Migration of Natural Killer Cells. Matrix interaction, locomotion and regulation of matrix metalloproteinases (MMPs) by IL-2 and chemokines

Activated natural killer (NK) cells are effective anti-tumour cells. In order to reach target cells in a tumour mass they need to migrate in the extravascular space. The process of tumour localisation begins when the NK cell is attracted in the blood stream, and utilisation of matrix-degrading enzymes is crucial for passing of the basal membrane (BM) and for locomotion outside the vascular bed. NK cells express several members of the family of matrix-degrading enzymes, matrix metalloproteinases (MMPs). The aim of this study was to gain more knowledge on the regulation of NK cell migration that affects infiltration of the extracellular matrix (ECM) equivalent Matrigel. In specific; morphologically study NK cell locomotion in a matrix environment; identify the repertoire of MMPs expressed by freshly isolated human NK cells and the human NK cell lines YT and NK-92; explore the role of MMPs in NK cell migration and investigate the effect of IL-2 and chemokine stimulation as well as matrix (Matrigel) contact on NK cells’ migratory ability and MMP expression. IL-2-activated mouse A-NK cells cultured in Matrigel revealed two different patterns of matrix disintegration depending on their time in culture, and similar differences were found between two human NK cell lines. Younger (≤ 5 days) mouse A-NK and NK-92 cells gave rise to a general widespread matrix reorganisation, interpreted to be due to direct release of soluble matrix-degrading enzymes. Older (≥ 6 days) mouse A-NK and YT cells instead produced large excavations in the Matrigel. These cavities could be explained by a release of proteoglycan-rich material with matrix-dilating properties, combined with associated matrix-degrading proteases. The IL 2 independent NK cell line YT and freshly isolated human NK cells was used to investigate the effects of IL-2 stimulation on NK cell migration and MMP expression and production. IL-2 stimulation of the YT cell line demonstrated opposing effects related to the duration of stimulation. A rapid stimulatory response at about 2-4h on MMP production, and a later negative effect on MMP expression and MMP-9 production was seen after prolonged stimulation (≥ 24h). Both responses correspondingly affected the migratory ability. In freshly isolated NK cells, migration increased MMP-dependently in response to IL-2 and MT6-MMP expression increased. MMP-13, MT3- and MT6-MMP, previously not described in NK cells, was found to be expressed by freshly isolated human NK cells. While matrix (Matrigel) contact did not affect MMP expression in either the NK-92 or YT cell line, the chemokine CX3CL1 was found to increase NK-92 cells’ MMP-9 production significantly, but had no effect on their migration. These findings increase our understanding of how NK cell migration is regulated and provide one further step in the development of strategies to achieve greater number of tumour infiltrating NK cells

Comparison of a Genetic Algorithm Variable Selection and Interval Partial Least Squares for quantitative analysis of lactate in PBS

Blood lactate is an important biomarker that has been linked to morbidity and mortality of critically ill patients, acute ischemic stroke, septic shock, lung injuries, insulin resistance in diabetic patients, and cancer. Currently, the clinical measurement of blood lactate is done by collecting intermittent blood samples. Therefore, noninvasive, optical measurement of this significant biomarker would lead to a big leap in healthcare. This study, presents a quantitative analysis of the optical properties of lactate. The benefits of wavelength selection for the development of accurate, robust, and interpretable predictive models have been highlighted in the literature. Additionally, there is an obvious, time- and cost-saving benefit to focusing on narrower segments of the electromagnetic spectrum in practical applications. To this end, a dataset consisting of 47 spectra of Na-lactate and Phosphate Buffer Solution (PBS) was produced using a Fourier transform infrared spectrometer, and subsequently, a comparative study of the application of a genetic algorithm-based wavelength selection and two interval selection methods was carried out. The high accuracy of predictions using the developed models underlines the potential for optical measurement of lactate. Moreover, an interesting finding is the emergence of local features in the proposed genetic algorithm, while, unlike the investigated interval selection methods, no explicit constraints on the locality of features was imposed. Finally, the proposed genetic algorithm suggests the formation of α-hydroxy-esters methyl lactate in the solutions while the other investigated methods fail to indicate this

