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The breast tumor microenvironment alters the phenotype and function of natural killer cells

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Cellular & Molecular Immunology 2016年第5期13卷 628-639页

作者： Tamara Krnetal Amy Gillgrass Marianne Chew ali A. ashkar Department of Pathology and Hamilton. ON. Canada. Molecular Medicine McMaster Immunology Research Center and Institute for Infectious Disease McMaster University

Natural killer （NK） ceils are innate immune cells with the ability to identify and eliminate transformed cells. However, within tumors, many studies have described NK cells as non-functional. The developmental stage of tumor-associated NK cells and how this may relate to functionality has not been explored. We examined the developmental state of NK cells from polyoma middle T antigen （pyMT） transgenic mouse （MMTV-pMT） breast tumors. In pyMT tumors, NK cells were immature as evidenced by their decreased expression of DX5 and their CD27~~WCD1 lbI^w phenotype. These immature NK cells also had increased expression of NKG2A and expressed low levels of NKp46, perforin, and granzyme B. In contrast, splenic NK cells isolated from the same mice maintained their maturity and their expression of activation markers. To delineate whether the tumor microenvironment directly alters NK cells, we adoptively transferred labeled NK cells and followed their activation status in both the spleen and the tumor. NK cells that arrived at the tumor had half the expression of NKp46 within three days of transfer in comparison to those which arrived at the spleen. In an effort to modify the tumor microenvironment and assess the plasticity of intratumoral NK cells, we treated pyMT tumors with IL-12 and anti-TGF-β. After one week of treatment, the maturity of tumor-associated NK cells was increased; thus, indicating that these cells possess the ability to mature and become activated. A better understanding of how NK cells are modified by the tumor microenvironment will held to develop strategies aimed at bolstering immune resoonses against tumors.

关键词： Tumor NK cells Innate immunity tumor immunology

Shining light on the significance of NK cell CD56 brightness

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Cellular & Molecular Immunology 2018年第12期15卷 1071-1073页

作者： Sophie M.Poznanski ali A.ashkar Department of Pathology and Molecular Medicine McMaster Immunology Research CentreMcMaster UniversityHamiltonONCanada McMaster University 1280 Main Street WestMDCL 4015HamiltonONCanada

CD56 is a fundamental marker in the determination of human natural killer(NK)cell *** degree of CD56 expression is ubiquitously used to define human NK cell maturation,functional,and tissue-specific subsets,yet a unifying implication for the degree of CD56 expression in NK cells remains *** blood(PB)-NK cells are dichotomized into CD56bright,which highly express CD56,and CD56dim,which have lower CD56 ***,CD56bright NK cells are considered to be a less mature,immunoregulatory subset with a greater propensity for cytokine production,whereas CD56dim are more mature with greater cytotoxic *** PB-NK cells are primarily CD56dim with only a minor CD56bright population,NK cells in secondary lymphoid and other tissues are predominantly CD56bright.1 It has been shown that the interaction of CD56 with human fibroblast cells can promote the differentiation of CD56bright to CD56dim NK cells.2 However,considering the importance and the extent of use of this marker in NK cell biology,relatively little is known about how downregulation of CD56 contributes to NK cell maturation,what role the degree of CD56 expression plays in contexts separate from NK cell maturation,and whether CD56 has an active functional role in mature NK cells.

关键词： CD56 expression. bright

Humanized mice are susceptible to Salmonella typhi infection

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Cellular & Molecular Immunology 2011年第1期8卷 83-87页

作者： M Firoz Mian Elisabeth A Pek Meghan J Chenoweth ali a ashkar Institute for Infectious Disease Research Centre for Gene TherapeuticsDepartment of Pathology and Molecular MedicineMcMaster UniversityHamiltonOntarioCanada

Salmonella enterica serovar Typhi is a pathogen that only infects ***,there is no animal model for studying this ***,alymphoid RAG2^(-/-)/γc^(-/-) mice engrafted with human leukocytes,known as humanized mice,have been successfully utilized to develop experimental models for several human-specific viral infections,including HIV,human-like dengue fever and hepatitis C *** is known about the usefulness and feasibility of the humanized mouse model for the study of human-specific bacterial pathogens,such as *** aim of this study was to determine if Salmonella enterica serovar Typhi could establish productive infection in humanized *** we report that intravenous inoculation of *** into humanized mice,but not controls,established *** *** bacterial loads were found in the liver,spleen,blood and bone marrow of mice reconstituted with human leukocytes,but not in the unreconstituted control ***,***-infected humanized mice lost significant body weight,and some of the infected mice displayed neurological *** data suggest,for the first time,that humanized mice are susceptible to *** challenge and that this model can be utilized to study the pathogenesis of *** develop novel therapeutic strategies.

