Identification of 3,4-Dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine Derivatives as Novel Selective Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase

Plasmodium falciparum’s resistance to available antimalarial drugs highlights the need for the development of novel drugs. Pyrimidine de novo biosynthesis is a validated drug target for the prevention and treatment of malaria infection. P. falciparum dihydroorotate dehydrogenase (PfDHODH) catalyzes the oxidation of dihydroorotate to orotate and utilize ubiquinone as an electron acceptor in the fourth step of pyrimidine de novo biosynthesis. PfDHODH is targeted by the inhibitor DSM265, which binds to a hydrophobic pocket located at the N-terminus where ubiquinone binds, which is known to be structurally divergent from the mammalian orthologue. In this study, we screened 40,400 compounds from the Kyoto University chemical library against recombinant PfDHODH. These studies led to the identification of 3,4-dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine and its derivatives as a new class of PfDHODH inhibitor. Moreover, the hit compounds identified in this study are selective for PfDHODH without inhibition of the human enzymes. Finally, this new scaffold of PfDHODH inhibitors showed growth inhibition activity against P. falciparum 3D7 with low toxicity to three human cell lines, providing a new starting point for antimalarial drug development.     

Imaging "invisible" dopant atoms in semiconductor nanocrystals

Nanometer-scale semiconductors that contain a few intentionally added impurity atoms can provide new opportunities for controlling electronic properties. However, since the physics of these materials depends strongly on the exact arrangement of the impurities, or dopants, inside the structure, and many impurities of interest cannot be observed with currently available imaging techniques, new methods are needed to determine their location. We combine electron energy loss spectroscopy with annular dark-field scanning transmission electron microscopy (ADF-STEM) to image individual Mn impurities inside ZnSe nanocrystals. While Mn is invisible to conventional ADF-STEM in this host, our experiments and detailed simulations show consistent detection of Mn. Thus, a general path is demonstrated for atomic-scale imaging and identification of individual dopants in a variety of semiconductor nanostructures.     

Global/local analysis of composite plates with cutouts

 The study focuses on the development of a simple and accurate global/local method for calculating the static response of stepped, simply-supported, isotropic and composite plates with circular and elliptical cutouts. The approach primarily involves two steps. In the first step a global approach, the Ritz method, is used to calculate the response of the structure. Displacement based Ritz functions for the plate without the cutout are augmented with a perturbation function, which is accurate for uniform thickness plates only, to account for the cutout. The Ritz solution does not accurately satisfy the natural boundary conditions at the cut-out boundary, nor does it accurately model the discontinuities caused by abrupt thickness changes. Therefore, a second step, local in nature is taken in which a small area in the vicinity of the hole and encompassing other points of singularities is discretized using a fine finite element mesh. The displacement boundary conditions for the local region are obtained from the global Ritz analysis. The chosen perturbation function is reliable for circular cutout in uniform plates, therefore elliptical cutouts were suitably transformed to circular shapes using conformal mapping. The methodology is then applied to the analysis of composite plates, and its usefulness successfully proved in such cases. The proposed approach resulted in accurate prediction of stresses, with considerable savings in CPU time and data storage for composite flat panels.     

Mucosal microcirculation and angiogenesis in gastrointestinal tract

In this review, various aspects of gastrointestinal microcirculation were described. Endothelin-1, vasoconstrictor, is elevated in gastric mucosa, causes gastric ischemia and results in gastric ulceration in human and animals under physical stress. Vasodilators such as NO anticipate the alove actions of endothelin, and thereby protect mucosa from injury. Once ulcer is developed, angiogenesis plays a key role in its healing. Various growth factors, cyclooxygenases-1 and -2, and non-peptide angiogenic factors stimulate this phenomenon and participate in ulcer healing. However, acidic conditions, H. pylori and its product, ammonia, suppress angiogenesis in vitro and in vivo. These evidences may explain why ulcer heals so slowly in gastroduodenal mucosa.     

Performance analysis of dynamic channel assignment algorithms in cellular mobile systems with hand‐off

In this paper, the traffic performance of dynamic channel assignment (DCA) in cellular mobile system with hand‐off is investigated. A traffic model for cellular system incorporating hand‐off is established first. Under the framework of the model, a hand‐off priority scheme is developed to reduce the forced termination of calls in progress. This paper analyses and derives the traffic performance bound for DCA strategies with hand‐off by extending the maximum packing (MP) scheme to include the hand‐off procedure. For practical implementation, a distributed DCA algorithm (DDCA) is also proposed. A non‐priority scheme and the proposed priority scheme can be combined with either MP or DDCA. It is shown that the simulation results of DDCA scheme are comparable with the analytical bounds given by MP for both the non‐prioritized case and prioritized case. A reasonable trade‐off between the new call blocking probability and forced termination probability can be achieved by using the proposed prioritized scheme in DCA. Copyright © 2002 John Wiley & Sons, Ltd.     

