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The re-entry trajectory of maneuvering vehicles with medium to high hypersonic lift-to-drag ratios is generally planned using quasi-equilibrium flight conditions known from Space Shuttles. They may exhibit an oscillation re-entry phenomenon termed skip re-entry when related components or sensors fail. However, conventional re-entry guidance only considers quasi-equilibrium flights and ignores the possibility of the occurrence of an unexpected skip trajectory; this may lead to the failure of the re-entry mission due to a lack of a corresponding guidance strategy. However, the detection of a skip trajectory is the necessary reference for the decision-making of calling a related guidance algorithm that helps improve the safety of vehicle re-entry. Herein, a skip re-entry detection and trajectory control solution is proposed to play an emergency role in the cases of skip re-entry. Firstly, the oscillation frequency characteristics of the linearized re-entry motion equation of a vehicle are analyzed, and an approximate analytical relationship is constructed for skip altitude estimation. Then, the residual deviation between the altitude feedback data and the estimated skip altitude is calculated and compared with the threshold to determine the occurrence of skip re-entry. In addition, a method for controlling the skip re-entry trajectory with the range extension is developed by controlling the bank angle with a fixed angle of attack profile, satisfying the path constraint requirements. The results indicate that the method effectively performs skip re-entry detection and that it can help extend the range of the vehicles in abnormal re-entry scenarios, keeping the flight within the path constraints and guiding it to the expected location.Interleukin-6 (IL-6) signaling is a crucial regulatory event important for many biological functions, such as inflammation and tissue regeneration. Accordingly, several pathological conditions are associated with dysregulated IL-6 activity, making it an attractive therapeutic target. For instance, blockade of IL-6 or its α-receptor (IL-6R) by monoclonal antibodies has been successfully used to treat rheumatoid arthritis. However, based on different signaling modes, IL-6 function varies between pro- and anti-inflammatory activity, which is critical for therapeutic intervention. So far, three modes of IL-6 signaling have been described, the classic anti-inflammatory signaling, as well as pro-inflammatory trans-signaling, and trans-presentation. The IL-6/IL-6R complex requires an additional β-receptor (gp130), which is expressed on almost all cells of the human body, to induce STAT3 (signal transducer and activator of signal transcription 3) phosphorylation and subsequent transcriptional regulation. In contrast, the IL-6R is expressed on a limited number of cells, including hepatocytes and immune cells. However, the proteolytic release of the IL-6R enables trans-signaling on cells expressing gp130 only. Here, we demonstrate a fourth possibility of IL-6 signaling that we termed joint reconstituted signaling (JRS). We show that IL-6R on extracellular vesicles (EVs) can also be transported to and fused with other cells that lack the IL-6R on their surface. Importantly, JRS via EVs induces delayed STAT3 phosphorylation compared to the well-established trans-signaling mode. EVs isolated from human serum were already shown to carry the IL-6R, and thus this new signaling mode should be considered with regard to signal intervention.Aims T1-mapping is considered a surrogate marker of acute myocardial inflammation. However, in diffuse cutaneous systemic sclerosis (dcSSc) this might be confounded by coexisting myocardial fibrosis. We hypothesized that T1-based indices should not by themselves be considered as indicators of myocardial inflammation in dcSSc patients. Methods/results A cohort of 59 dcSSc and 34 infectious myocarditis patients was prospectively evaluated using a 1.5-Tesla system for an indication of suspected myocardial inflammation and was compared with 31 healthy controls. Collectively, 33 (97%) and 57 (98%) of myocarditis and dcSSc patients respectively had ≥1 pathologic T2-based index. However, 33 (97%) and 45 (76%) of myocarditis and dcSSc patients respectively had ≥1 pathologic T2-based index. T2-signal ratio was significantly higher in myocarditis patients compared with dcSSc patients (2.5 (0.6) vs. 2.1 (0.4), p less then 0.001). Early gadolinium enhancement, late gadolinium enhancement and T2-mapping did not differ significantly between groups. However, both native T1-mapping and extracellular volume fraction were significantly lower in myocarditis compared with dcSSc patients (1051.0 (1027.0, 1099.0) vs. 1120.0 (1065.0, 1170.0), p less then 0.001 and 28.0 (26.0, 30.0) vs. 31.5 (30.0, 33.0), p less then 0.001, respectively). The original Lake Louise criteria (LLc) were positive in 34 (100%) myocarditis and 40 (69%) dcSSc patients, while the updated LLc were positive in 32 (94%) and 44 (76%) patients, respectively. Both criteria had good agreement with greater but nonsignificant discordance in dcSSc patients. Conclusions ~25% of dcSSc patients with suspected myocardial inflammation had no CMR evidence of acute inflammatory processes. T1-based indices should not be used by themselves as surrogates of acute myocardial inflammation in dcSSc patients.COVID-19 caused rapid mass infection worldwide. Understanding its transmission characteristics, including heterogeneity and the emergence of super spreading events (SSEs) where certain individuals infect large numbers of secondary cases, is of vital importance for prediction and intervention of future epidemics. Here, we collected information of all infected cases (135 cases) between 21 January and 26 February 2020 from official public sources in Tianjin, a metropolis of China, and grouped them into 43 transmission chains with the largest chain of 45 cases and the longest chain of four generations. Utilizing a heterogeneous transmission model based on branching process along with a negative binomial offspring distribution, we estimated the reproductive number R and the dispersion parameter k (lower value indicating higher heterogeneity) to be 0.67 (95% CI 0.54-0.84) and 0.25 (95% CI 0.13-0.88), respectively. A super-spreader causing six infections was identified in Tianjin. In addition, our simulation allowing for heterogeneity showed that