The present work describes how water-miscible natural polyamine (NPA) spermidine (SPD) alters the conformational stability and dynamics of horse myoglobin (h-Mb) at pH 7.4. Analysis of thermal- and chemical-induced unfolding profiles of h-Mb at different concentrations of SPD at pH 7.4 revealed that SPD (≥5 mM) reduces the conformational stability of h-Mb. The effect of SPD was further corroborated using MD simulations, which showed that SPD (≥5 mM) enhanced the conformational fluctuations and reduced the structural stability of h-Mb. The SPD concentration effect on the thermodynamic equilibria (KU) of h-Mb was translated to the changes in preferential interaction coefficient (ΔΓ23) and hydration number (ΔΓw). The finding of the positive value of ΔΓ23 and the negative value of ΔΓw suggests that the interaction of SPD with h-Mb and the exclusion of water from the protein reduce the conformational stability of h-Mb. Analysis of SPD effects on enthalpy-entropy plots and temperature dependence of unfolding free energy of h-Mb suggests that the SPD forms soft, attractive enthalpic interactions with h-Mb. Analysis of SPD impact on the urea-concentration-dependent thermal unfolding midpoint temperature showed that SPD exhibits an additive effect to the urea-mediated decrease in the thermal stability of h-Mb.

Benzimidazoles and their derivatives represent an essential class of bioactive molecules. Benzimidazole derivatives hold mechanical, biochemical, and pharmaceutical significance, and they can also serve as ligands for transition metals. Benzimidazole derivatives are known to exhibit a wide range of biological activities and can be synthesized using various solvents and ring-closing reagents. The present review focuses on the comparative synthesis of benzimidazole derivatives using both microwave and thermal methods. It has been observed that the microwave and thermal methods of synthesizing benzimidazoles and their derivatives offer several advantages, including increased yield (up to 10% to 50%) and significantly reduced reaction time (reduced by 96% to 98%) compared to conventional synthesis methods. The synthesized compounds are subjected to in vitro antibacterial and antifungal activity evaluations. Additionally, it has been observed that certain compounds exhibit remarkable anticancer activity.

Analysis of glycine (GLY) and its methyl derivatives (N-methylglycine (MG), N, N-dimethylglycine (DMG), and glycine betaine (GB)) impacts on heat/chemical denaturation profiles of cytochrome c (H-Cyt c), molecular dynamic (MD) simulations of H-Cyt c, and CO-dissociation kinetics of natively folded carbonmonoxy-cytochrome c (MG-CO state) in aqueous or denaturant media provided important information: 1) osmolytes increase the local, global, and structural stability of H-Cyt c in the following order: GLY>MG>DMG>GB, 2) osmolytes oppose the denaturant impact to decrease the thermal stability of H-Cyt c, and it follows the order GLY>MG>DMG>GB, and 3) osmolytes decrease the structural and conformational-fluctuations of H-Cyt c. The translation of osmolyte concentration-dependent unfolding free energy to preferential hydration parameter and analysis of GLY and its methyl derivative effects on enthalpy-entropy plots and stability profiles revealed that, besides the preferential exclusion of osmolytes, the soft repulsive interactions of osmolytes with protein contribute to the osmolyte-induced enhancement in the conformational stability of H-Cyt c.

Osmotic Computing (OC) has emerged as a system that allows seamless integration of IoT-Edge-Cloud continuum. It aims at optimizing the orchestration and distribution of resources to IoT devices across edge and cloud environments. It enhances service delivery and optimizes response time by dynamically adapting to changing network workloads. This research paper presents a novel method for decision-making in OC environment using Deep Q-Networks (DQN) to intelligently manage and allocate resources. The proposed method has two different operations: service migration and task offloading. Using reinforcement learning, DQN-osmosis learns to make optimal decisions based on current state metrics, such as resource usage. The algorithm adapts to varying network situations and ensures effective resource allocation and enhanced performance. The mathematical model, that forms the basis of the proposed DQN-based approach is also presented. The model is explained through simulations. The results of the model demonstrate enhancements in the speed of task processing and the overall efficiency of the IoT system, proving the effectiveness of DQN in Osmotic Computing paradigm. To validate the hypothesis that the DQN-based framework performs better than other three methods, i.e., Random Agent, Q-Learning, and SARSA algorithm, Wilcoxon signed-rank test is performed. This non-parametric test compares the performance metric of the proposed method with above three algorithms. The results confirm the effectiveness of the proposed method.

