Design of secure and robust cognitive system for malware detection

Machine learning based malware detection techniques rely on grayscale images of malware and tends to classify malware based on the distribution of textures in graycale images. Albeit the advancement and promising results shown by machine learning techniques, attackers can exploit the vulnerabilities by generating adversarial samples. Adversarial samples are generated by intelligently crafting and adding perturbations to the input samples. There exists majority of the software based adversarial attacks and defenses. To defend against the adversaries, the existing malware detection based on machine learning and grayscale images needs a preprocessing for the adversarial data. This can cause an additional overhead and can prolong the real-time malware detection. So, as an alternative to this, we explore RRAM (Resistive Random Access Memory) based defense against adversaries. Therefore, the aim of this thesis is to address the above mentioned critical system security issues. The above mentioned challenges are addressed by demonstrating proposed techniques to design a secure and robust cognitive system. First, a novel technique to detect stealthy malware is proposed. The technique uses malware binary images and then extract different features from the same and then employ different ML-classifiers on the dataset thus obtained. Results demonstrate that this technique is successful in differentiating classes of malware based on the features extracted. Secondly, I demonstrate the effects of adversarial attacks on a reconfigurable RRAM-neuromorphic architecture with different learning algorithms and device characteristics. I also propose an integrated solution for mitigating the effects of the adversarial attack using the reconfigurable RRAM architecture.Comment: arXiv admin note: substantial text overlap with arXiv:2104.0665

HMGCS2 is a key ketogenic enzyme potentially involved in type 1 diabetes with high cardiovascular risk.

Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined. To learn more about biological pathways that are potentially involved in T1D with cardiac dysfunction, we sought to identify differentially expressed genes in the T1D heart. Our study used T1D mice with severe hyperglycemia along with significant deficits in echocardiographic measurements. Microarray analysis of heart tissue RNA revealed that the T1D mice differentially expressed 10 genes compared to control. Using Ingenuity Pathway Analysis (IPA), we showed that these genes were significantly involved in ketogenesis, cardiovascular disease, apoptosis and other toxicology functions. Of these 10 genes, the 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 (HMGCS2) was the highest upregulated gene in T1D heart. IPA analysis showed that HMGCS2 was center to many biological networks and pathways. Our data also suggested that apart from heart, the expression of HMGCS2 was also different in kidney and spleen between control and STZ treated mice. In conclusion, The HMGCS2 molecule may potentially be involved in T1D induced cardiac dysfunction

Inflammatory Serine Proteases Play a Critical Role in the Early Pathogenesis of Diabetic Cardiomyopathy.

BACKGROUND/AIMS: Diabetic cardiomyopathy (DCM) is characterized by structural and functional alterations that can lead to heart failure. Several mechanisms are known to be involved in the pathogenesis of DCM, however, the molecular mechanism that links inflammation to DCM is incompletely understood. To learn about this mechanism, we investigated the role of inflammatory serine proteases (ISPs) during the development of DCM. METHODS: Eight weeks old mice with deletion of dipeptidyl peptidase I (DPPI), an enzyme involved in the maturation of major ISPs, and wild type (WT) mice controls were injected with streptozotocin (50 mg/kg for 5 days intraperitoneally) and studied after 4, 8, 16, and 20 week after induction of type 1 diabetes mellitus (T1DM). Induction of diabetes was followed by echocardiographic measurements, glycemic and hemoglobulin A1c profiling, immunoblot, qPCR, enzyme activity assays, and immunohistochemistry (IHC) analysis of DPPI, ISPs, and inflammatory markers. Fibrosis was determined from left ventricular heart by Serius Red staining and qPCR. Apoptosis was determined by TUNEL assay and immunoblot analysis. RESULTS: In the diabetic WT mice, DPPI expression increased along with ISP activation, and DPPI accumulated abundantly in the left ventricle mainly from infiltrating neutrophils. In diabetic DPPI-knockout (DPPI-KO) mice, significantly decreased activation of ISPs, myocyte apoptosis, fibrosis, and cardiac function was improved compared to diabetic WT mice. In addition, DPPI-KO mice showed a decrease in overall inflammatory status mediated by diabetes induction which was manifested by decreased production of pro-inflammatory cytokines like TNF-α, IL-1β and IL-6. CONCLUSION: This study elucidates a novel role of ISPs in potentiating the immunological responses that lead to the pathogenesis of DCM in T1DM. To the best of our knowledge, this is the first study to report that DPPI expression and activation promotes the inflammation that enhances myocyte apoptosis and contributes to the adverse cardiac remodeling that subsequently leads to DCM

