3SAT on an all-to-all-connected CMOS Ising solver chip.

This work solves 3SAT, a classical NP-complete problem, on a CMOS-based Ising hardware chip with all-to-all connectivity. The paper addresses practical issues in going from algorithms to hardware. It considers several degrees of freedom in mapping the 3SAT problem to the chip-using multiple Ising formulations for 3SAT; exploring multiple strategies for decomposing large problems into subproblems that can be accommodated on the Ising chip; and executing a sequence of these subproblems on CMOS hardware to obtain the solution to the larger problem. These are evaluated within a software framework, and the results are used to identify the most promising formulations and decomposition techniques. These best approaches are then mapped to the all-to-all hardware, and the performance of 3SAT is evaluated on the chip. Experimental data shows that the deployed decomposition and mapping strategies impact SAT solution quality: without our methods, the CMOS hardware cannot achieve 3SAT solutions on SATLIB benchmarks. Under the assumption of some hardware improvements, our chip-based 3SAT solver demonstrates a remarkable 250 × acceleration compared to Tabu search in dwave-hybrid on a CPU.

Comparative pathogenicity of BA.2.12, BA.5.2 and XBB.1 with the Delta variant in Syrian hamsters.

Omicron variant is evolving into numerous sub variants with time and the information on the characteristics of these newly evolving variants are scant. Here we performed a pathogenicity evaluation of Omicron sub variants BA.2.12, BA.5.2 and XBB.1 against the Delta variant in 6-8-week-old Syrian hamster model. Body weight change, viral load in respiratory organs by real time RT-PCR/titration, cytokine mRNA quantification and histopathological evaluation of the lungs were performed. The intranasal infection of the BA.2.12, BA.5.2 and XBB.1 variants in hamster model resulted in body weight loss/reduced weight gain, inflammatory cytokine response and interstitial pneumonia with lesser severity compared to the Delta variant infection. Among the variants studied, BA.2.12 and XBB.1 showed lesser viral shedding through the upper respiratory tract, whereas the BA.5.2 showed comparable viral RNA shedding as that of the Delta variant. The study shows that the Omicron BA.2 sub variants may show difference in disease severity and transmissibility amongst each other whereas the overall disease severity of the Omicron sub variants studied were less compared to the Delta variant. The evolving Omicron sub variants and recombinants should be monitored for their properties.

Needle-free injection system delivery of ZyCoV-D DNA vaccine demonstrated improved immunogenicity and protective efficacy in rhesus macaques against SARS-CoV-2.

The apprehension of needles related to injection site pain, risk of transmitting bloodborne pathogens, and effective mass immunization have led to the development of a needle-free injection system (NFIS). Here, we evaluated the efficacy of the NFIS and needle injection system (NIS) for the delivery and immunogenicity of DNA vaccine candidate ZyCoV-D in rhesus macaques against SARS-CoV-2 infection. Briefly, 20 rhesus macaques were divided into 5 groups (4 animals each), that is, I (1 mg dose by NIS), II (2 mg dose by NIS), III (1 mg dose by NFIS), IV (2 mg dose by NFIS) and V (phosphate-buffer saline [PBS]). The macaques were immunized with the vaccine candidates/PBS intradermally on Days 0, 28, and 56. Subsequently, the animals were challenged with live SARS-CoV-2 after 15 weeks of the first immunization. Blood, nasal swab, throat swab, and bronchoalveolar lavage fluid specimens were collected on 0, 1, 3, 5, and 7 days post infection from each animal to determine immune response and viral clearance. Among all the five groups, 2 mg dose by NFIS elicited significant titers of IgG and neutralizing antibody after immunization with enhancement in their titers postvirus challenge. Besides this, it also induced increased lymphocyte proliferation and cytokine response. The minimal viral load post-SARS-CoV-2 challenge and significant immune response in the immunized animals demonstrated the efficiency of NFIS in delivering 2 mg ZyCoV-D vaccine candidate.