The current study focuses on the experimental evidence to describe the molecular mechanism by which the sugars modulate the thermodynamic stability of hen egg-white lysozyme (Lyz) at pH 2.3. Analysis of thermal and chemical denaturation curves of Lyz under variable concentrations of sugar (trehalose, sucrose, maltose, glucose, ribose, glycerol) at pH 2.3 depicted important results: (i) sugar increases the thermodynamic stability of Lyz, and it typically tracks the order as: trehalose > sucrose > maltose > glucose > ribose > glycerol, and (ii) sugar increases the thermodynamic stability of Lyz via preferential exclusion of sugar at the protein surface, but the repulsive enthalpic interactions of sugar with protein also add to the sugar-mediated increase in thermodynamic stability of the protein. Analysis of the sugar effect on denaturant concentration dependent denaturation free energy of Lyz at pH 2.3 revealed that the sugar counteracts the denaturant (urea, guanidinium chloride (GdnCl)) efficacy to decrease the thermodynamic stability of Lyz. Furthermore, the counteraction efficiency of sugar on denaturant impact to decrease thermodynamic stability of Lyz typically tracks the order as: trehalose > sucrose > maltose > glucose > ribose > glycerol.

Pyrimidine is a pharmacologically important moiety that exhibits diverse biological activities. This review reflects the growing significance of transition metal-catalyzed reactions for the synthesis of pyrimidines (with no discussion being made on the transition metal-catalyzed functionalization of pyrimidines). The effect of different catalysts on the selectivity/yields of pyrimidines and catalyst recyclability (wherever applicable) are described, together with attempts to illustrate the role of the catalyst through mechanisms. Although several methods have been researched for synthesizing this privileged scaffold, there has been a considerable push to expand transition metal-catalyzed, sustainable, efficient and selective synthetic strategies leading to pyrimidines. The aim of the authors with this update (2017-2023) is to drive the designing of new transition metal-mediated protocols for pyrimidine synthesis.

In the current era, catalysts have gained intensive research interest in development of sustainable energy as well as environmental remediation. Recent exploration of novel two-dimensional (2D) materials can offer unparalleled superiorities in catalysis due to their novel geometric structure and electronic properties (e.g. intrinsically anisotropic electronic, thermoelectric, mechanical, and transport properties). Phosphorene, composed of a single atomic layer of black phosphorous, has emerged as a potential single elemental 2D material that bridges the gap between 2D metal chalcogenides and graphene in terms of physical properties. The puckered structure of phosphorene imparts great potential for their catalytic applications such as the generation and storage of clean energy (e.g. photovoltaic cells, supercapacitors, lithium-ion batteries, solar water splitting, and hydrogen/oxygen evolution reactions (HER/OER). In this review, an emphasis is placed on describing phosphorene in terms of its structural features (e.g. presence of defects) and catalytic properties along with synthesis strategies (e.g. liquid phase exfoliation, mechanical exfoliation, plasma exfoliation, and electrochemical exfoliation). This review is thus expected to provide comprehensive information on the current status of phosphorene as a catalyst (e.g. photocatalyst, electrocatalyst, and thermocatalyst) based on a combination of computational and experimental results.

Intelligent Transportation System (ITS) is becoming essential to modern transportation. Due to rise in the number of intelligent vehicles, memory and computation resource allocation closer to the user is becoming increasingly important. With the advent of Mobile Edge Computing, a new processing site is available that can provide memory and computational resource to lower the burden on the core network. However, handling multiple intelligent vehicles near-site requires fast handling of service requests. This paper proposes OsCoMIT, an Osmotic Computing based task segregation and resource allocation framework to handle services decomposed into macroservices and microservices at the edge network. For resource allocation the Proportional Fairness algorithm considers the requirements of the vehicles and maps them to the resources that result in less internal fragmentation. The effectiveness of the proposed framework is demonstrated on Intelligent Transportation System in 5G network using simulation and numerical analysis. It is found that the Proportional Fairness (PF) algorithm is better than the First Come First Serve (FCFS) and Priority Scheduling (PS) Algorithm in terms for memory and computation resource. It maximizes the system’s utility while ensuring fairness and QoS requirements. The performance of OsCoMIT framework is validated statistically using one-way analysis of variance (ANOVA) with 95 F_critical in case of memory and computation resources, which shows the significant improvement.

