Docking Processes Research Articles

Risk Analysis on Autonomous Vessels based on Systems Theory – Application of NET-HARMS method

Abstract The shift towards Maritime Autonomous Surface Ships is a significant development in the maritime logistics industry, with the potential to enhance efficiency, safety, and environmental sustainability. However, the integration of autonomous systems also presents new challenges and risks, particularly in the absence of empirical data for traditional risk assessment methodologies. This research tackles this problem by utilizing the Net-worked Hazard Analysis and Risk Management System (Net-HARMS) method, a systems thinking method that hasn’t been previously employed in examining MASS. The method analyses the risks associated with the EC-funded, H2020, MOSES Project, which included a concept for automating the manoeuvring and docking processes with autonomous tugboats. The Net-HARMS method offers a comprehensive and holistic approach to risk assessment, overcoming the limitations of conventional probabilistic models. By constructing a Hierarchical Task Analysis and a task network, the research maps the system’s operational framework and explores task interdependencies. The use of a risk mode taxonomy allows for the identification of task-specific and emergent risks, which are then assessed by utilising the risk matrix of the Risk-Based Assessment Tool developed by DNV, to assess the final risk as a function of the effectiveness of each risk mitigation layer and the severity of the identified task consequences. The findings provide valuable insights into critical tasks requiring enhanced risk control measures and contribute to the development of safety constraints necessary for the successful implementation of autonomous shipping technologies. By applying Net-HARMS method to the realm of autonomous ships, this research not only fills a significant gap in maritime risk analysis but also sets a precedent for future studies in this rapidly evolving field.

Identification of novel PHGDH inhibitors based on computational investigation: an all-in-one combination strategy to develop potential anti-cancer candidates.

Biological studies have elucidated that phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme in the serine synthesis pathway in humans that is abnormally expressed in numerous cancers. Inhibition of the PHGDH activity is thought to be an attractive approach for novel anti-cancer therapy. The development of structurally diverse novel PHGDH inhibitors with high efficiency and low toxicity is a promising drug discovery strategy. A ligand-based 3D-QSAR pharmacophore model was developed using the HypoGen algorithm methodology of Discovery Studio. The selected pharmacophore model was further validated by test set validation, cost analysis, and Fischer randomization validation and was then used as a 3D query to screen compound libraries with various chemical scaffolds. The estimated activity, drug-likeness, molecular docking, growing scaffold, and molecular dynamics simulation processes were applied in combination to reduce the number of virtual hits. The potential candidates against PHGDH were screened based on estimated activity, docking scores, predictive absorption, distribution, metabolism, excretion, and toxicity (ADME/T) properties, and molecular dynamics simulation. Finally, an all-in-one combination was employed successfully to design and develop three potential anti-cancer candidates.

Research on visual servo strategy for the uncalibrated non-standard manipulator

Abstract Aiming at the problem that the hand-eye calibration of the uncalibrated non-standard manipulator cannot be addressed by the general calibration method, i.e., the eye-in-hand and eye-to-hand calibration method of the visual servo system was proposed to guide the manipulator without calibration. First, a camera was installed on the manipulator to complete the eye-in-hand calibration and achieve transformation from the end coordinate system to the camera coordinate system. Second, a second camera was used to achieve eye-to-hand calibration and obtain the transformation relationship from the end coordinate system to the calibration board. The entire calibration process only requires the collection of images from two scenarios, i.e., the docking and the completion of the docking processes. The implementation results show that the rotation error between groups is less than 1.5°, and the translation error between groups is less than 8 mm. Therefore, the proposed visual servo strategy can accurately guide the uncalibrated non-standard manipulator.

Rethinking Sweetener Discovering: Multiparameter Modeling of Molecular Docking Results between the T1R2-T1R3 Receptor and Compounds with Different Tastes.

