Polarization and Strong Infra-Red Activity in Compressed Solid Hydrogen

Under a pressure of ~150 GPa solid molecular hydrogen undergoes a phase transition accompanied by a dramatic rise in infra-red absorption in the vibron frequency range. We use the Berry's phase approach to calculate the electric polarization in several candidate structures finding large, anisotropic dynamic charges and strongly IR-active vibron modes. The polarization is shown to be greatly affected by the overlap between the molecules in the crystal, so that the commonly used Clausius-Mossotti description in terms of polarizable, non-overlapping molecular charge densities is inadequate already at low pressures and even more so for the compressed solid.Comment: To appear in Phys. Rev. Let

Wannier-function description of the electronic polarization and infrared absorption of high-pressure hydrogen

We have constructed maximally-localized Wannier functions for prototype structures of solid molecular hydrogen under pressure, starting from LDA and tight-binding Bloch wave functions. Each occupied Wannier function can be associated with two paired protons, defining a ``Wannier molecule''. The sum of the dipole moments of these ``molecules'' always gives the correct macroscopic polarization, even under strong compression, when the overlap between nearby Wannier functions becomes significant. We find that at megabar pressures the contributions to the dipoles arising from the overlapping tails of the Wannier functions is very large. The strong vibron infrared absorption experimentally observed in phase III, above ~ 150 GPa, is analyzed in terms of the vibron-induced fluctuations of the Wannier dipoles. We decompose these fluctuations into ``static'' and ``dynamical'' contributions, and find that at such high densities the latter term, which increases much more steeply with pressure, is dominant.Comment: 17 pages, two-column style with 14 postscript figures embedded. Uses REVTEX and epsf macro

Phase III crystal structure and 115 K phase transition of hexamethylbenzene

High-resolution spectroscopic data—Raman, infrared, and electronic—have been employed for the study of low-temperature, phase III, hexamethylbenzene and its associated λ-type phase transition. Phase III is trigonal, with point group S 6 and one molecule per primitive unit cell, giving an S 6 site group, an S 6 molecular group, and a trivial interchange group. The λ-type phase transition is not second order, and it is not related to a free rotation of the methyl groups. Restricted, geared methyl-group rotations do exist both above and below the phase transition temperature, and are sensitive to it. The molecular point symmetry is S 6 in phase III and effectively so in phase II.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44839/1/10870_2005_Article_BF01239675.pd

Adeno-Associated Viral Vector-Mediated Transgene Expression Is Independent of DNA Methylation in Primate Liver and Skeletal Muscle

Recombinant adeno-associated viral (rAAV) vectors can support long-term transgene expression in quiescent tissues. Intramuscular (IM) administration of a single-stranded AAV vector (ssAAV) in the nonhuman primate (NHP) results in a peak protein level at 2–3 months, followed by a decrease over several months before reaching a steady-state. To investigate transgene expression and vector genome persistence, we previously demonstrated that rAAV vector genomes associate with histones and form a chromatin structure in NHP skeletal muscle more than one year after injection. In the mammalian nucleus, chromatin remodeling via epigenetic modifications plays key role in transcriptional regulation. Among those, CpG hyper-methylation of promoters is a known hallmark of gene silencing. To assess the involvement of DNA methylation on the transgene expression, we injected NHP via the IM or the intravenous (IV) route with a recombinant ssAAV2/1 vector. The expression cassette contains the transgene under the transcriptional control of the constitutive Rous Sarcoma Virus promoter (RSVp). Total DNA isolated from NHP muscle and liver biopsies from 1 to 37 months post-injection was treated with sodium bisulfite and subsequently analyzed by pyrosequencing. No significant CpG methylation of the RSVp was found in rAAV virions or in vector DNA isolated from NHP transduced tissues. Direct de novo DNA methylation appears not to be involved in repressing transgene expression in NHP after gene transfer mediated by ssAAV vectors. The study presented here examines host/vector interactions and the impact on transgene expression in a clinically relevant model

Designer Gene Delivery Vectors: Molecular Engineering and Evolution of Adeno-Associated Viral Vectors for Enhanced Gene Transfer

Gene delivery vectors based on adeno-associated virus (AAV) are highly promising due to several desirable features of this parent virus, including a lack of pathogenicity, efficient infection of dividing and non-dividing cells, and sustained maintenance of the viral genome. However, several problems should be addressed to enhance the utility of AAV vectors, particularly those based on AAV2, the best characterized AAV serotype. First, altering viral tropism would be advantageous for broadening its utility in various tissue or cell types. In response to this need, vector pseudotyping, mosaic capsids, and targeting ligand insertion into the capsid have shown promise for altering AAV specificity. In addition, library selection and directed evolution have recently emerged as promising approaches to modulate AAV tropism despite limited knowledge of viral structure–function relationships. Second, pre-existing immunity to AAV must be addressed for successful clinical application of AAV vectors. “Shielding” polymers, site-directed mutagenesis, and alternative AAV serotypes have shown success in avoiding immune neutralization. Furthermore, directed evolution of the AAV capsid is a high throughput approach that has yielded vectors with substantial resistance to neutralizing antibodies. Molecular engineering and directed evolution of AAV vectors therefore offer promise for generating ‘designer’ gene delivery vectors with enhanced properties