Expectation-Based Probabilistic Naive Approach for Forecasting Involving Optimized Parameter Estimation.

This paper presents a forecasting technique based on the principle of naïve approach imposed in a probabilistic sense, thus allowing to express the prediction as the statistical expectation of known observations with a weight involving an unknown parameter. This parameter is learnt from the given data through minimization of error. The theoretical foundation is laid out, and the resulting algorithm is concisely summarized. Finally, the technique is validated on several test functions (and compared with ARIMA and Holt-Winters), special sequences and real-life covid-19 data. Favorable results are obtained in every case, and important insight about the functioning of the technique is gained.

Protective efficacy of COVAXIN® against Delta and Omicron variants in hamster model.

The immunity acquired after natural infection or vaccinations against SARS-CoV-2 tend to wane with time. Here, we compared the protective efficacy of COVAXIN® following two- and three-dose immunizations against the Delta variant and also studied the efficacy of COVAXIN® against Omicron variants in a Syrian hamster model. Despite the comparable neutralizing antibody response against the homologous vaccine strain in both the two-dose and three-dose immunized groups, considerable reduction in the lung disease severity was observed in the 3 dose immunized group after Delta variant challenge. In the challenge study using the Omicron variants, i.e., BA.1.1 and BA.2, lesser virus shedding, lung viral load and lung disease severity were observed in the immunized groups. The present study shows that administration of COVAXIN® booster dose will enhance the vaccine effectiveness against the Delta variant infection and give protection against the BA.1.1 and BA.2 variants.

Ayurveda in Knee Osteoarthritis-Secondary Analyses of a Randomized Controlled Trial.

Background: Ayurveda is widely practiced in South Asia in the treatment of osteoarthritis (OA). The aim of these secondary data analyses were to identify the most relevant variables for treatment response and group differences between Ayurvedic therapy compared to conventional therapy in knee OA patients. Methods: A total of 151 patients (Ayurveda n = 77, conventional care n = 74) were analyzed according to the intention-to-treat principle in a randomized controlled trial. Different statistical approaches including generalized linear models, a radial basis function (RBF) network, exhausted CHAID, classification and regression trees (CART), and C5.0 with adaptive boosting were applied. Results: The RBF network implicated that the therapy arm and the baseline values of the WOMAC Index subscales might be the most important variables for the significant between-group differences of the WOMAC Index from baseline to 12 weeks in favor of Ayurveda. The intake of nutritional supplements in the Ayurveda group did not seem to be a significant factor in changes in the WOMAC Index. Ayurveda patients with functional limitations > 60 points and pain > 25 points at baseline showed the greatest improvements in the WOMAC Index from baseline to 12 weeks (mean value 107.8 ± 27.4). A C5.0 model with nine predictors had a predictive accuracy of 89.4% for a change in the WOMAC Index after 12 weeks > 10. With adaptive boosting, the accuracy rose to 98%. Conclusions: These secondary analyses suggested that therapeutic effects cannot be explained by the therapies themselves alone, although they were the most important factors in the applied models.

SARS-CoV-2 Kappa Variant Shows Pathogenicity in a Syrian Hamster Model.

