Selective-Area Growth of Heavily \u3cem\u3en\u3c/em\u3e–Doped GaAs Nanostubs on Si(001) by Molecular Beam Epitaxy

Using an aspect ratio trapping technique, we demonstrate molecular beam epitaxy of GaAs nanostubs on Si(001) substrates. Nanoholes in a SiO2 mask act as a template for GaAs-on-Si selective-area growth(SAG) of nanostubs 120 nm tall and ≤100 nm in diameter. We investigate the influence of growthparameters including substrate temperature and growth rate on SAG. Optimizing these parameters results in complete selectivity with GaAsgrowth only on the exposed Si(001). Due to the confined-geometry, strain and defects in the GaAs nanostubs are restricted in lateral dimensions, and surface energy is further minimized. We assess the electrical properties of the selectively grownGaAs nanostubs by fabricating heterogeneous p+–Si/n+–GaAs p–n diodes

Investigating the functionality of an OCT4-short response element in human induced pluripotent stem cells.

Pluripotent stem cells offer great therapeutic promise for personalized treatment platforms for numerous injuries, disorders, and diseases. Octamer-binding transcription factor 4 (OCT4) is a key regulatory gene maintaining pluripotency and self-renewal of mammalian cells. With site-specific integration for gene correction in cellular therapeutics, use of the OCT4 promoter may have advantages when expressing a suicide gene if pluripotency remains. However, the human OCT4 promoter region is 4 kb in size, limiting the capacity of therapeutic genes and other regulatory components for viral vectors, and decreasing the efficiency of homologous recombination. The purpose of this investigation was to characterize the functionality of a novel 967bp OCT4-short response element during pluripotency and to examine the OCT4 titer-dependent response during differentiation to human derivatives not expressing OCT4. Our findings demonstrate that the OCT4-short response element is active in pluripotency and this activity is in high correlation with transgene expression in vitro, and the OCT4-short response element is inactivated when pluripotent cells differentiate. These studies demonstrate that this shortened OCT4 regulatory element is functional and may be useful as part of an optimized safety component in a site-specific gene transferring system that could be used as an efficient and clinically applicable safety platform for gene transfer in cellular therapeutics

Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma.

Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy (1H HR-MAS). Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy

Magnesium: Pathophysiological mechanisms and potential therapeutic roles in intracerebral hemorrhage

Intracerebral hemorrhage (ICH) remains the second-most common form of stroke with high morbidity and mortality. ICH can be divided into two pathophysiological stages: an acute primary phase, including hematoma volume expansion, and a subacute secondary phase consisting of blood-brain barrier disruption and perihematomal edema expansion. To date, all major trials for ICH have targeted the primary phase with therapies designed to reduce hematoma expansion through blood pressure control, surgical evacuation, and hemostasis. However, none of these trials has resulted in improved clinical outcomes. Magnesium is a ubiquitous element that also plays roles in vasodilation, hemostasis, and blood-brain barrier preservation. Animal models have highlighted potential therapeutic roles for magnesium in neurological diseases specifically targeting these pathophysiological mechanisms. Retrospective studies have also demonstrated inverse associations between admission magnesium levels and hematoma volume, hematoma expansion, and clinical outcome in patients with ICH. These associations, coupled with the multifactorial role of magnesium that targets both primary and secondary phases of ICH, suggest that magnesium may be a viable target of study in future ICH studies

Hepatic tristetraprolin promotes insulin resistance through RNA destabilization of FGF21

The role of posttranscriptional metabolic gene regulatory programs in diabetes is not well understood. Here, we show that the RNA-binding protein tristetraprolin (TTP) is reduced in the livers of diabetic mice and humans and is transcriptionally induced in response to insulin treatment in murine livers in vitro and in vivo. Liver-specific Ttp-KO (lsTtp-KO) mice challenged with high-fat diet (HFD) have improved glucose tolerance and peripheral insulin sensitivity compared with littermate controls. Analysis of secreted hepatic factors demonstrated that fibroblast growth factor 21 (FGF21) is posttranscriptionally repressed by TTP. Consistent with increased FGF21, lsTtp-KO mice fed HFD have increased brown fat activation, peripheral tissue glucose uptake, and adiponectin production compared with littermate controls. Downregulation of hepatic Fgf21 via an adeno-associated virus-driven shRNA in mice fed HFD reverses the insulin-sensitizing effects of hepatic Ttp deletion. Thus, hepatic TTP posttranscriptionally regulates systemic insulin sensitivity in diabetes through liver-derived FGF21

Nanoscale structuring of tungsten tip yields most coherent electron point-source

This report demonstrates the most spatially-coherent electron source ever reported. A coherence angle of 14.3 +/- 0.5 degrees was measured, indicating a virtual source size of 1.7 +/-0.6 Angstrom using an extraction voltage of 89.5 V. The nanotips under study were crafted using a spatially-confined, field-assisted nitrogen etch which removes material from the periphery of the tip apex resulting in a sharp, tungsten-nitride stabilized, high-aspect ratio source. The coherence properties are deduced from holographic measurements in a low-energy electron point source microscope with a carbon nanotube bundle as sample. Using the virtual source size and emission current the brightness normalized to 100 kV is found to be 7.9x10^8 A/sr cm^2

Accurate Hydrogen Spectral Simulations with a Compact Model Atom

Many large scale numerical simulations of astrophysical plasmas must also reproduce the hydrogen ionization and the resulting emission spectrum, in some cases quite accurately. We describe a compact model hydrogen atom that can be readily incorporated into such simulations. It reproduces the recombination efficiency and line spectrum predicted by much larger calculations for a very broad range of densities and temperatures. Uncertainties in hydrogen collision data are the largest source of differences between our compact atom and predictions of more extensive calculations, and underscore the need for accurate atomic data.Comment: 18 pages, prepared in MS-Word, Postscript only, 12 Figures, also available at http://www.pa.uky.edu/~ferguson/bib/bib.html, accepted for publication in the Astrophysical Journa