Pyrrole is an important aromatic heterocyclic scaffold found in many natural products and predominantly used in pharmaceuticals. Continuous efforts are being made to design and synthesize various pyrrole derivatives using different synthetic procedures. Among them, the Clauson–Kaas reaction is a very old and well-known method for synthesizing a large number of N-substituted pyrroles. In recent years, due to global warming and environmental concern, research laboratories and pharmaceutical industries around the world are searching for more environmentally friendly reaction conditions for synthesizing compounds. As a result, this review describes the use of various eco-friendly greener protocols to synthesize N-substituted pyrroles. This synthesis involves the reaction of various aliphatic/aromatic primary amines, and sulfonyl primary amines with 2,5-dimethoxytetrahydrofuran in the presence of numerous acid catalysts and transition metal catalysts. The goal of this review is to summarize the synthesis of various N-substituted pyrrole derivatives using a modified Clauson–Kaas reaction under diverse conventional and greener reaction conditions.

Biocatalytic reductive amination reactions with reductiveaminases(RedAms) are emerging transformations with a high potential valuefor pharmaceutical synthesis. Here, we report the identification andengineering of a RedAm to catalyze a reductive amination reaction,making a key intermediate in the synthesis of an investigational cyclin-dependentkinase (CDK) inhibitor, using the relatively bulky benzylamine asa nucleophile. The engineered enzyme contains six mutations with respectto the wild-type and displays high productivity at high substrateconcentrations (50-fold improved over the wild-type). After the optimizedenzyme variant was identified, crystal structures of both the wild-typeand mutant enzymes were solved and used to rationalize how structuralchanges to the RedAm improved its performance under process conditions.Results suggest that mutations affecting both substrate binding andenzyme thermostability contribute to improved enzyme performance.By enabling the multikilogram-scale synthesis of the chiral intermediate,this work highlights the versatility and industrial utility of RedAm-catalyzedreductive amination.

This study aims to fabricate customized Ankle Foot Orthosis (cAFO) using Additive Manufacturing (AM), for investigating the effectiveness of straight Carbon Fibre Strut (CFS) that enhances push-off limits of drop foot (DF) gait. Three patients with unilateral DF were studied and two different host materials were used to fabricate cAFO from two different AM machines. A comparative quantitative study between the gait pattern of normal foot and DF (on affected side for same patient) for CFS efficacy was done by conducting two gait trials: with and without cAFO. The study shows CFS with cAFO is an effective additive manufactured mechanical component for DF patients to improve lower extremity functionality. CFS stores and releases energy during various phases of the gait cycle required for normal gait functionality for instance an improvement can be seen in deviation in ankle power to +36.84 % and +60.57 % for patients under consideration. In design domain, previous studies confined to L shaped strut, also clinical validation of straight strut is very limited. In this article clinical validation of straight strut with rectangular cross-section on DF patient is presented by using state-of-the-art tools, gait lab and design software's, resulting in better customization and ankle-foot mobility with reduced plantarflexion.

The small organic molecules, known as osmolytes being ubiquitously present in different cell types, affect protein folding, stability and aggregation. However, it is unknown how the osmolytes affect the nanomechanical unfolding behavior of protein domain. Here, we show the osmolyte-dependent mechanical unfolding properties of protein titin immunoglobulin-27 (I27) domain using an atomic force microscopy (AFM)-based single-molecule force spectroscopy. We found that amines and methylamines improved the mechanical stability of I27 domain, whereas polyols had no effect. Interestingly, glycine betaine (GB) or trimethylamine-N-oxide (TMAO) increased the average unfolding force of the protein domain. The kinetic parameters analyzed at single-molecule level reveal that stabilizing effect of osmolytes is due to a decrease in the unfolding rate constant of I27, which was confirmed by molecular dynamics simulations. Our study reveals different effects that diverse osmolytes have on the mechanical properties of the protein, and suggests the potential use of osmolytes in modulating the mechanical stability of proteins required for various nano-biotechnological applications.