Objectives: The emergence of SARS-CoV-2 lineage B.1.617 variants in India has been associated with a surge in the number of daily infections. We investigated the pathogenic potential of Kappa (B.1.617.1) variant in Syrian golden hamsters. Methods: Two groups of Syrian golden hamsters (18 each) were inoculated intranasally with SARS-CoV-2 isolates, B.1 (D614G) and Kappa variant, respectively. The animals were monitored daily for the clinical signs and body weight. Throat swab, nasal wash, and organ samples (lungs, nasal turbinate, trachea) were collected and screened using SARS-CoV-2-specific RT-qPCR. Histopathologic evaluation of the lung samples was performed. Results: The hamsters infected with the Kappa variant demonstrated increased body weight loss compared to the B.1 lineage isolate. The highest viral RNA load was observed in the nasal turbinate and lung specimens of animals infected with both variants. A significantly higher sgRNA load was observed in the nasal swabs (7 DPI), trachea (3 DPI), and lungs (3 DPI) of hamsters infected with the Kappa variant. Neutralizing antibody response generated in the B.1 lineage-infected hamster sera were comparable against both B.1 and Kappa variant in contrast to Kappa variant-infected hamsters, which showed lower titers against B.1 lineage isolate. Gross and microscopic evaluation of the lung specimens showed severe lung lesions in hamsters infected with Kappa variant compared to B.1. Conclusions: The study demonstrates pathogenicity of Kappa variant in hamsters evident with reduced body weight, high viral RNA load in lungs, and pronounced lung lesions. Both Kappa variant- and B.1-infected hamsters produced neutralizing antibodies against both variants studied.

Pathogenicity of SARS-CoV-2 Omicron (R346K) variant in Syrian hamsters and its cross-neutralization with different variants of concern.

BACKGROUND: SARS-CoV-2 Omicron variant is rampantly spreading across the globe. We assessed the pathogenicity and immune response generated by BA.1.1 sub-lineage of SARS-CoV-2 [Omicron (R346K) variant] in 5 to 6-week old Syrian hamsters and compared the observations with that of Delta variant infection. METHODS: Virus shedding, organ viral load, lung disease and immune response generated in hamsters were sequentially assessed. FINDINGS: The disease characteristics of the Omicron (R346K) variant were found to be similar to that of the Delta variant infection in hamsters like viral replication in the respiratory tract and interstitial pneumonia. The Omicron (R346K) infected hamsters demonstrated lesser body weight reduction and viral RNA load in the throat swab and nasal wash samples in comparison to the Delta variant infection. The viral load in the lungs and nasal turbinate samples and the lung disease severity of the Omicron (R346K) infected hamsters were found comparable with that of the Delta variant infected hamsters. Neutralizing antibody response against Omicron (R346K) variant was detected from day 5 and the cross-neutralization titre of the sera against other variants showed severe reduction ie., 7 fold reduction against Alpha and no titers against B.1, Beta and Delta. INTERPRETATION: This preliminary data shows that Omicron (R346K) variant infection can produce moderate to severe lung disease similar to that of the Delta variant and the neutralizing antibodies produced in response to Omicron (R346K) variant infection shows poor neutralizing ability against other co-circulating SARS-CoV-2 variants like Delta which necessitates caution as it may lead to increased cases of reinfection. FUNDING: This study was supported by Indian Council of Medical Research as an intramural grant (COVID-19) to ICMR-National Institute of Virology, Pune.

Nipah Virus Outbreak in Kerala State, India Amidst of COVID-19 Pandemic.

We report here a Nipah virus (NiV) outbreak in Kozhikode district of Kerala state, India, which had caused fatal encephalitis in a 12-year-old boy and the outbreak response, which led to the successful containment of the disease and the related investigations. Quantitative real-time reverse transcription (RT)-PCR, ELISA-based antibody detection, and whole genome sequencing (WGS) were performed to confirm the NiV infection. Contacts of the index case were traced and isolated based on risk categorization. Bats from the areas near the epicenter of the outbreak were sampled for throat swabs, rectal swabs, and blood samples for NiV screening by real-time RT-PCR and anti-NiV bat immunoglobulin G (IgG) ELISA. A plaque reduction neutralization test was performed for the detection of neutralizing antibodies. Nipah viral RNA could be detected from blood, bronchial wash, endotracheal (ET) secretion, and cerebrospinal fluid (CSF) and anti-NiV immunoglobulin M (IgM) antibodies from the serum sample of the index case. Rapid establishment of an onsite NiV diagnostic facility and contact tracing helped in quick containment of the outbreak. NiV sequences retrieved from the clinical specimen of the index case formed a sub-cluster with the earlier reported Nipah I genotype sequences from India with more than 95% similarity. Anti-NiV IgG positivity could be detected in 21% of Pteropus medius (P. medius) and 37.73% of Rousettus leschenaultia (R. leschenaultia). Neutralizing antibodies against NiV could be detected in P. medius. Stringent surveillance and awareness campaigns need to be implemented in the area to reduce human-bat interactions and minimize spillover events, which can lead to sporadic outbreaks of NiV.

