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Search Results: 1 - 10 of 495536 matches for " M. H. Verheije "
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Retargeting of Viruses to Generate Oncolytic Agents
M. H. Verheije,P. J. M. Rottier
Advances in Virology , 2012, DOI: 10.1155/2012/798526
Abstract: Oncolytic virus therapy is based on the ability of viruses to effectively infect and kill tumor cells without destroying the normal tissues. While some viruses seem to have a natural preference for tumor cells, most viruses require the modification of their tropism to specifically enter and replicate in such cells. This review aims to describe the transductional targeting strategies currently employed to specifically redirect viruses towards surface receptors on tumor cells. Three major strategies can be distinguished; they involve (i) the incorporation of new targeting specificity into a viral surface protein, (ii) the incorporation of a scaffold into a viral surface protein to allow the attachment of targeting moieties, and (iii) the use of bispecific adapters to mediate targeting of a virus to a specified moiety on a tumor cell. Of each strategy key features, advantages and limitations are discussed and examples are given. Because of their potential to cause sustained, multiround infection—a desirable characteristic for eradicating tumors—particular attention is given to viruses engineered to become self-targeted by the genomic expression of a bispecific adapter protein. 1. Introduction Cancer is one of the major health problems of our times. Though the prognosis for people diagnosed with, at least some forms of, cancer has increased considerably, it is more typical a disease of which treatment is initially effective, to be followed later by an irreversible and eventually fatal relapse. Already for decades, cancer treatment is based on three types of approaches: surgery, radio-, and chemotherapy. While the scientific and technological advancements have improved the efficacy of each of these classical approaches tremendously, and while also some new therapies have evolved including immunotherapy, the treatments apparently fail to eradicate all residual tumor cells or metastases completely. Therefore, additional means are urgently required to support or replace the conventional therapies. Hence, a variety of new approaches is currently being explored, one of which is based on the use of viruses. Oncolytic viruses are defined by their ability to specifically kill tumor cells, but to leave the normal tissues unharmed. Their most characteristic features, thus, are their target specificity and their cytolytic capacity. Ideally, they exhibit additional features including, but not limited to, a high reproductive capacity in vivo, the ability to recruit uninfected neighboring cells (syncytia formation), the ability to infect both dividing and nondividing
Mouse Hepatitis Coronavirus RNA Replication Depends on GBF1-Mediated ARF1 Activation
Monique H. Verheije,Matthijs Raaben,Muriel Mari,Eddie G. te Lintelo,Fulvio Reggiori,Frank J. M. van Kuppeveld,Peter J. M. Rottier,Cornelis A. M. de Haan
PLOS Pathogens , 2008, DOI: 10.1371/journal.ppat.1000088
Abstract: Coronaviruses induce in infected cells the formation of double membrane vesicles, which are the sites of RNA replication. Not much is known about the formation of these vesicles, although recent observations indicate an important role for the endoplasmic reticulum in the formation of the mouse hepatitis coronavirus (MHV) replication complexes (RCs). We now show that MHV replication is sensitive to brefeldin A (BFA). Consistently, expression of a dominant-negative mutant of ARF1, known to mimic the action of the drug, inhibited MHV infection profoundly. Immunofluorescence analysis and quantitative electron microscopy demonstrated that BFA did not block the formation of RCs per se, but rather reduced their number. MHV RNA replication was not sensitive to BFA in MDCK cells, which are known to express the BFA-resistant guanine nucleotide exchange factor GBF1. Accordingly, individual knockdown of the Golgi-resident targets of BFA by transfection of small interfering RNAs (siRNAs) showed that GBF1, but not BIG1 or BIG2, was critically involved in MHV RNA replication. ARF1, the cellular effector of GBF1, also appeared to be involved in MHV replication, as siRNAs targeting this small GTPase inhibited MHV infection significantly. Collectively, our results demonstrate that GBF1-mediated ARF1 activation is required for efficient MHV RNA replication and reveal that the early secretory pathway and MHV replication complex formation are closely connected.
Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner
Christine Burkard,Monique H. Verheije,Oliver Wicht,Sander I. van Kasteren,Frank J. van Kuppeveld,Bart L. Haagmans,Lucas Pelkmans,Peter J. M. Rottier,Berend Jan Bosch,Cornelis A. M. de Haan
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1004502
Abstract: Enveloped viruses need to fuse with a host cell membrane in order to deliver their genome into the host cell. While some viruses fuse with the plasma membrane, many viruses are endocytosed prior to fusion. Specific cues in the endosomal microenvironment induce conformational changes in the viral fusion proteins leading to viral and host membrane fusion. In the present study we investigated the entry of coronaviruses (CoVs). Using siRNA gene silencing, we found that proteins known to be important for late endosomal maturation and endosome-lysosome fusion profoundly promote infection of cells with mouse hepatitis coronavirus (MHV). Using recombinant MHVs expressing reporter genes as well as a novel, replication-independent fusion assay we confirmed the importance of clathrin-mediated endocytosis and demonstrated that trafficking of MHV to lysosomes is required for fusion and productive entry to occur. Nevertheless, MHV was shown to be less sensitive to perturbation of endosomal pH than vesicular stomatitis virus and influenza A virus, which fuse in early and late endosomes, respectively. Our results indicate that entry of MHV depends on proteolytic processing of its fusion protein S by lysosomal proteases. Fusion of MHV was severely inhibited by a pan-lysosomal protease inhibitor, while trafficking of MHV to lysosomes and processing by lysosomal proteases was no longer required when a furin cleavage site was introduced in the S protein immediately upstream of the fusion peptide. Also entry of feline CoV was shown to depend on trafficking to lysosomes and processing by lysosomal proteases. In contrast, MERS-CoV, which contains a minimal furin cleavage site just upstream of the fusion peptide, was negatively affected by inhibition of furin, but not of lysosomal proteases. We conclude that a proteolytic cleavage site in the CoV S protein directly upstream of the fusion peptide is an essential determinant of the intracellular site of fusion.
Using of the generalized special relativity (GSR) in estimating the neutrino masses to explain the conversion of electron neutrinos  [PDF]
M. H. M. Hilo
Natural Science (NS) , 2011, DOI: 10.4236/ns.2011.34044
Abstract: In this work the Generalized Special Relativity (GSR) is utilized to estimate masses of some elementary particles such as, neutrinos. These results are found to be in conformity with experimental and theoretical data. The results obtained may explain some physical phenomena, such as, conversion of neutrinos from type to type when solar neutrino reaches the Earth.
Filtered Ring Derived from Discrete Valuation Ring and Its Properties  [PDF]
M. H. Anjom Shoa, M. H. Hosseini
Advances in Pure Mathematics (APM) , 2014, DOI: 10.4236/apm.2014.43011
Abstract:

