Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.

Evolution and Prospects of Foundation Models: From Large Language Models to Large Multimodal Models

Since the 1950s,when the Turing Test was introduced,there has been notable progress in machine language intelligence.Language modeling,crucial for AI development,has evolved from statistical to neural models over the last two decades.Recently,transformer-based Pre-trained Language Models(PLM)have excelled in Natural Language Processing(NLP)tasks by leveraging large-scale training corpora.Increasing the scale of these models enhances performance significantly,introducing abilities like context learning that smaller models lack.The advancement in Large Language Models,exemplified by the development of ChatGPT,has made significant impacts both academically and industrially,capturing widespread societal interest.This survey provides an overview of the development and prospects from Large Language Models(LLM)to Large Multimodal Models(LMM).It first discusses the contributions and technological advancements of LLMs in the field of natural language processing,especially in text generation and language understanding.Then,it turns to the discussion of LMMs,which integrates various data modalities such as text,images,and sound,demonstrating advanced capabilities in understanding and generating cross-modal content,paving new pathways for the adaptability and flexibility of AI systems.Finally,the survey highlights the prospects of LMMs in terms of technological development and application potential,while also pointing out challenges in data integration,cross-modal understanding accuracy,providing a comprehensive perspective on the latest developments in this field.

Effects of Andrade and Burgers rheologies on glacial isostatic adjustment modeling in Antarctica

Variations in ice mass deform the Earth and modify its gravity field,a process known as Glacial Isostatic Adjustment(GIA).GIA in Antarctica remains poorly constrained due to the cumulative effect of past and present ice-mass changes,the unknown history of the past ice-mass change,and the uncertainties on the mechanical properties of the Earth.This paper investigates the effect of using Andrade and Burgers viscoelastic rheologies,rather than the commonly used Maxwell rheology,to model GIA-induced deformation in Antarctica.The Love number and Green's function formalism are used to compute the radial surface displacements and the gravity changes induced by the past and present ice-mass changes.We consider an Earth model whose elastic properties and radial structure are averaged from the Preliminary Reference Earth Model and two viscosity profiles to account for the recently published results on the present ice-mass changes.Using the three rheological laws affects the temporal response of the Earth differently,leading to smaller discrepancies than those induced by the two viscosity structures.The differences are the largest between Maxwell and Burgers rheologies during the 100-1000 years following the beginning of the surface-mass change.Results show that using the Andrade and Burgers rheologies allows the Earth to respond on decennial to centennial time scales,up to 10 m more than Maxwell.Considering only the recent ice-mass changes,the deformation rates derived from Burgers and Andrade rheologies are several times larger than those estimated by Maxwell rheology.

An extended micromechanical-based plastic damage model for understanding water effects on quasi-brittle rocks

Water effects on the mechanical properties of rocks have been extensively investigated through experiments and numerical models.However,few studies have established a comprehensive link between the microscopic mechanisms of water-related micro-crack and the constitutive behaviors of rocks.In this work,we shall propose an extended micromechanical-based plastic damage model for understanding weakening effect induced by the presence of water between micro-crack’s surfaces on quasi-brittle rocks,based on the Mori-Tanaka homogenization and irreversible thermodynamics framework.Regarding the physical mechanism,water strengthens micro-crack propagation,which induces damage evolution during the pre-and post-stage,and weakens the elastic effective properties of rock matrix.After proposing a special calibration procedure for the determination of model parameters based on the laboratory compression tests,the proposed micromechanical-based model is verified by comparing the model predictions to the experimental results.The model effectively captures the mechanical behaviors of quasibrittle rocks subjected to the weakening effects of water.

