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Abstract Chalcogenide phase-change materials (PCMs) are showing versatile possibilities in cutting-edge applications, including non-volatile memory, neuromorphic computing, and nano-photonics. However, for embedded phase-change memory applications, conventional PCMs suffer from insufficient thermal stability because of their relatively low crystallization temperatures (T x). Although doping with additional alloying elements could improve the amorphous stability, it also increases the tendency towards compositional partitioning and phase separation. Recently, a two-dimensional (2D) layered compound CrGeTe3 (CrGT) was developed as a PCM, showing a high T x ~ 276 °C with an inverse change in resistive-switching character upon phase transition. Here, we report a high-throughput materials screening for 2D layered phase-change chalcogenides. We aim to clarify whether the high T x and the inverse electrical resistance contrast are intrinsic features of 2D PCMs. In total, twenty-five 2D chalcogenides with CrGT trilayer structures have been identified from a large database. We then focused on selected layered tellurides by performing thorough ab initio simulations and experimental investigations and confirming that their amorphous phase indeed has a much higher T x than conventional PCMs. We attribute this enhanced amorphous stability to the structurally complex nuclei required to render crystallization possible. Overall, we regard InGeTe3 as a balanced 2D PCM with both high thermal stability and large electrical contrast for embedded memory applications.

The intestinal microbiota and its metabolites are essential for the health and growth development of animals. Current research indicates that sex has a certain impact on the structure and function of the intestinal microbiota, but there are few reports on sex differences in intestinal microbiota metabolites, including those of castrated male animals. This study aimed to explore the impact of sex on the intestinal microbial metabolites of Hainan special wild boars (10 entire male pigs, 10 female pigs, and 10 castrated male pigs, denoted EM, FE, and CM, respectively) by employing non-targeted metabolomics and gas chromatography. A total of 1086 metabolites were detected, with the greatest number of differential metabolites observed between EM and FE (54 differential metabolites, including 18 upregulated and 36 downregulated metabolites), the fewest between CM and FE (7 differential metabolites, including 1 upregulated and 6 downregulated metabolites), and an intermediate number between CM and EM (47 differential metabolites, including 35 upregulated and 12 downregulated metabolites). Differential metabolites were involved in more pathways between EM and FE and between CM and EM, including amino acid metabolism and digestive system pathways, whereas differential metabolites were involved in the fewest pathways between CM and FE. Correlation analysis showed Ruminococcaceae UCG-009, uncultured_bacterium_o_SAR324_cladeMarine_group_B, and Candidatus Saccharimonas contributed to the production of metabolites such as trehalose, docosatrienoic acid, D(−)-beta-hydroxy butyric acid, and acetyl-DL-leucine. The levels of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid were significantly higher in EM than in FE, with CM falling between the two. Streptococcus, Lachnospiraceae_NK4A136_group and Rikenellaceae_RC9_gut_group showed a significant positive correlation with the production of short-chain fatty acids (SCFAs), while [Eubacterium]_coprostanoligenes_group, uncultured_bacterium_f_p–251–o5 and Ruminococcaceae_UCG–005 showed a significant negative correlation with the generation of SCFAs. This study provides foundational data and significant insights into precision feeding strategies for Hainan special wild boars of different sexes, as well as the study of sex differences in intestinal microbial metabolites in animals.

Hypersonic vehicles are susceptible to considerable aerodynamic heating and noticeable aerothermoelastic effects during flight due to their high speeds. Functionally graded materials (FGMs), which enable continuous changes in material properties by varying the ratio of different materials, provide both thermal protection and load-bearing capabilities. Therefore, they are widely used in thermal protection structures for hypersonic vehicles. In this work, the aerothermoelastic behaviors of functionally graded (FG) plates under arbitrary temperature fields are analyzed via a semianalytical method. This research develops a method considering the influence of thermal loading, specifically the decrease in stiffness due to thermal stresses, as well as the correlation between material properties and temperatures under arbitrary temperature fields, based on Ritz’s method. The classical plate theory, von–Karman’s large defection plate theory and piston theory are employed to formulate the strain energy, kinetic energy and external work functions of the system. This paper presents a novel analysis of static aerothermoelasticity of FG plates, in addition to the linear/nonlinear flutter under arbitrary temperature fields, such as uniform, linear and nonlinear temperature fields. In addition, the effects of the volume fraction index, dynamic pressure, and temperature increase on the aerothermoelastic characteristics of FG plates are analyzed.

