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.

EXISTENCE AND UNIQUENESS OF SOLUTIONS FOR NONLINEAR FRACTIONAL DIFFERENTIAL EQUATIONS WITH NON-SEPARATED TYPE INTEGRAL BOUNDARY CONDITIONS

In this paper, we study a boundary value problem of nonlinear fractional dif- ferential equations of order q （1 〈 q 〈 2） with non-separated integral boundary conditions. Some new existence and uniqueness results are obtained by using some standard fixed point theorems and Leray-Schauder degree theory. Some illustrative examples are also presented. We extend previous results even in the integer case q = 2.

On a Discrete Fractional Boundary Value Problem with Nonlocal Fractional Boundary Conditions

In this paper, we investigate the nonlinear fractional difference equation with nonlocal fractional boundary conditions. We derive the Green's function for this problem and show that it satisfies certain properties. Some existence results are obtained by means of nonlinear alternative of Leray-Schauder type theorem and Krasnosel-skii's fixed point theorem.

满足条件(P)的循环序S-系对序幺半群的同调分类

研究同余λ(x ^(p),x^( q))的一些重要性质,单循环序S-系S/λ(x,x^(2))满足条件(P)和强平坦性的等价刻画以及满足条件(P)的循环序S-系对序幺半群的同调分类.

S弯收扩喷管过膨胀状态下流动分离特性研究

为了研究S弯收扩喷管过膨胀状态下的流动分离特性,数值模拟了不同落压比(NPR)下S弯收扩喷管内的流动特征。结果表明:在落压比为2.0时,喷管内发生非对称分离,出现非对称的双“λ”激波结构,喷流整体向上偏转,上侧出现限制性流动分离RSS,下侧出现自由性流动分离FSS,并产生三维分离涡,喷流出现明显的三维效应。随着落压比从高度过膨胀状态下开始增加,喷管下侧保持FSS不变,喷管上侧RSS逐渐向后移动,直至与外界大气相连,转变为FSS,之后随着落压比增加,上下侧分离结构逐渐对称。推力矢量角随着落压比的增加先增加,后在极小的落压比变化范围内快速降低,直至变为0°,之后保持0°不变。

Shifting balance from neurodegeneration to regeneration of the brain: a novel therapeutic approach to Alzheimer's disease and related neurodegenerative conditions

Neurodegeneration is one of the biggest public health problems in modern society. Age-associated neurodegeneration, which is accelerated several-fold in Alzheimer＇s disease （AD） alone, is not only an enormous social and economic burden to the affected in- dividuals and their families, but is also a great scientific challenge. Currently 25-35 million people worldwide suffer from AD, the single largest cause of dementia in middle- to old-aged individuals. These numbers are projected to triple by 2050 if no treatment to prevent or reverse AD is developed.

Spline Fictitious Boundary Element Alternating Method for Edge Crack Problems with Mixed Boundary Conditions

The alternating method based on the fundamental solutions of the infinite domain containing a crack,namely Muskhelishvili’s solutions,divides the complex structure with a crack into a simple model without crack which can be solved by traditional numerical methods and an infinite domain with a crack which can be solved by Muskhelishvili’s solutions.However,this alternating method cannot be directly applied to the edge crack problems since partial crack surface of Muskhelishvili’s solutions is located outside the computational domain.In this paper,an improved alternating method,the spline fictitious boundary element alternating method(SFBEAM),based on infinite domain with the combination of spline fictitious boundary element method(SFBEM)and Muskhelishvili’s solutions is proposed to solve the edge crack problems.Since the SFBEM and Muskhelishvili’s solutions are obtained in the framework of infinite domain,no special treatment is needed for solving the problem of edge cracks.Different mixed boundary conditions edge crack problems with varies of computational parameters are given to certify the high precision,efficiency and applicability of the proposed method compared with other alternating methods and extend finite element method.