Molecular docking has been widely applied in the discovery of new sweeteners, yet the interpretation of computational results sometimes remains difficult. Here, the interaction between the T1R2-T1R3 sweet taste receptor and 66 tasting compounds, including 26 sweet, 19 bitter, and 21 sour substances was investigated by batch molecular docking processes. Statistical analysis of the docking results generated two novel methods of interpreting taste properties. Quantitative correlation between relative sweetness (RS) and docking results created a multiparameter model to predict sweetness intensity, whose correlation coefficient r = 0.74 is much higher than r = 0.17 for the linear correlation model between sweetness and binding energy. The improved correlation indicated that docking results besides binding energy contain undiscovered information about the ligand-protein interaction. Qualitative discriminant analysis of different tasting molecules generated an uncorrelated linear discriminant analysis (UDLA) model, which achieved an overall 93.1% accuracy in discriminating the taste of molecules, with specific accuracy for verifying sweet, bitter, and sour compounds reaching 88.0%, 92.1%, and 100%. These unprecedented models provide a unique perspective for interpreting computational results and may inspire future research on sweetener discovery.

New bivalent metal chelates based on an NO-donor Schiff base ligand: synthesis, structural characterization, DFT simulation, biological evaluation, and molecular docking analysis

It is crucial to establish a correlation between the chemical structure of transition metal chelates and their anticipated biological activity to create efficient bioinorganic medications. Thus, new bivalent transition metal chelates; M = Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II), were easily synthesized from an innovative bidentate NO-donor Schiff base ligand (HL). A comprehensive series of physicochemical techniques like FT-IR, 1H NMR, ESR, TGA and UV–Vis spectroscopy was used to characterize the synthesized compounds. The metal is evidently coupled to two ligands through the deprotonated enolic oxygen and nitrogen atoms of imine groups in all chelates. The obtained analytical and spectroscopic data revealed that the chelates of Mn(II), Co(II), Ni(II) and Cu(II) adopted octahedral structures with two coordinated water molecules. On the other hand, the Zn(II) chelate was found to be a tetrahedron, while the Cd(II) one was a distorted tetrahedron. The energy optimized geometry of HL and some of its chelates as well as their quantum reactivity descriptors were estimated by DFT analysis. The antimicrobial and cytotoxicity screening exhibited that the compounds were bioactive with various biological activities. In addition, the binding interaction characteristics of the ligand and the Cu(II), Zn(II) and Cd(II) chelates were validated by molecular docking processes using three macromolecular biological receptors (Aureolysin, Staphylococcus Aureus metalloproteinase (1BQB), a penicillin-binding protein 3 from Escherichia Coli (4PJP) and a B-DNA (1BNA). The biological findings were correlated with the calculated DFT data and molecular docking results.

In vitro and in silico scolicidal effect of sanguinarine on the hydatid cyst protoscoleces.

We aimed to investigate the scolicidal effects of sanguinarine on hydatid cyst protoscoleces (PSCs) in vitro and in silico. Different targets were docked into the active sites of sanguinarine. Molecular docking processes and visualization of interactions were performed using AutoDock Vina and Discovery Studio Visualizer. Binding energy was calculated and compared (kcal/mol). PSCs were aspirated from the hydatid cysts and washed. The sediments of PSCs were then exposed to various concentrations (50, 25, 12, 6, 3, and 1 μg/mL) of sanguinarine. The viability test was finally evaluated by the Trypan blue solution 4%. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPX), and catalase were analyzed to assess the level of oxidative stress-treated PSCs. Caspase-3 activity rate was determined to evaluate cell apoptosis in treated PSCs. Among the receptors, acetylcholinesterase was identified as the excellent target, with Vina score of -11.8. Sanguinarine showed high scolicidal effects after 12, 24, and 48 h. Also, in the first hour of exposure to the drug, caspase-3 activity and MDA level significantly increased, but the levels of GSH and GPx had a significant reduction after 12, 24, and 48 h (P < 0.05). The findings of this study revealed that sanguinarine have potent scolicidal effects in vitro and in silico and could be considered an opportunity for the introduction of a novel and safe therapeutic agent for the treatment of cystic echinococcosis. However, supplementary studies will be desired to prove the current findings by examining sanguinarine in a clinical setting.