关键词： animal model humanized mice RAG2-/-γc-/- Salmonella typhi

Genuine entanglement under squeezed generalized amplitude damping channels with memory

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Chinese Physics B 2024年第2期33卷 158-163页

作者： Mazhar ali Department of Electrical Engineering Faculty of EngineeringIslamic University MadinahMadinah 107Saudi Arabia

We study genuine entanglement among three qubits undergoing a noisy process that includes dissipation, squeezing,and decoherence. We obtain a general solution and analyze the asymptotic quantum states. We find that most of these asymptotic states can be genuinely entangled depending upon the parameters of the channel, memory parameter, and the parameters of the initial states. We study Greenberger–Horne–Zeilinger(GHZ) states and W states, mixed with white noise,and determine the conditions for them to be genuinely entangled at infinity. We find that for these mixtures, it is possible to start with a bi-separable state(with a specific mixture of white noise) and end with genuine entangled states. However, the memory parameter μ must be very high. We find that in contrast to the two-qubit case, none of the three-qubit asymptotic states for n → ∞ are genuinely entangled.

关键词： genuine entanglement squeezed thermal baths multipartite states

Heat transfer analysis in particle-laden flows using the immersed boundary method

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Particuology 2024年第7期90卷 394-403页

作者： ali Abbas Zaidi Department of Mechanical Engineering University of Manitoba75A Chancellors CircleWinnipegR3T 5V6Canada

This paper investigates an efficient immersed boundary method(IBM)for multiple-core CPU machines with local grid refinement for the calculation of heat transfer between fluids and finite-sized *** fluid momentum equations are solved by using the fractional step method,while the energy equation is solved by employing the second-order Adams-Bashforth *** efficient load balancing between the CPU cores,the coupling between particles and fluid is obtained by applying the body force in the fluid equations,which depends on the solid volume fraction of particles contained in each grid cell,and then by linearly interpolating the particle temperature and velocity on the fluid grid cell(in place of the delta function commonly used in literature).Several test cases from the literature are studied,and good agreement is observed between the simulation results and the ***,a scaling study on multiple core machines is performed,demonstrating the proposed IBM's capabilities for a significant reduction in processing time.

关键词： Heat transfer Immersed boundary method Particle resolved direct numerical simulations Fluid solid interactions

Simulation of the deformable lateral boundaries in biaxial test using DEM

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Particuology 2024年第5期88卷 161-175页

作者： ali Momeni Barry Clarke Yong Sheng ali Hassanpour WSP 3 Wellington PlaceLeedsLS1 4APUK Hull University HullHU6 7RXUK School of Civil Engineering University of LeedsLeedsLS2 9JTUK School of Computer Science University of HullHullHU6 7RXUK School of Chemical and Process Engineering University of LeedsLeedsLS2 9JTUK

Applying the discrete element method(DEM)in soil mechanics can provide abundant information at the particle-scale and facilitates illustration of the macro-mechanical behaviour of soils based on the inter-particle *** triaxial test is one of the most common laboratory methods to study the macro-mechanical behaviour of particulate materials such as ***,many problems in geotechnical design can be assumed and simplified as a plane strain *** a biaxial test can be conducted to reproduce the macro-mechanical behaviour of soil,where the sample is enclosed by two horizontal rigid platens and a vertical latex membrane,which is a deformable continuous element and allows the enclosed specimen to deform freely while maintaining confining stress during *** paper presents an algorithm to represent physical and mechanical characteristics of latex membrane in the 2D DEM simulation of biaxial test using the PFC^(2D) *** investigate the impact of the lateral boundary conditions on the micro-macro mechanical behaviours of soil samples,two sets of DEM biaxial tests are conducted,*** rigid and deformable lateral boundary *** DEM modeling results indicate that the lateral boundary conditions have a significant effect on the micro-scale fabric properties,thickness and inclination of the shear *** comparison between these two simulations also demonstrates that the lateral boundary conditions play a major role in the peak and post-peak stress-strain behaviours as well as the dilation and critical state behaviours of granular soils.

