APPLICATION RESEARCH OF COMBINATION PRINCIPLE IN CAD FEATURE RECOGNIZATION

The method of extracting the basic features of part from the file of STEPAP214 of 3-D model is proposed. All faces in the file are the minimal elements. The combination isdone for the faces with geometry restrictions and some attributes by the theory of the bestalphabetic tree which is constructed by HU--TUCKER algorithm in combination principle. So the basicfeatures could be attained. This provides the research basis to the more share and integration ofCAD information in the virtual enterprises. Finally, a case is used to illustrate the validity ofthe approach.

Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

Design Principles and Mechanistic Understandings of Non-Noble-Metal Bifunctional Electrocatalysts for Zinc-Air Batteries

Zinc-air batteries(ZABs)are promising energy storage systems because of high theoretical energy density,safety,low cost,and abundance of zinc.However,the slow multi-step reaction of oxygen and heavy reliance on noble-metal catalysts hinder the practical applications of ZABs.Therefore,feasible and advanced non-noble-metal elec-trocatalysts for air cathodes need to be identified to promote the oxygen catalytic reaction.In this review,we initially introduced the advancement of ZABs in the past two decades and provided an overview of key developments in this field.Then,we discussed the work-ing mechanism and the design of bifunctional electrocatalysts from the perspective of morphology design,crystal structure tuning,interface strategy,and atomic engineering.We also included theoretical studies,machine learning,and advanced characterization technologies to provide a comprehensive understanding of the structure-performance relationship of electrocatalysts and the reaction pathways of the oxygen redox reactions.Finally,we discussed the challenges and prospects related to designing advanced non-noble-metal bifunctional electrocatalysts for ZABs.

Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival

BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.

Advances in extracellular vesicle-based combination therapies for spinal cord injury

Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.

Adaptive Optimal Discrete-Time Output-Feedback Using an Internal Model Principle and Adaptive Dynamic Programming

In order to address the output feedback issue for linear discrete-time systems, this work suggests a brand-new adaptive dynamic programming(ADP) technique based on the internal model principle(IMP). The proposed method, termed as IMP-ADP, does not require complete state feedback-merely the measurement of input and output data. More specifically, based on the IMP, the output control problem can first be converted into a stabilization problem. We then design an observer to reproduce the full state of the system by measuring the inputs and outputs. Moreover, this technique includes both a policy iteration algorithm and a value iteration algorithm to determine the optimal feedback gain without using a dynamic system model. It is important that with this concept one does not need to solve the regulator equation. Finally, this control method was tested on an inverter system of grid-connected LCLs to demonstrate that the proposed method provides the desired performance in terms of both tracking and disturbance rejection.

A Numerical Study on Effects of Land-Surface Heterogeneity from "Combined Approach" on Atmospheric Process Part I: Principle and Method

A method based on Giorgi (1997a, 1997b) and referred to as ’ combined approach’, which is a combi-nation of mosaic approach and analytical-statistical-dynamical approach, is proposed. Compared with those of other approaches, the main advantage of the combined approach is that it not only can represent both interpatch and intrapatch variability, but also cost less computational time when the land surface heterogeneity is considered. Because the independent variable of probability density function (PDF) is ex-tended to the single valued function of basic meteorological characteristic quantities, which is much more universal, the analytical expressions of the characteristic quantities (e.g., drag coefficient, snow coverage, leaf surface aerodynamical resistance) affected by roughness length are derived , when the roughness length(and / or the zero plane displacement) heterogeneity has been mainly taken into account with the approach. On the basis of the rule which the PDF parameters should follow, we choose a function y of the roughness length z 0 as the PDF independent variable, and set different values of the two parameters width ratio αn and height ratio γ of PDF (here a linear, symmetric PDF is applied) for sensitivity experiments, from which some conclusions can be drawn, e.g., relevant characteristic terms show different sensitivities to the heterogeneous characteristic (i.e., roughness length), which suggests that we should consider the heterogeneities of the more sensitive terms in our model instead of the heterogeneities of the rest, and which also implies that when the land surface scheme is coupled into the global or regional atmospheric model, sensitivity tests against the distribution of the heterogeneous characteristic are very necessary; when the parameter αn is close to zero, little heterogeneity is represented, and αn differs with cases, which have an upper limit of about 0.6; in the reasonable range of αn, a peak-like distribution of roughness length can be depicted by a small value of γ, etc.. Key words Representation of land surface heterogeneity - “ Combined approach” - Numerical experiment This work was supported by the National Sciences Foundation of China, Grant No.49875005 and the State Key Project (973) G19990434 (03).