The analysis of flight loads during symmetric aircraft maneuvers is an essential but computationally intensive task in aircraft design. The significant structural elastic deformation in modern aircraft further complicates this work, adding to the computational demands. Therefore, improving the analysis efficiency of flight loads during maneuvers is crucial for accelerating design interactions and shortening the development cycle. This study explores a method for analyzing flight loads in the time domain during maneuvers of elastic aircraft by introducing a database of high-precision rigid-body aerodynamic loads. Furthermore, it combines the gradient-enhanced Kriging model to efficiently predict elastic flight loads during longitudinal maneuvers. The results indicate that the proposed surrogate-based method has high fitting accuracy with significantly improved computational efficiency, providing a new approach for efficient analysis of flight loads during aircraft maneuvers.

Automatic generation control (AGC) plays a crucial role in frequency control and economic dispatch of electric power systems. However, AGC systems, relying heavily on frequency and tie-line power measurements, are vulnerable to cyber-attacks. A novel false data injection attack (FDIA) algorithm targeting AGC is proposed, which requires no model information and parameter values. To this end, we first derive the maximum likelihood estimation of the multivariate Ornstein-Uhlenbeck (OU) process, based on which AGC parameters, topology information, and the conditional variance of states can be extracted purely from eavesdropped sensor data (frequency, tie-line power, reference power). Then we will exploit the extracted information to design FDIA vectors by solving an optimization problem, which can bypass conventional AGC defense mechanisms. Numerical studies in 2-area and 3-area systems show that the proposed FDIA algorithm can deteriorate the system’s frequency within several minutes when measurement noise, transmission delay, and computational time are considered.

Abstract Background The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads rapidly and insidiously. Coronavirus disease 2019 (COVID-19) screening is an important means of blocking community transmission in China, but the costs associated with testing are high. Quarantine capacity and medical resources are also threatened. Therefore, we aimed to evaluate different screening strategies to balance outbreak control and consumption of resources. Methods A community network of 2000 people, considering the heterogeneities of household size and age structure, was generated to reflect real contact networks, and a stochastic individual-based dynamic model was used to simulate SARS-CoV-2 transmission and assess different whole-area nucleic acid screening strategies. We designed a total of 87 screening strategies with different sampling methods, frequencies of screening, and timings of screening. The performance of these strategies was comprehensively evaluated by comparing the cumulative infection rates, the number of tests, and the quarantine capacity and consumption of medical resource, which were expressed as medians (95% uncertainty intervals, 95% UIs). Results To implement COVID-19 nucleic acid testing for all people (Full Screening), if the screening frequency was four times/week, the cumulative infection rate could be reduced to 13% (95% UI: 1%, 51%), the miss rate decreased to 2% (95% UI: 0%, 22%), and the quarantine and medical resource consumption was lower than higher-frequency Full Screening or sampling screening. When the frequency of Full Screening increased from five to seven times/week (which resulted in a 2581 increase in the number of tests per positive case), the cumulative infection rate was only reduced by 2%. Screening all people weekly by splitting them equally into seven batches could reduce infection rates by 73% compared to once per week, which was similar to Full Screening four times/week. Full Screening had the highest number of tests per positive case, while the miss rate, number of tests per positive case, and hotel quarantine resource consumption in Household-based Sampling Screening scenarios were lower than Random Sampling Screening. The cumulative infection rate of Household-based Sampling Screening or Random Sampling Screening seven times/week was similar to that of Full Screening four times/week. Conclusions If hotel quarantine, hospital and shelter hospital capacity are seriously insufficient, to stop the spread of the virus as early as possible, high-frequency Full Screening would be necessary, but intermediate testing frequency may be more cost-effective in non-extreme situations. Screening in batches is recommended if the testing capacity is low. Household-based Sampling Screening is potentially a promising strategy to implement. Graphical Abstract

Abstract The layered crystal structure of Cr2Ge2Te6 shows ferromagnetic ordering at the two‐dimensional limit, which holds promise for spintronic applications. However, external voltage pulses can trigger amorphization of the material in nanoscale electronic devices, and it is unclear whether the loss of structural ordering leads to a change in magnetic properties. Here, it is demonstrated that Cr2Ge2Te6 preserves the spin‐polarized nature in the amorphous phase, but undergoes a magnetic transition to a spin glass state below 20 K. Quantum‐mechanical computations reveal the microscopic origin of this transition in spin configuration: it is due to strong distortions of the CrTeCr bonds, connecting chromium‐centered octahedra, and to the overall increase in disorder upon amorphization. The tunable magnetic properties of Cr2Ge2Te6 can be exploited for multifunctional, magnetic phase‐change devices that switch between crystalline and amorphous states.