The Quantum Condition That Should Have Been Assumed by Bohr When Deriving the Energy Levels of a Hydrogen Atom

Bohr assumed a quantum condition when deriving the energy levels of a hydrogen atom. This famous quantum condition was not derived logically, but it beautifully explained the energy levels of the hydrogen atom. Therefore, Bohr’s quantum condition was accepted by physicists. However, the energy levels predicted by the eventually completed quantum mechanics do not match perfectly with the predictions of Bohr. For this reason, it cannot be said that Bohr’s quantum condition is a perfectly correct assumption. Since the mass of an electron which moves inside a hydrogen atom varies, Bohr’s quantum condition must be revised. However, the newly derived relativistic quantum condition is too complex to be assumed at the beginning. The velocity of an electron in a hydrogen atom is known as the Bohr velocity. This velocity can be derived from the formula for energy levels derived by Bohr. The velocity v of an electron including the principal quantum number n is given by αc/n. This paper elucidates the fact that this formula is built into Bohr’s quantum condition. It is also concluded in this paper that it is precisely this velocity formula that is the quantum condition that should have been assumed in the first place by Bohr. From Bohr’s quantum condition, it is impossible to derive the relativistic energy levels of a hydrogen atom, but they can be derived from the new quantum condition. This paper proposes raising the status of the previously-known Bohr velocity formula.

Bioleaching behavior and surface property of pyrites in different metallogenic conditions

The bioleaching behaviors and surface properties of pyrites in two metallogenic conditions by Sulfobacillus thermosulfidooxidans were investigated by adsorption tests, zeta-potential measurements and bioleaching experiments. It is found that there were significant differences in the microorganism adsorption capacity, electrokinetic properties and bioleaching behaviors for the two pyrites. The S. thermosulfidooxidans adsorption capacity on high temperature hydrothermal(hy_high_temp) pyrite is larger than that on sendimentary coal(sed_coal) pyrite. It may be that more extracellular polymeric substances(EPS) is produced when it is difficult for microorganism to make use of hy_high_temp pyrite as source of energy, and get leaching bacteria attached to pyrite by means of EPS. The zeta-potential measurements indicated that zeta-potential value of hy_high_temp pyrite was higher than that of sed_coal pyrite in pH range of 2–10. After interacting with cells, the IEP(Iso-Electric Point) of hy_high_temp pyrite shifted obviously to that of bacterial. In contrast, the IEP of sed_coal pyrite remained unchanged nearly. The bioleaching results showed that hy_high_temp pyrite did not dissolve and the leaching extent was only 0.82%, while that of sed_coal pyrite was 34.59%. Attempts were taken to illustrate the remarkable difference between bioleaching results of two pyrites from a semiconductor energy band theory perspective.

Intranasal Administration of Conditioned Medium from Cultured Mesenchymal Stem Cells Improves Cognitive Impairment in Olfactory Bulbectomized Mice

Alzheimer’s disease (AD) is the common cause of dementia which shows the neuro-pathologies like an accumulation of amyloid-β (Aβ) and degeneration of cholinergic neuron. Olfactory bulbectomized (OBX) mice show some of AD features, so they have been used to research as AD model. Mesenchymal stem cells (MSCs) can differentiate into many kinds of cells, including neuronal cells. In this study, we intranasally administrated the conditioned medium derived from cultured umbilical cord (UC) MSCs. The intranasal administration of the MSCs medium restored the cognitive impairment observed in OBX mice. In addition, the decreased number of choline acetyltransferase-positive cells in the medial septum was restored by the conditioned medium administration. In conclusion, MSCs-derived conditioned medium may have protective effects of cholinergic neurons in the medial septum, thereby rescuing the cognitive impairment of OBX.

Electrical Power Losses in a Photovoltaic Solar Cell Operating under Partial Shading Conditions

The aim of this paper is to determine the power losses recorded by a PV generator operating under partial shading conditions. These losses are evaluated through two distinct methods. The first method is based on mathematical modeling, while the second is based on Simulink’s physical model. The losses recorded are considerable and increase as a function of the increase in the percentage of shading up to a limit value where they become constant in the case where an ideal by-pass diode is connected in parallel with the modules. This limit value is non-existent in the case where the bypass diode is not ideal, which in fact corresponds to the real model. However, it emerges that the power losses are minimized in a PV system comprising bypass diodes, in particular in the case where the partial shading is considerable.

