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In normal B-cells, Bruton tyrosine kinase (Btk), a non-receptor tyrosine kinase involved in B-cell receptor (BCR) signalling, is essential for cell survival and maturation. Not surprisingly, Btk is also implicated in the pathogenesis of B-cell lymphomas, like Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma (MCL) and Waldenström’s Macroglobulinemia (WM), which are driven by aberrant BCR signalling. Thus, targeting Btk represents a promising therapeutic strategy in the treatment of B-cell lymphoma patients. Ibrutinib, a selective Btk inhibitor, has already been approved as second-line treatment of CLL/SLL, MCL and WM patients, while more clinical studies of ibrutinib and novel Btk inhibitors are currently under way. In light of results of the RESONATE-2 trial, the approval of ibrutinib as a first-line treatment of CLL/SLL may well be approaching. Herein, we review Btk’s role in normal and malignant BCR signalling, as well as ibrutinib’s performance in B-cell lymphoma treatment and prognosis.

Nanoencapsulated phase change materials (nePCMs) are nowadays under research for thermal energy storage purposes. NePCMs are composed of a phase change core surrounded by a shell that confines the core when molten. One of the main concerns of nePCMs when subjected to thermal processes is the mechanical failure of the passivation shell initially present in commercial metallic nanoparticles. In order to overcome this issue, multi-coated nePCMs, based on the synthesis of an additional coating by atomic layer deposition, appear to be as a candidate solution. With the objective of studying the influence of the composition and thickness of the additional nePCM shells on their probability of failure, a numerical tool combining a thermomechanical finite element model with phase change and Monte Carlo algorithms is developed. This tool also allows including the uncertainty of material and geometrical properties into the numerical analysis to account for their influence in the mechanical performance of nePCMs. In the present work, the mechanical reliability of SiO2 and Al2O3 coatings on Sn@SnOx nanoparticles is assessed by considering both deterministic and probabilistic failure criteria and Al2O3 coatings appear to have a better mechanical performance than their SiO2 counterparts.

ABSTRACTThe concept of Industry 4.0, as a means to move forward in the industrial ecosystem, has reached an important turning point. Where do we stand now in terms of industrial innovation and transition? This opinion paper provides an overview of the situation in the Netherlands, a reflection on what has been achieved by the Industry 4.0 paradigm, and the necessary way forward to solidify its implementation. Tentative results reveal that the pervasiveness of Industry 4.0 applications is sector-specific. This work provides industrial stakeholders and academics with useful suggestions and a possible path to move towards better integration of Industry 4.0 in company reality. In this opinion paper, we employ a mixed methods research methodology to argue that, based on our findings on industrial adaptation in The Netherlands, Industry 4.0 is the outcome of an evolutionary process and not of a revolution, as it is often claimed.

Additive manufacturing (AM), specifically Directed Energy Deposition (DED)-Arc, holds great potential for the fabrication of individually designed components. In the construction industry, the demand for tailored steel nodes is increasing, particularly for large-scale structures, where high-strength steel deployment can significantly reduce material consumption and production time. However, the thermal material deposition process has a strong impact on the technical properties of high-strength steel. Parameters like heat input, interpass temperature (IPT), and cooling strategies modulate cooling times and peak temperatures in thermal cycles, which are crucial for estimating mechanical properties indispensable for safety certification. The development of digital twins or digital shadows emerges as the primary approach for quality assurance and certification, deploying real-time monitoring of manufacturing parameters such as voltage, current, wire feed, thermal history, and bead shapes. This data can be correlated with specific regions in the fabricated part to draw quality inferences. To interpret this data effectively, an understanding of the influence of these process parameters on resultant properties is indispensable. Given that the resulting microstructure strongly depends on the thermal history in AM parts, temperature monitoring during DED-Arc using thermography emerges as a promising method. This article aims at providing fundamental knowledge about phase transformations of a high strength steel feedstock under repeated reheating and gaining comprehensive knowledge about microstructural evolution during DED-Arc Additive Manufacturing. This is done by the analysis of time-temperature profiles, resulting microstructure and mechanical properties, linking it to CCT diagrams. A novel approach for describing the degree of tempering in different regions of the samples by deploying tempering parameters for anisothermal heat treatments is presented. By using this approach, an estimation about the resulting microstructure and hence the mechanical properties can be drawn.

