Effect of foundation nonlinearity on the nonlinear transient response of orthotropic shallow spherical shells

Summary Interaction of clamped orthotropic shallow spherical shells with nonlinear elastic foundations is studied under transient loads. The effect of softening and hardening foundation nonlinearities on the response behaviour of shallow shells has been investigated. Detailed analysis depicting the influence of hardening type foundation nonlinearity on the maximum response of orthotropic shallow spherical shells has been conducted. The numerical results suggest that for the shell-foundation interaction problems undergoing moderately large deformations, the nonlinear model for the foundation must be considered.

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Einfluß der Bettungsnichtlinearität auf die nichtlineare transiente Antwort von orthotropen, leicht gekrümmten Schalen

übersicht Es wird die Wechselwirkung eingespannter orthotroper, leicht gekrümmter Schalen mit nichtnichtlinearer elastischer Bettung unter transienter Belastung behandelt. Dabei wird der Einfluß der erweichenden und der verfestigenden Nichtlinearität der Bettung auf das Antwortverhalten der schwach gekrümmten Schalen untersucht. Speziell wird der Einfluß der verfestigenden Bettungsnichtlinearität auf extreme Antwortverhalten von orthotropen, schwach sphärischen Schalen im einzelnen analysiert. Die numerischen Ergebnisse machen deutlich, daß bei Wechselwirkungsproblemen von Schale und Bettung mit mäßig großen Deformationen das nichtlineare Modell der Einbettung betrachtet werden muß.

     

Stability and dynamic analysis of partially cracked thin orthotropic microplates under thermal environment: an analytical approach

Abstract

An analytical model is proposed to analyze the vibration and buckling problem of partially cracked thin orthotropic microplate in the presence of thermal environment. The differential governing equation for the cracked plate is derived using the classical plate theory in conjunction with the strain gradient theory of elasticity. The crack is modeled using appropriate crack compliance coefficients based on the simplified line spring model. The influence of thermal environment is incorporated in governing equation in form thermal moments and in-plane compressive forces. The governing equation for cracked plate has been solved analytically to get fundamental frequency and central deflection of plate. To demonstrate the accuracy of the present model, few comparison studies are carried out with the published literature. The stability and dynamic characteristics of the cracked plate are studied considering various parameters such as crack length, plate thickness, change in temperature, and internal length scale of microstructure. It has been concluded that the frequency and deflection are affected by crack length, temperature, and internal length scale of microstructure. Furthermore, to study the buckling behavior of cracked plate, the classical relations for critical buckling load and critical buckling temperature is also proposed considering the effect of crack length, temperature, and internal length scale of microstructure.     

Quantitative surface field analysis: learning causal models to predict ligand binding affinity and pose

We introduce the QuanSA method for inducing physically meaningful field-based models of ligand binding pockets based on structure-activity data alone. The method is closely related to the QMOD approach, substituting a learned scoring field for a pocket constructed of molecular fragments. The problem of mutual ligand alignment is addressed in a general way, and optimal model parameters and ligand poses are identified through multiple-instance machine learning. We provide algorithmic details along with performance results on sixteen structure-activity data sets covering many pharmaceutically relevant targets. In particular, we show how models initially induced from small data sets can extrapolatively identify potent new ligands with novel underlying scaffolds with very high specificity. Further, we show that combining predictions from QuanSA models with those from physics-based simulation approaches is synergistic. QuanSA predictions yield binding affinities, explicit estimates of ligand strain, associated ligand pose families, and estimates of structural novelty and confidence. The method is applicable for fine-grained lead optimization as well as potent new lead identification.     

Diastereoselective synthesis of D-threo-sphinganine,L-erythro-sphinganine and (−)-spisulosine through asymmetric α-hydroxylation of a higher homologue of Garner's aldehyde

A diastereoselective route to the synthesis of D-threo-sphinganine, L-erythro-sphinganine and (?)-spisulosine from the higher homologue of Garner's aldehyde prepared from l-aspartic acid is reported. While the starting material contains one of the stereocenters in the target molecules, the other is generated by proline-catalyzed asymmetric α-hydroxylation of the aldehyde function. The two diastereomers of sphinganine are prepared from the same starting material and using the same sequence of reactions, but for the proline isomer used as the catalyst. The method described is simple and efficient and can easily be extended for the synthesis of other sphingoid bases.     

