Synthesis of distributed systems Annual report, 1 Sep. 1967 - 31 Aug. 1968

Synthesis of distributed systems with application to feedback networks for phase shift oscillator

Synthesis of distributed systems Final report, 1 Sep. 1966 - 31 Aug. 1969

Algorithm for synthesis of distributed systems to solve circuit design problem

Automatic detection of polypoid skin lesions: The squash sign

“Earlier detection of malignant melanoma can save lives. Automatic in-vivo methods of melanoma detection including smart-phone applications are now available, but specificity is low, i.e. too many benign lesions are detected as possible melanomas. Polypoids, elevated and rounded lesions are one class of benign lesions. These raised lesions with piecewise circular borders, predominantly intradermal nevi and cutaneous polyps (IDNs), are always benign. Variegated coloring present in polypoid lesions can lead physicians to perform an unneeded biopsy. Contact dermatoscope plates with gel squash these lesions, leaving a “squash sign” marker of benignancy which can be automatically detected. We present a method to automatically recognize the squash sign in raised benign skin lesions. This method is a two-stage process. First an algorithm is implemented to narrow down upon the region of interest which is the area where the squash sign may possibly be present in the lesion. In the second stage, image features are extracted from the lesion as a whole and the region of interest described above, to mathematically model these benign lesions. The data set for training and testing set consisted of a variety of images containing intradermal nevi and cutaneous polyps, malignant melanomas and other benign lesions. All the images had a spatial resolution of 1024 by 768. It was observed that the mathematical model was able to recognize over 64% of the intradermal nevi and cutaneous polyps on both the training and testing sets. This method has the potential to reduce the number of false diagnoses in automatic melanoma detection devices”--Abstract, page iv

Structure-Based Site of Metabolism (SOM) Prediction of Ligand for CYP3A4 Enzyme: Comparison of Glide XP and Induced Fit Docking (IFD)

Metabolism is one of the prime reasons where most of drugs fail to accomplish their clinical trials. The enzyme CYP3A4, which belongs to the superfamily of cytochrome P450 enzymes (CYP), helps in the metabolism of a large number of drugs in the body. The enzyme CYP3A4 catalyzes oxidative chemical processes and shows a very broad range of ligand specificity. The understanding of the compound’s structure where oxidation would take place is crucial for the successful modification of molecules to avoid unwanted metabolism and to increase its bioavailability. For this reason, it is required to know the site of metabolism (SOM) of the compounds, where compounds undergo enzymatic oxidation. It can be identified by predicting the accessibility of the substrate’s atom toward oxygenated Fe atom of heme in a CYP protein. The CYP3A4 enzyme is highly flexible and can take significantly different conformations depending on the ligand with which it is being bound. To predict the accessibility of substrate atoms to the heme iron, conventional protein-rigid docking methods failed due to the high flexibility of the CYP3A4 protein. Herein, we demonstrated and compared the ability of the Glide extra precision (XP) and Induced Fit docking (IFD) tool of Schrodinger software suite to reproduce the binding mode of co-crystallized ligands into six X-ray crystallographic structures. We extend our studies toward the prediction of SOM for compounds whose experimental SOM is reported but the ligand-enzyme complex crystal structure is not available in the Protein Data Bank (PDB). The quality and accuracy of Glide XP and IFD was determined by calculating RMSD of docked ligands over the corresponding co-crystallized bound ligand and by measuring the distance between the SOM of the ligand and Fe atom of heme. It was observed that IFD reproduces the exact binding mode of available co-crystallized structures and correctly predicted the SOM of experimentally reported compounds. Our approach using IFD with multiple conformer structures of CYP3A4 will be one of the effective methods for SOM predictionAuthor A.P.S. is grateful to the University Grants Commission, New Delhi for the financial assistance under the major research project (42-677/2013 (SR)) and Dr. Babasaheb Ambedkar Marathwada University, Aurangabad for the research grant (STAT/VI/RG/Dept/2019-20/309-10)S

Facile synthesis of novel coumarin derivatives, antimicrobial analysis, enzyme assay, docking study, ADMET prediction and toxicity study

