BMS Derivatives C7-Linked to β-Cyclodextrin and Hyperbranched Polyglycerol Retain Activity against R5-HIV-1NLAD8 Isolates and Can Be Deemed Potential Microbicides

Amides from indole-3-glyoxylic acid and 4-benzoyl-2-methylpiperazine, which are related to entry inhibitors developed by Bristol-Myers Squibb (BMS), have been synthesized with aliphatic chains located at the C7 position of the indole ring. These spacers contain an azido group suitable for the well-known Cu(I)-catalyzed (3+2)-cycloaddition or an activated triple bond for the nucleophilic addition of thiols under physiological conditions. Reaction with polyols (β-cyclodextrin and hyperbranched polyglycerol) decorated with complementary click partners has afforded polyol-BMS-like conjugates that are not cytotoxic (TZM.bl cells) and retain the activity against R5-HIV-1_NLAD8 isolates. Thus, potential vaginal microbicides based on entry inhibitors, which can be called of 4^th generation, are reported here for the first time.     

Experimental determination of 3D crack propagation scenario in resistance spot welds of a martensitic stainless steel

International Journal of Fracture - The development of high-performance automotive steels involves increasingly complex chemistries and heat treating sequences, to produce stronger and lighter...     

FOS: a low-power cache organization for multicores

The Journal of Supercomputing - The cache hierarchy of current multicore processors typically consists of one or two levels of private caches per core and a large shared last-level cache. This...     

Temperature stability of a pure metakaolin based K-geopolymer: Part 2. Variations in the mesoporous network and its rehydration stability

The thermal behavior of a model MK-based K-geopolymer was investigated between room temperature and 1400°C in order to evaluate its potentiality for high-temperature applications. The purpose of our study was to monitor the behavior of a geopolymer during a temperature rise in order to better understand its variations with respect to temperature. The works from the present paper focus only changes in the porous network; it follows a first part devoted to variations in the mineral matrix. The results obtained here show that the geopolymer material preserves its porous integrity up to 800°C, while maintaining the reversibility of water exchanges corresponding to about 25 weight percent. Together with the results of part 1, the findings of this study allow us to affirm that geopolymer materials are only very little affected by temperatures up to 800°C, or even 900°C (keeping its mesoporous amorphous structure).     

<Emphasis Type="Italic">K</Emphasis>-space data processing for magnetic resonance elastography (MRE)

Objective

Magnetic resonance elastography (MRE) requires substantial data processing based on phase image reconstruction, wave enhancement, and inverse problem solving. The objective of this study is to propose a new, fast MRE method based on MR raw data processing, particularly adapted to applications requiring fast MRE measurement or high elastogram update rate.

Materials and methods

The proposed method allows measuring tissue elasticity directly from raw data without prior phase image reconstruction and without phase unwrapping. Experimental feasibility is assessed both in a gelatin phantom and in the liver of a porcine model in vivo. Elastograms are reconstructed with the raw MRE method and compared to those obtained using conventional MRE. In a third experiment, changes in elasticity are monitored in real-time in a gelatin phantom during its solidification by using both conventional MRE and raw MRE.

Results

The raw MRE method shows promising results by providing similar elasticity values to the ones obtained with conventional MRE methods while decreasing the number of processing steps and circumventing the delicate step of phase unwrapping. Limitations of the proposed method are the influence of the magnitude on the elastogram and the requirement for a minimum number of phase offsets.

Conclusion

This study demonstrates the feasibility of directly reconstructing elastograms from raw data.

     

Efficiency of magnetic coupled boost DC‐DC converters mainly dedicated to renewable energy systems: influence of the coupling factor

This paper presents a specific analysis of an individual basic magnetically coupled direct current‐to‐direct current (DC–DC) converter specially designed for integration in a distributed architecture of renewable energy generators for smart grid applications. In such distributed architecture dedicated for renewable energy, parallel high‐voltage DC presents many advantages over the classical centralized one. We show that in such setup, high voltage can be advantageously produced using a specific magnetically coupled boost converter, and we point out the influence of the coupling factor, generally considered equal to one, on the overall performance of the converter and on the global energy efficiency of the installation. In this study, the generalized concepts of system energy parameters of DC–DC converters are introduced and applied to the transient analysis. Consequently, the operation of a magnetic coupled DC–DC converter with a recovery stage is modeled. The simulation results are compared with those of the behavioral study, deduced from the model pointing out the large influence of the coupling factor value on the global behavior and mainly on the value of the recovery voltage, in all the various parts of the switching cycle. The renewable energy generator operating parameters, such as current and voltage values, can then be predicted in a more useful way to compute new similar DC–DC converter systems. Copyright © 2014 John Wiley & Sons, Ltd.     

