This paper investigates the finite-time preview saturated control problem for linear parameter-varying systems with input saturation. The external disturbances and input saturation, previewable reference signals, and parameter variations are considered simultaneously. First, using the error system method, we construct an augmented error system with previewed information. This transforms the finite-time preview saturated control problem into a finite-time stabilization problem. Next, static output-feedback controllers are used to guarantee the finite-time boundedness of the closed-loop system. Sufficient conditions guarantee the existence of the desired controllers are obtained using linear matrix inequalities. At last, we use a numerical simulation to show the proposed design method's effectiveness.
Root hemiparasitic Pedicularis kansuensis is an invasive native species in China and has been expanding in the Bayanbulak Grassland of Xinjiang Uygur Autonomous Region over the past decade, threatening the local livestock industry. To understand why this damaging species expands in some areas but not in others, we compared soil water content, soil nutrient status, and plant community structures between heavily infected and non-infected sites. We hypothesized that soil nutrient levels and plant species composition would be more beneficial to the spatial expansion of P. kansuensis in heavily infected areas than in non-infected ones. Quadrat (1 m × 1 m) surveys were carried out in the Bayanbulak Grassland. Species number, percent vegetation cover, aboveground plant biomass, plant height, and relative frequency were recorded. Three topsoil samples were taken at 0–10 cm depth from each quadrat and their nutrient statuses were determined. The results showed that (1) P. kansuensis invasion reduces the species richness of the community compared to the uninvaded area (3.07%), but increases the canopy cover overall (16.99%); (2) soil water content (SW) and soil nutrient content are the main factors that determine invasion by P. kansuensis, and SW plays the more important role; (3) SW controls P. kansuensis leaf stoichiometry, decreases the Ratio of leaf nitrogen (LN) to leaf phosphorus (LP), and affects LP (P < 0.005). Finally, after combining the results, we found that the soil factor accounted for 46.50% and plants accounted for 22.50% of P. kansuensis invasions in the Bayanbulak Grassland.
Leishmania is the causative agent of the tropical neglected disease leishmaniasis and infects macrophages as its definitive host cell . In order to sustain and propagate infections, Leishmania parasites have to complete cycles of exit and re-infection. Yet, the mechanism driving the parasite spread to other cells remains unclear. Recent studies reported pro-inflammatory monocytes as replicative niche of L. major and showed prolonged expression of IL-1β at the site of infection, indicating an activation of the NLRP3 inflammasome and pointing towards pyroptosis as a possible mechanism of parasite spread. To address the species-specific inflammasome activation of human cells we characterized the BLaER1 macrophages as a model for L. major infection. We found that Leishmania can infect, activate and develop in BLaER1 macrophages similar as they can do in primary human macrophages. Harnessing the possibilities of this infection model, we first showed that BLaER1 GSDMD-/- cells, which carry a deletion of the pore-forming protein gasdermin D, are more resistant to pyroptotic cell death and, concomitantly, display a strongly delayed release of intracellular parasite. Using that knockout in a co-incubation assay in comparison with wild type BLaER1 cells, we demonstrate that impairment of the pyroptosis pathway leads to lower rates of parasite spread to new host cells, thus, implicating pyroptotic cell death as a possible exit mechanism of L. major in pro-inflammatory microenvironments.
A Case of TAFRO syndrome after COVID-19 vaccinationHitomi Hirosea, Hitoshi Suzukia,c*, Yukako Umezawaa, Masako Iwasakia, Hiromitsu Fukudaa, Hisatsugu Takaharaa, Shigeki Tomitab, Yusuke Suzukica. Department of Nephrology, b. Department of Pathology, Juntendo University Urayasu Hospital, Chiba, Japan. c. Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan.Correspondence to:Hitoshi Suzuki, M.D., Ph.DDepartment of Nephrology, Juntendo University Urayasu Hospital2-1-1 Tomioka, Urayasu-shi, Chiba 279-0021, JapanEmail: firstname.lastname@example.orgKey words: COVID-19, mRNA vaccine, TAFRO syndrome, renal dysfunction
We present a 35-year-old male who sustained a right hip GSI. Delayed THA with a two-step sequential approach is feasible management in this situation in order to manage soft tissue and decrease infection rate. At one-year follow-up visit the pain was relieved and function improved significantly and had no complaints.
