The oscillatory behaviour of the power system is an aspect that is significantly affected by the increasing integration of converter-based generation sources. Several works address the impact of ...non-synchronous generation on the operation of the system from different points of view, but only a few studies focus on power-frequency oscillations with a prevalence of generation sources interfaced through power electronics. A lack of research can be found in particular in the comparative analysis of the two main control strategies for power converters, namely grid-following and grid-forming. The article aims to contribute to this direction, starting from a theoretical analysis of the two control structures and then examining the case study of an existing transmission system. The research provides a specific insight into the fundamental aspects related to synchronisation mechanism and inertial capabilities of both grid-following with synthetic inertia and grid-forming controls. The difference in the relationship between synchronisation unit and inertial capability is recognised as the fundamental aspect determining the different impacts on the oscillatory characteristics of the system. The observation derived in the theoretical analysis is then applied to an actual power system with a high predominance of converter-based generation, considering the Colombian interconnected national system as a case study.
Introduction
The use of biological therapy is becoming increasingly common in patients with hidradenitis suppurativa (HS). Levels of serum TNF‐alfa and IL17 support the role of an immune system ...dysregulation in the pathogenesis of HS. Brodalumab targets the receptor A of IL‐17, thus having a promising role in the treatment of HS.
Material and methods
A multicenter retrospective observational open‐label study was conducted in two tertiary hospitals. Adults with moderate to severe HS under treatment with brodalumab 210 mg at week 0, 1, 2 and then every 2 weeks were included and assessed at weeks 0 and 16 which was the median follow‐up time. Demographic and disease‐related variables as well as response parameters (HiSCR and IHS4) and safety data were recorded and analysed.
Results
A total of 16 patients (75% males) were included in our study. 50% of patients presented an inflammatory phenotype and mean BMI was 28.37. HiSCR was achieved in 50% of patients and mean IHS4 decreased from 24.13 to 16.81 (p = 0.002). No differences were found between those who achieved HiSCR and those who did not. Grade 2 adverse events were reported in three patients with no fatal outcomes and treatment discontinuation was advised in four patients.
Conclusions
Brodalumab seems to be effective and safe in patients with moderate to severe HS, even in those that did not respond to adalimumab, which, at the moment, is the only widely approved biologic for this indication. Thus, it stands as an interesting option for the treatment of HS.
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•A conceptual design of a reactive distillation process for isobutyl acetate synthesis.•Esterification of acetic acid and isobutanol using Amberlyst 15 as catalysts.•Static and ...reactive residue curve maps analyses were used.•Rigorous simulation and optimization was carried out.•Urethane grade isobutyl acetate can be obtained as bottoms product.
This work studies the conceptual design of a Reactive Distillation (RD) process for isobutyl acetate production by esterification of acetic acid and isobutanol. Static and reactive residue curve map analyses were used to assess RD feasibility, and to identify suitable operating conditions for industrial implementation. The maps were obtained using validated phase equilibria and reaction kinetic models by coupling Aspen plus V.10 and Python. Afterwards, conceptual design outputs were used for a rigorous simulation and optimization of the process. The obtained results indicate that pure isobutyl acetate cannot be obtained as pure product from the RD column as it is a saddle node. However, isobutyl acetate can be obtained as bottom product at enough purity to fulfil urethane grade specifications. A final reactive distillation configuration was developed enabling to obtain almost complete reactants conversion, with a molar composition of isobutyl acetate > 99 % wt. at the bottoms of the column. According to the optimal operating conditions, isobutyl acetate via RD can be produced under an energy intensity of 0.77 kW/kgIbAC, a mass intensity of 1.16 kgreactants/kgIbAC, a productivity of 328.7 kgIbAC/m3h, and a production cost of 0.98 USD/ kgIbAC.
The aim of the present study was to evaluate the effect of obesity on the osseointegration of implants with hydrophobic and hydrophilic surfaces.
