Pivotal Advance: Eosinophil infiltration of solid tumors is an early and persistent inflammatory host response

Tumor-associated eosinophilia has been observed in numerous human cancers and several tumor models in animals; however, the details surrounding this eosinophilia remain largely undefined and anecdotal. We used a B16-F10 melanoma cell injection model to demonstrate that eosinophil infiltration of tumors occurred from the earliest palpable stages with significant accumulations only in the necrotic and capsule regions. Furthermore, the presence of diffuse extracellular matrix staining for eosinophil major basic protein was restricted to the necrotic areas of tumors, indicating that eosinophil degranulation was limited to this region. Antibody-mediated depletion of CD4+ T cells and adoptive transfer of eosinophils suggested, respectively, that the accumulation of eosinophils is not associated with T helper cell type 2-dependent immune responses and that recruitment is a dynamic, ongoing process, occurring throughout tumor growth. Ex vivo migration studies have identified what appears to be a novel chemotactic factor(s) released by stressed/dying melanoma cells, suggesting that the accumulation of eosinophils in tumors occurs, in part, through a unique mechanism dependent on a signal(s) released from areas of necrosis. Collectively, these studies demonstrate that the infiltration of tumors by eosinophils is an early and persistent response that is spatial-restricted. It is more important that these data also show that the mechanism(s) that elicit this host response occur, independent of immune surveillance, suggesting that eosinophils are part of an early inflammatory reaction at the site of tumorigenesis. © Society for Leukocyte Biology

Defining a link with asthma in mice congenitally deficient in eosinophils

Eosinophils are often dominant inflammatory cells present in the lungs of asthma patients. Nonetheless, the role of these leukocytes remains poorly understood. We have created a transgenic line of mice (PHIL) that are specifically devoid of eosinophils, but otherwise have a full complement of hematopoietically derived cells. Allergen challenge of PHIL mice demonstrated that eosinophils were required for pulmonary mucus accumulation and the airway hyperresponsiveness associated with asthma. The development of an eosinophi-less mouse now permits an unambiguous assessment of a number of human diseases that have been linked to this granulocyte, including allergic diseases, parasite infections, and tumorigenesis

A causative relationship exists between eosinophils and the development of allergic pulmonary pathologies in the mouse

Asthma and mouse models of allergic respiratory inflammation are invariably associated with a pulmonary eosinophilia; however, this association has remained correlative. In this report, a causative relationship between eosinophils and allergen-provoked pathologies was established using eosinophil adoptive transfer. Eosinophils were transferred directly into the lungs of either naive or OVA-treated IL-5-/- mice. This strategy resulted in a pulmonary eosinophilia equivalent to that observed in OVA-treated wild-type animals. A concomitant consequence of this eosinophil transfer was an increase in Th2 bronchoalveolar lavage cytokine levels and the restoration of intracellular epithelial mucus in OVA-treated IL-5-/- mice equivalent to OVA-treated wild-type levels. Moreover, the transfer also resulted in the development of airway hyperresponsiveness. These pulmonary changes did not occur when eosinophils were transferred into naive IL-5-/- mice, eliminating nonspecific consequences of the eosinophil transfer as a possible explanation. Significantly, administration of OVA-treated IL-5-/- mice with GK1.5 (anti-CD4) Abs abolished the increases in mucus accumulation and airway hyperresponsiveness following adoptive transfer of eosinophils. Thus, CD4+ T cell-mediated inflammatory signals as well as signals derived from eosinophils are each necessary, yet alone insufficient, for the development of allergic pulmonary pathology. These data support an expanded view of T cell and eosinophil activities and suggest that eosinophil effector functions impinge directly on lung function

Pathways of SME Internationalization: a bibliometric and systematic review

Business is dynamic and rapidly changing. Global markets were previously the playing field of multinational corporations (MNCs), while small and medium enterprises (SMEs) were local; however, the removal of imposed barriers, and recent technological advances in manufacturing, transportation and communications have indorsed SMEs and international entrepreneurs (IE) global access. SMEs and IEs are increasingly fueling economic growth and innovation and these trends are presenting both opportunities and challenges to both MNCs and SMEs in the global arena. This review systematically examines comparative SME and IE research, analyzing (after fine tuning) 762 articles published in leading journals from 1992 to September 2018. Our bibliometric and systematic review classifies SME and IE research findings into three echelons: (i) subjects; (ii) theories; and (iii) methods

