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A central component in simulating cardiac electrophysiology is the numerical solution of nonlinear ordinary differential equations, also called cardiac ionic cell models, that describe cross-cell-membrane ion transport. Biophysically detailed cell models often require a considerable amount of computation, including calls to special mathematical functions. This paper systematically studies how to efficiently use modern multicore CPUs for this costly computational task. We start by investigating the code restructurings needed to effectively enable compiler-supported SIMD vectorisation, which is the most important performance booster in this context. It is found that suitable OpenMP directives are sufficient for achieving both vectorisation and parallelisation. We then continue with an evaluation of the performance optimisation technique of using lookup tables. Due to increased challenges for automated vectorisation, the obtainable benefits of lookup tables are dependent on the hardware platforms chosen. Throughout the study, we report detailed time measurements obtained on Intel Xeon, Xeon Phi, AMD Epyc and two ARM processors including Fujitsu A64FX, while attention is also paid to the impact of SIMD vectorisation and lookup tables on the computational accuracy. As a realistic example, the benefits of performance enhancement are demonstrated by a 109-run ensemble on the Oakforest-PACS system, where code restructurings and SIMD vectorisation yield an 84% reduction in computing time, corresponding to 63,270 node hours.There is a critical need for an oral-killed Salmonella vaccine for broilers. Chitosan nanoparticle (CNP) vaccines can be used to deliver Salmonella antigens orally. We investigated the efficacy of a killed Salmonella CNP vaccine on broilers. CNP vaccine was synthesized using Salmonella enterica serovar Enteritidis (S. Enteritidis) outer membrane and flagella proteins. CNP was stable at acidic conditions by releasing 14% of proteins at pH 5.5. At 17 h post-incubation, the cumulative protein release for CNP was 75% at pH 7.4. Two hundred microliters of PBS with chicken red blood cells incubated with 20 μg/ml CNP released 0% hemoglobin. Three hundred chicks were allocated into 1) Control, 2) Challenge, 3) Vaccine + Challenge. At d1 of age, chicks were spray-vaccinated with PBS or 40 mg CNP. At d7 of age, chicks were orally-vaccinated with PBS or 20 μg CNP/bird. At d14 of age, birds were orally-challenged with PBS or 1 × 107 CFU/bird of S. Enteritidis. The CNP-vaccinated birds had higher antigen-specific IgY/IgA and lymphocyte-proliferation against flagellin (p less then 0.05). At 14 days post-infection, CNP-vaccinated birds reversed the loss in gut permeability by 13% (p less then 0.05). At 21 days post-infection, the CNP-vaccinated birds decreased S. Enteritidis in the ceca and spleen by 2 Log10 CFU/g, and in the small intestine by 0.6 Log10 CFU/g (p less then 0.05). We conclude that the CNP vaccine is a viable alternative to conventional Salmonella poultry vaccines.As the largest internal organ, the liver is the key hub for many physiological processes. Previous research on the liver has been mainly conducted on animal models and cell lines, in which not only there are deficiencies in species variability and retention of heritable material, but it is also difficult for primary hepatocytes to maintain their metabolic functions after in vitro expansion. Because of the increased burden of liver disease worldwide, there is a growing demand for 3D in vitro liver models-Liver Organoids. Based on the type of initiation cells, the liver organoid can be classified as PSC-derived or ASC-derived. Liver organoids originated from ASC or primary sclerosing cholangitis, which are co-cultured in matrix gel with components such as stromal cells or immune cells, and eventually form three-dimensional structures in the presence of cytokines. Liver organoids have already made progress in drug screening, individual medicine and disease modeling with hereditary liver diseases, alcoholic or non-alcoholic liver diseases and primary liver cancer. In this review, we summarize the generation process of liver organoids and the current clinical applications, including disease modeling, drug screening and individual medical treatment, which provide new perspectives for liver physiology and disease research.Background The heme biosynthesis (HB) involves eight subsequent enzymatic steps. Erythropoietic protoporphyria (EPP) is caused by loss-of-function mutations in the ferrochelatase (FECH) gene, which in the last HB step inserts ferrous iron into protoporphyrin IX (PPIX) to form heme. Aim and method The aim of this work was to for the first time analyze the mRNA expression of all HB genes in peripheral blood samples of patients with EPP having the same genotype FECH c.