Feesers Inc v. Michael Foods Inc

USDC for the Middle District of Pennsylvani

PVN-LOT-120-AD-060

Buku ini ditulis oleh para ahli ekonomi politik internasional sebagai referensi untuk memahami perkembangan neoliberal. Proyek neoliberalisme yang sudah lama diterapkan telah menyebabkan efek destruktif yang luar biasa. Ironisnya, proyek ini semakin hegemonik dan sulit dibendung. Negara berkembang menjadi lahan empuk dimana revisi atas kapitalisme dijalankan. Melalui buku ini, konsep governance, modal social dan pembangunan social ala neoliberal lainnya dikritik secara total. Governance sekedar manajemen konflik antar aktor untuk memfasilitasi akumulasi kapital. Sementara “modal sosial” dikooptasi sebagai aset bagi terciptanya kohesi social guna memperlancar akumulasi modal. Buku ini dibagi menjadi tiga bagian. Bagian I: Ekonomi Politik Governance Neoliberal Global, membahas mengenai istilah governance, geneologi, diskursus, swaregulasi, kemitraan, dsb. Bagian II: Modal Sosial sebagai Kelanjutan Developmentalisme, membahas antara lain: fondasi ekonomi makro, dan modal sosial. Bab III: Strategi Neoliberal Pemerintah melalui Masyarakat, antara lain berisi bahasan tentang: pemerintah, strategi bantuan Negara, optimalisasi modal, putaran etnografis, dan pengelolaan konflik.Kata kunci: liberalisme, politik ekonomi, governanc

PVN-LOT-026-A-014

xiv, 300 hlm.:ilus.: 23 c

The Manipulated Mechanism: Towards an Account of the Experimental Discovery of Mechanistic Explanations

Recent work in the philosophy of biology has sought after an account of mechanistic explanation. Biologists frequently encounter causal relationships that beg for explanation. For example, genes appear to encode for particular phenotypes. How does gene expression work? Biologists posit mechanisms to explain the link between cause and effect. Thus, gene expression would be explained by an appeal to a complex mechanism linking the gene to the phenotype, as such an appeal will provide answers to broad ranges of how and why questions about the causal relationship, and predict novel effects. Here, I focus on a recent problem raised for mechanistic explanation. Mechanism discovery is an inferential process which takes empirical data as premises, and produces a causal model of a mechanism as the conclusion. Such an inferential process requires rules, yet few accounts of mechanistic explanation attempt to provide them. Such inferential rules could be used to answer related normative questions facing accounts of mechanistic explanation. In particular, they can be brought to bear on questions of explanatory relevance: Which components are part of the mechanism, and how can we know? and questions of explanatory adequacy: When is a mechanistic explanation a good explanation? I argue that a formal account of mechanistic explanation grounded in a manipulationist account of causation can answer these kinds of question. A thoroughgoing defense of my account, however, requires that I defend its assumptions. Among the assumptions is the highly contentious principle known as `modularity\u27. Modularity is the claim that we must be able to independently manipulate each of the various components in a mechanism. The final chapters of my dissertation focus on a thoroughgoing defense of modularity against claims that it is frequently violated, conceptually intractable, or simply inapplicable to especially biological systems

Vals Thermal Baths

Material of interest: Valser Quartzrite. Properties of material: This stone unique to the area has an unique blend of quartz and feldspar crystals giving it a green hue.https://openscholarship.wustl.edu/bcs/1108/thumbnail.jp

The Good Ole\u27 Boys: Antitrust Issues in America\u27s Largest Spectator Sport

xviii, 442 hlm.; 24 c

The Fairness Doctrine: Its Limits and Occasions in West Virginia Advertising

xiv, 348 hlm.; 24 c

Spectator 1958-05-01

X, 290 hlm.; 28 c