6,654 research outputs found
Advances in Alzheimer's disease: from bench to bedside
published_or_final_versio
Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway
Cerebrospinal fluid (CSF) includes conserved factors whose function is largely unexplored. To assess the role of CSF during embryonic development, CSF was repeatedly drained from embryonic zebrafish brain ventricles soon after their inflation. Removal of CSF increased cell death in the diencephalon, indicating a survival function. Factors within the CSF are required for neuroepithelial cell survival as injected mouse CSF but not artificial CSF could prevent cell death after CSF depletion. Mass spectrometry analysis of the CSF identified retinol binding protein 4 (Rbp4), which transports retinol, the precursor to retinoic acid (RA). Consistent with a role for Rbp4 in cell survival, inhibition of Rbp4 or RA synthesis increased neuroepithelial cell death. Conversely, ventricle injection of exogenous human RBP4 plus retinol, or RA alone prevented cell death after CSF depletion. Zebrafish rbp4 is highly expressed in the yolk syncytial layer, suggesting Rbp4 protein and retinol/RA precursors can be transported into the CSF from the yolk. In accord with this suggestion, injection of human RBP4 protein into the yolk prevents neuroepithelial cell death in rbp4 loss-of-function embryos. Together, these data support the model that Rbp4 and RA precursors are present within the CSF and used for synthesis of RA, which promotes embryonic neuroepithelial survival
Preserved neural dynamics across animals performing similar behaviour
Animals of the same species exhibit similar behaviours that are advantageously adapted to their body and environment. These behaviours are shaped at the species level by selection pressures over evolutionary timescales. Yet, it remains unclear how these common behavioural adaptations emerge from the idiosyncratic neural circuitry of each individual. The overall organization of neural circuits is preserved across individuals1 because of their common evolutionarily specified developmental programme2-4. Such organization at the circuit level may constrain neural activity5-8, leading to low-dimensional latent dynamics across the neural population9-11. Accordingly, here we suggested that the shared circuit-level constraints within a species would lead to suitably preserved latent dynamics across individuals. We analysed recordings of neural populations from monkey and mouse motor cortex to demonstrate that neural dynamics in individuals from the same species are surprisingly preserved when they perform similar behaviour. Neural population dynamics were also preserved when animals consciously planned future movements without overt behaviour12 and enabled the decoding of planned and ongoing movement across different individuals. Furthermore, we found that preserved neural dynamics extend beyond cortical regions to the dorsal striatum, an evolutionarily older structure13,14. Finally, we used neural network models to demonstrate that behavioural similarity is necessary but not sufficient for this preservation. We posit that these emergent dynamics result from evolutionary constraints on brain development and thus reflect fundamental properties of the neural basis of behaviour
Reconstructing pedigrees: some identifiability questions for a recombination-mutation model
Pedigrees are directed acyclic graphs that represent ancestral relationships
between individuals in a population. Based on a schematic recombination
process, we describe two simple Markov models for sequences evolving on
pedigrees - Model R (recombinations without mutations) and Model RM
(recombinations with mutations). For these models, we ask an identifiability
question: is it possible to construct a pedigree from the joint probability
distribution of extant sequences? We present partial identifiability results
for general pedigrees: we show that when the crossover probabilities are
sufficiently small, certain spanning subgraph sequences can be counted from the
joint distribution of extant sequences. We demonstrate how pedigrees that
earlier seemed difficult to distinguish are distinguished by counting their
spanning subgraph sequences.Comment: 40 pages, 9 figure
An inflatable and wearable wireless system for making 32-channel electroencephalogram measurements
© 2001-2011 IEEE. Potable electroencephalography (EEG) devices have become critical for important research. They have various applications, such as in brain-computer interfaces (BCI). Numerous recent investigations have focused on the development of dry sensors, but few concern the simultaneous attachment of high-density dry sensors to different regions of the scalp to receive qualified EEG signals from hairy sites. An inflatable and wearable wireless 32-channel EEG device was designed, prototyped, and experimentally validated for making EEG signal measurements; it incorporates spring-loaded dry sensors and a novel gasbag design to solve the problem of interference by hair. The cap is ventilated and incorporates a circuit board and battery with a high-tolerance wireless (Bluetooth) protocol and low power consumption characteristics. The proposed system provides a 500/250 Hz sampling rate, and 24 bit EEG data to meet the BCI system data requirement. Experimental results prove that the proposed EEG system is effective in measuring audio event-related potential, measuring visual event-related potential, and rapid serial visual presentation. Results of this work demonstrate that the proposed EEG cap system performs well in making EEG measurements and is feasible for practical applications
Quantum field theoretic approach to neutrino oscillations in matter
We consider neutrino oscillations in non-uniform matter in a quantum field
theoretic (QFT) approach, in which neutrino production, propagation and
detection are considered as a single process. We find the conditions under
which the oscillation probability can be sensibly defined and demonstrate how
the properly normalized oscillation probability can be obtained in the QFT
framework. We derive the evolution equation for the oscillation amplitude and
discuss the conditions under which it reduces to the standard
Schr\"odinger-like evolution equation. It is shown that, contrary to the common
usage, the Schr\"odinger-like evolution equation is not applicable in certain
cases, such as oscillations of neutrinos produced in decays of free pions
provided that sterile neutrinos with eV exist.Comment: LaTeX, 24 pages + 16 pages of appendices, 1 figure. V2: typos
correcte
Attainment of treat-to-target endpoints in SLE patients with high disease activity in the atacicept phase 2b ADDRESS II study
OBJECTIVE
Low disease activity (LDA) and remission are emerging treat-to-target (T2T) endpoints in SLE. However, the rates at which these endpoints are met in patients with high disease activity (HDA) are unknown. Atacicept, which targets B lymphocyte stimulator and a proliferation-inducing ligand, improved disease outcomes in SLE patients with HDA (SLEDAI-2K ≥10) at baseline in the phase 2b ADDRESS II study. This is a post hoc analysis of T2T endpoints in these patients.
