CardS4: modal theorem proving on Java smart cards, Journal of Telecommunications and Information Technology, 2002, nr 4

We describe a successful implementation of a theorem prover for modal logic S4 that runs on a Java smart card with only 512 KBytes of RAM and 32 KBytes of EEPROM. Since proof search in S4 can lead to infinite branches, this is “proof of principle” that non-trivial modal deduction is feasible even on current Java cards. We hope to use this prover as the basis of an on-board security manager for restricting the flow of “secrets” between multiple applets residing on the same card, although much work needs to be done to design the appropriate modal logics of “permission” and “obligations”. Such security concerns are the major impediments to the commercial deployment of multi-application smart cards

Effects of the Metal Ion on the Mechanism of Phosphodiester Hydrolysis Catalyzed by Metal-Cyclen Complexes

In this study, mechanisms of phosphodiester hydrolysis catalyzed by six di- and tetravalent metal-cyclen (M-C) complexes (Zn-C, Cu-C, Co-C, Ce-C, Zr-C and Ti-C) have been investigated using DFT calculations. The activities of these complexes were studied using three distinct mechanisms: (1) direct attack (DA), (2) catalyst-assisted (CA), and (3) water-assisted (WA). All divalent metal complexes (Zn-C, Cu-C and Co-C) coordinated to the BNPP substrate in a monodentate fashion and activated its scissile phosphoester bond. However, all tetravalent metal complexes (Ce-C, Zr-C, and Ti-C) interacted with BNPP in a bidentate manner and strengthened this bond. The DAmechanism was energetically the most feasible for all divalent M-C complexes, while the WAmechanism was favored by the tetravalent complexes, except Ce-C. The divalent complexes were found to be more reactive than their tetravalent counterparts. Zn-C catalyzed the hydrolysis with the lowest barrier among all M-C complexes, while Ti-C was the most reactive tetravalent complex. The activities of Ce-C and Zr-C, except Ti-C, were improved with an increase in the coordination number of the metal ion. The structural and mechanistic information provided in this study will be very helpful in the development of more efficient metal complexes for this critical reaction

An Extended Polyanion Activation Surface in Insulin Degrading Enzyme

Insulin degrading enzyme (IDE) is believed to be the major enzyme that metabolizes insulin and has been implicated in the degradation of a number of other bioactive peptides, including amyloid beta peptide (Aβ), glucagon, amylin, and atrial natriuretic peptide. IDE is activated toward some substrates by both peptides and polyanions/anions, possibly representing an important control mechanism and a potential therapeutic target. A binding site for the polyanion ATP has previously been defined crystallographically, but mutagenesis studies suggest that other polyanion binding modes likely exist on the same extended surface that forms one wall of the substrate-binding chamber. Here we use a computational approach to define three potential ATP binding sites and mutagenesis and kinetic studies to confirm the relevance of these sites. Mutations were made at four positively charged residues (Arg 429, Arg 431, Arg 847, Lys 898) within the polyanion-binding region, converting them to polar or hydrophobic residues. We find that mutations in all three ATP binding sites strongly decrease the degree of activation by ATP and can lower basal activity and cooperativity. Computational analysis suggests conformational changes that result from polyanion binding as well as from mutating residues involved in polyanion binding. These findings indicate the presence of multiple polyanion binding modes and suggest the anion-binding surface plays an important conformational role in controlling IDE activity

Application of nanotechnology to herbal antioxidants as improved phytomedicine: An expanding horizon.

Phytotherapy, based on medicinal plants, have excellent potential in managing several diseases. A vital part of the healthcare system is herbal medicines, consisting of therapeutic agents with high safety profile and no or least adverse effects. Herbs or medicinal plants show anticancer, antioxidant, and gene-protective activity, which is useful for pharmaceutical industries. In vitro, the extract of antioxidant compounds prevents the growth of colon and liver cancer cells, followed by a dose-dependent method. The screening of extracts is done by using in vitro models. Reactive oxygen species (ROS) and free radicals lead to diseases based on age which promotes oxidative stress. Different types of ROSs available have central roles in the normal physiology and functioning of processes. Herbal or traditional plant medicines have rich antioxidant activity. Despite the limited literature on the health effect of herbal extract or spices. There are many studies examining the encouraging health effects of single phytochemicals instigating from the medicinal plant. This review provides a detailed overview on herbal antioxidants and how application of nanotechnology can improve its biological activity in managing several major diseases, and having no reported side effects

