VacSIM: Learning effective strategies for COVID-19 vaccine distribution using reinforcement learning.

A COVID-19 vaccine is our best bet for mitigating the ongoing onslaught of the pandemic. However, vaccine is also expected to be a limited resource. An optimal allocation strategy, especially in countries with access inequities and temporal separation of hot-spots, might be an effective way of halting the disease spread. We approach this problem by proposing a novel pipeline VacSIM that dovetails Deep Reinforcement Learning models into a Contextual Bandits approach for optimizing the distribution of COVID-19 vaccine. Whereas the Reinforcement Learning models suggest better actions and rewards, Contextual Bandits allow online modifications that may need to be implemented on a day-to-day basis in the real world scenario. We evaluate this framework against a naive allocation approach of distributing vaccine proportional to the incidence of COVID-19 cases in five different States across India (Assam, Delhi, Jharkhand, Maharashtra and Nagaland) and demonstrate up to 9039 potential infections prevented and a significant increase in the efficacy of limiting the spread over a period of 45 days through the VacSIM approach. Our models and the platform are extensible to all states of India and potentially across the globe. We also propose novel evaluation strategies including standard compartmental model-based projections and a causality-preserving evaluation of our model. Since all models carry assumptions that may need to be tested in various contexts, we open source our model VacSIM and contribute a new reinforcement learning environment compatible with OpenAI gym to make it extensible for real-world applications across the globe.

Chitosan coated synergistically engineered nanoemulsion of Ropinirole and nigella oil in the management of Parkinson's disease: Formulation perspective and In vitro and In vivo assessment.

The research presented aims at developing Ropinirole hydrochloride (RHCl) nanoemulsion (NE) with nigella oil for Parkinson's disease (PD). In silico study was done to explore interactions of ropinirole and thymoquinone at receptor site (TNF-α and NFK-ß). Ropinirole and Thymoquinone forms a hydrogen bond with residue Arginine 201 and residue Arginine 253 with a bond length of 1.89 Å and 2.30 Å at the NF-κß receptor. NE was optimized using Central Composite Rotatable Design (CCRD). The globule size of chitosan coated NE, Polydispersity index (PDI) and zeta potential were 183.7 ± 5.2 nm, 0.263 ± 0.005, and 24.9 mV respectively. NE exhibited 85.28% transmittance showing the formulation was clear and transparent. TEM showed that NE had spherical globules with no aggregation. The formulation had a stable pH value of 5.8 ± 0.18. In vitro release and permeation studies exhibited 2 folds and 3.4 folds enhancement when compared with the drug suspension. Neurobehavioral activity and biochemical parameters corroborated well with the pharmacokinetic results. Histopathological study and immunohistochemical analysis were performed to get better picture of 6-OHDA induced toxicity and reversal of PD symptoms. Thus, the NE tailored is a promising synergistic approach yielding enticing outcomes for better management of PD related symptoms.

Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS.

Atazanavir (ATZ) presents poor brain availability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of NeuroAIDS. The utilization of nanostructured lipid carriers (NLCs) in conjunction with the premeditated use of excipients can be a potential approach for overcoming the limited ATZ brain delivery. METHODS: ATZ-loaded NLC was formulated using the quality by design-enabled approach and further optimized by employing the Box-Behnken design. The optimized nanoformulation was then characterized for several in vitro and in vivo assessments. RESULTS: The optimized NLC showed small particle size of 227.6 ± 5.4 nm, high entrapment efficiency (71.09% ± 5.84%) and high drug loading capacity (8.12% ± 2.7%). The release pattern was observed to be biphasic exhibiting fast release (60%) during the initial 2 h, then trailed by the sustained release. ATZ-NLC demonstrated a 2.36-fold increase in the cumulative drug permeated across the rat intestine as compared to suspension. Pharmacokinetic studies revealed 2.75-folds greater Cmax in the brain and 4-fold improvement in brain bioavailability signifying the superiority of NLC formulation over drug suspension. CONCLUSION: Thus, NLC could be a promising avenue for encapsulating hydrophobic drugs and delivering it to their target site. The results suggested that increase in bioavailability and brain-targeted delivery by NLC, in all plausibility, help in improving the therapeutic prospects of atazanavir.

Purification/annealing of graphene with 100-MeV Ag ion irradiation.

Studies on interaction of graphene with radiation are important because of nanolithographic processes in graphene-based electronic devices and for space applications. Since the electronic properties of graphene are highly sensitive to the defects and number of layers in graphene sample, it is desirable to develop tools to engineer these two parameters. We report swift heavy ion (SHI) irradiation-induced annealing and purification effects in graphene films, similar to that observed in our studies on fullerenes and carbon nanotubes (CNTs). Raman studies after irradiation with 100-MeV Ag ions (fluences from 3 × 10(10) to 1 × 10(14) ions/cm(2)) show that the disorder parameter α, defined by I D/I G ratio, decreases at lower fluences but increases at higher fluences beyond 1 × 10(12) ions/cm(2). This indicates that SHI induces annealing effects at lower fluences. We also observe that the number of graphene layers is reduced at fluences higher than 1 × 10(13) ions/cm(2). Using inelastic thermal spike model calculations, we estimate a radius of 2.6 nm for ion track core surrounded by a halo extending up to 11.6 nm. The transient temperature above the melting point in the track core results in damage, whereas lower temperature in the track halo is responsible for annealing. The results suggest that SHI irradiation fluence may be used as one of the tools for defect annealing and manipulation of the number of graphene layers. PACS: 60.80.x; 81.05.ue.