Reliability analysis of shuffle-exchange network systems

Shuffle-exchange networks (SENs) have been widely considered as practical interconnection systems due to their size of its switching elements (SEs) and uncomplicated configuration. SEN is a network among a large class of topologically equivalent multistage interconnection networks (MINs) that includes omega, indirect binary n-cube, baseline, and generalized cube. In this paper, SEN with additional stages that provide more redundant paths are analyzed. A common network topology with a 2×2 basic building block in a SEN and its variants in terms of extra-stages is investigated. As an illustration, three types of SENs are compared: SEN, SEN with an additional stage (SEN+), and SEN with two additional stages (SEN+2). Finally, three measures of reliability: terminal, broadcast, and network reliability for the three SEN systems are analyzed.     

Growth, structure, and properties of BiFeO3/-BiCrO3 films obtained by dual cross beam PLD

The properties of epitaxial Bi(2)FeCrO(6) thin films, recently synthesized by pulsed laser deposition, have partially confirmed the theoretical predictions (i.e., a magnetic moment of 2 micro(B) per formula unit and a polarization of approximately 80 microC/cm(2) at 0 K). The existence of magnetic ordering at room temperature for this material is an unexpected, but very promising, result that needs to be further investigated. Because magnetism is assumed to arise from the exchange interaction between the Fe and Cr cations, the magnetic behavior is strongly dependent on both their ordering and the distance between them. We present here the successful synthesis of epitaxial Bi(2)Fe(x)CryO(6) (BFCO x/y) films grown on SrTiO3 substrates using dual crossed-beam, pulsed-laser deposition. The crystal structure of the films has different types of (111)-oriented superstructures, depending on the deposition conditions. The multiferroic character of BFCO (x/y) films is proven by the presence of both ferroelectric and magnetic hysteresis at room temperature. The oxidation state of Fe and Cr ions in the films is shown to be 3+ only, and the difference in macroscopic magnetization with Fe/Cr ratio composition could only be due to ordering of the Cr(3+) and Fe(3+) cations to the modification of the exchange interaction between them.     

Effect of Nickel-Cobalt-Zinc Ferrite Filler on Electrical and Mechanical Properties of Thermoplastic Natural Rubber Composites

Thermoplastic natural rubber (TPNR) as polymer matrix was prepared by the melt blending method. Nickel-cobalt-zinc (NiCoZn) ferrite as a filler was prepared by the double-stage sintering method in air. The filler was incorporated in the polymer matrix using a Brabender internal mixer. The filler content was varied from 0 to 30 wt.%. The morphological study of the fractured surface using a scanning electron microscope (SEM) shows the effects of strain. The X-ray diffraction (XRD) indicates the coexistence of both the ferrite and thermoplastic. Electrical properties were studied using a high frequency response analyzer (HFRA) at room temperature (298°K). The results show that resistivity (ρ) decreases, but the dielectric constant increases, with increasing filler content. The resistivity and dielectric constant for all the composites are in the range of 8.9 × 10⁶–9.7 × 10⁵ Ωm and 33–72, respectively. A sharp change in both quantities around 15 wt.% filler content is interpreted as due to the transition from a dispersed system to an attached system. The tensile study shows that the elongation at break point and the tensile strength of the composite at room temperature decrease with increasing filler content. The hardness of the samples decreases with increasing filler content.     

Efficient Organic Photovoltaic Cells Based on Nanocrystalline Mixtures of Boron Subphthalocyanine Chloride and C60

The electrical and structural behavior of uniformly mixed films of boron subphthalocyanine chloride (SubPc) and C₆₀ and their performance in organic photovoltaic cells is explored. Device performance shows a strong dependence on active‐layer donor–acceptor composition, and peak efficiency is realized at 80 wt.% C₆₀. The origin of this C₆₀‐rich optimum composition is elucidated in terms of morphological changes in the active layer upon diluting SubPc with C₆₀. While neat SubPc is found to be amorphous, mixed films containing 80 wt.% C₆₀ show clear nanocrystalline domains of SubPc. Supporting electrical characterization indicates that this change in morphology coincides with an increase in the hole mobility of the SubPc:C₆₀ mixture, with peak mobility observed at a composition of 80 wt.% C₆₀. Organic photovoltaic cells constructed using this optimum SubPc:C₆₀ ratio realize a power conversion efficiency of (3.7 ± 0.1)% under 100 mW cm^?2 simulated AM1.5G solar illumination.