scholarly journals A hypothesis for theta rhythm frequency control in CA1 microcircuits

2020 ◽  
Author(s):  
Frances K Skinner ◽  
Scott Rich ◽  
Anton R Lunyov ◽  
Jeremie Lefebvre ◽  
Alexandra P Chatzikalymniou
Keyword(s):  
Building Block ◽  
Theta Rhythm ◽  
Computational Models ◽  
Cell Model ◽  
Frequency Control ◽  
Network Models ◽  
Underlying Mechanism ◽  
Response Curves ◽  
Excitatory Cell ◽  
The Impact

ABSTRACTComputational models of neural circuits with varying levels of biophysical detail have been generated in pursuit of an underlying mechanism explaining the ubiquitous hippocampal theta rhythm. However, within the theta rhythm are at least two types with distinct frequencies associated with different behavioural states, an aspect that must be considered in pursuit of these mechanistic explanations. Here, using our previously developed excitatory-inhibitory network models that generate theta rhythms, we investigate the robustness of theta generation to intrinsic neuronal variability by building a database of heterogeneous excitatory cells and implementing them in our microcircuit model. We specifically investigate the impact of three key ‘building block’ features of the excitatory cell model that underlie our model design: these cells’ rheobase, their capacity for post-inhibitory rebound, and their spike-frequency adaptation. We show that theta rhythms at various frequencies can arise dependent upon the combination of these building block features, and we find that the speed of these oscillations are dependent upon the excitatory cells’ response to inhibitory drive, as encapsulated by their phase response curves. Taken together, these findings support a hypothesis for theta frequency control that includes two aspects: (i) an internal mechanism that stems from the building block features of excitatory cell dynamics; (ii) an external mechanism that we describe as ‘inhibition-based tuning’ of excitatory cell firing. We propose that these mechanisms control theta rhythm frequencies and underlie their robustness.

scholarly journals A Hypothesis for Theta Rhythm Frequency Control in CA1 Microcircuits

2021 ◽  
Vol 15 ◽  
Author(s):  
Frances K. Skinner ◽  
Scott Rich ◽  
Anton R. Lunyov ◽  
Jeremie Lefebvre ◽  
Alexandra P. Chatzikalymniou
Keyword(s):  
Building Block ◽  
Theta Rhythm ◽  
Computational Models ◽  
Cell Model ◽  
Frequency Control ◽  
Network Models ◽  
Underlying Mechanism ◽  
Response Curves ◽  
Excitatory Cell ◽  
The Impact

Computational models of neural circuits with varying levels of biophysical detail have been generated in pursuit of an underlying mechanism explaining the ubiquitous hippocampal theta rhythm. However, within the theta rhythm are at least two types with distinct frequencies associated with different behavioral states, an aspect that must be considered in pursuit of these mechanistic explanations. Here, using our previously developed excitatory-inhibitory network models that generate theta rhythms, we investigate the robustness of theta generation to intrinsic neuronal variability by building a database of heterogeneous excitatory cells and implementing them in our microcircuit model. We specifically investigate the impact of three key “building block” features of the excitatory cell model that underlie our model design: these cells' rheobase, their capacity for post-inhibitory rebound, and their spike-frequency adaptation. We show that theta rhythms at various frequencies can arise dependent upon the combination of these building block features, and we find that the speed of these oscillations are dependent upon the excitatory cells' response to inhibitory drive, as encapsulated by their phase response curves. Taken together, these findings support a hypothesis for theta frequency control that includes two aspects: (i) an internal mechanism that stems from the building block features of excitatory cell dynamics; (ii) an external mechanism that we describe as “inhibition-based tuning” of excitatory cell firing. We propose that these mechanisms control theta rhythm frequencies and underlie their robustness.