Sixty-four male rats were distributed among four ...experimental groups: H-HB (Healthy/Hydrophobic): healthy animals with hydrophobic implants; H-HL (Healthy/Hydrophilic): healthy animals with hydrophilic implants; O-HB (Obese/Hydrophobic): animals with induced obesity and hydrophobic implants; O-HL (Obese/Hydrophilic): animals with induced obesity and hydrophilic implants. One hundred and twenty-eight implants were installed in the tibiae of the animals bilaterally (64 on the left tibiae and 64 on the right one) after 75 days of a specific diet (standard or high-fat diet) and euthanasia was performed in the experimental periods of 15 and 45 days after implant placement. Bone formation was assessed by biomechanical analysis (on the left tibiae of each animal), and microtomographic and histomorphometric analyses (on the right tibiae of each animal). Statistical analysis was performed using the Shapiro-Wilk test for normality and ANOVA followed by Tukey test to observe whether there was a significant difference between groups (p < 0.05); the t-test was used to compare the animals' body weight.
The biomechanical analysis showed an increase in the removal torque value of animals after 45 days in comparison to after 15 days, with the exception of O-HB groups. The microtomographic analysis demonstrated no significant differences in the mineralized bone tissue volume between the groups. In the histomorphometric analysis, the H-HL/45 day group/period demonstrated higher bone-implant contact, in comparison to H-HL/15 days and the O-HL/45 day group/period showed an increase in bone area between the implant threads, in comparison to O-HL/15 days.
In conclusion, obesity does not interfere with the osseointegration of hydrophobic and hydrophilic implants.
Transmembrane protein 16 F (TMEM16F) is a Ca
-activated homodimer which functions as an ion channel and a phospholipid scramblase. Despite the availability of several TMEM16F cryogenic electron ...microscopy (cryo-EM) structures, the mechanism of activation and substrate translocation remains controversial, possibly due to restrictions in the accessible protein conformational space. In this study, we use atomic force microscopy under physiological conditions to reveal a range of structurally and mechanically diverse TMEM16F assemblies, characterized by variable inter-subunit dimerization interfaces and protomer orientations, which have escaped prior cryo-EM studies. Furthermore, we find that Ca
-induced activation is associated to stepwise changes in the pore region that affect the mechanical properties of transmembrane helices TM3, TM4 and TM6. Our direct observation of membrane remodelling in response to Ca
binding along with additional electrophysiological analysis, relate this structural multiplicity of TMEM16F to lipid and ion permeation processes. These results thus demonstrate how conformational heterogeneity of TMEM16F directly contributes to its diverse physiological functions.
Seizures represent a frequent symptom in gliomas and significantly impact patient morbidity and quality of life. Although the pathogenesis of tumor-related seizures is not fully understood, ...accumulating evidence indicates a key role of the peritumoral microenvironment. Brain cancer cells interact with neurons by forming synapses with them and by releasing exosomes, cytokines, and other small molecules. Strong interactions among neurons often lead to the synchronization of their activity. In this paper, we used an in vitro model to investigate the role of exosomes released by glioma cell lines and by patient-derived glioma stem cells (GSCs). The addition of exosomes released by U87 glioma cells to neuronal cultures at day in vitro (DIV) 4, when neurons are not yet synchronous, induces synchronization. At DIV 7-12 neurons become highly synchronous, and the addition of the same exosomes disrupts synchrony. By combining Ca
imaging, electrical recordings from single neurons with patch-clamp electrodes, substrate-integrated microelectrode arrays, and immunohistochemistry, we show that synchronization and de-synchronization are caused by the combined effect of (i) the formation of new neuronal branches, associated with a higher expression of Arp3, (ii) the modification of synaptic efficiency, and (iii) a direct action of exosomes on the electrical properties of neurons, more evident at DIV 7-12 when the threshold for spike initiation is significantly reduced. At DIV 7-12 exosomes also selectively boost glutamatergic signaling by increasing the number of excitatory synapses. Remarkably, de-synchronization was also observed with exosomes released by glioma-associated stem cells (GASCs) from patients with low-grade glioma but not from patients with high-grade glioma, where a more variable outcome was observed. These results show that exosomes released from glioma modify the electrical properties of neuronal networks and that de-synchronization caused by exosomes from low-grade glioma can contribute to the neurological pathologies of patients with brain cancers.
Reversing brain aging may be possible through systemic interventions such as exercise. We found that administration of circulating blood factors in plasma from exercised aged mice transferred the ...effects of exercise on adult neurogenesis and cognition to sedentary aged mice. Plasma concentrations of glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (Gpld1), a GPI-degrading enzyme derived from liver, were found to increase after exercise and to correlate with improved cognitive function in aged mice, and concentrations of Gpld1 in blood were increased in active, healthy elderly humans. Increasing systemic concentrations of Gpld1 in aged mice ameliorated age-related regenerative and cognitive impairments by altering signaling cascades downstream of GPI-anchored substrate cleavage. We thus identify a liver-to-brain axis by which blood factors can transfer the benefits of exercise in old age.
