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Immunotherapy and checkpoint inhibitors for gliomas

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Neuroimmunology and Neuroinflammation 2018年第11期5卷 19-34页

作者： clairice M.Pearce Matthew R.chrostek Emily G.Fellows Nikolas G.Toman Sarah K.Tran Andrew T.crane walter c.low Department of Neurosurgery University of Minnesota Medical SchoolMinneapolisMN 55455USA Masonic cancer center University of Minnesota Medical SchoolMinneapolisMN 55455USA Brain Tumor Program University of Minnesota Medical SchoolMinneapolisMN 55455USA

Glioma treatments are faced with challenges, including the inability to fully eliminate cancer stem cells, the immunosuppressive tumor microenvironment, and the blood brain barrier. Although progress has been made with surgical, radiation, and chemotherapies, prognosis for patients remains poor. Rapidly emerging immunotherapies may be able to address the challenges that conventional techniques cannot. Immunotherapies manipulate the patient's immune system to selectively combat malignancies. Therapies often work to enhance T-cell and natural killer (NK) cell function, which can both eliminate tumor cells and enhance remission. Vaccines encourage in vivo development of anti-tumor T-cells and NK cells, while adoptive transfer techniques focus on engineering immune cells ex vivo before reintroducing them to patients. Vaccine and adoptive transfer therapies have been shown to induce enhanced immune responses in patients but have not always correlated with improved outcomes, likely because of the tumor immunosuppressive microenvironment. checkpoint inhibitors can impair these tumor immunosuppressive capabilities. Although no one treatment has been able to consistently eliminate gliomas and maintain remission, combinations of vaccines or adoptive transfer techniques in conjunction with immune checkpoint inhibitors offers promise.

关键词： Glioma immunotherapy checkpoint inhibitors vaccines T-cells dendritic cells

Nonlinear response of a multidirectional negative-stiffness isolation system via semirecursive multibody dynamic approach

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International Journal of Mechanical System Dynamics 2024年第3期4卷 258-277页

作者： Wei Dai Biagio carboni Giuseppe Quaranta Yongjun Pan walter Lacarbonara college of Mechanical and Vehicle Engineering Chongqing UniversityChongqingChina Department of Structural and Geotechnical Engineering Sapienza University of RomeRomeItaly

This paper investigates an innovative negative-stiffness device(NSD)that modifies the apparent stiffness of the supported structure for seismic *** NSD comprises a lower base on the bottom and a cap on the top,together with a connecting rod,vertical movable wall,and compressed elastic spring,as well as circumferentially arranged,pretensioned external ropes,and inclined shape memory *** configuration can deliver negative stiffness and energy dissipation in any direction within the horizontal plane.A numerical model of the device is developed through a two-step semirecursive method to obtain the force–displacement characteristic *** a model is first validated through comparison with the results obtained via the commercial software ***,a large parametric study is performed to assess the role and the influence of each design variable on the overall response of the proposed *** guidelines are drawn from this analysis to guide the system design and optimization.

关键词： multibody system negative stiffness semirecursive approach seismic protection vibration isolation

The Paris 2024 Olympic and Paralympic Games

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Journal of Sport and Health Science 2024年第6期13卷 717-718页

作者： walter Herzog Human Performance Laboratory Faculty of KinesiologyUniversity of CalgaryCalgaryAB T2N 1N4Canada

The first modern Olympic Games took place in Athens in *** in those early days of the Olympics only amateur and gentleman athletes were allowed to participate,today Olympic athletes are highly trained professionals often dedicating decades of preparation for the chance to compete in the Olympic *** sharp contrast to these highly trained athletes,the world’s population becomes less physically active on average,resulting in an obesity epidemic with associated metabolic syndrome and increased mortality through non-communicable diseases(e.g.,collins et al.^(1)).

关键词： Olympic allowed sharp

Intraocular pressure before and after capsulorhexis using two viscoelastic substances and two surgical approaches in enucleated porcine eyes

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1156-1160页

作者： chiraz Ben Abdallah walter Sekundo Markus SLadewig Daniel M.Handzel Augenzentrum Osthessen Fulda 36037Germany University Eye Hospital Philipps-University Marburg 35043Germany University Eye Hospital Philipps-University Campus FuldaFulda 36043Germany

AIM:To investigate the influence of ophthalmic viscoelastic devices(OVDs)and different surgical approaches on the intraocular pressure(IOP)before and after creation of the curvilinear circular capsulorhexis(ccc)as a measure for anterior chamber stability during this ***:Prospective experimental WetLab study carried out on enucleated porcine *** was measured before and after ccc with the icare Rebound tonometer(icare ic200;icare Finland Oy,Vantaa,Finland).The OVDs used were a cohesive one[Z-Hyalin,carl Zeiss Meditec AG,Germany;hyaluronic acid(HA)]and a dispersive[Z-celcoat,carl Zeiss Meditec AG,Germany;hydroxy propylmethylcellulosis(HPMc)].The ccc was created using Utrata forceps or 23 g microforceps in different combinations with the ***:Using the Utrata forceps the IOP dropped from 63.65±6.44 to 11.25±3.63 mm Hg during the *** use of different OVDs made no *** the 23 g microforceps the IOP dropped from 65.35±8.15 to 36.55±6.09 mm *** difference between IOP drop using either Utrata forceps or 23 g microforceps was highly significant regardless of the OVD ***:Using the sideport for the creation of the capsulorhexis leads to a lesser drop in IOP during this maneuver compared to the main incision in enucleated porcine *** use of different OVD has no significant influence on IOP drop.