Anisotropic etching mechanisms of 4H-SiC:Experimental and first-principles insights

Molten-alkali etching has been widely used to reveal dislocations in 4H silicon carbide(4H-SiC),which has promoted the identification and statistics of dislocation density in 4H-SiC single crystals.However,the etching mechanism of 4H-SiC is limited misunderstood.In this letter,we reveal the anisotropic etching mechanism of the Si face and C face of 4H-SiC by combining molten-KOH etching,X-ray photoelectron spectroscopy(XPS)and first-principles investigations.The activation energies for the molten-KOH etching of the C face and Si face of 4H-SiC are calculated to be 25.09 and 35.75 kcal/mol,respectively.The molten-KOH etching rate of the C face is higher than the Si face.Combining XPS analysis and first-principles calculations,we find that the molten-KOH etching of 4H-SiC is proceeded by the cycling of the oxidation of 4H-SiC by the dissolved oxygen and the removal of oxides by molten KOH.The faster etching rate of the C face is caused by the fact that the oxides on the C face are unstable,and easier to be removed with molten alkali,rather than the C face being easier to be oxidized.

Scientific principles for accelerating the Sustainable Development Goals

The Sustainable Development Goals(SDGs)are significantly off-course as we reach the midpoint of their 2030 deadline.From a scientific perspective,the critical challenge in achieving the SDGs lies in the need for more scientific principles to understand the complex socio-ecological systems(SES)and their interactions influencing the 17 SDGs.Here,we propose a scientific framework to clarify the common scientific principles and the rational treatment of diversity under these principles.The framework’s core is revealing the complex mechanisms underlying the achievement of each Sustainable Development Goal(SDG)and SDG interactions.Building upon the identified mechanisms,complex SES models can be established,and the implementation of SDGs can be formulated as a multi-objective optimization problem,seeking a compromise in competition between essential costs and desired benefits.Our framework can assist countries,and even the world in accelerating progress towards the SDGs.

Strong invariance principle for a counterbalanced random walk

We study a counterbalanced random walkS_(n)=X_(1)+…+X_(n),which is a discrete time non-Markovian process andX_(n) are given recursively as follows.For n≥2,X_(n) is a new independent sample from some fixed law̸=0 with a fixed probability p,andX_(n)=−X_(v(n))with probability 1−p,where v(n)is a uniform random variable on{1;…;n−1}.We apply martingale method to obtain a strong invariance principle forS_(n).

Optimization principle of combined surface and underground mining and its applications

The pit limit optimization is discussed, which is one of the most important problems in the combined min-ing method, on the basis of the economic model of ore-blocks. A new principle of the limit optimization is put for-ward through analyzing the limitations of moving cone method under such conditions. With a view to recovering asmuch mineral resource as possible and making the maximum profit from the whole deposit, the new principle is tomaximize the sum of gain from both open-pit and underground mining. The mathematical models along the horizon-tal and vertical directions and modules for software package (DM&MCAD) have been developed and tested inTonglushan Copper Mine. It has been proved to be rather effective in the mining practice.

