Dynamic response of elastic beam to a moving pulse: finite element analysis of critical velocity

Dynamic behaviour of a semi-infinite elastic beam subjected to a moving single sinusoidal pulse was investigated by using finite element method associated with dimensionless analysis. The typical features of the equivalent stress and beam deflection were presented. It is found that the average value of maximal equivalent stress in the beam reaches its maximum value when the velocity of moving pulse is closed to a critical velocity. The critical velocity decreases as the pulse duration increases. The material, structural and load parameters influencing the critical velocity were analysed. An empirical formula of the critical velocity with respect to the speed of elastic wave, the gyration radius of the cross-section and the pulse duration was obtained

Epitaxial Growth of Germanium on Silicon for Light Emitters

National Basic Research Program of China [2007CB613404, 2012CB933503]; National Natural Science Foundation of China [61036003, 60837001, 61176092]; Fundamental Research Funds for the Central Universities [2010121056]This paper describes the role of Ge as an enabler for light emitters on a Si platform. In spite of the large lattice mismatch of similar to 4.2% between Ge and Si, high-quality Ge layers can be epitaxially grown on Si by ultrahigh-vacuum chemical vapor deposition. Applications of the Ge layers to near-infrared light emitters with various structures are reviewed, including the tensile-strained Ge epilayer, the Ge epilayer with a delta-doping SiGe layer, and the Ge/SiGe multiple quantum wells on Si. The fundamentals of photoluminescence physics in the different Ge structures are discussed briefly

Interfacial Stress in the Development of Biologics: Fundamental Understanding, Current Practice, and Future Perspective

Biologic products encounter various types of interfacial stress during development, manufacturing, and clinical administration. When proteins come in contact with vapor–liquid, solid–liquid, and liquid–liquid surfaces, these interfaces can significantly impact the protein drug product quality attributes, including formation of visible particles, subvisible particles, or soluble aggregates, or changes in target protein concentration due to adsorption of the molecule to various interfaces. Protein aggregation at interfaces is often accompanied by changes in conformation, as proteins modify their higher order structure in response to interfacial stresses such as hydrophobicity, charge, and mechanical stress. Formation of aggregates may elicit immunogenicity concerns; therefore, it is important to minimize opportunities for aggregation by performing a systematic evaluation of interfacial stress throughout the product development cycle and to develop appropriate mitigation strategies. The purpose of this white paper is to provide an understanding of protein interfacial stability, explore methods to understand interfacial behavior of proteins, then describe current industry approaches to address interfacial stability concerns. Specifically, we will discuss interfacial stresses to which proteins are exposed from drug substance manufacture through clinical administration, as well as the analytical techniques used to evaluate the resulting impact on the stability of the protein. A high-level mechanistic understanding of the relationship between interfacial stress and aggregation will be introduced, as well as some novel techniques for measuring and better understanding the interfacial behavior of proteins. Finally, some best practices in the evaluation and minimization of interfacial stress will be recommended

No ordinary proteins: Adsorption and molecular orientation of monoclonal antibodies

The interaction of monoclonal antibodies (mAbs) with air/water interfaces plays a crucial role in their overall stability in solution. We aim to understand this behavior using pendant bubble measurements to track the dynamic tension reduction and x-ray reflectivity to obtain the electron density profiles (EDPs) at the surface. Native immunoglobulin G mAb is a rigid molecule with a flat, “Y” shape, and simulated EDPs are obtained by rotating a homology construct at the surface. Comparing simulations with experimental EDPs, we obtain surface orientation probability maps showing mAbs transition from flat-on Y-shape configurations to side-on or end-on configurations with increasing concentration. The modeling also shows the presence of β sheets at the surface. Overall, the experiments and the homology modeling elucidate the orientational phase space during different stages of adsorption of mAbs at the air/water interface. These finding will help define new strategies for the manufacture and storage of antibody-based therapeutics

Diet-derived circulating antioxidants and risk of epilepsy: A study combining metabolomics and mendelian randomization

Background: Previous studies offer inconclusive results on the association between diet-derived circulating antioxidants and epilepsy. Objective: This study aims to assess oxidative stress presence in epilepsy patients' circulation and investigate the causal link between diet-derived circulating antioxidants and epilepsy. Methods: Untargeted metabolomics analysis was conducted on plasma samples from 62 epileptic patients and 20 healthy individuals to evaluate oxidative stress based on metabolite alterations in epilepsy patients' circulation. Two-sample Mendelian Randomization (MR) analysis examined the causation between diet-derived circulating antioxidants (measured by absolute levels and relative metabolite concentrations) and epilepsy, utilizing the inverse-variance weighted (IVW) method as the primary outcome, with complementary MR analysis methods (MR Egger, weighted median, weighted mode, and simple mode). Results: Untargeted metabolomics analysis revealed elevated circulating oxidizing metabolites (palmitic acid, oleic acid, linoleic acid, and myristic acid) and reduced reducing metabolites (glutamine) in epilepsy patients, providing robust evidence of oxidative stress. The IVW analysis indicated significantly reduced epilepsy risk (odds ratio: 0.552; 95% confidence interval: 0.335–0.905, P = 0.018) with genetically determined higher absolute circulating β-carotene. However, other diet-derived circulating antioxidants (lycopene, retinol, ascorbic acid, and selenium) and antioxidant metabolites (α-tocopherol, γ-tocopherol, ascorbic acid, and retinol) did not significantly associate with epilepsy risk. Additional MR analysis methods and heterogeneity assessments confirmed the results' robustness. Conclusion: This study provides compelling evidence of oxidative stress in epilepsy patients' circulation. However, the majority of diet-derived circulating antioxidants (lycopene, retinol, ascorbic acid, vitamin E, and selenium) are unlikely to causally associate with reduced epilepsy risk, except for β-carotene