Sensitivity Analysis and Uncertainty Quantification for Rim Seal Ingestion With 1-D Network Models

2020 ◽  
Author(s):  
Alejandro Pozo Dominguez ◽  
Nicholas Hills ◽  
Simao Marques
Keyword(s):  
Computational Models ◽  
Network Models ◽  
Geometrical Parameters ◽  
High Pressure Turbine ◽  
Gas Network ◽  
Hot Gas ◽  
Limited Success ◽  
Secondary Air ◽  
The Impact ◽  
Influential Parameters

Abstract Accurate prediction of turbine rim seal ingestion remains a challenge, even sophisticated unsteady computational models have had limited success due to the complexity and uncertainties present in this type of problems. For this reason, it is of interest to perform stochastic analysis taking into account the variability in the input parameters as well as uncertainties and assumptions associated with a given model of choice. This study focuses on a Secondary Air System (SAS) of a gas turbine, considering a generic cavity in a high pressure turbine (HPT) in which hot gas ingestion occurs and uncertainty in geometrical, operational and modelling parameters is present. Several statistical methods are applied to a 1D gas network model in order to evaluate the impact of the tolerances of the main geometrical parameters in the output, followed by a broader analysis including other operational and modelling variables. Results indicate that most influential parameters are the sealant mass flow rate, a modelling constant and the minimum gap of the wheelspace cavity.

scholarly journals Curcumin Protects an SH-SY5Y Cell Model of Parkinson’s Disease Against Toxic Injury by Regulating HSP90

2018 ◽  
Vol 51 (2) ◽  
pp. 681-691 ◽  
Author(s):  
Qiuling Sang ◽  
Xiaoyang Liu ◽  
Libo Wang ◽  
Ling Qi ◽  
Wenping Sun ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Cell Proliferation ◽  
Parkinson's Disease ◽  
Cell Model ◽  
B Cell Lymphoma ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Enzyme Linked Immunosorbent Assay ◽  
Western Blot Assay ◽  
The Impact

Background/Aims: We aimed to explore the protective role of curcumin (Cur) in a cell model of Parkinson’s disease (PD) and its underlying mechanism. Methods: In this study, genes concerned with PD-related keywords were screened within DiGSeE database. The association network between Cur and selected genes was downloaded from STITCH, with the interactions analyzed by STRING. We built a mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+)-induced SH-SY5Y cell model of PD. Cell morphology was observed under an electron microscope. MTT assay was applied to detect cell proliferation rate. Western blot assay was conducted to determine the level of apoptotic markers, including cleaved caspase 3, Bcl-2-associated X protein (Bax) and B-cell lymphoma-extra-large (Bcl-xl). Tyrosine hydroxylase (TH), dopamine transporter (DAT) protein levels and dopamine (DA) concentration were identified as dopaminergic neuron markers and measured by western blotting or Enzyme-linked immunosorbent assay (ELISA). Results: Cur rescued the toxicity effects of MPP+ on SH-SY5Y cells, by controlling morphological change, promoting cell proliferation and inhibiting apoptosis. Of all PD-related genes, HSP90 played an important role in Cur-gene network. HSP90 protein level was elevated by MPP+, whereas Cur could reverse this effect. Silencing of HSP90 significantly attenuated the curative effect introduced by Cur, while HSP90 overexpression enhanced the impact of Cur on PD. Conclusion: Cur can effectively inhibit the toxic effect of MPP+ on SH-SY5Y cells and significantly reduce the adverse effects of MPP+ on dopaminergic neurons via up-regulation of HSP90.

scholarly journals Evaluation of the impact of compliance of precast discs of overlapping on the work of the frame of a multi-storey building

2019 ◽  
Vol 97 ◽  
pp. 04022
Author(s):  
Nikolay Trekin ◽  
Emil Kodysh ◽  
Alexander Bybka ◽  
Alexander Yamalov ◽  
Nikita Konkov
Keyword(s):  
Economic Performance ◽  
Computational Models ◽  
Precast Concrete ◽  
Building Frames ◽  
Frame Building ◽  
Numerical Studies ◽  
Frame Buildings ◽  
The Impact ◽  
Structural Solutions ◽  
Storey Building

