Finding intermediates in the O2 activation pathways of non-heme iron oxygenases

Intermediates in the reaction cycle of an oxygenase are usually very informative with respect to the chemical mechanism of O 2 activation and insertion. However, detection of these intermediates is often complicated by their short lifetime and the regulatory mechanism of the enzyme designed to ensure specificity. Here, the methods used to detect the intermediates in an extradiol dioxygenase, a Rieske cis-dihydrodiol dioxygenase, and soluble methane monooxygenase are discussed. The methods include the use of alternative, chromophoric substrates, mutagenesis of active site catalytic residues, forced changes in substrate binding order, control of reaction rates using regulatory proteins, and initialization of catalysis in crystallo.     

Effect of N-Vinyl-2-Pyrrolidone (NVP), a Bromodomain-Binding Small Chemical,on Osteoblast and Osteoclast Differentiation and Its Potential Application for Bone Regeneration

The human skeleton is a dynamic and remarkably organized organ system that provides mechanical support and performs a variety of additional functions. Bone tissue undergoes constant remodeling; an essential process to adapt architecture/resistance to growth and mechanical needs, but also to repair fractures and micro-damages. Despite bone’s ability to heal spontaneously, certain situations require an additional stimulation of bone regeneration, such as non-union fractures or after tumor resection. Among the growth factors used to increase bone regeneration, bone morphogenetic protein-2 (BMP2) is certainly the best described and studied. If clinically used in high quantities, BMP2 is associated with various adverse events, including fibrosis, overshooting bone formation, induction of inflammation and swelling. In previous studies, we have shown that it was possible to reduce BMP2 doses significantly, by increasing the response and sensitivity to it with small molecules called “BMP2 enhancers”. In the present study, we investigated the effect of N-Vinyl-2-pyrrolidone (NVP) on osteoblast and osteoclast differentiation in vitro and guided bone regeneration in vivo. We showed that NVP increases BMP2-induced osteoblast differentiation and decreases RANKL-induced osteoclast differentiation in a dose-dependent manner. Moreover, in a rabbit calvarial defect model, the histomorphometric analysis revealed that bony bridging and bony regenerated area achieved with NVP-loaded poly (lactic-co-glycolic acid (PLGA) membranes were significantly higher compared to unloaded membranes. Taken together, our results suggest that NVP sensitizes BMP2-dependent pathways, enhances BMP2 effect, and inhibits osteoclast differentiation. Thus, NVP could prove useful as “osteopromotive substance” in situations where a high rate of bone regeneration is required, and in the management of bone diseases associated with excessive bone resorption, like osteoporosis.     

Synthesis of multistream heat exchangers by thermally linked two-stream modules

A simple yet very efficient algorithm has been devised for the analysis of multistream heat exchangers. In this approach, an n-stream heat exchanger is considered as a stack of (n ? 1) two-stream exchangers separated by diabatic partitions. Starting from the analysis of the basic two-stream units the entire heat exchanger can be designed non-iteratively. The validity of the algorithm has been established through a number of examples, comprising of two-steam exchanger with external heat leakage, three-stream and four-stream exchangers. Excellent agreements with experimental results and published simulation have been observed. Finally the most crucial assumption made in the present work has been assessed critically and its justification has been provided.     

Effect of Impact Angle on Ceramic Deposition Behavior in Composite Cold Spray: A Finite-Element Study

During the cold spraying of particle-reinforced metal matrix composite coatings (ceramic and metal particles mixture) on metal substrates, ceramic particles may either get embedded in the substrate/deposited coating or may rebound from the substrate surface. In this study, the dependence of the ceramic rebounding phenomenon on the spray angle and its effect on substrate erosion have been analyzed using finite-element analysis. From the numerical simulations, it was found that the ceramic particle density and substrate material strength played the major roles in determining the embedding and ceramic retention behavior. Substrate material erosion also influenced the ceramic retention, and the material loss increased as the impact angles decreased from normal. In general, the results concluded that decreasing the impact angle promoted the retention possibility of ceramics in the substrate. This study provides new theoretical insights into the effect of spray angles on the ceramic retention and suggests a new route toward optimizing the spraying process to increase the ceramic retention in composite coatings cold spray.     

