Novel Semliki Forest virus vectors with reduced cytotoxicity and temperature sensitivity for long-term enhancement of transgene expression.

Alphaviral vectors inhibit host cell protein synthesis and are cytotoxic. To overcome these limitations, we modified the nonstructural protein-2 (nsP2) gene in the Semliki Forest virus (SFV) vector, pSFV1. Packaging of SFV replicons with two point mutations in nsP2 resulted in high-titer recombinant SFV(PD) particles. SFV(PD) led to more efficient host cell protein synthesis, exhibited reduced cytotoxicity and improved cell survival, and allowed greater and prolonged transgene expression than the original vector, SFV. In dissociated hippocampal neurons and organotypic rat hippocampal slices, SFV(PD) infection preserved neuronal morphology and synaptic function more efficiently than SFV. Combination of the two point mutations with a replication-persistent mutation in nsP2 resulted in a highly temperature-sensitive vector, SFV(PD713P), which efficiently transduced neurons in hippocampal slice cultures. At 31 °C, SFV(PD713P) allowed continuous transgene expression in BHK cells, at amounts comparable to SFV(PD). These new SFV mutants are expected to substantially broaden the application of alphaviral vectors in neurons and other mammalian cells

Temperature dependence of D'yakonov-Perel' spin relaxation in zinc blende semiconductor quantum structures

The D'yakonov-Perel' mechanism, intimately related to the spin splitting of the electronic states, usually dominates the spin relaxation in zinc blende semiconductor quantum structures. Previously it has been formulated for the two limiting cases of low and high temperatures. Here we extend the theory to give an accurate description of the intermediate regime which is often relevant for room temperature experiments. Employing the self-consistent multiband envelope function approach, we determine the spin splitting of electron subbands in n-(001) zinc blende semiconductor quantum structures. Using these results we calculate spin relaxation rates as a function of temperature and obtain excellent agreement with experimental data.Comment: 9 pages, 4 figure

Gate-controlled Guiding of Electrons in Graphene

Ballistic semiconductor structures have allowed the realization of optics-like phenomena in electronics, including magnetic focusing and lensing. An extension that appears unique to graphene is to use both n and p carrier types to create electronic analogs of optical devices having both positive and negative indices of refraction. Here, we use gate-controlled density with both p and n carrier types to demonstrate the analog of the fiber-optic guiding in graphene. Two basic effects are investigated: (1) bipolar p-n junction guiding, based on the principle of angle-selective transmission though the graphene p-n interface, and (2) unipolar fiber-optic guiding, using total internal reflection controlled by carrier density. Modulation of guiding efficiency through gating is demonstrated and compared to numerical simulations, which indicates that interface roughness limits guiding performance, with few-nanometer effective roughness extracted. The development of p-n and fiber-optic guiding in graphene may lead to electrically reconfigurable wiring in high-mobility devices.Comment: supplementary materal at http://marcuslab.harvard.edu/papers/OG_SI.pd

Effective connectivity reveals strategy differences in an expert calculator

Mathematical reasoning is a core component of cognition and the study of experts defines the upper limits of human cognitive abilities, which is why we are fascinated by peak performers, such as chess masters and mental calculators. Here, we investigated the neural bases of calendrical skills, i.e. the ability to rapidly identify the weekday of a particular date, in a gifted mental calculator who does not fall in the autistic spectrum, using functional MRI. Graph-based mapping of effective connectivity, but not univariate analysis, revealed distinct anatomical location of “cortical hubs” supporting the processing of well-practiced close dates and less-practiced remote dates: the former engaged predominantly occipital and medial temporal areas, whereas the latter were associated mainly with prefrontal, orbitofrontal and anterior cingulate connectivity. These results point to the effect of extensive practice on the development of expertise and long term working memory, and demonstrate the role of frontal networks in supporting performance on less practiced calculations, which incur additional processing demands. Through the example of calendrical skills, our results demonstrate that the ability to perform complex calculations is initially supported by extensive attentional and strategic resources, which, as expertise develops, are gradually replaced by access to long term working memory for familiar material

Study of two G-protein coupled receptor variants of human trace amine-associated receptor 5

Here we report the study of two bioengineered variants of human trace amine-associated receptor 5 (hTAAR5) that were expressed in stable tetracycline-inducible HEK293S cell lines. A systematic detergent screen showed that fos-choline-14 was the optimal detergent to solubilize and subsequently purify the receptors. Milligram quantities of both hTAAR5 variants were purified to near homogeneity using immunoaffinity chromatography followed by gel filtration. Circular dichroism showed that the purified receptors had helical secondary structures, indicating that they were properly folded. The purified receptors are not only suitable for functional analyses, but also for subsequent crystallization trials. To our knowledge, this is the first mammalian TAAR that has been heterologously expressed and purified. Our study will likely stimulate in the development of therapeutic drug targets for TAAR-associated diseases, as well as fabrication of TAAR-based sensing devices