Construction of Wave-free Potentials and Multipoles in a Two-layer Fluid Having Free-surface Boundary Condition with Higher-order Derivatives

There is a large class of problems in the field of fluid structure interaction where higher-order boundary conditions arise for a second-order partial differential equation. Various methods are being used to tackle these kind of mixed boundary-value problems associated with the Laplace’s equation （or Helmholtz equation） arising in the study of waves propagating through solids or fluids. One of the widely used methods in wave structure interaction is the multipole expansion method. This expansion involves a general combination of a regular wave, a wave source, a wave dipole and a regular wave-free part. The wave-free part can be further expanded in terms of wave-free multipoles which are termed as wave-free potentials. These are singular solutions of Laplace’s equation or two-dimensional Helmholz equation. Construction of these wave-free potentials and multipoles are presented here in a systematic manner for a number of situations such as two-dimensional non-oblique and oblique waves, three dimensional waves in two-layer fluid with free surface condition with higher order partial derivative are considered. In particular, these are obtained taking into account of the effect of the presence of surface tension at the free surface and also in the presence of an ice-cover modelled as a thin elastic plate. Also for limiting case, it can be shown that the multipoles and wave-free potential functions go over to the single layer multipoles and wave-free potential.

DATA MODELING METHOD BASED ON PARTIAL LEAST SQUARE REGRESSION AND APPLICATIO N IN CORRELATION ANALYSIS OF THE STATOR BARS CONDITION PARAMETERS

Objective To investigate v arious data message of the stator bars condition parameters under the condition that only a few samples are available, especially about correlation information between the nondestructive parameters and residual breakdown voltage of the stat or bars. Methods Artificial stator bars is designed to simulat e the generator bars. The partial didcharge( PD) and dielectric loss experiments are performed in order to obtain the nondestructive parameters, and the residua l breakdown voltage acquired by AC damage experiment. In order to eliminate the dimension effect on measurement data, raw data is preprocessed by centered-compr ess. Based on the idea of extracting principal components, a partial least squar e (PLS) method is applied to screen and synthesize correlation information betwe en the nondestructive parameters and residual breakdown voltage easily. Moreover , various data message about condition parameters are also discussed. Re sults Graphical analysis function of PLS is easily to understand vario us data message of the stator bars condition parameters. The analysis Results ar e consistent with result of aging testing. Conclusion The meth od can select and extract PLS components of condition parameters from sample dat a, and the problems of less samples and multicollinearity are solved effectively in regression analysis.

Stabilization of Discrete-time 2-D T-S Fuzzy Systems Based on New Relaxed Conditions

This paper is concerned with the problem of stabilization of the Roesser type discrete-time nonlinear 2-D system that plays an important role in many practical applications. First, a discrete-time 2-D T-S fuzzy model is proposed to represent the underlying nonlinear 2-D system. Second, new quadratic stabilization conditions are proposed by applying relaxed quadratic stabilization technique for 2-D case. Third, for sake of further reducing conservatism, new non-quadratic stabilization conditions are also proposed by applying a new parameter-dependent Lyapunov function, matrix transformation technique, and relaxed technique for the underlying discrete-time 2-D T-S fuzzy system. Finally, a numerical example is provided to illustrate the effectiveness of the proposed results.

Investigation of Numerical Conditions of Moving Particle Semi‑implicit for Two‑Dimensional Wedge Slamming

The sensitivity of moving particle semi-implicit(MPS)simulations to numerical parameters is investigated in this study.Although the verifcation and validation(V&V)are important to ensure accurate numerical results,the MPS has poor perfor-mance in convergences with a time step size.Therefore,users of the MPS need to tune numerical parameters to ft results into benchmarks.However,such tuning parameters are not always valid for other simulations.We propose a practical numerical condition for the MPS simulation of a two-dimensional wedge slamming problem(i.e.,an MPS-slamming condition).The MPS-slamming condition is represented by an MPS-slamming number,which provides the optimum time step size once the MPS-slamming number,slamming velocity,deadrise angle of the wedge,and particle size are decided.The simulation study shows that the MPS results can be characterized by the proposed MPS-slamming condition,and the use of the same MPS-slamming number provides a similar fow.

