1,008 research outputs found
Complex sequencing rules of birdsong can be explained by simple hidden Markov processes
Complex sequencing rules observed in birdsongs provide an opportunity to
investigate the neural mechanism for generating complex sequential behaviors.
To relate the findings from studying birdsongs to other sequential behaviors,
it is crucial to characterize the statistical properties of the sequencing
rules in birdsongs. However, the properties of the sequencing rules in
birdsongs have not yet been fully addressed. In this study, we investigate the
statistical propertiesof the complex birdsong of the Bengalese finch (Lonchura
striata var. domestica). Based on manual-annotated syllable sequences, we first
show that there are significant higher-order context dependencies in Bengalese
finch songs, that is, which syllable appears next depends on more than one
previous syllable. This property is shared with other complex sequential
behaviors. We then analyze acoustic features of the song and show that
higher-order context dependencies can be explained using first-order hidden
state transition dynamics with redundant hidden states. This model corresponds
to hidden Markov models (HMMs), well known statistical models with a large
range of application for time series modeling. The song annotation with these
models with first-order hidden state dynamics agreed well with manual
annotation, the score was comparable to that of a second-order HMM, and
surpassed the zeroth-order model (the Gaussian mixture model (GMM)), which does
not use context information. Our results imply that the hierarchical
representation with hidden state dynamics may underlie the neural
implementation for generating complex sequences with higher-order dependencies
Quantum key distribution and 1 Gbit/s data encryption over a single fibre
We perform quantum key distribution (QKD) in the presence of 4 classical
channels in a C-band dense wavelength division multiplexing (DWDM)
configuration using a commercial QKD system. The classical channels are used
for key distillation and 1 Gbps encrypted communication, rendering the entire
system independent from any other communication channel than a single dedicated
fibre. We successfully distil secret keys over fibre spans of up to 50 km. The
separation between quantum channel and nearest classical channel is only 200
GHz, while the classical channels are all separated by 100 GHz. In addition to
that we discuss possible improvements and alternative configurations, for
instance whether it is advantageous to choose the quantum channel at 1310 nm or
to opt for a pure C-band configuration.Comment: 9 pages, 7 figure
Phase transition from a to superconductor
We study the phase transition from a to
superconductor using the tight-binding model of two-dimensional cuprates. As
the temperature is lowered past the critical temperature , first a superconducting phase is created. With further reduction of
temperature, the phase is created at temperature
. We study the temperature dependencies of the order parameter,
specific heat and spin susceptibility in these mixed-angular-momentum states on
square lattice and on a lattice with orthorhombic distortion. The
above-mentioned phase transitions are identified by two jumps in specific heat
at and .Comment: Latex file, 5 pages, 6 postscript figures, Accepted in Physical
Review
Spatial heterogeneity and peptide availability determine CTL killing efficiency in vivo
The rate at which a cytotoxic T lymphocyte (CTL) can survey for infected cells is a key ingredient of models of vertebrate immune responses to intracellular pathogens. Estimates have been obtained using in vivo cytotoxicity assays in which peptide-pulsed splenocytes are killed by CTL in the spleens of immunised mice. However the spleen is a heterogeneous environment and splenocytes comprise multiple cell types. Are some cell types intrinsically more susceptible to lysis than others? Quantitatively, what impacts are made by the spatial distribution of targets and effectors, and the level of peptide-MHC on the target cell surface? To address these questions we revisited the splenocyte killing assay, using CTL specific for an epitope of influenza virus. We found that at the cell population level T cell targets were killed more rapidly than B cells. Using modeling, quantitative imaging and in vitro killing assays we conclude that this difference in vivo likely reflects different migratory patterns of targets within the spleen and a heterogeneous distribution of CTL, with no detectable difference in the intrinsic susceptibilities of the two populations to lysis. Modeling of the stages involved in the detection and killing of peptide-pulsed targets in vitro revealed that peptide dose influenced the ability of CTL to form conjugates with targets but had no detectable effect on the probability that conjugation resulted in lysis, and that T cell targets took longer to lyse than B cells. We also infer that incomplete killing in vivo of cells pulsed with low doses of peptide may be due to a combination of heterogeneity in peptide uptake and the dissociation, but not internalisation, of peptide-MHC complexes. Our analyses demonstrate how population-averaged parameters in models of immune responses can be dissected to account for both spatial and cellular heterogeneity
TOM40 Mediates Mitochondrial Dysfunction Induced by α-Synuclein Accumulation in Parkinson's Disease.