High Fat Diet Upregulates Fatty Acid Oxidation and Ketogenesis via Intervention of PPAR-γ

Background/Aims: Systemic hyperlipidemia and intracellular lipid accumulation induced by chronic high fat diet (HFD) leads to enhanced fatty acid oxidation (FAO) and ketogenesis. The present study was aimed to determine whether activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) by surplus free fatty acids (FA) in hyperlipidemic condition, has a positive feedback regulation over FAO and ketogenic enzymes controlling lipotoxicity and cardiac apoptosis. Methods: 8 weeks old C57BL/6 wild type (WT) or PPAR-γ-/- mice were challenged with 16 weeks 60% HFD to induce obesity mediated type 2 diabetes mellitus (T2DM) and diabetic cardiomyopathy. Treatment course was followed by echocardiographic measurements, glycemic and lipid profiling, immunoblot, qPCR and immunohistochemistry (IHC) analysis of PPAR-γ and following mitochondrial metabolic enzymes 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2), mitochondrial β- hydroxy butyrate dehydrogenase (BDH1) and pyruvate dehydrogenase kinase isoform 4 (PDK4). In vivo model was translated in vitro, with neonatal rat cardiomyocytes (NRCM) treated with PPAR-γ agonist/antagonist and PPAR-γ overexpression adenovirus in presence of palmitic acid (PA). Apoptosis was determined in vivo from left ventricular heart by TUNEL assay and immunoblot analysis. Results: We found exaggerated circulating ketone bodies production and expressions of the related mitochondrial enzymes HMGCS2, BDH1 and PDK4 in HFD-induced diabetic hearts and in PA-treated NRCM. As a mechanistic approach we found HFD mediated activation of PPAR-γ is associated with the above-mentioned mitochondrial enzymes. HFD-fed PPAR-γ-/-mice display decreased hyperglycemia, hyperlipidemia associated with increased insulin responsiveness as compared to HFD-fed WT mice PPAR-γ-/–HFD mice demonstrated a more robust functional recovery after diabetes induction, as well as significantly reduced myocyte apoptosis and improved cardiac function. Conclusions: PPAR-γ has been described previously to regulate lipid metabolism and adipogenesis. The present study suggests for the first time that increased PPAR-γ expression by HFD is responsible for cardiac dysfunction via upregulation of mitochondrial enzymes HMGCS2, BDH1 and PDK4. Targeting PPAR-γ and its downstream mitochondrial enzymes will provide novel strategies in preventing metabolic and myocardial dysfunction in diabetes mellitus

A Case Control Study on Risk Factors and Drug Prescription Patterns in Glaucoma at a tertiary eye care center in a city of Western India

Introduction: Glaucoma is an idiopathic, progressive optic disc neuropathy complicating into irreversible blindness if untreated. Early diagnosis by screening cases from high-risk populations has a pivotal role in managing this major public health problem with high treatment expenditures. Objectives: To identify the various ocular and non ocular risk factors of glaucoma and to identify the drug prescription pattern among glaucoma patients.Method: This was an observational, case-control study including 165 adult Glaucoma patients on treatment as cases and 165 age and sex-matched healthy individuals as controls, all of which were randomly selected from the patients visiting a tertiary eye care center. Various risk factors, drug prescription pattern and symptoms of the patients were recorded and analyzed.Results: A total of 165 adult Glaucoma patients and age and gender matched 165 controls were enrolled. Majority of the patients (41.21%) complained of blurring of vision at the time of study. The Odds ratios for Family history, Hypertension, Diabetes Mellitus, Migraine, Sleep apnea and Smoking showed strong association as risk factors for Glaucoma and the differences between the two groups were statistically significant (p value < 0.05). The mean number of drugs per prescription ± SD was 1.88 ± 0.79. Fixed drug formulations were prescribed in 42.4% patients. All the drugs were prescribed by their brand names and majority of them were in the form of eye drops.Conclusion: Primary Open Angle Glaucoma (POAG) was the most common subtype in the study. Age, Family history, Myopia, Hypertension, Diabetes Mellitus, Sleep Apnea, Migraine, Corticosteroid usage and Smoking emerged as putative risk factors. In consistence with present guidelines, Prostaglandin analogs were the most prescribed antiglaucoma drugs. The considerable proportion of asymptomatic cases (23%) suggests the need for periodic eye examinations to detect glaucomatous changes at an early stag