This study aspires to evaluate the antibacterial and inhibitory effects of carbohydrate digestive enzymes in tree leaves that are widely distributed in the Mediterranean region. Leaves were sequentially extracted with solvents of increasing polarity. The results demonstrated a wide range of phenolic (3.5–770.7 mg gallic acid equivalent g−1) and flavonoid (0.2–321.3 mg catechin equivalent g−1) contents in leaf extracts. The minimum inhibitory and bactericidal concentration of leaf extracts was determined for six bacteria using the broth microdilution method. The polar extracts of carob, lentisk, and white mulberry leaves exerted strong antibacterial potency against Gram-positive bacteria, while the susceptibility of Escherichia coli on relative apolar extracts of carob, fig, and olive leaves was also observed. In parallel, the inhibitory effects of leaf extracts on carbohydrate digestive enzymes were evaluated. A robust inhibition of α-glucosidase was found for carob and lentisk leaf extracts, followed by extracts produced by white mulberry and olive leaves. Carob and lentisk leaves also act as a-amylase inhibitors at high concentrations. Overall, this study provides valuable data for the nutraceutical value of the “forgotten” treasure of Mediterranean tree leaves and assesses these plants as potential sources of antibacterial and carbohydrate digestive enzyme inhibitory agents for drug discovery.

Plants possess endless structural and chemical diversity, which is peerless with any synthetic library of small biomolecules, inspiring novel drug discovery. Plants are widely applied to encounter global health challenges such as antimicrobial resistance and diabetes. The objective of this work was to evaluate the antibacterial and antidiabetic potency of native plants grown in Cyprus. All plants were sequentially extracted with solvents of increasing polarity, namely hexane, acetone, methanol, and water. First, the phenolic and flavonoid contents of the extracts were assessed. Afterwards, the bacteriostatic and bactericidal potency of plant extracts were tested against a panel of six bacteria using the broth microdilution method, whereas the inhibitory effects on alpha-glucosidase and alpha-amylase enzymes were also determined with the employment of microplate assays. The results highlighted the superiority of Sarcopoterium spinosum as a potential enzyme inhibitor, while a knowledge base was also acquired for the inhibitory potential of all plants. Daucus carota, Ferula communis, and Tordylium.aegyptiacum displayed additionally outstanding bacteriostatic and bactericidal effects on Gram-positive bacteria at concentrations of 250 µg mL−1 and 500 µg mL−1. Overall, the present study describes the antibacterial and inhibitory activity against carbohydrate digestive enzymes of native plants grown in Cyprus delivering the first reports for many plant species.

Abstract Intravascular surgical instruments require precise navigation within narrow vessels, necessitating maximum flexibility, minimal diameter, and high degrees of freedom. Existing tools often lack control during insertion due to undesirable bending, limiting vessel accessibility and risking tissue damage. Next-generation instruments aim to develop hemocompatible untethered devices controlled by external magnetic forces. Achieving this goal remains complex due to testing and implementation challenges in clinical environments. Here we assess the operational effectiveness of hemocompatible untethered magnetic robots using an ex vivo porcine aorta model. The results demonstrate a linear decrease in the swimming speed of untethered magnetic robots as arterial blood flow increases, with the capability to navigate against a maximum arterial flow rate of 67 mL/min. The untethered magnetic robots effectively demonstrate locomotion in a difficult-to-access target site, navigating through the abdominal aorta and reaching the distal end of the renal artery.

