Molecular mechanochemistry: low force switch slows enzymatic cleavage of human type I collagen monomer

In vertebrate animals, fibrillar collagen accumulates, organizes, and persists in structures which resist mechanical force. This antidissipative behavior is possibly due to a mechanochemical force-switch which converts collagen from enzyme-susceptible to enzyme-resistant. Degradation experiments on native tissue and reconstituted fibrils suggest that collagen/enzyme kinetics favor the retention of loaded collagen. We used a massively parallel, single molecule, mechanochemical reaction assay to demonstrate that the effect is derivative of molecular mechanics. Tensile loads higher than 3 pN dramatically reduced (10×) the enzymatic degradation rate of recombinant human type I collagen monomers by Clostridium histolyticum compared to unloaded controls. Because bacterial collagenase accesses collagen at multiple sites and is an aggressive cleaver of the collagen triple helical domain, the results suggest that collagen molecular architecture is generally more stable when mechanically strained in tension. Thus the tensile mechanical state of collagen monomers is likely to be correlated to their longevity in tissues. Further, strain-actuated molecular stability of collagen may constitute the fundamental basis of a smart structural mechanism which enhances the ability of animals to place, retain, and load-optimize material in the path of mechanical forces.     

Nonlinear-forced vibrations of piezoelectrically actuated viscoelastic cantilevers

This paper aims to study the nonlinear-forced vibrations of a viscoelastic cantilever with a piecewise piezoelectric actuator layer on its top surface using the method of Multiple Scales. The governing equation of motion is a second-order nonlinear ordinary differential equation with quadratic and cubic nonlinearities which appear in stiffness, inertia, and damping terms. The nonlinear terms are due to the piezoelectricity, viscoelasticity, and geometry of the system. Forced vibrations of the system are investigated in the cases of primary resonance and non-resonance hard excitation including subharmonic and superharmonic resonances. Analytical expressions for frequency responses are derived, and the effects of different parameters including damping coefficient, thickness to width ratio of the beam, length and position of the piezoelectric layer, density of the beam, and the piezoelectric coefficient on the frequency-response curves are discussed for each case. It is shown that in all these cases, the response of the system follows a softening behavior due to the existence of the piezoelectric layer. The piezoelectric layer provides an effective tool for active control of vibration. In addition, the effect of the viscoelasticity of the beam on passive control of amplitude of vibration is illustrated.     

Choosing the optimal intervention method to reduce human-related machine failures

This paper presents a novel method to quantify the effects of human-related factors on the risk of failure in manufacturing industries. When failures can be caused by operators, the decision maker must intervene to mitigate operator-related risk. There are numerous intervention methods possible; we develop a revenue model that provides the decision-maker with a systematic tool to perform a cost-benefit analysis, balancing the advantage of risk reduction, against the direct cost of the intervention method.     

Effects of operator learning on production output: a Markov chain approach

We develop a Markov chain approach to forecast the production output of a human-machine system, while encompassing the effects of operator learning. This approach captures two possible effects of learning: increased production rate and reduced downtime due to human error. In the proposed Markov chain, three scenarios are possible for the machine at each time interval: survival, failure, and repair. To calculate the state transition probabilities, we use a proportional hazards model to calculate the hazard rate, in terms of operator-related factors and machine working age. Given the operator learning curves and their effect on reducing human error over time, the proposed approach is considered to be a non-homogeneous Markov chain. Its result is the expected machine uptime. This quantity, along with production forecasting at various operator skill levels, provides us with the expected production output.     