Rational design and eco-friendly one-pot multicomponent synthesis of novel ethylidenehydrazineylthiazol-4(5H)-ones as potential apoptotic inducers targeting wild and mutant EGFR-TK in triple negative breast cancer

A novel series of ethylidenehydrazineylthiazol-4(5H)-ones were synthesized using various eco-friendly one-pot multicomponent synthetic techniques. The anticancer activity of compounds (4a-m) was tested against 11 cancer cell lines. While the IC50 of all compounds was evaluated against the most sensitive cell lines (MDA-MB-468 and FaDu). Our SAR study pinpointed that compound 4a, having a phenyl substituent, exhibited a significant growth inhibition % against all cancer cell lines. The frontier anticancer candidates against the MDA-MB-468 were also examined against the wild EGFR (EGFR-WT) and mutant EGFR (EGFR-T790M) receptors. Most of the synthesized compounds exhibited a higher inhibitory potential against EGFR-T790M than the wild type of EGFR. Remarkably, compound 4k exhibited the highest inhibitory activity against both EGFR-WT and EGFR-T790M with IC50 values (0.051 and 0.021 µM), respectively. The pro-apoptotic protein markers (p53, BAX, caspase 3, caspase 6, caspase 8, and caspase 9) and the anti-apoptotic key marker (BCL-2) were also measured to propose a mechanism of action for the compound 4k as an apoptotic inducer for MDA-MB-468. Investigation of the cell cycle arrest potential of compound 4k was also conducted on MDA-MB-468 cancer cells. We also evaluated the inhibitory activities of compounds (4a-m) against both EGFR-WT and EGFR-T790M using two different molecular docking processes.

Stiffness Design of Active Capture Claw-Type Docking Mechanism for Lunar Sample Return

The docking mechanism is the key system for realizing the lunar-orbit docking mission of two spacecraft, which needs to have both capture correction and connection hold functions. The different stiffness requirements between the capture correction process, where low stiffness is desired, and the connection hold process, where high stiffness is desired, pose a significant challenge to the design of the docking mechanism. In this paper, an active capture claw docking mechanism is designed. Under the constraints of being lightweight and having an envelope size, three sets of independent claw mechanisms are designed using the modular design idea to achieve the performance optimization and function integration of the docking mechanisms. The theoretical model of the collision dynamics between the active and passive docking mechanisms is established; the stiffness value range of the docking mechanism is determined, and the typical docking conditions are simulated and verified. The results show that the stiffness design in this paper can satisfy the requirements of the two docking processes. The active capture claw docking mechanism developed was applied to the lunar surface sample return mission successfully and played an important role in the lunar-orbit docking mission.

Platinum and Palladium Compounds: Disrupting the Ergosterol Pathway in Trypanosoma cruzi.

Current treatment for Chagas' disease is based on two drugs, Nifurtimox and Benznidazol, which have limitations that reduce the effectiveness and continuity of treatment. Thus, there is an urgent need to develop new safe and effective drugs. In previous work, two new metal-based compounds with trypanocidal activity, Pd-dppf-mpo and Pt-dppf-mpo, were fully characterized. To unravel the mechanism of action of these two analogous metal-based drugs, high throughput omics studies were performed. A multimodal mechanism of action was postulated with several candidates as molecular targets. In this work, we validated the ergosterol biosynthesis pathway as a target for these compounds through the determination of sterol levels in treated parasites. Moving forward in the attempt to understand the molecular level at which these compounds participate, two enzymes that met eligibility criteria at different levels were selected for further studies: phosphomevalonate kinase (PMK) and lanosterol 14-α demethylase (CYP51). Molecular docking processes were carried out to search for potential sites of interaction for both enzymes. To validate these candidates, a gain-of-function strategy was used, through the generation of overexpressing PMK and CYP51 parasites. Results here presented confirm that the mechanism of action of Pd-dppf-mpo and Pt-dppf-mpo compounds involves the inhibition of both enzymes.

