Analysis of a family of unstable lattice orientations in (110) channel die compression

Summary The family of f.c.c. crystal orientations defined by loading direction (110) and any channel die constraint direction between ( ) and ( ) is kinematically unstable. We establish that the experimentally observed finite rotation of the lattice about the loading axis, for initial orientations in this range, is uniquely predicted by the constraints and critical slip-system inequalities without regard to particular hardening theory. We further establish that experimental information on the changing constraint stress would serve to distinguish among theories. Predictions of three specific hardening rules, including classical Taylor hardening and the simple theory, are illustrated for initial constraint directions ( ) and ( ). For the first of these orientations the predictions include constraint stress, lattice rotation, active and latent hardening, and overall crystal shearing to a logarithmic compressive strain of 1.0.     

Isentropic exponents of real gases and application for the air at temperatures from 150 K to 450 K

Summary Three real gas isentropic exponentsk _Tv,k _rv,k _pT are introduced, which when used in place of the classical isentropic exponentk=c _p/c in the ideal gas isentropic change equations, the latter may describe very accurately the isentropic change of real gases. The usual practice of employing exponentk may lead to considerably incorrect results even when the value ofk corresponds to the correct local value ofc _p/c _v of the real gas under examination. The numerical values of the new exponents are calculated in the case of real air for temperatures from 150 K to 450 K and pressures from 1 bar to 1000 bar. It is seen that at low temperatures and high pressures the values of the new exponents differ considerably from the values of the classical exponentk. Therefore, the error resulting by approximating, as is usually the case, the behaviour of real gases by the ideal gas isentropic change equations in a stepwise fashion with exponentk instead of the new exponents, is considerable. It follows that exponentk, which appears in various relations in thermodynamics, fluid mechanics, gasdynamics, heat transfer etc., should be suitably replaced by combinations of the three exponents. Related numerical examples, made in the case of real air, showed that the use ofk leads (in the temperature and pressure ranges examined) to a 5% error in the calculation of blowby rate in internal combustion enginers, high pressure compressors or steam turbines and to a 50% error in the calculation of the isentropic expansion or compression.Nomenclature A _ij,B _i,N _ij,O _ij,Q _ij Coefficients - c Velocity - c _p Specific heat under constant pressure - c _v Specific heat under constant volume - h Specific enthalpy - k Isentropic exponent,k=c _p/c _v - k _pT Real gas isentropic exponent corresponding to the pair of variablesp,T - k _pv Real gas isentropic exponent corresponding to the pair of variablesp, v - k _Tv Real gas isentropic exponent corresponding to the pair of variablesT,v - M Mach number,M=c/ - p Pressure - p _c Pressure at the critical point - R Constant of the air,R=287.22 J/kg K - s Specific entropy - T Temperature - T _c Temperature at the critical point - v Specific volume - v _c Specific volume at the critical point - z Compressibility factor - Sound velocity - T Temperature increment With 14 Figures     

On some new variational formulations and finite element models in classical elastoplasticity

Summary The paper deals with the systematic development of variational methods and associated finite element schemes for the approximate analysis of elastoplastic continua. The major difference between these novel models and existing ones consists in treating the yield condition as an a posteriori (natural) constraint and not as an a priori (essential) constraint. The advantages of this approach over existing ones are pointed out and discussed from a theoretical and a computational standpoint as well.With 1 Figure     

Activation of hydrogen storage materials in the Li–Mg–N–H system: Effect on storage properties

We investigate the thermodynamics, kinetics, and capacity of the hydrogen storage reaction: Li₂Mg(NH)₂ + 2H₂  Mg(NH₂)₂ + 2LiH. Starting with LiNH₂ and MgH₂, two distinct procedures have been previously proposed for activating samples to induce the reversible storage reaction. We clarify here the impact of these two activation procedures on the resulting capacity for the Li–Mg–N–H reaction. Additionally, we measure the temperature-dependent kinetic absorption data for this hydrogen storage system. Finally, our experiments confirm the previously reported formation enthalpy (ΔH), hydrogen capacity, and pressure–composition–isotherm (PCI) data, and suggest that this system represents a kinetically (but not thermodynamically) limited system for vehicular on-board storage applications.     

