Harvey: A Greybox Fuzzer for Smart Contracts

We present Harvey, an industrial greybox fuzzer for smart contracts, which are programs managing accounts on a blockchain. Greybox fuzzing is a lightweight test-generation approach that effectively detects bugs and security vulnerabilities. However, greybox fuzzers randomly mutate program inputs to exercise new paths; this makes it challenging to cover code that is guarded by narrow checks, which are satisfied by no more than a few input values. Moreover, most real-world smart contracts transition through many different states during their lifetime, e.g., for every bid in an auction. To explore these states and thereby detect deep vulnerabilities, a greybox fuzzer would need to generate sequences of contract transactions, e.g., by creating bids from multiple users, while at the same time keeping the search space and test suite tractable. In this experience paper, we explain how Harvey alleviates both challenges with two key fuzzing techniques and distill the main lessons learned. First, Harvey extends standard greybox fuzzing with a method for predicting new inputs that are more likely to cover new paths or reveal vulnerabilities in smart contracts. Second, it fuzzes transaction sequences in a targeted and demand-driven way. We have evaluated our approach on 27 real-world contracts. Our experiments show that the underlying techniques significantly increase Harvey's effectiveness in achieving high coverage and detecting vulnerabilities, in most cases orders-of-magnitude faster; they also reveal new insights about contract code.Comment: arXiv admin note: substantial text overlap with arXiv:1807.0787

Effect of low temperature and ice treatments on the post-harvest quality of selected cultivars of cauliflower, cabbage and kohlrabi : an analysis of antioxidant activity, total phenol and L-ascorbic acid

Brassica, the only vegetable crop attributed with the potential to protect cancer and cardiovascular diseases were investigated in present study. The antioxidant activity, total phenol and L-ascorbic acid in 3 selected cultivars of cauliflower, cabbage and kohlrabi grown in Ås Norway (59°40’N) were stored at 0 °C, 5 °C and ice for 6-7 weeks. Antioxidants were analyzed by FRAP Assay in Konelab, total phenols by Follin-Ciocalteu’s phenol Reagent (FCR) in Konelab and L-ascorbic acid by HPLC. Overall, the low temperature enhanced the postharvest quality of selected vegetables. There was a variation in the content of antioxidant from 0.19-0.78 mmol/100g FW, 0.22-1.92 mmol/100g FW and 0.30-0.45 mmol/100g FW in cauliflower, cabbage and kohlrabi respectively where the exceptionally highest value was observed in ice stored red cabbage cv. Rovite (1.92 mmol/100g FW). The total phenol in the present study as a part of antioxidant was found to be varying from 39.14-85.39 mg GAE/100g FW, 29.12-166.89 mg GAE/100g FW and 26.81-42.27 mg GAE/100g FW in cauliflower, cabbage and kohlrabi respectively. Here, the dramatically high total phenol among the studied Brassica was noticed in Rovite stored in ice storage condition. Among treatments, the antioxidant activity and total phenolics increased at both 0 °C and 5 °C storage conditions in cauliflower while they did not significantly increase in cabbage and kohlrabi. Unlike 0 °C and 5 °C, the storage treatment in ice exhibited mixed effects with significant increase in the amount of antioxidant activity and total phenol in cauliflower cultivars (Flamenco and Celio) and cabbage cultivars (Castello and Rovite) or no significant increase in cauliflower cv. Nemo, cabbage cv. Bartolo or even decrease in kohlrabi cultivars. In the same way, L-ascorbic acid was ranging from 51.62-75.18 mg L-asc/100g FW, 32.77-46.27 mg L-asc/100g FW and 25.93-39.02 mg L-asc/100g FW respectively in cauliflower, cabbage and kohlrabi; with the highest value in cauliflower (Celio) at 0 °C. The analysis of L-ascorbic acid at different treatments in cauliflower cultivars illustrated that ice was the best storage condition though it decreased significantly in Celio. Meanwhile, L-ascorbic acid content decreased in cabbage and kohlrabi cultivars during storage except red cabbage (Rovite) where it increased significantly. Moreover, the variation in the content of dry matter in cauliflower, cabbage and kohlrabi ranged from 5.54-8.56%, 5.85-9.61% and 3.93-5.70% respectively; with a highest value in Bartolo cabbage at harvest and depicted a declining trend over storage among all the crops under study. The two-way Anova analysis and Turkey’s LSD for the treatment means revealed that the low temperature treatment of 0 °C was the best storage condition for the selected Brassica vegetables as it reduces the ongoing metabolism to the minimum. The present study thus suggests that this low temperature treatment preferably 0 °C can be used to commercially store Brassica vegetables

