A Facile Synthesis of 1,5-Disubstituted Tetrazole Peptidomimetics by Desulfurization/Electrocyclization of Thiopeptides

The cis-amide bond isostere, 1,5-disubstituted tetrazole,has been introduced in the peptide backbone by a simple route starting from the thiopeptide. The desired 1,5-disubstituted tetrazole peptidomimetics were synthesized by the desulfurization of thiopeptides by using HgCl2 in the presence of NaN3/TEA in DMF in good yields. Various other thiophilic reagents including hypervalent iodine reagents failed to deliver the tetrazole product with the exception of CBr4/PPh3, which resulted in moderate yields. The advantage of the present protocol over previous methods has been demonstrated by the selective insertion of tetrazole into peptide-thiopeptide hybrids. Also, the protocol is compatible with commonly employed urethane protecting groups (Fmoc, Boc, and Cbz) in peptide chemistry. Thiopeptide Boc-Pro-CSNH]-Val-OMe (2i) and two tetrazole peptidomimetics Cbz-Ala-CN4]-Phe-OMe (3d) and Boc-Pro-CN4]-Val-OMe (3i) were obtained as single crystals and their molecular structures have been confirmed by X-ray crystallography.

Differential dynamics of the serotonin(1A) receptor in membrane bilayers of varying cholesterol content revealed by all atom molecular dynamics simulation

The serotonin(1A) receptor belongs to the superfamily of G protein-coupled receptors (GPCRs) and is a potential drug target in neuropsychiatric disorders. The receptor has been shown to require membrane cholesterol for its organization, dynamics and function. Although recent work suggests a close interaction of cholesterol with the receptor, the structural integrity of the serotonin(1A) receptor in the presence of cholesterol has not been explored. In this work, we have carried out all atom molecular dynamics simulations, totaling to 3s, to analyze the effect of cholesterol on the structure and dynamics of the serotonin(1A) receptor. Our results show that the presence of physiologically relevant concentration of membrane cholesterol alters conformational dynamics of the serotonin(1A) receptor and, on an average lowers conformational fluctuations. Our results show that, in general, transmembrane helix VII is most affected by the absence of membrane cholesterol. These results are in overall agreement with experimental data showing enhancement of GPCR stability in the presence of membrane cholesterol. Our results constitute a molecular level understanding of GPCR-cholesterol interaction, and represent an important step in our overall understanding of GPCR function in health and disease.

Effect of strain rate response and pin diameter on mechanically mixed layer formation and wear mechanisms in a Ti6Al4V-SS316L pair

Three mechanisms operate during wear of materials. These mechanisms include the Strain Rate Response (SRR - effect of strain rate on plastic deformation), Tribo-Chemical Reactions (TCR) and formation of Mechanically Mixed Layers (MML). The present work investigates the effect of these three in context of the formation of MML. For this wear experiments are done on a pin-on-disc machine using Ti64 as the pin and SS316L as the disc. It is seen that apart from the speed and load, which control the SRR and TCR, the diameter of the pin controls the formation of MML, especially at higher speeds.

High speed liquid crystal over silicon display based on the flexoelectro-optic effect.

One of the key technologies to evolve in the displays market in recent years is liquid crystal over silicon (LCOS) microdisplays. Traditional LCOS devices and applications such as rear projection televisions, have been based on intensity modulation electro-optical effects, however, recent developments have shown that multi-level phase modulation from these devices is extremely sought after for applications such as holographic projectors, optical correlators and adaptive optics. Here, we propose alternative device geometry based on the flexoelectric-optic effect in a chiral nematic liquid crystal. This device is capable of delivering a multilevel phase shift at response times less than 100 microsec which has been verified by phase shift interferometry using an LCOS test device. The flexoelectric on silicon device, due to its remarkable characteristics, enables the next generation of holographic devices to be realized.

抗癌药长春新碱及其与微管蛋白相互作用的电化学研究

在0.05 mol/L Tris，0.15 mol/L NaCl溶液中，用吸附伏安法研究长春新碱(VCR)，其峰电位在-1.68 V(vs. Ag/AgCl)，峰电流与1.0*10^{-8}～2.0*10^{-7}mol/L VCR浓度成正比，检测限为7.0*l0^{-9} mol/L，用常规脉冲极谱法、线性扫描和循环伏安法等研究该体系的电化学行为，实验表明，电极还原过程为具有吸附特征的不可逆过程。VCR的吸附符合Frumkin吸附等温式。也研究了VCR与微管蛋白的相互作用。实验表明，VCR与微管蛋白形成一电活性的结合物，这一结合物具有吸附性，且还原过程也为不可逆过程。

Low-temperature growth of carbon nanotubes by plasma-enhanced chemical vapor deposition

Vertically aligned carbon nanotubes were grown at temperatures as low as 120degreesC by plasma-enhanced chemical vapor deposition. A systematic study of the temperature dependence of the growth rate and the structure of the as-grown nanotubes is presented using a C2H2/NH3 system and nickel as the catalyst. The activation energy for the growth rate was found to be 0.23 eV, much less than for thermal chemical vapor deposition (1.2-1.5 eV). This suggests growth occurs by surface diffusion of carbon on nickel. The result could allow direct growth of nanotubes onto low-temperature substrates like plastics, and facilitate the integration in sensitive nanoelectronic devices. (C) 2003 American Institute of Physics.