Data from satellite, aircraft, drone, and ground-based measurements have already shown that canopy-scale sun-induced chlorophyll fluorescence (SIF) is tightly related to photosynthesis, which is linked to vegetation carbon assimilation. However, our ability to effectively use those findings are hindered by confounding factors, including canopy structure, fluctuations in solar radiation, and sun–canopy geometry that highly affect the SIF signal. Thus, disentangling these factors has become paramount in order to use SIF for monitoring vegetation functioning at the canopy scale and beyond. Active chlorophyll fluorescence measurements (FyieldLIF), which directly measures the apparent fluorescence yield, have been widely used to detect physiological variation of the vegetation at the leaf scale. Recently, the measurement of FyieldLIF has become feasible at the canopy scale, opening up new opportunities to decouple structural, biophysical, and physiological components of SIF at the canopy scale. In this study, based on top-of-canopy measurements above a mature deciduous forest, reflectance (R), SIF, SIF normalized by incoming photosynthetically active radiation (SIFy), FyieldLIF, and the ratio between SIFy and FyieldLIF (named Φk) were used to investigate the effects of canopy structure and shadows on the diurnal and seasonal dynamics of SIF. Further, random forest (RF) models were also used to not only predict FyieldLIF and Φk, but also provide an interpretation framework by considering additional variables, including the R in the blue, red, green, red-edge, and near-infrared bands; SIF; SIFy; and solar zenith angle (SZA) and solar azimuth angle (SAA). Results revealed that the SIF signal is highly affected by the canopy structure and sun–canopy geometry effects compared to FyieldLIF. This was evidenced by the weak correlations obtained between SIFy and FyieldLIF at the diurnal timescale. Furthermore, the daily mean SIF‾y captured the seasonal dynamics of daily mean F‾yieldLIF and explained 58 % of its variability. The findings also revealed that reflectance in the near-infrared (R-NIR) and the NIRv (the product of R-NIR and normalized difference vegetation index (NDVI)) are good proxies of Φk at the diurnal timescale, while their correlations with Φk decrease at the seasonal timescale. With FyieldLIF and Φk as outputs and the abovementioned variables as predictors, this study also showed that the RF models can explain between 86 % and 90 % of FyieldLIF, as well as 60 % and 70 % of Φk variations under clear-sky conditions. In addition, the predictor importance estimates for FyieldLIF RF models revealed that R at 410, 665, 740, and 830 nm; SIF; SIFy; SZA; and SAA emerged as the most useful and influential factors for predicting FyieldLIF, while R at 410, 665, 705, and 740 nm; SZA; and SAA are crucial for predicting Φk. This study highlighted the complexity of interpreting diurnal and seasonal dynamics of SIF in forest canopies. These dynamics are highly dependent on the complex interactions between the structure of the canopy, the vegetation biochemical properties, the illumination angles (SZA and SAA), and the light conditions (ratio of diffuse to direct solar radiation). However, such measurements are necessary to better separate the variability in SIF attributable to radiation and measurement conditions from the subtler variability attributable to plant physiological processes.

Objective Findings from adult studies suggest that tronco-conical cuffs provide more accurate blood pressure (BP) measurements in individuals with obesity. The aim of the present study was to examine differences in office blood pressure (BP) levels using conical cuffs compared to standard-shaped cylindrical cuffs in children and adolescents with obesity.Design and method We performed an observational study, including 37 children and adolescents with obesity, who were consequently recruited from the outpatient clinics of the Obesity and Cardiovascular Risk Unit at General University Hospital Consortium of Valencia. Arm circumference AC was measured in all participants, and the appropriate cuff size was selected for both conical and cylindrical cuffs.Results Mean participants’ age was 11.8[Formula: see text]2.5 years, mean BMI was 28.8[Formula: see text]3.4 kg/m2, mean BMI z-score was 2.12[Formula: see text]0.32, and mean AC was 30.0[Formula: see text]3.6 cm. There was no statistical significance in BP levels measured by cylindrical compared to conical cuffs (mean difference cylindrical-conical cuff was −0.22[Formula: see text]6.55 mmHg for SBP, −0.02[Formula: see text]0.81 for SBP z-score, −0.70[Formula: see text]4.95 mmHg for DBP, and −0.06[Formula: see text]0.44 for DBP z-score). A significant positive association was found between the measurements obtained by cylindrical and conical cuffs in both mean and z-score SBP and DBP values (p