In this paper we show that if R is a discrete valuation ring, then R is a filtered ring. We prove some properties and relation when R is a discrete valuation ring.

Antireflection Coating at Metamaterial Waveguide Structure by Using Superlattices (LANS)  [PDF]
H. M. Mousa
Journal of Modern Physics (JMP) , 2014, DOI: 10.4236/jmp.2014.58074
Abstract:

The characteristics of electromagnetic wave reflection and transmission by multilayered structures consisting of a pair of left-handed material (LHM) and superlattices (LANS) slabs inserted between two semi-infinite dielectric media are investigated for photovoltaic and solar energy applications. Maxwell’s equations are used to determine the electric and magnetic fields of the perpendicular polarized wave incident at each layer. Snell’s law is applied and the boundary conditions are imposed at each layer interface to calculate the reflected and transmitted coefficients of the structure. The reflected, transmitted powers are determined using these coefficients by a recursive method. The reflected and transmitted powers are computed in both visible and microwave spectral band with the appropriate LHM for each band and appropriate location of LANS in the structure. They are illustrated as a function of the incident wavelength, angle of incidence, magnetic fraction of LANS and thickness of the slabs with the emphasis on the appropriate refractive indices. I found that, zero reflectance and maximum transmittance of the incident powers are achieved for visible spectral band at a single frequency if LHM and LANS have the same refractive index of opposite signs with the same width and more magnetic material of LANS while the reflected power is zero for less magnetic material of LANS in the microwave spectral band which realizes antireflection coating in this structure.

Schrödinger Operators on Graphs and Branched Manifolds  [PDF]
M. H. Numan Elsheikh
Journal of Applied Mathematics and Physics (JAMP) , 2014, DOI: 10.4236/jamp.2014.22001
Abstract:

We consider the Schrodinger operators on graphs with a finite or countable number of edges and Schr?dinger operators on branched manifolds of variable dimension. In particular, a description of self-adjoint extensions of symmetric Schr?dinger operator, initially defined on a smooth function, whose support does not contain the branch points of the graph and branch points of the manifold. These results are obtained for graphs with a single vertex, graphs with multiple vertices and graphs with a single vertex and countable set of rays.

Exact Traveling Wave Solutions of Nano-Ionic Solitons and Nano-Ionic Current of MTs Using the exp(-φ (ξ ))-Expansion Method  [PDF]
Emad H. M. Zahran
Advances in Nanoparticles (ANP) , 2015, DOI: 10.4236/anp.2015.42004
Abstract: In this work, the exp(-φ (ξ )) -expansion method is used for the first time to investigate the exact traveling wave solutions involving parameters of nonlinear evolution equations. When these parameters are taken to be special values, the solitary wave solutions are derived from the exact traveling wave solutions. The validity and reliability of the method are tested by its applications to Nano-ionic solitons wave’s propagation along microtubules in living cells and Nano-ionic currents of MTs which play an important role in biology.
Exact Traveling Wave Solutions for Nano-Solitons of Ionic Waves Propagation along Microtubules in Living Cells and Nano-Ionic Currents of MTs  [PDF]
Emad H. M. Zahran
World Journal of Nano Science and Engineering (WJNSE) , 2015, DOI: 10.4236/wjnse.2015.53010
Abstract: In this work, the extended Jacobian elliptic function expansion method is used as the first time to evaluate the exact traveling wave solutions of nonlinear evolution equations. The validity and reliability of the method are tested by its applications to nano-solitons of ionic waves propagation along microtubules in living cells and nano-ionic currents of MTs which play an important role in biology.
Numerical Studies of Resonance and Secular Effects of Gravitational Waves  [PDF]
M. H. A. Youssef
World Journal of Mechanics (WJM) , 2018, DOI: 10.4236/wjm.2018.85013
Abstract: This work deals with the numerical solution of the gravitational waves effects on the orbital elements of the planets in case of commensurability between the wave’s frequency ng and the planet’s mean motion np. Taking Mercury and Pluto as practical examples for low frequency and high frequency, the variations of the orbital elements of Mercury due to resonance of gravitational wave are different and small than the perturbation on Pluto. The amount of changing in the orbital elements under the effects of gravitational waves is different from planet to planet according to the planet’s mean motion np. For low frequency ng, the secular variation in orbital elements will be negative (i.e. decreasing) in the inclination, semi-major axis and the eccentricity (i, a, e) like as Pluto. For high frequency ng like Mercury, the secular variation in all the orbital elements will be positive (i.e. increasing). The perturbation on all the orbital elements of two planets is changing during each revolution except the eccentricity e of Mercury and the mean anomaly M of Mercury and Pluto during the time.
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