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Microphysiological systems for solid tumor immunotherapy:opportunities and challenges

Microsystems & Nanoengineering 2023年第6期9卷 77-106页

作者： sara Abizanda-Campo María Virumbrales-Muñoz Mouhita Humayun Ines Marmol David j.Beebe Ignacio Ochoa sara Oliván j.se M.Ayuso Department of Dermatology University of Wisconsin-MadisonMadisonWIUSA University of Wisconsin Carbone Cancer Center MadisonWIUSA Department of Biomedical Engineering University of WisconsinMadisonWIUSA Tissue Microenvironment Lab(TME lab) Aragón Institute of Engineering Research(I3A)University of ZaragozaZaragozaSpain Instituto de Investigación Sanitaria Aragón(IISA) ZaragozaSpain Centro Investigación Biomédica en Red.Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN)ZaragozaSpain Department of Obstetrics and Gynecology University of Wisconsin-MadisonMadisonWIUSA Department of Biological Engineering Massachusetts Institute of Technology CambridgeCambridgeMAUSA Department of Pathology&Laboratory Medicine University of WisconsinMadisonWIUSA

Immunotherapy remains more effective for hematologic tumors than for solid *** of the main challenges to immunotherapy of solid tumors is the immunosuppressive microenvironment these tumors generate,which limits the cytotoxic capabilities of immune effector cells(e.g.,cytotoxic T and natural killer cells).This microenvironment is characterized by hypoxia,nutrient starvation,accumulated waste products,and acidic ***-hij.cked cells,such as fibroblasts,macrophages,and T regulatory cells,also contribute to this inhospitable microenvironment for immune cells by secreting immunosuppressive cytokines that suppress the antitumor immune response and lead to immune ***,there is a strong interest in developing new drugs and cell formulations that modulate the tumor microenvironment and reduce tumor cell immune *** systems(MPSs)are versatile tools that may accelerate the development and evaluation of these therapies,although specific examples showcasing the potential of MPSs remain *** in microtechnologies have led to the development of sophisticated microfluidic devices used to recapitulate tumor *** resulting models,also known as microphysiological systems(MPSs),are versatile tools with which to decipher the molecular mechanisms driving immune cell antitumor cytotoxicity,immune cell exhaustion,and immune cell exclusion and to evaluate new targeted ***,we review existing microphysiological platforms to study immuno-oncological applications and discuss challenges and opportunities in the field.

关键词： immunotherapy versatile solid

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Characterization of Placic Horizons in Ironstone Soils of Louisiana, USA

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Pedosphere 2010年第4期20卷 409-418页

作者： D. C. WEINDORF N. BAKR Y. ZHU B. HAGGARD S. johnson j. DAIGLE Louisiana State University Agricultural Center 307 MB Sturgis Hall Baton Rouge LA 70803 (USA) United States Department of Agriculture-Natural Resources Conservation Service 3737 Government Street AlexandriaLA 71302 (USA)

Placic horizons, defined as thin, wavy, hardened layers of iron and organic matter, are rare within the United States, occurring only in Washington, Alaska, and Hawaii. While ironstone is common in many soils of the southeastern United States, it is not known to contain appreciable organic matter. As a pilot study evaluating the j.stification for a larger study on ironstone in Louisiana, a 40 m lateral exposure with suspected placic horizons was evaluated in Vernon Parish, Louisiana. Results of laboratory analysis show elevated levels of iron and organic matter in the suspect horizons that meet the criteria of placic horizons as defined by the Soil Survey Staff. Based on the results of this study, additional evaluation of multiple pedons with similar features is warranted. Should additional pedons demonstrate similar properties, a new great group of 'Petrudepts' would be needed to describe both the placic horizons in the pedon and the udic moisture regime in which they occur.

关键词： ortstein pedon petroferric contact Petrudepts

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Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural Regeneration Research 2025年第7期20卷 2011-2012页

作者： Sharon j.Brown Rafael j.Yáñez-Muñoz Heidi R.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson Center for Inherited Neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

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Mowing and fertilizer effects on seedling establishment in a successional old field

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j.urnal of Plant Ecology 2011年第3期4卷 157-168页

作者： David j.Gibson j.red Urban sara G.Baer Department of Plant Biology and Center for Ecology Southern Illinois University CarbondaleCarbondaleIL 62901USA

Aims We used a 10-year field experiment that consisted of mowing and fertilizer treatments to evaluate the role of niche limitation in seedling establishment of species from different functional groups and of varying local abundance in an old field undergoing *** Seedlings of nine different species were planted into a successional field subj.cted to mowing and fertilizer treatments for 10 years that resulted in different plant communities and resource *** representative of the factorial combination of three functional groups(C4 grasses,C3 grasses and legumes)and three abundance categories(abundant,present,or absent in the old field)were planted in four treatments resulting from the factorial combination of annual spring mowing(mowed and unmowed)and fertilizer application(annually fertilized and unfertilized).Survivorship,relative growth rate(RGR)and biomass were measured to determine the role of niche limitation on recruitment and *** Findings Mowing increased the establishment success of *** had little influence on seedling performance and survivorship.C3 grasses had the highest survivorship,while C4 grasses and legumes had equivalent RGRs,but higher than C3 *** contrast,survivorship of legumes was unrelated to mowing or fertilizer,suggesting that establishment of this functional group was dependent on other,unmeasured conditions or *** already present,but at low abundance,performed better than locally abundant or absent *** limitation may restrict the arrival of a ***,recruitment and establishment was subj.ct to niche limitation,which varied among species,functional groups and whether a species is already resident at the site and its ***,species interactions restrict establishment during old-field succession,supporting the niche limitation hypothesis.

