The mouse homolog of the human Miller-Dieker chromosomal region (MDCR) maps to mouse chromosome 11 in close proximity to Mov9 and D11Nds1

Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 have been shown to stimulate the synthesis of acute-phase proteins; however, few studies have examined the effect of these cytokines on gluconeogenesis. We investigated the effects of these cytokines on gluconeogenesis in primary cultures of rat hepatocytes. Incubation of hepatocytes for 24 hours with TNF-alpha or IL-1 alpha did not affect gluconeogenesis. Hepatocytes incubated with 100 pmol/L and 1 nmol/L IL-6 had a dose-dependent increase (P < .05) in gluconeogenesis (2.6 +/- 0.1 and 3.2 +/- 0.1 pmol/10(6) cells/min, respectively) as compared with controls (2.0 +/- 0.1).     

Microstructure and mechanical properties of modified and non-modified stir-cast Al-Si hypoeutectic alloys

The microstructure and mechanical properties of modified and non-modified stir-cast commercial aluminium alloys A-S7G03 and A-S4G have been investigated. Stir casting of these alloys resulted in spherical and/or rosette shape primary -phase, and the eutectic silicon was broken into miniature needle morphology. This stir-cast structure slightly improved the mechanical properties in comparison to those of conventionally cast alloys, however the fracture of the stir-cast alloys revealed intergranular brittle fracture. The addition of 0.02% strontium, in the form of Al-5 mass% Sr master alloy, during stir casting modified the eutectic silicon into a very fine spheroidal morphology, while the -phase particle showed the same morphology as the stir-cast alloys. This novel structure resulted in significant improvement of mechanical properties. The elongation of the modified stir-cast alloys was five times greater than that of the non-modified one. A transgranular mode of fracture was observed for the modified stircast alloys, moreover smooth ripple and dimple patterns were observed reflecting the high ductility of the modified stir-cast alloys.     

Calcium carbonate and ammonium polyphosphate flame retardant additives formulated to protect ethylene vinyl acetate copolymer against fire: Hydrated or carbonated calcium?

In this study, the effect of the chemical nature of different calcium (Ca)-based minerals as flame retardant additives in combination with ammonium polyphosphate (APP), in 1:1 proportions, on the flame retardancy behavior and performance of ethylene vinyl acetate copolymer was discussed. Combining APP with partly and completely hydrated calcium oxide led to superior flame-retardant function detected in mass loss calorimeter measurements with respect to the corresponding system containing carbonated calcium. This privileged character was attributed to the higher reactivity of hydrated Ca-based fillers toward APP in comparison with Ca carbonate, which induced the formation of an intumescent residue. The difference between reactivity potential of hydrated and dry Ca was demonstrated by the newly formed thermally stable species, and further evidenced by thermogravimetric analysis performed on APP/fillers blends. Moreover, the presence of more crystalline domains in the Ca/phosphorus-based compounds was evidenced by XRD analysis of the mass loss calorimeter test residues. The results of this work highlight the role of blend additive systems on the performance of flame retardancy of polymer materials.     

Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2

Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PL^pro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide ( 2 b ), which is known to bind into the S3 and S4 pockets of the SARS-CoV PL^pro. Moreover, we report the discovery of isoindolines as a new class of potent PL^pro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PL^pro are valuable starting points for the development of new pan-coronaviral inhibitors.     

Development of Covalent Chitosan-Polyethylenimine Derivatives as Gene Delivery Vehicle: Synthesis,Characterization, and Evaluation

There is an increasing interest in cationic polymers as important constituents of non-viral gene delivery vectors. In the present study, we developed a versatile synthetic route for the production of covalent polymeric conjugates consisting of water-soluble depolymerized chitosan (dCS; M_W 6–9 kDa) and low molecular weight polyethylenimine (PEI; 2.5 kDa linear, 1.8 kDa branched). dCS-PEI derivatives were evaluated based on their physicochemical properties, including purity, covalent bonding, solubility in aqueous media, ability for DNA condensation, and colloidal stability of the resulting polyplexes. They were complexed with non-integrating DNA vectors coding for reporter genes by simple admixing and assessed in vitro using liver-derived HuH-7 cells for their transfection efficiency and cytotoxicity. Using a rational screening cascade, a lead compound was selected (dCS-Suc-LPEI-14) displaying the best balance of biocompatibility, cytotoxicity, and transfection efficiency. Scale-up and in vivo evaluation in wild-type mice allowed for a direct comparison with a commercially available non-viral delivery vector (in vivo-jetPEI). Hepatic expression of the reporter gene luciferase resulted in liver-specific bioluminescence, upon intrabiliary infusion of the chitosan-based polyplexes, which exceeded the signal of the in vivo jetPEI reference formulation by a factor of 10. We conclude that the novel chitosan-derivative dCS-Suc-LPEI-14 shows promise and potential as an efficient polymeric conjugate for non-viral in vivo gene therapy.     

