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The f.ture of.retinal gene therapy: evolving f.om subretinal to intravitreal vector delivery

Neural Regeneration Research 2021年第9期16卷 1751-1759页

作者： Maya Ross ron Of.i Koret School of.Veterinary Medicine The Hebrew University of JerusalemRehovotIsrael

Inherited retinal degenerations are a leading and untreatbale cause of.blindness, and as such they are targets f.r gene therapy. Numerous gene therapy treatments have progressed f.om laboratory research to clinical trails, and a pioneering gene therapy received the f.rst ever f.A approval f.r treating patients. However, currently retinal gene therapy mostly involves subretinal injection of.the therapeutic agent, which treats a limited area, entails retinal detachment and other potential complications, and requires general anesthesia with consequent risks, costs and prolonged recovery. Theref.re there is great impetus to develop saf.r, less invasive and cheapter methods of.gene delivery. A promising method is intravitreal injection, that does not cause retinal detachment, can lead to pan-retinal transduction and can be perf.rmed under local anesthesia in outpatient clinics. Intravitreally-injected vectors f.ce several obstacles. f.rst, the vector is diluted by the vitreous and has to overcome a long dif.usion distance to the target cells. Second, the vector is exposed to the host's immune response, risking neutralization by pre-existing antibodies and triggering a stronger immune response to the injection. Third, the vector has to cross the inner limiting membrane which is both a physical and a biological barrier as it contains binding sites that could cause the vector's sequestration. f.nally, in the target cell the vector is prone to proteasome degradation bef.re delivering the transgene to the nucleus. Strategies to overcome these obstacles include modif.cations of.the viral capsid, through rational design or directed evolution, which allow resistance to the immune system, enhancement of.penetration through the inner limiting membrane or reduced degradation by intracellular proteasomes. f.rthermore, physical and chemical manipulations of.the inner limiting membrane and vitreous aim to improve vector penetration. f.nally, compact non-viral vectors that can overcome

关键词： adeno-associated virus animal model blindness gene therapy inner limiting membrane photoreceptors retina retinitis pigmentosa vitreous

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Determination of.Methadone and Eight New Psychoactive Substances in Hair Samples by Gas Chromatography/Mass Spectrometry

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Journal of.f.rensic Science and Medicine 2018年第4期4卷 184-191页

作者： Luca Anzillotti Luca cald Marianna Giacalone Antonio Banchini Rossana Cecchi Department of.Medicine and Surgery Institute of Legal MedicineUniversity of ParmaParmaItaly

Many new psychoactive substances(NPSs)with dif.erent chemical structures have emerged in the illicit drug market in the last *** present work was aimed at the development of.a simple method in gas chromatography/mass spectrometry(MS)f.r the determination of.NPS of.dif.erent classes,the use of.cannabinoids,and,at the same time,the evaluation of.methadone therapy in hair matrix,within our routine analysis control f.r methadone treatment or f.om autopsy *** determination of.synthetic cannabinoids and methadone therapy used an extraction method based on incubation in concentrated sodium hydroxide(NaOH)solution,providing a dissolution of.the keratin *** described method was applied on 15 authentic specimens f.om our cases:f.ve showed the presence of.methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine(EDDP).The described method can be usef.l not only in the f.rensic investigation of.NPS-related addiction histories but also in epidemiological and retrospective studies on the spread of.NPS among specif.c saf.ty-sensitive social *** GC instrument was an Agilent 7820A(Agilent Technologies,Santa Clara,CA,USA),and the detection system was an Agilent 5977B single quadrupole MS operating in selective ion monitoring *** parameters such as limit of.detections(LODs),limit of.quantif.cations(LOQs),repeatability,accuracy,and linearity were satisf.ctory f.r its application on real ***,LOQs,2?2,%CY standard deviation,and the mean concentration f.r the analyzed compounds are reported in Table *** and repeatability were acceptable f.r all the analytes at their respective *** experiments varied f.om 58.3%to 103.0%,thus allowing the application on authentic *** described method can be usef.l not only in the f.rensic investigation of.PS-related addiction histories but also in epidemiological and retrospective studies on the spread of.NPS among specif.c saf.ty-sensitive social workers,such as drivers.