Abstract Background The continuous mutation of severe acute respiratory syndrome coronavirus 2 has made the coronavirus disease 2019 (COVID-19) pandemic complicated to predict and posed a severe challenge to the Beijing 2022 Winter Olympics and Winter Paralympics held in February and March 2022. Methods During the preparations for the Beijing 2022 Winter Olympics, we established a dynamic model with pulse detection and isolation effect to evaluate the effect of epidemic prevention and control measures such as entry policies, contact reduction, nucleic acid testing, tracking, isolation, and health monitoring in a closed-loop management environment, by simulating the transmission dynamics in assumed scenarios. We also compared the importance of each parameter in the combination of intervention measures through sensitivity analysis. Results At the assumed baseline levels, the peak of the epidemic reached on the 57th day. During the simulation period (100 days), 13,382 people infected COVID-19. The mean and peak values of hospitalized cases were 2650 and 6746, respectively. The simulation and sensitivity analysis showed that: (1) the most important measures to stop COVID-19 transmission during the event were daily nucleic acid testing, reducing contact among people, and daily health monitoring, with cumulative infections at 0.04%, 0.14%, and 14.92% of baseline levels, respectively (2) strictly implementing the entry policy and reducing the number of cases entering the closed-loop system could delay the peak of the epidemic by 9 days and provide time for medical resources to be mobilized; (3) the risk of environmental transmission was low. Conclusions Comprehensive measures under certain scenarios such as reducing contact, nucleic acid testing, health monitoring, and timely tracking and isolation could effectively prevent virus transmission. Our research results provided an important reference for formulating prevention and control measures during the Winter Olympics, and no epidemic spread in the closed-loop during the games indirectly proved the rationality of our research results. Graphical Abstract

Background In preclinical studies, combining M9241 (a novel immunocytokine containing interleukin (IL)-12 heterodimers) with avelumab (anti-programmed death ligand 1 antibody) resulted in additive or synergistic antitumor effects. We report dose-escalation and dose-expansion results from the phase Ib JAVELIN IL-12 trial investigating M9241 plus avelumab.Methods In the dose-escalation part of JAVELIN IL-12 (NCT02994953), eligible patients had locally advanced or metastatic solid tumors; in the dose-expansion part, eligible patients had locally advanced or metastatic urothelial carcinoma (UC) that had progressed with first-line therapy. Patients received M9241 at 4, 8, 12, or 16.8 µg/kg every 4 weeks (Q4W) plus avelumab 10 mg/kg every 2 weeks (Q2W, dose levels (DLs) 1–4) or M9241 16.8 µg/kg Q4W plus avelumab 800 mg once a week for 12 weeks followed by Q2W (DL5/dose expansion). Primary endpoints for the dose-escalation part were adverse events (AEs) and dose-limiting toxicities (DLTs), and those for the dose-expansion part were confirmed best overall response (BOR) per investigator (Response Evaluation Criteria in Solid Tumors V.1.1) and safety. The dose-expansion part followed a two-stage design; 16 patients were enrolled and treated in stage 1 (single-arm part). A futility analysis based on BOR was planned to determine whether stage 2 (randomized controlled part) would be initiated.Results At data cut-off, 36 patients had received M9241 plus avelumab in the dose-escalation part. All DLs were well tolerated; one DLT occurred at DL3 (grade 3 autoimmune hepatitis). The maximum-tolerated dose was not reached, and DL5 was declared the recommended phase II dose, considering an observed drug–drug interaction at DL4. Two patients with advanced bladder cancer (DL2 and DL4) had prolonged complete responses. In the dose-expansion part, no objective responses were recorded in the 16 patients with advanced UC; the study failed to meet the criterion (≥3 confirmed objective responses) to initiate stage 2. Any-grade treatment-related AEs occurred in 15 patients (93.8%), including grade ≥3 in 8 (50.0%); no treatment-related deaths occurred. Exposures for avelumab and M9241 concentrations were within expected ranges.Conclusions M9241 plus avelumab was well tolerated at all DLs, including the dose-expansion part, with no new safety signals. However, the dose-expansion part did not meet the predefined efficacy criterion to proceed to stage 2.

