10,294 research outputs found
1012-101 Vascular Smooth Muscle-Directed Adenovlral Vectors
Gene transfer to the vascular wall utilizing locally-delivered recombinant adenoviral vectors has shown promise as a novel technique for therapeutic as well as experimental modulation of vascular wall gene expression. Infusion of such vectors using porous balloon catheters (PBC) has previously been demonstrated to result in transduction of extravascular cells at the delivery site, as well as substantial systemic transduction as a consequence of release of vector into the circulation. Introduction of a vascular-directed promoter into the adenoviral vector should thus contribute to targeting the expression of genes to the vascular wall, while reducing peri-vascular and systemic expression. In order to test the feasibility of utilizing the vascular smooth muscle α-actin (SMA) promoter to confer tissue specificity upon a recombinant adenoviral vector, we constructed an adenovirus (AvLacZ5) employing a 1.1 kilobase region of the murine SMA promoter to direct the expression of the nuclear-targeted beta-galactosidase (lacZ) gene and evaluated gene transduction by this vector, in comparison with a vector differing only by the presence of the RSV-LTR promoter. Several cell types were used as targets, including bovine aortic smooth muscle cells (BASMC). human pulmonary epithelial carcinoma cells (A549 cells), and transformed human embryonic kidney epithelial cells which are competent to replicate these adenoviral vectors (293 cells). The vector incorporating the SMA promoter demonstrated substantial selectivity for vascular smooth muscle gene expression, with typical transductions carried out in parallel under identical conditions manifesting 90â95% lacZ-expressing BASMC, 0.3% lacZ-positive A549 cells, and 4% positive 293 cells. Conversely, parallel transductions with the vector employing the RSV promoter typically resulted in 95â99% lac-expressing 293 cells at vector concentrations yielding only 5â10% positive BASMC. These data support cell lineage-specificity of AvLacZ5 at the level of promoter function rather than due to intrinsic cellular differences in capacity for adenovirally-mediated transduction. However, it is notable that a limited subpopulation of 293 cells clearly are able to direct sufficient transcription from the SMA promoter sequences chosen to yield detectable lacZ expression; the molecular basis for this heterogeneity of expression remains to be determined. Adenoviral vectors utilizing these promoter sequences may render vascular-restricted gene transfer feasible when used in conjunction with mechanical devices providing a component of spatial localization
The radical left's turn towards civil society in Greece: One strategy, two paths
The Communist Party of Greece (KKE) and the Coalition of the Radical Left (SYRIZA) made remarkable âturns towards civil societyâ over the last decade. It is argued that this was primarily a response aimed at strengthening their social legitimacy, which had reached its lowest point in the early 1990s. Differences in the way the two parties attempted to stabilise and engage their membership and re-establish links to trade unions and new social movements can be attributed to their distinct ideological and organisational legacies. Despite those differences, their respective linkage strategies were both successful until the game-changing 2012 Greek national elections, which brought about the remarkable rise of SYRIZA and the electoral demise of the KKE
Mean-Field vs Monte-Carlo equation of state for the expansion of a Fermi superfluid in the BCS-BEC crossover
The equation of state (EOS) of a Fermi superfluid is investigated in the
BCS-BEC crossover at zero temperature. We discuss the EOS based on Monte-Carlo
(MC) data and asymptotic expansions and the EOS derived from the extended BCS
(EBCS) mean-field theory. Then we introduce a time-dependent density
functional, based on the bulk EOS and Landau's superfluid hydrodynamics with a
von Weizs\"acker-type correction, to study the free expansion of the Fermi
superfluid. We calculate the aspect ratio and the released energy of the
expanding Fermi cloud showing that MC EOS and EBCS EOS are both compatible with
the available experimental data of Li atoms. We find that the released
energy satisfies an approximate analytical formula that is quite accurate in
the BEC regime. For an anisotropic droplet, our numerical simulations show an
initially faster reversal of anisotropy in the BCS regime, later suppressed by
the BEC fluid.Comment: 13 pages, 3 figures, presented to the 15th International Laser
Physics Workshop (Lausanne, July 24-28, 2006); to be published in Laser
Physic
Pre- and postnatal development of GABA receptors in Macaca monkey visual cortex
GABA is a putative inhibitory neurotransmitter in adult mammalian visual cortex but also has been implicated as playing a crucial role in cortical information processing during development. In order to understand better the role of GABA during primate visual cortex development, we have examined the time course of GABAA and GABAB receptor ontogenesis in 18 Macaca nemestrina monkeys ranging from fetal day 61 (F61d) to adulthood. The GABA and benzodiazepine binding sites of the GABAA receptor were detected by 3H-muscimol (3H-MS) and 3H- flunitrazepam (3H-FZ), respectively. GABAB receptors were detected by 3H-baclofen (3H-BA). All ligands were visualized by in vitro autoradiography. Quantitative analysis of film density was done to compare laminar changes during pre- and postnatal development. Saturation binding experiments were done for MS and FZ binding sites to determine receptor number (Bmax) and