The work reports the synthesis under solvent-free condition using the ionic liquid [Et3NH][HSO4] as a catalyst of fifteen novel 3-((dicyclohexylamino)(substituted phenyl/heteryl)-methyl)-4-hydroxy-2H-chromen-2-onederivatives 4a–o as potential antimicrobial agents. The structures of the synthesized compounds were confirmed by IR, 1H-NMR, 13C-NMR, mass spectral studies and elemental analyses. All the synthesized compounds were evaluated for their in vitro antifungal and antibacterial activity. The compound 4k bearing 4-hydroxy-3-ethoxy group on the phenyl ring was found to be the most active antifungal agent. The compound 4e bearing a 2,4-difluoro group on the phenyl ring was found to be the most active antibacterial agent. The mode of action of the most promising antifungal compound 4k was established by an ergosterol extraction and quantitation assay. From the assay it was found that 4k acts by inhibition of ergosterol biosynthesis in C. albicans. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds to the active site of lanosterol 14α-demethylase, which suggests that the tested compounds inhibit the synthesis of this enzyme. The synthesized compounds were analyzed for in silico ADMET properties to establish oral drug like behavior and showed satisfactory results. To establish the antimicrobial selectivity and safety, the most active compounds 4e and 4k were further tested for cytotoxicity against human cancer cell line HeLa and were found to be non-cytotoxic in nature. An in vivo acute oral toxicity study was also performed for the most active compounds 4e and 4k and results indicated that the compounds are non-toxic.S

Movement of \u3ci\u3eStriacosta albicosta\u3c/i\u3e (Smith) (Lepidoptera: Noctuidae) Larvae on Transgenic \u3ci\u3eBt\u3c/i\u3e and Non-\u3ci\u3eBt\u3c/i\u3e Maize

Exposure of lepidopteran pests to Bacillus thuringiensis (Bt) proteins has been shown to affect the behavior of larvae, including increased movement and avoidance of Bt-expressing plants or diet. Therefore, we hypothesized that the behavior of western bean cutworm, Striacosta albicosta (Smith) (Lepidoptera: Noctuidae), an important pest of maize, could be affected when exposed to Bt plants. To test this hypothesis, we conducted a series of artificial arena and on-plant experiments to determine S. albicosta neonate behavior when exposed to Bt and non-Bt plant tissue. Video tracking experiments presented neonate larvae with the choice of Bt or non-Bt pollen in a Petri dish for 15 min while being video recorded for analysis with EthoVision software. This study showed an increase in mean velocity and total time spent moving for larvae in the presence of Cry1F vs. non-Bt when compared with Vip3A vs. non-Bt or Cry1F vs. Vip3A. However, there was no difference in total distance moved or time spent in the food zone for all scenarios. Maize tissue choice experiments allowed neonatal larvae the choice of feeding on Bt or non-Bt tassel or leaves for 9 h in Petri dish arenas. This experiment showed that larvae preferred tassel tissue over leaves but did not indicate that larvae could distinguish between Bt and non-Bt tissue. In contrast, on-plant experiments (including a whole plant neonate dispersal study under controlled conditions and an in-field silking behavior experiment) indicated that the presence of Cry1F and Vip3A Bt toxins increased plant abandonment, suggesting that larvae are able to detect and avoid Bt toxins. The discrepancy of these results is likely due to the on-plant studies providing more field-realistic environmental conditions and a longer duration of exposure to Bt toxins for the behavioral experiments. Our results represent the first steps in understanding the complex behavior of S. albicosta when exposed to Bt plants. A better understanding of the response of larvae when exposed to Bt traits can aid in the management of this pest, particularly for the design of resistance management strategies and refuge design

Optimal Sensor Placement with Adaptive Constraints for Nuclear Digital Twins

Given harsh operating conditions and physical constraints in reactors, nuclear applications cannot afford to equip the physical asset with a large array of sensors. Therefore, it is crucial to carefully determine the placement of sensors within the given spatial limitations, enabling the reconstruction of reactor flow fields and the creation of nuclear digital twins. Various design considerations are imposed, such as predetermined sensor locations, restricted areas within the reactor, a fixed number of sensors allocated to a specific region, or sensors positioned at a designated distance from one another. We develop a data-driven technique that integrates constraints into an optimization procedure for sensor placement, aiming to minimize reconstruction errors. Our approach employs a greedy algorithm that can optimize sensor locations on a grid, adhering to user-defined constraints. We demonstrate the near optimality of our algorithm by computing all possible configurations for selecting a certain number of sensors for a randomly generated state space system. In this work, the algorithm is demonstrated on the Out-of-Pile Testing and Instrumentation Transient Water Irradiation System (OPTI-TWIST) prototype vessel, which is electrically heated to mimic the neutronics effect of the Transient Reactor Test facility (TREAT) at Idaho National Laboratory (INL). The resulting sensor-based reconstruction of temperature within the OPTI-TWIST minimizes error, provides probabilistic bounds for noise-induced uncertainty and will finally be used for communication between the digital twin and experimental facility