The article provides an analysis and justification of the need to take into account the compliance of discs of overlapping and coatings when calculating frames from precast concrete structures. Previously conducted full-scale experiments showed that the rigidity of the precast overlapping with full filling of the seams, in comparison with the monolithic overlapping, decreases by 3-15 times due to the ductility of the joints. The use of refined computational models of structural solutions for frames, which take into account the compliance of the conjugations of elements, makes it possible to trace possible redistribution of efforts. Such an approach when reconstructing, it is possible to optimally select and calculate the enforcement of structure, and on new designing, to increase reliability and / or improve the economic performance of frame buildings. According to the results of analytical studies, formulas were adopted for the parameters that allow one to take into account the overall compliance of overlapping disks and coatings in computational models of building frames. Numerical studies on the computational model of a frame building made it possible to evaluate the effect of accounting for compliance on the stress-strain state of a multi-storey frame.

scholarly journals SIRT1 attenuates sepsis-induced acute kidney injury via Beclin1 deacetylation-mediated autophagy activation

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Zhiya Deng ◽  
Maomao Sun ◽  
Jie Wu ◽  
Haihong Fang ◽  
Shumin Cai ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Protective Effect ◽  
Cell Model ◽  
Kidney Injury ◽  
Underlying Mechanism ◽  
Autophagy Induction ◽  
Promising Therapeutic Approach ◽  
Related Proteins ◽  
Caecal Ligation And Puncture

AbstractOur previous studies showed that silent mating-type information regulation 2 homologue-1 (SIRT1, a deacetylase) upregulation could attenuate sepsis-induced acute kidney injury (SAKI). Upregulated SIRT1 can deacetylate certain autophagy-related proteins (Beclin1, Atg5, Atg7 and LC3) in vitro. However, it remains unclear whether the beneficial effect of SIRT1 is related to autophagy induction and the underlying mechanism of this effect is also unknown. In the present study, caecal ligation and puncture (CLP)-induced mice, and an LPS-challenged HK-2 cell line were established to mimic a SAKI animal model and a SAKI cell model, respectively. Our results demonstrated that SIRT1 activation promoted autophagy and attenuated SAKI. SIRT1 deacetylated only Beclin1 but not the other autophagy-related proteins in SAKI. SIRT1-induced autophagy and its protective effect against SAKI were mediated by the deacetylation of Beclin1 at K430 and K437. Moreover, two SIRT1 activators, resveratrol and polydatin, attenuated SAKI in CLP-induced septic mice. Our study was the first to demonstrate the important role of SIRT1-induced Beclin1 deacetylation in autophagy and its protective effect against SAKI. These findings suggest that pharmacologic induction of autophagy via SIRT1-mediated Beclin1 deacetylation may be a promising therapeutic approach for future SAKI treatment.

scholarly journals Evaluation of a Coupled Model to Predict the Impact of Adaptive Behaviour in the Thermal Sensation of Occupants of Naturally Ventilated Buildings in Warm-Humid Regions

2020 ◽  
Vol 13 (1) ◽  
pp. 255
Author(s):  
Luciano C. de Faria ◽  
Marcelo A. Romero ◽  
Lúcia F. S. Pirró
Keyword(s):  
Computational Models ◽  
Thermal Sensation ◽  
Coupled Model ◽  
Adaptive Behaviour ◽  
Humid Climate ◽  
Clothing Insulation ◽  
Tropical Regions ◽  
Naturally Ventilated Buildings ◽  
Adaptive Behaviours ◽  
The Impact

Improving indoor environment quality and making urban centres in tropical regions more sustainable has become a challenge for which computational models for the prediction of thermal sensation for naturally ventilated buildings (NVBs) have major role to play. This work performed analysis on thermal sensation for non-residential NVBs located in Brazilian tropical warm-humid climate and tested the effectiveness of suggested adaptive behaviours to mitigate warm thermal sensation. The research method utilized transient computational fluid dynamics models coupled with a dynamic model for human thermophysiology to predict thermal sensation. The calculated results were validated with comparison with benchmark values from questionnaires and from field measurements. The calculated results for dynamic thermal sensation (DTS) seven-point scale showed higher agreement with the thermal sensation vote than with the predicted mean vote. The test for the suggested adaptive behaviours considered reducing clothing insulation values from 0.18 to 0.32 clo (reducing DTS from 0.1 to 0.9), increasing the air speed in 0.9 m/s (reducing DTS from 0.1 to 0.9), and applying both suggestions together (reducing DTS from 0.1 to 1.3) for five scenarios with operative temperatures spanning 34.5–24.0 °C. Results quantified the tested adaptive behaviours’ efficiency showing applicability to improve thermal sensation from slightly-warm to neutral.