Novel NADPH Oxidase-2 Inhibitors as Potential Anti-Inflammatory and Neuroprotective Agents

A family of seven NADPH oxidase enzymes (Nox1-5, Duox1-2) has been implicated in a variety of diseases, including inflammatory lung diseases, neurodegenerative diseases, cardiovascular diseases, and cancer. Here, we report the results of our studies aimed at developing novel brain-permeable Nox2 inhibitors with potential application as neuroprotective agents. Using cell-based assays, we identified a novel Nox2 inhibitor, TG15-132, that prevents PMA-stimulated oxygen consumption and reactive oxygen species (superoxide radical anion and hydrogen peroxide) formation upon acute treatment in differentiated HL60 cells. Long-term treatment with TG15-132 attenuates the induction of genes encoding Nox2 subunits, several inflammatory cytokines, and iNOS in differentiated THP-1 cells. Moreover, TG15-132 shows a relatively long plasma half-life (5.6 h) and excellent brain permeability, with a brain-to-plasma ratio (>5-fold) in rodent models. Additionally, TG15-132 does not cause any toxic effects on vital organs or blood biomarkers of toxicity in mice upon chronic dosing for seven days. We propose that TG15-132 may be used as a Nox2 inhibitor and a potential neuroprotective agent, with possible further structural modifications to increase its potency

Evaluation of a new serological test for syphilis based on chemiluminescence assay in a tertiary care hospital

Context: Syphilis is a transfusion transmissible infections and it is mandatory to do serological test for syphilis (STS) on all donor blood samples. STS is usually based on detection of antibodies against the cardiolipin-lecithin antigen or against the Treponema-specific antigen. STS with good sensitivity and specificity helps enhance blood safety and consolidation of STS along with other transfusion transmittable infections such as human immunodeficiency virus, hepatitis-C virus, and hepatitis-B virus helps in reducing the errors and enhances efficiency. Aims: This study was designed to evaluate the performance of newly introduced VITROS ® syphilis Treponema pallidum agglutination (TPA) assay based on enhanced chemiluminescence principle for its analytical performance for use as a STS on donor blood samples at a tertiary care health center in National Capital Region, India. Materials and Methods: A total of 108 random blood units collected from the donors (both voluntary and replacement donors) and 28 known syphilis sero-reactive samples stored at −20°C, were used to evaluate the performance of VITROS ® syphilis TPA assay based on enhanced chemiluminescence assay on VITROS ® ECiQ immunodiagnostics system along with its analytical performance in terms of its sensitivity, precision, cross-reactivity and interference studies. Results: VITROS ® syphilis TPA showed 100% sensitivity and specificity with precision (20 days study) of <10% co-efficient of variation. There was no cross-reactivity with other viral and auto-immune antibodies. No interference was observed from endogenous interfering substances like free hemoglobin or fats. Conclusions: Performance of the VITROS ® syphilis TPA assay meets the requirements for its use as STS in blood bank, thus allowing consolidation with other transfusion transmittable infections screening assay on chemiluminescence platform, which is highly valuable for optimizing workflow and efficiency

Pharmacological antagonism of EP2 receptor does not modify basal cardiovascular and respiratory function, blood cell counts, and bone morphology in animal models.