Microscopic Observation and Stability Study on the Fe_3s_4 Nanocrystals Synthesizedunder Thermal and Humid Conditions

Fe3S4 is important magnetic mineral that widely exists in the sediments of lakes and oceans. It can not only instruct reducing environment that contains organic matter and sulfate, but also provide paleomagnetic signal for paleoenvironmet research. Simultaneously, as a new type of magnetic material, it causes attention. Because Fe3S4 generally exists as an unstable intermediate, it is stringent in preparation conditions. Although some scholars have conducted on the synthesis experiments of Fe3S4 materials, the research on its stable conditions, formation mechanism and evolution process is not yet depth. Accordingly, defining the stable conditions and revealing evolution law of Fe3S4 nanocrystals have important significance for the determination of environmental conditions and the preparation of pure Fe3S4 nanomaterials.

Navier’s slip condition on time dependent Darcy-Forchheimer nanofluid using spectral relaxation method

In industrial applications involving metal and polymer sheets, the flow situation is strongly unsteady and the sheet temperature is a mixture of prescribed surface temperature and heat flux. Further, a proper choice of cooling liquid is also an important component of the analysis to achieve better outputs. In this paper, we numerically investigate Darcy-Forchheimer nanoliquid flows past an unsteady stretching surface by incorporating various effects, such as the Brownian and thermophoresis effects, Navier’s slip condition and convective thermal boundary conditions. To solve the governing equations, using suitable similarity transformations, the nonlinear ordinary differential equations are derived and the resulting coupled momentum and energy equations are numerically solved using the spectral relaxation method. Through the systematically numerical investigation, the important physical parameters of the present model are analyzed. We find that the presence of unsteadiness parameter has significant effects on velocity, temperature, concentration fields, the associated heat and mass transport rates. Also, an increase in inertia coefficient and porosity parameter causes an increase in the velocity at the boundary.

Investigation of nanofluid flow in a vertical channel considering polynomial boundary conditions by Akbari-Ganji’s method

In this research,a vertical channel containing a laminar and fully developed nanofluid flow is investigated.The channel surface’s boundary conditions for temperature and volume fraction functions are considered qth-order polynomials.The equations related to this problem have been extracted and then solved by the AGM and validated through the Runge-Kutta numerical method and another similar study.In the study,the effect of parameters,including Grashof number,Brownian motion parameter,etc.,on the motion,velocity,temperature,and volume fraction of nanofluids have been analyzed.The results demonstrate that increasing the Gr number by 100%will increase the velocity profile function by 78%and decrease the temperature and fraction profiles by 20.87%and 120.75%.Moreover,rising the Brownian motion parameter in five different sizes(0.1,0.2,0.3,0.4,and 0.5)causes lesser velocity,about 24.3%at first and 4.35%at the last level,and a maximum 52.86%increase for temperature and a 24.32%rise for ψ occurs when N b rises from 0.1 to 0.2.For all N_(t) values,at least 55.44%,18.69%,for F(η),andΩ(η),and 20.23%rise for ψ(η)function is observed.Furthermore,enlarging the N r parameter from 0.25 to 0.1 leads F(η)to rise by 199.7%,fluid dimensionless temperature,and dimensional volume fraction to decrease by 18%and 92.3%.In the end,a greater value of q means a more powerful energy source,amplifying all velocity,temperature,and volume fraction functions.The main novelty of this research is the combined convection qth-order polynomials boundary condition applied to the channel walls.Moreover,The AMG semi-analytical method is used as a novel method to solve the governing equations.

AMBARZUMYAN’S THEOREM WITH EIGENPARAMETER IN THE BOUNDARY CONDITIONS

In this paper, the classical Ambarzumyan’s theorem for the regular SturmLiouville problem is extended to the case in which the boundary conditions are eigenparameter dependent. Specifically, we show that if the spectrum of the operator D 2 ＋q with eigenparameter dependent boundary conditions is the same as the spectrum belonging to the zero potential, then the potential function q is actually zero.

Physical Conditions of China's Adult Population

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