Investigation of the phytochemical composition, antioxidant, antibacterial, anti-osteoarthritis, and wound healing activities of selected vegetable waste

Agri-food wastes, produced following industrial food processing, are mostly discarded, leading to environmental hazards and losing the nutritional and medicinal values associated with their bioactive constituents. In this study, we performed a comprehensive analytical and biological evaluation of selected vegetable by-products (potato, onion, and garlic peels). The phytochemical analysis included UHPLC-ESI-qTOF-MS/MS in combination with molecular networking and determination of the total flavonoid and phenolic contents. Further, the antimicrobial, anti-osteoarthritis and wound healing potentials were also evaluated. In total, 47 compounds were identified, belonging to phenolic acids, flavonoids, saponins, and alkaloids as representative chemical classes. Onion peel extract (OPE) showed the higher polyphenolic contents, the promising antioxidant activity, the potential anti-osteoarthritis activity, and promising antimicrobial activity, especially against methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, OPE revealed to have promising in vivo wound healing activity, restoring tissue physiology and integrity, mainly through the activation of AP-1 signaling pathway. Lastly, when OPE was loaded with nanocapsule based hydrogel, the nano-formulation revealed enhanced cellular viability. The affinities of the OPE major metabolites were evaluated against both p65 and ATF-2 targets using two different molecular docking processes revealing quercetin-3,4′-O-diglucoside, alliospiroside C, and alliospiroside D as the most promising entities with superior binding scores. These results demonstrate that vegetable by-products, particularly, those derived from onion peels can be incorporated as natural by-product for future evaluation against wounds and osteoarthritis.

Measuring Point Planning and Fitting Optimization of the Flange and Spigot Structures of Aeroengine Rotors

An optimized measuring point planning and fitting method for rotor flange and spigot structures was proposed to achieve precise measurement of position and pose of the aeroengine rotors during docking processes. Firstly, the impact of circumferential phase angle, distribution range angle, total number of measuring points, and number of distribution rings on measurement uncertainty was analyzed. The measuring point planning schemes for flange and spigot were proposed. Secondly, the Gauss Newton iterative solution principle considering damping factors was clarified. Subsequently, an optimized iterative reweighting method consisting of weight iterative estimation, singular value detection under the Chauvenet criterion, and clustering detection was proposed for fitting the flange annular end face. A mapping point total least squares method with practical geometric significance was proposed for fitting the spigot cylinder face. Finally, measuring and fitting experiments were performed. The singular measuring point detection methods were verified. Under the optimized fitting methods, the goodness of fit and average orthogonal distance of flange and spigot structures are 0.756 and 0.089 mm, respectively, which have higher fitting accuracy than the other traditional methods.

In Silico Analysis of Pongamia pinnata to Inhibit Neuronal Apoptosis after Ischemic Stroke via NMDAR and Caspase-3

Highlight: The potential of Pongamia pinnata as an inhibitor of apoptosis in ischemic stroke has never been evaluated before. Pongamia pinnata has potential to inhibit neuronal apoptosis via NMDAR and Caspase-3 in ischemic stroke. Karanjachromene has the best binding interaction to inhibit NMDAR. ABSTRACT Introduction: One of the cardiovascular diseases with the highest mortality rate is stroke. Stroke is the second-leading cause of death worldwide. Each year, 12.2 million new cases of stroke occur, of which 7.6 million are ischemic strokes. In ischemic stroke, there are several pathways that cause neuronal apoptosis. The activity of NMDAR and caspase-3 is one of the pathways. Pongamia pinnata phytochemicals have a neuroprotective function against neurological disorders. However, its use as an inhibitor of apoptosis in ischemic stroke has never been evaluated before. Objective: This research was designed to evaluate the phytochemicals of Pongamia pinnata as inhibitors of neuronal apoptosis in ischemic stroke using an in silico study. Methods: This study used four main phytochemicals of Pongamia pinnata, namely Karanjin, Karanjachromene, Pongapin, and Pongachromene. The protein targets for neuronal apoptosis were NMDAR and caspase-3. The molecular docking processes were ligand preparation, protein preparation, grid box determination, molecular docking, and visualized molecular docking. Results: In silico results showed that at NMDAR target proteins, Karanjin, Karanjachromene, Pongapin, and Pongachromene have binding energies of -5.12, -5.83, -5.03, and -5.13 kcal/mol. At protein targets, Caspase-3, Karanjin, Karanjachromene, Pongapin, and Pongachromene have binding energies of -4.87, -4.98, -4.88, and -5.08 kcal/mol. Conclusion: The phytochemicals of Pongamia pinnata have the potential to inhibit neuronal apoptosis via NMDAR and caspase-3 in ischemic stroke. The binding of Karanjachromene to NMDAR demonstrated the compound's best interaction.

