729 research outputs found
A Non-intrusive Approach for Physics-constrained Learning with Application to Fuel Cell Modeling
A data-driven model augmentation framework, referred to as Weakly-coupled
Integrated Inference and Machine Learning (IIML), is presented to improve the
predictive accuracy of physical models. In contrast to parameter calibration,
this work seeks corrections to the structure of the model by a) inferring
augmentation fields that are consistent with the underlying model, and b)
transforming these fields into corrective model forms. The proposed approach
couples the inference and learning steps in a weak sense via an alternating
optimization approach. This coupling ensures that the augmentation fields
remain learnable and maintain consistent functional relationships with local
modeled quantities across the training dataset. An iterative solution procedure
is presented in this paper, removing the need to embed the augmentation
function during the inference process. This framework is used to infer an
augmentation introduced within a Polymer electrolyte membrane fuel cell (PEMFC)
model using a small amount of training data (from only 14 training cases.)
These training cases belong to a dataset consisting of high-fidelity simulation
data obtained from a high-fidelity model of a first generation Toyota Mirai.
All cases in this dataset are characterized by different inflow and outflow
conditions on the same geometry. When tested on 1224 different configurations,
the inferred augmentation significantly improves the predictive accuracy for a
wide range of physical conditions. Predictions and available data for the
current density distribution are also compared to demonstrate the predictive
capability of the model for quantities of interest which were not involved in
the inference process. The results demonstrate that the weakly-coupled IIML
framework offers sophisticated and robust model augmentation capabilities
without requiring extensive changes to the numerical solver
Applications of Direct Injection Soft Chemical Ionisation-Mass Spectrometry for the Detection of Pre-blast Smokeless Powder Organic Additives
Analysis of smokeless powders is of interest from forensics and security perspectives. This article reports the detection of smokeless powder organic additives (in their pre-detonation condition), namely the stabiliser diphenylamine and its derivatives 2-nitrodiphenylamine and 4-nitrodiphenylamine, and the additives (used both as stabilisers and plasticisers) methyl centralite and ethyl centralite, by means of swab sampling followed by thermal desorption and direct injection soft chemical ionisation-mass spectrometry. Investigations on the product ions resulting from the reactions of the reagent ions H3O+ and O2+ with additives as a function of reduced electric field are reported. The method was comprehensively evaluated in terms of linearity, sensitivity and precision. For H3O+, the limits of detection (LoD) are in the range of 41-88 pg of additive, for which the accuracy varied between 1.5 and 3.2%, precision varied between 3.7 and 7.3% and linearity showed R20.9991. For O2+, LoD are in the range of 72 to 1.4 ng, with an accuracy of between 2.8 and 4.9% and a precision between 4.5 and 8.6% and R20.9914. The validated methodology was applied to the analysis of commercial pre-blast gun powders from different manufacturers.(VLID)4826148Accepted versio
Randomly Evolving Idiotypic Networks: Structural Properties and Architecture
We consider a minimalistic dynamic model of the idiotypic network of
B-lymphocytes. A network node represents a population of B-lymphocytes of the
same specificity (idiotype), which is encoded by a bitstring. The links of the
network connect nodes with complementary and nearly complementary bitstrings,
allowing for a few mismatches. A node is occupied if a lymphocyte clone of the
corresponding idiotype exists, otherwise it is empty. There is a continuous
influx of new B-lymphocytes of random idiotype from the bone marrow.
B-lymphocytes are stimulated by cross-linking their receptors with
complementary structures. If there are too many complementary structures,
steric hindrance prevents cross-linking. Stimulated cells proliferate and
secrete antibodies of the same idiotype as their receptors, unstimulated
lymphocytes die.
