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Background Waning antibody levels post-vaccination and the emergence of variants of concern (VOCs) capable of evading protective immunity have raised the need for booster vaccinations. However, which combination of coronavirus disease 2019 (COVID-19) vaccines offers the strongest immune response against the Omicron variant is unknown. Methods This randomized, participant-blinded, controlled trial assessed the reactogenicity and immunogenicity of different COVID-19 vaccine booster combinations. A total of 100 BNT162b2-vaccinated individuals were enrolled and randomized 1:1 to either homologous (BNT162b2 + BNT162b2 + BNT162b2; “BBB”) or heterologous messenger RNA (mRNA) (BNT162b2 + BNT162b2 + mRNA-1273; “BBM”) booster vaccine. The primary end point was the level of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type and VOCs at day 28. Results A total of 51 participants were allocated to BBB and 49 to BBM; 50 and 48, respectively, were analyzed for safety and immunogenicity outcomes. At day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBB (22 382 IU/mL; 95% confidence interval [CI], 18 210 to 27 517) vs BBM (29 751 IU/mL; 95% CI, 25 281 to 35 011; P = .034) as was the median level of neutralizing antibodies: BBB 99.0% (interquartile range [IQR], 97.9% to 99.3%) vs BBM 99.3% (IQR, 98.8% to 99.5%; P = .021). On subgroup analysis, significant higher mean spike antibody titer, median surrogate neutralizing antibody level against all VOCs, and live Omicron neutralization titer were observed only in older adults receiving BBM. Both vaccines were well tolerated. Conclusions Heterologous mRNA-1273 booster vaccination compared with homologous BNT123b2 induced a stronger neutralizing response against the Omicron variant in older individuals. Clinical Trials Registration NCT05142319.

OBJECTIVE: To investigate the expectations of patients for total knee arthroplasty (TKA), and to analyze its influencing factors. METHODS: Experimental design: Single center, retrospective, multiple regression analysis. The data including the age, height, and weight of 108 patients undergoing unilateral TKA due to end-stage osteoarthritis were obtained. The patients' preoperative Hospital for Special Surgery (HSS) knee arthroplasty expectation score, the Western Ontario and McMaster Universities (WOMAC) score, Knee Society score (KSS), the MOS 36-item short-from health survey (SF-36) score, and visual analogue scale (VAS) were evaluated, and the 30-second chair-stand test (30-CST), 40-meter fast-paced walk test (40-FPWT), 12-level stair-climb test (12-SCT), 3-meter timed up-and-go test (TUG), 6-minute walk test (6-MWT), and recorded daily steps for 7 consecutive days were performed. The SPSS 22.0 software was used for statistical analysis. The observed values of various data were described. Pearson correlation analysis was used to evaluate the correlation between various parameters, and the multi-factor linear regression analysis was used to investigate the influencing factors of the patients preoperative expectation scores. RESULTS: The average expectation score of this group of patients was 58.98±5.44. In the Pearson correlation analysis, the patient's preoperative expectation had a weak correlation to the result of the patient's 12-SCT, TUG, 6-MWT, KSS function score, and SF-36 mental component score (correlation coefficient 0.1-0.3). The patient's preoperative expectation had a moderate correlation to the patient's daily average steps, 30-CST, 40-FPWT, KSS, WOMAC and its pain, stiffness, function scores, SF-36 physical functioning, role-physical, bodily pain, vitality, and physical component score (correlation coefficient 0.3-0.6). In the multivariate linear regression analysis, only the results of 30-CST and the role-physical, bodily pain and vitality in the SF-36 scale were related to the patient's expectation score (P < 0.05). CONCLUSION: The estimated expectation score of patients before TKA is not high. Patients with more severe preoperative pain, worse physical function, and lower overall health are more eager to improve after surgery. Thus surgeons must communicate fully with patients with unrealistic expectations before surgery in order to obtain more satisfactory results postoperatively.

