Sol-Gel Transition and Structural Evolution on Multicomponent Gels Derived from the Alumina-Silica System

The capacity of the sol-gel process of producing highly pure, homogeneous alumina-silica based materials had been demonstrated in the last few years. However, a full understanding on the mechanisms associated to sol formation and sol to gel transition has not yet been achieved and is required for the development of a new generation of nano-structurally tailored materials that will significantly enhance the technological importance of the sol-gel process. In this work, tetraethyl orthosilicate (TEOS) and aluminum isopropoxide were used to prepare materials within the entire silica-alumina system. Process parameters, such as gelation time, were correlated to variables of the initial stage of the process, such as pH, temperature of hydrolysis and water/alkoxide ratio. The obtained gels were dried at 105°C and subsequently heat treated at 500 and 1100°C for 3 hours. X-ray diffraction and infrared spectroscopy were used to characterize the materials and phase transformations. Structural information obtained from phase characterization and phase transformations was correlated to the effects of the process variables on sol formation and gelation, providing insights related to the mechanisms involved. The influence of temperature of aluminum isopropoxide hydrolysis on peptization and gelation of the mixtures was noted. The different behavior of mixtures hydrolyzed at low and high temperatures was suggested to be caused by different mechanisms of surface charge formation on the structurally different aluminum hydroxides. Monophasic and diphasic mullite xerogels were produced by changing temperature of aluminum isopropoxide hydrolysis, and led to formation of mullite and Al−Si spinel phases respectively, when treated at 1100°C.     

Antisense-mediated isoform switching of steroid receptor coactivator-1 in the central nucleus of the amygdala of the mouse brain

Background

Antisense oligonucleotide (AON)-mediated exon skipping is a powerful tool to manipulate gene expression. In the present study we investigated the potential of exon skipping by local injection in the central nucleus of the amygdala (CeA) of the mouse brain. As proof of principle we targeted the splicing of steroid receptor coactivator-1 (SRC-1), a protein involved in nuclear receptor function. This nuclear receptor coregulator exists in two splice variants (SRC-1a and SRC-1e) which display differential distribution and opposing activities in the brain, and whose mRNAs differ in a single SRC-1e specific exon.

Methods

For proof of principle of feasibility, we used immunofluorescent stainings to study uptake by different cell types, translocation to the nucleus and potential immunostimulatory effects at different time points after a local injection in the CeA of the mouse brain of a control AON targeting human dystrophin with no targets in the murine brain. To evaluate efficacy we designed an AON targeting the SRC-1e-specific exon and with qPCR analysis we measured the expression ratio of the two splice variants.

Results

We found that AONs were taken up by corticotropin releasing hormone expressing neurons and other cells in the CeA, and translocated into the cell nucleus. Immune responses after AON injection were comparable to those after sterile saline injection. A successful shift of the naturally occurring SRC-1a:SRC-1e expression ratio in favor of SRC-1a was observed, without changes in total SRC-1 expression.

Conclusions

We provide a proof of concept for local neuropharmacological use of exon skipping by manipulating the expression ratio of the two splice variants of SRC-1, which may be used to study nuclear receptor function in specific brain circuits. We established that exon skipping after local injection in the brain is a versatile and useful tool for the manipulation of splice variants for numerous genes that are relevant for brain function.     

Hydration properties of aqueous Pb(II) ion

Using density functional theory and polarized continuum models, we have determined the most probable coordination number and structure of the first hydration shell of aqueous Pb(II). The geometries and hydration free energies of Pb(H2O)(1-9)(2+) were examined and benchmarked against experimental values. The free energies of hydration of Pb(H2O)(6-8)(2+) were found to match the experimental value within 10 kcal/mol. Moreover, based upon our thermochemical results for single water addition, primary hydration numbers of 6, 7, and 8 are all thermally accessible at STP. Use of a small-core 60 electron effective core potential (ECP) with the aug-cc-pvdz-PP basis on Pb resulted in structures that are significantly less hemidirected than predicted when using the large-core 78 electron ECP and the lanl2DZ basis on the metal. Our results imply that the hemi- to holo-directed transition in Pb(II)-water complexes is driven by coordination number and not hybridization of the 6s lone-pair orbital or enhanced covalent bonding in the Pb-OH2 bond. In addition to basis set effects, the influence of different solvation models on hydration reactions has further been examined so as to determine the relative accuracy of the calculated hydration thermochemistry.     

Vibrational analysis study of aluminum trifluoride phases

The vibrational modes of three solid AlF3 phases (alpha, beta, and amorphous high surface area AlF3) are investigated. Calculations have been performed using hybrid exchange correlation functionals to determine the equilibrium geometries and Gamma-point phonon frequencies for the alpha-AlF3 and beta-AlF3 phases. The calculated optical modes are in excellent agreement with experiment. The IR absorption of the amorphous, glasslike high surface area (HS)-AlF3 is also discussed. Deconvolution of the broad envelope of IR stretches and bending vibrations identifies the components of the observed broad band. From the IR vibrational spectrum it has been shown that both short-range and medium-range disorder are present within HS-AlF3. Structural phase transitions are identified by their phase transition temperature Tc, measured by thermal analysis.     

AES and FTIR characterization of sol–gel alumina films

In this work we obtained sol–gel alumina coatings on AISI 304 stainless steel substrates. Alumina sols were prepared by using aluminum isopropoxide (AI) as precursor, acetic acid (HOAc) as catalyst, ethanol (C₂H₅OH) or isopropanol (C₃H₈O) as solvent, and water. The as-prepared solutions were deposited on stainless steel substrates by means of the dip-coating technique. The obtained composites were characterized by Fourier transform infrared spectroscopy (FTIR) and Auger electron spectroscopy (AES). We observed that the concentration of AlO type bonds in the obtained alumina coatings depends on the solvent type used, temperature and peptization state of the sol, withdrawal speed, and number of dipping cycles. AES experiments showed that the interface formed between the alumina coating and substrate surface is in general formed by several layers of different chemical compositions.     

Cyclodextrin-based Nanosponges for Drug Delivery

Nanosponges were prepared from β-cyclodextrins as nanoporous materials for possible use as carriers for drug delivery. The structure of β-cyclodextrin-based nanosponges was principally investigated by FT-IR, DSC and RX analyses. Sizes, morphology and toxicity were also examined. The capacity of the nanosponges to incorporate molecules within their structure was evaluated using drugs with different structures and solubilities. The nanosponges were found capable of carrying both lipophilic and hydrophilic drugs and of improving the solubility of poorly water-soluble molecules.