4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone, a second-generation antineoplastic agent of the alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazone series

4-Methyl-5-amino-1-formylisoquinoline thiosemicarbazone (MAIQ-1) was studied to determine its potential for clinical trail as a second-generation antineoplastic agent of the alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazone class. MAIQ-1 was shown to be among the most potent known inhibitors of the major target for the expression of antineoplastic activity by this class of agents, the enzyme ribonucleoside diphosphate reductase, requiring only 0.06 micronM for 50% inhibition. This potency at the enzymatic level was consistent with its antineoplastic activity against the murine neoplasms Sarcoma 180, Leukemia L1210, Leukemia P388, and the B16 melanoma. The acetylation of the 5-amino group of the model substrate 5-amino-1,4-dimethylisoquinoline was lower than that of 5-amino-1-methylisoquinoline when incubated with acetyl-coenzyme A and rat liver homogenate. This finding suggests that the presence of the 4-methyl function offers steric hinderance to enzymatic substitution of the adjacent 5-amino group. In vivo metabolism of MAIQ-1 in mice, studied with [3'-14C]MAIQ-1 showed that relatively slow excretion of this agent occurred, since the cumulative urinary excretion of radioactivity was only 35% in 48 HR. About 51% of excreted urinary radioactivity was present in chromatograms in an area corresponding to the iron chelate of MAIQ-1, and only a minor quantity of material migrating like acetylated MAIQ-1 was present in urine, a finding consistent with enzymatic data with liver homogenates. The results indicate that MAIQ-1 has the antineoplastic activity, enzyme inhibitory potency, and relative resistance to metabolic inactivation required of an agent of this class for clinical trials.     

BRDF Representation and Acquisition

Photorealistic rendering of real world environments is important in a range of different areas; including Visual Special effects, Interior/Exterior Modelling, Architectural Modelling, Cultural Heritage, Computer Games and Automotive Design. Currently, rendering systems are able to produce photorealistic simulations of the appearance of many real‐world materials. In the real world, viewer perception of objects depends on the lighting and object/material/surface characteristics, the way a surface interacts with the light and on how the light is reflected, scattered, absorbed by the surface and the impact these characteristics have on material appearance. In order to re‐produce this, it is necessary to understand how materials interact with light. Thus the representation and acquisition of material models has become such an active research area. This survey of the state‐of‐the‐art of BRDF Representation and Acquisition presents an overview of BRDF (Bidirectional Reflectance Distribution Function) models used to represent surface/material reflection characteristics, and describes current acquisition methods for the capture and rendering of photorealistic materials.     

Partial Conductivities in SrTiO3: Bulk Polarization Experiments, Oxygen Concentration Cell Measurements, and Defect-Chemical Modeling

Knowledge of the exchange kinetics of O₂ in SrTiO₃ allows us to design appropriate strategies to separate the ionic and the electronic conductivity. In the low-temperature range, where the overall surface reaction is very slow compared to bulk diffusion and measuring time, electrochemical cells of the type Pt|SrTiO₃|Pt are self-blocking and self-sealing and a Wagner–Hebb-type polarization succeeds without the necessity of using selectively blocking electrodes. In the present study the ionic conductivity data obtained for Feand Ni-doped SrTiO₃ in this way are compared to data obtained from the analysis of the oxygen partial pressure dependence of the total conductivity as well as to defect chemical calculations. In complete contrast to the low temperature situation, at high temperatures, where the surface reaction is fast, the emf technique is conveniently applicable. Results are presented for Pt, O₂|SrTiO₃|O₂, Pt cells. The conductivity behavior of SrTi(Fe)O₃ as a function of temperature (20°–1000°C) is complex, due to partially frozen-in equilibria, but even details can be quantitatively understood in terms of a simple defect chemistry. The turnover of the diffusion-controlled regime to the surface reaction-controlled regime can be shifted to significantly lower temperatures by using YBa₂Cu₃O_7–8 electrodes.     

A method for estimating the accuracy of quadrature output sensors

The errors of quadrature signal interpolation are analyzed. Quantitative assessment of the noise effect and the quadrature signal distortion is given. A method for estimating the accuracy of quadrature output sensors is proposed.     