The developing technology on innovative touchscreen applied in the cockpit can integrate control inputs and outputs on the same display in flight operations. Flight systems could be updated by modifying the touchscreen user interface without the complicated processes on reconfiguring cockpit panels. There is a potential risk on touchscreen components constrained by the issues associated with inadvertent touch, which may be defined as any system detectable touch issued to the touch sensors without the pilot’s operational consent. Pilots’ visual behaviours can be explored by using eye trackers to analyze the relationship between eye scan patterns and attention shifts while conducting monitoring tasks in flight operations. This research aims to evaluate human-computer interactions using eye tracker to investigate the safety concerns on implementation of touchscreen in flight operations. The scenario was set to conduct an instrument landing on the final approach using future system simulator. Participants were required to interact with all the control surfaces and checklists using the touchscreens located on different areas in the cockpit. Each participant performed landing scenario as pilot-flying (PF) and pilot-monitoring (PM) in random sequence. Currently PF and PM perform different tasks related to control inputs and control outputs monitoring in the flight deck. The PF’s primary obligation is to fly the aircraft’s flight path, and the PM’s main responsibility is to monitor the aircraft’s flight path and cross-check to the PF’s operational behaviours. By analyzing participants’ visual behaviours and scanning patterns, the findings on HCI related to applying touchscreen for future flight deck design would be applicable. There are some benefits on the implementation touchscreen for future flight deck design if the human-centred design principle can be integrated in the early stage.

The evolution of gamma-secretase modulators (GSMs) through the introduction of novel heterocycles with the goal of aligning activity for reducing the levels of Aβ42 and properties consistent with a drug-like molecule are described. The insertion of a methoxypyridine motif within the tetracyclic scaffold provided compounds with improved activity for arresting Aβ42 production as well as improved properties, including solubility. In vivo pharmacokinetic analysis demonstrated that several compounds within the novel series were capable of crossing the BBB and accessing the therapeutic target. Treatment with methoxypyridine-derived compound 64 reduced Aβ42 levels in the plasma of J20 mice, in addition to reducing Aβ42 levels in the plasma and brain of Tg2576 mice.

International audience; With the most recent releases of MD-JEEP, new relevant features have been included to our software tool. MD-JEEP solves instances of the class of Discretizable Distance Geometry Problems (DDGPs), which ask to find possible realizations, in a Euclidean space, of a simple weighted undirected graph for which distance constraints between vertices are given, and for which a discretization of the search space can be supplied. Since its version 0.3.0, MD-JEEP is able to deal with instances containing interval data. We focus in this short paper on the most recent release MD-JEEP 0.3.2: among the new implemented features, we will focus our attention on three features: (i) an improved procedure for the generation and update of the boxes used in the coarse-grained representation (necessary to deal with instances containing interval data); (ii) a new procedure for the selection of the so-called discretization vertices (necessary to perform the discretization of the search space); (iii) the implementation of a general parser which allows the user to easily load DDGP instances in a given specified format. The source code of MD-JEEP 0.3.2 is available on GitHub, where the reader can find all additional details about the implementation of such new features, as well as verify the effectiveness of such features by comparing MD-JEEP 0.3.2 with its previous releases.

The hail day climatology from 1961 to 2005 was previously studied based on hundreds of surface stations in China. Recently, both hail occurrence and maximum hail diameter (MHD) data from more than 2000 surface stations were released by the National Meteorological Information Center of China. These data enable hail climatology to be explored using both hail frequency (HF), which is defined as annual mean hail occurrence, and MHD records from more stations over the entire country. Following quality control, hail data from 2254 stations were selected for the period of 1980–2015. In general, HF increased with station topography height, with a maximum of more than 30 events per year in the Tibetan Plateau and a minimum of less than 1 event per year in southern China, whereas the station mean MHD decreased with topography height. The highest peak of the 80th-percentile cumulative distribution function of the annual MHD cycle in southern China occurred in May but was delayed to July in the north. Severe hail (MHD ≥ 20 mm; 5.32% of all cases) mainly occurred along the edge of the plain, near the mountainsides, and was most likely to develop in the afternoon.