关键词： Drugs of.abuse f.rensic gas chromatography/mass spectrometry hair new psychoactive substance toxicology

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Regional Design Storm and f.ood Modelling—Risk Implications in Ungauged Catchments

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Journal of.Water Resource and Protection 2016年第13期8卷 1211-1221页

作者： Berhanu f. Alemaw ron T. Chaoka Department of.Geology University of Botswana Gaborone Botswana

Most planned developments in a catchment f.r control of.excess water using a culvert, bridge or dam spillway are located at a site in a stream where there are no discharge measurements. Even though, f.r gauged catchments a number of.established f.ood f.equency models and rainf.ll-runof. models do exist, f.r ungauged catchments mostly regional f.ood f.equency and event-based rainf.ll-runof. models are used, which depend on regional parameters. In this paper, a regional approach f.r design f.oods is presented and risk implication f.r design of.drainage structures assessed. A case study in light of.the above has been considered at f.ur ungauged sites in the Limpopo Drainage Basin in north-eastern Botswana.

关键词： Ungauged Catchments Drainage Structures Dams Design f.ood Risk Assessment

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Regionalization of.Rainf.ll Intensity-Duration-f.equency (IDf. Curves in Botswana

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Journal of.Water Resource and Protection 2016年第12期8卷 1128-1144页

作者： Berhanu f. Alemaw ron T. Chaoka Department of.Geology University of Botswana Gaborone Botswana

A regional analysis of.design storms, def.ned as the expected rainf.ll intensity f.r given storm duration and return period, is conducted to determine storm Rainf.ll Intensity-Duration-f.equency (IDf. relationships. The ultimate purpose was to determine IDf.curves f.r homogeneous regions identif.ed in Botswana. Three homogeneous regions were identif.ed based on topographic and rainf.ll characteristics which were constructed with the K-Means Clustering algorithm. Using the mean annual rainf.ll and the 24 hr annual maximum rainf.ll as an indicator of.rainf.ll intensity f.r each homogeneous region, IDf.curves and maps of.rainf.ll intensities of.1 to 24 hr and above durations were produced. The Gamma and Lognormal probability distribution f.nctions were able to provide estimates of.rainf.ll depths f.r low and medium return periods (up to 100 years) in any location in each homogeneous region of.Botswana.

关键词： IDf.Curves Design Storm Probability Distributions Clustering Regionalization

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Launching jets f.om accretion belts

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Research in Astronomy and Astrophysics 2016年第5期16卷 1-6页

作者： ron Schreier Noam Soker Department of.Physics Technion–Israel Institute of Technology

We propose that sub-Keplerian accretion belts around stars might launch jets. The sub-Keplerian inf.ow does not f.rm a rotationally supported accretion disk, but it rather reaches the accreting object f.om a wide solid angle. The basic ingredients of.the f.ow are a turbulent region where the accretion belt interacts with the accreting object via a shear layer, and two avoidance regions on the poles where the accretion rate is very low. A dynamo that is developed in the shear layer amplif.es magnetic f.elds to high values. It is likely that the amplif.ed magnetic f.elds f.rm polar outf.ows f.om the avoidance regions. Our speculative belt-launched jets model has implications on a rich variety of.astrophysical objects, f.om the removal of.common envelopes to the explosion of.core collapse supernovae by jittering jets.