This work describes the fabrication of a carbon fabric polydimethylsiloxane (PDMS)-based strain sensor to monitor the human kinematics with high flexibility, durability, and sensitivity. A flexible stretchable strain sensor is fabricated by using activated carbon fabric and PDMS to form the nanocomposite film. For the fabrication of the flexible sensor, robustness, and durability of electrodes are essential for its performance. To create robust electrodes, a novel idea of using snap buttons is introduced. Various material, electrical and mechanical characteristics of the sensor samples have been analyzed and discussed. To understand the behavior of the sensor under varied environmental conditions, variations with respect to changes in temperature, humidity, and moisture conditions are comprehensively studied. The developed sensor has Young's modulus of elasticity (0.0127 MPa), high gauge factor (25.9), faster response time (~ms), excellent cyclic repeatability, and robustness to variation in temperature and humidity. Finally, the developed sensor is tested on the forefinger, wrist, and knees for monitoring human motions while performing different physical activities. The developed sensor has shown promising results and will be useful for applications across the field of wearable electronics and biomedical devices.

Passerini reaction is one of the most versatile reactions studied in organic chemistry and the products derived from the reaction have found their utilizing in various fields, such as natural product chemistry, heterocyclic chemistry, biomedical science, pharmaceutical industry, macrocyclic chemistry, polymer science and carbohydrate chemistry. Over the years, multicomponent reactions, especially Passerini reaction has become an important approach for the design and synthesis of macromolecules and polymeric materials. It allows for easy modification of the polymeric material, thus enabling the synthesis of multifunctional materials. Herein, we have discussed the synthesis and applications of Passerini reaction in polymer chemistry.

Multicomponent reactions (MCRs) cover strategically employed chemical transformations that incorporate three or more reactants in one pot leading to a functionalized final product. Thus, it is an ideal tool to achieve high levels of complexity, diversity, yields of desired products, atom economy, and reduced reaction times. Sugars belong to the class of naturally occurring compounds with fascinating applications in the field of drug discovery due to the presence of various hydroxy groups and well-defined stereochemistry. However, their potential in MCRs has been realized only recently. This account describes recent advances in the synthesis of sugar-derived heterocycles synthesized by MCRs. We hope to encourage the synthetic and medicinal chemistry community to apply this powerful MCR chemistry to generate novel glycoconjugate challenges.1 Introduction2 Synthesis of Various Functionalized Sugar Compounds2.1 Passerini and Ugi Multicomponent Reactions2.2 Petasis Reaction2.3 Hantzsch Reaction2.4 Domino Ferrier–Povarov Reaction2.5 Marckwald Reaction2.6 Groebke–Blackburn–Bienaymé (GBB) Reaction2.7 Prins–Ritter Reaction2.8 Debus–Radziszewski Imidazole Synthesis Reaction2.9 Mannich Reaction2.10 A3-Coupling Reaction2.11 [3+2]-Cycloaddition Reactions2.12 Miscellaneous Reactions3 Conclusion

It is well known that saving energy is one of the most important concerns of every industry and its utilization or the possible mode/devices for the transferring of it is an important parameter. For chemical industries, heat exchangers are backbone of them. Now a days Nano-fluids along with heat exchanger can be an option to enhance the heat transfer rate. So, Shell and Tube heat exchanger are frequently using by the several industries for heat removal/exchange purposes. These Nano-particles or Nano-fluids help to increase the heat transfer rate by providing large surface area. Using this quality of Nano-fluid along with Shell and Tube heat exchanger is main focus of present work. So, an attempt is made to perform the analysis for quantification of the effects of concentration of nanofluid on the various design parameter of Shell-Tube heat exchanger device i.e., heat transfer characteristic and fluid flow characteristic and also studied the effect of nanofluid concentration on thermal physical properties of Al2O3-water and CuO-water based nanofluid. Results are suggested better heat transfer capabilities of Nano-fluid over normal by doing comparable study for the nanofluid in terms of thermo-physical properties that is thermal conductivity, density and viscosity with base fluid in Shell-Tube heat exchanger. It can suggest easily that nanofluid gives excellent heat transfer coefficient than pure water (base fluid) so the result comes out in the form of reduced area for heat transfer with similar heat exchange capacity. Effect of Nano-particles concentration on the values of Reynolds number (Re) and Prandtl number (Pr) was also observed and it is found that Re and Pr is decreases with increasing value of particle concentration in the base fluid.