the outbreak in Tianjin would have caused 165 infections and sustained for 7.56 generations on average if no control measures had been taken by local government since 28 January. Our results highlighted more efforts are needed to verify the transmission heterogeneity of COVID-19 in other populations and its contributing factors.Transforming growth factor beta3 (TGFB3) gene mutations in patients of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD1) and Loeys-Dietz syndrome-5 (LDS5)/Rienhoff syndrome are associated with cardiomyopathy, cardiac arrhythmia, cardiac fibrosis, cleft palate, aortic aneurysms, and valvular heart disease. Although the developing heart of embryos express Tgfb3, its overarching role remains unclear in cardiovascular development and disease. We used histological, immunohistochemical, and molecular analyses of Tgfb3-/- fetuses and compared them to wildtype littermate controls. The cardiovascular phenotypes were diverse with approximately two thirds of the Tgfb3-/- fetuses having one or more cardiovascular malformations, including abnormal ventricular myocardium (particularly of the right ventricle), outflow tract septal and alignment defects, abnormal aortic and pulmonary trunk walls, and thickening of semilunar and/or atrioventricular valves. Ventricular septal defects (VSD) including the perimembranous VSDs were observed in Tgfb3-/- fetuses with myocardial defects often accompanied by the muscular type VSD. In vitro studies using TGFβ3-deficient fibroblasts in 3-D collagen lattice formation assays indicated that TGFβ3 was required for collagen matrix reorganization. Biochemical studies indicated the 'paradoxically' increased activation of canonical (SMAD-dependent) and noncanonical (MAP kinase-dependent) pathways. TGFβ3 is required for cardiovascular development to maintain a balance of canonical and noncanonical TGFβ signaling pathways.Glutamic acid decarboxylase (GAD) is an intracellular enzyme whose physiologic function is the decarboxylation of glutamate to gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter within the central nervous system. GAD antibodies (Ab) have been associated with multiple neurological syndromes, including stiff-person syndrome, cerebellar ataxia, and limbic encephalitis, which are all considered to result from reduced GABAergic transmission. The pathogenic role of GAD Ab is still debated, and some evidence suggests that GAD autoimmunity might primarily be cell-mediated. Diagnosis relies on the detection of high titers of GAD Ab in serum and/or in the detection of GAD Ab in the cerebrospinal fluid. Due to the relative rarity of these syndromes, treatment schemes and predictors of response are poorly defined, highlighting the unmet need for multicentric prospective trials in this population. Here, we reviewed the main clinical characteristics of neurological syndromes associated with GAD Ab, focusing on pathophysiologic mechanisms.While few studies have revealed the biological properties of brassicasterol, a phytosterol, against some biological and molecular targets, it is believed that there are still many activities yet to be studied. In this work, brassicasterol exerts a therapeutic utility in an in vitro setting against herpes simplex virus type 1 (HSV-1) and Mycobacterium tuberculosis (Mtb) as well as a considerable inhibitory property against human angiotensin-converting enzyme (ACE) that plays a dynamic role in regulating blood pressure. The antireplicative effect of brassicasterol against HSV-1 is remarkably detected (50% inhibitory concentration (IC50) 1.2 µM; selectivity index (SI) 41.7), while the potency of its effect is ameliorated through the combination with standard acyclovir with proper SI (IC50 0.7 µM; SI 71.4). Moreover, the capacity of this compound to induce an adequate level of antituberculosis activity against all Mtb strains examined (minimum inhibitory concentration values ranging from 1.9 to 2.4 µM) is revealed. The anti-ACE effect (12.3 µg/mL; 91.2% inhibition) is also ascertained. Molecular docking analyses propose that the mechanisms by which brassicasterol induces anti-HSV-1 and anti-Mtb might be related to inhibiting vital enzymes involved in HSV-1 replication and Mtb cell wall biosynthesis. In summary, the obtained results suggest that brassicasterol might be promising for future anti-HSV-1, antituberculosis, and anti-ACE drug design.Aujeszky's disease is one of the main pig viral diseases and results in considerable economic losses in the pork production industry. The disease can be controlled using preventive measures such as improved stock management and vaccination throughout the pig-rearing period. We developed a stochastic model based on Population Dynamics P systems (PDP) models for a standard pig production system to differentiate between the effects of pig farm management regimes and vaccination strategies on the control of Aujeszky's disease under several different epidemiological scenarios. Our results suggest that after confirming the diagnosis, early vaccination of most of the population (>75%) is critical to decrease the spread of the virus and minimize its impact on pig productivity. The direct economic cost of an outbreak of Aujeszky's disease can be extremely high on a previously uninfected farm (from 352-792 Euros/sow/year) and highlights the positive benefits of investing in vaccination measures to control infections. We demonstrate the usefulness of computational models as tools in the evaluation of preventive medicine programs aimed at limiting the impact of disease on animal production.Retinal prostheses are implantable devices that aim to restore the vision of blind patients suffering from retinal degeneration, mainly by artificially stimulating the remaining retinal neurons. Some retinal prostheses have successfully reached the stage of clinical trials; however, these devices can only restore vision partially and remain insufficient to enable patients to conduct everyday life independently. The visual acuity of the artificial vision is limited by various factors from both engineering and physiological perspectives. To overcome those issues and further enhance the visual resolution of retinal prostheses, a variety of retinal prosthetic approaches have been proposed, based on optimization of the geometries of electrode arrays and stimulation pulse parameters. Other retinal stimulation modalities such as optics, ultrasound, and magnetics have also been