Taming Food-Drug Interaction Risk: Potential Inhibitory Effects of Citrus Juices on Cytochrome Liver Enzymes Can Safeguard the Liver from Overdose Paracetamol-Induced Hepatotoxicity.

Paracetamol overdose is the leading cause of drug-induced hepatotoxicity worldwide. Because of N-acetyl cysteine's limited therapeutic efficacy and safety, searching for alternative therapeutic substitutes is necessary. This study investigated four citrus juices: Citrus sinensis L. Osbeck var. Pineapple (pineapple sweet orange), Citrus reticulata Blanco × Citrus sinensis L. Osbeck (Murcott mandarin), Citrus paradisi Macfadyen var. Ruby Red (red grapefruit), and Fortunella margarita Swingle (oval kumquat) to improve the herbal therapy against paracetamol-induced liver toxicity. UHPLC-QTOF-MS/MS profiling of the investigated samples resulted in the identification of about 40 metabolites belonging to different phytochemical classes. Phenolic compounds were the most abundant, with the total content ranked from 609.18 to 1093.26 μg gallic acid equivalent (GAE)/mL juice. The multivariate data analysis revealed that phloretin 3',5'-di-C-glucoside, narirutin, naringin, hesperidin, 2-O-rhamnosyl-swertisin, fortunellin (acacetin-7-O-neohesperidoside), sinensetin, nobiletin, and tangeretin represented the crucial discriminatory metabolites that segregated the analyzed samples. Nevertheless, the antioxidant activity of the samples was 1135.91-2913.92 μM Trolox eq/mL juice, 718.95-3749.47 μM Trolox eq/mL juice, and 2304.74-4390.32 μM Trolox eq/mL juice, as revealed from 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid, ferric-reducing antioxidant power, and oxygen radical absorbance capacity, respectively. The in vivo paracetamol-induced hepatotoxicity model in rats was established and assessed by measuring the levels of hepatic enzymes and antioxidant biomarkers. Interestingly, the concomitant administration of citrus juices with a toxic dose of paracetamol effectively recovered the liver injury, as confirmed by normal sections of hepatocytes. This action could be due to the interactions between the major identified metabolites (hesperidin, hesperetin, phloretin 3',5'-di-C-glucoside, fortunellin, poncirin, nobiletin, apigenin-6,8-digalactoside, 6',7'-dihydroxybergamottin, naringenin, and naringin) and cytochrome P450 isoforms (CYP3A4, CYP2E1, and CYP1A2), as revealed from the molecular docking study. The most promising compounds in the three docking processes were hesperidin, fortunellin, poncirin, and naringin. Finally, a desirable food-drug interaction was achieved in our research to overcome paracetamol overdose-induced hepatotoxicity.

Ship Autonomous Berthing Simulation Based on Covariance Matrix Adaptation Evolution Strategy

Existing research on auto-berthing of ships has mainly focused on the design and implementation of controllers for automatic berthing. For the real automatic docking processes, not only do external environmental perturbations need to be taken into account but also motion paths, docking strategies and ship mechanical constraints, which are important influential factors to measure autonomous docking methods. Through a literature review of ship path planning and motion control for automatic berthing, it is found that many studies ignore the interference of the actual navigational environment, especially for ships sailing at slow speed when berthing, or do not consider the physical constraints of the steering gear and the main engine. In this paper, we propose a hybrid approach for autonomous berthing control systems based on a Linear Quadratic Regulator (LQR) and Covariance Matrix Adaptation Evolution Strategy (CMA-ES), which systematically addresses the problems involved in the berthing process, such as path planning, optimal control, adaptive berthing strategies, dynamic environmental perturbations and physically enforced structural constraints. The berthing control system based on the LQR and modified LQR-CMA-ES have been validated by simulation work. The simulation results show that the proposed method is able to achieve the automatic docking of the ship well and the system is robust and well adapted to environmental disturbances at slow speed when docking.