The EP2 receptor has emerged as a therapeutic target with exacerbating role in disease pathology for a variety of peripheral and central nervous system disorders. We and others have recently demonstrated beneficial effects of EP2 antagonists in preclinical models of neuroinflammation and peripheral inflammation. However, it was earlier reported that mice with global EP2 knockout (KO) display adverse phenotypes on fertility and blood pressure. Other studies indicated that EP2 activation with an agonist has a beneficial effect of healing fractured bone in animal models. These results impeded the development of EP2 antagonists, and EP2 antagonism as therapeutic strategy. To determine whether treatment with EP2 antagonist mimics the adverse phenotypes of the EP2 global KO mouse, we tested two EP2 antagonists TG11-77. HCl and TG6-10-1 in mice and rats while they are on normal or high-salt diet, and by two different administration protocols (acute and chronic). There were no adverse effects of the antagonists on systolic and diastolic blood pressure, heart rate, respiratory function in mice and rats regardless of rodents being on a regular or high salt diet. Furthermore, chronic exposure to TG11-77. HCl produced no adverse effects on blood cell counts, bone-volume and bone-mineral density in mice. Our findings argue against adverse effects on cardiovascular and respiratory systems, blood counts and bone structure in healthy rodents from the use of small molecule reversible antagonists for EP2, in contrast to the genetic ablation model. This study paves the way for advancing therapeutic applications of EP2 antagonists against diseases involving EP2 dysfunction

Evaluation of nonspecific treponemal test rapid plasma reagin in comparison with specific treponemal test immunochromatographic assay for screening healthy blood donors

Introduction: Serological tests for syphilis (STS) contributed greatly to the detection of Treponema pallidum infection in blood donors and especially in those who were not identified during the medical selection. Most of the blood centers use nontreponemal tests due to lesser cost, ease of performance, and their ability to pick up early primary stage infection, despite reported high false positivity. However, increasingly large number of blood centers have begun testing with the treponemal tests such as immuno-chromatographic assay (ICA) which is possibly easier and more objective than rapid plasma reagin (RPR), albeit slightly expensive. It is with this background that we undertook a head-to-head comparison of nontreponemal test RPR with treponemal test ICA in over 10,000 consecutive blood donor samples with confirmation of all reactive and discordant samples by fluorescent treponemal antibody absorption assay (FTA-ABS) as the gold standard. Materials and Methods: The study was conducted in the department of transfusion medicine in a large tertiary care hospital in India. Consecutive blood donors from July 2014 to January 2015 were evaluated simultaneously for antitreponemal antibodies by solid phase ICA (SD BIOLINE Syphilis 3.0, Alere Medical Pvt. Ltd., USA), RPR (Immutrep RPR, Omega Diagnostics, Scotland, UK) and FTA-ABS (Biocientifica SA, FTA-ABS, Argentina). Performances of both the assays were evaluated in statistical terms. Results: A total of 10,200 donor samples were evaluated. There were 10,124 confirmed concordant negatives. Thirty-eight samples were concordant positive. Thirty-eight samples (thirty samples were ICA positive and RPR negative and eight samples were RPR positive and ICA negative) were discordant. The sensitivity of ICA was higher (93%) as compared to that of RPR (66%), whereas the specificity of RPR was higher (83%) than that of ICA (66%). Positive predictive value (PPV) of both the tests was similar while negative predictive value (NPV) of ICA was higher (86%) than that of RPR (60%). Youden's index was 0.81 for ICA whereas it was 0.62 for RPR. Conclusion: ICA has a better sensitivity than the RPR and thus seems to be more appropriate test for screening in blood donors

Autologous peripheral blood stem cell harvest: Collection efficiency and factors affecting it