utilized to address the limitations in conventional electrical stimulation. Although none of these approaches have been clinically proven to fully restore the function of a degenerated retina, the extensive efforts made in this field have demonstrated a series of encouraging findings for the next generation of retinal prostheses, and these could potentially enhance the visual acuity of retinal prostheses. In this article, a comprehensive and up-to-date overview of retinal prosthetic strategies is provided, with a specific focus on a quantitative assessment of visual acuity results from various retinal stimulation technologies. The aim is to highlight future directions toward high-resolution retinal prostheses.Aimed at improving upon the disadvantages of the single centralized Kalman filter for integrated navigation, including its fragile robustness and low solution accuracy, a nonlinear double model based on the improved decentralized federated extended Kalman filter (EKF) for integrated navigation is proposed. The multisensor error model is established and simplified in this paper according to the near-ground short distance navigation applications of small unmanned aerial vehicles (UAVs). In order to overcome the centralized Kalman filter that is used in the linear Gaussian system, the improved federated EKF is designed for multisensor-integrated navigation. Subsequently, because of the navigation requirements of UAVs, especially for the attitude solution accuracy, this paper presents a nonlinear double model that consists of the nonlinear attitude heading reference system (AHRS) model and nonlinear strapdown inertial navigation system (SINS)/GPS-integrated navigation model. Moreover, the common state parameters of the nonlinear double model are optimized by the federated filter to obtain a better attitude. The proposed algorithm is compared with multisensor complementary filtering (MSCF) and multisensor EKF (MSEKF) using collected flight sensors data. The simulation and experimental tests demonstrate that the proposed algorithm has a good robustness and state estimation solution accuracy.Increased global temperatures and climatic anomalies, such as heatwaves, as a product of climate change, are impacting the heat stress levels of farm animals. These impacts could have detrimental effects on the milk quality and productivity of dairy cows. This research used four years of data from a robotic dairy farm from 36 cows with similar heat tolerance (Model 1), and all 312 cows from the farm (Model 2). These data consisted of programmed concentrate feed and weight combined with weather parameters to develop supervised machine learning fitting models to predict milk yield, fat and protein content, and actual cow concentrate feed intake. Results showed highly accurate models, which were developed for cows with a similar genetic heat tolerance (Model 1 n = 116, 456; R = 0.87; slope = 0.76) and for all cows (Model 2 n = 665, 836; R = 0.86; slope = 0.74). Furthermore, an artificial intelligence (AI) system was proposed to increase or maintain a targeted level of milk quality by reducing heat stress that could be applied to a conventional dairy farm with minimal technology addition.Cyanobacteria are known to produce a large diversity of specialized metabolites that can cause severe (eco)toxicological effects. In the lagoon of Tahiti, the benthic cyanobacterium Leibleinia gracilis is commonly found overgrowing the proliferative macroalga Turbinaria ornata or dead branching corals. The specialized metabolome of the cyanobacterium L. gracilis was therefore investigated together with its variability on both substrates and changes in environmental parameters. For the study of the metabolome variability, replicates of L. gracilis were collected in the same location of the lagoon of Tahiti before and after a raining event, both on dead corals and on T. ornata. The variability in the metabolome was inferred from a comparative non-targeted metabolomic using high resolution mass spectrometry (MS) data and a molecular network analysis built through MS/MS analyses. Oxidized fatty acid derivatives including the unusual 11-oxopalmitelaidic acid were found as major constituents of the specialized metabolome of this species. Significant variations in the metabolome of the cyanobacteria were observed, being more important with a change in environmental factors. Erucamide was found to be the main chemical marker highly present when the cyanobacterium grows on the macroalga. This study highlights the importance of combined approaches in metabolomics and molecular networks to inspect the variability in the metabolome of cyanobacteria with applications for ecological questions.Geranyl diphosphate synthase (GPPS) is a plastid localized enzyme that catalyzes the biosynthesis of Geranyl diphosphate (GPP), which is a universal precursor of monoterpenes. Wintersweet (Chimonanthus praecox L.), a famous deciduous flowering shrub with a strong floral scent character, could have GPPS-like homologs that are involved in monoterpenes biosynthesis, but it remains unclear. In the present study, five full-length GPPS and geranylgeranyl diphosphate synthases (GGPPS) genes were identified in the wintersweet transcriptome database. The isolated cDNAs showed high protein sequence similarity with the other plants GPPS and GGPPS. The phylogenetic analysis further classified these cDNAs into four distinct clades, representing heterodimeric GPPS small subunits (SSU1 and SSU2), homodimeric GPPS, and GGPPS. Analysis of temporal expression revealed that all genes have the highest transcript level at the full-open flower stage. From tissue-specific expression analysis, CpGPPS.SSU1 and CpGGPPS1 were predominantly expressed in petal and flower, whereas CpGPPS.SSU2, GPPS, and GGPPS2 showed a constitutive expression. Additionally, the subcellular localization assay identified the chloroplast localization of SSUs and GGPPSs proteins, and the yeast two-hybrid assay showed that both CpGPPS.SSU1 and CpGPPS.SSU2 can interact with the GGPPS proteins. Taken together, these preliminary results suggest that the heterodimeric GPPS can regulate floral scent biosynthesis in wintersweet flower.The popularity of electric bicycles in China makes them a common transportation mode for people to commute and move around. However, with the increase in traffic volumes for both vehicles and electric bicycles, urban traffic safety and congestion