Abstract Metavalent bonding (MVB) is characterized by the competition between electron delocalization as in metallic bonding and electron localization as in covalent or ionic bonding, serving as an essential ingredient in phase‐change materials for advanced memory applications. The crystalline phase‐change materials exhibits MVB, which stems from the highly aligned p orbitals and results in large dielectric constants. Breaking the alignment of these chemical bonds leads to a drastic reduction in dielectric constants. In this work, it is clarified how MVB develops across the so‐called van der Waals‐like gaps in layered Sb2Te3 and Ge–Sb–Te alloys, where coupling of p orbitals is significantly reduced. A type of extended defect involving such gaps in thin films of trigonal Sb2Te3 is identified by atomic imaging experiments and ab initio simulations. It is shown that this defect has an impact on the structural and optical properties, which is consistent with the presence of non‐negligible electron sharing in the gaps. Furthermore, the degree of MVB across the gaps is tailored by applying uniaxial strain, which results in a large variation of dielectric function and reflectivity in the trigonal phase. At last, design strategies are provided for applications utilizing the trigonal phase.

Microstructured materials, characterized by their lower weight and multifunctionality, have great application prospects in the aerospace field. Optimization methods play a pivotal role in enhancing the design efficiency of both macrostructural and microstructural topology (MMT) for aircraft. This paper proposes a multiscale aeroelastic optimization method for wing structure and material considering realistic aerodynamic loads for large aspect ratio wings with significant aeroelastic effects. The aerodynamic forces are calculated by potential flow theory and the aeroelastic equilibrium equations are solved through finite element method. The parallel design of the wing MMT is achieved by utilizing the optimization criterion (OC) method based on sensitivity information. The optimization results indicate that wing elastic effects reinforce the outer section of the wing structure compared with the optimization results obtained under rigid aerodynamic forces. As the optimization constraints become more rigorous, the optimization results show that the components with larger loads are strengthened. Furthermore, the method presented in this paper can effectively optimize the wing structure under complex boundary conditions to achieve a reasonable stiffness distribution in the wing.

In enzyme-like catalytic reactions, the size effect of nanoparticles has been an essential yet unclear factor for the catalytic activity of nanozymes. Moreover, the synthesis of nanozymes with controllable size and electronic structures represents a grand challenge, which limits the systemic exploration the underlying nature of their structure–property relations and practical application. In this work, we proposed a novel strategy to regulate the size of Pt (0.55 ∼ 2.81 nm) by atomic layer deposition for precisely tailoring Pt-based nanozymes. The size-dependent electronic and kinetic effects have been observed for the peroxidase-like reaction and antibacterial process, revealing a volcano-type dependence of intrinsic activity on Pt nanoparticle sizes, and the optimum Pt nanoparticle size was found to be ca. 1.69 nm. A combination of kinetic study and XPS analyses, as well as multiple nanozyme characterizations, demonstrates that Pt nanoparticles with an appropriate size contribute to proper affinity to the substrates, relating to a high ratio of Pt0/Pt2+ on the surface of Pt nanoparticles, which is beneficial to obtain the excellent catalytic performance and antibacterial activity. Our work provides insights for an in-depth understanding size-dependent catalytic mechanism of nanozymes during antibacterial processes.

Abstract To ensure reasonable reactive power distribution and voltage standard, a large number of STATCOMs are integrated to wind farms and afflux stations. However, the issue of device tripping caused by the interaction between STATCOMs is emerging. This paper sets out to bring a clear understanding of the fault mechanism of single STATCOM tripping caused by the harmonic circulation between STATCOMs in a clustered wind‐farm afflux station in North‐China grid. The equivalent circuit of harmonic circulation between two paralleled STATCOMs based on cascaded H‐bridge topology is established first. Thereafter, the intrinsic relationship between high‐order harmonic circulation and inter‐converter harmonic voltage difference as well as the phase deviation of SPWM carriers are analysed. A generalized model is also built to estimate the higher‐order harmonics. The impact of non‐characteristic harmonics on DC voltage of each H‐bridge cell is investigated by calculating the difference of active power flowing through DC capacitors. It is pointed out that the harmonic circulation is one of the main reasons resulting in the DC overvoltage protection action of STATCOM. Finally, the correctness of theoretical analysis is verified by real‐time simulation and hardware experiments.