Development of poly(vinyl chloride)/wood composites. A literature review

Poly(vinyl chloride)/wood fiber (flour) composites are currently experiencing a dramatic increase in use. Most of them are used to produce window/door profiles, decking, railing, and siding by using conical counterrotating intermeshing twin‐screw extruders. Heat stabilizers, processing aids, impact modifiers, lubricants, and pigments are still important for PVC/wood composite formulations. Poly[methylene(polyphenyl isocyanate)] (PMPPIC), γ‐aminopropyltriethoxysilane, maleated polypropylene (MAPP), and copper metallic complex have proved to be effective coupling agents for this composite system. Mechanical properties of PVC/wood composites can be enhanced by combining wood with mica or glass fibers to form hybrid reinforcements. Ultraviolet light resistance and weathering dimensional stabilities of PVC/wood composites are superior to those of natural wood. Density reduction can be achieved through the microcellular foaming technique by using chemical blowing agents, such as azodicarbonamide and sodium bicarbonate, or physical blowing agents, such as carbon dioxide. J. Vinyl Addit. Technol. 10:59–69, 2004. © 2004 Society of Plastics Engineers.     

Scalable,low complexity,and fast greedy scheduling heuristics for highly heterogeneous distributed computing systems

For heterogeneous distributed computing systems, important design issues are scalability and system optimization. Given such systems, it is crucial to develop low computational complexity algorithms to schedule tasks in a manner that exploits the heterogeneity of the resources and applications. In this paper, we report and evaluate three scalable, and fast scheduling heuristics for highly heterogeneous distributed computing systems. We conduct a comprehensive performance evaluation study using simulation. The benchmarking outlines the performance of the schedulers, representing scalability, makespan, flowtime, computational complexity, and memory utilization. The set of experimental results shows that our heuristics perform as good as the traditional approaches, for makespan and flowtime, while featuring lower complexity, lower running time, and lower used memory. The experimental results also detail the various scenarios under which certain algorithms excel and fail.     

Alkaline fuel cells: contemporary advancement and limitations

ZeTek Power recently introduced mass manufacturable and cost effective alkaline fuel cells on the market. Today's research is focused on further improvement both in terms of performance increase and cost reduction. This research is classically performed using small (4 cm²) experimental electrodes in the half-cell configuration. This allows the primary electrochemical losses in an anode or cathode to be determined independently. Additional performance losses occur when one integrates large electrodes into a module of 24 cells and in a stack comprised of many modules. By comparing the performance of half-cell experiments to that of modules, these losses can be distinguished and addressed. The information thus obtained, both for the small electrodes and in up-scaling is vital if one is to identify the key areas in which improvement is possible and where to focus future research. Furthermore, the identification of the losses in a module and system allows us to predict the final performance from half-cell measurements of a new laboratory scale experimental electrode.     

Induction of DNA-double-strand breaks by auger electrons from 99mTc complexes with DNA-binding ligands

The potential of certain Auger electron emitting nuclides for systemic radiotherapeutic applications has recently gained much attention. In particular, the ability of several nuclides, including 111In, 125I, and 123I, to induce DNA double-strand breaks (dsb), a good indicator of cytotoxicity, has been extensively studied. However, this ability has never previously been shown experimentally for 99mTc, which, besides the well-known gamma radiation that is used for diagnostic applications, also emits an average of 1.1 conversion electrons and 4 Auger or Coster-Kronig electrons per decay. Owing to the short range of Auger electrons, the radionuclide needs to be located very close to the DNA for dsb to occur. We synthesized two cationic 99mTcI-tricarbonyl complexes with pendant DNA binders, pyrene and anthraquinone. The X-ray crystal structures of the two complexes could be elucidated. Linear dichroism and UV/Vis spectroscopy revealed that the complex with pyrene intercalates DNA with a stability constant, K, of 1.1 x 10(6) M(-1), while the analogous complex with anthraquinone interacts with DNA in a groove-binding mode and has an affinity value of K=8.9 x 10(4) M(-1). We showed with phiX174 double-stranded DNA that the corresponding 99mTc complexes induce a significant amount of dsb, whereas non-DNA-binding [TcO4]- and nonradioactive Re compounds did not. These results indicate that the Auger electron emitter 99mTc can induce dsb in DNA when decaying in its direct vicinity and this implies potential for systemic radiotherapy with 99mTc complexes.