Depending on few parameters, the autonomous system evolves randomly towards
patterns of highly organized architecture, where the nodes can be classified
into groups according to their statistical properties. We observe and describe
analytically the building principles of these patterns, which allow to
calculate number and size of the node groups and the number of links between
them. The architecture of all patterns observed so far in simulations can be
explained this way. A tool for real-time pattern identification is proposed.Comment: 19 pages, 15 figures, 4 table
Orexinergic Input to Dopaminergic Neurons of the Human Ventral Tegmental Area
The mesolimbic reward pathway arising from dopaminergic (DA) neurons of the ventral tegmental area (VTA) has been
strongly implicated in reward processing and drug abuse. In rodents, behaviors associated with this projection are
profoundly influenced by an orexinergic input from the lateral hypothalamus to the VTA. Because the existence and
significance of an analogous orexigenic regulatory mechanism acting in the human VTA have been elusive, here we
addressed the possibility that orexinergic neurons provide direct input to DA neurons of the human VTA. Dual-label
immunohistochemistry was used and orexinergic projections to the VTA and to DA neurons of the neighboring substantia
nigra (SN) were analyzed comparatively in adult male humans and rats. Orexin B-immunoreactive (IR) axons apposed to
tyrosine hydroxylase (TH)-IR DA and to non-DA neurons were scarce in the VTA and SN of both species. In the VTA,
15.062.8% of TH-IR perikarya in humans and 3.260.3% in rats received orexin B-IR afferent contacts. On average, 0.2460.05 and 0.0560.005 orexinergic appositions per TH-IR perikaryon were detected in humans and rats, respectively. The majority(86–88%) of randomly encountered orexinergic contacts targeted the dendritic compartment of DA neurons. Finally, DA neurons of the SN also received orexinergic innervation in both species. Based on the observation of five times heavierorexinergic input to TH-IR neurons of the human, compared with the rat, VTA, we propose that orexinergic mechanism acting in the VTA may play just as important roles in reward processing and drug abuse in humans, as already established
well in rodents
Selective Reagent Ion Mass Spectrometric Investigations of the Nitroanilines
This paper presents an investigation of proton and charge transfer reactions to 2-, 3- and 4-nitroanilines (C6H6N2O2) involving the reagent ions H3O+·(H2O)n (n=0, 1 and 2) and O2+, respectively, as a function of reduced electric field (60-240 Td), using Selective Reagent Ion-Time-of-Flight-Mass Spectrometry (SRI-ToF-MS). To aid in the interpretation of the H3O+·(H2O)n experimental data, the proton affinities and gas-phase basicities for the three nitroaniline isomers have been determined using density functional theory. These calculations show that proton transfer from both the H3O+ and H3O+·H2O reagent ions to the nitroanilines will be exoergic and hence efficient, with the reactions proceeding at the collisional rate. For proton transfer from H3O+ to the NO2 sites, the exoergicities are 171 kJ mol-1 (1.8 eV), 147 kJ mol-1 (1.5 eV) and 194 kJ mol-1 (2.0 eV) for 2-, 3- and 4-nitroanilines, respectively. Electron transfer from all three of the nitroanilines is also significantly exothermic by approximately 4 eV. Although a substantial transfer of energy occurs during the ion/molecule reactions, the processes are found to predominantly proceed via non-dissociative pathways over a large reduced electric field range. Only at relatively high reduced electric fields (>180 Td) is dissociative proton and charge transfer observed. Differences in fragment product ions and their intensities provide a means to distinguish the isomers, with proton transfer distinguishing 2-nitroaniline (2-NA) from 3- and 4-NA, and charge transfer distinguishing 4-NA from 2- and 3-NA, thereby providing a means to enhance selectivity using SRI-ToF-MS.(VLID)4826158Version of recor
T Cell Responses to Neural Autoantigens Are Similar in Alzheimer’s Disease Patients and Age-Matched Healthy Controls
Alzheimer’s disease (AD), a chronic multifactorial and complex neurodegenerative disorder is a leading cause of dementia. Recently, neuroinflammation has been hypothesized as a contributing factor to AD pathogenesis. The role of adaptive immune responses against neuronal antigens, which can either confer protection or induce damage in AD, has not been fully characterized. Here, we measured T cell responses to several potential antigens of neural origin including amyloid precursor protein (APP), amyloid beta (Aβ), tau, α-synuclein, and transactive response DNA binding protein (TDP-43) in patients with AD and age-matched healthy controls (HC). Antigen-specific T cell reactivity was detected for all tested antigens, and response to tau-derived epitopes was particularly strong, but no significant differences between individuals with AD and age-matched HC were identified. We also did not observe any correlation between the antigen-specific T cell responses and clinical variables including age, gender, years since diagnosis and cognitive score. Additionally, further characterization did not reveal any differences in the relative frequency of major Peripheral Blood Mononuclear Cells (PBMC) subsets, or in the expression of genes between AD patients and HC. These observations have not identified a key role of neuronal antigen-specific T cell responses in AD
Randomly Evolving Idiotypic Networks: Modular Mean Field Theory
We develop a modular mean field theory for a minimalistic model of the
idiotypic network. The model comprises the random influx of new idiotypes and a
deterministic selection. It describes the evolution of the idiotypic network
towards complex modular architectures, the building principles of which are
known. The nodes of the network can be classified into groups of nodes, the
modules, which share statistical properties. Each node experiences only the
mean influence of the groups to which it is linked. Given the size of the
groups and linking between them the statistical properties such as mean
occupation, mean life time, and mean number of occupied neighbors are
calculated for a variety of patterns and compared with simulations. For a
pattern which consists of pairs of occupied nodes correlations are taken into
account.Comment: 14 pages, 8 figures, 4 table
Loss of VGLUT3 Produces Circadian-Dependent Hyperdopaminergia and Ameliorates Motor Dysfunction and l-Dopa-Mediated Dyskinesias in a Model of Parkinson\u27s Disease.