Abstract Background Dental caries is the most prevalent condition globally. Despite improvements over the past few decades, there remains a significant disease burden in childhood. Epidemiological surveys provide insight to disease patterns and trends, and have traditionally focused on obvious decay which are inconsistent with contemporary clinical criteria. This study examined the distribution of dental caries in 12- and 15-year-olds in England, Wales and Northern Ireland, by severity threshold, at surface, tooth and child level and explored its association with socioeconomic, psychological and behavioural factors. Methods Data from 12- and 15-year-olds in the 2013 Children’s Dental Health Survey (CDHS 2013) were analysed at three levels, taking account of dental caries thresholds which involved recording both clinical decay [visual enamel caries (AV) and above] and obvious decay [non-cavitated dentine lesions (2V) and above]. Negative binomial regression was used to identify factors associated with dental caries experience at both thresholds. Results The prevalence and severity of dental caries experience was higher among 15-year-olds at all levels. Visual change in enamel (AV) was by far the most common stage of caries recorded in both ages. The average number of surfaces with obvious decay experience, which has been the traditional epidemiological threshold, in 12- and 15-year-olds was 2.3 and 3.9 respectively. The corresponding values under the clinical decay threshold were higher, at 3.9 and 5.9 respectively. Visualisation of the distribution of dental caries at surface/tooth-level exhibited horizontal symmetry and to a lesser extent vertical symetry. In the adjusted models for both ages, country/region, school type, area deprivation, high frequency sugar consumption and irregular dental attendance were associated with greater caries experience in both groups. Dental anxiety was inversely associated with caries experience among 15-year-olds. Conclusion This research highlights the importance of recognising dental caries patterns by surface, tooth and child-level amongst adolescents and the value of reporting dental caries distribution by threshold in epidemiological surveys, including its relevance for clinical care. Inclusion of enamel caries reveals the extent of caries management required at a point when non-invasive care is possible, emphasising the importance of prevention through contemporary primary care, which includes supporting self-care.

In this paper, an online model-free method is proposed to estimate the dynamic model of a power system with distributed renewable energy sources (RES). The proposed method, requiring no knowledge of network topology and model parameters, is computationally efficient and can be implemented online. The impact of missing PMUs is evaluated in detail, which shows that most entries of the dynamic model can still be well estimated in the case of missing PMUs. Simulation studies in the modified IEEE 68-bus system demonstrate that the proposed method can provide accurate estimation of the dynamic model in different operating conditions. The method can help detect topology change even when some PMUs are lost.

High-temperature and high-light are the main adversity stresses faced by strawberry seedlings and open-field cultivation in summer. Chitosan (CTS) is widely used in agriculture as a soil amendment, plant growth regulator, and promoter of cold resistance. However, the effects of CTS on strawberry seedlings under the combined stress of high-temperature and high-light are unclear. This study aimed to determine the effect of CTS on strawberry seedlings under the combined stress of high-temperature and high-light. In this study, Xuelixiang strawberry was used as the experimental plant material. The leaves were sprayed with 100 mg/Kg CTS or deionized aqueous solution and placed under high-temperature and high-light (38 °C, 1800 μ mol·m−2·s−1, respectively) for 8 h. In addition, a suitable temperature and light (23 °C, 400 μ mol·m−2·s−1, respectively) was sprayed with deionized water as a control. The results showed that compared with non-CTS treatment, the chlorophyll (Chl) content in strawberry plants increased by 16.9% after CTS treatment; the net CO2 exchange (Pn) increased by 74.9%; and the maximum photochemical efficiency increased by 20.1%. In addition, CTS treatment increased the content of antioxidants; increased osmotic adjustment substances; improved the activity of reduced glutathione with reduced ascorbic acid (AsA-GSH) circulating antioxidant enzymes; removed reactive oxygen species in plants in time; and reduced the damage of reactive oxygen species to photosynthetic organs and cell membranes, thereby reducing high-temperature and high-light injury to strawberry seedlings. This study shows that CTS can improve the negative effects of high-temperature and high-light stress on strawberry seedlings.

The increasing structural flexibility of large aircraft leads to significant aeroelastic effects. More efficient topology optimization techniques are required for the design to further take advantage of aeroelasticity and obtain lightweight structures. This paper proposes a moving boundary meshfree topology optimization that combines the Galerkin method of weighted residuals and non-uniform rational B-splines (NURBS). The solution domain is described by the control points of NURBS and its property is calculated adaptively with an integration subtraction technique. The minimal compliance is searched for using the globally convergent method of moving asymptotes (GCMMA) by designing the locations of control points as subject to volume and flux constraints. The method is first applied to a typical two-dimensional design example with symmetric boundary conditions. The results show that the shape constraints can be conveniently applied, and smoother boundaries are obtained with fewer parameters. Then, a three-dimensional wing structure with asymmetric boundary conditions is optimized. A three-dimensional flight load that combines the high-order-panel and meshfree methods is employed to calculate the elastic loads and update asymmetric external loads during the optimization process. The designed wing satisfies engineering requirements and the presented method can solve the practical topology optimization problems of three-dimensional structures.