ForceGen 3D structure and conformer generation: from small lead-like molecules to macrocyclic drugs

We introduce the ForceGen method for 3D structure generation and conformer elaboration of drug-like small molecules. ForceGen is novel, avoiding use of distance geometry, molecular templates, or simulation-oriented stochastic sampling. The method is primarily driven by the molecular force field, implemented using an extension of MMFF94s and a partial charge estimator based on electronegativity-equalization. The force field is coupled to algorithms for direct sampling of realistic physical movements made by small molecules. Results are presented on a standard benchmark from the Cambridge Crystallographic Database of 480 drug-like small molecules, including full structure generation from SMILES strings. Reproduction of protein-bound crystallographic ligand poses is demonstrated on four carefully curated data sets: the ConfGen Set (667 ligands), the PINC cross-docking benchmark (1062 ligands), a large set of macrocyclic ligands (182 total with typical ring sizes of 12–23 atoms), and a commonly used benchmark for evaluating macrocycle conformer generation (30 ligands total). Results compare favorably to alternative methods, and performance on macrocyclic compounds approaches that observed on non-macrocycles while yielding a roughly 100-fold speed improvement over alternative MD-based methods with comparable performance.     

Modification of Kagan's amide for improved activity as Chiral Solvating Agent in enantiodiscrimination during NMR analysis

A modification is proposed in Kagan's amide in order to improve its ability to offer stronger hydrogen bonding and hence better ability to bind with substrates. Introduction of chlorine in the amide aromatic ring along with the two nitro groups, increases the acidic character of amide hydrogen and makes the hydrogen bond stronger, the concept is tested by making three derivatives of Kagan's amide and the effect is confirmed by nmr analysis. The modified chlorinated Kagan's amides were then tested as chiral solvating agents for detection of optical purity of several types of substrates where the supramolecular recognition is measured by in situ nmr analysis. Several guest molecules such as amide, sulfoxide, epoxy-keto, hydroxy acid, diacid and phosphoric acid were scanned for this study and its efficiency is further established by comparison with samples of known optical purity.     

A convenient method for the synthesis of fluorinated α-cyanoacetates via phase-transfer catalysis

A simple and convenient method for the synthesis of fluorinated α-cyanoacetate derivatives has been developed by using electrophilic fluorination of allyl and benzyl substituted α-cyanoacetates with N-fluorobenzensulfonimide (NFSI) as electrophilic fluorinating agent via phase transfer catalysis. The reaction is transition metal free and carried out in aqueous and mild reaction conditions in the presence of readily available tetra-N-butylammonium iodide (TBAI) as phase-transfer catalyst.     

Electroanalytical Sensor for Diabetic Foot Ulcer Monitoring with Integrated Electronics for Connected Health Application

L‐tyrosine is an amino acid, the concentration of which is found to be highly elevated in patients suffering from diabetic foot ulcer (DFU). The latter proves to be fatal when it turns out chronic and may lead to amputation. The conventional clinical diagnostic methods are costly and time consuming, in which case, the condition of patient(s) may deteriorate long before proper treatment commences. Herein, we report the development of smart band‐aid for real time monitoring of L‐tyrosine by employing enzymatic bio‐sensor using α‐MnO₂/tyrosinase. The smart band‐aid was further integrated with portable electronics capable of wireless data transmission to a personal digital assistant, and its tyrosine sensing performance was evaluated. Anodic current was found to vary linearly with the concentrations of L‐tyrosine in the range of 5 nM–500 μM. The developed sensor displayed a limit of detection and sensitivity of 0.71 nM and 0.67 μA/nM/mm² respectively, with a stability of 25 days. The developed sensor was validated using a commercial impedance analyzer. The impedance response was found to be consistent with the cyclic voltammogram obtained and demonstrated to be a linear function of tyrosine concentration. The developed sensing platform combines early diagnosis with connected health technologies, thus, fitting well into modern healthcare needs.     

Repurposing metocurine as main protease inhibitor to develop novel antiviral therapy for COVID-19

Structural Chemistry - The outbreak of severe acute respiratory syndrome coronavirus-2 is causing a serious disaster through coronavirus disease-19 (COVID-19) around the globe. A large segment of...