Assessment of Lockdown Effect in Some States and Overall India: A Predictive Mathematical Study on COVID-19 Outbreak

In the absence of neither an effective treatment or vaccine and with an incomplete understanding of the epidemiological cycle, Govt. has implemented a nationwide lockdown to reduce COVID-19 transmission in India. To study the effect of social distancing measure, we considered a new mathematical model on COVID-19 that incorporates lockdown effect. By validating our model to the data on notified cases from five different states and overall India, we estimated several epidemiologically important parameters as well as the basic reproduction number ($R_{0}$). Combining the mechanistic mathematical model with different statistical forecast models, we projected notified cases in the six locations for the period May 17, 2020, till May 31, 2020. A global sensitivity analysis is carried out to determine the correlation of two epidemiologically measurable parameters on the lockdown effect and also on $R_{0}$. Our result suggests that lockdown will be effective in those locations where a higher percentage of symptomatic infection exists in the population. Furthermore, a large scale COVID-19 mass testing is required to reduce community infection. Ensemble model forecast suggested a high rise in the COVID-19 notified cases in most of the locations in the coming days. Furthermore, the trend of the effective reproduction number ($R_{t}$) during the projection period indicates if the lockdown measures are completely removed after May 17, 2020, a high spike in notified cases may be seen in those locations. Finally, combining our results, we provided an effective lockdown policy to reduce future COVID-19 transmission in India.Comment: 43 pages, 17 figure

Plasmodium yoelii-Infected A. stephensi Inefficiently Transmit Malaria Compared to Intravenous Route

It was recently reported that when mosquitoes infected with P. berghei sporozoites feed on mice, they deposit approximately 100–300 sporozoites in the dermis. When we inoculate P. yoelii (Py) sporozoites intravenously (IV) into BALB/c mice, the 50% infectious dose (ID50) is often less than 3 sporozoites, indicating that essentially all Py sporozoites in salivary glands are infectious. Thus, it should only take the bite of one infected mosquito to infect 100% of mice. In human subjects, it takes the bite of at least 5 P. falciparum-infected mosquitoes to achieve 100% blood stage infection. Exposure to 1–2 infected mosquitoes only leads to blood stage infection in approximately 50% of subjects. If mosquitoes carrying Py sporozoites inoculate 100–300 sporozoites per bite, and 1 to 2 mosquito bites achieve 50% blood stage infection rates, then this would suggest that the majority of sporozoites inoculated by mosquitoes into the dermis are not responsible for a productive infection, or that a significant number of sporozoite-infected mosquitoes do not inoculate any sporozoites. The objective of this study was to determine if this is the case. We therefore studied the infectivity to mice of the bites of 1, 2, 4, or 5–8 Py-infected mosquitoes. The bite of one Py sporozoite-infected mosquito caused blood stage infection in 41.4% (12/29) of mice, two bites infected 66.7% (22/33), four bites infected 75% (18/24), and five to eight bites infected 100% (21/21). These findings demonstrate that inoculation of sporozoites by mosquito bite is much less efficient than IV inoculation of Py sporozoites by needle and syringe. Such data may have implications for determining the best route and dose of administration to humans of our attenuated P. falciparum sporozoite vaccine, the scientific basis of which is immunity by bites from irradiated infected mosquitoes, and suggest that the challenge is to develop a method of administration that approximates IV inoculation, not one that mimics mosquito bite

Integrated Architecture for Neural Networks and Security Primitives using RRAM Crossbar

This paper proposes an architecture that integrates neural networks (NNs) and hardware security modules using a single resistive random access memory (RRAM) crossbar. The proposed architecture enables using a single crossbar to implement NN, true random number generator (TRNG), and physical unclonable function (PUF) applications while exploiting the multi-state storage characteristic of the RRAM crossbar for the vector-matrix multiplication operation required for the implementation of NN. The TRNG is implemented by utilizing the crossbar's variation in device switching thresholds to generate random bits. The PUF is implemented using the same crossbar initialized as an entropy source for the TRNG. Additionally, the weights locking concept is introduced to enhance the security of NNs by preventing unauthorized access to the NN weights. The proposed architecture provides flexibility to configure the RRAM device in multiple modes to suit different applications. It shows promise in achieving a more efficient and compact design for the hardware implementation of NNs and security primitives

Non-equilibrium VLS-grown stable ST12-Ge thin film on Si substrate: A study on strain-induced band-engineering

The current work describes a novel method of growing thin films of stable crystalline ST12-Ge, a high pressure polymorph of Ge, on Si substrate by a non-equilibrium VLS-technique. The study explores the scheme of band engineering of ST12-Ge by inducing process-stress into it as a function of the growth temperature and film thickness. In the present work, ST12-Ge films are grown at 180 C - 250 C to obtain thicknesses of ~4.5-7.5 nm, which possess extremely good thermal stability up to a temperature of ~350 C. Micro-Raman study shows the stress induced in such ST12-Ge films to be compressive in nature and vary in the range of ~0.5-7.5 GPa. The measured direct band gap is observed to vary within 0.688 eV to 0.711 eV for such stresses, and four indirect band gaps are obtained to be 0.583 eV, 0.614-0.628 eV, 0.622-0.63 eV and 0.623-0.632 eV, accordingly. The corresponding band structures for unstrained and strained ST12-Ge are calculated by performing DFT simulation, which shows that a compressive stress transforms the fundamental band gap at M-G valley from indirect to direct one. Henceforth, the possible route of strain induced band engineering in ST12-Ge is explored by analyzing all the transitions in strained and unstrained band structures along with substantiation of the experimental results and theoretical calculations. The investigation shows that unstrained ST12-Ge is a natural n-type semiconductor which transforms into p-type upon incorporation of a compressive stress of ~5 GPa, with the in-plane electron effective mass components at M-G band edge to be ~0.09 me. Therefore, such band engineered ST12-Ge exhibits superior mobility along with its thermal stability and compatibility with Si, which can have potential applications to develop high-speed MOS devices for advanced CMOS technology