Exploring the effects of taurolidine on tumor weight and microvessel density in a murine model of osteosarcoma

Background:Osteosarcoma is the most common malignant primary bone tumor.The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy.Moreover,current treatment regimens bear a significant risk of serious side effects.Thus,there is an unmet clinical need for effective therapies with improved safety profiles.Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines.Methods:In this study,we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma.K7M2 murine osteosarcoma cells were injected,both intramuscular and intraperitoneal,into 60 BALB/c mice on day zero.Animals were then randomized to receive treatment with taurolidine 2%(800 mg/kg),taurolidine 1%(400 mg/kg),or NaCl 0.9%control for seven days by intravenous or intraperitoneal administration.Results:After 35 days,mice were euthanized,and the tumors were harvested for analysis.Eighteen mice were excluded from the analysis due to complications.Body weight was significantly lower in the 2%taurolidine intraperitoneal treatment group from day 9 to 21,consistent with elevated mortality in this group.Intraperitoneal tumor weight was significantly lower in the 1%(p=0.003)and 2%(p=0.006)intraperitoneal taurolidine treatment groups compared to the control.No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine.There were no significant differences in microvessel density or mitotic rate between treatment groups.Reduced body weight and elevated mortality in the 2%taurolidine intraperitoneal group suggest that the lower 1%dose is preferable.Conclusions:In conclusion,there is no evidence of antiangiogenic activity,and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited.Moreover,its toxic profile grants further evaluation.Given these observations,further research is necessary to refine the use of taurolidine in osteosarcoma treatment.

Effects of carrier density and interactions on pairing symmetry in a t_(2g) model

By utilizing the fluctuation exchange approximation method,we perform a study on the superconducting pairing symmetry in a t_(2g) three-orbital model on the square lattice.Although the tight-binding parameters of the model are based on Sr_(2)RuO_(4),we have systematically studied the evolution of superconducting pairing symmetry with the carrier density and interactions,making our findings relevant to a broader range of material systems.Under a moderate Hund’s coupling,we find that spin fluctuations dominate the superconducting pairing,leading to a prevalent spin-singlet pairing with a d_(x^(2)-y^(2))-wave symmetry for the carrier density within the range of n=1.5-4 per site.By reducing the Hund’s coupling,the charge fluctuations are enhanced and play a crucial role in determining the pairing symmetry,leading to a transition of the pairing symmetry from the spin-singlet d_(x^(2)-y^(2))-wave to the spin-triplet p-wave.Furthermore,we find that the superconducting pairings are orbital dependent.As the carrier density changes from n=4 to n=1.5,the active orbitals for superconducting pairing shift from the quasi-two-dimensional orbital dxy to the quasi-one-dimensional orbitals d_(xz) and d_(yz).

Assessing the effects of model parameter assumptions on surface-wave inversion results

Surface-wave inversion is a powerful tool for revealing the Earth's internal structure.However,aside from shear-wave velocity(v_(S)),other parameters can influence the inversion outcomes,yet these have not been systematically discussed.This study investigates the influence of various parameter assumptions on the results of surface-wave inversion,including the compressional and shear velocity ratio(v_(P)/v_(S)),shear-wave attenuation(Q_(S)),density(ρ),Moho interface,and sedimentary layer.We constructed synthetic models to generate dispersion data and compared the obtained results with different parameter assumptions with those of the true model.The results indicate that the v_(P)/v_(S) ratio,Q_(S),and density(ρ) have minimal effects on absolute velocity values and perturbation patterns in the inversion.Conversely,assumptions about the Moho interface and sedimentary layer significantly influenced absolute velocity values and perturbation patterns.Introducing an erroneous Mohointerface depth in the initial model of the inversion significantly affected the v_(S) model near that depth,while using a smooth initial model results in relatively minor deviations.The assumption on the sedimentary layer not only affects shallow structure results but also impacts the result at greater depths.Non-linear inversion methods outperform linear inversion methods,particularly for the assumptions of the Moho interface and sedimentary layer.Joint inversion with other data types,such as receiver functions or Rayleigh wave ellipticity,and using data from a broader period range or higher-mode surface waves,can mitigate these deviations.Furthermore,incorporating more accurate prior information can improve inversion results.