UNLABELLED: The striatum is essential for many aspects of mammalian behavior, including motivation and movement, and is dysfunctional in motor disorders such as Parkinson\u27s disease. The vesicular glutamate transporter 3 (VGLUT3) is expressed by striatal cholinergic interneurons (CINs) and is thus well positioned to regulate dopamine (DA) signaling and locomotor activity, a canonical measure of basal ganglia output. We now report that VGLUT3 knock-out (KO) mice show circadian-dependent hyperlocomotor activity that is restricted to the waking cycle and is due to an increase in striatal DA synthesis, packaging, and release. Using a conditional VGLUT3 KO mouse, we show that deletion of the transporter from CINs, surprisingly, does not alter evoked DA release in the dorsal striatum or baseline locomotor activity. The mice do, however, display changes in rearing behavior and sensorimotor gating. Elevation of DA release in the global KO raised the possibility that motor deficits in a Parkinson\u27s disease model would be reduced. Remarkably, after a partial 6-hydroxydopamine (6-OHDA)-mediated DA depletion (∼70% in dorsal striatum), KO mice, in contrast to WT mice, showed normal motor behavior across the entire circadian cycle. l-3,4-dihydroxyphenylalanine-mediated dyskinesias were also significantly attenuated. These findings thus point to new mechanisms to regulate basal ganglia function and potentially treat Parkinson\u27s disease and related disorders.
SIGNIFICANCE STATEMENT: Dopaminergic signaling is critical for both motor and cognitive functions in the mammalian nervous system. Impairments, such as those found in Parkinson\u27s disease patients, can lead to severe motor deficits. Vesicular glutamate transporter 3 (VGLUT3) loads glutamate into secretory vesicles for neurotransmission and is expressed by discrete neuron populations throughout the nervous system. Here, we report that the absence of VGLUT3 in mice leads to an upregulation of the midbrain dopamine system. Remarkably, in a Parkinson\u27s disease model, the mice show normal motor behavior. They also show fewer abnormal motor behaviors (dyskinesias) in response to l-3,4-dihydroxyphenylalanine, the principal treatment for Parkinson\u27s disease. The work thus suggests new avenues for the development of novel treatment strategies for Parkinson\u27s disease and potentially other basal-ganglia-related disorders
Locomotor hyperactivity in 14-3-3Zeta KO mice is associated with dopamine transporter dysfunction
Dopamine (DA) neurotransmission requires a complex series of enzymatic reactions that are tightly linked to catecholamine exocytosis and receptor interactions on pre- and postsynaptic neurons. Regulation of dopaminergic signalling is primarily achieved through reuptake of extracellular DA by the DA transporter (DAT) on presynaptic neurons. Aberrant regulation of DA signalling, and in particular hyperactivation, has been proposed as a key insult in the presentation of schizophrenia and related neuropsychiatric disorders. We recently identified 14-3-3ζ as an essential component of neurodevelopment and a central risk factor in the schizophrenia protein interaction network. Our analysis of 14-3-3ζ-deficient mice now shows that baseline hyperactivity of knockout (KO) mice is rescued by the antipsychotic drug clozapine. 14-3-3ζ KO mice displayed enhanced locomotor hyperactivity induced by the DA releaser amphetamine. Consistent with 14-3-3ζ having a role in DA signalling, we found increased levels of DA in the striatum of 14-3-3ζ KO mice. Although 14-3-3ζ is proposed to modulate activity of the rate-limiting DA biosynthesis enzyme, tyrosine hydroxylase (TH), we were unable to identify any differences in total TH levels, TH localization or TH activation in 14-3-3ζ KO mice. Rather, our analysis identified significantly reduced levels of DAT in the absence of notable differences in RNA or protein levels of DA receptors D1–D5. Providing insight into the mechanisms by which 14-3-3ζ controls DAT stability, we found a physical association between 14-3-3ζ and DAT by co-immunoprecipitation. Taken together, our results identify a novel role for 14-3-3ζ in DA neurotransmission and provide support to the hyperdopaminergic basis of pathologies associated with schizophrenia and related disorders.H Ramshaw, X Xu, EJ Jaehne, P McCarthy, Z Greenberg, E Saleh, B McClure, J Woodcock, S Kabbara, S Wiszniak, Ting-Yi Wang, C Parish, M van den Buuse, BT Baune, A Lopez and Q Schwar
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