Evaluación del marango (Moringa oleifera lam) como una alternativa en la alimentación de cerdos de engorde

El presente trabajo se realizó en la Finca "Santa Rosa" propiedad de las UNA, ubicada en Sabana Grande, Managua. El objetivo general del estudio fue: Evaluar el uso del Marango

Switch-level timing verification for CMOS circuits. A semianalytic approach

The paper describes a semianalytic slope delay model for CMOS switch-level timing verification. It is characterised by classification of the effects of the input slope, internal size and load capacitance of a logic gate on delay time, and then the use of a series of carefully chosen analytic functions to estimate delay times under different circumstances. In the field of VLSI analysis, this model achieves improvements in speed and accuracy compared with conventional approaches to transistor-level and switch-level simulation.

El acompañamiento a los padres con un recién nacido grave cercano a la muerte

Resumen: Desde su experiencia personal como profesional de la salud en el área de Pediatría, el autor menciona y reflexiona acerca de la relación médicopaciente que debe darse en las salas de pediatría, en especial en aquellos casos que presentan enfermedades graves y terminales. Si bien informa conocimientos que versan sobre la salud de los recién nacidos, hace hincapié en la necesidad de generar un buen acompañamiento de los padres para afrontar aquellos difíciles momentos. Para comprender y abordar la relación médico paciente y el acompañamiento a los padres de recién nacidos graves o en que la muerte es inminente, se va a enfocar el tema desde cinco perspectivas: 1) El recién nacido. 2) Los padres. 3) El equipo de salud. 4) La relación médico paciente. 5) El paso a la medicina paliativa.

Probing protein aggregation with quartz crystal microbalances.

The supra-molecular self-assembly of peptides and proteins is a process which underlies a range of normal and aberrant biological pathways in nature, but one which remains challenging to monitor in a quantitative way. We discuss the experimental details of an approach to this problem which involves the direct measurement in vitro of mass changes of the aggregates as new molecules attach to them. The required mass sensitivity can be achieved by the use of a quartz crystal transducer-based microbalance. The technique should be broadly applicable to the study of protein aggregation, as well as to the identification and characterisation of inhibitors and modulators of this process.

Las relaciones entre texto y música en la producción del rey Don Denis de Portugal

Integran este número de la revista ponencias presentadas en Studia Hispanica Medievalia VIII: Actas de las IX Jornadas Internacionales de Literatura Española Medieval, 2008, y de Homenaje al Quinto Centenario de Amadis de Gaula.

Evaluación de trece genotipos mejorados de frijol rojo (Phaseolus vulgaris L.) apante 2005, Yolaina, Nueva Guinea, RAAS

El presente trabajo fue establecido en la comunidad Yolaina, municipio de Nueva Guinea, RAAS en la finca del productor Calixto Silva en la época de apante 2005-2006. El objetivo planteado fue evaluar el comportamiento agronómico de trece genotipos de frijol rojo, de las cuales se seleccionarían dos con las mejores características. El diseño utilizado fue un BCA con tres repeticiones, las variables fueron hábito de crecimiento, adaptación vegetativa, vainas por plantas, granos por vainas, severidad a mustia hilachosa y mancha angular, días a madurez fisiológica, plantas cosechadas y rendimiento . Entre los resultados se destacan los siguientes: no se observaron diferencia significativa en rendimiento entre los genotipos estudiados. SRC 56-3 sin embargo, mostró la mejor tendencia para la variable mencionada. En cuanto a valor comercial los genotipos mejor clasificados fueron SRS 6-6, MPN 104-96 y MPN 105-17. Para la variable tolerancia a mustia hilachosa los genotipos más tolerantes fueron MPN 105-17, MPN y 103-137, los genotipos más susceptibles fueron MPN 104-96 y SRS 15-14. Con relación a mancha angular, los genotipos más tolerantes fueron MPN 101-12-1, MPN 104-96 y el SRS 6-6, el genotipo más susceptible fue MPN 103-137. En la variable rendimiento se encontró diferencias altamente significativas entre tratamiento, obteniendo una media de rendimiento de 1559.82 Kg. ha- 1. En conclusión se puede decir que el ensayo no permitió la identificación de materiales con rendimiento significativamente superior al testigo utilizado en el presente estudio, aunque el valor promedio obtenido para esta variable refleja una buena adaptación de los genotipos a la zona donde se evaluaron.