Introduction: Nasolacrimal duct obstruction (NLDO) is the most common cause of childhood epiphora. Congenital NLDO is usually conservatively management in the first year of life, failing which surgical interventions such as syringing and probing (S&P), insertion of stents (intubation) or dacryocystorhinostomy (DCR) are offered in a stepwise manner. Methods: This is a retrospective study at a tertiary paediatric hospital. Nasolacrimal surgeries were retrieved from Hospital Episodes Statistics (HES) data for a 5-year period between May 2017 to April 2022. Retrospective case note review was undertaken looking into demographics, presentation, surgical interventions, and outcomes (resolved, partially resolved or persistent). Results: In our institution, NLDO surgeries are performed on a joint ophthalmology/ENT list. A total of 301 procedures were performed on 218 patients (293 eyes). Causes for epiphora were Congenital NLDO (n=193, 88.5%), Secondary NLDO (n=10, 4.6%), Dacryocystitis/Mucocele (n=8, 3.67%) among others. Median age at first procedure was 26 months (range 2-189). Median number of procedures for congenital NLDO is 1(range 1-5). Complete resolution of symptoms was achieved by syringing and probing in 133 cases (73%), intubation in 23 cases (78%) and DCR in 7 cases(58.3%). Patients with craniofacial syndromes required a statistically significant higher number of DCRs. Overall, epiphora was completed resolved in 81% cases, 6.3% partially resolved and is persistent in 12.7%. Conclusion: Multi-disciplinary approach to NLDO ensured efficient delivery of care by minimising number of procedures and hospital attendance. Congenital NLDO can be successfully treated in vast majority of cases with S&P and intubation. In cases with anatomical abnormalities, DCR should be considered early.
The influence of preloading on the residual fatigue life of nickel-based superalloys under elevated temperatures was investigated experimentally. A powder metallurgy nickel-based superalloy FGH96 was preloaded with different number of cycles, and the residual fatigue life was tested under subsequent high-amplitude loads. The test results show that the fatigue life of the material was increased when the preloading cycle number was within a specific range. At the same time, the fatigue life of virgin specimens under high-amplitude loads shows little scatter, which provides the possibility to consider the strengthening effect of low-amplitude loads. A novel damage accumulation model was proposed to incorporate the strengthening effect of low-amplitude loads into the life prediction framework. The proposed model provides better life prediction than some existing models. Finally, the proposed model was validated using experimental data for various materials under the low-high loading sequence.
Gametic isolation is thought to play an important role in the evolution of reproductive isolation in broadcast-spawning marine invertebrates. However, it remains uncertain whether gametic isolation typically develops early in the speciation process or accumulates after other reproductive barriers are already in place. It is also unknown whether gametic incompatibilities have effectively prevented introgression during later stages of divergence. Here, we use phylogenomic approaches to test whether the well-documented asymmetric gametic incompatibilities between strongylocentrotid urchins have been effective in preventing introgression. Despite a well-supported species tree, we found considerable phylogenetic discordance that cannot be explained by incomplete lineage sorting alone. There was strong support for introgression between at least four pairs of extant taxa: S. pallidus ↔ S. droebachiensis, S. intermedius ↔ S. pallidus, S. purpuratus ↔ S. fragilis, and M. franciscanus ↔ P. depressus. There was additional evidence for introgression on internal branches of the phylogeny. Although gametic incompatibilities may be important in species recognition and the maintenance of species boundaries in strongylocentrotid urchins, gametic isolation does not appear to have been an effective barrier to introgression. The continued divergence in the face of widespread introgression indicates that other reproductive isolating barriers likely exist and may have been more critical in establishing reproductive isolation early in speciation.