Mg-stabilised Na-β’’-alumina solid electrolyte (Mg-BASE) for Na-ion batteries was synthesised and fabricated into 3D structures via direct ink writing (DIW), an extrusion-based additive manufacturing process. To produce a water-based ink with optimum viscoelastic properties and supreme printing quality, a comprehensive investigation of ink formulation and printing parameters was conducted. The sintered 3D structures of Mg-BASE, fabricated via direct ink writing, achieved relative density of 98.0 ± 1.1 % with β’’ phase fraction of 99.7 wt% whilst bulk ionic conductivity of 0.081 S⋅cm−1 at 350 °C was obtained. XRD results indicated that Mg-BASE fabricated via DIW may have different c-axis orientation than conventional dry-pressed pellets, leading to the improved bulk ionic conductivity.

Extensive research efforts have been devoted to using greenhouse gas CO2 in upgrading bio-derived feedstock to value-added chemicals using the oxidative dehydrogenation route (CO2-ODH) with low-energy input. To realize the effective deployment of CO2-ODH at an industrial scale, it is imperative to advance the development of robust catalysts that can selectively catalyze C-H over C-C bonds, while simultaneously demonstrating thermodynamic stability to coke formation or sintering. Transition metal-based catalysts exhibit significant potential for being highly selective and reactive in the simultaneous conversion of CO2 and hydrocarbons, owing to their surface reducibility, well-balanced acid/base properties, and dynamic oxygen storage capacity. To stimulate further optimization, it's crucial to discover key design principles, potential trends and descriptors, and effective strategies to fine-tune the catalyst materials. This review comprehensively examines experimental and theoretical research aimed at pinpointing the key catalytic characteristics that affect selectivity in transition metal-based mono, bi, and multimetal oxides. It covers aspects like combinations of active metals and supports, effects of composition and alloying, interfacial structures, adsorption strengths, dynamics of in-situ restructuring, defect creation, surface morphology, and electronic properties, among others. We wrap up by suggesting approaches to overcome present obstacles in catalyst design and reactor technology, potentially bridging the lab-to-industry gap in this domain.

Gram-negative bacteria from the Bacteroidota phylum possess a type-IX secretion system (T9SS) for protein secretion, which requires cargoes to have a C-terminal domain (CTD). Structurally analysed CTDs are from Porphyromonas gingivalis proteins RgpB, HBP35, PorU and PorZ, which share a compact immunoglobulin-like antiparallel 3+4 β-sandwich (β1–β7). This architecture is essential as a P. gingivalis strain with a single-point mutant of RgpB disrupting the interaction of the CTD with its preceding domain prevented secretion of the protein. Next, we identified the C-terminus (‘motif C-t.’) and the loop connecting strands β3 and β4 (‘motif Lβ3β4’) as conserved. We generated two strains with insertion and replacement mutants of PorU, as well as three strains with ablation and point mutants of RgpB, which revealed both motifs to be relevant for T9SS function. Furthermore, we determined the crystal structure of the CTD of mirolase, a cargo of the Tannerella forsythia T9SS, which shares the same general topology as in Porphyromonas CTDs. However, motif Lβ3β4 was not conserved. Consistently, P. gingivalis could not properly secrete a chimaeric protein with the CTD of peptidylarginine deiminase replaced with this foreign CTD. Thus, the incompatibility of the CTDs between these species prevents potential interference between their T9SSs.

