A high affinity, antidote-controllable prothrombin and thrombin-binding RNA aptamer inhibits thrombin generation and thrombin activity: An antidote-controllable prothrombin RNA aptamer

The conversion of prothrombin to thrombin is one of two non-duplicated enzymatic reactions during coagulation. Thrombin has long been considered an optimal anticoagulant target because it plays a crucial role in fibrin clot formation by catalyzing the cleavage of fibrinogen, upstream coagulation cofactors, and platelet receptors. Although a number of anti-thrombin therapeutics exist, it is challenging to use them clinically due to their propensity to induce bleeding. Previously, we isolated a modified RNA aptamer (R9D-14) that binds prothrombin with high affinity and is a potent anticoagulant in vitro

Multi-Scale Modeling of HIV Infection in vitro and APOBEC3G-Based Anti-Retroviral Therapy

The human APOBEC3G is an innate restriction factor that, in the absence of Vif, restricts HIV-1 replication by inducing excessive deamination of cytidine residues in nascent reverse transcripts and inhibiting reverse transcription and integration. To shed light on impact of A3G-Vif interactions on HIV replication, we developed a multi-scale computational system consisting of intracellular (single-cell), cellular and extracellular (multicellular) events by using ordinary differential equations. The single-cell model describes molecular-level events within individual cells (such as production and degradation of host and viral proteins, and assembly and release of new virions), whereas the multicellular model describes the viral dynamics and multiple cycles of infection within a population of cells. We estimated the model parameters either directly from previously published experimental data or by running simulations to find the optimum values. We validated our integrated model by reproducing the results of in vitro T cell culture experiments. Crucially, both downstream effects of A3G (hypermutation and reduction of viral burst size) were necessary to replicate the experimental results in silico. We also used the model to study anti-HIV capability of several possible therapeutic strategies including: an antibody to Vif; upregulation of A3G; and mutated forms of A3G. According to our simulations, A3G with a mutated Vif binding site is predicted to be significantly more effective than other molecules at the same dose. Ultimately, we performed sensitivity analysis to identify important model parameters. The results showed that the timing of particle formation and virus release had the highest impacts on HIV replication. The model also predicted that the degradation of A3G by Vif is not a crucial step in HIV pathogenesis

Industrial applications of powder x-ray diffraction analysis to the TiH/sub x/-KCLO/sub 4/ pyrotechnic system

Powder x-ray diffraction techniques were utilized in the evaluation of locally synthesized TiH/sub x/ materials to assist in evolving the best method for preparing such hydride materials, in the production of baseline data for TiH/sub x/ and KClO/sub 4/ starting materials, and in the determination of the phases present in their various blends. Such methods concurrently afforded routine support for other project teams investigating container and bridgewire corrosion phenomena, material and device handling and storage factors, alternative milling and blending effects, particle size classification consequences, reaction product identification, etc. A 12-kW rotating anode x-ray generator was used in the effort. A reference pattern was obtained for the nonstoichiometric fluorite-structured ..gamma..-TiH/sub 2-y/ phase. A quality lattice parameter as a function of stoichiometry curve was deduced from the phase analyses. Detection limits of minor amounts of various substances were also assessed. 9 tables. (DLC