Due to the complexity and particularity of the joined wing layout, traditional design methods for the global stiffness of a high-aspect wing are not applicable for a joined wing. Herein, a beam-frame model and a three-dimensional wing-box model are built to solve the global stiffness aeroelastic optimization design problem for a joined wing. The goal is to minimize the weight, and the constraints are the overall aeroelastic requirements. Based on a genetic algorithm, two methods for the beam-frame model and one method for the three-dimensional model are used for comparative analysis. The results show that the optimization method for a diagonal beam section and the optimization method for an exponential/linear combination function fit are adequate for optimizing and designating the joined wing global stiffness. The distributions obtained using the two methods have good consistency and are similar to the distribution of the three-dimensional model. The stiffness distribution data and the beam section parameters can be converted from each other, which is convenient for redesigning the structure parameters using the stiffness distribution data, and is valuable for engineering applications.

The cecum of poultry harbors a complex and dynamic microbial community which plays important roles in preventing pathogen colonization, detoxifying harmful substances, nutrient processing, and harvesting of the ingestion. Understanding and optimizing microbial communities could help improve agricultural productivity. In this study, we analyzed the composition and function of cecal microbiota of Wenchang chicken (a native breed of Bantam) before and after fattening, using high throughput sequencing technology. High-throughput sequencing of the 16S rRNA genes V3-V4 hypervariable regions was used to characterize and compare the cecal microbiota of Wenchang chicken before fattening (free-range in hill) and after fattening (cage raising). Sixteen phyla were shared by the 20 samples. Firmicutes and Bacteroidetes were the top two abundant phyla being 80% of the total microbiota. Samples of chickens prior to fattening were more dispersed than those after fattening. Twenty four microbes could be considered as biomarkers and 3 phyla revealed differences by variance analysis which could distinguish the two groups. Cecal microbiota in the before fattening group had higher abundance of functions involved in digestive system and biosynthesis of other secondary metabolites. The composition and function of cecal microbiota in Wenchang chicken before and after fattening under the two feeding modes, free range in hillside and cage raising, were found to be different. These results can be attributed to the differences in feeding modes and growth stages. In-depth study on the functions and interactions of intestinal microbiota can help us in developing strategies for raising Wenchang chickens and provide valuable information for the study of microbiota in the chicken gut.

The gut microbiome plays an important role in the health and disease status of the host. Research on the effect of sex on animal intestinal microorganisms is still limited; and the effect of castration on the gut microbiome of male pigs has not been fully investigated. In this study, 30 Hainan special wild boars at the same growth stage were divided into three groups (10 entire males, 10 females, and 10 castrated males). High-throughput 16S rRNA sequencing was used to investigate the fecal microbiota of the Hainan special wild boar. Firmicutes, Bacteroidetes, Actinobacteria, Spirochaetes, and Proteobacteria were the five dominant phyla found in the specimens. The relative abundance of Bacteroidetes was higher in the microbiota of female pigs than in male pigs, while Firmicutes was on the contrary. The percentage of Streptococcus and Lactobacillus was higher in males than females. The microbial diversity of females was significantly higher compared to males; castration increased the intestinal microbial diversity of males. Functional prediction showed that male fecal microorganisms were rich in membrane transport and carbohydrate metabolism; energy metabolism, glycan biosynthesis, and metabolism of cofactors and vitamins were rich in the female group; the fecal microorganisms of castrated males had higher membrane transport abundance.

In this paper, we present an integration subtraction technique to model holes interactively in a predesigned domain for adaptive problems. This technique involves two approaches, the normal subtraction technique and the moving subtraction technique. In the basic normal subtraction technique, the predesigned domain can be meshed using any methods as an initial integration background cell for meshfree analysis. Holes are described using closed non-uniform rational B-spline (NURBS) curves to preserve the exact computer-aided design (CAD) geometry and are meshed alone using the homotopic method, so they can easily be subtracted from the predesigned domain with no refinement. On the other hand, when the hole size is varying, the moving subtraction technique, in which only the changing part between the new and old boundaries needs to be integrated and subtracted, is more efficient. Compared with the standard radial point interpolation method (RPIM) and finite element method (FEM) in three linear elastic examples with different holes, the excellent accuracy and good efficiency of the proposed method are demonstrated, and its feasibility in complex topology problems is verified.