Alpha-synuclein (α-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels of mitochondrial DNA (mtDNA) deletions. We now addressed the question, whether alterations in a component of the mitochondrial import machinery -TOM40- might contribute to the mitochondrial dysfunction and damage in PD. For this purpose, we studied levels of TOM40, mtDNA deletions, oxidative damage, energy production, and complexes of the respiratory chain in brain homogenates as well as in single neurons, using laser-capture-microdissection in transgenic mice overexpressing human wildtype α-Syn. Additionally, we used lentivirus-mediated stereotactic delivery of a component of this import machinery into mouse brain as a novel therapeutic strategy. We report here that TOM40 is significantly reduced in the brain of PD patients and in α-Syn transgenic mice. TOM40 deficits were associated with increased mtDNA deletions and oxidative DNA damage, and with decreased energy production and altered levels of complex I proteins in α-Syn transgenic mice. Lentiviral-mediated overexpression of Tom40 in α-Syn-transgenic mice brains ameliorated energy deficits as well as oxidative burden. Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in α-Synucleinopathies
Systematics of two-component superconductivity in from microwave measurements of high quality single crystals
Systematic microwave surface impedance measurements of YBCO single crystals
grown in crucibles reveal new properties that are not directly seen
in similar measurements of other YBCO samples. Two key observations obtained
from complex conductivity are: a new normal conductivity peak at around 80K and
additional pairing below 65K. High pressure oxygenation of one of the crystals
still yields the same results ruling out any effect of macroscopic segregation
of O-deficient regions. A single complex order parameter cannot describe these
data, and the results suggest at least two superconducting components.
Comparisons with model calculations done for various decoupled two-component
scenarios (i.e. s+d, d+d) are presented. Systematics of three single crystals
show that the 80K quasiparticle peak is correlated with the normal state
inelastic scattering rate. Close to Tc, the data follow a mean-field behavior.
Overall, our results strongly suggest the presence of multiple pairing
temperature and energy scales in .Comment: 14 pages, 2-column, Revtex, 5 embedded postscript figures, uses
graphicx. Postscript version also available at
http://sagar.physics.neu.edu/preprints.htm
First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial
BACKGROUND: Org 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data. METHODS: In the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg. RESULTS: Within the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter. CONCLUSIONS: Org 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics
Extended pharmacodynamic responses observed upon PROTAC-mediated degradation of RIPK2.
Proteolysis-Targeting Chimeras (PROTACs) are heterobifunctional small-molecules that can promote the rapid and selective proteasome-mediated degradation of intracellular proteins through the recruitment of E3 ligase complexes to non-native protein substrates. The catalytic mechanism of action of PROTACs represents an exciting new modality in drug discovery that offers several potential advantages over traditional small-molecule inhibitors, including the potential to deliver pharmacodynamic (PD) efficacy which extends beyond the detectable pharmacokinetic (PK) presence of the PROTAC, driven by the synthesis rate of the protein. Herein we report the identification and development of PROTACs that selectively degrade Receptor-Interacting Serine/Threonine Protein Kinase 2 (RIPK2) and demonstrate in vivo degradation of endogenous RIPK2 in rats at low doses and extended PD that persists in the absence of detectable compound. This disconnect between PK and PD, when coupled with low nanomolar potency, offers the potential for low human doses and infrequent dosing regimens with PROTAC medicines
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Human resource allocation management in multiple projects using sociometric techniques
This article describes a new application of key psychological concepts in the area of Sociometry for the selection of workers within organizations in which projects are developed. The project manager can use a new procedure to determine which individuals should be chosen from a given pool of resources and how to combine them into one or several simultaneous groups/projects in order to assure the highest possible overall work efficiency from the standpoint of social interaction. The optimization process was carried out by means of matrix calculations performed using a computer or even manually, and based on a number of new ratios generated ad-hoc and composed on the basis of indices frequently used in Sociometry
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