This paper aims at highlighting and interpreting current empirical facets of the Greek educational pathogeny through a sociological approach. Especially, the paper tries to investigate the relationship between education and employment in modern Greece based on the annual statistical report of KANEP/GSEE, choosing both selected facets and sociologically interpreted issues such as public and private expenditure, trends on specialties, outcomes of initial training teacher's profile etc. According to this data, the main political challenge is based on both the decrease of public expenditure and the maintenance of significantly high levels of household expenditure. Additionally, current trends, such as «brain drain» or migration of highly educated people, prove that Greek public universities' learning outcomes remain competitive and effective through the framework of a global labour market, notwithstanding the harsh critique blaming them for «statism» and mismatching with the labour needs.

An attempt was made to evaluate the elongation level as a stressor on biodegradable starch films reinforced with nanoclay using a simple linear model. A total of 120 film units were subjected to increasing elongation levels and the exact break time of the failed units was monitored. Nine different attempts were made to fit the data distribution and the lognormal distribution was chosen as the most suitable because it resulted in the lowest values of the regression fit indices −2LL, AICc and BIC. Following the selection of the best fit, it was, generally, observed that an increase in the elongation level resulted in the decreasing exact break time of the films. Among several models, the best fit was provided by the simple linear model. Based on this model, the acceleration factor was estimated, and it was shown that it increased exponentially while increasing the elongation level. Finally, the probability of failure and the hazard rate of the film units as a function of the elongation level were estimated, demonstrating the applicability of this method as a tool for food packaging film failure prediction.

A destructive degradation model was applied on films made from different concentrations of starch, glycerol and nanoclay using various elongation levels as a stress variable at different stress times and stretch cycles. The log tensile quotient (logarithm of the tensile strength to the corresponding break cycle) was recorded as the response variable. The log tensile quotient increased, and the log exact break time decreased, as the elongation level increased. The treatment containing the highest starch and nanoclay and lowest glycerol content proved to be the most resistant to stress conditions and the most versatile in relation to the varying log tensile quotients, while the treatments containing the lowest nanoclay and highest glycerol contents, regardless of the starch concentration, manifested the lowest log tensile quotient at higher levels of log exact break time. According to multiple regression findings, the break cycle governed mostly the stress conditions in the degradation model, followed by the sample ID and the log exact break time. The term log tensile quotient, attempted for the first time on data concerning biodegradable films enhanced with nanoclay, seems very promising for deeper research due to its ability to retrieve predictive information from survival equations and to discriminate the difference between film structures.

The binary Fe–Ni system offers alloys with notably low linear coefficients of thermal expansion (CTE), contingent upon their Ni content. In this respect twin-wire arc additive manufacturing (T-WAAM) presents the opportunity of in-situ alloying through the simultaneous feeding of two metal wires into a weld pool to obtain desired alloy compositions. This study aims to deposit a graded wall with Ni contents targeted at 42, 46, and 52 wt% in the building direction of the wall, along with a block comprising of 46 wt% Ni, employing the T-WAAM approach. The results show effective incorporation of additional Ni into the weld pool and geometrically stable weld beads in the continuous metal transfer mode during the T-WAAM process. This mode led to the defect-free and chemically stable deposition of the graded wall and the block with average Ni contents of 42.3 ± 1.1, 45.8 ± 1.4, 52.6 ± 0.8 wt%, and 46.4 ± 0.9 wt%, respectively. The measured Curie temperatures of the as-deposited alloys and the mean CTE values of alloy 46 were found to be comparable to the commercial alloys. In summary, this study validates the feasibility of in-situ deposition of low thermal expansion alloy compositions, thereby enabling the possibility of on-demand thermal expansion properties.

Abstract We investigate a class of mass deformations that connect pairs of 2d (0, 2) gauge theories associated to different toric Calabi-Yau 4-folds. These deformations are generalizations to 2d of the well-known Klebanov-Witten deformation relating the 4d gauge theories for the ℂ2 /ℤ2 × ℂ orbifold and the conifold. We investigate various aspects of these deformations, including their connection to brane brick models and the relation between the change in the geometry and the pattern of symmetry breaking triggered by the deformation. We also explore how the volume of the Sasaki-Einstein 7-manifold at the base of the Calabi-Yau 4-fold varies under deformation, which leads us to conjecture that it quantifies the number of degrees of freedom of the gauge theory and its dependence on the RG scale.