Key Issues for Modelling, Operation, Management and Diagnosis of Lithium Batteries: Current States and Prospects

1 Introduction.With the continuous growth of the global population,the energy demand continues to increase.However,due to the dominance of fossil fuels in global energy and fossil fuels are non-renewable,it has led to the global energy crisis[1].Besides,the use of fossil fuels will generate a mass of air pollutants(e.g.,carbon dioxide,sulfur dioxide,etc.),which will cause serious environmental pollution,climate change[2],etc.To resolve the aforementioned issues,countries around the world have implemented a variety of measures hoping to fundamentally adjust the global energy structure and achieve sustainable development.Thereinto,“Paris Agreement”reached in 2015 under the framework of“United Nations Framework Convention on Climate Change”aims to control the increase in the average temperature of the globe to within 2°C below preindustrial levels,and thereafter to peak global greenhouse gas emissions as soon as possible,continuously decreasing thereafter[3].United Kingdom plans to reduce the average exhaust emissions of“new cars”to approximately 50–70 g/km by 20230,which is roughly half of what it is now[4].In addition,China proposed a plan at“United Nations General Assembly”in 2020 to peak carbon dioxide emissions by 2030 and strive to achieve carbon neutrality by 2060.It is a fact that the whole world is committed to changing the current energy structure,protecting the Earth’s ecology,and achieving global sustainable development[5].

Comparisons of Wave Force Model Effects on the Structural Responses and Fatigue Loads of a Semi-Submersible Floating Wind Turbine

The selection of wave force models will significantly impact the structural responses of floating wind turbines.In this study,comparisons of wave force model effects on the structural responses and fatigue loads of a semi-submersible floating wind turbine(SFWT)were conducted.Simulations were performed by employing the Morison equation(ME)with linear or second-order wave kinematics and potential flow theory(PFT)with first-or second-order wave forces.A comparison of regular waves,irregular waves,and coupled wind/waves analyses with the experimental data showed that many of the simulation results and experimental data are relatively consistent.However,notable discrepancies are found in the response amplitude operators for platform heave,tower base bending moment,and tension in mooring lines.PFT models give more satisfactory results of heave but more significant discrepan-cies in tower base bending moment than the ME models.In irregular wave analyses,low-frequency resonances were captured by PFT models with second-order difference-frequency terms,and high-frequency resonances were captured by the ME models or PFT models with second-order sum-frequency terms.These force models capture the response frequencies but do not reasonably predict the response amplitudes.The coupled wind/waves analyses showed more satisfactory results than the wave-only analyses.However,an important detail to note is that this satisfactory result is based on the overprediction of wind-induced responses.

Evaluation of the effects of health education interventions for hypertensive patients based on the health belief model

BACKGROUND Hypertension is a major risk factor for cardiovascular disease and stroke,and its prevalence is increasing worldwide.Health education interventions based on the health belief model(HBM)can improve the knowledge,attitudes,and behaviors of patients with hypertension and help them control their blood pressure.AIM To evaluate the effects of health education interventions based on the HBM in patients with hypertension in China.METHODS Between 2021 and 2023,140 patients with hypertension were randomly assigned to either the intervention or control group.The intervention group received health education based on the HBM,including lectures,brochures,videos,and counseling sessions,whereas the control group received routine care.Outcomes were measured at baseline,three months,and six months after the intervention and included blood pressure,medication adherence,self-efficacy,and perceived benefits,barriers,susceptibility,and severity.RESULTS The intervention group had significantly lower systolic blood pressure[mean difference(MD):-8.2 mmHg,P<0.001]and diastolic blood pressure(MD:-5.1 mmHg,P=0.002)compared to the control group at six months.The intervention group also had higher medication adherence(MD:1.8,P<0.001),self-efficacy(MD:12.4,P<0.001),perceived benefits(MD:3.2,P<0.001),lower perceived barriers(MD:-2.6,P=0.001),higher perceived susceptibility(MD:2.8,P=0.002),and higher perceived severity(MD:3.1,P<0.001)than the control group at six months.CONCLUSION Health education interventions based on the HBM effectively improve blood pressure control and health beliefs in patients with hypertension and should be implemented in clinical practice and community settings.

