Utilizing Model Nanostructured Porous Inorganic Compounds Such as Silica to Beneficially Confine “Bio”-Relevant Molecules and Demonstrate their Potential in Therapeutics

Abstract | The importance of well-defined inorganic porous nanostructured materials in the context of biotechnological applications such as drug delivery and biomolecular sensing is reviewed here in detail. Under optimized conditions, the confinement of “bio”-relevant molecules such as pharmaceutical drugs, enzymes or proteins inside such inorganic nanostructures may be remarkably beneficial leading to enhanced molecular stability, activity and performance. From the point of view of basic research, molecular confinement inside nanostructures poses several formidable and intriguing problems of statistical mechanics at the mesoscopic scale. The theoretical comprehension of such non-trivial issues will not only aid in the interpretation of observed phenomena but also help in designing better inorganic nanostructured materials for biotechnological applications.

Spark plasma sintering of novel ZrB2-SiC-TiSi2 composites with better mechanical properties

We report here the development of ultrafine grained ZrB2-SiC composites using TiSi2 as the sintering aid and spark plasma sintering (SPS) as the processing technique. It was observed that the presence of TiSi2 improved the sinterability of the composites, such that near theoretical densification (99.9%) could be achieved for ZrB2-18 wt.% SiC-5 wt.% TiSi2 composites after SPS at 1600 degrees C for 10 min at 50 MPa. Use of innovative multi stage sintering (MSS) route, which involved holding the samples at lower (intermediate) temperatures for some time before holding at the final temperature, while keeping the net holding time to 10 min, allowed attainment of full densification of ZrB2-18 wt.% SiC-2.5 wt.% TiSi2 at a still lower final temperature of 1500 degrees C at 30 MPa. TEM observations, which revealed the presence of anisotropic ZrB2 grains with faceted grain boundaries and TiSi2 at the intergranular regions, suggested the occurrence of liquid phase sintering in the presence of TiSi2. No additional phase was detected in XRD as well as TEM, which confirmed the absence of any sintering reaction. The as developed composites possessed an excellent combination of Vickers hardness and indentation toughness, both of which increased with increase in TiSi2 content, such that the ZrBi2-18 wt.% SiC-5 wt.% TiSi2 (SPS processed at 1600 degrees C) possessed hardness of similar to 20 GPa and indentation toughness of similar to 5 MPa m(1/2). The use of MSS SPS at 1500 degrees C for ZrBi2-18 wt.% SiC-2.5 wt.% TiSi2 composite resulted in improvement in hardness of up to similar to 27 GPa and attainment of high flexural strength of similar to 455 MPa. (C) 2011 Elsevier B.V. All rights reserved.

Higher topoisomerase 2 alpha gene transcript levels predict better prognosis in GBM patients receiving temozolomide chemotherapy: identification of temozolomide as a TOP2A inhibitor

The search for molecular markers which predict response to chemotherapy is an important aspect of current neuro-oncology research. MGMT promoter methylation is the only proved marker of glioblastoma. The purpose of this study was to assess the effect of topoisomerase expression on glioblastoma survival and study the mechanisms involved. The transcript levels of all isoforms of the topoisomerase family in all grades of diffuse astrocytoma were assessed. A prospective study of patients with glioblastoma treated by a uniform treatment procedure was performed with the objective of correlating outcome with gene expression. The ability of TOP2A enzyme to relax the super coiled plasmid DNA in the presence of temozolomide was evaluated to assess its effect on TOP2A. The temozolomide cyctotoxicity of TOP2A-silenced U251 cells was assessed. The transcript levels of TOP2A, TOP2B, and TOP3A are upregulated significantly in GBM in comparison with lower grades of astrocytoma and normal brain samples. mRNA levels of TOP2A correlated significantly with survival of the patients. Higher TOP2A transcript levels in GBM patients predicted better prognosis (P = 0.043; HR = 0.889). Interestingly, we noted that temozolomide inhibited TOP2A activity in in-vitro enzyme assays. We also noted that siRNA knock down of TOP2A rendered a glioma cell line resistant to temozolomide chemotherapy. We demonstrated for the first time that temozolomide is also a TOP2A inhibitor and established that TOP2A transcript levels determine the chemosensitivity of glioblastoma to temozolomide therapy. Very high levels of TOP2A are a good prognostic indicator in GBM patients receiving temozolomide chemotherapy.

Interdependent cache analyses for better precision and safety

One of the challenges for accurately estimating Worst Case Execu-tion Time(WCET) of executables is to accurately predict their cache behaviour. Various techniques have been developed to predict the cache contents at different program points to estimate the execution time of memory-accessing instructions. One of the most widely used techniques is Abstract Interpretation based Must Analysis, which de-termines the cache blocks guaranteed to be present in the cache, and hence provides safe estimation of cache hits and misses. However,Must Analysis is highly imprecise, and platforms using Must Analysis have been known to produce blown-up WCET estimates. In our work, we propose to use May Analysis to assist the Must Analysis cache up-date and make it more precise. We prove the safety of our approach as well as provide examples where our Improved Must Analysis provides better precision. Further, we also detect a serious flaw in the original Persistence Analysis, and use Must and May Analysis to assist the Persistence Analysis cache update, to make it safe and more precise than the known solutions to the problem.