Abstract Sensitization to Staphylococcus aureus enterotoxins A (SEA) and B (SEB) has been associated with asthma severity, exacerbations, and disease control. Our study aimed to investigate if there are differences in serum SEA-IgE and SEB-IgE levels between patients with chronic obstructive pulmonary disease (COPD), asthma, and controls, and to assess the association between SE sensitization and COPD clinical parameters and Th2 inflammation biomarkers in two well-defined COPD cohorts. Our findings suggest that COPD patients do not exhibit higher SEA and SEB sensitization compared to asthma patients and controls. However, in COPD patients, the presence of atopy and allergy is associated with positivity for SEA-IgE and SEB-IgE. Consequently, these allergens may aid in identifying atopic or allergic subgroups within the COPD population, but they are not directly associated with the diagnosis of COPD, elevated circulating blood eosinophils, or fractional exhaled nitric oxide (FENO) levels.

Evidence shows that neurodegenerative and neuropsychiatric disorders are influenced by alterations in the gut microbiome. Various diseases have been linked to microbiome dysbiosis, yet there are inconclusive data regarding which microorganisms are associated with each disorder. The aim of our study is to systematically review the recent literature of the past decade to clarify whether the gut microbiome contributes to the understanding of pathogenesis and progression of neurodegenerative disorders. Most included studies showed a strong correlation between the relative abundance of certain microorganisms, mainly species of the phyla Firmicutes and Bacteroidetes, and disorders such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). It is speculated that the microorganisms and their byproducts have a significant role in brain protein accumulation, neuro-inflammation, and gut permeability. The estimation of microbial populations could potentially improve clinical outcomes and hinder the progression of the disease. However, further research is needed to include more diseases and larger patient samples and identify specific species and subspecies associated with these disorders.

Hydroxycinnamic acids are an essential phenolic group in honey that are related with its diverse health effects. Furthermore, they can be considered as potential biomarkers for botanical and geographical origin. The extraction of hydroxycinnamic acids from honey requires complicated extraction techniques due to their low contents and matrix particularity. The goal of the present work was to develop a green sample preparation method for the solubilization of hydroxycinnamic acids in honey samples. Thus, a Box–Behnken design has been used to investigate the effect of four factors: (i) percentage of ethanol (60–90%, v/v), (ii) temperature (30–60 °C), (iii) solvent-honey ratio (10–30 mL g−1), and (iv) sonication time (10–40 min) on the contents of caffeic, chlorogenic, and ferulic acids. Based on the desirability index, the ultrasound-assisted mixing of honey with 60.0% (v/v) ethanol at a solvent-honey ratio of 10 mL g−1 for a period of 17.8 min at a temperature of 54.6 °C resulted in the maximum solubilization of hydroxycinnamates. Subsequently, the greenness of developed method was assessed and applied successfully on the analysis of honeys. The present study reports for first time the hydroxycinnamic acid fingerprint of multi-floral honey produced in Cyprus.

Verticillium dahliae (Vd) and Fusarium oxysporum f. sp. lycopersici (Fol) are two major fungal pathogens that infect tomato plants, causing significant challenges in their control since both pathogens can persist in the soil for several years even in the absence of a host plant and no effective fungicides are available at present. This study investigated the efficacy of two biocontrol formulations, Clonotri (containing Trichoderma and Clonostachys microorganisms) and Strepse (comprising Streptomyces and Pseudomonas microorganisms), against Vd and Fol and their impact on tomato fruit quality and yield under greenhouse conditions. The pathogenicity experiment demonstrated that the Clonotri formulation, containing Trichoderma and Clonostachys spores, significantly reduced Fusarium wilt disease by 32% compared to the control group. However, in the Vd pathogenicity experiment, the formulations did not exhibit disease reduction, although treatment with Strepse, containing Streptomyces and Pseudomonas microorganisms, resulted in a preserved total fruit number when compared to uninfected plants. Analysis of fruit quality attributes revealed no significant differences among the various interventions. Furthermore, Fol infection in the first fruit set significantly increased fruit firmness, while Vd infection resulted in elevated levels of total soluble solids in fruits. These findings demonstrate that the evaluated biocontrol formulations provide a degree of protection against fungal wilt pathogens in tomato plants and can increase yield in greenhouse conditions while having minimal impact on overall fruit quality attributes.