scholarly journals Braided composite stent for peripheral vascular applications

2020 ◽  
Vol 9 (1) ◽  
pp. 1137-1146
Author(s):  
Qingli Zheng ◽  
Pengfei Dong ◽  
Zhiqiang Li ◽  
Ying Lv ◽  
Meiwen An ◽  
...  
Keyword(s):  
Computational Models ◽  
Surface Coverage ◽  
Mechanical Performance ◽  
Wire Diameter ◽  
Orthogonal Experimental Design ◽  
Braided Composite ◽  
Nitinol Wire ◽  
Radial Strength ◽  
Braiding Angle ◽  
The Impact

AbstractBraided composite stent (BCS), woven with nitinol wires and polyethylene terephthalate (PET) strips, provides a hybrid design of stent. The mechanical performance of this novel stent has not been fully investigated yet. In this work, the influence of five main design factors (number of nitinol wires, braiding angle, diameter of nitinol wire, thickness and stiffness of the PET strip) on the surface coverage, radial strength, and flexibility of the BCS were systematically studied using computational models. The orthogonal experimental design was adopted to quantitatively analyze the sensitivity of multiple factors using the minimal number of study cases. Results have shown that the nitinol wire diameter and the braiding angle are two most important factors determining the mechanical performance of the BCS. A larger nitinol wire diameter led to a larger radial strength and less flexibility of the BCS. A larger braiding angle could provide a larger radial strength and better flexibility. In addition, the impact of the braiding angle decreased when the stent underwent a large deformation. At the same time, the impact of the PET strips increased due to the interaction with nitinol wires. Moreover, the number of PET strips played an important role in the surface coverage. This study could help understand the mechanical performance of BCS stent and provides guidance on the optimal design of the stent targeting less complications.

The Impact of an Improved Flaw Model on a Pressurized Thermal Shock Evaluation

2002 ◽  
Author(s):  
T. L. Dickson ◽  
F. A. Simonen
Keyword(s):  
Thermal Shock ◽  
Computational Models ◽  
The United States ◽  
Pressure Vessels ◽  
Pressurized Water ◽  
Evaluation Program ◽  
Pressurized Thermal Shock ◽  
Computational Methodology ◽  
The Impact ◽  
Flaw Characterization

The current regulations for pressurized thermal shock (PTS) were derived from computational models that were developed in the early-mid 1980s. The computational models utilized in the 1980s conservatively postulated that all fabrication flaws in reactor pressure vessels (RPVs) were inner-surface breaking flaws. It was recognized at that time that flaw-related data had the greatest level of uncertainty of the inputs required for the probabilistic-based PTS evaluations. To reduce this uncertainty, the United States Nuclear Regulatory Commission (USNRC) has in the past few years supported research at Pacific Northwest National Laboratory (PNNL) to perform extensive nondestructive and destructive examination of actual RPV materials. Such measurements have been used to characterize the number, size, and location of flaws in various types of welds and the base metal used to fabricate RPVs. The USNRC initiated a comprehensive project in 1999 to re-evaluate the current PTS regulations. The objective of the PTS Re-evaluation program has been to incorporate advancements and refinements in relevant technologies (associated with the physics of PTS events) that have been developed since the current regulations were derived. There have been significant improvements in the computational models for thermal hydraulics, probabilistic risk assessment (PRA), human reliability analysis (HRA), materials embrittlement effects on fracture toughness, and fracture mechanics methodology. However, the single largest advancement has been the development of a technical basis for the characterization of fabrication-induced flaws. The USNRC PTS-Revaluation program is ongoing and is expected to be completed in 2002. As part of the PTS Re-evaluation program, the updated risk-informed computational methodology as implemented into the FAVOR (Fracture Analysis of Vessels: Oak Ridge) computer code, including the improved PNNL flaw characterization, was recently applied to a domestic commercial pressurized water reactor (PWR). The objective of this paper is to apply the same updated computational methodology to the same PWR, except utilizing the 1980s flaw model, to isolate the impact of the improved PNNL flaw characterization on the PTS analysis results. For this particular PWR, the improved PNNL flaw characterization significantly reduced the frequency of RPV failure, i.e., by between one and two orders of magnitude.

