Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

Modernising autism spectrum disorder model engineering and treatment via CRISPR-Cas9:A gene reprogramming approach

A neurological abnormality called autism spectrum disorder(ASD)affects how a person perceives and interacts with others,leading to social interaction and communication issues.Limited and recurring behavioural patterns are another feature of the illness.Multiple mutations throughout development are the source of the neurodevelopmental disorder autism.However,a well-established model and perfect treatment for this spectrum disease has not been discovered.The rising era of the clustered regularly interspaced palindromic repeats(CRISPR)-associated protein 9(Cas9)system can streamline the complexity underlying the pathogenesis of ASD.The CRISPR-Cas9 system is a powerful genetic engineering tool used to edit the genome at the targeted site in a precise manner.The major hurdle in studying ASD is the lack of appropriate animal models presenting the complex symptoms of ASD.Therefore,CRISPR-Cas9 is being used worldwide to mimic the ASD-like pathology in various systems like in vitro cell lines,in vitro 3D organoid models and in vivo animal models.Apart from being used in establishing ASD models,CRISPR-Cas9 can also be used to treat the complexities of ASD.The aim of this review was to summarize and critically analyse the CRISPRCas9-mediated discoveries in the field of ASD.

High-resolution neutronics model for ^(238)Pu production in high-flux reactors

We proposed and compared three methods(filter burnup,single energy burnup,and burnup extremum analysis)to build a high-resolution neutronics model for 238Pu production in high-flux reactors.The filter burnup and single energy burnup methods have no theoretical approximation and can achieve a spectrum resolution of up to~1 eV,thereby constructing the importance curve and yield curve of the full energy range.The burnup extreme analysis method combines the importance and yield curves to consider the influence of irradiation time on production efficiency,thereby constructing extreme curves.The three curves,which quantify the transmutation rate of the nuclei in each energy region,are of physical significance because they have similar distributions.A high-resolution neutronics model for ^(238)Pu production was established based on these three curves,and its universality and feasibility were proven.The neutronics model can guide the neutron spectrum optimization and improve the yield of ^(238)Pu by up to 18.81%.The neutronics model revealed the law of nuclei transmutation in all energy regions with high spectrum resolution,thus providing theoretical support for high-flux reactor design and irradiation production of ^(238)Pu.

Fractal and Multifractal Modeling of Hydrothermal Mineral Deposit Spectrum: Application to Gold Deposits in Abitibi Area, Ontario, Canada

A number of fractal/multifractal methods are introduced for quantifying the mineral deposit spectrum which include a number-size model, grade-tonnage model, power spectrum model, multifractal model and an eigenvalue spectrum model. The first two models characterize mineral deposits spectra based on relationships among the measures of mineral deposits. These include the number of deposits, size of deposits, concentration and volume of mineral deposits. The last three methods that deal with the spatial-temporal spectra of mineral deposit studies are all expected to be popularized in near future. A case study of hydrothermal gold deposits from the Abitibi area, a world-class mineral district, is used to demonstrate the principle as well as the applications of methods proposed in this paper. It has been shown that fractal and multifractal models are generally applicable to modeling of mineral deposits and occurrences. Clusters of mineral deposits were identified by several methods including the power spectral analysis, singularity analysis and the eigenvalue analysis. These clusters contain most of the known mineral deposits in the Timmins and Kirkland Lake camps.

Identification of the unknown shielding parameters with gammaray spectrum using a derivative-free inverse radiation transport model

Identifying the unknown geometric and material information of a multi-shield object by analyzing the radiation signature measurements is always an important problem in national and global security. In order to identify the unknown shielding layer thicknesses of a source/shield system with gamma-ray spectra, we have developed a derivative-free inverse radiation transport model based on a differential evolution algorithm with global and local neighbourhoods(IRT-DEGL). In the present paper, the IRT-DEGL model is further extended for estimating the unknown thicknesses with random initial guesses and material mass densities of multi-shielding layers as well as their combinations. Using the detected gamma-ray spectra,the illustration of inverse studies is implemented and the main influence factors for inverse results are also analyzed.