The Bomanins (Boms) are a family of a dozen secreted peptides that mediate the innate immune response governed by the Drosophila Toll receptor. We recently showed that deleting a cluster of 10 Bom genes blocks Toll-mediated defenses against a range of fungi and gram-positive bacteria. Here, we characterize the activity of individual Bom family members. We provide evidence that the Boms overlap in function and that a single Bom gene encoding a mature peptide of just 16 amino acids can act largely or entirely independent of other family members to provide phenotypic rescue in vivo. We further demonstrate that the Boms function in Drosophila humoral immunity, mediating the killing of the fungal pathogen Candida glabrata in an in vitro assay of cell-free hemolymph. In addition, we find that the level of antifungal activity both in vivo and in vitro is linked to the level of Bom gene expression. Although Toll dictates expression of the antimicrobial peptides (AMPs) drosomycin and metchnikowin, we find no evidence that Boms act by modifying the expression of the mature forms of these antifungal AMPs.

Subchondral bone has been identified as an attractive target for KOA. To determine whether a minimally invasive micro-scaffolds could be used to induce regeneration of knee subchondral bone lesions, and to examine the protective effect of subchondral bone regeneration on upper cartilage, a ready-to-use injectable treatment with nanohydroxyapatite-chitosan-gelatin micro-scaffolds (HaCGMs) is proposed. Human-infrapatellar-fat-pad-derived adipose stem cells (IPFP-ASCs) were used as a cellular model to examine the osteo-inductivity and biocompatibility of HaCGMs, which were feasibly obtained with potency for multi-potential differentiations. Furthermore, a subchondral bone lesion model was developed to mimic the necrotic region removing performed by surgeons before sequestrectomy. HaCGMs were injected into the model to induce regeneration of subchondral bone. HaCGMs exhibited desirable swelling ratios, porosity, stiffness, and bioactivity and allowed cellular infiltration. Eight weeks after treatment, assessment via X-ray imaging, micro-CT imaging, and histological analysis revealed that rabbits treated with HaCGMs had better subchondral bone regeneration than those not treated. Interestingly, rabbits in the HaCGM treatment group also exhibited improved reservation of upper cartilage compared to those in other groups, as shown by safranin O-fast green staining. Present study provides an in-depth demonstration of injectable HaCGM-based regenerative therapy, which may provide an attractive alternative strategy for treating KOA.

The response of hailstorm intensity to climate variability/change has become a topic of community interest recently. But the lack of persistent and homogenous observations makes it difficult to confidently describe its interannual variations. Hail size, as a common indicator of hailstorm intensity, displays distinct regional variability. Here, for the first time, we show robust evidence of a decrease in hail size using continuous and coherent hail size records from 2,254 manned stations in China since 1980. The stations were categorized based on their elevation: plateaus (above 2000 m), foothills (between 500 and 2000 m), and plains (below 500 m). Compared with 1980–1997, the hail size spectra from 1998 to 2015 all shifted toward smaller sizes significantly in plateaus, foothills, and plains. The proportion of overall hail events with maximum sizes of at least 5 and 20 mm significantly decreased since 1980. Meanwhile, the annual mean size of hail above 10 and 20 mm significantly decreased during the research period, especially after 1990. These changes in the hail size spectra may imply a weakened intensity of hailstorms in China in recent decades.

Natural hailstones were collected and analyzed in the laboratory not only for their physical properties (e.g., structure, density, shape, and air bubbles), but also for their chemical properties (e.g., organic particles, biological particles, and water-soluble ions), which can help a clear understanding on microphysics and development of hailstorms. Aerosol particles were carried up from the atmospheric boundary layer to the free atmosphere into the cloud base by updrafts, and could be scavenged into cloud water droplets and ice particles to act as cloud condensation nuclei (CCN) and ice nuclei (IN), further affecting hailstones formation. Interactions between aerosols and hailstones have been studied usually by models, because it is difficult to study the processes involved in this interaction in deep convective storms using instruments in the laboratory.Water-soluble particles, which can initiate the liquid phase much more effectively than insoluble particles can, have been less well studied in hailstones. This is particularly true in comparison with the number of studies undertaken to determine the levels of surface pollution. Understanding the role of these water-soluble matters in hailstorm is of great significance but remains a lack of evidence that what kind of particles could be scavenged by hailstone, including nucleation scavenging and impaction scavenging.