Cleidocranial dysplasia (CCD) is an autosomal dominant inheritable skeletal disorder characterized by cranial dysplasia, clavicle hypoplasia and dental abnormalities. This disease is mainly caused by heterozygous mutations in RUNX2, a gene that encodes an osteoblast-specific transcription factor. In the present study, mutational analyses of RUNX2 gene were performed on four unrelated Chinese patients with CCD. Four different RUNX2 mutations were detected in these patients, including one nonsense mutation (c.199C>T p.Q67X) and three missense mutations (c.338T>G p.L113R, c.557G>C p.R186T and c.673C>T p.R225W). Among them, two mutations (c.199C>T p.Q67X and c.557G>C p.R186T) were novel and the other two had been reported in previous literatures. Except for Q67X mutation located in the Q/A domain, other three mutations were clustered within the highly conserved Runt domain. Green fluorescent protein (GFP) and RUNX2 fusion protein analyses in vitro showed that nuclear accumulation of RUNX2 protein was disturbed by Q67X mutation, while the other two mutations (c.338T>G p.L113R and c.557G>C p.R186T) had no effects on the subcellular distribution of RUNX2. Luciferase reporter assay demonstrated that all the three novel RUNX2 mutations significantly reduced the transactivation activity of RUNX2 on osteocalcin promoter. Our findings enrich the evidence of molecular genetics that the mutations of RUNX2 gene are responsible for CCD.

The increasing demands for travelling comfort and reduction of carbon dioxide emissions have been considered substantially in the stage of conceptual aircraft design. However, the design of a modern aircraft is a multidisciplinary process, which requires the coordination of information from several specific disciplines, such as structures, aerodynamics, control, etc. To address this problem with adequate accuracy, the multidisciplinary analysis and optimization (MAO) method is usually applied as a systematic and robust approach to solve such complex design issues arising from industries. Since MAO method is tedious and computationally expensive, genetic programming (GP)-based metamodeling techniques incorporating MAO are proposed as an effective approach to minimize the wing stiffness of a large aircraft subject to aerodynamic, aeroelastic and stability constraints in the conceptual design phase. Based on the linear small-disturbance theory, the state-space equation is employed for stability analysis. In the process of multidisciplinary analysis, aeroelastic response simulations are performed using Nastran. To construct metamodels representing the responses of the interests with high accuracy as well as less computational burden, optimal Latin hypercube design of experiments (DoE) is applied to determine the optimized distribution of sampling points. Following that, parametric optimization is carried out on metamodels to obtain the optimal wing geometry shape, elastic axis positions and stiffness distribution, and then the solution is verified by finite element simulations. Finally, the superiority of the GP-based metamodel technique over genetic algorithm is demonstrated by multidisciplinary design optimization of a representative beam-frame wing structure in terms of accuracy and efficiency. The results also show that GP metamodel-based strategy for solving MAO problems can provide valuable insights to tailoring parameters for the effective design of a large aircraft in the conceptual phase.

BackgroundInduction chemotherapy is a common therapeutic option for patients with locoregionally-advanced head and neck cancer (HNC), but it remains unclear which patients will benefit. In this study, we searched for biomarkers predicting the response of patients with locoregionally-advanced HNC to induction chemotherapy by evaluating the expression pattern of DNA repair proteins.MethodsExpression of a panel of DNA-repair proteins in formalin-fixed paraffin embedded specimens from a cohort of 37 HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation were analyzed using quantitative immunohistochemistry.ResultsWe found that XPF (an ERCC1 binding partner) and phospho-MAPKAP Kinase 2 (pMK2) are novel biomarkers for HNSCC patients undergoing platinum-based induction chemotherapy. Low XPF expression in HNSCC patients is associated with better response to induction chemoradiotherapy, while high XPF expression correlates with a worse response (p = 0.02). Furthermore, low pMK2 expression was found to correlate significantly with overall survival after induction plus chemoradiation therapy (p = 0.01), suggesting that pMK2 may relate to chemoradiation therapy.ConclusionsWe identified XPF and pMK2 as novel DNA-repair biomarkers for locoregionally-advanced HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation. Our study provides insights for the use of DNA repair biomarkers in personalized diagnostics strategies. Further validation in a larger cohort is indicated.