关键词： disturbance niche limitation plant functional group seedlings succession

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A review of ecological impacts of global climate change on persistent organic pollutant and mercury pathways and exposures in arctic marine ecosystems

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Current Zoology 2015年第4期61卷 617-628页

作者： Melissa A. MCKINNEY sara PEDRO Rune DIETZ Christian SONNE Aaron T. FISK Denis ROY Bj.rn M. j.NSSEN Robert j. LETCHER Department of Natural Resources and the Environment University of Connecticut Storrs CT 06269 USA Center for Environmental Sciences and Engineering University of Connecticut Storrs CT 06269 USA Department of Bioscience Arctic Research Centre Aarhus University Roskilde DK-4000 Denmark Great Lakes Institute for Environmental Research University of Windsor Windsor ON N9B 3P4 Canada Department of Biology Norwegian University of Science and Technology Trondheim NO-7491 Norway Wildlife and Landscape Science Directorate Science and Technology Branch Environment Canada National Wildlife Research Centre Carleton University Ottawa ON K1A 0H3 Canada

Bioaccumulative and biomagnifying contaminants, such as persistent organic pollutants （POPs） and mercury （Hg）, have for decades been recognized as a health concern in arctic marine biota. In recent years, global climate change （GCC） and related loss of arctic sea ice have been observed to be driving substantial change in arctic ecosystems. This review summarizes findings documenting empirical links between GCC-induced ecological changes and alterations in POP and Hg exposures and pathways in arctic marine ecosystems. Most of the studies have reported changes in POP or Hg concentrations in tissue in relation to GCC-induced changes in species trophic interactions. These studies have typically focused on the role of changes in abun- dance, habitat range or accessibility of prey species, particularly in relation to sea ice changes. Yet, the ecological change that re- suited in contaminant trend changes has often been unclear or assumed. Other studies have successfully used chemical tracers, such as stable nitrogen and carbon isotope ratios and fatty acid signatures to link such ecological changes to contaminant level variations or trends. Lower sea ice linked-diet changes/variation were associated with higher contaminant levels in some popula- tions of polar bears, ringed seals, and thick-billed murres, but the influence of changing trophic interactions on POP levels and trends varied widely in both magnitude and direction. We suggest that future research in this new area of GCC-linked ecotox- icology should focus on routine analysis of ancillary ecological metrics with POP and Hg studies, simultaneous consideration of the multiple mechanisms by which GCC and contaminant interactions can occur, and targeted research on changing exposures and toxicological effects in species known to be sensitive to both GCC and contaminants [Current Zoology 61 （4）： 617-628, 2015].

关键词： Climate change Ecological change Contaminants Trends Arctic Marine ecosystems

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A RAPID ASSESSMENT APPROACH FOR EVALUATING SILVER CARP GENDER

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水生生物学报 2018年第6期42卷 1081-1083页

作者： WOLF Michael C. PHELPS Quinton E. SEIBERT j.stin R. TRIPP sara j. Department of Natural Resources Fish and Wildlife Division204 Main Street East BaudetteMinnesota 56623USA West Virginia University Division of Forestry and Natural Resources307C Percival HallMorgantownWest Virginia 26505USA Southeast Missouri State University Biology Department 1 University Plaza Cape GirardeauMissouri 63701USA Big Rivers and Wetlands Field Station Missouri Department of Conservation3815 East Jackson BoulevardJacksonMissouri 63755USA

Silver carp Hypophthalmichthys molitrix were introduced into the U.S. to control water quality in aquaculture ponds. From this point of origin, silver carp escaped into nearby rivers through multiple flood events. Because of their documented negative effects on native biota, silver carp have been labeled as problematic. Therefore, evaluating the biology and ecology of these non-indigenous species is critical. Multiple parameters are needed to evaluate silver carp populations(length, weight, age, and sex). Furthermore, developing methods for rapidly acquiring these data are needed. In relation to sex determination, sexual dimorphism was observed where males exhibit distinct pectoral fin ray features. Specifically, males have pronounced ridges or a "rough patch" on the dorsal surface of pectoral fins. Therefore, to test if this was an applicable way of determining silver carp gender; silver carp were collected from Midwestern U.S. rivers(N=2015) in the fall of 2011(N=870), spring of 2012(N=645), winter of 2013—2014(N=202) and summer2015(N=323) via electrofishing. For each silver carp collected, presence(e.g., rough patch) or absence(e.g.,smooth) of pronounced ridges on the top side of the pectoral fins was recorded, and an incision was made in the body cavity to identify gender. Based on the results of our evaluation, gender was correctly identified over99% of the time(2006 out of 2015) based on the pectoral fin dimorphism. In the samples taken in the winter of 2013—2014 and summer of 2015, accuracy for silver carp shorter than 300 mm and longer than 800 mm was 53.7%(19 out of 41) while accuracy for silver carp between 300 mm and 800 mm total length was 98.9%(289 out of 292). This study provides a rapid assessment approach for evaluating silver carp gender.