Effective field theory for massive gravitons and gravity in theory space

We introduce a technique for restoring general coordinate invariance into theories where it is explicitly broken. This is the analog for gravity of the Callan-Coleman-Wess-Zumino formalism for gauge theories. We use this to elucidate the properties of interacting massless and massive gravitons. For a single graviton with a Planck scale M_Pl and a mass m_g, we find that there is a sensible effective field theory which is valid up to a high-energy cutoff Λ parametrically above m_g. Our methods allow for a transparent understanding of the many peculiarities associated with massive gravitons, among them the need for the Fierz-Pauli form of the Lagrangian, the presence or absence of the van Dam-Veltman-Zakharov discontinuity in general backgrounds, and the onset of non-linear effects and the breakdown of the effective theory at large distances from heavy sources. The natural sizes of all non-linear corrections beyond the Fierz-Pauli term are easily determined. The cutoff scales as Λ∼(m_g⁴M_Pl)^1/5 for the Fierz-Pauli theory, but can be raised to Λ∼(m_g²M_Pl)^1/3 in certain non-linear extensions. Having established that these models make sense as effective theories, there are a number of new avenues for exploration, including model building with gravity in theory space and constructing gravitational dimensions.     

Designing a New 4:2 Compressor Using an Efficient Multi-Layer Full-Adder Based on Nanoscale Quantum-Dot Cellular Automata

Quantum-dot Cellular Automata (QCA) is novel prominent nanotechnology. It promises a substitution to Complementary Metal–Oxide–Semiconductor (CMOS) technology with a higher scale integration, smaller size, faster speed, higher switching frequency, and lower power consumption. It also causes digital circuits to be schematized with incredible velocity and density. The full adder, compressor, and multiplier circuits are the basic units in the QCA technology. Compressors are an important class of arithmetic circuits, and researchers can use quantum compressors in the structure of complex systems. In this paper, first, a novel three-input multi-layer full-adder in QCA technology is designed, and based on it, a new multi-layer 4:2 compressor is presented. The proposed QCA-based full-adder and compressor uses an XOR gate. The proposed design offers good performance regarding the delay, area size, and cell number comparing to the existing ones. Also, in this gate, the output signal is not enclosed, and we can use it easily. The accuracy of the suggested circuits has been assessed with the utilization of QCADesigner 2.0.3. The results show that the proposed 4:2 compressor architecture utilizes 75 cell and 1.25 clock phases, which are efficient than other designs.

     

Synthesis,cytotoxic assessment,and molecular docking studies of 2,6-diaryl-substituted pyridine and 3,4- dihydropyrimidine-2(1H)-one scaffolds

Cancer is one of the main global health problems. In order to develop novel antitumor agents, we synthesized 3,4-dihydropyrimidine-2(1H)-one (DHPM) and 2,6-diaryl-substituted pyridine derivatives as potential antitumor structures and evaluated their cytotoxic effects against several cancer cell lines. An easy and convenient method is reported for the synthesis of these derivatives, employing cobalt ferrite (CoFe ₂ O ₄ @SiO ₂ -SO ₃ H) magnetic nanoparticles under microwave irradiation and solvent-free conditions. The structural characteristics of the prepared nanocatalyst were investigated by FTIR, XRD, SEM, and TGA techniques. In vitro cytotoxic effects of the synthesized products were assessed against the human breast adenocarcinoma cell line (MCF-7), gastric adenocarcinoma (AGS), and human embryonic kidney (HEK293) cells via MTT assay. The results indicated that compound 4r (DHPM derivative) was the most toxic molecule against the MCF-7 cell line (IC ₅₀ of 0.17 μg/mL). Moreover, compounds 4j and 4r (DHPM derivatives) showed excellent cytotoxic activities against the AGS cell line, with an IC ₅₀ of 4.90 and 4.97 μg/mL, respectively. Although they are pyridine derivatives, compounds 5g and 5m were more active against the MCF-7 cell line. Results showed that the candidate compounds exhibited low cytotoxicity against HEK293 cells. The kinesin Eg5 inhibitory potential of the candidate compounds was evaluated by molecular docking. The docking results showed that, among the pyridine derivatives, compound 5m had the most free energy of binding (–9.52 kcal/mol) and lowest Ki (0.105 μM), and among the pyrimidine derivatives, compound 4r had the most free energy of binding (–7.67 kcal/mol) and lowest Ki (2.39 μM). Ligand-enzyme affinity maps showed that compounds 4r and 5m had the potential to interact with the Eg5 binding site via H-bond interactions to GLU116 and GLY117 residues. The results of our study strongly suggest that DHPM and pyridine derivatives inhibit important tumorigenic features of breast and gastric cancer cells. Our results may be helpful in the further design of DHPMs and pyridine derivatives as potential anticancer agents.     

