Binding of 2',5'-dideoxyadenosine to brain membranes. Comparison to P-site inhibition of adenylate cyclase

Membranes from rat cerebral cortex and striatum contain a relatively large number of high-affinity binding sites for [3H]2',5'-dideoxyadenosine, [3H]adenine arabinoside, and [3H]adenosine. The binding of [3H]2',5'-dideoxyadenosine and [3H]adenine arabinoside was virtually unaffected by relatively specific agonists and antagonists for adenosine receptors, such as 2-chloroadenosine, N6-phenylisopropyladenosine or theophylline. Binding of [3H]adenosine was partially blocked by such receptor ligands. The specific binding of all three ligands was antagonized by a variety of adenosine analogs which inhibit adenylate cyclase by interaction with the so-called P-site associated with this enzyme. However, potencies of adenosine analogs as P-site inhibitors of adenylate cyclase and as antagonists of binding do not correlate well. 5'-Methylthioadenosine had high potency and efficacy versus binding of [3H]2',5'-dideoxyadenosine but had virtually no effect on activity of adenylate cyclase. 2-Fluoroadenosine was less potent than adenosine as an antagonist of specific binding of [3H]2',5'-dideoxyadenosine, while 2-fluoroderivatives of adenosine, adenine arabinoside and adenine xylofuranoside were more potent than the parent compounds as P-site inhibitors. The significance of the binding sites for [3H]2',5'-dideoxyadenosine remains unclear, but their presence complicates the use of [3H]adenosine and certain analogs as ligands for adenosine membrane sites associated with adenylate cyclase.     

Contact angle of surfactant solutions on precipitated surfactant surfaces. II. Effects of surfactant structure,presence of a subsaturated surfactant,pH, and counterion/surfactant ratio

The contact angle of a saturated aqueous surfactant solution on the precipitate of that surfactant was measured by using the sessile drop method. The sodium and calcium salts of alkyl sulfates (C₁₂, C₁₄, and C₁₈) had advancing contact angles higher than those of alkyl trimethylammonium bromides (C₁₄, C₁₆, and C₁₈). The measured advancing contact angles for several surfactant solutions did not substantially change with varying surfactant/counterion ratios; therefore, the precipitating counterion concentration (e.g., water hardness) had little effect on the wettability. The contact angles of fatty acid (C₁₂ and C₁₆) solutions did not show any dependence on pH between a pH of 4 and 10. The contact angles of saturated calcium dodecanoate (CaC₁₂) solutions containing a second subsaturated surfactant (sodium dodecyl sulfate: NaDS) decreased with increasing NaDS concentrations until reaching the critical micelle concentration of the surfactant mixture. These results show that the second suractant can act as a wetting agent in this saturated surfactant system. Application of Young’s equation to contact angles showed that the solid/liquid surface tension can change substantially with surfactant concentration and be important in addition to the liquid/vapor surface tension in reducing contact angles. Application of the Zisman equation results in a “critical” surface tension for the CaC₁₂ or soap scum of 25.5 mN/m, which is comparable to difluoroethene.     

Machine Learning with Dimensionality Reduction for DDoS Attack Detection

With the advancement of internet, there is also a rise in cybercrimes and digital attacks. DDoS (Distributed Denial of Service) attack is the most dominant weapon to breach the vulnerabilities of internet and pose a significant threat in the digital environment. These cyber-attacks are generated deliberately and consciously by the hacker to overwhelm the target with heavy traffic that genuine users are unable to use the target resources. As a result, targeted services are inaccessible by the legitimate user. To prevent these attacks, researchers are making use of advanced Machine Learning classifiers which can accurately detect the DDoS attacks. However, the challenge in using these techniques is the limitations on capacity for the volume of data and the required processing time. In this research work, we propose the framework of reducing the dimensions of the data by selecting the most important features which contribute to the predictive accuracy. We show that the ‘lite’ model trained on reduced dataset not only saves the computational power, but also improves the predictive performance. We show that dimensionality reduction can improve both effectiveness (recall) and efficiency (precision) of the model as compared to the model trained on ‘full’ dataset.     

Multiphase Assembly of Small Molecule Microcrystalline Peptide Hydrogel Allows Immunomodulatory Combination Therapy for Long‐Term Heart Transplant Survival

Combination therapies that target multiple pathways involved in immune rejection of transplants hold promise for patients in need of restorative surgery. Herein, a noninteracting multiphase molecular assembly approach is developed to crystallize tofacitinib, a potent JAK1/3 inhibitor, within a shear‐thinning self‐assembled fibrillar peptide hydrogel network. The resulting microcrystalline tofacitinib hydrogel (MTH) can be syringe‐injected directly to the grafting site during surgery to locally deliver the small molecule. The rate of drug delivered from MTH is largely controlled by the dissolution of the encapsulated microcrystals. A single application of MTH, in combination with systemically delivered CTLA4‐Ig, a co‐stimulation inhibitor, affords significant graft survival in mice receiving heterotopic heart transplants. Locoregional studies indicate that the local delivery of tofacitinib at the graft site enabled by MTH is required for the observed enhanced graft survival.     

Optimization in development of acetaminophen syrup formulation

Formulation of acetaminophen syrup could be developed by an optimization technique to reduce the time and cost of study. Cosolvents were used in the formulation because of the low solubility of acetaminophen in water. They were composed of polyethylene glycol 4000, propylene glycol, sorbitol solution, and glycerin. Their effects on the solubility of acetaminophen and the pH of formulations were investigated. Effects on taste and price were calculated based on their properties. Simulation study of the effect of cosolvents upon the formulation scores was performed, using an algorithm based upon a simulated annealing concept to achieve the global optima and heuristic optimization concept to accelerate convergence. The program written as a Visual Basic module within Microsoft Access 97 was used to simulate and assess the optimal cosolvent amounts to achieve the most desirable formulations automatically according to the specified criteria. Formulators could customize the optimal formulation according to their needs and cost constraints by redefining the desirable outcomes in the source code of the program.     

Localization of adipose tissue embedded biliary tree vessels by use of near-infrared diffuse photon propagation models: a computational feasibility study

Biliary tree structures are embedded in adipose tissue and, therefore, cannot be visualized directly by the surgeon during cholecystectomy operations. This can lead to inadvertent injuries with serious complications for the patient. Computational studies were performed to assess the feasibility of noninvasively localizing these structures from spectrally resolved near-infrared reflectance measurements. Methodologies were developed for vessel localization, both on the adipose tissue surface and depthwise, by use of semi-infinite and two-layer models of diffuse photon propagation in tissues, respectively. The simulation results, along with some preliminary experimental measurements on tissue-simulating phantoms, prove the feasibility of these methods and show promise for their future clinical application.