A Systems-Based Analysis of Plasmodium vivax Lifecycle Transcription from Human to Mosquito

Most of the 250 million malaria cases outside of Africa are caused by the parasite Plasmodium vivax. Although drugs can be used to treat P. vivax malaria, drug resistance is spreading and there is no available vaccine. Because this species cannot be readily grown in the laboratory there are added challenges to understanding the function of the many hypothetical genes in the genome. We isolated transcriptional messages from parasites growing in human blood and in mosquitoes, labeled the messages and measured how their levels for different parasite growth conditions. The data for 5,419 parasite genes shows extensive changes as the parasite moves between human and mosquito and reveals highly expressed genes whose proteins might represent new therapeutic targets for experimental vaccines. We discover sets of genes that are likely to play a role in the earliest stages of hepatocyte infection. We find intriguing differences in the expression patterns of different blood stage parasites that may be related to host-response status

Establishment of an In Vitro Assay for Assessing the Effects of Drugs on the Liver Stages of Plasmodium vivax Malaria

Plasmodium vivax (Pv) is the second most important human malaria parasite. Recent data indicate that the impact of Pv malaria on the health and economies of the developing world has been dramatically underestimated. Pv has a unique feature in its life cycle. Uninucleate sporozoites (spz), after invasion of human hepatocytes, either proceed to develop into tens of thousands of merozoites within the infected hepatocytes or remain as dormant forms called hypnozoites, which cause relapses of malaria months to several years after the primary infection. Elimination of malaria caused by Pv will be facilitated by developing a safe, highly effective drug that eliminates Pv liver stages, including hypnozoites. Identification and development of such a drug would be facilitated by the development of a medium to high throughput assay for screening drugs against Pv liver stages. We undertook the present pilot study to (1) assess the feasibility of producing large quantities of purified, vialed, cryopreserved Pv sporozoites and (2) establish a system for culturing the liver stages of Pv in order to assess the effects of drugs on the liver stages of Pv. We used primaquine (PQ) to establish this assay model, because PQ is the only licensed drug known to clear all Pv hepatocyte stages, including hypnozoites, and the effect of PQ on Pv hepatocyte stage development in vitro has not previously been reported. We report that we have established the capacity to reproducibly infect hepatoma cells with purified, cyropreserved Pv spz from the same lot, quantitate the primary outcome variable of infected hepatoma cells and demonstrate the inhibitory activity of primaquine on the infected hepatoma cells. We have also identified small parasite forms that may be hypnozoites. These data provide the foundation for finalizing a medium throughput, high content assay to identify new drugs for the elimination of all Pv liver stages

Protective effects of selenium on oxidative damage and oxidative stress related gene expression in rat liver under chronic poisoning of arsenic

Arsenic (As) is a toxic metalloid existing widely in the environment, and chronic exposure to it through contaminated drinking water has become a global problem of public health. The present study focused on the protective effects of selenium on oxidative damage of chronic arsenic poisoning in rat liver. Rats were divided into four groups at random and given designed treatments for 20 weeks. The oxidative damage of liver tissue was evaluated by lipid peroxidation and antioxidant enzymes. Oxidative stress related genes were detected to reflect the liver stress state at the molecular level. Compared to the control and Na2SeO3 groups, the MDA content in liver tissue was decreased and the activities of antioxidant enzymes were increased in the Na2SeO3 intervention group. The mRNA levels of SOD1, CAT, GPx and Txnrd1 were increased significantly (P < 0.05) in the combined Na2SeO3 + NaAsO2 treatment group. The expressions of HSP70 and HO-1 were significantly (P < 0.05) increased in the NaAsO2 group and reduced in the combined treatment group. The results indicate that long-term intake of NaAsO2 causes oxidative damage in the rat liver, and Na2SeO3 protects liver cells by adjusting the expression of oxidative stress related genes to improve the activities of antioxidant enzymes. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved

Delineation of Stage Specific Expression of Plasmodium falciparum EBA-175 by Biologically Functional Region II Monoclonal Antibodies

EBA-175 binds its receptor sialic acids on glycophorin A when invading erythrocytes. The receptor-binding region (RII) contains two cysteine-rich domains with similar cysteine motifs (F1 and F2). Functional relationships between F1 and F2 domains and characterization of EBA-175 were studied using specific monoclonal antibodies (mAbs) against these domains..The role of the F1 and F2 domains in erythrocyte invasion and binding was elucidated with mAbs. These mAbs interfere with native EBA-175 binding to erythrocyte in a synergistic fashion. The stage specific expression of EBA-175 showed that the primary focus of activity was the merozoite stage. A recombinant RII protein vaccine consisting of both F1 and F2 domains that could induce synergistic activity should be optimal for induction of antibody responses that interfere with merozoite invasion of erythrocytes