Causal theory on acceleration of seed germination in the vicinity of high voltage direct current transmission line.

Seed germination is the primary stage of growth in a seed. A wealth of experiments exist in literature to support the existence of correlation between seed germination to the electric and magnetic fields. This becomes more important as researchers have suggested to develop technologies to build ecologically clean and environment-friendly solutions to agricultural practices. Although the literature supports the existence of seed germination acceleration, the lack of a definite causal theory has been observed by numerous researchers over decades. After considering all the existing experimental data, we have formulated a causal theory to explain the factors influencing seed germination around high voltage DC transmission lines. This work opens new avenues of research in this field.

Interpositional elbow arthroplasty using fascia lata autograft in stiff elbow: Case series of 8 patients.

INTRODUCTION: Constrain of a total elbow replacement and elbow arthrodesis are too much for the working population to bear. As such interpositional elbow arthroplasty using fascia lata autologous graft to reconstruct the elbow joint is a viable option in this age group. MATERIALS AND METHOD: 8 patients were operated for arthritic stiff elbow, and joint reconstruction was done using fascia lata autologous graft, with out the use of any hinged external fixator. Pre-operative and post-operative functional assessment was done using Mayo Elbow Performance Score (MEPS) and statistically measured using a paired t-test. Result There was significant improvement in range of motion in coronal (flexion-extension) and axial (supination-protonation) with p-value of <0.001. The mean pre-operative MEPI increased from 40.6 points to 91.9 points (p < 0.0001). All parameters of MEPI had statistically significant improvement with exception of stability (p-value = 0.0824).

Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques.

The COVID-19 pandemic is a global health crisis that poses a great challenge to the public health system of affected countries. Safe and effective vaccines are needed to overcome this crisis. Here, we develop and assess the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine in rhesus macaques. Twenty macaques were divided into four groups of five animals each. One group was administered a placebo, while three groups were immunized with three different vaccine candidates of BBV152 at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which exhibited interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. This vaccine candidate BBV152 has completed Phase I/II (NCT04471519) clinical trials in India and is presently in phase III, data of this study substantiates the immunogenicity and protective efficacy of the vaccine candidates.

Immunogenicity and protective efficacy of BBV152, whole virion inactivated SARS- CoV-2 vaccine candidates in the Syrian hamster model.

The availability of a safe and effective vaccine would be the eventual measure to deal with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) threat. Here, we have assessed the immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidates BBV152A, BBV152B, and BBV152C in Syrian hamsters. Three dose vaccination regimes with vaccine candidates induced significant titers of SARS-CoV-2-specific IgG and neutralizing antibodies. BBV152A and BBV152B vaccine candidates remarkably generated a quick and robust immune response. Post-SARS-CoV-2 infection, vaccinated hamsters did not show any histopathological changes in the lungs. The protection of the hamster was evident by the rapid clearance of the virus from lower respiratory tract, reduced virus load in upper respiratory tract, absence of lung pathology, and robust humoral immune response. These findings confirm the immunogenic potential of the vaccine candidates and further protection of hamsters challenged with SARS-CoV-2. Of the three candidates, BBV152A showed the better response.

Theoretical foundation of a scheme for the study of dielectrics by analyzing the distortion in fringing field.