Better QOS with W/T SPR codes for the transmission of multimedia signals in Optical CDMA networks

In this paper optical code-division multiple-access (O-CDMA) packet network is considered, which offers inherent security in the access networks. The application of O-CDMA to multimedia transmission (voice, data, and video) is investigated. The simultaneous transmission of various services is achieved by assigning to each user unique multiple code signatures. Thus, by applying a parallel mapping technique, we achieve multi-rate services. A random access protocol is proposed, here, where all distinct codes are used, for packet transmission. The codes, Optical Orthogonal Code (OOC), or 1D codes and Wavelength/Time Single-Pulse-per-Row (W/T SPR), or 2D codes, are analyzed. These 1D and 2D codes with varied weight are used to differentiate the Quality of Service (QoS). The theoretical bit error probability corresponding to the quality of each service is established using 1D and 2D codes in the receiver noiseless case and compared. The results show that, using 2D codes QoS in multimedia transmission is better than using 1D codes.

Better early osteogenesis of electroconductive hydroxyapatite-calcium titanate composites in a rabbit animal model

In view of the fact that bone healing can be enhanced due to external electric field application, it is important to assess the influence of the implant conductivity on the bone regeneration in vivo. To address this issue, this study reports the in vivo biocompatibility property of multistage spark plasma sintered hydroxyapatite (HA)-80 wt % calcium titanate (CaTiO3) composites and monolithic HA, which have widely different conductivity property (14 orders of magnitude difference). The ability of bone regeneration was assessed by implantation in cylindrical femoral bone defects of rabbit animal model for varying time period of 1, 4, and 12 weeks. The overall assessment of the histology results suggests that the progressive healing of bone defects around HA-80 wt % CaTiO3 is associated with a better efficacy with respect to (w.r.t) early stage neobone formation, which is histomorphometrically around 140% higher than monolithic HA. Overall, this study demonstrates that the in vivo biocompatibility property of HA-80 wt % CaTiO3 with respect to local effects after 12 weeks of implantation is not compromised both qualitatively and quantitatively, and a comparison with control implant (HA) points toward the critical role of electrical conductivity on better early stage bone regeneration. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 842-851, 2014.

Metal nanoparticles as better protein-aggregation prevention agents than chaperones

Prevention or suppression of protein aggregation is of great importance in the context of protein storage, transportation and delivery. Traditionally chaperones or other chemically active agents are used to stop or diffuse native protein aggregation. We have used gold nanoparticles to prevent thermal aggregation of alcohol dehydrogenase (ADH), a protein that maintains the alcohol level in the liver and stomach. A light-scattering assay has been used to investigate the effect of gold nanoparticles on thermal aggregation of ADH and the result of our study has been summarized in Fig. 1. The scattered light intensity from the solution containing ADH decreases when 45 nm gold nanoparticles are added prior to heating (thermal denaturation) the solution, which indicates prevention of aggregation. The aggregation of the protein is suppressed to the extent of 96% with picomolar concentration of 45 nm gold nanoparticles while micromolar amounts of other proteins and biological substances are necessary to achieve the same effect. The extent varies with the size and the concentration of the gold NPs for the same protein concentration.

Zinc oxide based photocatalysis: tailoring surface-bulk structure and related interfacial charge carrier dynamics for better environmental applications

As an alternative to the gold standard TiO2 photocatalyst, the use of zinc oxide (ZnO) as a robust candidate for wastewater treatment is widespread due to its similarity in charge carrier dynamics upon bandgap excitation and the generation of reactive oxygen species in aqueous suspensions with TiO2. However, the large bandgap of ZnO, the massive charge carrier recombination, and the photoinduced corrosion-dissolution at extreme pH conditions, together with the formation of inert Zn(OH)(2) during photocatalytic reactions act as barriers for its extensive applicability. To this end, research has been intensified to improve the performance of ZnO by tailoring its surface-bulk structure and by altering its photogenerated charge transfer pathways with an intention to inhibit the surface-bulk charge carrier recombination. For the first time, the several strategies, such as tailoring the intrinsic defects, surface modification with organic compounds, doping with foreign ions, noble metal deposition, heterostructuring with other semiconductors and modification with carbon nanostructures, which have been successfully employed to improve the photoactivity and stability of ZnO are critically reviewed. Such modifications enhance the charge separation and facilitate the generation of reactive oxygenated free radicals, and also the interaction with the pollutant molecules. The synthetic route to obtain hierarchical nanostructured morphologies and study their impact on the photocatalytic performance is explained by considering the morphological influence and the defect-rich chemistry of ZnO. Finally, the crystal facet engineering of polar and non-polar facets and their relevance in photocatalysis is outlined. It is with this intention that the present review directs the further design, tailoring and tuning of the physico-chemical and optoelectronic properties of ZnO for better applications, ranging from photocatalysis to photovoltaics.

Estrategias metacognitivas de comprensión lectora y eficacia en la Asignatura Lengua y Literatura

Resumen: La investigación llamada “Estrategias metacognitivas de comprensión lectora y rendimiento en la Asignatura Lengua y Literatura” tiene como objetivo identificar las estrategias metacognitivas en comprensión lectora y determinar su relación con las calificaciones finales en la asignatura Lengua y Literatura. La hipótesis de este estudio es que los estudiantes con mayor utilización de estrategias metacognitivas en comprensión lectora, presentan un rendimiento mayor en la asignatura de Lengua y Literatura. Se trabajó sobre una muestra de 207 adolescentes de ambos sexos que cursaban 7º, 8º y 9º año del EGB3. Según los resultados de la investigación existe una relación significativa positiva de la estrategia de metacognición global con el rendimiento en la asignatura Lengua y Literatura.