Tau truncation in the pathogenesis of Alzheimer's disease:a narrative review

Alzheimer's disease is characterized by two major neuropathological hallmarks—the extracellularβ-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein.Recent studies suggest that dysregulation of the microtubuleassociated protein Tau,especially specific proteolysis,could be a driving force for Alzheimer's disease neurodegeneration.Tau physiologically promotes the assembly and stabilization of microtubules,whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers,resulting in them gaining prion-like characteristics.In addition,Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner.This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments,investigates the role of specific truncations in physiological and pathological states of Alzheimer's disease,and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer's disease.

Continuity of truncated Hardy-Littlewood maximal function

This paper focuses on the continuity of the truncated Hardy-Littlewood maximal function.We first show that the truncated Hardy-Littlewood maximal function is lower semi-continuous.Then by investigating the behavior of the truncated Hardy-Littlewood maximal function when the truncated parameterγchanges,we obtain an equivalent condition of the continuity of the truncated Hardy-Littlewood maximal function.

Analytical Solution and Simplified Formula for Added Mass of Horizontal and Vertical Motions of Truncated Cylinders Under Earthquake Action

This paper investigates the hydrodynamic characteristics of floating truncated cylinders undergoing horizontal and vertical motions due to earthquake excitations in the finite water depth.The governing equation of the hydrodynamic pressure acting on the cylinder is derived based on the radiation theory with the inviscid and incompressible assumptions.The governing equation is solved by using the method of separating variables and analytical solutions are obtained by assigning reasonable boundary conditions.The analytical result is validated by a numerical model using the exact artificial boundary simulation of the infinite water.The main variation and distribution characteristics of the hydrodynamic pressure acting on the side and bottom of the cylinder are analyzed for different combinations of wide-height and immersion ratios.The added mass coefficient of the cylinder is calculated by integrating the hydrodynamic pressure and simplified formulas are proposed for engineering applications.The calculation results show that the simplified formulas are in good agreement with the analytical solutions.

Parametric instability in the pure-quartic nonlinear Schrödinger equation

We study the nonlinear stage of modulation instability(MI)in the non-intergrable pure-quartic nonlinear Schrödinger equation where the fourth-order dispersion is modulated periodically.Using the three-mode truncation,we reveal the complex recurrence of parametric resonance(PR)breathers,where each recurrence is associated with two oscillation periods(PR period and internal oscillation period).The nonlinear stage of parametric instability admits the maximum energy exchange between the spectrum sidebands and central mode occurring outside the MI gain band.

CRISPR/Cas9-mediated NlInR2 mutants:Analyses of residual mRNA and truncated proteins

CRISPR/Cas9 technology is a powerful genome manipulation tool in insects.However,little is known about whether mRNA and protein of a target gene are completely cleared in homozygous mutants.This study generated homozygous mutants of the insulin receptor gene 2(NlInR2)in the brown planthopper(Nilaparvata lugens)using CRISPR/Cas9 genome editing.Both frameshift mutants,E5_D17 and E6_I7,differentiated towards long wings,but there were differences in wing morphology,with E5_D17 showing wing deformities.Subsequent investigations revealed the presence of residual expression of NlInR2 mRNA in both mutants,as well as the occurrence of spliceosomes featuring exon skipping splicing in E5_D17.Additionally,the E5_D17 exhibited the detection of N-terminally truncated NlInR2 protein.RNA interference experiments indicated that the knockdown of NlInR2 expression in the E5_D17 mutant line increased the proportion of wing deformities from 11.1 to 65.6%,suggesting that the residual NlInR2 mRNA of the E5_D17 mutant might have retained some genetic functions.Our results imply that systematic characterization of residual protein expression or function in CRISPR/Cas9-generated mutant lines is necessary for phenotypic interpretation.

