2,077 research outputs found
The hypothesis of the moving comb in frequency shifted feedback lasers
International audienceThe use of frequency-shifted feedback (FSF) lasers in optical metrology is based on a unique coherence property: the appearance of beats in the noise spectrum at the output of a two-beam interferometer, whose frequencies vary linearly with the path delay of the interferometer. A description of the output of a FSF laser as a moving comb of optical frequencies is generally admitted to explain these specific coherence properties. Here starting from the model of a passive FSF cavity seeded by spontaneous emission we give a rigorous description of the time-spectrum properties of FSF lasers and show that the moving comb exists only in the limit of small frequency shift
Plenoptic microscope based on laser optical feedback imaging (LOFI)
We present an overview of the performances of a plenoptic microscope which
combines the high sensitivity of a laser optical feedback imaging setup , the
high resolution of optical synthetic aperture and a shot noise limited signal
to noise ratio by using acoustic photon tagging. By using an adapted phase
filtering, this microscope allows phase drift correction and numerical
aberration compensation (defocusing, coma, astigmatism ...). This new kind of
microscope seems to be well adapted to make deep imaging through scattering and
heterogeneous media
Cerebrospinal fluid neurogranin in Alzheimer's disease studies: are immunoassay results interchangeable?
CSF levels of the BACE1 substrate NRG1 correlate with cognition in Alzheimer’s disease
Background:
The presynaptic protein neuregulin1 (NRG1) is cleaved by beta-site APP cleaving enzyme 1 (BACE1) in a similar way as amyloid precursor protein (APP) NRG1 can activate post-synaptic receptor tyrosine-protein kinase erbB4 (ErbB4) and was linked to schizophrenia. The NRG1/ErbB4 complex is neuroprotective, can trigger synaptogenesis and plasticity, increases the expression of NMDA and GABA receptors, and can induce neuroinflammation. This complex can reduce memory formation. In Alzheimer’s disease (AD) brains, NRG1 accumulates in neuritic plaques. It is difficult to determine if NRG1 has beneficial and/or detrimental effects in AD. BACE1 levels are increased in AD brains and cerebrospinal fluid (CSF) and may lead to enhanced NRG1 secretion, but no study has assessed CSF NRG1 levels in AD and mild cognitive impairment (MCI) patients.
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Methods:
This retrospective study included 162 patients suffering from AD dementia (54), MCI with progression to AD dementia (MCI-AD) (27), non-AD MCI (30), non-AD dementias (30), and neurological controls (27). All patients had neurological examinations, brain MRI, and neuropsychological evaluations. After written informed consent and using enzyme-linked immunosorbent assays (ELISAs), CSF samples were evaluated for Aβ1–42, Aβ1–40, total tau (T-tau), phosphorylated tau on threonine 181 (P-tau), BACE1, growth-associated protein 43 (GAP 43), neurogranin (Ng), and NRG1.
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Results:
Levels of NRG1 were significantly increased in the CSF of AD (+ 36%) and MCI-AD (+ 28%) patients compared to neurological controls and also non-AD MCI and non-AD dementias. In addition, in AD and MCI-AD patients, NRG1 levels positively correlated with Aβ1–42 but not with T-tau, P-tau, and BACE1 levels and negatively correlated with MMSE scores. A longitudinal follow-up study of AD patients revealed a trend (p = 0.08) between CSF NRG1 levels and cognitive decline. In the overall population, NRG1 correlated with MMSE and the synaptic biomarkers GAP 43 and neurogranin.
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Conclusions:
Our results showed that CSF NRG1 levels are increased in AD and MCI-AD as compared to controls and other dementias. CSF NRG1 levels are associated with cognitive evolution, and a major outcome of our findings is that synaptic NRG1 could be involved in the pathophysiology of AD. Modulating brain NRG1 activity may represent a new therapeutic target in AD
Analytical solution of an irreversible surface reaction model
In this work, we consider a simple model of reaction-limited annihilation A + B → 0 with a random source and desorption in the spirit of the reaction model proposed by Fitchthorn, Ziff, and Gulari, and we solve it exactly using a spin model. We show that the situation is similar to a diffusion-limited kinetic situation (though diffusion was a priori absent from the model). We find the occurrence of a large-scale organization phenomenon at low dimension called segregation, and for a finite size system, a transition to a saturated state at low desorption probability. We show how this transition is affected by the dimensionality of the substrate. We also show how the fluctuation spectrum of two quantities such as the saturation and the reaction rate can be drastically different, the first being universal and the other sensitive to the geometry of the substrate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45164/1/10955_2005_Article_BF01049590.pd
Dissection of synaptic pathways through the CSF biomarkers for predicting Alzheimer's disease