Combination Activity of Standard Antituberculosis Drugs and Extracts of Medicinal Plants Commonly Used in Traditional Treatment of Tuberculosis in Uganda

Introduction: Resistance to antituberculosis drugs and adverse drug reactions remain the leading causes of tuberculosis therapeutic failure globally. Despite the increasing acceptance of medicinal plant use in combination with conventional antituberculosis drugs in treatment of tuberculosis (TB) in Uganda, there is paucity of knowledge on their combination effect. Aim: This research aimed to determine combination activity of standard antituberculosis drugs with extracts of Zanthoxylum leprieurii Guill. & Perr. and Rubia cordifolia L., the two common antituberculosis medicinal plants in Uganda, against pansensitive (H37Rv) and multi-drug resistant (MDR) Mycobacterium tuberculosis strains. Materials and Methods: Two reference MTB strains (H37Rv and MDR strain) were inoculated on Middlebrook 7H11 medium containing a combination of standard antituberculosis drugs and methanol extracts of Z. leprieurii and R. cordifolia at varying concentrations. The number of colonies on the plates was observed and counted weekly for up to 8 weeks. In vitro combination activity was determined using proportion method. Mean percentage inhibition was calculated for the reduction of number of colonies on drug-extract combination medium in relation to drug-extract-free control medium. Results: Drug-extract combinations showed good combination activity against Mycobacterium tuberculosis strains when compared with individual standard anti-TB drugs. This was more exhibited against MDR strain. There was however a reduction in percentage inhibition when extracts were combined with ethambutol and streptomycin against H37Rv strain. Conclusions: Zanthoxylum leprieurii and Rubia cordifolia in combination with standard anti-TB drugs exhibited increased in vitro activity against Mycobacterium tuberculosis, especially MDR-TB strain. This justifies the local use of these plants in traditional treatment of tuberculosis especially in resistant cases in Uganda.

A Bioequivalence Study of Empagliflozin/Metformin Fixed-Dose Combination in Healthy Subjects under Fasting Conditions

Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fasting conditions. Methods: This was a phase I, randomized, single-dose, two-period, two-sequence, crossover study to evaluate the bioequivalence (BE) profiles of two fixed-dose combinations (FDCs) of empagliflozin/metformin. Cmax, AUC0-t and AUC0-∞ from test and reference formulations were evaluated to access BE. The plasma concentrations were measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. Of the 24 subjects enrolled, 23 completed both periods of the study. The two formulations test and reference were considered bioequivalent if 90% confidence interval (CI) fell within 80.00% - 125.00% for Cmax, AUC0-t and AUC0-∞. Tolerability and safety were assessed throughout the study. Results: The pharmacokinetic (PK) parameters were similar between the test product (T) and reference product (R) Synjardy®. The 90% CI of the test/reference ratios of log-transformed PK parameters point estimates was Cmax: 89.87% (85.68% - 94.27%), AUC0-t: 87.91% (83.65% - 92.39%) and AUC0-∞: 87.16% (82.80% - 91.75%) to empagliflozin and Cmax: 92.19% (87.95% - 96.65%), AUC0-t: 91.38% (84.42% - 98.91%) and AUC0-∞: 93.78% (83.82% - 104.93%) to metformin respectively (90% CI for all PK parameters fell within 80.00% - 125.00%). Conclusion: Our results demonstrated BE between the test and reference formulations of oral tablets of empagliflozin 12.5 mg/metformin 1000 mg (FDC) in healthy male subjects under fasting conditions.

Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy

Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.

First‑principles study on electronic structure,optical and magnetic properties of rare earth elements X(X=Sc,Y,La,Ce,Eu)doped with two‑dimensional GaSe

The electronic structure,magnetic,and optical properties of two-dimensional(2D)GaSe doped with rare earth elements X(X=Sc,Y,La,Ce,Eu)were calculated using the first-principles plane wave method based on den-sity functional theory.The results show that intrinsic 2D GaSe is a p-type nonmagnetic semiconductor with an indi-rect bandgap of 2.6611 eV.The spin-up and spin-down channels of Sc-,Y-,and La-doped 2D GaSe are symmetric,they are non-magnetic semiconductors.The magnetic moments of Ce-and Eu-doped 2D GaSe are 0.908μ_(B)and 7.163μ_(B),which are magnetic semiconductors.Impurity energy levels appear in both spin-up and spin-down chan-nels of Eu-doped 2D GaSe,which enhances the probability of electron transition.Compared with intrinsic 2D GaSe,the static dielectric constant of the doped 2D GaSe increases,and the polarization ability is strengthened.The ab-sorption spectrum of the doped 2D GaSe shifts in the low-energy direction,and the red-shift phenomenon occurs,which extends the absorption spectral range.The optical reflection coefficient of the doped 2D GaSe is improved in the low energy region,and the improvement of Eu-doped 2D GaSe is the most obvious.