关键词： cataract surgery ophthalmosurgical viscoelastic device intraocular pressure capsulorhexis enucleated porcine eye

A simple laboratory method for the generation of mixed brominated-chlorinated paraffin single chain mixtures

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Emerging contaminants 2024年第2期10卷 90-97页

作者： walter Vetter clara Hägele Karin Herrmann Tobias Schulz Sina Schweizer University of Hohenheim Institute of Food Chemistry(170b)Garbenstr.2870599StuttgartGermany

Brominated-chlorinated paraffins(Br-cPs)are a comparably new compound class that features both cl and Br atoms on one or several alkane *** to legal restrictions in the use of conventional chlorinated paraffins(cPs),Br-cPs have the potential to become emerging ***,their determination is hampered by the lack of suitable reference ***,we present a simple synthesis procedure with single chain alkanes that leads to Br-cPs with∼4–8 chlorine and 1 to 4 bromine substituents according to gas chromatography with electron capture negative ion mass spectrometry(Gc/EcNI-MS).The single-chain Br-cP mixtures were obtained by the shared chlorination and bromination of eight single-chain alkanes(c10 to c17)at two reaction times,*** carbon content of the 16 single-chain Br-cP products,determined by elemental analysis(EA),ranged from 30.8 to 43.8%.The typical hump peak known from cPs was detected with Gc with flame ionization detection(Gc/FID),electron capture detection(Gc/EcD)and Gc/*** complexity indicated that low-resolution mass spectrometry is not sufficient for an adequate analysis of Br-cPs.A mathematical formula was developed which allows to calculate all possible combinations of Br and cl that are in line with the carbon *** proton magnetic resonance spectroscopy(1H NMR)spectra showed similarities to the ones of cPs with one chemical shift range for protons on nonhalogenated carbons and one for protons with one halogen on the same carbon.

关键词： NMR) mixtures alkanes

Pumping-induced Well Hydraulics and Groundwater Budget in a Leaky Aquifer System with Vertical Heterogeneity in Aquitard Hydraulic Properties

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Acta Geologica Sinica(English Edition) 2024年第2期98卷 477-490页

作者： ZHUANG chao LÜchenyang YAN Long LI Yabing ZHOU Zhifang WANG Jinguo DOU Zhi walter A.ILLMAN School of Earth Sciences and Engineering Hohai UniversityNanjing 211100China School of Geography Earth and Environmental SciencesUniversity of BirminghamBirmingham B152TTU.K. Department of Modern Mechanics University of Science and Technology of ChinaHefei 230027China Department of Earth and Environmental Sciences University of WaterlooOntario N2L 3G1Canada

In groundwater hydrology,aquitard heterogeneity is often less considered compared to aquifers,despite its significant impact on groundwater hydraulics and groundwater resources evaluation.A semi-analytical solution is derived for pumping-induced well hydraulics and groundwater budget with consideration of vertical heterogeneity in aquitard hydraulic conductivity(K)and specific storage(S_(s)).The proposed new solution is innovative in its partitioning of the aquitard into multiple homogeneous sub-layers to enable consideration of various forms of vertically heterogeneous K or S_(s).Two scenarios of analytical investigations are explored:one is the presence of aquitard interlayers with distinct K or S_(s) values,a common field-scale occurrence;another is an exponentially depth-decaying aquitard S_(s),a regional-scale phenomenon supported by statistical *** investigations reveal that a low-K interlayer can significantly increase aquifer drawdown and enhance aquifer/aquitard depletion;a high-S_(s) interlayer can noticeably reduce aquifer drawdown and increase aquitard *** of low-K or high-S_(s) interlayers also significantly impact well hydraulics and groundwater *** the context of an exponentially depth-decaying aquitard S_(s),a larger decay exponent can enhance aquifer *** using current models with a vertically homogeneous aquitard,half the sum of the geometric and harmonic means of exponentially depth-decaying aquitard S_(s) should be used to calculate aquitard depletion and unconfined aquifer leakage.