Rapid characterization the chemical constituents of Bergenia purpurascens and explore potential mechanism in treating osteoarthritis by ultra high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry combined with network pharmacology

In recent years, direct and indirect evidence has been found of the efficacy of the traditional Chinese medicine Bergenia purpurascens in treating arthritis and osteoarthritis. Several major components, such as bergenin and 11‐O‐galloylbergenin, have good anti‐inflammatory activity. Since research on the chemical components of Bergenia purpurascens and related mechanisms for the treatment of osteoarthritis has never been performed, this study aimed to analyze the chemical components of Bergenia purpurascens through ultra high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry technology and the UNIFI screening platform to predict the underlying mechanisms in treating osteoarthritis by analyzing the network pharmacology. In total, 43 chemical constituents were identified, mainly flavonoids (18), phenolic glycosides (13), and organic acids (7). Among them, 16 components were found in Bergenia purpurascens for the first time. Through the analysis of network pharmacology, several potential candidate targets and pathways were initially predicted, including AKT1, MAPK1, and MAPK3, as well as the apoptosis, estrogen, and MAPK signaling pathways. Bergenin, 11‐O‐galloylbergenin, arbutin, catechin‐3‐O‐gallate, and other components play a synergistic role in treating osteoarthritis. This study analyzed the chemical components of Bergenia purpurascens and preliminarily revealed potential mechanisms of treating osteoarthritis, providing a basis for further evaluating the drug's efficacy.     

Study of mechanism and kinetic modeling of CO hydrogenation reaction over the impregnated Co-Ni/Al2O3 catalyst

An investigation of the kinetic and mechanism of CO hydrogenation reaction was performed on impregnated Co-Ni/Al₂O₃. Determination of kinetic parameters from the experiments was carried out in a micro fixed-bed reactor. Kinetic evaluations were performed under various operational conditions of T = 473–673 K, p = 1–14 bar, H₂/CO = 1–3, and GHSV = 4,500 hr⁻¹. Kinetic models and rate equations for CO consumption were obtained by using two main-type rate equations of Langmuir-Hinshelwood-Hougen-Watson (LHHW) and Eley-Rideal (ER). Estimation of various kinetic parameters was performed using a nonlinear regression method. According to the obtained experimental results and using statistical criteria, one kinetic expression based on the LHHW mechanism (-r_CO = k_p.b_CO.P_CO. b_H2. P_H2/[1+ b_CO.P_CO + b_H2.P_H2]²) was chosen as the best-fitted model. For this fitted model, the activation energy was found to be 109.2 kJ/mol. Characterization of the catalyst was also performed using X-ray diffraction (XRD), BET, scanning electron microscopy (SEM), and energy-dispersive x-ray spectrometer (EDS) techniques.     

Assessment of Luminescent Downshifting Layers for the Improvement of Light‐Harvesting Efficiency in Dye‐Sensitized Solar Cells

Luminescence downshifting (LDS) of light can be a practical photon management technique to compensate the narrow absorption band of high‐extinction‐coefficient dyes in dye‐sensitized solar cells (DSSCs). Herein, an optical analysis on the loss mechanisms in a reflective LDS (R‐LDS)/DSSC configuration is reported. For squaraine dye (550–700 nm absorption band) and CaAlSiN₃:Eu²⁺ LDS material (550–700 nm emission band), the major loss channels are found to be non‐unity luminescence quantum efficiency (QE) and electrolyte absorption. By using an ideal LDS layer (QE=100 %), a less absorbing electrolyte (Co‐based), and antireflection coatings, approximately 20 % better light harvesting is obtained. If the absorption/emission band of dye/LDS is shifted to 800 nm, a maximal short‐circuit current density (J_sc) of 22.1 mA cm^?2 can be achieved. By putting the LDS layer in front of the DSSC (transmissive mode), more significant loss channels are observed, and hence a lower overall efficiency than the R‐LDS configuration.