Stereoscopically Observed Deformations of a Compliant Abdominal Aortic Aneurysm Model

2011 ◽  
Vol 133 (11) ◽  
Author(s):  
Clark A. Meyer ◽  
Eric Bertrand ◽  
Olivier Boiron ◽  
Valérie Deplano
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Computational Models ◽  
Imaging System ◽  
Strain Differences ◽  
Cyclic Strain ◽  
Experimental Models ◽  
Body Motion ◽  
Abdominal Aortic ◽  
The Impact

A new experimental setup has been implemented to precisely measure the deformations of an entire model abdominal aortic aneurysm (AAA). This setup addresses a gap between the computational and experimental models of AAA that have aimed at improving the limited understanding of aneurysm development and rupture. The experimental validation of the deformations from computational approaches has been limited by a lack of consideration of the large and varied deformations that AAAs undergo in response to physiologic flow and pressure. To address the issue of experimentally validating these calculated deformations, a stereoscopic imaging system utilizing two cameras was constructed to measure model aneurysm displacement in response to pressurization. The three model shapes, consisting of a healthy aorta, an AAA with bifurcation, and an AAA without bifurcation, were also evaluated with computational solid mechanical modeling using finite elements to assess the impact of differences between material properties and for comparison against the experimental inflations. The device demonstrated adequate accuracy (surface points were located to within 0.07 mm) for capturing local variation while allowing the full length of the aneurysm sac to be observed at once. The experimental model AAA demonstrated realistic aneurysm behavior by having cyclic strains consistent with reported clinical observations between pressures 80 and 120 mm Hg. These strains are 1–2%, and the local spatial variations in experimental strain were less than predicted by the computational models. The three different models demonstrated that the asymmetric bifurcation creates displacement differences but not cyclic strain differences within the aneurysm sac. The technique and device captured regional variations of strain that are unobservable with diameter measures alone. It also allowed the calculation of local strain and removed rigid body motion effects on the strain calculation. The results of the computations show that an asymmetric aortic bifurcation created displacement differences but not cyclic strain differences within the aneurysm sac.

Protective Effect of Butylphthalide on Neuronal Apoptosis in Parkinson Rats and Its Effect on miR-146a-5p Expression and Phosphatidylinositide 3-Kinases/Protein Kinase B Pathway

2021 ◽  
Vol 11 (10) ◽  
pp. 1908-1917
Author(s):  
Rongkang Mai ◽  
Yiyao Cao ◽  
Huitian Yu ◽  
Yong Zheng ◽  
Juke Huang
Keyword(s):  
Cell Model ◽  
Morphological Changes ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Line ◽  
Vehicle Group ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Oil Emulsion ◽  
The Impact

80 male Wistar rats were stochastically assigned to Sham + Vehicle group, Sham + BUT group, PD + Vehicle group and PD + BUT group. Rotenone PD model rats were prepared by subcutaneous injection of rotenone sunflower oil emulsion 2 mg/(kg · d) for 5 consecutive weeks. Butylphthalide 80 mg/(kg · d) were given to the rats in Sham + BUT group and PD + BUT group by gavage from the first day of rotenone injection for 5 weeks. Subsequently, the motor retardation ability and the morphological changes of the substantia nigra (SN) of each group were evaluated. Meanwhile, the levels of neuronal injury, apoptosis, inflammation and oxidative stress in each group of rats were assayed. The impact of BUT treatment on miR-146a-5p expression and PI3K/AKT signal pathway in rat brain tissue was assayed. Finally, by constructing a PD cell model of the neurotoxin 6-hydroxydopamine (6-OHDA)-treated human neuroblastoma cell line SH-SY5Y, the in vitro anti-PD pharmacological effect of BUT was further verified.

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