problems are rising due to traffic conflicts between these two modes. To regulate travel behavior, it is essential to analyze the mode choice and route choice behaviors of travelers. This study proposes a combined modal split and multiclass traffic user equilibrium model formulated as a complementarity problem (CP) to simultaneously characterize the mode choice behavior and route choice behavior of both vehicle and electric bicycle users. This model captures the impacts of route travel time and out-of-pocket cost on travelers' route choice behaviors. Further, modified Bureau of Public Roads (BPR) functions are developed to model the travel times of links with and without physical separation between vehicle lanes and bicycle lanes. This study also analyzes the conditions for uniqueness of the equilibrium solution. A Newton method is developed to solve the proposed model. Numerical examples with different scales are used to validate the proposed model. The results show that electric bicycles are more favored by travelers during times of high network congestion. In addition, total system travel time can be reduced significantly through physical separation of vehicle lanes from electric bicycle lanes to minimize their mutual interference.Due to their mechanical properties, ranging from flexible to hard materials, polyurethanes (PUs) have been widely used in many industrial and biomedical applications. PUs' characteristics, along with their biocompatibility, make them successful biomaterials for short and medium-duration applications. The morphology of PUs includes two structural phases hard and soft segments. Their high mechanical resistance featuresare determined by the hard segment, while the elastomeric behaviour is established by the soft segment. The most important biomedical applications of PUs include antibacterial surfaces and catheters, blood oxygenators, dialysis devices, stents, cardiac valves, vascular prostheses, bioadhesives/surgical dressings/pressure-sensitive adhesives, drug delivery systems, tissue engineering scaffolds and electrospinning, nerve generation, pacemaker lead insulation and coatings for breast implants. The diversity of polyurethane properties, due to the ease of bulk and surface modification, plays a vital role in their applications.Background (E)-methyl-cinnamate (EMC), a phytochemical constituent isolated from Alpinia katsumadai Hayata, is a natural flavor compound with anti-inflammatory properties, which is widely used in the food and commodity industry. However, the pharmacological effects of methyl-cinnamate on pre-osteoblasts remain unknown. This study aimed to investigate the pharmacological effects and mechanisms of EMC in pre-osteoblast MC3T3-E1 cells (pre-osteoblasts). Methods Cell viability and apoptosis were evaluated using the MTT assay and TUNEL staining. Cell migration and osteoblast differentiation were examined using migration assays, as well as alkaline phosphatase activity and staining assays. Western blot analysis was used to examine intracellular signaling pathways and apoptotic proteins. Results EMC decreased cell viability with morphological changes and increased apoptosis in pre-osteoblasts. EMC also induced the cleavage of Poly (ADP-ribose) polymerase (PARP) and caspase-3 and reduced the expression of anti-apoptotic proteins. In addition, EMC increased TUNEL-positive cells in pre-osteoblasts, decreased the activation of mitogen-activated protein kinases, and suppressed cell migration rate in pre-osteoblasts. Subsequently, EMC inhibited the osteoblast differentiation of pre-osteoblasts, as assessed by alkaline phosphatase staining and activity assays. Conclusion These findings demonstrate that EMC has a pharmacological and biological role in cell survival, migration, and osteoblast differentiation. It suggests that EMC might be a potential phytomedicine for treating abnormalities of osteoblast function in bone diseases.Polymeric chemosensors are vital sensing tools because of higher sensitivity compared to their monomeric counterparts and tunable mechanical properties. This study focuses on the incorporation of a hydroxyaromatic 1,2,3-triazole sensor, 2-(4-phenyl 1H-1,2,3-triazol-1-yl)phenol (PTP), into polymers. By itself, the triazole has a selective, fluorometric response to the fluoride, acetate, and dihydrogen phosphate anions, and is most responsive to fluoride. Current investigations probe the suitability of various polymeric backbones for the retention and enhancement of the triazole's sensing capabilities. Backbones derived from acrylic acid, methyl methacrylate, divinylbenzene, and styrene were explored. UV-illumination, Nuclear Magnetic Resonance (NMR) titration, and ultraviolet-visible (UV-Vis) absorption and fluorescence spectroscopy studies are used to investigate the performance of newly synthesized polymers and the derivatives of PTP that serve as the polymers' precursors. Among the polymers investigated, copolymers with styrene proved best; these systems retained the sensing capabilities and were amenable to tuning for sensitivity.Ultrasonography is widely used in veterinary medicine for the diagnosis of pregnancy, and can also be used to monitor abnormal pregnancies, embryonic resorption, or fetal abortion. Ultrasonography plays an important role in modern-day cetacean preventative medicine because it is a non-invasive technique, it is safe for both patient and operator, and it can be performed routinely using trained responses that enable medical procedures. Reproductive success is an important aspect of dolphin population health, as it is an indicator of the future trajectory of the population. The aim of this study is to provide additional relevant data on feto-maternal ultrasonographic monitoring in bottlenose dolphin (Tursiops truncatus) species, for both the clinicians and for in situ population studies. From 2009 to 2019, serial ultrasonographic exams of 11 healthy bottlenose dolphin females kept under human care were evaluated over the course of 16 pregnancies. A total of 192 ultrasound exams were included in the study. For the first time, the sonographic findings of the bottlenose dolphin organogenesis and their correlation with the stage of pregnancy are described. Furthermore, this is the first report that forecasts the cephalic presentation of the calf at birth, according to its position within the uterus.In this study, ternary ecological concrete (TEC) mixtures were produced with partial substitution of the ordinary Portland cement (OPC) by 10%, 20%, and 30% of sugar cane bagasse ash (SCBA) and silica fume (SF); a control mixture (100% OPC) was prepared according to ACI 211.1 standard. The studied TEC specimens were reinforced with AISI 304 stainless steel and AISI 1018 carbon steel rebars. TEC reinforced specimens were immersed in two different electrolytes, a control (DI-water) and 3.5 wt.