1,948 research outputs found
A case of TDP-43 type C pathology presenting as nonfluent variant primary progressive aphasia
We report a case of rapidly progressive nonfluent variant PPA (nfvPPA), age at onset 77 years old and disease duration 3.3 years, who came to post mortem and was found to have TDP-43 type C pathology, an unusual finding for nfvPPA. All prior TDP-43 type C cases from the UCL FTD cohort (n=25) had a semantic variant PPA (svPPA) phenotype, with all having a younger age at onset and longer disease duration than the nfvPPA case. Volumetric analysis of MRI from the nfvPPA case, twelve of the svPPA cases and ten age-matched controls was performed. Whilst left frontal and insular volumes were lower in the nfvPPA case compared with svPPA, cortical and medial temporal lobe volumes were lower (particularly on the right) in the svPPA group compared with the nfvPPA patient. Such anatomical involvement is likely to be consistent with the presence of a nonfluent aphasia (left frontal lobe and insula), and only mild semantic deficit early in the illness (left but not right temporal lobe). Such unique cases add to the heterogeneity of the FTD spectrum
Accretion, Primordial Black Holes and Standard Cosmology
Primordial Black Holes evaporate due to Hawking radiation. We find that the
evaporation time of primordial black holes increase when accretion of radiation
is included.Thus depending on accretion efficiency more and more number of
primordial black holes are existing today, which strengthens the idea that the
primordial black holes are the proper candidate for dark matter.Comment: 11 pages, 3 figure
National issues in technology transfer
A well-accepted definition of technology transfer is “the movement of know how, technique, and technology across organizational boundaries.” If you accept this definition, then what is interesting about it is that nobody knows how to do it very well… as a nation, that is. Different nations do different pieces of it better than others. You find the Japanese running around looking at us to see how to do technology transfers from universities to industry, which they do badly. We run around looking at the Japanese to find out how to transfer technology from corporate R&D to manufacturing. And the Europeans are running around looking at both of us
Microwave amplification with nanomechanical resonators
Sensitive measurement of electrical signals is at the heart of modern science
and technology. According to quantum mechanics, any detector or amplifier is
required to add a certain amount of noise to the signal, equaling at best the
energy of quantum fluctuations. The quantum limit of added noise has nearly
been reached with superconducting devices which take advantage of
nonlinearities in Josephson junctions. Here, we introduce a new paradigm of
amplification of microwave signals with the help of a mechanical oscillator. By
relying on the radiation pressure force on a nanomechanical resonator, we
provide an experimental demonstration and an analytical description of how the
injection of microwaves induces coherent stimulated emission and signal
amplification. This scheme, based on two linear oscillators, has the advantage
of being conceptually and practically simpler than the Josephson junction
devices, and, at the same time, has a high potential to reach quantum limited
operation. With a measured signal amplification of 25 decibels and the addition
of 20 quanta of noise, we anticipate near quantum-limited mechanical microwave
amplification is feasible in various applications involving integrated
electrical circuits.Comment: Main text + supplementary information. 14 pages, 3 figures (main
text), 18 pages, 6 figures (supplementary information
The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein
The folding pathway and rate coefficients of the folding of a knotted protein
are calculated for a potential energy function with minimal energetic
frustration. A kinetic transition network is constructed using the discrete
path sampling approach, and the resulting potential energy surface is
visualized by constructing disconnectivity graphs. Owing to topological
constraints, the low-lying portion of the landscape consists of three distinct
regions, corresponding to the native knotted state and to configurations where
either the N- or C-terminus is not yet folded into the knot. The fastest
folding pathways from denatured states exhibit early formation of the
N-terminus portion of the knot and a rate-determining step where the C-terminus
is incorporated. The low-lying minima with the N-terminus knotted and the
C-terminus free therefore constitute an off-pathway intermediate for this
model. The insertion of both the N- and C-termini into the knot occur late in
the folding process, creating large energy barriers that are the rate limiting
steps in the folding process. When compared to other protein folding proteins
of a similar length, this system folds over six orders of magnitude more
slowly.Comment: 19 page
Laser cooling of a diatomic molecule
It has been roughly three decades since laser cooling techniques produced
ultracold atoms, leading to rapid advances in a vast array of fields.