Multivariate form of Hermite sampling series

In this paper,we establish a new multivariate Hermite sampling series involving samples from the function itself and its mixed and non-mixed partial derivatives of arbitrary order.This multivariate form of Hermite sampling will be valid for some classes of multivariate entire functions,satisfying certain growth conditions.We will show that many known results included in Commun Korean Math Soc,2002,17:731-740,Turk J Math,2017,41:387-403 and Filomat,2020,34:3339-3347 are special cases of our results.Moreover,we estimate the truncation error of this sampling based on localized sampling without decay assumption.Illustrative examples are also presented.

Modified DS np Chart Using Generalized Multiple Dependent State Sampling under Time Truncated Life Test

This study presents the design of a modified attributed control chart based on a double sampling(DS)np chart applied in combination with generalized multiple dependent state(GMDS)sampling to monitor the mean life of the product based on the time truncated life test employing theWeibull distribution.The control chart developed supports the examination of the mean lifespan variation for a particular product in the process of manufacturing.Three control limit levels are used:the warning control limit,inner control limit,and outer control limit.Together,they enhance the capability for variation detection.A genetic algorithm can be used for optimization during the in-control process,whereby the optimal parameters can be established for the proposed control chart.The control chart performance is assessed using the average run length,while the influence of the model parameters upon the control chart solution is assessed via sensitivity analysis based on an orthogonal experimental design withmultiple linear regression.A comparative study was conducted based on the out-of-control average run length,in which the developed control chart offered greater sensitivity in the detection of process shifts while making use of smaller samples on average than is the case for existing control charts.Finally,to exhibit the utility of the developed control chart,this paper presents its application using simulated data with parameters drawn from the real set of data.

Quercetin inhibits truncated isoform of dopamine-and cAMP-regulated phosphoprotein as adjuvant treatment for trastuzumab therapy resistance in HER2-positive breast cancer

Trastuzumab resistance is one of the causes of poor prognosis in patients with human epidermal growth factor receptor 2(HER2)-positive(HER2+)breast cancer(BC).The truncated isoform of dopamine-and cAMPregulated phosphoprotein(t-DARPP)has been reported to be involved in trastuzumab therapy resistance and promoting tumor progression.To evaluate the t-DARPP expression in BC,paired tumors and surrounding normal tissues were analyzed by real-time polymerase chain reaction and confirmed higher DARPP-32 kDa family mRNA expression in HER2+BC tumor tissues.We established 2 patient-derived xenografts(PDX)mice models to test the efficacy of trastuzumab,named model 1(non-responder)and model 2(responder).t-DARPP and p95-HER2 protein-protein interactions were detected in PDX tumor tissue from non-responders using Förster resonance energy transfer assays.Instead,there is no response from the responder.Furthermore,mechanistic studies using transwell and western blot assays demonstrated that t-DARPP could upregulate epithelial-mesenchymal transition signaling proteins,enhance p95-HER2 expression and promote cell migration.We found that quercetin effectively reduced t-DARPP expression in HER2+BC cells.In t-DARPP ShRNA-suppressed cells,quercetin synergistically enhanced trastuzumab-induced apoptotic cell death and G2/M phase arrest.In conclusion,the combination of quercetin and trastuzumab treatment by targeting t-DARPP in HER2+BC patients has the potential as a biomarker for mitigating drug resistance.

Factorized Smith Method for A Class of High-Ranked Large-Scale T-Stein Equations

We introduce a factorized Smith method(FSM)for solving large-scale highranked T-Stein equations within the banded-plus-low-rank structure framework.To effectively reduce both computational complexity and storage requirements,we develop techniques including deflation and shift,partial truncation and compression,as well as redesign the residual computation and termination condition.Numerical examples demonstrate that the FSM outperforms the Smith method implemented with a hierarchical HODLR structured toolkit in terms of CPU time.