AUTOREGRESSIVE MODEL AND POWER SPECTRUM CHARATERISTICS OF CURRENT SIGNAL IN HIGH FREQUENCY GROUP PULSE MICRO-ELECTROCHEMICAL MACHINING

The identification of the inter-electrode gap size in the high frequency group pulse micro-electrochemical machining （HGPECM） is mainly discussed. The auto-regressive（AR） model of group pulse current flowing across the cathode and the anode are created under different situations with different processing parameters and inter-electrode gap size. The AR model based on the current signals indicates that the order of the AR model is obviously different relating to the different processing conditions and the inter-electrode gap size; Moreover, it is different about the stability of the dynamic system, i.e. the white noise response of the Green＇s function of the dynamic system is diverse. In addition, power spectrum method is used in the analysis of the dynamic time series about the current signals with different inter-electrode gap size, the results show that there exists a strongest power spectrum peak, characteristic power spectrum（CPS）, to the current signals related to the different inter-electrode gap size in the range of 0～5 kHz. Therefore, the CPS of current signals can implement the identification of the inter-electrode gap.

A new spatial coherence model and analytical coeffi cients for multi-support response spectrum combination

In this paper, a new spatial coherence model of seismic ground motions is proposed by a fitting procedure. The analytical expressions of modal combination （correlation） coefficients of structural response are developed for multi-support seismic excitations. The coefficients from both the numerical integration and analytical solutions are compared to verify the accuracy of the solutions. It is shown that the analytical expressions of numerical modal combination coefficients are of high accuracy. The results of random responses of an example bridge show that the analytical modal combination coefficients developed in this paper are accurate enough to meet the requirements needed in practice. In addition, the computational efficiency of the analytical solutions of the modal combination coefficients is demonstrated by the response computation of the example bridge. It is found that the time required for the structural response analysis by using the analytical modal combination coefficients is less than 1/20 of that using numerical integral methods.

The Structure of Essential Spectra and Discrete Spectrum of Three-Electron Systems in the Impurity Hubbard Model—Quartet State

We consider a three-electron system in the Impurity Hubbard model with a coupling between nearest-neighbors. Our research aim consists of studying the structure of essential spectrum and discrete spectra of the energy operator of three-electron systems in the impurity Hubbard model in the quartet state of the system in a v-dimensional lattice. We have reduced the study of the spectrum of the three-electron quartet state operator in the impurity Hubbard model to the study of the spectrum of a simpler operator. We proved the essential spectra of the three-electron systems in the Impurity Hubbard model in the quartet state is the union of no more than six segments, and the discrete spectrum of the system is consists of no more than four eigenvalues.

Analysis of prompt fission neutron spectrum and multiplicity for ^(237)Np(n, f) in the frame of multi-modal Los Alamos model

The improved version of Los Alamos model with the multi-modal fission approach is used to analyse the prompt fission neutron spectrum and multiplicity for the neutron-induced fission of 237Np. The spectra of neutrons emitted from fragments for the three most dominant fission modes （standard Ⅰ, standard Ⅱ and superlong） are calculated separately and the total spectrum is synthesized. The multi-modal parameters contained in the spectrum model are determined on the basis of experimental data of fission fragment mass distributions. The calculated total prompt fission neutron spectrum and multiplicity are better agreement with the experimental data than those obtained from the conventional treatment of the Los Alamos model.

Understanding autism spectrum disorders with animal models:applications,insights,and perspectives

Autism spectrum disorder(ASD)is typically characterized by common deficits in social skills and repetitive/stereotyped behaviors.It is widely accepted that genetic and environmental factors solely or in combination cause ASD.However,the underlying pathogenic mechanism is unclear due to its highly heterogeneous nature.To better understand the pathogenesis of ASD,various animal models have been generated,which can be generally divided into genetic,environment-induced,and idiopathic animal models.In this review,we summarize the common animals used for ASD study and then discuss the applications,clinical insights,as well as challenges and prospects of current ASD animal models.

An ocean current inversion accuracy analysis based on a Doppler spectrum model

Microwave remote sensing is one of the most useful methods for observing the ocean parameters. The Doppler frequency or interferometric phase of the radar echoes can be used for an ocean surface current speed retrieval,which is widely used in spaceborne and airborne radars. While the effect of the ocean currents and waves is interactional. It is impossible to retrieve the ocean surface current speed from Doppler frequency shift directly. In order to study the relationship between the ocean surface current speed and the Doppler frequency shift, a numerical ocean surface Doppler spectrum model is established and validated with a reference. The input parameters of ocean Doppler spectrum include an ocean wave elevation model, a directional distribution function, and wind speed and direction. The suitable ocean wave elevation spectrum and the directional distribution function are selected by comparing the ocean Doppler spectrum in C band with an empirical geophysical model function（CDOP）. What is more, the error sensitivities of ocean surface current speed to the wind speed and direction are analyzed. All these simulations are in Ku band. The simulation results show that the ocean surface current speed error is sensitive to the wind speed and direction errors. With VV polarization, the ocean surface current speed error is about 0.15 m/s when the wind speed error is 2 m/s, and the ocean surface current speed error is smaller than 0.3 m/s when the wind direction error is within 20° in the cross wind direction.