Unfortunately laser cooling has not yet been extended to molecules because of
their complex internal structure. However, this complexity makes molecules
potentially useful for many applications. For example, heteronuclear molecules
possess permanent electric dipole moments which lead to long-range, tunable,
anisotropic dipole-dipole interactions. The combination of the dipole-dipole
interaction and the precise control over molecular degrees of freedom possible
at ultracold temperatures make ultracold molecules attractive candidates for
use in quantum simulation of condensed matter systems and quantum computation.
Also ultracold molecules may provide unique opportunities for studying chemical
dynamics and for tests of fundamental symmetries. Here we experimentally
demonstrate laser cooling of the molecule strontium monofluoride (SrF). Using
an optical cycling scheme requiring only three lasers, we have observed both
Sisyphus and Doppler cooling forces which have substantially reduced the
transverse temperature of a SrF molecular beam. Currently the only technique
for producing ultracold molecules is by binding together ultracold alkali atoms
through Feshbach resonance or photoassociation. By contrast, different proposed
applications for ultracold molecules require a variety of molecular
energy-level structures. Our method provides a new route to ultracold
temperatures for molecules. In particular it bridges the gap between ultracold
temperatures and the ~1 K temperatures attainable with directly cooled
molecules (e.g. cryogenic buffer gas cooling or decelerated supersonic beams).
Ultimately our technique should enable the production of large samples of
molecules at ultracold temperatures for species that are chemically distinct
from bialkalis.Comment: 10 pages, 7 figure
Wisdom tooth extraction causing lingual nerve and styloglossus muscle damage: a mimic of multiple cranial nerve palsies
The combination of tongue hemianaesthesia, dysgeusia, dysarthria and dysphagia suggests the involvement of multiple cranial nerves. We present a case with sudden onset of these symptoms immediately following wisdom tooth extraction and highlight the clinical features that allowed localisation of the lesion to a focal, iatrogenic injury of the lingual nerve and adjacent styloglossus muscle
Modeling the dynamics of glacial cycles
This article is concerned with the dynamics of glacial cycles observed in the geological record of the Pleistocene Epoch. It focuses on a conceptual model proposed by Maasch and Saltzman [J. Geophys. Res.,95, D2 (1990), pp. 1955-1963], which is based on physical arguments and emphasizes the role of atmospheric CO2 in the generation and persistence of periodic orbits (limit cycles). The model consists of three ordinary differential equations with four parameters for the anomalies of the total global ice mass, the atmospheric CO2 concentration, and the volume of the North Atlantic Deep Water (NADW). In this article, it is shown that a simplified two-dimensional symmetric version displays many of the essential features of the full model, including equilibrium states, limit cycles, their basic bifurcations, and a Bogdanov-Takens point that serves as an organizing center for the local and global dynamics. Also, symmetry breaking splits the Bogdanov-Takens point into two, with different local dynamics in their neighborhoods
Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B
Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone
Laser Cooling of Optically Trapped Molecules
Calcium monofluoride (CaF) molecules are loaded into an optical dipole trap
(ODT) and subsequently laser cooled within the trap. Starting with
magneto-optical trapping, we sub-Doppler cool CaF and then load CaF
molecules into an ODT. Enhanced loading by a factor of five is obtained when
sub-Doppler cooling light and trapping light are on simultaneously. For trapped
molecules, we directly observe efficient sub-Doppler cooling to a temperature
of . The trapped molecular density of
cm is an order of magnitude greater than in the initial sub-Doppler
cooled sample. The trap lifetime of 750(40) ms is dominated by background gas
collisions.Comment: 5 pages, 5 figure
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