Future therapeutic implications of new molecular mechanism of colorectal cancer

High incidence(10.2%)and mortality(9.2%)rates led to the ranking of colorectal cancer(CRC)as the second most malignant tumor spectrum worldwide in 2020.Treatment strategies are becoming highly dependent on the molecular characteristics of CRC.The classical theories accept two models depicting the origin of CRC:The progression of adenoma to cancer and transformation from serrated polyps to cancer.However,the molecular mechanism of CRC development is very complex.For instance,CRCs originating from laterally spreading tumors(LST)do not adhere to any of these models and exhibit extremely serious progression and poor outcomes.In this article,we present another possible pathway involved in CRC development,particularly from LST,with important molecular characteristics,which would facilitate the design of a novel strategy for targeted therapy.

A joint absorbing boundary for the multiple-relaxation-time lattice Boltzmann method in seismic acoustic wavefield modeling

Conventional seismic wave forward simulation generally uses mathematical means to solve the macroscopic wave equation,and then obtains the corresponding seismic wavefield.Usually,when the subsurface structure is finely constructed and the continuity of media is poor,this strategy is difficult to meet the requirements of accurate wavefield calculation.This paper uses the multiple-relaxation-time lattice Boltzmann method(MRT-LBM)to conduct the seismic acoustic wavefield simulation and verify its computational accuracy.To cope with the problem of severe reflections at the truncated boundaries,we analogize the viscous absorbing boundary and perfectly matched layer(PML)absorbing boundary based on the single-relaxation-time lattice Boltzmann(SRT-LB)equation to the MRT-LB equation,and further,propose a joint absorbing boundary through comparative analysis.We give the specific forms of the modified MRT-LB equation loaded with the joint absorbing boundary in the two-dimensional(2D)and three-dimensional(3D)cases,respectively.Then,we verify the effects of this absorbing boundary scheme on a 2D homogeneous model,2D modified British Petroleum(BP)gas-cloud model,and 3D homogeneous model,respectively.The results reveal that by comparing with the viscous absorbing boundary and PML absorbing boundary,the joint absorbing boundary has the best absorption performance,although it is a little bit complicated.Therefore,this joint absorbing boundary better solves the problem of truncated boundary reflections of MRT-LBM in simulating seismic acoustic wavefields,which is pivotal to its wide application in the field of exploration seismology.

Explicit Isogeometric Topology Optimization Method with Suitably Graded Truncated Hierarchical B-Spline

This work puts forward an explicit isogeometric topology optimization(ITO)method using moving morphable components(MMC),which takes the suitably graded truncated hierarchical B-Spline based isogeometric analysis as the solver of physical unknown(SGTHB-ITO-MMC).By applying properly basis graded constraints to the hierarchical mesh of truncated hierarchical B-splines(THB),the convergence and robustness of the SGTHB-ITOMMC are simultaneously improved and the tiny holes occurred in optimized structure are eliminated,due to the improved accuracy around the explicit structural boundaries.Moreover,an efficient computational method is developed for the topological description functions(TDF)ofMMC under the admissible hierarchicalmesh,which consists of reducing the dimensionality strategy for design space and the locally computing strategy for hierarchical mesh.We apply the above SGTHB-ITO-MMC with improved efficiency to a series of 2D and 3Dcompliance design problems.The numerical results show that the proposed SGTHB-ITO-MMC method outperforms the traditional THB-ITO-MMCmethod in terms of convergence rate and efficiency.Therefore,the proposed SGTHB-ITO-MMC is an effective way of solving topology optimization(TO)problems.

Isolated left ventricular apical hypoplasia:Systematic review and analysis of the 37 cases reported so far