This paper presents a scheme for the study of dielectrics. For this purpose, fringing field is employed, which is usually considered an undesired effect. Two non-ideal capacitors are placed one beneath the other, which have a region of interlinking fringing fields. If the fringing fields are canceled out, it is called diminutive physically parallel orientation. This capacitor arrangement is placed in a Wheatstone bridge setup, so whenever a dielectric sample is placed within the main capacitor, then it creates distortion in the interlinking fringing fields. This is canceled out when the circuit is balanced, which happens at an optimum plate separation. Thus, the proposed scheme can be used to study fringing field intensity, sense the movement of a dielectric liquid, measure dielectric properties such as permittivity, study materials and biological substances, etc. This work is expected to find application in industrial sensing. Researchers will also find some interesting ideas to ponder upon.

Hall effect instruments, evolution, implications, and future prospects.

Since the revolution in solid state electronics, many innovative principles were investigated for a better and simpler design. Thus, Hall effect-based sensors and instruments gained importance. To employ this principle in several operating conditions and with different setups, several researchers contributed significantly over the decades, which ultimately led to the establishment of industries producing a wide range of Hall devices. The objective of this paper is to review the available configurations and current status of the Hall effect-based technologies. A detailed discussion is carried out on the various types of existing Hall-based devices, such as linear sensors, field-programmable sensors, switches, latches, speed and directional sensors, and vane sensors. The effect of materials and the influence of several undesired effects (such as offset voltage, temperature, noise, and drift) are also investigated. The compensation/reduction techniques are mentioned therein, and interested researchers are encouraged for the development of new techniques. This paper concludes with the discussion on the market scenario (such as electronics sector and automotive industry) and progression in current research on Hall devices while projecting some new research directions in this field.

Detection of coronaviruses in Pteropus & Rousettus species of bats from different States of India.

Background & objectives: Bats are considered to be the natural reservoir for many viruses, of which some are potential human pathogens. In India, an association of Pteropus medius bats with the Nipah virus was reported in the past. It is suspected that the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also has its association with bats. To assess the presence of CoVs in bats, we performed identification and characterization of bat CoV (BtCoV) in P. medius and Rousettus species from representative States in India, collected during 2018 and 2019. Methods: Representative rectal swab (RS) and throat swab specimens of Pteropus and Rousettus spp. bats were screened for CoVs using a pan-CoV reverse transcription-polymerase chain reaction (RT-PCR) targeting the RNA-dependent RNA polymerase (RdRp) gene. A single-step RT-PCR was performed on the RNA extracted from the bat specimens. Next-generation sequencing (NGS) was performed on a few representative bat specimens that were tested positive. Phylogenetic analysis was carried out on the partial sequences of RdRp gene sequences retrieved from both the bat species and complete viral genomes recovered from Rousettus spp. Results: Bat samples from the seven States were screened, and the RS specimens of eight Rousettus spp. and 21 Pteropus spp. were found positive for CoV RdRp gene. Among these, by Sanger sequencing, partial RdRp sequences could be retrieved from three Rousettus and eight Pteropus bat specimens. Phylogenetic analysis of the partial RdRp region demonstrated distinct subclustering of the BtCoV sequences retrieved from these Rousettus and Pteropus spp. bats. NGS led to the recovery of four sequences covering approximately 94.3 per cent of the whole genome of the BtCoVs from Rousettus bats. Three BtCoV sequences had 93.69 per cent identity to CoV BtRt-BetaCoV/GX2018. The fourth BtCoV sequence was 96.8 per cent identical to BtCoV HKU9-1. Interpretation & conclusions: This study was a step towards understanding the CoV circulation in Indian bats. Detection of potentially pathogenic CoVs in Indian bats stresses the need for enhanced screening for novel viruses in them. One Health approach with collaborative activities by the animal health and human health sectors in these surveillance activities shall be of use to public health. This would help in the development of diagnostic assays for novel viruses with outbreak potential and be useful in disease interventions. Proactive surveillance remains crucial for identifying the emerging novel viruses with epidemic potential and measures for risk mitigation.

A Molecular Approach on the Protective Effects of Mangiferin Against Diabetes and Diabetes-related Complications.