% MgSO4 solution, for 180 days. The electrochemical corrosion was monitored by corrosion potential (Ecorr) according to ASTM C-876-15 standard, and the linear polarization resistance (LPR) technique using ASTM G59 standard. The Ecorr and current density icorr results show that AISI 304 stainless steel rebars have a high corrosion resistance, with icorr values below 0.1 µA/cm2, which is interpreted as a level of negligible corrosion. The best corrosion performance was found for the TEC mixture made with a 20% addition of blend of sugar cane bagasse ash-silica fume (SCBA-SF) to the OPC.Hand gesture classification and finger angle estimation are both critical for intuitive human-computer interaction. However, most approaches study them in isolation. We thus propose a dual-output deep learning model to enable simultaneous hand gesture classification and finger angle estimation. Data augmentation and deep learning were used to detect spatial-temporal features via a wristband with ten modified barometric sensors. Ten subjects performed experimental testing by flexing/extending each finger at the metacarpophalangeal joint while the proposed model was used to classify each hand gesture and estimate continuous finger angles simultaneously. A data glove was worn to record ground-truth finger angles. Overall hand gesture classification accuracy was 97.5% and finger angle estimation R 2 was 0.922, both of which were significantly higher than shallow existing learning approaches used in isolation. The proposed method could be used in applications related to the human-computer interaction and in control environments with both discrete and continuous variables.Late-arriving patients have become a prominent concern in several ambulatory care clinics across the globe. Accommodating them could lead to detrimental ramifications such as schedule disruption and increased waiting time for forthcoming patients, which, in turn, could lead to patient dissatisfaction, reduced care quality, and physician burnout. However, rescheduling late arrivals could delay access to care. This paper aims to predict the patient-specific risk of late arrival using machine learning (ML) models. Data from two different ambulatory care facilities are extracted, and a comprehensive list of predictor variables is identified or derived from the electronic medical records. A comparative analysis of four ML algorithms (logistic regression, random forests, gradient boosting machine, and artificial neural networks) that differ in their training mechanism is conducted. The results indicate that ML algorithms can accurately predict patient lateness, but a single model cannot perform best with respect to predictive performance, training time, and interpretability. Prior history of late arrivals, age, and afternoon appointments are identified as critical predictors by all the models. The ML-based approach presented in this research can serve as a decision support tool and could be integrated into the appointment system for effectively managing and mitigating tardy arrivals.Mechanotransduction translates forces into biological responses and regulates cell functionalities. It is implicated in several diseases, including laminopathies which are pathologies associated with mutations in lamins and lamin-associated proteins. These pathologies affect muscle, adipose, bone, nerve, and skin cells and range from muscular dystrophies to accelerated aging. Although the exact mechanisms governing laminopathies and gene expression are still not clear, a strong correlation has been found between cell functionality and nuclear behavior. New theories base on the direct effect of external force on the genome, which is indeed sensitive to the force transduced by the nuclear lamina. Nuclear lamina performs two essential functions in mechanotransduction pathway modulating the nuclear stiffness and governing the chromatin remodeling. Indeed, A-type lamin mutation and deregulation has been found to affect the nuclear response, altering several downstream cellular processes such as mitosis, chromatin organization, DNA replication-transcription, and nuclear structural integrity. In this review, we summarize the recent findings on the molecular composition and architecture of the nuclear lamina, its role in healthy cells and disease regulation. We focus on A-type lamins since this protein family is the most involved in mechanotransduction and laminopathies.Detection and quantification of pathogenic free-living amoebae (FLA) in water samples is critical for assessing water quality and for disease management issues. The most probable number (MPN) is commonly used to account for FLA in water. Nevertheless, this requires a high number of water replicates and working volumes, and a consequent number of non-nutrient agar (NNA)-plates seeded with Escherichia coli. Herein, we aimed at optimizing this difficult method, taking also into account key factors such as (i) the counting method, (ii) the delay between sample collection and sample processing, and (iii) the temperature during water sample transportation. To simplify the MPN method, we filtrated 1 × 1000 and 1 × 100 mL water samples, and cellulose acetate filters were cut in 10 parts and inverted on NNA-plates overlaid with E. coli. The comparison between the classical and our optimized MPN method showed that the final counts were similar, therefore validating the use of the optimized method. Our results also showed that for thermophilic FLA (such as Naegleria fowleri), water samples can be kept at around +30°C and processed within 24 h. This improved MPN method is now routinely used in our laboratory to control Naegleria sp. in the water samples in Guadeloupe.The phenolic fraction of the extra virgin olive oil (EVOO) has been studied over the past two decades because of its important health protective properties. Numerous studies have been performed in order to clarify the most crucial factors that affect the concentration of the EVOO's phenolic fraction and many contradictory results have