Monitoring the malolactic fermentation process is strictly required to guarantee the sensorial quality and freshness of red wines. This could be achieved by in-field and real-time continuous ...measurements of l-malate concentration in the fermentation tanks. The potential of a miniaturized amperometric bienzymatic biosensor as an analytical tool to be applied in such scenario is described in this paper. The biosensor comprises a thin-film gold electrode as transducer, malate dehydrogenase (MDH) and diaphorase (DP) enzymes together with nicotinamide adenine dinucleotide (NAD+) cofactor as the selective receptor and an adequate redox mediator to record the corresponding amperometric signal. Three different biosensor architectures are studied, whose main differences lie in the immobilization of the different chemical components onto the electrode surface. In all cases a fast-electrosynthethized polypyrrole (PPy) membrane is generated for this purpose. The experimental conditions are optimized and the best architecture shows a sensitivity of 1365 ± 110 mA M−1 cm−2 and a detection limit of 6.3 × 10−8 M in a concentration range of 1 × 10−7 M – 1 × 10−6 M. The biosensor presents an excellent working stability as it retains above 90% of its sensitivity after 37 days, thus enabling the monitoring of the malolactic fermentation of three red wines. The obtained results show excellent agreement with the standard colorimetric method.
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•Bienzymatic electrochemical biosensor for l-malate.•Malate dehydrogenase and diaphorase enzymes entrapped into an electrosynthesized polypyrrole film.•Optimized redox mediator also incorporated into the polymeric film.•Long-term stability for over 37 days.•Application to l-malic acid determination during the malolactic fermentation of red wines.
IntroductionThe increased risk of myocardial infarction (MI) in type 2 diabetes mellitus (T2DM) is well documented. Polymorphisms in APOA1 and APOB genes allow us to identify new genetic markers in ...the Mexican population with T2DM and MI. Material and methodsWe studied 135 patients with DMT2 and MI (DI); another 85 non-infarcted diabetic individuals with DMT2 but without previous ischemic events (NID) and 242 healthy subjects (HS). All three groups were selected with the aim to investigate the association between the polymorphisms and infarction when T2DM is present or absent. Results-75 G>A polymorphism: Differences were found in genotype distribution between DI and NID individuals (OR = 2.01, 95% CI: 1.117-3.623, p = 0.019) with an increased risk for A in the dominant model (OR = 1.77, 95% CI: 1.020-3.084, p = 0.042); also concentrations of ApoA-I for A/A were lower in comparison with G/A (p = 0.038) and LDL-C and HDL-C levels were lower in G/A compared to G/G carriers. 83 C>T polymorphism of APOA1: For DI individuals, HDL-C was lower in T/T compared to C/C and triglyceride levels were lower in C/T compared to C/C carriers. ConclusionsThe -75 G>A APOA1 polymorphism could be considered as a susceptibility factor for myocardial infarction in individuals with T2DM and 2488 C>T APOB polymorphism is associated with changes in HDL-C and LDL-C and triglycerides in the same group.
The COVID-19 pandemic brought attention to our limited understanding of human olfactory physiology. While the cellular composition of the human olfactory epithelium is similar to that of other ...vertebrates, its functional properties are largely unknown. We prepared acute slices of human olfactory epithelium from nasal biopsies and used the whole-cell patch-clamp technique to record electrical properties of cells. We measured voltage-gated currents in human olfactory sensory neurons and supporting cells, and action potentials in neurons. Additionally, neuronal inward current and action potentials responses to a phosphodiesterase inhibitor suggested a transduction cascade involving cAMP as a second messenger. Furthermore, responses to odorant mixtures demonstrated that the transduction cascade was intact in this preparation. This study provides the first electrophysiological characterization of olfactory sensory neurons in acute slices of the human olfactory epithelium, paving the way for future research to expand our knowledge of human olfactory physiology.
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•Acute slices of human olfactory epithelium are viable for patch-clamp recordings•Supporting cells (non-neuronal) exhibit outward voltage-gated currents•Olfactory sensory neurons display diverse patterns of action potentials•Olfactory sensory neurons respond to odorants and other stimuli
Neuroscience; Sensory neuroscience
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