关键词： Discrete element method Biaxial test Deformable boundaries Shear band Critical state Fabric anisotropy Geometrical stability index

Interferon-β induced in female genital epithelium by HIV-1 glycoprotein 120 via Toll-like-receptor 2 pathway acts to protect the mucosal barrier

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Cellular & Molecular Immunology 2019年第2期16卷 178-194页

作者： Aisha Nazli Sara Dizzell Muhammad Atif Zahoor Victor H Ferreira Jessica Kafka Matthew William Woods Michel Ouellet ali a ashkar Michel J Tremblay Dawn ME Bowdish Charu Kaushic McMaster Immunology Research Centre Michael G.DeGroote Center for Learning and DiscoveryMcMaster UniversityHamiltonON L8S 4K1Canada Department of Pathology and Molecular Medicine McMaster UniversityHamiltonON L8S 4K1Canada Department of Medical Biology Laval UniversityQuebec CityQC G1V 0A6Canada

More than 40%of HIV infections occur via female reproductive tract(FRT)through heterosexual *** cells that line the female genital mucosa are the first line of defense against HIV-1 and other sexually transmitted *** sentient cells recognize and respond to external stimuli by induction of a range of carefully balanced innate immune ***,we have shown that in response to HIV-1 gp120,the genital epithelial cells(GECs)from upper reproductive tract induce an inflammatory response that may facilitate HIV-1 translocation and *** this study,we report that the endometrial and endocervical GECs simultaneously induce biologically active interferon-β(IFNβ)antiviral responses following exposure to HIV-1 that act to protect the epithelial tight junction *** innate antiviral response was directly induced by HIV-1 envelope glycoprotein gp120 and addition of gp120 neutralizing antibody inhibited IFNβ***-βwas induced by gp120 in upper GECs through Toll-like receptor 2 signaling and required presence of heparan sulfate on epithelial cell *** induction of IFNβwas dependent upon activation of transcription factor IRF3(interferon regulatory factor 3).The IFNβwas biologically active,had a protective effect on epithelial tight junction barrier and was able to inhibit HIV-1 infection in TZM-bl indicator cells and HIV-1 replication in T *** is the first report that recognition of HIV-1 by upper GECs leads to induction of innate antiviral *** could explain the overall low infectivity of HIV-1 in the FRT and could be exploited for HIV-1 prophylaxis.

关键词： antiviral response genital epithelium HIV-1 IFN-β innate immunity IRF-3 mucosal barrier TLR2

Sensing the heavy water concentration in an H_(2)O-D_(2)O mixture by solid-solid phononic crystals

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Chinese Physics B 2024年第4期33卷 493-498页

作者： Mohammadreza Rahimi ali Bahrami Optoelectronic and Nanophotonics Research Laboratory(ONRL) Faculty of Electrical EngineeringSahand University of TechnologyTabrizIran

A new method based on phononic crystals is presented to detect the concentration of heavy water(D_(2)O)in an H_(2)O-D_(2)O *** have been obtained and analyzed in the concentration range of 0%-10%and 90%-100%D_(2)O.A proposed structure of tungsten scatterers in an aluminum host is *** order to detect the target material,a cavity region is considered as a sound wave resonator in which the target material with different concentrations of D_(2)O is *** changing the concentration of D_(2)O in the H_(2)O-D_(2)O mixture,the resonance frequency undergoes a frequency *** 1%change in D_(2)O concentration in the H_(2)O-D_(2)O mixture causes a frequency change of about 120 *** finite element method is used as the numerical method to calculate and analyze the natural frequencies and transmission spectra of the proposed *** performance evaluation index shows a high Q factor up to 1475758 and a high sensitivity up to 13075,which are acceptable values for sensing *** other figures of merit related to the detection performance also indicate high-quality performance of the designed sensor.

关键词： phononic crystals sensor H_(2)O-D_(2)O mixture cavity

Note on Lower Triassic Gondolelloid Conodont Rediversifications with Emphasis on the Spathian Recovery

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Journal of Earth Science 2024年第4期35卷 1236-1242页

作者： ali Murat Kilic Department of Geological Engineering Faculty of EngineeringBalikesir UniversityBalikesir99100Turkey

Conodonts,as a biotic group,next to ammonoids,pollen and spores,crustaceans and vertebrates,provide proxy clues for environment and age assessments of the rocks in which they *** are widely used for Triassic marine ***,there are various discussions about their multielement taxonomy and evolutionary lineages(e.g.,generation,speciation).Although first studies reported that most Triassic conodont species were unimembrate,studies carried out in the following years maintained that all Triassic conodonts were *** statistical reconstructions of a number of Triassic apparatuses were attempted,the discovery of fused clusters and natural assemblages has subsequently demonstrated that Triassic conodonts are indeed multimembrate,and all of the elements exist together in the same *** present paper aims to clarify the evolutionary relationship and array of some Lower Triassic *** dagisi *** described.

关键词： Triassic Spathian conodont Columbitella Siberia environmental geology