been reported. Having as target to maximize the phenolic content of EVOO and its healthy properties we investigated the impact of harvest time, malaxation temperature, and malaxation duration on the concentration of individual phenols in extra virgin olive oil. Olive oil was prepared in a lab-scale olive mill from different varieties in Greece. The extraction process for cultivar (cv) Koroneiki samples was performed at five different harvest periods from the same trees with three different malaxation temperatures and five different malaxation duration times (N = 75). Similar types of experiments were also performed for other varieties cv Athenolia (N = 20), cv Olympia (N = 3), cv Kalamata (N = 3), and cv Throubolia Aegean (N=3) in order to compare the changes in the phenolic profile during malaxation. The quantitative analysis of the olive oil samples with NMR showed that the total phenolic content has a negative correlation with the ripening degree and the malaxation time. The NMR data we collected helped us to quantitate not only the total phenolic content but also the concentration of the major phenolic compounds such as oleocanthal, oleacein, oleokoronal, and oleomissional. We noticed different trends for the concentration of these phenols during malaxation process and for different malaxation temperatures. The different trends of the concentration of the individual phenols during malaxation and the completely different behavior of each variety revealed possible biosynthetic formation steps for oleocanthal and oleacein and may explain the discrepancies reported from previous studies.Faustovirus is a recently discovered genus of large DNA virus infecting the amoeba Vermamoeba vermiformis, which is phylogenetically related to Asfarviridae. To better understand the diversity and evolution of this viral group, we sequenced six novel Faustovirus strains, mined published metagenomic datasets and performed a comparative genomic analysis. Genomic sequences revealed three consistent phylogenetic groups, within which genetic diversity was moderate. The comparison of the major capsid protein (MCP) genes unveiled between 13 and 18 type-I introns that likely evolved through a still-active birth and death process mediated by intron-encoded homing endonucleases that began before the Faustovirus radiation. Genome-wide alignments indicated that despite genomes retaining high levels of gene collinearity, the central region containing the MCP gene together with the extremities of the chromosomes evolved at a faster rate due to increased indel accumulation and local rearrangements. The fluctuation of the nucleotide composition along the Faustovirus (FV) genomes is mostly imprinted by the consistent nucleotide bias of coding sequences and provided no evidence for a single DNA replication origin like in circular bacterial genomes.During the aging process of an organism, the skin gradually loses its structural and functional characteristics. The skin becomes more fragile and vulnerable to damage, which may contribute to age-related diseases and even death. Skin aging is aggravated by the fact that the skin is in direct contact with extrinsic factors, such as ultraviolet irradiation. While calorie restriction (CR) is the most effective intervention to extend the lifespan of organisms and prevent age-related disorders, its effects on cutaneous aging and disorders are poorly understood. This review discusses the effects of CR and its alternative dietary intake on skin biology, with a focus on skin aging. CR structurally and functionally affects most of the skin and has been reported to rescue both age-related and photo-induced changes. The anti-inflammatory, anti-oxidative, stem cell maintenance, and metabolic activities of CR contribute to its beneficial effects on the skin. To the best of the author's knowledge, the effects of fasting or a specific nutrient-restricted diet on skin aging have not been evaluated; these strategies offer benefits in wound healing and inflammatory skin diseases. In addition, well-known CR mimetics, including resveratrol, metformin, rapamycin, and peroxisome proliferator-activated receptor agonists, show CR-like prevention against skin aging. An overview of the role of CR in skin biology will provide valuable insights that would eventually lead to improvements in skin health.Preconception care (PCC) is acknowledged as a vital preventive health measure aiming to promote health today and for subsequent generations. We aimed to describe the content and context of PCC delivery in a very remote Australian Aboriginal Community Controlled Health Service setting. A retrospective audit was undertaken to identify what PCC was delivered between 2011 and 2018 to 127 Aboriginal women who had at least one pregnancy during this period. Of 177 confirmed pregnancies, 121 had received PCC prior to the pregnancy. Sexually transmissible infection screening (71%) was the most common care delivered, followed by folic acid prescription (57%) and smoking cessation support (43%). Younger women received PCC less often, particularly screening for modifiable pregnancy risk factors. Rates of prediabetes/diabetes, albuminuria, overweight/obesity and smoking were high amongst those screened (48-60%). PCC was usually patient-initiated and increased significantly over the audit period. Presentation for antenatal care in the first trimester of pregnancy was high at 73%. Opportunities to increase PCC delivery include integration with routine health checks, pregnancy tests and chronic disease programs. PCC programs codesigned with young people are also recommended. All primary care providers should be supported and assisted to provide opportunistic PCC and health promotion.Identification of mosquito species is necessary for determining the entomological components of malaria transmission, but it can be difficult in morphologically similar species. DNA sequences are largely used as an additional tool for species recognition, including those that belong to species complexes. Kerteszia mosquitoes are vectors of human and simian malaria in the Neotropical Region, but there are few DNA sequences of Kerteszia species in public databases. In order to provide relevant information about diversity and improve knowledge in taxonomy of Kerteszia species in Peru, we sequenced part of the mitochondrial genome, including the cytochrome c oxidase I (COI) barcode region. Phylogenetic analyses structured all