BACKGROUND Isolated left ventricular apical hypoplasia(ILVAH),also known as truncated left ventricle(LV),is a very unusual cardiomyopathy.It is characterised by a truncated,spherical,and non-apex forming LV.The true apex is occupied by the right ventricle.Due to the rarity of the disease,just a few case reports and limited case series have been published in the field.AIM To analysing the so far 37 reported ILVAH cases worldwide.METHODS The electronic databases PubMed and Scopus were investigated from their establishment up to December 13,2022.RESULTS The majority of cases reported occurred in males(52.7%).Mean age at diagnosis was 26.1±19.6 years.More than a third of the patients were asymptomatic(35.1%).The most usual clinical presentation was breathlessness(40.5%).The most commonly detected electrocardiogram changes were T wave abnormalities(29.7%)and right axis deviation with poor R wave progression(24.3%).Atrial fibrillation/flutter was detected in 24.3%.Echocardiography was performed in 97.3%of cases and cardiac MRI in 91.9%of cases.Ejection fraction was reduced in more than a half of patients(56.7%).An associated congenital heart disease was found in 16.2%.Heart failure therapy was administered in 35.1%of patients.The outcome was favorable in the vast majority of patients,with just one death.CONCLUSION ILVAH is a multifaceted entity with a so far unpredictable course,ranging from benign until the elderly to sudden death during adolescence.

基于TTLS算法的超声断层成像方法研究

超声医学成像因非侵入式、成本低且实时性好而被广泛应用。超声波动方程具有严重的离散不适定问题,迭代化与正则化结合可以解决这一问题,但重建图像质量较差。为解决这一问题,本文在矩量法基础上,引入Tikhonov-Gaussian方法中的滤波因子,用于校正较小奇异值,将复杂的不适定问题转化为容易求解的最小二乘问题,重构出高质量图像。通过实验数据分析,改进后的截断完全最小二乘算法(truncated total least squares,TTLS)重建质量更高,效果更好,相对误差降低了1.16201%,峰值信噪比提高了0.29132%,信噪比提高了3.0269%,结构相似性提高了1.72531%,图像对比度提高了14.21319%。

Evolutionary Plasmonic Properties of Single Truncated Ag Nanowire-on-Au Film Nanocavity

Noble metal nanocavities have been widely demonstrated to possess great potential applications in nanooptics and nanophotonics due to their extraordinary localized surface plasmon resonance.However,most metal nanocrystals synthesized by chemical methods often suffer from truncation with different degrees due to oxidation and dissolution of metal atoms at corner and edges.We investigate the influence of shape truncation on the plasmonic properties of single Ag nanowire on Au film nanocavity using the finite difference time domain method.When the Ag nanowire(the circumradius R_(2)=50 nm)is gradually truncated from pentagonal to circular geometry,the scattering peak position of the nanocavity shows prominent blue shift from 962 nm to 608 nm,suggesting a nonnegligible role of truncation on plasmonic properties.The electric field strength and charge distribution of the structure reveal the evolution from dipole mode to quadrupole mode.It is also found that the plasmon resonance wavelength is linearly dependent on the truncation ratio R_(1)/R_(2)(R_(1) is the inradius)and the modulation slope is also reliable to the size of Ag nanowire.Our observations could shed light on developing high-performance tunable optical nano-devices in future.

Truncating PICK1 Variant Identified in Azoospermia Affected Mitochondrial Dysfunction in Knockout Mice

Objective The protein interacting with C kinase 1(PICK1)plays a critical role in vesicle trafficking,and its deficiency in sperm cells results in abnormal vesicle trafficking from Golgi to acrosome,which eventually disrupts acrosome formation and leads to male infertility.Methods An azoospermia sample was filtered,and the laboratory detection and clinical phenotype indicated typical azoospermia in the patient.We sequenced all of the exons in the PICK1 gene and found that there was a novel homozygous variant in the PICK1 gene,c.364delA(p.Lys122SerfsX8),and this protein structure truncating variant seriously affected the biological function.Then we constructed a PICK1 knockout mouse model using clustered regularly interspaced short palindromic repeat cutting technology(CRISPRc).Results The sperm from PICK1 knockout mice showed acrosome and nucleus abnormalities,as well as dysfunctional mitochondrial sheath formation.Both the total sperm and motility sperm counts were decreased in the PICK1 knockout mice compared to wild-type mice.Moreover,the mitochondrial dysfunction was verified in the mice.These defects in the male PICK1 knockout mice may have eventually led to complete infertility.Conclusion The c.364delA novel variant in the PICK1 gene associated with clinical infertility,and pathogenic variants in the PICK1 may cause azoospermia or asthenospermia by impairing mitochondrial function in both mice and humans.