Invar alloys exhibit low thermal expansion and are useful in applications requiring dimensional stability when subject to temperature changes. Conventional production of Invar faces certain challenges that can be offset by exploiting additive manufacturing processes. This study employed pulsed gas tungsten arc welding (GTAW) to deposit Invar 36 alloy blocks at five heat inputs (HI) ranging from 200 to 550 J mm−1. The results show that the microstructure comprised of columnar grains and remained in the austenitic phase regardless of the HI. Ductility dip cracking was found to prevail in all the blocks except the block deposited at the lowest HI. The decreased susceptibility to cracking with a reduction in the HI was due to the preservation of the grain boundary area, consequently leading to an improved partitioning of strain among the grain boundaries. On lowering the HI from 550 to 200 J mm−1 the average yield strength, tensile strength and elongation improved by 16%, 23% and 38%, respectively. The HI had a negligible effect on the mean linear coefficient of thermal expansion (CTE) in different temperature ranges as the CTE values were nearly identical between the blocks deposited at 200 and 550 J mm−1. In general, the CTE in the building direction was slightly higher than the travel direction, with a maximum difference between the CTE of the two directions being 15%. In summary, this work demonstrates the application of the cold wire GTAW process as an alternative to conventional/laser based methods for realizing the functional properties of Invar.

Objectives To develop an intensive training programme for ultrasound (US)-guided synovial tissue (ST) biopsy on knees and wrists in inflammatory arthritis and to assess the learning curve, patient tolerability, sample quality and trainees’ expectations.Methods Active or remission rheumatoid arthritis patients were enrolled. Nine trainees joined the 4-month programme in a centre experienced in performing US-guided ST biopsies consisting of four sequential phases: (1) observation, (2) performance of guided step-by-step phases, (3) execution of the whole procedure on paired joints (knees or wrists) of the same patient in parallel with the trainer and (4) performance of the procedure autonomously. Sample representativity was assessed by histology, and procedure-related adverse events were recorded. Before and after the programme, trainees’ expectations and perceptions were collected.Results 328 ST biopsy procedures were included. The rate of trainees’ informative samples was: (1) comparable to the trainers in active and remission knees, but lower in active wrists (70% for trainees vs 100% for trainers, p=0.06) in phase 3; (2) excellent on active knees and wrists (91.9% and 90.9% respectively) but lower (77.6%, p=0.0089) on remission knees in phase 4. Procedures performed by trainees did not affect patient tolerability. Trainees’ expectations about procedure-related invasiveness and pain infliction decreased while the difficulty of procedure execution on active wrists and remission knees remained perceived as moderately difficult.Conclusions This intensive training programme develops advanced skills in the performance of US-guided ST biopsy on knees and wrists, yielding high-quality specimens available for basic and translational studies on inflammatory joint diseases.