Optimization of the spark plasma sintering processing parameters affecting the properties of polyimide

The present study deals with the optimization of polyimide (PI) mechanical properties, obtained by Spark Plasma Sintering (SPS), by using a method combining Design of Experiments (DOE) with physical, structural, and mechanical characterizations. The effects of SPS parameters such as temperature, pressure, dwell time, and cooling rate on the density, mechanical properties, and structure of PI were investigated. The experimental results revealed that the mechanical properties of the material were optimized by raising the sintering temperature up to 350°C. The optimized SPS processing parameters were a temperature of 350°C, a pressure of 40 MPa, and a dwell time of 5 min. Under these conditions, a relative density of 99.6% was reached within only a few minutes. The corresponding mechanical properties consisted of Young's modulus of 3.43 GPa, a Shore D hardness of 87.3, and a compressive strength of 738 MPa for a maximum compressive strain of 61.8%. Moreover, when working at 320°C and at 100 MPa, an increase in the dwell time was necessary to enhance the properties. Contrary to the other parameters, the cooling rate appeared to be a non‐significant parameter. Finally, correlations between the PI structure and the mechanical properties were made to demonstrate the densification mechanisms. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41542.     

Three-Dimensional Cell Culture: A Breakthrough in Vivo

Cell culture is an important tool for biological research. Two-dimensional cell culture has been used for some time now, but growing cells in flat layers on plastic surfaces does not accurately model the in vivo state. As compared to the two-dimensional case, the three-dimensional (3D) cell culture allows biological cells to grow or interact with their surroundings in all three dimensions thanks to an artificial environment. Cells grown in a 3D model have proven to be more physiologically relevant and showed improvements in several studies of biological mechanisms like: cell number monitoring, viability, morphology, proliferation, differentiation, response to stimuli, migration and invasion of tumor cells into surrounding tissues, angiogenesis stimulation and immune system evasion, drug metabolism, gene expression and protein synthesis, general cell function and in vivo relevance. 3D culture models succeed thanks to technological advances, including materials science, cell biology and bioreactor design.     

Near-threshold fatigue propagation of physically through-thickness short and long cracks in a low alloy steel

In this paper, the near-threshold fatigue behavior of physically through-thickness short cracks and of long cracks in a low alloy steel is investigated by experiments in ambient air. Physically through-thickness short fatigue cracks are created by gradually removing the plastic wake of long cracks in compact tension specimens. The crack closure is systematically measured using the compliance variation technique with numerical data acquisition and filtering for accurate detection of the stress intensity factor (SIF) at the crack opening. Based on the experimental results, the nominal threshold SIF range is shown to be dependent on the crack length and the characteristic of the crack wake which is strongly dependent on the loading history. The effective threshold SIF range and the relation between the crack propagation rate and the effective SIF range after the crack closure correction are shown to be independent on crack length and loading history. The shielding effect of the crack closure is shown to be related to the wake length and load history. The effective threshold SIF range and the relationship between the crack growth rate and the effective SIF range appear to be unique for this material in ambient air. These properties can be considered as specific fatigue properties of the couple material/ambient air environment.     

Solid-Phase Synthesis of Substrate-Based Dipeptides and Heterocyclic Pseudo-dipeptides as Potential NO Synthase Inhibitors

More than 160 arginine analogues modified on the C-terminus via either an amide bond or a heterocyclic moiety (1,2,4-oxadiazole, 1,3,4-oxadiazole and 1,2,4-triazole) were prepared as potential inhibitors of NO synthases (NOS). A methodology involving formation of a thiocitrulline intermediate linked through its side-chain on a solid support followed by modification of its carboxylate group was developed. Finally, the side-chain thiourea group was either let unchanged, S-alkylated (Me, Et) or guanidinylated (Me, Et) to yield respectively after TFA treatment the corresponding thiocitrulline, S-Me/Et-isothiocitrulline and N-Me/Et-arginine substrate analogues. They all were tested against three recombinant NOS isoforms. Several compounds containing a S-Et- or a S-Me-Itc moiety and mainly belonging to both the dipeptide-like and 1,2,4-oxadiazole series were shown to inhibit nNOS and iNOS with IC₅₀ in the 1–50 μM range. Spectral studies confirmed that these new compounds interacted at the heme active site. The more active compounds were found to inhibit intra-cellular iNOS expressed in RAW264.7 and INS-1 cells with similar efficiency than the reference compounds L-NIL and SEIT.