关键词： Invasive species Gender assessment

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A structural topological optimization method for multi-displacement constraints and any initial topology configuration

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Acta Mechanica Sinica 2010年第5期26卷 735-744页

作者： j. H. Rong j. H. Yi School of Automotive and Mechanical Engineering Changsha University of Science and TechnologyChangsha 410076 China

In density-based topological design, one expects that the final result consists of elements either black （solid material） or white （void）, without any grey areas. Moreover, one also expects that the optimal topology can be obtained by starting from any initial topology configuration. An improved structural topological optimization method for multidisplacement constraints is proposed in this paper. In the proposed method, the whole optimization process is divided into two optimization adj.stment phases and a phase transferring step. Firstly, an optimization model is built to deal with the varied displacement limits, design space adj.stments, and reasonable relations between the element stiffness matrix and mass and its element topology variable. Secondly, a procedure is proposed to solve the optimization problem formulated in the first optimization adj.stment phase, by starting with a small design space and advancing to a larger deign space. The design space adj.stments are automatic when the design domain needs expansions, in which the convergence of the proposed method will not be affected. The final topology obtained by the proposed procedure in the first optimization phase, can approach to the vicinity of the optimum topology. Then, a heuristic algorithm is given to improve the efficiency and make the designed structural topology black/white in both the phase transferring step and the second optimization adj.stment phase. And the optimum topology can finally be obtained by the second phase optimization adj.stments. Two examples are presented to show that the topologies obtained by the proposed method are of very good 0/1 design distribution property, and the computational efficiency is enhanced by reducing the element number of the design structural finite model during two optimization adj.stment phases. And the examples also show that this method is robust and practicable.

关键词： Topological optimization Displacement constraint Continuum structure Design space adj.stment Rational approximation material model

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Unimodal Sequences of Gorenstein Ideals of Codimension 4

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Acta Mathematica Sinica,English Series 1998年第4期14卷 563-568页

作者： Hyoung j. Ko Department of Mathematics. Yonsei University 134 Shinchon-dong Seodaemun-gu. Seoul Korea 120-749

We present Gorenstein ideals of condimension 4 which have unimodal Hilbert functions.

关键词： k-configuration Hilbert function Minimal free resolution Gorenstein ideal of codimension 4

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Positron emission particle tracking——Application and labelling techniques

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Particuology 2008年第1期6卷 16-23页

作者： David j. Parker School of Physics and Astronomy the University of Birmingham Edgbaston Birmingham B15 2TT UK

The positron emission particle tracking （PEPT） technique has been widely used in science and engineering to obtain detailed information on the motion and flow fields of fluids or granular materials in multiphase systems, for example, fluids in rock cracks, chemical reactors and food processors; dynamic behaviour of granular materials in chemical reactors, granulators, mixers, dryers, rotating kilns and ball mills. The information obtained by the PEPT technique can be used to optimise the design, operational conditions for a wide range of industrial process systems, and to evaluate modelling work. The technique is based on tracking radioactively labelled particles （up to three particles） by detecting the pairs of backto-back 511 keV γ-rays arising from annihilation of emitted positrons. It therefore involves a positron camera, location algorithms for calculating the tracer location and speed, and tracer labelling techniques. This paper will review the particle tracking technique from tracking algorithm, tracer labelling to their application.

关键词： PEPT Tracer Algorithm Tracking

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Formalisms to Support the Definition of Processes

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j.urnal of Computer Science & Technology 2009年第2期24卷 198-211页

作者： Leon j. Osterweil Department of Computer Science University of Massachusetts Amherst

This paper emphasizes the importance of defining processes rigorously, completely, clearly, and in detail in order to support the complex proj.cts that are essential to the modern world. The paper argues that such process definitions provide needed structure and context for the development of effective software systems. The centrality of process is argued by enumerating seven key ways in which processes and their definitions are expected to provide important benefits to society. The paper provides an example of a process formalism that makes good progress towards the difficult goal of being simultaneously rigorous, detailed, broad, and clear. Early experience suggests that these four key characteristics of this formalism do indeed seem to help it to support meeting the seven key benefits sought from process definitions. Additional research is suggested in order to gain more insights into needs in the area of process definition formalisms.

关键词： processes process definition process language

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