In situ Profiles of Oxygen Diffusion in SrTiO3: Bulk Behavior and Boundary Effects

Diffusion profiles have been recorded in situ and evaluated using an optical technique. In this way, bulk diffusion coefficients have been reliably and quantitatively measured. It is shown that the values agree with calculations without using adjustable parameters if the coupling of the diffusing species to internal redox changes of the dopants is accounted for. Measurements on single crystals and on bicrystals with and without crack formation provide worthwhile information on the influence of free relaxed surfaces, freshly produced (crack) surfaces, and grain boundaries on the surface reaction rate and diffusional process. The inward diffusion of oxygen via crack surfaces is characterized by enhanced diffusion coefficients.     

Lower bounds on memory requirements for statically scheduled DSP programs

This paper presents novel techniques for computing the minimum number of memory locations in statically scheduled digital signal processing (DSP) programs. Two related problems are considered. In the first problem, we compute the minimum number of memory locations required for a scheduled program assuming that no circuit transformations (such as pipelining and retiming) are to be performed after scheduling. For this problem, we consider memory minimization for theoperation-constrained, processor-constrained andunconstrained memory models which represent various restrictions on how data can be allocated to memory. Then we consider the second problem, where memory minimization for a scheduled program is considered simultaneously with retiming using a variation of the retiming problem referred to as theminimum physical storage location (MPSL) retiming. While both problems consider memory minimization for scheduled programs, the second problem minimizes memory using retiming whereas the first problem performs no retiming. The scheduling results obtained from the MARS design system are used to compare memory requirements in the context of both of these problems. Our experiments show that MARS performs an optimal retiming for the schedule it generates. These memory requirements are then compared with an integer linear programming solution to the scheduling problem which is optimal under the unconstrained memory model. It is concluded that the schedule obtained by the MARS system achieves optimality or near-optimality with respect to register minimization.     

Different Roles of p62 (SQSTM1) Isoforms in Keratin-Related Protein Aggregation

p62/Sequestosome-1 (p62) is a multifunctional adaptor protein and is also a constant component of disease-associated protein aggregates, including Mallory–Denk bodies (MDBs), in steatohepatitis and hepatocellular carcinoma. We investigated the interaction of the two human p62 isoforms, p62-H1 (full-length isoform) and p62-H2 (partly devoid of PB1 domain), with keratins 8 and 18, the major components of MDBs. In human liver, p62-H2 is expressed two-fold higher compared to p62-H1 at the mRNA level and is present in slightly but not significantly higher concentrations at the protein level. Co-transfection studies in CHO-K1 cells, PLC/PRF/5 cells as well as p62⁻ total-knockout and wild-type mouse fibroblasts revealed marked differences in the cytoplasmic distribution and aggregation behavior of the two p62 isoforms. Transfection-induced overexpression of p62-H2 generated large cytoplasmic aggregates in PLC/PRF/5 and CHO-K1 cells that mostly co-localized with transfected keratins resembling MDBs or (transfection without keratins) intracytoplasmic hyaline bodies. In fibroblasts, however, transfected p62-H2 was predominantly diffusely distributed in the cytoplasm. Aggregation of p62-H2 and p62ΔSH2 as well as the interaction with K8 (but not with K18) involves acquisition of cross-β-sheet conformation as revealed by staining with luminescent conjugated oligothiophenes. These results indicate the importance of considering p62 isoforms in protein aggregation disease.     

Design of a Zero‐Gap Laboratory‐Scale Polymer Electrolyte Membrane Alkaline Water Electrolysis Stack

The development of a zero‐gap alkaline water electrolysis stack based on a heterogeneous anion‐selective polymer electrolyte membrane is reported. A bipolar electrode arrangement was selected as the most appropriate one. The design was targeted to verify the suitability of the membrane electrode assembly design and the functionality of the gas separator system developed together with the purity of the gases produced. The influence of various operational regimes on the purity of the gases was investigated. Last, but not least, a validation of the mathematical model to be used for scale‐up of the cell, foreseen for the next step of the project, was performed.