A Study on Knowledge, Attitude &amp; Practice Regarding Mosquito Borne Diseases in an Urban Area of Bhavnagar

Abstract : Introduction: Objective: Method

Manure microbial communities and resistance profiles reconfigure after transition to manure pits and differ from those in fertilized field soil

In agricultural settings, microbes and antimicrobial resistance genes (ARGs) have the potential to be transferred across diverse environments and ecosystems. The consequences of these microbial transfers are unclear and understudied. On dairy farms, the storage of cow manure in manure pits and subsequent application to field soil as a fertilizer may facilitate the spread of the mammalian gut microbiome and its associated ARGs to the environment. To determine the extent of both taxonomic and resistance similarity during these transitions, we collected fresh manure, manure from pits, and field soil across 15 different dairy farms for three consecutive seasons. We used a combination of shotgun metagenomic sequencing and functional metagenomics to quantitatively interrogate taxonomic and ARG compositional variation on farms. We found that as the microbiome transitions from fresh dairy cow manure to manure pits, microbial taxonomic compositions and resistance profiles experience distinct restructuring, including decreases in alpha diversity and shifts in specific ARG abundances that potentially correspond to fresh manure going from a gut-structured community to an environment-structured community. Further, we did not find evidence of shared microbial community or a transfer of ARGs between manure and field soil microbiomes. Our results suggest that fresh manure experiences a compositional change in manure pits during storage and that the storage of manure in manure pits does not result in a depletion of ARGs. We did not find evidence of taxonomic or ARG restructuring of soil microbiota with the application of manure to field soils, as soil communities remained resilient to manure-induced perturbation

Tadalafil Enhances Immune Signatures in Response to Neoadjuvant Nivolumab in Resectable Head and Neck Squamous Cell Carcinoma

Purpose: We hypothesize that the addition of the phosphodiesterase-5 inhibitor tadalafil to the PD-1 inhibitor nivolumab, is safe and will augment immune-mediated antitumor responses in previously untreated squamous cell carcinoma of the head and neck (HNSCC). Patients and methods: We conducted a two-arm multi-institutional neoadjuvant randomized trial in any-stage resectable HNSCC (NCT03238365). Patients were stratified at randomization by human papillomavirus (HPV) status. Patients in both arms received nivolumab 240 mg intravenously on days 1 and 15 followed by surgery on day 28. Those in the combination therapy arm also received tadalafil 10 mg orally once daily for 4 weeks. Imaging, blood, and tumor were obtained pretreatment and posttreatment for correlative analysis. Results: Neoadjuvant therapy was well-tolerated with no grade 3 to 5 adverse events and no surgical delays. Twenty-five of 46 (54%) evaluable patients had a pathologic treatment response of ≥20%, including three (7%) patients with a complete pathologic response. Regardless of HPV status, tumor proliferation rate was a negative predictor of response. A strong pretreatment T-cell signature in the HPV-negative cohort was a predictor of response. Tadalafil altered the immune microenvironment, as evidenced by transcriptome data identifying enriched B- and natural killer cell gene sets in the tumor and augmented effector T cells in the periphery. Conclusions: Preoperative nivolumab ± tadalafil is safe in HNSCC and results in more than 50% of the patients having a pathologic treatment response of at least 20% after 4 weeks of treatment. Pretreatment specimens identified HPV status-dependent signatures that predicted response to immunotherapy while posttreatment specimens showed augmentation of the immune microenvironment with the addition of tadalafil

Plasmodium vivax malaria with thrombocytopenia presenting as Subarachnoid Hemorrhage in an elderly male

It is of common belief that plasmodium vivax causes benign malaria. But there are lots of evidence now available to suggest that it can cause complicated malaria, even cerebral malaria like plasmodium falciparum. We present a case of an elderly male who presented to us with drowsiness and later diagnosed as having subarachnoid hemorrhage (SAH) due to severe thrombocytopenia caused by plasmodium vivax infection