Variable-coupling-induced optical trapping in optical waveguides via dressed continuum

We have studied a photonic structure, based on a semi-classical approach, considering simultaneous interaction of two side-coupled bent waveguides having variable coupling interactions (Gaussian and exponential-type) with a dressed continuum. We have examined the condition of optical trapping in spatial domain during propagation of a light field through the waveguide. The variation in parametric conditions leading to a typical trapping (quasi-trapping) phenomenon for both the cases of exponential and Gaussian coupling interactions is discussed. Simulation of such phenomenon of trapping in our macroscopic photonic structure is possible for all even relative positions of the side waveguides coupled to the dressed continuum. As far as the onset of quasi-trapping is concerned, the coupling width in the Gaussian coupling case is smaller than that in the exponential case. In this context, the Gaussian profile is found more tolerant than the exponential one so far as the separation between the side-coupled waveguides is concerned. Perfect trapping is observed to sustain by setting proper conditions while launching initial light in the side waveguides.     

Optimization Methods for Post-Bond Testing of 3D Stacked ICs

Testing of three-dimensional (3D) stacked ICs (SICs) is starting to receive considerable attention in the semiconductor industry. Since the die-stacking steps of thinning, alignment, and bonding can introduce defects, there may be a need to test multiple subsequent partial stacks during 3D assembly. We address the problem of test-architecture optimization for 3D stacked ICs to minimize overall test time when either the complete stack only, or the complete stack and multiple partial stacks, need to be tested. A general solution to this problem provides several options for 3D stack testing in a unified framework. We show that optimal test-architecture solutions and test schedules for multiple test insertions are different from their counterparts for a single final stack test. In addition, we present optimization techniques for the testing of TSVs and die-external logic in combination with the dies in the stack.     

Folate receptor targeted, carboxymethyl chitosan functionalized iron oxide nanoparticles: a novel ultradispersed nanoconjugates for bimodal imaging

This article delineates the design and synthesis of a novel, bio-functionalized, magneto-fluorescent multifunctional nanoparticles suitable for cancer-specific targeting, detection and imaging. Biocompatible, hydrophilic, magneto-fluorescent nanoparticles with surface-pendant amine, carboxyl and aldehyde groups were designed using o-carboxymethyl chitosan (OCMC). The free amine groups of OCMC stabilized magnetite nanoparticles on the surface allow for the covalent attachment of a fluorescent dye such as rhodamine isothiocyanate (RITC) with the aim to develop a magneto-fluorescent nanoprobe for optical imaging. In order to impart specific cancer cell targeting properties, folic acid and its aminated derivative was conjugated onto these magneto-fluorescent nanoparticles using different pendant groups (-NH(2), -COOH, -CHO). These newly synthesized iron-oxide folate nanoconjugates (FA-RITC-OCMC-SPIONs) showed excellent dispersibility, biocompatibility and good hydrodynamic sizes under physiological conditions which were extensively studied by a variety of complementary techniques. The cellular internalization efficacy of these folate-targeted and its non-targeted counterparts were studied using a folate-overexpressed (HeLa) and a normal (L929 fibroblast) cells by fluorescence microscopy and magnetically activated cell sorting (MACS). Cell-uptake behaviors of nanoparticles clearly demonstrate that cancer cells over-expressing the human folate receptor internalized a higher level of these nanoparticle-folate conjugates than normal cells. These folate targeted nanoparticles possess specific magnetic properties in the presence of an external magnetic field and the potential of these nanoconjugates as T(2)-weighted negative contrast MR imaging agent were evaluated in folate-overexpressed HeLa and normal L929 fibroblast cells.     

Vinylogous Organocatalytic Triple Cascade Reaction: Forging Six Stereocenters in Complex Spiro‐Oxindolic Cyclohexanes

We report a triple vinylogous cascade reaction, yielding valuable spiro‐oxindolic cyclohexane derivatives. The three‐component domino process proceeds by way of a catalyzed Michael/1,6‐addition/vinylogous aldol sequence affording the products with six stereogenic centers and very high control over the stereochemistry. The chemistry is based on a rare example of asymmetric 1,6‐addition to linear 2,4‐dienals proceeding with complete δ‐site selectivity. Key to the reaction development was a directing group positioned at the β‐dienal position, which was essential for achieving highly predictable reaction outcomes.

     

S-matrix of a slot-coupled circular to rectangular waveguide T-junction

An analysis of a slot-coupled T-junction consisting of a circular to rectangular waveguide is presented. The Galerkin method of moments with entire domain sinusoidal basis functions is used to solve the slot aperture electric field integral equations taking into account finite wall thickness. The slot coupler characteristics are deduced, including resonant length and dominant mode scattering. The theoretical results on the magnitude of the s-parameters are compared with experimental results. The effect of the variation of diameter of the circular waveguide as well as the width of the slot on the resonant length of the slot is also studied.