Background: Harvest of hematopoietic progenitor cells via leukapheresis is being used increasingly for transplants in India. Adequate yield of cells per kilogram body weight of recipient is required for successful engraftment. Collection efficiency (CE) is an objective quality parameter used to assess the quality of leukapheresis program. In this study, we calculated the CE of the ComTec cell separator (Fresenius Kabi, Germany) using two different formulae (CE1 and CE2) and analyzed various patient and procedural factors, which may affect it. Materials and Methods: One hundred and one consecutive procedures in 77 autologous donors carried out over 3 years period were retrospectively reviewed. Various characteristics like gender, age, weight, disease status, hematocrit, preprocedure total leukocyte count, preprocedure CD34 positive (CD34+) cells count, preprocedure absolute CD34+ cell count and processed apheresis volume effect on CE were compared. CE for each procedure was calculated using two different formulae, and results were compared using statistical correlation and regression analysis. Results: The mean CE1 and CE2 was 41.2 and 49.1, respectively. CE2 appeared to be more accurate indicator of overall CE as it considered the impact of continued mobilization of stem cells during apheresis procedure, itself. Of all the factors affecting CE, preprocedure absolute CD34+ was the only independent factor affecting CE. Conclusion: The only factor affecting CE was preprocedure absolute CD34+ cells. Though the mean CE2 was higher than CE1, it was not statistically significant

Chemical composition, pesticidal activities and in-silico investigation of Hedychium spicatum Sm. chloroform extract

Abstract The present study aimed to identify the bioactive constituents in the chloroform extract of H. spicatum rhizomes (HS-RCLE), further evaluated for its in-vitro pesticidal activities validating via molecular docking techniques. GC/MS analysis of HS-RCLE identified 14 compounds contributing 84.1 % of the total composition. The extract was dominated by oxygenated sesquiterpenes (43.1 %) with curcumenone (25.2 %) and coronarin E (14.8 %) as the major compounds. The extract recorded 89.4 % egg hatchability inhibition and 82.6 % immobility of Meloidogyne incognita, 66.7 % insecticidal activity on Spodoptera litura, 100 % phytotoxic activity on Raphanus raphanistrum seeds, and 74.7 % anti-fungal activity on Curvularia lunata at the respective highest dose studied. The biological activities were furthermore validated by using docking studies on certain proteins/enzymes namely acetylcholinesterase (PBD ID: IC2O), carboxylesterase (PDB ID: 1CI8), acetohydroxyacid synthase (PBD ID: 1YHZ) and trihydroxy naphthalene reductase (PBD ID: 3HNR). The bioactivity of the major constituents of the extract was predicted with the help of in silico PASS studies. HS-RCLE was observed to be a viable alternative source of natural pesticidal agents and paves the way for further studies on its mechanistic approaches and field trials to ascertain its pesticidal studies

Establishing a sample-to cut-off ratio for lab-diagnosis of hepatitis C virus in Indian context

Introduction: Lab-diagnosis of hepatitis C virus (HCV) is based on detecting specific antibodies by enzyme immuno-assay (EIA) or chemiluminescence immuno-assay (CIA). Center for Disease Control reported that signal-to-cut-off (s/co) ratios in anti-HCV antibody tests like EIA/CIA can be used to predict the probable result of supplemental test; above a certain s/co value it is most likely to be true-HCV positive result and below that certain s/co it is most likely to be false-positive result. A prospective study was undertaken in patients in tertiary care setting for establishing this "certain" s/co value. Materials and Methods: The study was carried out in consecutive patients requiring HCV testing for screening/diagnosis and medical management. These samples were tested for anti-HCV on CIA (VITROS ® Anti-HCV assay, Ortho-Clinical Diagnostics, New Jersey) for calculating s/co value. The supplemental nucleic acid test used was polymerase chain reaction (PCR) (Abbott). PCR test results were used to define true negatives, false negatives, true positives, and false positives. Performance of different putative s/co ratios versus PCR was measured using sensitivity, specificity, positive predictive value and negative predictive value and most appropriate s/co was considered on basis of highest specificity at sensitivity of at least 95%. Results: An s/co ratio of ≥6 worked out to be over 95% sensitive and almost 92% specific in 438 consecutive patient samples tested. Conclusion: The s/co ratio of six can be used for lab-diagnosis of HCV infection; those with s/co higher than six can be diagnosed to have HCV infection without any need for supplemental assays