Adaptive Random Effects/Coefficients Modeling

Adaptive fractional polynomial modeling of general correlated outcomes is formulated to address nonlinearity in means, variances/dispersions, and correlations. Means and variances/dispersions are modeled using generalized linear models in fixed effects/coefficients. Correlations are modeled using random effects/coefficients. Nonlinearity is addressed using power transforms of primary (untransformed) predictors. Parameter estimation is based on extended linear mixed modeling generalizing both generalized estimating equations and linear mixed modeling. Models are evaluated using likelihood cross-validation (LCV) scores and are generated adaptively using a heuristic search controlled by LCV scores. Cases covered include linear, Poisson, logistic, exponential, and discrete regression of correlated continuous, count/rate, dichotomous, positive continuous, and discrete numeric outcomes treated as normally, Poisson, Bernoulli, exponentially, and discrete numerically distributed, respectively. Example analyses are also generated for these five cases to compare adaptive random effects/coefficients modeling of correlated outcomes to previously developed adaptive modeling based on directly specified covariance structures. Adaptive random effects/coefficients modeling substantially outperforms direct covariance modeling in the linear, exponential, and discrete regression example analyses. It generates equivalent results in the logistic regression example analyses and it is substantially outperformed in the Poisson regression case. Random effects/coefficients modeling of correlated outcomes can provide substantial improvements in model selection compared to directly specified covariance modeling. However, directly specified covariance modeling can generate competitive or substantially better results in some cases while usually requiring less computation time.

Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease

BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic syndrome.Studies suggest ornithine aspartate(LOLA)as drug therapy.AIM To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD.METHODS Adult male Sprague Dawley rats were randomized into three groups:Control(10 rats fed with a standard diet),MASLD(10 rats fed with a high-fat and choline-deficient diet),and LOLA(10 rats receiving 200 mg/kg/d LOLA,after the 16th week receiving high-fat and choline-deficient diet).After 28 wk of the experiment,animals were euthanized,and feces present in the intestine were collected.Following fecal DNA extraction,the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™system.RESULTS Alpha and beta diversity metrics were comparable between MASLD and LOLA.3 OTUs were differentially abundant between MASLD and LOLA,which belong to the species Helicobacter rodentium,Parabacteroides goldsteinii,and Parabacteroides distasonis.The functional prediction provided two different metabolic profiles between MASLD and LOLA.The 9 pathways differentially abundant in MASLD are related to a change in energy source,adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis.The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate,including tricarboxylic acid cycle pathways,purine/guanosine nucleotides biosynthesis,pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis.CONCLUSION Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD,it was associated with changes in specific gut microbes and their related metabolic pathways.

Drivers for Inter-city Innovation Networks Across Chinese Cities:Modelling Physical Versus Intangible Effects

Cross-region innovation is widely recognized as an important source of the long-term regional innovation capacity.In the recent past,a growing number of studies has investigated the network structure and mechanisms of cross-region innovation collaboration in various contexts.However,existing research mainly focuses on physical effects,such as geographical distance and high-speed railway connections.These studies ignore the intangible drivers in a changing environment,the more digitalized economy and the increasingly solidified innovation network structure.Thus,the focus of this study is on estimating determinants of innovation networks,especially on intangible drivers,which have been largely neglected so far.Using city-level data of Chinese patents(excluding Hong Kong,Macao,and Taiwan Province of China),we trace innovation networks across Chinese cities over a long period of time.By integrating a measure on Information and Communications Technology(ICT)development gap and network structural effects into the general proximity framework,this paper explores the changing mechanisms of Chinese innovation networks from a new perspective.The results show that the structure of cross-region innovation networks has changed in China.As mechanisms behind this development,the results confirm the increasingly important role of intangible drivers in Chinese inter-city innovation collaboration when controlling for effects of physical proximity,such as geographical distance.Since digitalization and coordinated development are the mainstream trends in China and other developing countries,these countries'inter-city innovation collaboration patterns will witness dramatic changes under the influence of intangible drivers.