species of mosquitoes collected in Peru into a single clade, separate from the Brazilian species. The Peruvian clade was composed of two lineages, encompassing sequences from Anopheles Kerteszia boliviensis and Anopheles Kerteszia pholidotus. An. pholidotus sequences were recorded for the first time in Peru, whereas An. boliviensis sequences were for the first time published in the GenBank database. Sequences generated from specimens morphologically identified as Anopheles Kerteszia cruzii clustered into three separate clades according to the collection localities of Serra do Mar, Serra da Mantiqueira, and Serra da Cantareira, confirming An. cruzii as a species complex, composed of at least three putative species.Syndecan-4 is a member of the syndecan family of transmembrane heparan sulfate proteoglycans, and is involved in cell protection, proliferation, and the blood coagulation-fibrinolytic system in vascular endothelial cells. Heparan sulfate chains enable fibroblast growth factor-2 (FGF-2) to form a complex with its receptor and to transduce the cell growth signal. In the present study, bovine aortic endothelial cells were cultured, and the intracellular signal pathways that mediate the regulation of syndecan-4 expression in dense and sparse cultures by FGF-2 were analyzed. We demonstrated the cell density-dependent differential regulation of syndecan-4 expression. Specifically, we found that FGF-2 upregulated the synthesis of syndecan-4 in vascular endothelial cells via the MEK1/2-ERK1/2 pathway in dense cell cultures, with only a transcriptional induction of syndecan-4 at a low cell density via the Akt pathway. This study highlights a critical mechanism underlying the regulation of endothelial cell functions by proteoglycans.Biped robots are similar to human beings and have broad application prospects in the fields of family service, disaster rescue and military affairs. However, simplified models and fixed center of mass (COM) used in previous research ignore the large-scale stability control ability implied by whole-body motion. The present paper proposed a two-level controller based on a simplified model and whole-body dynamics. In high level, a model predictive control (MPC) controller is implemented to improve zero moment point (ZMP) control performance. In low level, a quadratic programming optimization method is adopted to realize trajectory tracking and stabilization with friction and joint constraints. The simulation shows that a 12-degree-of-freedom force-controlled biped robot model, adopting the method proposed in this paper, can recover from a 40 Nm disturbance when walking at 1.44 km/h without adjusting the foot placement, and can walk on an unknown 4 cm high stairs and a rotating slope with a maximum inclination of 10°. The method is also adopted to realize fast walking up to 6 km/h.We investigated the role of near infrared spectroscopy (NIRS) in identifying delayed cerebral ischemia (DCI) in patients with subarachnoid hemorrhage (SAH). We measured the cerebral regional oxygen saturation (rSO2) continuously for 14 days. The differences in rSO2 according to DCI were analyzed. We also compared the diagnostic accuracy of NIRS and transcranial Doppler ultrasonography (TCD) for DCI detection using the area under receiver operator characteristic (ROC) curve. Fifty-two patients treated with coil embolization were enrolled, including 18 with DCI (34.6%) and 34 without DCI (65.4%). Significant differences in rSO2 levels were observed from days 7 to 9. The rSO2 level was 60.95 (58.10-62.30) at day 7 in the DCI vs. 63.90 (62.50-67.10) in the non-DCI patients. By day 8, it was 59.50 (56.90-64.50) in the DCI vs. 63.30 (59.70-68.70) in the non-DCI cases. By day 9, it was 61.85 (59.40-65.20) in the DCI vs. 66.00 (62.70-68.30) in the non-DCI. A decline of >12.7% in SO2 rate yielded a sensitivity of 94.44% (95% CI 72.7-99.9%) and a specificity of 70.59% (95% CI 52.5-84.9%) for identifying DCI. Changes in NIRS tended to yield better diagnostic accuracy than TCD, but were not statistically significant. NIRS is a feasible method for real-time detection of DCI.A joint demosaicing and denoising task refers to the task of simultaneously reconstructing and denoising a color image from a patterned image obtained by a monochrome image sensor with a color filter array. Recently, inspired by the success of deep learning in many image processing tasks, there has been research to apply convolutional neural networks (CNNs) to the task of joint demosaicing and denoising. However, such CNNs need many training data to be trained, and work well only for patterned images which have the same amount of noise they have been trained on. In this paper, we propose a variational deep image prior network for joint demosaicing and denoising which can be trained on a single patterned image and works for patterned images with different levels of noise. We also propose a new RGB color filter array (CFA) which works better with the proposed network than the conventional Bayer CFA. Mathematical justifications of why the variational deep image prior network suits the task of joint demosaicing and denoising are also given, and experimental results verify the performance of the proposed method.Enzalutamide is the first second-generation nonsteroidal androgen receptor (AR) antagonist with a strong binding affinity to AR. Most significantly, enzalutamide can prolong not only overall survival time and metastatic free survival time for patients with lethal castration-resistant prostate cancer (CRPC), but also castration-resistant free survival time for patients with castration-sensitive prostate cancer (CSPC). Enzalutamide has thus been approved by the US Food and Drug Administration (FDA) for the treatment of both metastatic (in 2012) and non-metastatic (in 2018) CRPC, as well as CSPC (2019). This is an inspiring drug discovery story created by an amazing interdisciplinary collaboration. Equally important, the successful clinical use of enzalutamide proves the notion that the second-generation AR antagonists can serve as hormonal therapeutics for three forms of advanced prostate cancer. This has been further verified by the recent FDA approval of the other two second-generation AR antagonists, apalutamide and darolutamide, for the treatment of prostate cancer. This review focuses on the rational design and discovery of these three second-generation AR antagonists, and then highlights their syntheses, clinical studies, and use. Strategies to overcome the resistance to the second-generation AR antagonists are also reviewed.