An accurate estimation of vegetation gross primary productivity (GPP), which is the amount of carbon taken up by vegetation through photosynthesis for a given time and area, is critical for understanding terrestrial–atmosphere CO2 exchange processes and ecosystem functioning, as well as ecosystem responses and adaptations to climate change. Prior studies, based on ground, airborne, and satellite sun-induced chlorophyll fluorescence (SIF) observations, have recently revealed close relationships with GPP at different spatial and temporal scales and across different plant functional types (PFTs). However, questions remain regarding whether there is a unique relationship between SIF and GPP across different sites and PFTs and how we can improve GPP estimates using solely remotely sensed data. Using concurrent measurements of daily TROPOspheric Monitoring Instrument (TROPOMI) SIF (daily SIFd); daily MODIS Terra and Aqua spectral reflectance; vegetation indices (VIs, notably normalized difference vegetation index (NDVI), near-infrared reflectance of vegetation (NIRv), and photochemical reflectance index (PRI)); and daily tower-based GPP across eight major different PFTs, including mixed forests, deciduous broadleaf forests, croplands, evergreen broadleaf forests, evergreen needleleaf forests, grasslands, open shrubland, and wetlands, the strength of the relationships between tower-based GPP and SIFd at 40 Integrated Carbon Observation System (ICOS) flux sites was investigated. The synergy between SIFd and MODIS-based reflectance (R) and VIs to improve GPP estimates using a data-driven modeling approach was also evaluated. The results revealed that the strength of the hyperbolic relationship between GPP and SIFd was strongly site-specific and PFT-dependent. Furthermore, the generalized linear model (GLM), fitted between SIFd, GPP, and site and vegetation type as categorical variables, further supported this site- and PFT-dependent relationship between GPP and SIFd. Using random forest (RF) regression models with GPP as output and the aforementioned variables as predictors (R, SIFd, and VIs), this study also showed that the spectral reflectance bands (RF-R) and SIFd plus spectral reflectance (RF-SIF-R) models explained over 80 % of the seasonal and interannual variations in GPP, whereas the SIFd plus VI (RF-SIF-VI) model reproduced only 75 % of the tower-based GPP variance. In addition, the relative variable importance of predictors of GPP demonstrated that the spectral reflectance bands in the near-infrared, red, and SIFd appeared as the most influential and dominant factors determining GPP predictions, indicating the importance of canopy structure, biochemical properties, and vegetation functioning on GPP estimates. Overall, this study provides insights into understanding the strength of the relationships between GPP and SIF and the use of spectral reflectance and SIFd to improve estimates of GPP across sites and PFTs.

Abstract Human α2-macroglobulin (hα2M) is a large homotetrameric protein involved in the broad inhibition of endopeptidases. Following cleavage within a bait region, hα2M undergoes stepwise transitions from its native, expanded, highly flexible, active conformation to an induced, compact, triggered conformation. As a consequence, the peptidase is entrapped by an irreversible Venus flytrap mechanism. Given the importance of hα2M, biochemical studies galore over more than seven decades have attempted to ascertain its role, typically using authentic hα2M purified from frozen and non-frozen fresh blood plasma, and even outdated plasma. However, hα2M is sensitive once isolated and purified, and becomes heterogeneous during storage and/or freezing, raising concerns about the functional competence of frozen plasma-derived hα2M. We therefore used a combination of native and sodium dodecylsulfate polyacrylamide gel electrophoresis, affinity and ion-exchange chromatography, multi-angle laser light scattering after size-exclusion chromatography, free cysteine quantification, and peptidase inhibition assays with endopeptidases of two catalytic classes and three protein substrates, to characterize the biochemical and biophysical properties of hα2M purified ad hoc either from fresh plasma or frozen fresh plasma after thawing. We found no differences in the molecular or functional properties of the preparations, indicating that protective components in plasma maintain native hα2M in a functionally competent state despite freezing.

We investigate whether it is possible to distinguish chaotic time series from random time series using network theory. In this perspective, we selected four methods to generate graphs from time series: the natural, the horizontal, the limited penetrable horizontal visibility graph, and the phase space reconstruction method. These methods claim that the distinction of chaos from randomness is possible by studying the degree distribution of the generated graphs. We evaluated these methods by computing the results for chaotic time series from the 2D Torus Automorphisms, the chaotic Lorenz system, and a random sequence derived from the normal distribution. Although the results confirm previous studies, we found that the distinction of chaos from randomness is not generally possible in the context of the above methodologies.