269 research outputs found
Bidirectional optogenetic control of inhibitory neurons in freely-moving mice
Objective: Optogenetic manipulations of excitable cells enable activating or
silencing specific types of neurons. By expressing two types of exogenous
proteins, a single neuron can be depolarized using light of one wavelength and
hyperpolarized with another. However, routing two distinct wavelengths into the
same brain locality typically requires bulky optics that cannot be implanted on
the head of a freely-moving animal.
Methods: We developed a lens-free approach for constructing dual-color
head-mounted, fiber-based optical units: any two wavelengths can be combined.
Results: Here, each unit was comprised of one 450 nm and one 638 nm laser
diode, yielding light power of 0.4 mW and 8 mW at the end of a 50 micrometer
multimode fiber. To create a multi-color/multi-site optoelectronic device, a
four-shank silicon probe mounted on a microdrive was equipped with two
dual-color and two single-color units, for a total weight under 3 g. Devices
were implanted in mice expressing the blue-light sensitive cation channel ChR2
and the red-light sensitive chloride pump Jaws in parvalbumin-immunoreactive
(PV) inhibitory neurons. The combination of dual-color units with recording
electrodes was free from electromagnetic interference, and device heating was
under 7{\deg}C even after prolonged operation.
Conclusion: Using these devices, the same cortical PV cell could be activated
and silenced. This was achieved for multiple cells both in neocortex and
hippocampus of freely-moving mice.
Significance: This technology can be used for controlling spatially
intermingled neurons that have distinct genetic profiles, and for controlling
spike timing of cortical neurons during cognitive tasks.Comment: 11 pages, 9 figure
The Advantage of Using International Multimodel Ensemble for Seasonal Precipitation Forecast over Israel
This study analyzes the results of monthly and seasonal precipitation forecasting from seven different global climate forecast models for major basins in Israel within October–April 1982–2010. The six National Multimodel Ensemble (NMME) models and the ECMWF seasonal model were used to calculate an International Multimodel Ensemble (IMME). The study presents the performance of both monthly and seasonal predictions of precipitation accumulated over three months, with respect to different lead times for the ensemble mean values, one per individual model. Additionally, we analyzed the performance of different combinations of models. We present verification of seasonal forecasting using real forecasts, focusing on a small domain characterized by complex terrain, high annual precipitation variability, and a sharp precipitation gradient from west to east as well as from south to north. The results in this study show that, in general, the monthly analysis does not provide very accurate results, even when using the IMME for one-month lead time. We found that the IMME outperformed any single model prediction. Our analysis indicates that the optimal combinations with the high correlation values contain at least three models. Moreover, prediction with larger number of models in the ensemble produces more robust predictions. The results obtained in this study highlight the advantages of using an ensemble of global models over single models for small domain
Nonlinear Self-Calibrated Spectrometer with Single GeSe-InSe Heterojunction Device
Optical spectroscopy the measurement of electromagnetic spectra is
fundamental to various scientific domains and serves as the building block of
numerous technologies. Computational spectrometry is an emerging field that
employs an array of photodetectors with different spectral responses or a
single photodetector device with tunable spectral response, in conjunction with
numerical algorithms, for spectroscopic measurements. Compact single
photodetectors made from layered materials are particularly attractive, since
they eliminate the need for bulky mechanical and optical components used in
traditional spectrometers and can easily be engineered as heterostructures to
optimize device performance. However, compact tunable photodetectors are
typically nonlinear devices and this adds complexity to extracting optical
spectra from the device response. Here, we report on the training of an
artificial neural network (ANN) to recover the full nonlinear spectral
photoresponse of a nonlinear problem of high dimensionality of a single
GeSe-InSe p-n heterojunction device. We demonstrate the functionality of a
calibrated spectrometer in the spectral range of 400-1100 nm, with a small
device footprint of ~25X25 micrometers, and we achieve a mean reconstruction
error of 0.0002 for the power-spectrum at a spectral resolution of 0.35 nm.
Using our device, we demonstrate a solution to metamerism, an apparent matching
of colors with different power spectral distributions, which is a fundamental
problem in optical imaging.Comment: 15 pages, 5 figure
Efficient GRASP+VND and GRASP+VNS metaheuristics for the traveling repairman problem
The traveling repairman problem is a customer-centric routing problem, in which the total waiting time of the customers is minimized, rather than the total travel time of a vehicle. To date, research on this problem has focused on exact algorithms and approximation methods. This paper presents the first metaheuristic approach for the traveling repairman problem
Characterizing genomic alterations in cancer by complementary functional associations.
Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes
Vessel-Associated Transforming Growth Factor-Beta1 (TGF-β1) Is Increased in the Bronchial Reticular Basement Membrane in COPD and Normal Smokers
BACKGROUND: Transforming growth factor-beta1 (TGF-β1) is a multipotential cytokine with angiogenic activity. There are only limited data about its role in airway remodeling in COPD. We have previously shown that the reticular basement membrane (Rbm) is hypervascular in the airways of current smokers either with or without chronic obstructive pulmonary disease (COPD). This study evaluated TGF-β1 immunostaining in the Rbm and its relationship to vascularity in smokers with or without COPD. METHODOLOGY/PRINCIPAL FINDINGS: Bronchial biopsies from 15 smokers with normal lung function, 19 current and 14 ex-smokers with COPD were immunostained for TGF-β1 antibody and compared to 17 healthy controls. The percentage area of tissue and also number and area of vessels staining positively for TGF-β1 were measured and compared between groups. Some bronchial biopsies from current smoking COPD subjects were also stained for phosphorylated (active) Smad2/3. Epithelial TGF- β1 staining was not different between COPD current smokers and normal controls. TGF-β1 stained vessels in the Rbm were increased in smokers with normal lung function, current smoking COPD and ex-smokers with COPD compared to controls [median (range) for number of vessels/mm Rbm 2.5 (0.0-12.7), 3.4 (0.0-8.1) and 1.0 (0.0-6.3) vs. 0.0 (0.0-7.0), p<0.05]. Percentage of vessels stained was also increased in these clinical groups. Preliminary data suggest that in current smoking COPD subjects endothelial cells and cells in the Rbm stain positively for phosphorylated Smad2/3 suggesting TGF-β1 is functionally active in this situation. CONCLUSIONS/SIGNIFICANCE: Vessel-associated TGF-β1 activity is increased in the bronchial Rbm in smokers and especially those with COPD
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