Effects of Polygala fallax Hemsl Water Extract on a Mouse Model of Gastric Motility Disorders

[Objectives]To explore the effects of Polygona fallax Hemsl water extract on gastrointestinal motility in normal mice and gastric motility disorder model mice and approximate mechanism.[Methods]Using normal mice and mice with gastric motility disorders(modeled with atropine),the effects of different mass concentration groups of P.fallax Hemsl water extract(0.125,0.250,0.500 g/mL)and domperidone groups on gastric residual rate,small intestine propulsion rate,serum motilin(MLT),vasoactive intestinal peptide(VIP),and tissue morphology were studied.[Results]There was a highly significant difference(P<0.01)in the small intestine propulsion rate of liquid in normal mice among the different concentration groups of P.fallax Hemsl water extract compared to the blank group.The small intestine propulsion rate and gastric residue rate of semi-solid paste were statistically significant compared to the blank group(P<0.05).Among them,there was a highly significant difference between the high concentration group(67.75%±7.65%,46.5%±10.62%)and the medium concentration group(60.90%±5.87%,59.27%±7.82%)(P<0.01).There was statistical significance in normal mouse serum MLT content in the high concentration group(P<0.05).There was no effect on serum VIP levels in normal mice;no effect on the morphology of stomach and intestinal tissues of normal mice.The small intestine propulsion rate and gastric residue rate of liquid and semi-solid paste in mice with gastric motility disorders were statistically significant compared to the atropine group,with extremely significant differences(P<0.01).[Conclusions]P.fallax Hemsl water extract has a promoting effect on gastrointestinal motility.One of the specific mechanisms by which P.fallax Hemsl promotes gastrointestinal motility in normal mice may be related to the content of MLT in mouse serum.The mechanism of action in atropine induced gastric paresis mice may be related to the reactivation of M receptors,and the action mechanism of P.fallax Hemsl does not change the original histological basis.It can be inferred that P.fallax Hemsl water extract has a synergistic effect on promoting gastrointestinal motility through other mechanisms,but it is not fully understood and further in-depth research is needed.

Three Subjects and Seven Duties Model:Empowering Informatization Teaching Ability of Pre-Service Teachers

By constructing a model,this study seeks to provide suggestions for strengthening pre-service teachers’informatization teaching ability.It aims to answer the following research questions:(1)What do the pre-service teachers know about informatization instruction?What is their level of informatization teaching ability?(2)What factors influence pre-service teachers’ability to deliver informatization instruction?How to overcome the obstacles?The inquiry focuses on the theoretical exploration of informatization teaching ability,questionnaire,and interview analysis on the current condition and improvement of pre-service teachers’informatization teaching ability.The data from the questionnaire and interview of the pre-service teachers were evaluated from three dimensions:awareness and attitude towards informatization teaching,knowledge of informatization teaching,and the ability to apply informatization teaching skills innovatively and comprehensively.The 3S-7D(Three Subjects and Seven Duties)model consisting of three subjects and the seven duties that go with them is established.The three subjects include pre-service teachers,teacher educators,and higher education schools.The seven duties involve pre-service teachers demonstrating learning motivation,cross-discipline thinking,and information and communications technology mastery;teacher educators actively constructing informatization teaching practice and formative assessment;and higher education schools providing adequate hardware and software equipment while offering cooperative opportunities with primary and junior schools through institutionalization.