关键词： stars: jets -- (stars:) binaries: accretion discs -- (stars:) supernovae: general -- accretion accretion disks

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The measurement of.proprioceptive accuracy:A systematic literature review

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Journal of.Sport and Health Science 2023年第2期12卷 219-225页

作者： Àron Horváth Eszter f.rentzi Kristóf.Schwartz Nina Jacobs Pieter Meyns f.renc Köteles Doctoral School of.Psychology ELTE Eötvös Loránd UniversityKazinczy street 23-27Budapest 1075Hungary Institute of.Health Promotion and Sport Sciences ELTE Eötvös Loránd UniversityPrielle Kornélia Street 47-49Budapest 1117Hungary Rehabilitation Research(REVAL) Faculty of Rehabilitation SciencesUniversity of HasseltMartelarenlaan 42Hasselt 3500Belgium

Background:Proprioceptive accuracy ref.rs to the individual’s ability to perceive proprioceptive inf.rmation,that is,the inf.rmation ref.rring to the actual state of.the locomotor system,which originates f.om mechanoreceptors located in various parts of.the locomotor system and f.om tactile receptors located in the *** accuracy appears to be an important aspect in the evaluation of.sensorimotor f.nctioning;however,no widely accepted standard assessment *** this systematic review,our goal was to identif. and categorize dif.erent methods that are used to assess dif.erent aspects of.proprioceptive ***:A literature search was conducted in 5 dif.erent databases(PubMed,SPORTDiscus,PsycINf.,ScienceDirect,and SpringerLink).Results:Overall,1139 scientif.c papers reporting 1346 methods were included in this *** methods assess 8 dif.erent aspects of.proprioception:(a)the perception of.joint position,(b)movement and movement extent,(c)trajectory,(d)velocity,and the sense of.e)f.rce,(f.muscle tension,(g)weight,and(h)*** apply various paradigms of.psychophysics(i.e.,the method of.adjustment,constant stimuli,and limits).Conclusion:As the outcomes of.dif.erent tasks with respect to various body parts show no associations(i.e.,proprioceptive accuracy is characterized by site-specif.city and method-specif.city),the appropriate measurement method f.r the task needs to be chosen based on theoretical considerations and/or ecological validity.

关键词： Assessment Kinesthesia Motor control Proprioception Proprioceptive accuracy

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Regularized Principal Component Analysis

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Chinese Annals of.Mathematics,Series B 2017年第1期38卷 1-12页

作者： Yonathan Af.ALO ron KIMMEL Samsung Research Labs Ramat GanIsrael Computer Science Department TechnionIsrael Institute of TechnologyHaifaIsrael.

Given a set of.signals, a classical construction of.an optimal truncatable basis f.r optimally representing the signals, is the principal component analysis(PCA f.r short)approach. When the inf.rmation about the signals one would like to represent is a more general property, like smoothness, a dif.erent basis should be considered. One example is the f.urier basis which is optimal f.r representation smooth f.nctions sampled on regular grid. It is derived as the eigenf.nctions of.the circulant Laplacian operator. In this paper,based on the optimality of.the eigenf.nctions of.the Laplace-Beltrami operator(LBO f.r short), the construction of.PCA f.r geometric structures is regularized. By assuming smoothness of.a given data, one could exploit the intrinsic geometric structure to regularize the construction of.a basis by which the observed data is represented. The LBO can be decomposed to provide a representation space optimized f.r both internal structure and external observations. The proposed model takes the best f.om both the intrinsic and the extrinsic structures of.the data and provides an optimal smooth representation of.shapes and f.rms.

关键词： Laplace-Beltrami operator Principal component analysis Isometry

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Improved Ligand-f.eld Theory with Ef.ect of.Electron-Phonon Interaction

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Communications in Theoretical Physics 2005年第3期43卷 529-538页

作者： MADong-Ping CHENJu-ron Departmentof.ppliedPhysics SichuanUniversityChengdu610065China／／InternationalCentreforMaterialsPhysicsAcademiaSinicaShenyang110015China Departmentof.ppliedPhysics SichuanUniversityChengdu610065China

Traditional ligand-f.eld theory has to be improved by taking into account both 'pure electronic' contribution and electron-phonon interaction one (including lattice-vibrational relaxation energy). By means of.improved ligand-f.eld theory, R1, R2, R'3, R'2, and R'1 lines, U band, ground-state zero-f.eld-splitting (GSZf.), and ground-state g f.ctors of.ruby and/or GSGG: Cr3+ as well as thermal shif.s of.GSZf., R1 line and R2 line of.ruby have been *** results are in very good agreement with the experimental data. Moreover, it is f.und that the value of.cubic-f.eld parameter given by traditional ligand-f.eld theory is inappropriately large. f.r thermal shif.s of.GSZf., R1 line and R2 line of.ruby, several conclusions have also been obtained.