METHODS
Patients received weekly atacicept (75 or 150 mg s.c.) or placebo for 24 weeks (1:1:1 randomization). Attainment of three T2T endpoints, LDA (SLEDAI-2K ≤ 2), Lupus Low Disease Activity State (LLDAS) and remission (clinical SLEDAI-2K = 0, prednisone-equivalent ≤5mg/day and Physician’s Global Assessment <0.5), was assessed and compared with SLE Responder Index (SRI)-4 and SRI-6 response.
RESULTS
Of 306 randomized patients, 158 (51.6%) had baseline HDA. At week 24, 37 (23.4%) HDA patients attained LDA, 25 (15.8%) LLDAS and 17 (10.8%) remission. Each of these endpoints was more stringent than SRI-4 (n = 87; 55.1%) and SRI-6 (n = 67; 42.4%). Compared with placebo (n = 52), at week 24, patients treated with atacicept 150 mg (n = 51) were more likely to attain LDA [odds ratio (OR) 3.82 (95% CI: 1.44, 10.15), P = 0.007], LLDAS [OR 5.03 (95% CI: 1.32, 19.06), P = 0.018] or remission [OR 3.98 (95% CI: 0.78, 20.15), P = 0.095].
CONCLUSION
At week 24, LDA, LLDAS and remission were more stringent than SRI-4 and SRI-6 response, were attainable in the HDA population and discriminated between treatment with atacicept 150 mg and placebo. These results suggest that T2T endpoints are robust outcome measures in SLE clinical trials and support further evaluation of atacicept in SLE.
TRAIL REGISTRATION
ClinicalTrials.gov, http://clinicaltrials.gov, NCT01972568
A single-photon transistor using nano-scale surface plasmons
It is well known that light quanta (photons) can interact with each other in
nonlinear media, much like massive particles do, but in practice these
interactions are usually very weak. Here we describe a novel approach to
realize strong nonlinear interactions at the single-photon level. Our method
makes use of recently demonstrated efficient coupling between individual
optical emitters and tightly confined, propagating surface plasmon excitations
on conducting nanowires. We show that this system can act as a nonlinear
two-photon switch for incident photons propagating along the nanowire, which
can be coherently controlled using quantum optical techniques. As a novel
application, we discuss how the interaction can be tailored to create a
single-photon transistor, where the presence or absence of a single incident
photon in a ``gate'' field is sufficient to completely control the propagation
of subsequent ``signal'' photons.Comment: 20 pages, 4 figure
Perceptions and behaviors related to hand hygiene for the prevention of H1N1 influenza transmission among Korean university students during the peak pandemic period
<p>Abstract</p> <p>Background</p> <p>This study was performed to better assess the perceptions, motivating factors, and behaviors associated with the use of hand washing to prevent H1N1 influenza transmission during the peak pandemic period in Korea.</p> <p>Methods</p> <p>A cross-sectional survey questionnaire was completed by 942 students at a university campus in Suwon, Korea, between December 1 and 8, 2009. The survey included questions regarding individual perceptions, motivating factors, and behaviors associated with hand washing for the prevention of H1N1 influenza transmission.</p> <p>Results</p> <p>Compared to one year prior, 30.3% of participants reported increasing their hand washing frequency. Female students were more likely to practice more frequent hand washing. Women also perceived the effectiveness of hand washing to be lower, and illness severity and personal susceptibility to H1N1 infection to be higher. Study participants who were female (OR: 1.79-3.90) who perceived of hand washing to be effective (OR: 1.34-12.15) and illness severity to be greater (OR: 1.00-3.12) washed their hands more frequently.</p> <p>Conclusions</p> <p>Korean students increased their frequency of hand hygiene practices during the pandemic, with significant gender differences existing in the attitudes and behaviors related to the use of hand hygiene as a means of disease prevention. Here, the factors that affected hand washing behavior were similar to those identified at the beginning of the H1N1 or SARS pandemics, suggesting that public education campaigns regarding hand hygiene are effective in altering individual hand hygiene habits during the peak periods of influenza transmission.</p
SIGNATURE: A workbench for gene expression signature analysis
<p>Abstract</p> <p>Background</p> <p>The biological phenotype of a cell, such as a characteristic visual image or behavior, reflects activities derived from the expression of collections of genes. As such, an ability to measure the expression of these genes provides an opportunity to develop more precise and varied sets of phenotypes. However, to use this approach requires computational methods that are difficult to implement and apply, and thus there is a critical need for intelligent software tools that can reduce the technical burden of the analysis. Tools for gene expression analyses are unusually difficult to implement in a user-friendly way because their application requires a combination of biological data curation, statistical computational methods, and database expertise.</p> <p>Results</p> <p>We have developed SIGNATURE, a web-based resource that simplifies gene expression signature analysis by providing software, data, and protocols to perform the analysis successfully. This resource uses Bayesian methods for processing gene expression data coupled with a curated database of gene expression signatures, all carried out within a GenePattern web interface for easy use and access.</p> <p>Conclusions</p> <p>SIGNATURE is available for public use at <url>http://genepattern.genome.duke.edu/signature/</url>.</p
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