Effects of Continuous Precision Nursing Model on Knowledge, Attitudes, and Practices (KAP) Behavior and Cardiac Function in Patients after Percutaneous Coronary Angiography and Stent Implantation

Objective:To explore the impact of a continuous precision nursing model on patients’Knowledge,Attitudes,and Practices(KAP)and cardiac function during the nursing process of patients undergoing percutaneous coronary angiography and stent implantation.Methods:Ninety patients who underwent percutaneous coronary angiography and stent implantation in our hospital from April 2022 to April 2023 were selected and randomly divided into the control group(45 cases),in which routine nursing support was carried out during the treatment process,and the observation group(45 cases),in which continuous precision nursing model was carried out during the treatment process.Comparisons were made between the two groups of patients on their KAP,cardiac function,and quality of life during recovery.Results:There was no difference in the left ventricular ejection fraction(LVEF),cardiac output(CO),and cardiac index(CI)levels before intervention.After the intervention,the levels of cardiac function in the observation group were higher than those of the control group(P<0.05).There was no difference in the Exercise of Self-Care Agency(ESCA)self-care ability scale scores before the intervention.After the intervention,the observation group had higher ESCA scores than the control group(P<0.05).Conclusion:Implementation of a continuous precision nursing model in the care of patients undergoing percutaneous coronary angiography and stent implantation improved the patient’s cardiac function,and KAP,and promoted recovery.

Projecting Wintertime Newly Formed Arctic Sea Ice through Weighting CMIP6 Model Performance and Independence

Precipitous Arctic sea-ice decline and the corresponding increase in Arctic open-water areas in summer months give more space for sea-ice growth in the subsequent cold seasons. Compared to the decline of the entire Arctic multiyear sea ice,changes in newly formed sea ice indicate more thermodynamic and dynamic information on Arctic atmosphere–ocean–ice interaction and northern mid–high latitude atmospheric teleconnections. Here, we use a large multimodel ensemble from phase 6 of the Coupled Model Intercomparison Project(CMIP6) to investigate future changes in wintertime newly formed Arctic sea ice. The commonly used model-democracy approach that gives equal weight to each model essentially assumes that all models are independent and equally plausible, which contradicts with the fact that there are large interdependencies in the ensemble and discrepancies in models' performances in reproducing observations. Therefore, instead of using the arithmetic mean of well-performing models or all available models for projections like in previous studies, we employ a newly developed model weighting scheme that weights all models in the ensemble with consideration of their performance and independence to provide more reliable projections. Model democracy leads to evident bias and large intermodel spread in CMIP6 projections of newly formed Arctic sea ice. However, we show that both the bias and the intermodel spread can be effectively reduced by the weighting scheme. Projections from the weighted models indicate that wintertime newly formed Arctic sea ice is likely to increase dramatically until the middle of this century regardless of the emissions scenario.Thereafter, it may decrease(or remain stable) if the Arctic warming crosses a threshold(or is extensively constrained).

Anisotropic time-dependent behaviors of shale under direct shearing and associated empirical creep models

Understanding the anisotropic creep behaviors of shale under direct shearing is a challenging issue.In this context,we conducted shear-creep and steady-creep tests on shale with five bedding orientations (i.e.0°,30°,45°,60°,and 90°),under multiple levels of direct shearing for the first time.The results show that the anisotropic creep of shale exhibits a significant stress-dependent behavior.Under a low shear stress,the creep compliance of shale increases linearly with the logarithm of time at all bedding orientations,and the increase depends on the bedding orientation and creep time.Under high shear stress conditions,the creep compliance of shale is minimal when the bedding orientation is 0°,and the steady-creep rate of shale increases significantly with increasing bedding orientations of 30°,45°,60°,and 90°.The stress-strain values corresponding to the inception of the accelerated creep stage show an increasing and then decreasing trend with the bedding orientation.A semilogarithmic model that could reflect the stress dependence of the steady-creep rate while considering the hardening and damage process is proposed.The model minimizes the deviation of the calculated steady-state creep rate from the observed value and reveals the behavior of the bedding orientation's influence on the steady-creep rate.The applicability of the five classical empirical creep models is quantitatively evaluated.It shows that the logarithmic model can well explain the experimental creep strain and creep rate,and it can accurately predict long-term shear creep deformation.Based on an improved logarithmic model,the variations in creep parameters with shear stress and bedding orientations are discussed.With abovementioned findings,a mathematical method for constructing an anisotropic shear creep model of shale is proposed,which can characterize the nonlinear dependence of the anisotropic shear creep behavior of shale on the bedding orientation.