Neurodevelopmental Timing of Ethanol Exposure May Contribute to Observed Heterogeneity of Behavioral Deficits in a Mouse Model of Fetal Alcohol Spectrum Disorder (FASD)

Maternal drinking during pregnancy can result in a wide spectrum of cognitive and behavioral abnormalities termed fetal alcohol spectrum disorders (FASD). The heterogeneity observed in FASD-related phenotypes can be attributed to a number of environmental and genetic factors;however, ethanol dose and timing of exposure may have significant influences. Here, we report the behavioral effects of acute, binge-like ethanol exposure at three neurodevelopmental times corresponding to the first, second, and third trimester of human development in C57BL/6J mice. Results show that developmental ethanol exposure consistently delays the development of basic motor skill reflexes and coordination as well as impairs spatial learning and memory. Observed changes in activity and anxiety-related behaviors, however, appear to be dependent on timing of alcohol exposure. The variability in behaviors between different treatment models suggests that these may be useful in evaluating the mechanisms disrupted by ethanol at specific neurodevelopmental times. The results provide further evidence that, regardless of developmental stage, the developing brain is acutely sensitive to alcohol exposure.

Structure of Essential Spectrum and Discrete Spectra of the Energy Operator of Five-Electron Systems in the Hubbard Model. Third and Fourth Doublet States

We consider a five-electron system in the Hubbard model with a coupling between nearest-neighbors. The structure of essential spectrum and discrete spectrum of the systems in the third and fourth doublet states in a v-dimensional lattice is investigated. We prove that the essential spectrum of the system in a third doublet state consists is the union of at most four segments, and discrete spectrum of the system is empty. We show that the essential spectrum of the system in a fourth doublet state consists of the union of at most seven segments, and discrete spectrum of the system consists of no more than one point.

An unsupervised clustering method for nuclear magnetic resonance transverse relaxation spectrums based on the Gaussian mixture model and its application

To make the quantitative results of nuclear magnetic resonance(NMR) transverse relaxation(T;) spectrums reflect the type and pore structure of reservoir more directly, an unsupervised clustering method was developed to obtain the quantitative pore structure information from the NMR T;spectrums based on the Gaussian mixture model(GMM). Firstly, We conducted the principal component analysis on T;spectrums in order to reduce the dimension data and the dependence of the original variables. Secondly, the dimension-reduced data was fitted using the GMM probability density function, and the model parameters and optimal clustering numbers were obtained according to the expectation-maximization algorithm and the change of the Akaike information criterion. Finally, the T;spectrum features and pore structure types of different clustering groups were analyzed and compared with T;geometric mean and T;arithmetic mean. The effectiveness of the algorithm has been verified by numerical simulation and field NMR logging data. The research shows that the clustering results based on GMM method have good correlations with the shape and distribution of the T;spectrum, pore structure, and petroleum productivity, providing a new means for quantitative identification of pore structure, reservoir grading, and oil and gas productivity evaluation.

Slope wavenumber spectrum models of capillary and capillary-gravity waves

Capillary and capillary-gravity waves possess a random character, and the slope wavenumber spectra of them can be used to represent mean distributions of wave energy with respect to spatial scale of variability. But simple and practical models of the slope wavenumber spectra have not been put forward so far. In this article, we address the accurate definition of the slope wavenumber spectra of water surface capillary and capillary-gravity waves. By combining the existing slope wavenumber models and using the dispersion relation of water surface waves, we derive the slope wavenumber spectrum models of capillary and capillary-gravity waves. Simultaneously, by using the slope wavenumber models, the dependence of the slope wavenumber spectrum on wind speed is analyzed using data obtained in an experiment which was performed in a laboratory wind wave tank. Generally speaking, the slope wavenumber spectra are influenced profoundly by the wind speed above water surface. The slope wavenumber spectrum increases with wind speed obviously and do not cross each other for different wind speeds. But, for the same wind speed, the slope wavenumber spectra are essentially identical, even though the capillary and capillary-gravity waves are excited at different times and locations. Furthermore, the slope wavenumber spectra obtained from the models agree quite well with experimental results as regards both the values and the shape of the curve.