OBJECTIVE: To assess the ability of a combination of synaptic CSF biomarkers to separate AD and non-AD disorders and to help in the differential diagnosis between neurocognitive diseases. METHODS: Retrospective cross-sectional monocentric study. All participants explored with CSF assessments for neurocognitive decline were invited to participate. After complete clinical and imaging evaluations, 243 patients were included. CSF synaptic (GAP-43, neurogranin, SNAP-25 total, SNAP-25 aa40, synaptotagmin-1) and AD biomarkers were blindly quantified using ELISA or mass spectrometry. Statistical analysis compared CSF levels between various groups AD dementias n=81, MCI-AD n=30, other MCI n=49, other dementias (OD) n=49, neurological controls n=35) as well as their discriminatory powers. RESULTS: All synaptic biomarkers were significantly increased in MCI-AD and AD -dementias patients compared to other groups. All synaptic biomarkers could efficiently discriminate AD dementias from OD (AUC ≥0.80). All but synaptotagmin were also able to discriminate MCI-AD from controls (AUC ≥0.85) and AD dementias from controls (AUC ≥0.80). Overall, CSF SNAP 25aa40 had the highest discriminative power (AUC=0.93) between AD dementias and controls or OD, and AUC=0.90 between MCI-AD and controls. Higher levels were associated with two alleles of apolipoprotein E (APOE) ε4. CONCLUSION: All synaptic biomarkers tested had a good discriminatory power to distinguish patients with AD abnormal CSF from non-AD disorders. SNAP25aa40 demonstrated the highest power to discriminate AD CSF positive patients from non-AD patients and neurological controls in this cohort. CLASSIFICATION OF EVIDENCE: This retrospective study provides Class II evidence that CSF synaptic biomarkers discriminate patients with AD from non-AD patients
Full-length and C-terminal neurogranin in Alzheimer's disease cerebrospinal fluid analyzed by novel ultrasensitive immunoassays
Background: Neurogranin (Ng) is a neuron-specific and postsynaptic protein that is abundantly expressed in the
brain, particularly in the dendritic spine of the hippocampus and cerebral cortex. The enzymatic cleavage of Ng
produces fragments that are released into cerebrospinal (CSF), which have been shown to be elevated in
Alzheimer’s disease (AD) patients and predict cognitive decline. Thus, quantification of distinctive cleavage products
of Ng could elucidate different features of the disease.
Methods: In this study, we developed novel ultrasensitive single molecule array (Simoa) assays for measurement of
full-length neurogranin (FL-Ng) and C-terminal neurogranin (CT-Ng) fragments in CSF. The Ng Simoa assays were
evaluated in CSF samples from AD patients (N = 23), mild cognitive impairment due to AD (MCI-AD) (N = 18), and
from neurological controls (N = 26).
Results: The intra-assay repeatability and inter-assay precision of the novel methods had coefficients of variation
below 7% and 14%, respectively. CSF FL-Ng and CSF CT-Ng median concentrations were increased in AD patients
(6.02 ng/L, P < 0.00001 and 452 ng/L, P = 0.00001, respectively) and in patients with MCI-AD (5.69 ng/L, P < 0.00001
and 566 ng/L, P < 0.00001) compared to neurological controls (0.644 ng/L and 145 ng/L). The median CSF ratio of
CT-Ng/FL-Ng were decreased in AD patients (ratio = 101, P = 0.008) and in patients with MCI-AD (ratio = 115, P =
0.016) compared to neurological controls (ratio = 180). CSF of FL-Ng, CT-Ng, and ratio of CT-Ng/FL-Ng could each
significantly differentiate AD patients from controls (FL-Ng, AUC = 0.907; CT-Ng, AUC = 0.913; CT-Ng/FL-Ng, AUC =
0.775) and patients with MCI-AD from controls (FL-Ng, AUC = 0.937; CT-Ng, AUC = 0.963; CT-Ng/FL-Ng, AUC = 0.785).
Conclusions: Assessments of the FL-Ng and CT-Ng levels in CSF with the novel sensitive immunoassays provide a
high separation of AD from controls, even in early phase of the disease. The novel Ng assays are robust and highly
sensitive and may be valuable tools to study synaptic alteration in AD, as well as to monitor the effect on synaptic
integrity of novel drug candidates in clinical trials
High density plasma deposition of device quality silicon nitride. II. Effects of thickness on the electrical properties
Dielectric behavior of SiNx films, fabricated by microwave electron cyclotron resonance discharge, has been studied as a function of film thickness on the basis of the current–voltage and the capacitance–voltage characteristics. In the thickness range (20 nm,d,80 nm), the resistivity and the critical field for SiNx were found not to be sensitive to the film thickness ~d! and which was opposite to strong dependence of the dynamic dielectric constant e d on thickness. To explain the e d behavior as a function of d, a model based on trapped space charge effects is proposed. The dominant mode of electronic conduction, determined from J –E1/2 curves and Arrhenius plots of leakage current, appears to be Poole–Frenkel emission only for thicker films (d.20 nm). Finally, the spatial profile of fixed charges reveals that SiNx /Si interface has a much greater concentration of defects than the bulk film
Acousto-optic laser optical feedback imaging
We present a photon noise and diffraction limited imaging method combining
the imaging laser and ultrasonic waves. The laser optical feedback imaging
(LOFI) technique is an ultrasensitive imaging method for imaging objects
through or embedded within a scattering medium. However, LOFI performances are
dramatically limited by parasitic optical feedback occurring in the
experimental setup. In this work, we have tagged the ballistic photons by an
acousto-optic effect in order to filter the parasitic feedback effect and to
reach the theoretical and ultimate sensitivity of the LOFI technique. We
present the principle and the experimental setup of the acousto-optic laser
optical feedback imaging (AO-LOFI) technique, and we demonstrate the
suppression of the parasitic feedback
Characterization and localization of a 77 kDa protein related to the dystrophin gene family
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