[215dupT]; [315-48T > C] as compared to healthy controls by highly sensitive and specific digital PCR assays (dPCR). Results We confirmed a decreased FECH mRNA expression in patients with EPP. Further, we found increased ALAS2 and decreased ALAS1, CPOX, PPOX and HMBS mRNA expression in patients with EPP compared to healthy controls. ALAS2 correlated with FECH mRNA expression (EPP r = 0.63, p = 0.03 and controls r = 0.68, p = 0.02) and blood parameters like PPIX (EPP r = 0.58 p = 0.06). Conclusion Our method is the first that accurately quantifies HB mRNA from blood samples with potential applications in the monitoring of treatment effects of mRNA modifying therapies in vivo, or investigation of the HB pathway and its regulation. However, our findings should be studied in separated blood cell fractions and on the enzymatic level.Lung resection surgery carries significant risks of postoperative pulmonary complications (PPC). Cardiopulmonary exercise testing (CPET) is performed to predict risk of PPC in patients with severely reduced predicted postoperative forced expiratory volume in one second (FEV1) and diffusion of carbon monoxide (DLCO). Recently, resting end-tidal partial pressure of carbon dioxide (PETCO2) has been shown as a good predictor for increased risk of PPC. However, breath-breath breathing pattern significantly affects PETCO2. Resting physiologic dead space (VD), and physiologic dead space to tidal volume ratio (VD/VT), may be a better predictor of PPC than PETCO2. The objective of this study was to prospectively determine the utility of resting measurements of VD and VD/VT in predicting PPC in patients who underwent robotic-assisted lung resection for suspected or biopsy-proven lung malignancy. Thirty-five consecutive patients were included in the study. Patients underwent preoperative pulmonary function testing, sympbserved increase in resting VD may be a potentially useful predictor of PPC in patients undergoing robotic-assisted lung resection surgery for suspected or biopsy-proven lung malignancy. A large prospective study is needed for confirmation.Background and Purpose Delayed intraparenchymal hemorrhages (DIPHs) are one of the most serious complications of cerebral aneurysm treatment with flow diverters (FD), yet their causes are largely unknown. This study analyzes distal hemodynamic alterations induced by the treatment of intracranial aneurysms with FDs. Methods A realistic model of the brain arterial network was constructed from MRA images and extended with a constrained constructive optimization technique down to vessel diameters of approximately 50 μ m . Different variants of the circle of Willis were created by alternatively occluding communicating arteries. Collateral vessels connecting different arterial trees were then added to the model, and a distributed lumped parameter approach was used to model the pulsatile blood flow in the arterial network. The treatment of an ICA aneurysm was modeled by changing the local resistance, flow inertia, and compliance of the aneurysmal segment. Results The maximum relative change in distal pressure induced by the aneurysm treatment was below 1%. However, for certain combinations of the circle of Willis and distal collateralization, important flow reversals (with a wall shear stress larger than approximately 1.0 d y n e / c m 2 ) were observed in collateral vessels, both ipsilaterally and contralaterally to the treated aneurysm. progestogen Receptor antagonist Conclusion This study suggests the hypothesis that flow diverters treatment of intracranial aneurysms could cause important flow reversal in distal collaterals. Flow reversal has previously been shown to be pro-inflammatory and pro-atherogenic and could therefore have a detrimental effect on these collateral vessels, and thus could be a suitable explanation of DIPHs, while the small distal pressure increase is not.The purpose of the study was to explore the effects of SIRT3 inhibitor 3-TYP on acute liver failure (ALF) in mice and its underlying mechanism. The mice were treated with thioacetamide (TAA, 300 mg/kg) for inducing ALF model. 3-TYP (50 mg/kg) was administered 2 h prior to TAA. The liver histological changes were measured by HE staining. Blood samples were collected for analysis of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). MDA and GSH were used to evaluate the oxidative stress of liver. The expression levels of inflammatory cytokines (TNF-α and IL-1β) were measured by ELISA and Western blotting. The cell type expression of IL-1β in liver tissue was detected by immunofluorescent staining. The expression of SIRT3, MnSOD, ALDH2, MAPK, NF-κB, Nrf2/HO-1, p-elF2α/CHOP, and cleaved caspase 3 was determined by Western blotting. TUNEL staining was performed to detect the apoptosis cells of liver tissues. 3-TYP exacerbated the liver injury of ALF mice. 3-TYP increased the inflammatory responses and activation of MAPK and NF-κB pathways. In addition, 3-TYP administration enhanced the damage of oxidative stress, endoplasmic reticulum stress, and promoted hepatocyte apoptosis in ALF mice. 3-TYP exacerbates thioacetamide-induced hepatic injury in mice. Activation of SIRT3 could be a promising target for the treatment of ALF.Objective To develop a method for detection of bradycardia and ventricular tachycardia using the photoplethysmogram (PPG). Approach The detector is based on a dual-branch convolutional neural network (CNN), whose input is the scalograms of the continuous wavelet transform computed in 5-s segments. Training and validation of the CNN is accomplished using simulated PPG signals generated from RR interval series extracted from public ECG databases. Manually annotated real PPG signals from the PhysioNet/CinC 2015 Challenge Database are used for performance evaluation. The performance is compared to that of a pulse-based reference detector. Results The sensitivity/specificity were found to be 98.1%/97.9 and 76.6%/96.8% for the CNN-based detector, respectively, whereas the corresponding results for the pulse-based detector were 94.7%/99.8 and 67.1%/93.8%, respectively. Significance The proposed detector may be useful for continuous, long-term monitoring of bradycardia and tachycardia using wearable devices, e.g., wrist-worn devices, especially in situations where sensitivity is favored over specificity. The study demonstrates that simulated PPG signals are suitable for training and validation of a CNN.
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