Long term follow up after surgery in congenitally corrected transposition of the great arteries with a right ventricle in the systemic circulation

Aim of the study: To investigate the long-term outcome of surgical treatment for congenitally corrected transposition of the great arteries (CCTGA), in patients with biventricular repair with the right ventricle as systemic ventricle.Methods: A total of 32 patients with CCTGA were operated between January 1972 and October 2008. These operations comprised 18 patients with a repair with a normal left ventricular outflow tract, 11 patients with a Rastelli repair of the left ventricle to the pulmonary artery and 3 patients with a cardiac transplantation.Results: Excluding the cardiac transplantation patients, mean age at operation was 16 years (sd 15 years, range 1 week - 49 years). Median follow-up was 12 years (sd 10 years, range 7 days - 32 years). Survival obtained from Kaplan-Meier analysis at 20 years after surgery was 63% (CI 53-73%). For the non-Rastelli group these data at 20 years were

Superhard Phases of Simple Substances and Binary Compounds of the B-C-N-O System: from Diamond to the Latest Results (a Review)

The basic known and hypothetic one- and two-element phases of the B-C-N-O system (both superhard phases having diamond and boron structures and precursors to synthesize them) are described. The attention has been given to the structure, basic mechanical properties, and methods to identify and characterize the materials. For some phases that have been recently described in the literature the synthesis conditions at high pressures and temperatures are indicated.Comment: Review on superhard B-C-N-O phase

Polymorphism of the catechol-O-methyltransferase gene in Han Chinese patients with psoriasis vulgaris

Psoriasis vulgaris is defined by a series of linked cellular changes in the skin: hyperplasia of epidermal keratinocytes, vascular hyperplasia and ectasia, and infiltration of T lymphocytes, neutrophils and other types of leukocytes in the affected skin. Catechol-O-methyltransferase (COMT) 158 polymorphism can reduce the activity of the COMT enzyme that may trigger defective differentiation of keratinocytes in psoriasis. Immunocytes can degrade and inactivate catecholamines via monamine oxidase (MAO) and COMT in the cells. We hypothesized that the COMT-158G > A polymorphism was associated with the risk of psoriasis vulgaris in Han Chinese people. In a hospital-based case-control study, 524 patients with psoriasis vulgaris and 549 psoriasis-free controls were studied. COMT-158 G > A polymorphism was genotyped using the PCR sequence-specific primer (PCR-SSP) technique. We found no statistically significant association between the COMT-158 allele A and the risk of psoriasis vulgaris (p = 0.739 adjusted OR = 1.03; 95% CI = 0.81-1.31). This suggests that the COMT-158 G > A polymorphism may not contribute to the etiology of psoriasis vulgaris in the Han Chinese population

Markers of cerebral damage during delirium in elderly patients with hip fracture

BACKGROUND: S100B protein and Neuron Specific Enolase (NSE) can increase due to brain cell damage and/or increased permeability of the blood-brain-barrier. Elevation of these proteins has been shown after various neurological diseases with cognitive dysfunction. Delirium is characterized by temporal cognitive deficits and is an important risk factor for dementia. The aim of this study was to compare the level of S100B and NSE of patients before, during and after delirium with patients without delirium and investigate the possible associations with different subtypes of delirium. METHODS: The study population were patients aged 65 years or more acutely admitted after hip fracture. Delirium was diagnosed by the Confusion Assessment Method and the subtype by Delirium Symptom interview. In maximal four serum samples per patient S100B and NSE levels were determined by electrochemiluminescence immunoassay. RESULTS: Of 120 included patients with mean age 83.9 years, 62 experienced delirium. Delirious patients had more frequently pre-existing cognitive impairment (67% vs. 18%, p<0.001). Comparing the first samples during delirium to samples of non-delirious patients, a difference was observed in S100B (median 0.16 versus 0.10 ug/L, p=<0.001), but not in NSE (median 11.7 versus 11.7 ng/L, p=0.97). Delirious state (before, during, after) (p<0.001), day of blood withdrawal (p<0.001), pre- or postoperative status (p=0.001) and type of fracture (p=0.036) were all associated with S100B level. The highest S100B levels were found 'during' delirium. S100B levels 'before' and 'after' delirium were still higher than those from 'non-delirious' patients. No significant difference in S100B (p=0.43) or NSE levels (p=0.41) was seen between the hyperactive, hypoactive and mixed subtype of delirium. CONCLUSIONS: Delirium was associated with increased level of S100B which could indicate cerebral damage either due to delirium or leading to delirium. The possible association between higher levels of S100B during delirium and the higher risk of developing dementia after delirium is an interesting field for future research. More studies are needed to elucidate the role of S100B proteins in the pathophysiological pathway leading to delirium and to investigate its possibility as biomarker for deliriu