GABA, glutamine, glutamate oxidation and succinic semialdehyde dehydrogenase expression in human gliomas

Bioenergetic characterisation of malignant tissues revealed that different tumour cells can catabolise multiple substrates as salvage pathways, in response to metabolic stress. Altered metabolism in gliomas has received a lot of attention, especially in relation to IDH mutations, and the associated oncometabolite D-2-hydroxyglutarate (2-HG) that impact on metabolism, epigenetics and redox status. Astrocytomas and oligodendrogliomas, collectively called diffuse gliomas, are derived from astrocytes and oligodendrocytes that are in metabolic symbiosis with neurons; astrocytes can catabolise neuron-derived glutamate and gamma-aminobutyric acid (GABA) for supporting and regulating neuronal functions.Metabolic characteristics of human glioma cell models - including mitochondrial function, glycolytic pathway and energy substrate oxidation - in relation to IDH mutation status and after 2-HG incubation were studied to understand the Janus-faced role of IDH1 mutations in the progression of gliomas/astrocytomas. The metabolic and bioenergetic features were identified in glioma cells using wild-type and genetically engineered IDH1-mutant glioblastoma cell lines by metabolic analyses with Seahorse, protein expression studies and liquid chromatography-mass spectrometry.U251 glioma cells were characterised by high levels of glutamine, glutamate and GABA oxidation. Succinic semialdehyde dehydrogenase (SSADH) expression was correlated to GABA oxidation. GABA addition to glioma cells increased proliferation rates. Expression of mutated IDH1 and treatment with 2-HG reduced glutamine and GABA oxidation, diminished the pro-proliferative effect of GABA in SSADH expressing cells. SSADH protein overexpression was found in almost all studied human cases with no significant association between SSADH expression and clinicopathological parameters (e.g. IDH mutation).Our findings demonstrate that SSADH expression may participate in the oxidation and/or consumption of GABA in gliomas, furthermore, GABA oxidation capacity may contribute to proliferation and worse prognosis of gliomas. Moreover, IDH mutation and 2-HG production inhibit GABA oxidation in glioma cells. Based on these data, GABA oxidation and SSADH activity could be additional therapeutic targets in gliomas/glioblastomas

THE NEAR ULTRAVIOLET SPECTRA OF CRYSTALLINE HEXACHLORO-BENZENE AND 1,3,5−TRICHLOROBENZENE∗1,3,5-TRICHLOROBENZENE^{*}

*Work supported by the National Science Foundation.Author Institution: Department of Physics, Duke University“The absorption spectra of single crystals of hexachlorobenzene and of 1,3,5-trichlorobenzene in the near ultraviolet have been investigated. The experiments were performed with polarized light at $77^{\circ} K$ and at $4.2^{\circ} K$. No Davydov splitting has been observed in either spectrum. In both spectra the first absorption is relatively weak and strongly polarized, over 90% of the intensity being in the b-axis direction. These bands are assigned the $0-0$ transitions. Aside from the first band, the hexachlorobenzene spectrum has approximately equal intensity in the two polarization directions observed. The trichlorobenzene spectrum, on the other hand, is strongly polarized with about $70-80$ of the intensity in the direction perpendicular to the b-axis. In both crystals, the b-axis polarized spectrum is much sharper than the other component. In both crystals the b-axis can be assumed to be close to the molecular normal. The major parts of the transitions observed are therefore concluded to have an induced transition moment in the molecular planes but this is not the case for the $0-0$ band. The electronic transitions observed here are forbidden in the free molecule. The $0-0$ band may appear due to either crystal field perturbation or due to small molecular distortions or both. The first of these possibilities cannot be ruled out but it seems unlikely that the crystal field can induce a $0-0$ band polarized in a direction close to the molecular normal.

THEORY FOR THE INFRARED ABSORPTION INTENSITIES OF THE LATTICE VIBRATIONS OF MOLECULAR SOLIDS.

Author Institution: Department of Chemistry University of Southern California, Los Angeles, California, 90007A theory has been developed for the infrared transition dipole intensities of the lattice vibrations in molecular solids. For non-polar molecules like $N_{2}$ and $CO_{2}$ the origin of the intensities lies in the non-zero dipole derivatives where the dipole is induced by the molecular quadurupole moments of the neighboring molecules in the lattice. The distortion moment is neglected. The results of the theory have been applied to experimental information, as far as available, for $N_{2}, CO_{2}$, and CO. Agreement between theory and experiment is found to be very good to within the error of the experimental data, i.e. a factor of 2. The theory also accounts satisfactorily for failure to observe absorption in solid $O_{2}$ and $CH_{4}$ for sample thicknesses investigated to date