Different wave patterns for two-coupled Maccari's system with complex structure via truncated Painlevéapproach

We focused on the two-coupled Maccari's system.With the help of truncated Painlevéapproach(TPA),we express local solution in the form of arbitrary functions.From the solution obtained,using its appropriate arbitrary functions,we have generated the rogue wave pattern solutions,rogue wave solutions,and lump solutions.In addition,by controlling the values of the parameters in the solutions,we show the dynamic behaviors of the rogue wave pattern solutions,rogue wave solutions,and lump solutions with the aid of Maple tool.The results of this study will contribute to the understanding of nonlinear wave dynamics in higher dimensional Maccari's systems.

THE REGULARIZED SOLUTION APPROXIMATION OF FORWARD/BACKWARD PROBLEMS FOR A FRACTIONAL PSEUDO-PARABOLIC EQUATION WITH RANDOM NOISE

This paper deals with the forward and backward problems for the nonlinear fractional pseudo-parabolic equation ut+(-Δ)^(s1)ut+β(-Δ)^(s2)u=F(u,x,t)subject o random Gaussian white noise for initial and final data.Under the suitable assumptions s1,s2andβ,we first show the ill-posedness of mild solutions for forward and backward problems in the sense of Hadamard,which are mainly driven by random noise.Moreover,we propose the Fourier truncation method for stabilizing the above ill-posed problems.We derive an error estimate between the exact solution and its regularized solution in an E‖·‖Hs22norm,and give some numerical examples illustrating the effect of above method.

Elimination of the yellow pigment gene PSY-E2 tightly linked to the Fusarium head blight resistance gene Fhb7 from Thinopyrum ponticum

Fhb7 is a major gene that was transferred from Thinopyrum ponticum to chromosome 7D of wheat(Triticum aestivum)and confers resistance to both Fusarium head blight(FHB)and Fusarium crown rot(FCR).However,Fhb7 is tightly linked to the PSY-E2 gene,which causes yellow flour,limiting its application in breeding.To break this linkage,marker K-PSY was developed for tagging PSY-E2 and used with Fhb7 markers to identify recombination between the two genes.Screening 21,000 BC1F2 backcross progeny(Chinese Spring ph1bph1b*2/SDAU 2028)revealed two Fhb7^(+)wheat-Tp7el_(2)L lines,Shannong 2–16and Shannong 16–1,that carry a desired truncated Fhb7^(+)translocation segment without PSY-E2.The two lines show levels of resistance to FHB and FCR similar to those of the original translocation line SDAU 2028,but have white flour.To facilitate Fhb7 use in wheat breeding,STS markers were developed and used to isolate Fhb7 on a truncated Tp7el_(2) translocation segment.Near-isogenic lines carrying the Fhb7^(+)segment were generated in the backgrounds of three commercial cultivars,and Fhb7^(+)lines showed increased FHB and FCR resistance without yield penalty.The breakage of the tight linkage between Fhb7 and PSY-E2 via homoeologous recombination provides genetic resources for improvement of wheat resistance to FHB and FCR and permit the large-scale deployment of Fhb7 in breeding using marker-assisted selection.

Analytical wave solutions of an electronically and biologically important model via two efficient schemes

We search for analytical wave solutions of an electronically and biologically important model named as the Fitzhugh–Nagumo model with truncated M-fractional derivative, in which the expafunction and extended sinh-Gordon equation expansion(ESh GEE) schemes are utilized. The solutions obtained include dark, bright, dark-bright, periodic and other kinds of solitons. These analytical wave solutions are gained and verified with the use of Mathematica software. These solutions do not exist in literature. Some of the solutions are demonstrated by 2D, 3D and contour graphs. This model is mostly used in circuit theory, transmission of nerve impulses, and population genetics. Finally, both the schemes are more applicable, reliable and significant to deal with the fractional nonlinear partial differential equations.