The Distance Geometry Problem (DGP) asks whether a simple weighted undirected graph can be realized in a given space (generally Euclidean) so that a given set of distance constraints (associated to the edges of the graph) is satisfied. The Discretizable DGP (DDGP) represents a subclass of instances where the search space can be reduced to a discrete domain having the structure of a tree. In the ideal case where all distances are precise, the tree is binary and one singleton, representing one possible position for a vertex of the graph, is associated to every tree node. When the distance information is however not precise, the uncertainty on the distance values implies that a three-dimensional region of the search space needs to be assigned to some nodes of the tree. By using a recently proposed coarse-grained representation for DDGP solutions, we extend in this work the branch-and-prune (BP) algorithm so that it can efficiently perform an exhaustive search of the search domain, even when the uncertainty on the distances is important. Instead of associating singletons to nodes, we consider a pair consisting of a box and of a most-likely position for the vertex in this box. Initial estimations of the vertex positions in every box can be subsequently refined by using local optimization. The aim of this paper is two-fold: (i) we propose a new simple method for the computation of the three-dimensional boxes to be associated to the nodes of the search tree; (ii) we introduce the resolution parameter ρ, with the aim of controling the similarity between pairs of solutions in the solution set. Some initial computational experiments show that our algorithm extension, differently from previously proposed variants of the BP algorithm, is actually able to terminate the enumeration of the solution set by providing solutions that dilrer from one another accordingly to the given resolution parameter.

Transition metal oxides show great potential as electrocatalysts, owing to the low cost and rich chemical states. However, the limited surface areas, low intrinsic activity and poor hydrogen evolution reaction (HER) activity greatly restrict the application for overall water splitting. Herein, we have constructed S doped NiCo

Recently, long non-coding ribonucleic acids (lncRNAs) have attracted more attention for their roles in tumor progression. The aim of this study was to investigate the exact role of lncRNA MIAT in the progression of non-small cell lung cancer (NSCLC) and to explore the possible underlying mechanism.MIAT expression in NSCLC tissue samples was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The association between the expression of MIAT and the prognosis of NSCLC patients were explored. Furthermore, the wound healing assay and the transwell assay were conducted in vitro. In addition, the luciferase assay and the RNA immunoprecipitation assay (RIP) were used to elucidate the underlying mechanism.The MIAT expression in NSCLC tissues was significantly higher than that of the corresponding normal tissues. Meanwhile, the MIAT expression was associated with the overall survival time of NSCLC patients. The migration and invasion of cells were significantly promoted after MIAT was over-expressed in vitro. Meanwhile, the cell migration and cell invasion were obviously remarkedly inhibited after MIAT knock-down in vitro. Bioinformatics analysis predicted that microRNA-1246 (miR-1246) was as a novel target for MIAT. The expression of miR-1246 was significantly down-regulated or up-regulated after the overexpression or down-expression of MIAT, respectively. Further mechanism assays showed that miR-1246 was a direct target of MIAT in NSCLC.MIAT enhanced the NSCLC cell migration and invasion via targeting miR-1246, which might be a potential biomarker in NSCLC.

International audience; Given a set of points in a Euclidean space having dimension K > 0, we are interested in the problem of finding a realization of the same set in a Euclidean space having a lower dimension. In most situations, it is not possible to preserve all available interpoint distances in the new space, so that the best possible realization, which gives the minimal error on the distances, needs to be searched. This problem is known in the scientific literature as the Multidimensional Scaling (MDS). We propose a new methodology to discretize the search space of MDS instances, with the aim of performing an efficient enumeration of their solution sets. Some preliminary computational experiments on a set of artificially generated instances are presented. We conclude our paper with some future research directions.