关键词： hydrogeology aquitard vertical heterogeneity semi-analytical solution well hydraulics groundwater budget

Plant community on a volcano mountaintop reveals unique high-altitude vegetation in southeastern Brazil

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Journal of Mountain Science 2024年第9期21卷 3018-3030页

作者： Igor Musauer KESSOUS Ruy JoséValka ALVES Nílber Gonçalves da SILVA Amilcar walter SAPORETTI JUNIOR Biodiversity Laboratory Federal Institute of EducationScience and Technology of Southern Minas Gerais(IFSULDEMINAS)Av.Dirce Pereira Rosa300-Jardim Esperança37713-100Poços de CaldasMGBrazil Department of Botany National MuseumFederal University of Rio de JaneiroQuinta da Boa Vista s.n.São Cristóvão20949-040Rio de JaneiroRJBrazil Gothenburg Global Biodiversity centre Carl Skottsbergs Gata 22BSE 41319GothenburgSweden

Mountains exhibit a high degree of endemism and diversity,however,quantifying their biodiversity can be *** to islands,species isolation in mountainous regions results in comparable patterns of evolution and extinction,rendering their biodiversity unique and highly susceptible to anthropogenic *** topographic relief in mountains plays a crucial role in creating habitat complexity,which in turn contribute to high plant ***,we investigated plant diversity in the volcano mountaintop vegetation on the Poços de caldas Plateau,a region situated in the ecotone between the Atlantic Forest and cerrado,characterized by natural radiation and significant anthropogenic *** employed an automated approach through the filtering of georeferenced and non-georeferenced data to obtain a list of plant species in the ***,we statistically investigated the similarity among different high-altitude vegetations belonging to the campos de altitude from the Atlantic Forest and campos rupestres from the *** plateau exhibits high plant diversity,including 1,659 specific and infraspecific taxa,especially belonging to Asteraceae and *** analyses suggest that geographical distance is a strong predictor of dissimilarity and that the Poços de caldas Plateau is more floristically related to the campos rupestres,despite being associated with campos de *** region possesses a unique set of biodiversity,indicating that it may be a distinct ***,we hypothesize that Pleistocene events likely influenced the conformation of the current floristic composition in the region through species interchange between the cerrado and Atlantic *** study also highlights the few taxa assessed for conservation status and anthropogenic threats that this habitat is facing.

关键词： Atlantic Forest Biogeography cerrado community ecology Grassland

Between Quantum Mechanics and General Relativity

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Journal of Modern Physics 2024年第8期15卷 1199-1228页

作者： walter James christensen Jr. Department of Physics and Astronomy Cal Poly Pomona University Pomona USA

The origin of elementary particle mass is considered as a function of n-valued graviton quanta. To develop this concept we begin in a cold region of “empty space” comprised of only microscopic gravitons oscillating at angular frequency ω. From opposite directions enters a pair of stray protons. Upon colliding, heat and energy are released. customarily, this phase and what follows afterward would be described by Quantum chromodynamics (QcD). Instead, we argue for an intermediary step. One in which neighboring gravitons absorb discrete amounts of plane-wave energy. captured by the graviton, the planewave becomes a standing wave, whereupon its electromagnetic energy densities are converted into gravitational quanta. Immediately thereafter an elementary particle is formed and emitted, having both mass and spin. From absorption to conversion to emission occurs in less than 3.7 × 10−16 s. During this basic unit of hybrid time, general relativity and quantum physics unite into a common set of physical laws. As additional stray protons collide the process continues. Over eons, vast regions of spacetime become populated with low-mass particles. These we recognize to be dark matter by its effects on large scale structures in the universe. Its counterpart, dark energy, arises when the conversion of gravitational quanta to particle emission is interrupted. This causes the gravitational quanta to be ejected. It is recognized by its large scale effects on the universe.

关键词： Dark Matter and Energy Gravitational Quanta Graviton Standing Wave Schwarzschild Metric General Relativity Quantum Physics Unified Field Theory Blackholes

A METHOD TO GENERATE MATURE DENDRITIc cELLS FROM cRYOPRESERVED PBMc

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chinese Journal of cancer Research 2003年第1期15卷 9-13页

作者：吴安华张学 walter c.low Departments of Neurosurgery China Medical University Shenyang 110001 China cell Biology China Medical University Shenyang 110001 China Department of Neurosurgery University of Minnesota Medical School Minneapolis MN 55455 USA

Objective: To established methods for cryopreserving peripheral blood mononuclear cells (PBMcs) andproducing Dcs from cryopreserved PBMcs. Methods:Mature Dcs were generated from cryopreserved PBMcs by using IL-4, GM-cSF, TNF-a, IL-1b, IL-6, pgE2 and LPS. The phenotype of the resultant Dcs was investigated by flow cytometry. The functions of the resultant Dcs were verified by Elispot assay. Results: The resultant Dcs expressed high levels of HLA ABc, HLA DR, costimulatory molecules and the Dc maturation marker cD83. The mature Dcs wegenerated from frozen PBMcs were able to prime cD8 T cells into long term IFN-g producing peptide specific cTL. conclusion: The Dcs we developed from cryopreservedPBMc were fully mature and had the capability tostimulate immune reaction. Thus, we developed a method to generate functional mature Dc from cryopreservedPBMc.

关键词： Dendritic cell (Dc) Peripheral bloodmononuclear cell (PBMc) cytotoxic T lymphocyte (cTL)