Modern full-wave computational tools enable rigorous simulations of linear parts of complex microwave circuits within minutes, taking into account all physical electromagnetic (EM) phenomena. ...Non-linear components and other discrete elements of the hybrid microwave circuit are then easily added within the circuit simulator. This combined full-wave and circuit-based analysis is a must in the final stages of the circuit design, although initial designs and optimisations are still faster and more comfortably done completely in the circuit-based environment, which offers real-time solutions at the expense of accuracy. However, due to insufficient information and general lack of specific case studies, practitioners still struggle when choosing an appropriate analysis method, or a component model, because different choices lead to different solutions, often with uncertain accuracy and unexplained discrepancies arising between the simulations and measurements. We here design a reconfigurable power amplifier, as a case study, using both circuit-based solver and a full-wave EM solver. We compare numerical simulations with measurements on the manufactured prototypes, discussing the obtained differences, pointing out the importance of measured parameters de-embedding, appropriate modelling of discrete components and giving specific recipes for good modelling practices.
We reviewed stable gastric pentadecapeptide BPC 157-NO-system-relation, its close participation in Moncada's (maintained vascular integrity, platelets control) homeostatic healing response of ...NO-system to injury. Namely, BPC 157's particular healing effect also affects all events after vascular integrity loss (dependent on circumstances, it reduces either thrombosis (abdominal aorta anastomosis) or bleeding/thrombocytopenia (amputation, heparin, warfarin, aspirin)) and in a series of different injurious models, acute and chronic, BPC 157 consistently advances healing after severe injuries in various tissues spontaneously unable to heal; stimulates egr-1 and naB2 genes; exhibits high safety (LD1 not achieved)). Hypothesis, that BPC 157 (since formed constitutively in the gastric mucosa, stable in human gastric juice, along with significance of NO-synthase and the basal formation of NO in stomach mucosa, greater than that seen in other tissues) exhibits a general, effective competing both with L-arginine analogues (i. e., L-NAME) and L-arginine, and that this has some physiologic importance (NO-generation), later, practically supports its beneficial effects illustrating BPC 157 and NOsystem mutual (with L-NAME/L-arginine; alone and together) relations in (i) gastric mucosa and mucosal protection, following alcohol lesions, in cytoprotection course, NO-generation, and blood pressure regulation; (ii) alcohol acute/chronic intoxication, and withdrawal; (iii) cardiovascular disturbances, chronic heart failure, pulmonary hypertension, and arrhythmias; (iv) disturbances after hypokalemia and hyperkalemia, and potassium-cell membrane dysfunction; and finally, in (v) complex healing failure, proved by the fistulas healing, colocutaneous and esophagocutaneous. However, how this advantage of modulating NO-system (i. e., particular effect on eNOS gene), may be practically translated into an enhanced clinical performance remains to be determined.
Surgical aortic valve replacement (SAVR) represents a class I indication in symptomatic patients with severe aortic stenosis (AS). However, indications for early SAVR in asymptomatic patients with ...severe AS and normal left ventricular function remain debated.
The AVATAR trial (Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis) is an investigator-initiated international prospective randomized controlled trial that evaluated the safety and efficacy of early SAVR in the treatment of asymptomatic patients with severe AS, according to common criteria (valve area ≤1 cm
with aortic jet velocity >4 m/s or a mean transaortic gradient ≥40 mm Hg), and with normal left ventricular function. Negative exercise testing was mandatory for inclusion. The primary hypothesis was that early SAVR would reduce the primary composite end point of all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure compared with a conservative strategy according to guidelines. The trial was designed as event-driven to reach a minimum of 35 prespecified events. The study was performed in 9 centers in 7 European countries.
Between June 2015 and September 2020, 157 patients (mean age, 67 years; 57% men) were randomly allocated to early surgery (n=78) or conservative treatment (n=79). Follow-up was completed in May 2021. Overall median follow-up was 32 months: 28 months in the early surgery group and 35 months in the conservative treatment group. There was a total of 39 events, 13 in early surgery and 26 in the conservative treatment group. In the early surgery group, 72 patients (92.3%) underwent SAVR with operative mortality of 1.4%. In an intention-to-treat analysis, patients randomized to early surgery had a significantly lower incidence of primary composite end point than those in the conservative arm (hazard ratio, 0.46 95% CI, 0.23-0.90;
=0.02). There was no statistical difference in secondary end points, including all-cause mortality, first heart failure hospitalizations, major bleeding, or thromboembolic complications, but trends were consistent with the primary outcome.
In asymptomatic patients with severe AS, early surgery reduced a primary composite of all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure compared with conservative treatment. This randomized trial provides preliminary support for early SAVR once AS becomes severe, regardless of symptoms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02436655.
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•Detailed design space mapping for the combined graphene-metal waveguide resonators.•Design method to systematically achieve the specified tunable filtering response.•State-of-the-art ...full-wave numerical EM simulations and model parameter extraction.•Design curves for the combined graphene-metal filter tunability adjustment.•Fifth-order Chebyshev filter example and explanation of design trade-offs.
Tunable components and circuits, allowing for the fast switching between the states of operation, are among the basic building blocks for future communications and other emerging applications. Based on the previous thorough study of graphene based resonators, the design methodology for graphene tunable filters has been devised, outlined, as well as explained through an example of the fifth order filter. The desired filtering responses can be achieved with the material loss not higher than the loss corresponding to the previously studied single resonators, depending mostly on the quantity of graphene per resonator. The proposed design method relies on the detailed design space mapping; obtained data gives an immediate assessment of the feasibility of specifications with a particular filter order, maximal passband ripple level, desired bandwidth, and acceptable losses. The design process could be further automated by the knowledge based approach using the collected design space data.