Development and validation of a prediction model for early screening of people at high risk for colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still not optimistic.In China,the incidence of CRC in the Yangtze River Delta region is increasing dramatically,but few studies have been conducted.Therefore,it is necessary to develop a simple and efficient early screening model for CRC.AIM To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC.METHODS Data of 64448 participants obtained from Ningbo Hospital,China between 2014 and 2017 were retrospectively analyzed.The cohort comprised 64448 individuals,of which,530 were excluded due to missing or incorrect data.Of 63918,7607(11.9%)individuals were considered to be high risk for CRC,and 56311(88.1%)were not.The participants were randomly allocated to a training set(44743)or validation set(19175).The discriminatory ability,predictive accuracy,and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic(ROC)curves and calibration curves and by decision curve analysis.Finally,the model was validated internally using a bootstrap resampling technique.RESULTS Seven variables,including demographic,lifestyle,and family history information,were examined.Multifactorial logistic regression analysis revealed that age[odds ratio(OR):1.03,95%confidence interval(CI):1.02-1.03,P<0.001],body mass index(BMI)(OR:1.07,95%CI:1.06-1.08,P<0.001),waist circumference(WC)(OR:1.03,95%CI:1.02-1.03 P<0.001),lifestyle(OR:0.45,95%CI:0.42-0.48,P<0.001),and family history(OR:4.28,95%CI:4.04-4.54,P<0.001)were the most significant predictors of high-risk CRC.Healthy lifestyle was a protective factor,whereas family history was the most significant risk factor.The area under the curve was 0.734(95%CI:0.723-0.745)for the final validation set ROC curve and 0.735(95%CI:0.728-0.742)for the training set ROC curve.The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population.CONCLUSION The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age,BMI,WC,lifestyle,and family history exhibited high accuracy.

High-speed penetration of ogive-nose projectiles into thick concrete targets:Tests and a projectile nose evolution model

The majority of the projectiles used in the hypersonic penetration study are solid flat-nosed cylindrical projectiles with a diameter of less than 20 mm.This study aims to fill the gap in the experimental and analytical study of the evolution of the nose shape of larger hollow projectiles under hypersonic penetration.In the hypersonic penetration test,eight ogive-nose AerMet100 steel projectiles with a diameter of 40 mm were launched to hit concrete targets with impact velocities that ranged from 1351 to 1877 m/s.Severe erosion of the projectiles was observed during high-speed penetration of heterogeneous targets,and apparent localized mushrooming occurred in the front nose of recovered projectiles.By examining the damage to projectiles,a linear relationship was found between the relative length reduction rate and the initial kinetic energy of projectiles in different penetration tests.Furthermore,microscopic analysis revealed the forming mechanism of the localized mushrooming phenomenon for eroding penetration,i.e.,material spall erosion abrasion mechanism,material flow and redistribution abrasion mechanism and localized radial upsetting deformation mechanism.Finally,a model of highspeed penetration that included erosion was established on the basis of a model of the evolution of the projectile nose that considers radial upsetting;the model was validated by test data from the literature and the present study.Depending upon the impact velocity,v0,the projectile nose may behave as undistorted,radially distorted or hemispherical.Due to the effects of abrasion of the projectile and enhancement of radial upsetting on the duration and amplitude of the secondary rising segment in the pulse shape of projectile deceleration,the predicted DOP had an upper limit.