680 research outputs found
Fermionic WIMPs and Vacuum Stability in the Scotogenic Model
We demonstrate that the condition of vacuum stability severely restricts
scenarios with fermionic WIMP dark matter in the scotogenic model. The sizable
Yukawa couplings that are required to satisfy the dark matter constraint via
thermal freeze-out in these scenarios tend to destabilise the vacuum at scales
below that of the heaviest singlet fermion, rendering the model inconsistent
from a theoretical point of view. By means of a scan over the parameter space,
we study the impact of these renormalisation group effects on the viable
regions of this model. Our analysis shows that a fraction of more than 90% of
the points compatible with all known experimental constraints - including
neutrino masses, the dark matter density, and lepton flavour violation - is
actually inconsistent.Comment: 8 pages, 6 figures; content matches published versio
On the mechanism of TASK channel inhibition by G-Protein coupled receptors
Background K+ conductance TASK channels belong to the family of two pore domain potassium channels. They are involved in regulation of neuronal excitability, cardiovascular homeostasis and endocrine activity. TASK channel activity is down-regulated by activation Gq-protein coupled receptors (GqPCR). In various tissues this regulatory mechanism is crucial for proper organ function. Well studied examples of GqPCR mediated TASK channel inhibition are the cholinergic inhibition of IK,SO in cerebellar granule neurons, angiotensin II stimulated aldosterone secretion in adrenal zona-glomerulosa cells and vasoconstriction of the pulmonary artery by endothelin-1.
Despite intense research, the mechanism underlying this inhibition remains elusive. Strong evidence exists for two competing hypotheses: TASK channels could be either blocked directly by the Gq-alpha subunit released on GqPCR activation, or their closure could be a direct consequence of Phospholipase C (PLC)-mediated phosphatidyl-inositol(4,5)-bis-phosphate (PtdIns(4,5)P2) depletion.
In the present study I investigated the role of PLC mediated phosphoinositide cleavage in the process of TASK channel regulation by GqPCR in the intact cell. Recently developed genetically encoded switchable phosphoinositide-phosphatases were used to specifically deplete PtdIns(4,5)P2. Additionally, I interfered with PtdIns(4,5)P2 resynthesis and PLC activity. I found that blockage of PLC results in abolishment of GqPCR induced TASK inhibition. However depletion of the PLC substrate PtdIns(4,5)P2 alone was not sufficient to inhibit TASK.
These results show that PLC activation is an indispensable step in TASK channel inhibition. They further demonstrate that the depletion of PtdIns(4,5)P2 does not directly inhibit TASK and therefore suggest that a regulatory mechanism downstream of PtdIns(4,5)P2-hydrolysis mediates TASK channel inhibition
The ERGtools2 package: a toolset for processing and analysing visual electrophysiology data
Purpose: To introduce ERGtools2, an open-source R package for processing, analysing and long-term storing visual electrophysiology data. Methods: A dataset comprising Electroretinogram (ERG) recordings of C57Bl/6J mice, subjected to standard ISCEV stimuli, was used to present the functionality of ERGtools2. ERGtools2 stores and organizes all recordings, metadata, and measurement information from an individual examination in a single object, maintaining raw data throughout the analysis process. Results: A standard workflow is presented exemplifying how ERGtools2 can be used to efficiently import, pre-process and analyse ERG data. Following this workflow, basic ERG measurements and visualisation of a single exam as well as group statistics are obtained. Moreover, special use cases are described, including for the handling of noisy data and the storage of data in the HDF5 format to ensure long-term preservation and accessibility. Conclusions: ERGtools2 provides a comprehensive, flexible, and device-independent solution for visual electrophysiology data analysis. Its emphasis on maintaining raw data integrity, combined with advanced processing and analysis capabilities, makes it a useful tool for preclinical and clinical research applications. The open-source nature and the use of open data formats promote reproducibility and data sharing in visual neurosciences
Reconstruction and subsurface lattice distortions in the (2 × 1)O-Ni(110) structure: A LEED analysis
LEED analysis of the reconstructed (2 × 1)O-Ni(110) system clearly favors the “missing row” structure over the “saw-tooth” and “buckled row” models. By using a novel computational procedure 8 structural parameters could be refined simultaneously, leading to excellent R-factors (RZJ = 0.09, RP = 0.18). The adsorbed O atoms are located 0.2 Å above the long bridge sites in [001] direction, presumably with a slight displacement ( 0.1 Å) in [1 0] direction to an asymmetric adsorption site. The nearest-neighbor Ni---O bond lengths (1.77 Å) are rather short. The separation between the topmost two Ni layers is expanded to 1.30 Å (bulk value 1.25 Å), while that between the second and third layer is slightly contracted to 1.23 Å. The third layer is, in addition, slightly buckled (±0.05 Å). The results are discussed on the basis of our present general knowledge about the structure of adsorbate covered metallic surfaces
Autonomous Integration of TSN-unaware Applications with QoS Requirements in TSN Networks
Modern industrial networks transport both best-effort and real-time traffic.