Histone deacetylases (HDACs) are the major regulators of the balance of acetylation of histone and non-histone proteins. In contrast to other HDAC isoforms, HDAC6 is mainly involved in maintaining ...the acetylation balance of many non-histone proteins. Therefore, the overexpression of HDAC6 is associated with tumorigenesis, invasion, migration, survival, apoptosis and growth of various malignancies. As a result, HDAC6 is considered a promising target for cancer treatment. However, none of selective HDAC6 inhibitors are in clinical use, mainly because of the low efficacy and high concentrations used to show anticancer properties, which may lead to off-target effects. Therefore, HDAC6 inhibitors with dual-target capabilities represent a new trend in cancer treatment, aiming to overcome the above problems. In this review, we summarize the advances in tumor treatment with dual-target HDAC6 inhibitors.
Stable gastric pentadecapeptide BPC 157 is an anti-ulcer peptidergic agent, proven in clinical trials to be both safe in inflammatory bowel disease (PL-10, PLD-116, PL 14736) and wound healing, ...stable in human gastric juice, with no toxicity being reported. Recently, we claim that BPC 157 may be used as an antidote against NSAIDs. We focused on BPC 157 beneficial effects on stomach, duodenum, intestine, liver and brain injuries, adjuvant arthritis, pain, hyper/hypothermia, obstructive thrombus formation and thrombolysis, blood vessel function, counteraction of prolonged bleeding and thrombocytopenia after application of various anticoagulants and antiplatelet agents and wound healing improvement. The arguments for BPC 157 antidote activity (i.e., the role of BPC 157 in cytoprotection, being a novel mediator of Robert's cytoprotection and BPC 157 beneficial effects on NSAIDs mediated lesions in the gastrointestinal tract, liver and brain and finally, counteraction of aspirin-induced prolonged bleeding and thrombocytopenia) obviously have a counteracting effect on several established side-effects of NSAIDs use. The mentioned variety of the beneficial effects portrayed by BPC 157 may well be a foundation for establishing BPC 157 as a NSAIDs antidote since no other single agent has portrayed a similar array of effects. Unlike NSAIDs, a very high safety (no reported toxicity (LD1 could be not achieved)) profile is reported for BPC 157. Also, unlike the different dosage levels of aspirin, as a NSAIDs prototype, which differ by a factor of about ten, all these beneficial and counteracting effects of BPC 157 were obtained using the equipotent dosage (μg, ng/kg) in parenteral or peroral regimens.
Toxoplasma gondii is an obligate intracellular parasite infecting up to one third of the human population. The central event in the pathogenesis of toxoplasmosis is the conversion of tachyzoites into ...encysted bradyzoites. A novel approach to analyze the structure of in vivo-derived tissue cysts may be the increasingly used computational image analysis. The objective of this study was to quantify the geometrical complexity of T. gondii cysts by morphological, particle, and fractal analysis, as well as to determine if it is impacted by parasite strain, cyst age, and host type. A total of 31 images of T. gondii brain cysts of four type-2 strains (Me49, and local isolates BGD1, BGD14, and BGD26) was analyzed using ImageJ software. The parameters of interest included diameter, circularity, packing density (PD), fractal dimension (FD), and lacunarity. Although cyst diameter varied widely, its negative correlation with PD was observed. Circularity was remarkably close to 1, indicating a perfectly round shape of the cysts. PD and FD did not vary among cysts of different strains, age, and derived from mice of different genetic background. Conversely, lacunarity, which is a measure of heterogeneity, was significantly lower for BGD1 strain vs. all other strains, and higher for Me49 vs. BGD14 and BGD26, but did not differ among Me49 cysts of different age, or those derived from genetically different mice. The results indicate a highly uniform structure and occupancy of the different T. gondii tissue cysts. This study furthers the use of image analysis in describing the structural complexity of T. gondii cyst morphology, and presents the first application of fractal analysis for this purpose. The presented results show that use of a freely available software is a cost-effective approach to advance automated image scoring for T. gondii cysts.
Vitamin A and its metabolites are key regulators of the development of adipose tissue and associated metabolic complications. The aim of this study was to determine the effect of high fat diet and ...13-cis retinoic acid (13 cRA) application on metabolic parameters, adipogenic and inflammatory indicators in female Lewis rats. Female rats of Lewis strain were fed standard laboratory diet (STD) and high fat diet (HFD, 45% of saturated fatty acids) during 30 days. The groups were divided into additional 3 groups (6 rats each): two experimental groups that received 13 cRA orally on a daily basis during 30 days (7.5 mg/kg and 15 mg/kg, respectively) and the control group that was given sunflower oil. Animals were sacrificed after 60 days. Feeding of Lewis rats with chronic HFD diet with 13 cRA supplementation increased weight gain, adiposity index, dyslipidaemia, hyperleptinaemia, insulin resistance, VLDL concentrations, oxidative stress and atherogenic indices. Administration of 13 cRA in Lewis rats fed STD did not change the weight of the animals, but it slightly increased the atherogenic parameters. 13 cRA and HFD affect metabolic parameters, glucose and lipid metabolism in Lewis rats and its administration has a completely different effect on metabolism in rats fed STD, highlighting the complex role of vitamin A supplementation in obesity. Other factors, such as genetics, age, sex, adipose tissue distribution, also must be taken into consideration.
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