Comparative Structural Studies of Vpu Peptides in Phospholipid Monolayers by X-Ray Scattering

Vpu is an 81-residue HIV-1 accessory protein, its transmembrane and cytoplasmic domains each responsible for one of its two functions. Langmuir monolayers of phospholipid incorporating a membrane protein with a unidirectional vectorial orientation, on a semiinfinite aqueous subphase, provide one “membranelike” environment for the protein. The cytoplasmic domain's interaction with the surface of the phospholipid monolayer in determining the tertiary structure of the peptide within the monolayer was investigated, employing a comparative structural study of Vpu with its submolecular fragments Tm and TmCy truncated to different extents in the cytoplasmic domain, via synchrotron x-ray scattering utilizing a new method of analysis. Localizations of the transmembrane and cytoplasmic domains within the monolayer profile structure were similar for all three proteins, the hydrophobic transmembrane helix within the hydrocarbon chain region tilted with respect to the monolayer plane and the helices of the cytoplasmic domains lying on the surface of the headgroups parallel to the monolayer plane. The thickness of the hydrocarbon chain region, determined by the tilt of the hydrocarbon chains and transmembrane domain with respect to the monolayer plane, was slightly different for Tm, TmCy, and Vpu systematically with protein/lipid mole ratio. Localization of the helices in the cytoplasmic domains of the three proteins relative to the headgroups depends on their extents and amphipathicities. Thus, the interaction of the cytoplasmic domain of Vpu on the surface may affect the tilt of the transmembrane helix within the hydrocarbon chain region in determining its tertiary structure in the membrane

Physical and electrical properties of thermally oxidized dielectrics on Si-capped Ge-on-Si substrate

National Basic Research Program of China [2012CB933503]; National Natural Science Foundation of China [61036003, 61176092]; Fundamental Research Funds for the Central Universities [2010121056]Thermal oxidation of silicon (Si)-capped germanium (Ge) epilayer on Si substrate is performed to study the effect of the physical interface on the electrical properties of Ge metaloxide-semiconductor capacitors. During the growth and oxidation of the Si cap layer, Ge atoms diffuse through the Si cap layer, and they are oxidized to GeO2. Once the Si cap layer is consumed, more Ge suboxides are generated, resulting in the serious degradation of the capacitance-voltage characteristics. Both the positive fixed charges generated by the evaporation of GeO and the negative fixed charges induced by the formation of Si-O-dangling bonds are proposed to affect the flat-band voltage shifts. These results suggest that the deposition of a thin Si cap layer on Ge is effective in suppressing the generation of Ge sub-oxides during thermal oxidation, thereby improving the performance of Ge capacitors. (C) 2012 American Vacuum Society. [DOI: 10.1116/1.3668115

Modulation of Schottky Barrier Height of Metal/TaN/n-Ge Junctions by Varying TaN Thickness

This paper demonstrates experimentally the modulation of the Schottky barrier height (SBH) of metal/TaN/n-Ge junctions by varying the TaN thickness in a dual stacked metal layer. The effective SBH for the metal/TaN/n-Ge Schottky junctions, originally pinned at 0.53-0.61 eV, decays to 0.44 eV, the barrier height of TaN/n-Ge, with an increase in the TaN thickness from 0 to 10 nm, independent of the type of metal. Dipole formation at the TaN/Ge interface is proposed to alleviate the metal-induced gap states and shift the pinning level toward the conduction band. The modulation of the SBH can be ascribed to the interdiffusion between the cap metals (Al, Fe, and Ni) and TaN.National Basic Research Program of China [2012CB933503]; National Natural Science Foundation of China [61036003, 61176092]; Fundamental Research Funds for the Central Universities [2010121056]; Ph.D. Programs Foundation of Ministry of Education of China [20110121110025

A Model Membrane Protein for Binding Volatile Anesthetics

Earlier work demonstrated that a water-soluble four-helix bundle protein designed with a cavity in its nonpolar core is capable of binding the volatile anesthetic halothane with near-physiological affinity (0.7 mM K(d)). To create a more relevant, model membrane protein receptor for studying the physicochemical specificity of anesthetic binding, we have synthesized a new protein that builds on the anesthetic-binding, hydrophilic four-helix bundle and incorporates a hydrophobic domain capable of ion-channel activity, resulting in an amphiphilic four-helix bundle that forms stable monolayers at the air/water interface. The affinity of the cavity within the core of the bundle for volatile anesthetic binding is decreased by a factor of 4–3.1 mM K(d) as compared to its water-soluble counterpart. Nevertheless, the absence of the cavity within the otherwise identical amphiphilic peptide significantly decreases its affinity for halothane similar to its water-soluble counterpart. Specular x-ray reflectivity shows that the amphiphilic protein orients vectorially in Langmuir monolayers at higher surface pressure with its long axis perpendicular to the interface, and that it possesses a length consistent with its design. This provides a successful starting template for probing the nature of the anesthetic-peptide interaction, as well as a potential model system in structure/function correlation for understanding the anesthetic binding mechanism