Red Emissive Carbon Dots Prepared from Polymers as an Efficient Nanocarrier for Coptisine Delivery in vivo and in vitro

Negatively charged fluorescent carbon dots (CDs, E_m=608 nm) were hydrothermally prepared from thiophene phenylpropionic acid polymers and then successfully loaded with the positively charged anticancer cargo coptisine, which suffers from poor bioavailability. The formed CD-coptisine complexes were thoroughly characterized by particle size, morphology, drug loading efficiency, drug release, cellular uptake and cellular toxicity in vitro and antitumor activities in vivo. In this nano-carrier system, red emissive CDs possess multiple advantages as follows: 1) high drug loading efficiency (>96 %); 2) sustained drug release; 3) enhanced drug efficacy towards cancer cells; 4) EPR effect; 5) drug release tracing with near-infrared imaging. These properties indicated that red emissive CDs prepared from polymers could be used as a novel drug delivery system with integrated therapeutic and imaging functions in cancer therapy, which are expected to have great potential in future clinical applications.     

Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2

Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PL^pro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide ( 2 b ), which is known to bind into the S3 and S4 pockets of the SARS-CoV PL^pro. Moreover, we report the discovery of isoindolines as a new class of potent PL^pro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PL^pro are valuable starting points for the development of new pan-coronaviral inhibitors.     

Synthesis and Evaluation of Voltage-Gated Sodium Channel Blocking Pyrroline Derivatives Endowed with Both Antiarrhythmic and Antioxidant Activities

Under the hypothesis that cardioprotective agents might benefit from synergism between antiarrhythmic activity and antioxidant properties, a small series of mexiletine analogues were coupled with the 2,2,5,5-tetramethylpyrroline moiety, known for its antioxidant effect, in order to obtain dual-acting drugs potentially useful in the protection of the heart against post-ischemic reperfusion injury. The pyrroline derivatives reported herein were found to be more potent as antiarrhythmic agents than mexiletine and displayed antioxidant activity. The most interesting tetramethylpyrroline congener, a tert-butyl-substituted analogue, was at least 100 times more active as an antiarrhythmic than mexiletine.     

Stimuli-Responsive Nanomaterials for Smart Tumor-Specific Phototherapeutics

Phototherapy, a type of photoresponsive regulation of biological activities, together with additional stimuli-responsive features, offers significant potential for enhancing the precision and efficacy of cancer treatments. To achieve tumor-specific therapeutics, numerous studies have focused on the development of smart phototherapeutic nanomaterials (PNMs) that can respond to endogenous pathological characteristics (e. g., mild acidity, the overproduction of glutathione, the overproduction of hydrogen peroxide, the overexpression of specific surface receptors, etc.) present in the tumor and/or exogenous stimuli. Such responsiveness can effectively improve the physicochemical properties, cellular uptake, tumor-targeting performance, and pharmacokinetic profile of PNMs. Herein, we will systematically discuss recent advances in this field. Moreover, potential challenges and future directions in the development of stimuli-responsive PNMs are also presented to support the development of this emerging cutting-edge research area.     

Design,Synthesis and Biological Evaluation of Steroidal Glycoconjugates as Potential Antiproliferative Agents

To systematically evaluate the impact of neoglycosylation upon the anticancer activities and selectivity of steroids, four series of neoglycosides of diosgenin, pregnenolone, dehydroepiandrosterone and estrone were designed and synthesized according to the neoglycosylation approach. The structures of all the products were elucidated by NMR analysis, and the stereochemistry of C20-MeON-pregnenolone was confirmed by crystal X-ray diffraction. The compounds′ cytotoxicity on five human cancer cell lines was evaluated using a Cell Counting Kit-8 assay, and structure–activity relationships (SAR) are discussed. 2-deoxy-d -glucoside 5 k displayed the most potent antiproliferative activities against HepG2 cells with an IC₅₀ value of 1.5 μM. Further pharmacological experiments on compound 5 k on HepG2 cells revealed that it could cause morphological changes and cell-cycle arrest at the G0/G1 phase and then induced the apoptosis, which might be associated with the enhanced expression of high-mobility group Box 1 (HMGB1). Taken together, these findings prove that the neoglycosylation of steroids could be a promising strategy for the discovery of potential antiproliferative agents.     

A “Golden Age” for the discovery of new antileishmanial agents: Current status of leishmanicidal gold complexes and prospective targets beyond the trypanothione system

Leishmaniasis is one of the most neglected diseases worldwide and is considered a serious public health issue. The current therapeutic options have several disadvantages that make the search for new therapeutics urgent. Gold compounds are emerging as promising candidates based on encouraging in vitro and limited in vivo results for several Au^I and Au^III complexes. The antiparasitic mechanisms of these molecules remain only partially understood. However, a few studies have proposed the trypanothione redox system as a target, similar to the mammalian thioredoxin system, pointed out as the main target for several gold compounds with significant antitumor activity. In this review, we present the current status of the investigation and design of gold compounds directed at treating leishmaniasis. In addition, we explore potential targets in Leishmania parasites beyond the trypanothione system, taking into account previous studies and structure modulation performed for gold-based compounds.