RUNX2 is an important osteo-specific factor with crucial functions in bone formation and remodelling as well as resorption of teeth. Heterozygous mutation of RUNX2 can cause cleidocranial dysplasia (CCD), a systemic disease with extensive skeletal dysplasia and abnormality of tooth growth. In our study, dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) were isolated, cultured and identified from one patient with CCD and compared with normal controls. This CCD patient was confirmed to have a heterozygous frameshift mutation of RUNX2 (c.514delT, p.Ser172fs) in the previous study. The results showed that the proliferation abilities of DFCs and PDLCs were both disturbed by the RUNX2 mutation in the CCD patient compared with the normal control. A co-culture system of these cells with human peripheral blood mononuclear cells was then used to investigate the effect of RUNX2 mutation on osteoclastogenesis. We found that the RUNX2 mutation in CCD reduced the expression of osteoclast-related genes, such as RUNX2, CTR, CTSK, RANKL and OPG. The ability of osteoclastogenesis in DFCs and PDLCs detected by tartrate-resistant acid phosphatase staining in the co-culture system was also reduced by the RUNX2 mutation compared with the normal control. These outcomes indicate that the RUNX2 mutation disturbs the modulatory effects of DFCs and PDLCs on the differentiation of osteoclasts and osteoblasts, thereby interfering with bone remodelling. These effects may contribute in part to the pathological manifestations of retention of primary teeth and delayed eruption of permanent teeth in patients with CCD. [ABSTRACT FROM AUTHOR]

Background: Healthcare providers generate a huge amount of biomedical data stored in either legacy system (paper-based) format or electronic medical records (EMR) around the world, which are collectively referred to as big biomedical data (BBD). To realize the promise of BBD for clinical use and research, it is an essential step to extract key data elements from unstructured medical records into patient-centered electronic health records with computable data elements. Our objective is to introduce a novel solution, known as a double-reading/entry system (DRESS), for extracting clinical data from unstructured medical records (MR) and creating a semi-structured electronic health record database, as well as to demonstrate its reproducibility empirically.Methods: Utilizing the modern cloud-based technologies, we have developed a comprehensive system that includes multiple subsystems, from capturing MRs in clinics, to securely transferring MRs, storing and managing cloud-based MRs, to facilitating both machine learning and manual reading, and to performing iterative quality control before committing the semi-structured data into the desired database. To evaluate the reproducibility of extracted medical data elements by DRESS, we conduct a blinded reproducibility study, with 100 MRs from patients who have undergone surgical treatment of lung cancer in China. The study uses Kappa statistic to measure concordance of discrete variables, and uses correlation coefficient to measure reproducibility of continuous variables.Results: Using the DRESS, we have demonstrated the feasibility of extracting clinical data from unstructured MRs to create semi-structured and patient-centered electronic health record database. The reproducibility study with 100 patient's MRs has shown an overall high reproducibility of 98 %, and varies across six modules (pathology, Radio/chemo therapy, clinical examination, surgery information, medical image and general patient information).Conclusions: DRESS uses a double-reading, double-entry, and an independent adjudication, to manually curate structured data elements from unstructured clinical data. Further, through distributed computing strategies, DRESS protects data privacy by dividing MR data into de-identified modules. Finally, through internet-based computing cloud, DRESS enables many data specialists to work in a virtual environment to achieve the necessary scale of processing thousands MRs within days. This hybrid system represents probably a workable solution to solve the big medical data challenge. [ABSTRACT FROM AUTHOR]

Background: Severe early childhood caries (s-ECC), which has quite high prevalence among children, is a widespread problem with significant impacts among both developing and developed countries. At present, it is widely known that no early detective techniques and diagnostic tests could have high sensitivity and specificity when using for clinical screening of s-ECC. In this study, we had applied magnetic bead (MB)-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to screen distinctive candidate biomarkers of this disease, so as to establish protein profiles and diagnostic models of s-ECC.Methods: Firstly, we used the technique mentioned above to detect specifically expressed peptides in saliva samples from ten children with s-ECC, separately at the time point of before, 1 and 4 weeks after dental treatment. Then a diagnostic model for s-ECC was established with the K nearest-neighbour method, which was validated in another six children in the next stage of study. After that, linear ion trap-orbitrap-mass spectrometry (LTQ-Orbitrap-MS) was performed to identify which of the proteins in saliva might be the origination of these peptides.Results: We found that seven peptide peaks were significantly different when comparing the three time points, among them two were higher, while other five were lower in the pre-treatment s-ECC group compared with post-treatment. The sensitivity and specificity of the diagnostic model we built were both 83.3 %. Two of these peptides were identified to be segments of histatin-1, which was one important secretory protein in saliva.Conclusions: Hereby we confirmed that MB-based MALDI-TOF MS is an effective method for screening distinctive peptides from the saliva of junior patients with s-ECC, and histatin-1 may probably be one important candidate biomarker of this common dental disease. These findings might have bright prospect in future in establishing new diagnostic methods for s-ECC. [ABSTRACT FROM AUTHOR]