affinity (Kd) at selected pre- and postnatal ages. Both MS and FZ binding sites were present at F61d-72d throughout the cortical plate and marginal zone. FZ binding sites were more dense than MS binding sites over the cortical plate at young ages and were especially dense over the marginal zone. FZ binding sites also were present in lesser amounts over the subplate and intermediate zone, but not over the subventricular zone. By F119d-126d, layer 4 could be distinguished by its higher density for both ligands. The basic adult laminar pattern was established for both MS and BZ binding sites by birth (birth = F165d-170d). After birth, MS density increases dramatically in all layers, but layer 4C remains most dense to adulthood. FZ labeling is heavy in both layers 4 and 3 at birth but after 4 weeks after birth (P4 wk) it declines somewhat in the supragranular layers so that layer 4C now predominates. Labeling in layers 5/6 virtually disappears after birth. BA binding sites were present at F126d, at which time layer 4 was slightly lighter than the remainder of striate cortex; this laminar pattern remained basically the same throughout our series to adulthood. Competitive binding of agonist and antagonists for the GABAA receptor showed that MS binding characteristics were similar at F126d and P8.5 years (yr). MS binding site Bmax was about 8% of adult values at F72d, 24% by F126d, and 56% at F152d. Bmax then rose rapidly after birth to peak at P18wk at 169% of adult values, and then declined to P1yr. A second peak of 143% was found around P3.5yr, with adult values reached by P8.5yr.(ABSTRACT TRUNCATED AT 400 WORDS
Strong quantum fluctuation of vortices in the new superconductor
By using transport and magnetic measurement, the upper critical field
and the irreversibility line has been determined. A
big separation between and has been found showing the
existence of a quantum vortex liquid state induced by quantum fluctuation of
vortices in the new superconductor . Further investigation on the
magnetic relaxation shows that both the quantum tunneling and the thermally
activated flux creep weakly depends on temperature. But when the melting field
is approached, a drastic rising of the relaxation rate is observed.
This may imply that the melting of the vortex matter at a finite temperature is
also induced by the quantum fluctuation of vortices.Comment: 4 pages, 4 figure
Energy gaps in quantum first-order mean-field-like transitions: The problems that quantum annealing cannot solve
We study first-order quantum phase transitions in models where the mean-field
traitment is exact, and the exponentially fast closure of the energy gap with
the system size at the transition. We consider exactly solvable ferromagnetic
models, and show that they reduce to the Grover problem in a particular limit.
We compute the coefficient in the exponential closure of the gap using an
instantonic approach, and discuss the (dire) consequences for quantum
annealing.Comment: 6 pages, 3 figure
Magnetic order in GdBiPt studied by x-ray resonant magnetic scattering
Rare earth (R) half-Heusler compounds, RBiPt, exhibit a wide spectrum of
novel ground states. Recently, GdBiPt has been proposed as a potential
antiferromagnetic topological insulator (AFTI). We have employed x-ray resonant
magnetic scattering to elucidate the microscopic details of the magnetic
structure in GdBiPt below T_N = 8.5 K. Experiments at the Gd L_2 absorption
edge show that the Gd moments order in an antiferromagnetic stacking along the
cubic diagonal [1 1 1] direction satisfying the requirement for an AFTI, where
both time-reversal symmetry and lattice translational symmetry are broken, but
their product is conserved.Comment: 4 pages, 4 figure
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A randomised controlled trial of cognitive behavioural treatment for obsessive compulsive disorder in children and adolescents
Cognitive behaviour therapy (CBT) for young people with obsessive compulsive disorder (OCD) has become the treatment of first choice. However, the literature is largely based on studies emphasising exposure and response prevention. In this study, we report on a randomised controlled trial of CBT for young people carried out in typical outpatient clinic conditions which focused on cognitions. A randomised controlled trial compares 10 sessions of manualised cognitive behavioural treatment with a 12-week waiting list for adolescents and children with OCD. Assessors were blind to treatment allocation. 21 consecutive patients with OCD aged between 9 and 18 years were recruited. The group who received treatment improved more than a comparison group who waited for 3 months. The second group was treated subsequently using the same protocol and made similar gains. In conclusion, CBT can be delivered effectively to young people with OCD in typical outpatient settings
Ambiguity, multiple streams, and EU policy
The multiple streams framework draws insight from interactions between agency and institutions to explore the impact of context, time, and meaning on policy change and to assess the institutional and issue complexities permeating the European Union (EU) policy process. The authors specify the assumptions and structure of the framework and review studies that have adapted it to reflect more fully EU decision-making processes. The nature of policy entrepreneurship and policy windows are assessed to identify areas of improvement. Finally, the authors sketch out a research agenda that refines the logic of political manipulation which permeates the lens and the institutional complexity which frames the EU policy process
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