Disulfide Bridges Remain Intact while Native Insulin Converts into Amyloid Fibrils

Amyloid fibrils are β-sheet-rich protein aggregates commonly found in the organs and tissues of patients with various amyloid-associated diseases. Understanding the structural organization of amyloid fibrils can be beneficial for the search of drugs to successfully treat diseases associated with protein misfolding. The structure of insulin fibrils was characterized by deep ultraviolet resonance Raman (DUVRR) and Nuclear Magnetic Resonance (NMR) spectroscopy combined with hydrogen-deuterium exchange. The compositions of the fibril core and unordered parts were determined at single amino acid residue resolution. All three disulfide bonds of native insulin remained intact during the aggregation process, withstanding scrambling. Three out of four tyrosine residues were packed into the fibril core, and another aromatic amino acid, phenylalanine, was located in the unordered parts of insulin fibrils. In addition, using all-atom MD simulations, the disulfide bonds were confirmed to remain intact in the insulin dimer, which mimics the fibrillar form of insulin

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events

Low hydrocarbon solubility polymers: plasticization-resistant membranes for carbon dioxide removal from natural gas

Hydrocarbon polymers developed for CO2 removal from natural gas often lose their superior separation ability at field conditions. This deterioration in performance is primarily a result of polymer plasticization by natural gas components like higher hydrocarbons, which have high solubilities in these polymers. Polymers that have low solubilities for higher hydrocarbons may be less susceptible to plasticization by these penetrants and therefore exhibit more stable separation properties in actual field conditions. This study was undertaken to investigate the above premise through identification of low-hydrocarbon-solubility polymers and performing a fundamental study to assess the potential of such materials to be stable membranes for CO2 removal from natural gas. Hydrocarbon and fluorocarbon gas solubility measurements in hydrocarbon polymers and fluoropolymers reveal that interactions between hydrocarbon and fluorocarbon species result in lower solubilities of hydrocarbons in fluorocarbon polymers, and vice versa, than expected on the basis of empirical correlations. The influence of these interactions on gas permeability is greater in lower free volume materials. Interestingly, hydrocarbon solubility in fluoropolymers increases much less with increasing penetrant condensability than in hydrocarbon polymers, implying that large hydrocarbon compounds will exhibit much lower solubility in fluoropolymers than in hydrocarbon polymers. A commercial fluoropolymer, Hyflon AD 80, has much higher CO2 permeability than typical hydrocarbon polymers, but its CO2/CH4 selectivity is lower than these polymers. However, Hyflon AD 80 exhibits more stable gas separation properties than typical hydrocarbon polymers in the presence of CO2 and moderate amounts of large hydrocarbons. Materials selection guidelines for using fluoropolymers as plasticization-resistant coatings on existing hydrocarbon membranes require the fluoropolymer to have a lower ratio of higher hydrocarbon to CO2 (or CH4) solubility than the hydrocarbon polymer. The guidelines also require the coating to have a similar, or greater, diffusivity selectivity (size-selectivity) for gases than that of the hydrocarbon polymer. Permeability of highly condensable penetrants is often a function of their sorbed concentration in the polymer. A model is presented to rationally predict concentration and temperature dependent gas permeability in rubbery polymers, based on limited experimental data. The model satisfactorily describes vapor permeation in a commercial membrane, poly(dimethyl siloxane), and in poly(ethylene).Chemical Engineerin

Computational insights into the development of novel therapeutic strategies for Alzheimer's disease

β-amyloidosis and oxidative stress have been implicated as root causes of Alzheimer's disease (AD). Current potential therapeutic strategies for the treatment of AD include inhibition of amyloid β (Aβ) production, stimulation of Aβ degradation and prevention of Aβ oligomerization. However, efforts in this direction are hindered by the lack of understanding of the biochemical processes occurring at the atomic level in AD. A radically different approach to achieve this goal would be the application of comprehensive theoretical and computational techniques such as molecular dynamics, quantum mechanics, hybrid quantum mechanics/molecular mechanics, bioinformatics and rotational spectroscopy to investigate complex chemical and physical processes in β-amyloidosis and the oxidative stress mechanism. Results obtained from these studies will provide an atomic level understanding of biochemical processes occurring in AD and advance efforts to develop effective therapeutic strategies for this disease