Adaptive H_(∞)Filtering Algorithm for Train Positioning Based on Prior Combination Constraints

To solve the problem of data fusion for prior information such as track information and train status in train positioning,an adaptive H∞filtering algorithm with combination constraint is proposed,which fuses prior information with other sensor information in the form of constraints.Firstly,the train precise track constraint method of the train is proposed,and the plane position constraint and train motion state constraints are analysed.A model for combining prior information with constraints is established.Then an adaptive H∞filter with combination constraints is derived based on the adaptive adjustment method of the robustness factor.Finally,the positioning effect of the proposed algorithm is simulated and analysed under the conditions of a straight track and a curved track.The results show that the positioning accuracy of the algorithm with constrained filtering is significantly better than that of the algorithm without constrained filtering and that the algorithm with constrained filtering can achieve better performance when combined with track and condition information,which can significantly reduce the train positioning error.The effectiveness of the proposed algorithm is verified.

General Optimal Trajectory Planning:Enabling Autonomous Vehicles with the Principle of Least Action

This study presents a general optimal trajectory planning(GOTP)framework for autonomous vehicles(AVs)that can effectively avoid obstacles and guide AVs to complete driving tasks safely and efficiently.Firstly,we employ the fifth-order Bezier curve to generate and smooth the reference path along the road centerline.Cartesian coordinates are then transformed to achieve the curvature continuity of the generated curve.Considering the road constraints and vehicle dynamics,limited polynomial candidate trajectories are generated and smoothed in a curvilinear coordinate system.Furthermore,in selecting the optimal trajectory,we develop a unified and auto-tune objective function based on the principle of least action by employing AVs to simulate drivers’behavior and summarizing their manipulation characteristics of“seeking benefits and avoiding losses.”Finally,by integrating the idea of receding-horizon optimization,the proposed framework is achieved by considering dynamic multi-performance objectives and selecting trajectories that satisfy feasibility,optimality,and adaptability.Extensive simulations and experiments are performed,and the results demonstrate the framework’s feasibility and effectiveness,which avoids both dynamic and static obstacles and applies to various scenarios with multi-source interactive traffic participants.Moreover,we prove that the proposed method can guarantee real-time planning and safety requirements compared to drivers’manipulation.

The Five Principles of Peaceful Coexistence:Connotations in International Law and Contemporary Relevance

The year 2024 marks the 70th anniversary of the Five Principles of Peaceful Coexistence initiated by China.As an anchor foreign policy of New China and its first contribution of public product for the international community,the Five Principles have made a historic contribution to the building of a new type of just and equitable international relations,advancing the purposes and principles of the Charter of the United Nations,and becoming universally applicable basic norms for international relations and key fundamental principles of international law.

Stochastic Maximum Principle for Optimal Advertising Models with Delay and Non-Convex Control Spaces

In this paper we study optimal advertising problems that model the introduction of a new product into the market in the presence of carryover effects of the advertisement and with memory effects in the level of goodwill. In particular, we let the dynamics of the product goodwill to depend on the past, and also on past advertising efforts. We treat the problem by means of the stochastic Pontryagin maximum principle, that here is considered for a class of problems where in the state equation either the state or the control depend on the past. Moreover the control acts on the martingale term and the space of controls U can be chosen to be non-convex but now the space of controls U can be chosen to be non-convex. The maximum principle is thus formulated using a first-order adjoint Backward Stochastic Differential Equations (BSDEs), which can be explicitly computed due to the specific characteristics of the model, and a second-order adjoint relation.