γδ T cells have recently gained considerable attention as an attractive tool for cancer adoptive immunotherapy due to their potent anti-tumor activity and unique role in immunosurveillance. The remarkable success of engineered T cells for the treatment of hematological malignancies has revolutionized the field of adoptive cell immunotherapy. Accordingly, major efforts are underway to translate this exciting technology to the treatment of solid tumors and the development of allogeneic therapies. The unique features of γδ T cells, including their major histocompatibility complex (MHC)-independent anti-cancer activity, tissue tropism, and multivalent response against a broad spectrum of the tumors, render them ideal for designing universal 'third-party' cell products, with the potential to overcome the challenges of allogeneic cell therapy. In this review, we describe the crucial role of γδ T cells in anti-tumor immunosurveillance and we summarize the different approaches used for the ex vivo and in vivo expansion of γδ T cells suitable for the development of novel strategies for cancer therapy. We further discuss the different transduction strategies aiming at redirecting or improving the function of γδ T cells, as well as, the considerations for the clinical applications.This study applied an untargeted-targeted (UT) fingerprinting approach, based on comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-TOF MS), to assess the effects of rainfall and temperature (both seasonal and elevational) on the tea metabolome. By this strategy, the same compound found in multiple samples need only to be identified once, since chromatograms and mass spectral features are aligned in the data analysis process. Primary and specialized metabolites of leaves from two Chinese provinces, Yunnan (pu'erh) and Fujian (oolong), and a farm in South Carolina (USA, black tea) were studied. UT fingerprinting provided insight into plant metabolism activation/inhibition, taste and trigeminal sensations, and antioxidant properties, not easily attained by other analytical approaches. For example, pu'erh and oolong contained higher relative amounts of amino acids, organic acids, and sugars. Conversely, black tea contained less of all targeted compounds except fructose and glucose, which were more similar to oolong tea. Findings revealed compounds statistically different between spring (pre-monsoon) and summer (monsoon) in pu'erh and oolong teas as well as compounds that exhibited the greatest variability due to seasonal and elevational differences. The UT fingerprinting approach offered unique insights into how differences in growing conditions and commercial processing affect the nutritional benefits and sensory characteristics of tea beverages.Polymer materials offer several advantages as supports of biosensing platforms in terms of flexibility, weight, conformability, portability, cost, disposability and scope for integration. The present study reviews the field of electrochemical biosensors fabricated on modified plastics and polymers, focusing the attention, in the first part, on modified conducting polymers to improve sensitivity, selectivity, biocompatibility and mechanical properties, whereas the second part is dedicated to modified "environmentally friendly" polymers to improve the electrical properties. These ecofriendly polymers are divided into three main classes bioplastics made from natural sources, biodegradable plastics made from traditional petrochemicals and eco/recycled plastics, which are made from recycled plastic materials rather than from raw petrochemicals. Finally, flexible and wearable lab-on-a-chip (LOC) biosensing devices, based on plastic supports, are also discussed. This review is timely due to the significant advances achieved over the last few years in the area of electrochemical biosensors based on modified polymers and aims to direct the readers to emerging trends in this field.A simple, rapid, and accurate HPLC-UV method was developed for the determination of creatinine in pig urine. Usually, it is determined in urine in biomonitoring of xenobiotics to correct for variations in dilutions of urine samples. The colorimetric method (based on Jaffe reaction), which was mainly used for this purpose in mycotoxin biomonitoring, is not a reliable approach for pig urine. Therefore, a novel and accurate HPLC method for creatinine determination was developed. The sample preparation was based on the dilute and shoot approach. An HPLC separation was performed with a porous graphitic carbon column with an aqueous mobile phase to achieve satisfactory retention time for creatinine. The method has been successfully validated, applied for the determination of creatinine in pig urine, and compared with other methods commonly used for that purpose-a colorimetric method based on Jaffe reaction and commercial ELISA test. The developed HPLC method shows the highest precision and accuracy for pig urine samples. Finally, the method was applied as a normalization tool in LC-MS/MS mycotoxin biomarkers analysis. The standardization to a constant creatinine level (0.5 mg/mL) enables similar matrix effects for eleven mycotoxin biomarkers for pig urine samples with different creatinine levels.The interfaces of dissimilar materials play central roles in photophysical events in organic photovoltaics (OPVs). Depth profiles of electrostatic potential and contact-induced charges determine the energy-level lineup of the frontier orbitals at electrode/organic and organic heterointerfaces. They are critical for the elementary processes in an OPV cell, such as generation and diffusion of free carriers. A simple electrostatic model describes the energetics in organic heterojunctions supported by an electrode, and experiments via photoelectron spectroscopy and the Kelvin probe method validate the potential distribution in the stacking direction of the device. A comparative study has clarified the significance of Fermi-level pinning and resulting electrostatic fields in determining the energy-level alignment. In this review, we discuss how parameters of device constituents affect the distributions of potential and the dark charges in conventional OPVs comprising metallophthalocyanine and C60 as donor and acceptor, respectively.
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