To lower the risks of the real ship test of the cylinder oil of large marine low-speed two-stroke marine diesel engine, A 6S50ME marine diesel engine was selected to do bench test about cylinder oil. In the calibration condition, the test cylinder oil and the reference cylinder oil were compared. The test results show that the wear amount of cylinder liners, piston rings and piston-ring-grooves is consistent with the wear condition judged by the metal element content detected by the residual oil of the cylinder. At the same time, combined with the evaluation result of the detergency and dispersibility of the cylinder oil, it can effectively judge whether the oil product can be tested on the ship. Since wear volume of element Cr and Fe tends to the stabilization after 60 hours, so it is feasible to set the diesel engine bench test at 100 hours. In addition, special attention should be paid to the control of water outlet temperature and exhaust gas temperature in the test. The cylinder oil evaluated in the above way meets the requirements of OEM after the actual ship test. Thus, the assessment method of cylinder oil based on the bench test is feasible, and can greatly shorten the test time and reduce the test cost.

Based on the state-of-the art methods of gas turbine cascade heat transfer assessment, a theoretical model of the two-dimensional air turbine cascade is proposed, wherein gas flows past the turbine blade profile. The velocity, temperature, and pressure fields, as well as the heat transfer distribution along the pressure and suction surfaces, the leading and trailing edges of the turbine blade were computed via FLUENT software at different pressure ratios. This permitted of studying the heat transfer evolution at different pressure ratios in the same position and at the same pressure ratio in different positions. На основе разработанных методов оценки теплопередачи газовой ступени турбины предложенатеоретическая модель двухмерной ступени аэротурбины, в которой газ течет мимо контура лопасти турбины. Поля скоростей, температур и давлений, а также распределениекоэффициента теплопередачи вдоль поверхностей давления и разрежения, передней и задней кромок лопасти турбины рассчитывались с помощью программы FLUENT при разном отношении давлений. Это позволило исследовать эволюцию коэффициента теплопередачи при различном отношении давлений в одинаковом положении и при одинаковом отношении давлений в различных положениях. На основі розроблених методів оцінки теплопередачі газової ступені турбіни запропонована теоретична модель двомірної ступені аеротурбіни, в якій газ тече повз контуру лопаті турбіни. Поля швидкостей, температур і тисків, а також розподіл коефіцієнта теплопередачі вздовж поверхонь тиску і розрідження, передній і задній крайок лопаті турбіни розраховувалися за допомогою програми FLUENT при різному співвідношення тисків. Це дало змогу дослідити еволюцію коефіцієнта теплопередачі при різному ставленні тисків в однаковому становищі і при однаковому ставленні тисків в різних положеннях.

Summary Purpose (1) To identify bone-shape changes from baseline to 3-years after anterior cruciate ligament reconstruction (ACLR). (2) to assess association between changes in bone-shape from baseline to 6-months and changes in cartilage matrix and patient functions and symptoms from baseline to 3-years after ACLR. Methods Bilateral knees of 30 patients with unilateral ACL injuries were scanned at baseline, 6-months, 1-, 2-, and 3-years after ACLR. Bilateral knees of 13 controls were scanned at baseline, 1- and 3-years. Mean T1ρ and T2 values of each cartilage compartment were computed. Bone shape was quantified using statistical shape modeling (SSM) and 3D-MRI. Patient functions and symptoms were evaluated using Knee Injury and Osteoarthritis Outcome Score (KOOS). Results Statistically significant changes were observed in Femur 2 (medial femoral condyle [MF] shape), Femur 6 (intercondylar notch width), Tibia 1 (tibia plateau area), and Tibia 7 (medial tibia slope) over 3-years after ACLR. Statistically significant differences were observed between injured and control knees in several modes. Statistically significant correlations were found between changes in bone shape (ΔFemur 6, ΔFemur 8 [trochlea inclination and MF height], ΔTibia 1) from baseline to 6-months and that of cartilage T1ρ and T2 and KOOS from baseline to 3-years after ACLR. Conclusion Bone shape remodeling occurs after ACLR, and early bone shape changes (within 6 months) correlated with cartilage matrix and patient outcomes at 3-years after ACLR. Bone shape can be a promising imaging biomarker that stratifies patients at high risk for post-traumatic osteoarthritis (PTOA).