The role of networks to overcome large-scale challenges in tomography : the non-clinical tomography users research network

Our ability to visualize and quantify the internal structures of objects via computed tomography (CT) has fundamentally transformed science. As tomographic tools have become more broadly accessible, researchers across diverse disciplines have embraced the ability to investigate the 3D structure-function relationships of an enormous array of items. Whether studying organismal biology, animal models for human health, iterative manufacturing techniques, experimental medical devices, engineering structures, geological and planetary samples, prehistoric artifacts, or fossilized organisms, computed tomography has led to extensive methodological and basic sciences advances and is now a core element in science, technology, engineering, and mathematics (STEM) research and outreach toolkits. Tomorrow's scientific progress is built upon today's innovations. In our data-rich world, this requires access not only to publications but also to supporting data. Reliance on proprietary technologies, combined with the varied objectives of diverse research groups, has resulted in a fragmented tomography-imaging landscape, one that is functional at the individual lab level yet lacks the standardization needed to support efficient and equitable exchange and reuse of data. Developing standards and pipelines for the creation of new and future data, which can also be applied to existing datasets is a challenge that becomes increasingly difficult as the amount and diversity of legacy data grows. Global networks of CT users have proved an effective approach to addressing this kind of multifaceted challenge across a range of fields. Here we describe ongoing efforts to address barriers to recently proposed FAIR (Findability, Accessibility, Interoperability, Reuse) and open science principles by assembling interested parties from research and education communities, industry, publishers, and data repositories to approach these issues jointly in a focused, efficient, and practical way. By outlining the benefits of networks, generally, and drawing on examples from efforts by the Non-Clinical Tomography Users Research Network (NoCTURN), specifically, we illustrate how standardization of data and metadata for reuse can foster interdisciplinary collaborations and create new opportunities for future-looking, large-scale data initiatives

Pursuing the American Dream: Economic Mobility Across Generations

Pursuing the American Dream uses the most current data to measure mobility by family income, wealth, and personal earnings to reveal how closely tied a person’s place on the economic ladder is to that of his or her parents’. While a majority of Americans exceed their parents’ family income and wealth, the extent of their absolute mobility gains are not always enough to move them to a different rung of the economic ladder. Measuring both absolute and relative mobility, some of the highlights of the research include: Eighty-four percent of Americans have higher family incomes than their parents did. However, those born at the top and bottom of the income ladder are likely to stay there as adults. Over 40 percent of Americans raised in the bottom quintile of the family income ladder remain stuck there adults, and 70 percent remain below the middle. African Americans are still less likely to exceed their parents’ income than are whites and they are more likely to be stuck at the bottom of the economic ladder across a generation. A four-year college degree promotes upward mobility from the bottom and prevents downward mobility from the middle and the top.https://www.pewtrusts.org/en/research-and-analysis/reports/2012/07/10/pursuing-the-american-dream-economic-mobility-across-generation

Pursuing the American Dream: Economic Mobility Across Generations

Pursuing the American Dream uses the most current data to measure mobility by family income, wealth, and personal earnings to reveal how closely tied a person’s place on the economic ladder is to that of his or her parents’. While a majority of Americans exceed their parents’ family income and wealth, the extent of their absolute mobility gains are not always enough to move them to a different rung of the economic ladder. Measuring both absolute and relative mobility, some of the highlights of the research include: Eighty-four percent of Americans have higher family incomes than their parents did. However, those born at the top and bottom of the income ladder are likely to stay there as adults. Over 40 percent of Americans raised in the bottom quintile of the family income ladder remain stuck there adults, and 70 percent remain below the middle. African Americans are still less likely to exceed their parents’ income than are whites and they are more likely to be stuck at the bottom of the economic ladder across a generation. A four-year college degree promotes upward mobility from the bottom and prevents downward mobility from the middle and the top