Molecular Docking of Bicycloproline Derivative Synthetic Compounds on Envelope Protein: Anti-SARS-CoV-2 Drug Discovery

Background: Although a SARS-CoV-2 vaccine is readily available, new cases of COVID-19 are still occurring. New drug discovery is needed to treat COVID-19. Protein E is one of the potential targets. Two synthetic compounds of bicycloproline derivatives have the potential to be developed. Objective: This study aimed to estimate the interaction of bicycloproline compounds to protein E in-silico. Methods: There were two bicycloproline-derived compounds, MI-09 and MI-30, used in docking. Remdesivir was used as a reference ligand. The crystal structure of the E protein was created using homology modeling, while the test compound was drawn using the Marvin Sketch. MOE 2022.02 and BDS 2021 were used for docking and visualization processes. Results: The pentamer of the SARS-CoV-2 E protein obtained a clash score (1.06); poor rotatomer (0.00%); favored rotamers (98.11%); Ramachandran favored (96.43%); Ramachandran outlier (1.78%); Rama Z-score (-1.08); and mol probity (1.04). Research shows promising inhibition potential of the MI-09 and MI-30. The MI-30 has the best binding energy of -10.3326 kcal/mol. Conclusion: The docking results show that MI-30 has potency as an inhibitor of protein E and can be developed in treating COVID-19. Further research is needed to confirm the result by in vitro and in vivo studies.

Crosslinked and Multi-Responsive Polymeric Vesicles as a Platform to Study Enzyme-Mediated Undocking Behavior: Toward Future Artificial Organelle Communication.

Various cellular functions are successfully mimicked, opening the door to the next generation of therapeutic approaches and systems biology. Herein, the first steps are taken toward the construction of artificial organelles for mimicking cell communication by docking and undocking of cargo in the membrane of swollen artificial organelles. Stimuli-responsive and crosslinked polymeric vesicles are used to allow docking processes at acidic pH at which ferrocene units in the swollen membrane state can undergo desired specific host-guest interaction using β-cyclodextrin as model cargo. The release of the cargo mediated by two different enzymes, glucose oxidase and α-amylase, is investigated, triggered by distinct enzymatic undocking mechanisms. Different release times for a useful transport are shown that can be adapted to different communication pathways. In addition, Försterresonanceenergytransfer(FRET) experiments further support the hypotheses of host-guest inclusion complexation formation and their time-dependent breakdown. This work paves a way to a platform based on polymeric vesicles for synthetic biology, cell functions mimicking, and the construction of multifunctional cargo delivery system.

Bioactive fraction from Plumeria obtusa L. attenuates LPS-induced acute lung injury in mice and inflammation in RAW 264.7 macrophages: LC/QToF-MS and molecular docking

In this study, the anti-inflammatory effects of the methanolic extract (TE) of Plumeria obtusa L. (aerial parts) and its fractions were evaluated in vitro, and active fraction was evaluated in vivo. Among tested extracts, dichloromethane fraction (DCM-F) exhibited the strongest inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) in RAW 264.7 macrophages. The effect of DCM-F on LPS-induced acute lung injury (ALI) in mice was studied. The animals were divided into five groups (n = 7) randomly; Gp I: negative control, GP II: positive control (LPS group), GP III: standard (dexamethasone, 2 mg/kg b.wt), GP IV and V: DCM-F (100 mg/kg), and DEM-F (200 mg/kg), respectively. DCM-F at a dose of 200 mg/kg suppressed the ability of LPS to increase the levels of nitric oxide synthase (iNOS), NO, tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), as measured by ELISA. In addition, the expression of cyclooxygenase-2 (COX-2) was reduced (determined by immunohistochemistry) and the level of malondialdehyde (MDA) was decreased while that of catalase was restored to the normal values. Furthermore, the histopathological scores of inflammation induced by LPS were reduced. Twenty-two compounds were tentatively identified in DCM-F using LC/ESI-QToF with iridoids, phenolic derivatives and flavonoids as major constituents. Identified compounds were subjected to two different molecular docking processes against iNOS and prostaglandin E synthase-1 target receptors. Notably, protoplumericin A and 13-O-coumaroyl plumeride were the most promising members compared to the co-crystallized inhibitor in each case. These findings suggested that DCM-F attenuates the LPS-induced ALI in experimental animals through its anti-inflammatory and antioxidant potential.