Human activities have altered the composition of species assemblages through the introduction of non-native species and the extinction of threatened species. However, it remains unclear whether non-native species can compensate for the loss of threatened species and thus maintain ecosystem functioning. Here we tested whether non-natives are functionally and/or phylogenetically similar (compensation hypothesis) or distinct (shift hypothesis) from native and threatened species on bird assemblages in 267 regions worldwide. We show that non-native species were more functionally distinct from threatened species than expected by chance but more phylogenetically related. Globally, this results in an increase in the functional richness of bird assemblages due to the introduction of new functional traits but a decrease in the phylogenetic richness due to the potential loss of phylogenetically unique threatened species. Furthermore, these patterns vary across continents, revealing the role of human history and footprint across the world and outlining priority areas where international bird conservation should focus. In the context of the biodiversity crisis and the increasing number of non-native species worldwide, the changes in the functional and phylogenetic structure of the bird communities might increase the vulnerability of ecosystems.
α-Glucosidase (AG) is a bifunctional enzyme, it has a capacity to synthesize 2-O-α-D-glucopyranosyl-L-ascorbic acid (AA-2G) from L-ascorbic acid (L-AA) and low-cost maltose under mild conditions, but it can also hydrolyze AA-2G, which leads to low synthesis efficiency of AA-2G. Main Methods and Major Results This study introduces a rational molecular design strategy to regulate enzymatic reactions based on inhibiting the formation of ground state of enzyme-substrate complex. Y215 was analyzed as the key amino acid site affecting the affinity of AG to AA-2G and L-AA. For the purpose of reducing the hydrolysis efficiency of AA-2G, the mutant Y215W was obtained by analyzing the molecular docking binding energy and hydrogen bond formation between AG and the substrates. Compared with the wild type, Isothermal Titration Calorimetry(ITC) results showed that the equilibrium dissociation constant (KD) of the mutant for AA-2G was doubled; the Michaelis constant (Km) for AA-2G was reduced by 1.15 times; and the yield of synthetic AA-2G was increased by 39%. Conclusions and Implications Our work also provides a new reference strategy for the molecular modification of multifunctional enzymes and other enzymes in cascade reactions system.
Biocatalysis in high-concentration organic solvents has been applied to produce various industrial products with many advantages. However, using enzymes in organic solvents often suffers from inactivation or decreased catalytic activity and stability. So, improving the tolerance of enzymes in organic solvents is essential. Herein, the method of regional random mutation combined with combinatorial mutation was used to improve the resistance of transaminase from Aspergillus terreus (AtATA) in organic solvents, and the best mutant T23I/T200K/P260S (M3) was acquired. In different concentrations of dimethyl sulfoxide (DMSO), the catalytic efficiency toward 1-acetylnaphthalene and the stability were higher than the wild-type (WT) of AtATA. M3 also showed enhanced stability against six organic solvents with different oil-water partition coefficients (log P values). The results of decreased Root Mean Square Fluctuation (RMSF) values via 20-ns molecular dynamics simulations under different concentration DMSO revealed that mutant M3 had lower flexibility, acquiring a more stable protein structure and contributing to its organic solvents stability than WT. Intra- and intermolecular interaction analysis indicated that the increased hydrogen bonds and hydrophobic interactions within monomers or at the interface of two monomers also strengthened the stability of the overall structure against organic solvents. Furthermore, M3 was applied to convert 1-acetylnaphthalene for synthesizing (R)-(+)-1(1-naphthyl)-ethylamine ((R)-NEA), which was and an intermediate of Cinacalcet Hydrochloride. Moreover, 3~10 mM 1-acetylnaphthalene can be converted to (R)-NEA with 94.2~38.9% yield and a strict R-stereoselectivity within 10 h under 25% DMSO, which was higher than WT and expected to be a potential biocatalyst for industrial application.
This study's primary objective is to demonstrate how diffusion-thermo and thermal diffusion influence of peristaltic flow processes with slip boundaries when joule heating happens from the interior. Several operational factors and their impacts on the system were analysed, along with the corresponding graphs. As slip parameters rise, the axial pressure gradient fluid flow tends to drop. The pressure rate is demonstrated to drop in the backward and peristaltic pumping regions as the quantity of the second order slide parameter rises, whereas it rises in the co-pump zone. As slip parameters rise, fluid temperature and concentration tend to drop. Changes in the thermal diffusion and thermo diffusion factors cause changes in the fluid's temperature and concentration. The Nusselts number can be increased by increasing the Prandtl number, the thermo-diffusion constraint, the dufour number, and the Schmidt number. However, this will result in fewer Sherwood number.