ON MULTIPLE SOLUTIONS TO A LOW-SPECTRUM MODEL OF OCEANIC CURRENT DRIVEN BY THE BOUNDARY FORCE——THE BIMODALITY OF THE KUROSHIO SOUTH OF JAPAN

This low-spectrun medel study on the multiple solutions to a nonlinear quasi-geostrophic ocanic cur-rent equation shows that they depend on the combination of Ro, Re, λ and ε, that the bimedaity of theKuroshio depends strongly on the nonlinear effect represented by Ro and λ, and that its occurrenceprobability is reduced by the dissipation represented by Re and ε. The stability of solutions is discussed indetail with Hurwitz’s theory.

PREDICTION OF THE RHEOLOGICAL PROPERTIES OF STAR—TYPE BRANCHED POLYMER SOLUTIONS BY MEANS OF THE FIXED SPECTRUM MODEL

The Rouse-Zimm model with slippage was improved and the basic parameters of modelwere modified to explain the rheological properties of star-type branched polymersolutions. The theoretical results show good agreement with experimental data.

Implementing a multispecies size-spectrum model in a datapoor ecosystem

Multispecies ecological models have been used for predicting the effects of fishing activity and evaluating the performance of management strategies. Size-spectrum models are one type of physiologically-structured ecological model that provide a feasible approach to describing fish communities in terms of individual dietary variation and ontogenetic niche shift. Despite the potential of ecological models in improving our understanding of ecosystems, their application is usually limited for data-poor fisheries. As a first step in implementing ecosystem-based fisheries management（EBFM）, this study built a size-spectrum model for the fish community in the Haizhou Bay, China. We describe data collection procedures and model parameterization to facilitate the implementation of such size-spectrum models for future studies of data-poor ecosystems. The effects of fishing on the ecosystem were exemplified with a range of fishing effort and were monitored with a set of ecological indicators. Total community biomass, biodiversity index, W-statistic, LFI（Large fish index）, Mean W（mean body weight） and Slope（slope of community size spectra） showed a strong non-linear pattern in response to fishing pressure, and largest fishing effort did not generate the most drastic responses in certain scenarios. We emphasize the value and feasibility of developing size-spectrum models to capture ecological dynamics and suggest limitations as well as potential for model improvement. This study aims to promote a wide use of this type of model in support of EBFM.

An Appropriate Unidirectional Wave Spectrum Model for the Strait of Hormuz

The objective of this paper is to introduce an appropriate unidirectional wave spectrum model for the Strait of Hormuz. The research is focused on assessing performance of standard wave spectrum models in the region. By evaluating such models based on valuable measurement data recently published, the calibration procedure has been conducted on such standard models to reach a better concordance between a modified standard spectral model and observed field spectra. The calibration is performed initially with respect to four distinct directions related to four available measurement stations. So, it results in four sets of coefficients for a nominated model. Next, it is continued to reach just one model insensitive to directions. Results clearly showed that the International Towing Tank Conference （ITTC） model is more appropriate than Joint North Sea Wave Project （JONSWAP） and Pierson and Moskowitz （PM） models in this area, even without any calibration. However, modifications have been successful on improving the conformity of the model.

On Evaluating the Efficacy of Predictive Models for Cognitive Radio Spectrum Availability in Nigeria

In order to avoid the undesired interference with the activities of the primary users in cognitive radio networks, the secondary users are required to be able to predict the behavior of the primary users so as to leave the channel before the arrival of such licensed owner of the spectrum. While a number of existing literatures on cognitive radio spectrum prediction employ the use of propagation curves for predicting the spectrum holes otherwise known as TV white space, these models are built based on measurements conducted in regions that are different from Nigeria, suitability in terms of usage may therefore vary due to environmental factors and terrain profile. This work evaluates the efficacy of the developed model in predicting the cognitive spectrum availability in Nigeria. Models capable of predicting spectrum occupancy in the time domain using discrete-time two-state Markov chain with an appropriate Duty Cycle (DC) model and also a modified m-bell shaped exponential equation were formulated. The result obtained in all cases considered shows that the formulated models are appropriate to be used in any environment if the parameters were carefully extracted from the data. This work has also demonstrated that the accuracy of Markov chain models depends on the level of usage of a spectrum under consideration and may therefore not give desirable results when employed in some other spectrum.