BACKGROUND: Diabetes and its related complications are now a global health problem without an effective therapeutic approach. There are many herbal medicines which have attracted much attention as potential therapeutic agents in the prevention and treatment of diabetic complications due to their multiple targets. AIM: The aim of this study is to review available knowledge of mangiferin focusing on its mode of action. METHODS: Mangiferin was extensively reviewed for its antidiabetic activity using online database like Scopus, PubMed, and Google Scholar as well as some offline textbooks. A critical discussion based on the mechanism of action and the future perspectives is also given in the present manuscript. RESULTS: Mangiferin is a natural C-glucoside and mainly obtained from its primary source, the leaves of mango tree (Mangifera indica L.). Therapeutic and preventive properties of mangiferin include antimicrobial, anti-inflammatory, antioxidative, antiallergic, neuroprotective, and cognition-enhancing effects. It dissolves well in water, so it can be easily extracted into infusions and decoctions and hence, a number of researches have been made on the therapeutic effect of this molecule. Recently, mangiferin has been proved to be an effective remedy in diabetes and diabetes-related complications. It is a beneficial natural compound for type 2 diabetes mellitus as it improves insulin sensitivity, modulates lipid profile and reverts adipokine levels to normal. CONCLUSION: This study concludes that mangiferin has the potential to treat diabetes and it can be developed as a therapeutic agent for diabetes and the complications caused by diabetes.

Drimia indica: A Plant Used in Traditional Medicine and Its Potential for Clinical Uses.

Drimia indica (Roxb.) Jessop (Asparagaceae) is a reputed Ayurvedic medicine for a number of therapeutic benefits, including for cardiac diseases, indigestion, asthma, dropsy, rheumatism, leprosy, and skin ailments. The present work aimed to critically and extensively review its traditional uses, phytochemistry, pharmacology, toxicology, and taxonomy together with the mechanisms of action of selected extracts of D. indica. A systematic literature survey from scientific databases such as PubMed, Scopus, and Web of Science as well as from some textbooks and classical texts was conducted. The plant, mainly its bulb, contains various bioactive constituents, such as alkylresorcinols, bufadienolides, phytosterols, and flavonoids. Various scientific studies have proven that the plant has anthelmintic, anticancer, antidiabetic, antimicrobial, antioxidant, and wound healing activities. The present work concludes that D. indica has the potential to treat various diseases, mainly microbial infections. This review also suggests that bufadienolides, flavonoids, and steroids might be responsible for its bioactive potential.

Status of Indian medicinal plants in the International Union for Conservation of Nature and the future of Ayurvedic drugs: Shouldn't think about Ayurvedic fundamentals?

The present market for herbal drugs is estimated about ₹40 billion, which is expected to increase by 16% in next 3-4 years. The current production of many Ayurvedic herbs is less than their market demand, which incentivizes adulteration in the Ayurvedic drug supply chain. The present work aims to highlight the most used Ayurvedic plants that have been listed in the International Union for Conservation of Nature's "red list" of endangered or vulnerable plants. The future of Ayurvedic medicines from these listed plants is uncertain, as the collection of herbs from their natural habitat is prohibited and their cultivation does not meet market demands. Many of these plants, such as Taxus baccata and T. wallichiana, are endangered and are only grown in their natural habitats; their cultivation in other areas is impractical. This is the present state, and will worsen as demand continues to grow, with increasing populations and increasing adoption of this system of medicine. It is possible that in coming years most of the Ayurvedic drugs will be adulterated, and will cause only side effects rather than the therapeutic effects. The Ayurvedic fundamentals are under-explored areas where the Ayurvedic practitioners and research scientists can work together. The scientific work on the basic principles will unravel many unknown or little-known facts of this ancient science. Hence, the present review emphasizes the conservation of Ayurvedic herbs, minimization of the use of medicinal plants and the promotion of the research based on Ayurvedic fundamentals.