Time-Sensitive Networking (TSN) was introduced by the IEEE TSN Task Group as an
enhancement to Ethernet to provide high quality of service (QoS) for real-time
traffic. In a TSN network, applications signal their QoS requirements to the
network before transmitting data. The network then allocates resources to meet
these requirements. However, TSN-unaware applications can neither perform this
registration process nor profit from TSN's QoS benefits. The contributions of
this paper are twofold. First, we introduce a novel network architecture in
which an additional device autonomously signals the QoS requirements of
TSN-unaware applications to the network. Second, we propose a processing method
to detect real-time streams in a network and extract the necessary information
for the TSN stream signaling. It leverages a Deep Recurrent Neural Network
(DRNN) to detect periodic traffic, extracts an accurate traffic description,
and uses traffic classification to determine the source application. As a
result, our proposal allows TSN-unaware applications to benefit from TSNs QoS
guarantees. Our evaluations underline the effectiveness of the proposed
architecture and processing method.Comment: Preprint submitted to Computer Communications Journal, Elsevie
The functional characteristics of optogenetic gene therapy for vision restoration
Optogenetic strategies to restore vision in patients blind from end-stage retinal degenerations aim to render remaining retinal neurons light-sensitive. We present an innovative combination of multi-electrode array recordings together with a complex pattern-generating light source as a toolset to determine the extent to which neural retinal responses to complex light stimuli can be restored following viral delivery of red-shifted channelrhodopsin in the retinally degenerated mouse. Our data indicate that retinal output level spatiotemporal response characteristics achieved by optogenetic gene therapy closely parallel those observed for normal mice but equally reveal important limitations, some of which could be mitigated using bipolar-cell targeted gene-delivery approaches. As clinical trials are commencing, these data provide important new information on the capacity and limitations of channelrhodopsin-based gene therapies. The toolset we established enables comparing optogenetic constructs and stem-cell-based techniques, thereby providing an efficient and sensitive starting point to identify future approaches for vision restoration
A Fokker-Planck formalism for diffusion with finite increments and absorbing boundaries
Gaussian white noise is frequently used to model fluctuations in physical
systems. In Fokker-Planck theory, this leads to a vanishing probability density
near the absorbing boundary of threshold models. Here we derive the boundary
condition for the stationary density of a first-order stochastic differential
equation for additive finite-grained Poisson noise and show that the response
properties of threshold units are qualitatively altered. Applied to the
integrate-and-fire neuron model, the response turns out to be instantaneous
rather than exhibiting low-pass characteristics, highly non-linear, and
asymmetric for excitation and inhibition. The novel mechanism is exhibited on
the network level and is a generic property of pulse-coupled systems of
threshold units.Comment: Consists of two parts: main article (3 figures) plus supplementary
text (3 extra figures
Hairpin-Wicklungen für elektrische Fahrantriebe
Dieser Beitrag beschäftigt sich mit den zunehmend Verbreitung findenden Hairpin-Wicklungen unter den besonderen Randbedingungen elektrischer Fahrantriebe. Dabei wird bewusst auf den in der Literatur bekannten Vergleich zu konventionellen Wicklungen hinsichtlich Nutfüllfaktor und Kühlanbindung verzichtet. Stattdessen konzentriert sich der Beitrag zunächst auf die Stromverdrängung, ihre Abhängigkeiten sowie Möglichkeiten zur Reduzierung des Effekts, wobei ausschließlich Maßnahmen vorgestellt werden, die zum Stand der Technik großserientauglich sind. Darüber hinaus werden Potentiale im Layout der Spulenseiten und Wickelköpfe aufgezeigt, die weit über die Optionen von aus Endlosdraht hergestellten Wicklungen hinausgehen.This paper examines the increasingly popular hairpin windings under the dedicated boundary conditions of electrical drivetrains. A comparison to conventional windings regarding slot filling and cooling link will consciously be omitted since it is well known from literature. Instead, the paper concentrates on current displacement, its dependencies and possibilities for its reduction – with only measures being considered that state-of-the-art are suitable for mass-production. Furthermore, potentials in the layout of coil sides and end-windings are shown, which are far beyond the options of windings manufactured from continuous wire
Optogenetic vision restoration in the face of secondary and tertiary remodelling in the rd1 mouse retina
Photoreceptor loss in retinal degeneration is followed by progressive remodelling of the surviving retina, which may present a barrier to vision restoration. To determine the impact of remodelling on the retina’s suitability for therapeutic interventions, we track changes in visual code produced by the optogenetic actuator ReaChR expressed in ON-bipolar cells of the rd1 mouse at 3,5,9 and 12 months. Anatomical analyses confirm these ages encompass phase II (photoreceptor degeneration) to phase III (inner retinal thinning, dysmorphia, pigment epithelium infiltration) remodelling. Multi-electrode array recording from retinal ganglion cells reveal that ReaChR-driven responses to a range of visual stimuli are stable across this age range. Response amplitude, sensitivity and reproducibility all increased between 3 and 5 months, remaining consistent thereafter. Receptive field sizes, contrast sensitivity, and temporal frequency tuning showed minor changes with age. The diversity of retinal ganglion cell coding was maintained, reflected by the diversity captured by unsupervised functional clustering with 11 distinct visual channels retained across ages. Our data indicate that remodelling does not significantly impair, and at early stages may even enhance the surviving retina’s ability to support visual restoration. Clinical intervention thus remains viable throughout remodelling, suggesting a wide window in disease progression for therapeutic benefit
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