Isolation and Purification of Chromaffin Granules from Adrenal Glands and Cultured Neuroendocrine Cells.

Chromaffin granules isolated from adrenal glands constitute a powerful experimental tool to the study ofsecretory vesicle components and their participation in fusion and docking processes, vesicle aggregation, and interactions with cytosolic components. Although it is possible to isolate and purify chromaffin granules from adrenal glands of different species, bovine adrenal glands are the most used tissue source due to its easy handling and the large amount of granules that can be obtained from this tissue. In this chapter, we describe an easy-to-use and short-term protocol for efficiently obtaining highly purified chromaffin granules from bovine adrenal medulla. We additionally include protocols to isolate granules from cultured bovine chromaffin cells and PC12 cells, as well as a section to obtain chromaffin granules from mouse adrenal glands.

Novel 4-thiophenyl-pyrazole, pyridine, and pyrimidine derivatives as potential antitumor candidates targeting both EGFR and VEGFR-2; design, synthesis, biological evaluations, and in silico studies.

In this article, we continued our previous effort to develop new selective anticancer candidates based on the basic pharmacophoric requirements of both EGFR and VEGFR-2 inhibitors. Therefore, twenty-two novel 4-thiophenyl-pyrazole, pyridine, and pyrimidine derivatives were designed and examined as dual EGFR/VEGFR-2 inhibitors. Besides, the previously reported antimicrobial activities of the aforementioned nuclei motivated us to screen their antibacterial and antifungal activities as well. First, the antitumor activities of the newly synthesized derivatives were evaluated against two cancer cell lines (HepG-2 and MCF-7). Notably, compounds 2a, 6a, 7a, 10b, 15a, and 18a exhibited superior anticancer activities against both HepG-2 and MCF-7 cancer cell lines. These candidates were selected to further evaluate their anti-EGFR and anti-VEGFR-2 potentialities which were found to be very promising compared to erlotinib and sorafenib, respectively. Both 10b and 2a derivatives achieved better dual EGFR/VEGFR-2 inhibition with IC50 values of 0.161 and 0.141 μM and 0.209 and 0.195 μM, respectively. Moreover, the most active 10b was selected to evaluate the exact phase of cell cycle arrest and to investigate the exact mechanism of cancer cell death whether it be due to apoptosis or necrosis. On the other hand, all the synthesized compounds were tested against Gram-positive bacteria such as S. aureus and B. subtilis as well as Gram-negative bacteria such as E. coli and P. aeuroginosa. Also, the antifungal activity was investigated against C. albicans and A. flavus strains. The findings of the antimicrobial tests revealed that most of the investigated compounds exhibited strong to moderate antibacterial and antifungal effects. Furthermore, to understand the pattern by which the investigated compounds bound to the active site, all the newly synthesized candidates were subjected to two different docking processes into the EGFR and VEGFR-2 binding sites. Besides, we tried to correlate compound 10b and the reference drugs (erlotinib and sorafenib) through DFT calculations. Finally, following the biological data of the new pyrazole, pyridine, and pyrimidine derivatives as anticancer and antimicrobial candidates, we concluded a very interesting SAR for further optimization.

SMORES-EP, a modular robot with parallel self-assembly

Self-assembly of modular robotic systems enables the construction of complex robotic configurations to adapt to different tasks. This paper presents a framework for SMORES types of modular robots to efficiently self-assemble into tree topologies. These modular robots form kinematic chains that have been shown to be capable of a large variety of manipulation and locomotion tasks, yet they can reconfigure using a mobile reconfiguration. A desired kinematic topology can be mapped onto a planar pattern with optimal module assignment based on the modules' locations, then the mobile reconfiguration assembly process can be executed in parallel. A docking controller is developed to guarantee the success of docking processes. A hybrid control architecture is designed to handle a large number of modules and complex behaviors of each individual, and achieve efficient and robust self-assembly actions. The framework is demonstrated in both hardware and simulation on the SMORES-EP platform.