receptor antagonists AM281 and AM630, respectively. The anti-allodynic effects of CBD were partly reduced by AM630. (4) Conclusions: these findings indicate that intrathecal THC and CBD, individually and in combination, could provide a safe and effective treatment for nerve injury induced neuropathic pain.     

Synthesis and reactivity of coumarin 3,4-epoxide

Coumarin is used widely as a fragrance constituent and is administered clinically in the treatment of certain lymphedemas and malignancies. Although toxicity occurs only rarely in humans treated clinically with high-dose coumarin, it is well established that coumarin is hepatotoxic in the rat. This species difference in susceptibility to toxicity reflects the disparate metabolic processes occurring in humans and rodents. In humans, coumarin is converted extensively via cytochrome P450 2A6 to the nontoxic 7-hydroxycoumarin metabolite. In contrast, coumarin 3,4-epoxidation is thought to predominate in rodent species, resulting in the formation of several potentially toxic metabolites. Coumarin epoxide is thought to be highly unstable and has not been isolated synthetically or as a microsomal product. To address this issue, coumarin 3,4-epoxide was synthesized, and its stability and fate have been determined. Coumarin 3,4-epoxide was prepared by reacting coumarin with dimethyldioxirane. The epoxide was stable in organic solvents and survived conditions required for analysis by gas chromotography. Its structure was confirmed via 1H-NMR and gas chromatography-mass spectrometry-infrared spectroscopy (GC-MS-IR). In contrast, coumarin 3,4-epoxide was unstable in aqueous solution, converting within 20 sec to a ring-opened compound. Using GC-MS-IR analysis, the single coumarin 3,4-epoxide product was identified as o-hydroxyphenylacetaldehyde (o-HPA). Although other investigators have suggested that 3-hydroxycoumarin is an intermediate in o-HPA formation from coumarin 3,4-epoxide, we have demonstrated that 3-hydroxycoumarin, incubated in an aqueous system or with liver microsomal proteins, does not form o-HPA. Thus, the results of the present work establish that coumarin 3,4-epoxide can be synthesized and that o-HPA, which has previously been shown to be a prominent coumarin metabolite in rat liver microsomal incubations, is formed directly from coumarin 3,4-epoxide. These results suggest that both coumarin 3,4-epoxide and o-HPA may contribute to the hepatotoxicity of coumarin.     

A simulation methodology for heat and cold distribution in thermo-hydronic networks

This paper presents a simulation methodology to analyze hydronic heat distribution systems in a fast and user friendly way. As suggested in its name, the “Base Circuit Methodology” (BCM) is based on the observation that thermo-hydronic networks can be built up as a modular composition of elementary “Base Circuits” (BCs). Once the hydronic and thermodynamic behavior of such basic components is described in a set of dedicated equations, complex thermal distribution networks can easily be modeled by connecting the basic sub models. In addition to control performance simulations (accuracy, stability, speed) the BCM puts extra effort into energy efficiency analysis. In fact, every BC is a local sub unit in which heat flows are gathered, divided or changed in terms of temperature and/or flow. Therefore the BCM model setup yields the opportunity to analyze the net heat transport and its adaptations while crossing the network. Doing so, system designers get the efficiency variables more structured, leading to straightforward abilities to optimize heat and cold distribution. Practical examples prove the benefits of the methodology. Moreover, a test installation was built in which flows, pressures, and temperatures are confronted with the simulation results. The simulations are processed by means of the iterative equation solver EES (Engineering Equation Solver; ©F-chart) which has been experienced as a very compliant software package. As a result the methodology is delivered as a validated and open source library.     

Species by Environment Interactions Affect Pyrrolizidine Alkaloid Expression in <Emphasis Type="Italic">Senecio jacobaea</Emphasis>, <Emphasis Type="Italic">Senecio aquaticus</Emphasis>, and Their Hybrids

We examined the effects of water and nutrient availability on the expression of the defense pyrrolizidine alkaloids (PAs) in Senecio jacobaea and S. aquaticus. Senecio jacobaea, and S. aquaticus are adapted to different natural habitats, characterized by differing abiotic conditions and different selection pressures from natural enemies. We tested if PA concentration and diversity are plastic over a range of water and nutrient treatments, and also whether such plasticity is dependent on plant species. We also tested the hypothesis that hybridization may contribute to PA diversity within plants, by comparing PA expression in parental species to that in artificially generated F₁ hybrids, and also in later generation natural hybrids between S. jacobaea and S. aquaticus. We showed that total PA concentration in roots and shoots is not dependent on species, but that species determines the pattern of PA diversification. Pyrrolizidine alkaloid diversity and concentration are both dependent on environmental factors. Hybrids produce a putatively novel PA, and this PA is conserved in natural hybrids, that are backcrossed to S. jacobaea. Natural hybrids that are backcrossed several times to S. jacobaea are with regard to PA diversity significantly different from S. jacobaea but not from S. aquaticus, while F₁ hybrids are in all cases more similar to S. jacobaea. These results collectively suggest that PA diversity is under the influence of natural selection.     

Compact high-resolution spaceborne echelle grating spectrometer with acousto-optical tunable filter based order sorting for the infrared domain from 2.2 to 4.3 microm

A new compact spaceborne high-resolution spectrometer developed for the European Space Agency's Venus Express spacecraft is described. It operates in the IR wavelength range of 2.2 to 4.3 microm and measures absorption spectra of minor constituents in the Venusian atmosphere. It uses a novel echelle grating with a groove density of 4 lines/mm in a Littrow configuration in combination with an IR acousto-optic tunable filter for order sorting and an actively cooled HgCdTe focal plane array of 256 by 320 pixels. It is designed to obtain an instrument line profile of 0.2 cm(-1). First results on optical and spectral properties are reported.