Team formation in an environment where some relevant parameters are not known in advance is a challenging problem. Communicating automata and distributed algorithms have been used to describe protocols for team formation. A high-level specification provides a mathematical description of a protocol or a program. TLA + is a formal specification language designed to provide high-level specifications of concurrent and distributed systems. The associated model checker known as TLC is capable of model checking the TLA + specifications. Recently formal specification of a team formation protocol is given using TLA + when there is a single initiator (an agent or a robot), that initiates the team formation. Using TLA +, we examine the formal specification for the multiple initiator situation and demonstrate that a composition technique can yield a single monolithic specification for the multiple initiator situation from the single initiator situation specification. We have used models of varying sizes, and the TLC model checker has confirmed that the protocol’s specifications meet certain desired characteristics in each case.
Aim Dysfunction of nitric oxide (NO) – soluble guanylate cyclase (sGC) – cyclic guanosine monophosphate (cGMP) signalling is implicated in the pathophysiology of cognitive impairment and dementia. Zagociguat is a central nervous system-(CNS-) penetrant sGC stimulator designed to amplify NO-cGMP signalling in the CNS. This article reports on a phase 1b study evaluating the safety and pharmacodynamic effects of zagociguat. Methods In this randomized crossover study, 24 healthy participants ≥65 years of age were planned to receive 15 mg zagociguat or placebo once daily for two 15-day periods separated by a 27-day washout. Adverse events, vital signs, electrocardiograms, and laboratory tests to assess safety. Pharmacokinetics of zagociguat were evaluated in blood and CSF. Pharmacodynamic assessments included evaluation of cerebral blood flow, CNS tests, pharmaco-electroencephalography, passive leg movement, and biomarkers in blood, cerebrospinal fluid, and brain. Results Twenty-four participants were enrolled and 12 participants completed both treatment periods, while 12 participants completed only one treatment period. Zagociguat was well tolerated and penetrated the blood-brain barrier. Zagociguat induced modest decreases in blood pressure. No consistent effects of zagociguat on other pharmacodynamic parameters were detected. Conclusion Zagociguat was well tolerated and induced modest systemic blood pressure reductions consistent with other sGC stimulators. No clear pharmacodynamic effects of zagociguat were detected, perhaps due to optimal CNS function in healthy participants. Studies in participants with proven reduced cerebral blood flow or CNS function may be an avenue for further evaluation of the compound.
Recently, superparamagnetic silica encapsulated DNA microparticles (SiDNAFe) were designed and in various experiments used as a hydrological tracer. We investigated the effect of bed characteristics on the transport behaviour and especially the mass loss of SiDNAFe in open channel injection experiments. Hereto, a series of laboratory injection experiments were conducted with four channel bed conditions (no sediment, fine river sediment, coarse sand, and goethite-coated coarse sand) and two water qualities (tap water and Meuse water). Breakthrough curves (BTCs) were analysed and modelled. Mass loss of SiDNAFe was accounted for as a first-order decay process included in a 1-D advection and dispersion model with transient storage (OTIS). SiDNAFe BTCs could be adequately described by advection and dispersion with or without a first-order decay process. Mass loss of SiDNAFe increased as a function of the surface roughness of the beds. Retention of SiDNAFe due to surface roughness was 1-2 orders of magnitude greater than gravitational settling rates, as determined in Tang et al. (2022). We speculate this was due to boundary layer kinetic attachment. The dispersive behaviour of SiDNAFe generally mimicked that of NaCl tracer, although SiDNAFe traveled faster on average due to a smaller effective cross-sectional area. No pattern was observed between SiDNAFe mass recovery and water qualities used. DNA concentration data uncertainty was mostly associated with lower SiDNAFe concentrations in the BTCs. This research highlights that riverbeds are important sinks, and the surface roughness affects the fate and transport characteristics of SiDNAFe when in proximity to the water-sediment interface. SiDNAFe possess promising potential as a surrogate for multi-tracing micro-contaminants (e.g., microplastics) in large rivers, which could be a promising tool for enhancing understanding of hydrological processes.