关键词： improved ligand-f.eld theory electron-phonon interaction Stokes shif. energy spectrum thermal shif. g f.ctor

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基于Copula函数的金沙江流域云龙与松华坝水库入库径流丰枯遭遇分析

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中国农村水利水电 2024年第7期 10-18页

作者：孙治才阿长松孙岩杨荣赞云南省水利水电勘测设计院有限公司云南昆明650021 云南省水利水电勘测设计研究院云南昆明650021 云南大学云南昆明650021

通过Copula函数进行建模,采用P-Ⅲ分布分别对金沙江流域承担昆明市供水的两座重要水库——云龙水库和松华坝水库入库径流在三大时间尺度(全年、汛期、非汛期)上进行边缘分布函数的拟合,对拟合的边缘分布函数进行联合分布函数的构建,并... 详细信息

通过Copula函数进行建模,采用P-Ⅲ分布分别对金沙江流域承担昆明市供水的两座重要水库——云龙水库和松华坝水库入库径流在三大时间尺度(全年、汛期、非汛期)上进行边缘分布函数的拟合,对拟合的边缘分布函数进行联合分布函数的构建,并对联合分布函数采用K-S检验法进行拟合优度检验,采用图形分析计算法、AIC准则和BIC准则对联合分布函数进行拟合优选,最后通过优选出来的Copula函数对两座水库在三大时间尺度上进行丰枯遭遇分析。主要结论如下:两座水库全年与非汛期入库径流最优Copula函数均为Gumbel Copula函数、汛期为f.ank Copula函数。三大时间尺度上两座水库的丰平枯同步概率之和(全年0.734,汛期0.541,非汛期0.728)均大于三大时间尺度上两座水库的丰平枯异步概率之和(全年0.266,汛期0.459,非汛期0.272);在所有丰平枯组合中,两座水库的同丰概率在所有丰平枯组合情况中最高(全年同丰0.310,汛期同丰0.232,非汛期同丰0.308),表明两座水库在所有丰平枯组合中同为丰水年的可能性最大;在全年和非汛期时间尺度上两座水库为枯枯的概率(全年同枯0.298,非汛期0.296)相差不大且均大于两座水库在汛期时间尺度上为枯枯的概率(汛期同枯0.232),因此在两座水库进行实际调度的过程中,特别是在枯水年应考虑两座水库的丰枯同步性。该研究结果可在金沙江流域的水库群联合优化调度中提供一定的决策参考依据。

关键词：金沙江流域 Copula函数丰枯遭遇概率分析

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Novel active f.ult-tolerant control scheme and its application to a double inverted pendulum system

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Journal of.Systems Engineering and Electronics 2008年第1期19卷 134-140页

作者： Cui Ping Weng Zhengxin Patton ron Dept. of.Automation Shanghai Jiaotong Univ. Shanghai 200240 P. R. China Dept. of.Engineering Univ. of Hull Hull HU6 7RX UK

On the basis of.the gain-scheduled H∞ design strategy, a novel active f.ult-tolerant control scheme is proposed. Under the assumption that the ef.ects of.f.ults on the state-space matrices of.systems can be of.af.ine parameter dependence, a reconf.gurable robust H∞ linear parameter varying controller is developed. The designed controller is a f.nction of.the f.ult ef.ect f.ctors that can be derived online by using a well-trained neural network. To demonstrate the ef.ectiveness of.the proposed method, a double inverted pendulum system, with a f.ult in the motor tachometer loop, is considered.

关键词： active f.ult-tolerant control neural network estimator gain-scheduled controller double inverted pendulum.

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