State promotion of local public goods: The case of public libraries, 1880-1929

The public library movement of the late nineteenth and early twentieth centuries led to a significant expansion of library services across the United States. We study the impact of state-level institutional development on the creation of local public goods. State library commissions were modestly funded state entities charged with helping localities establish libraries. State library associations were voluntary organizations with a similar mission, having as members the librarians of existing public libraries. Library-enabling legislation clarified the legality and taxation possibilities for local government entities such as towns, municipalities and counties to support libraries. Employing panel data drawn from a series of detailed reports on public libraries conducted by the U.S. Bureau of Education, we use a difference-in-differences methodology to identify the impact of commissions, associations, and enabling legislation on library development in matched pairs of counties that straddle state borders. Our results suggest that state-level institutions and legislation had a statistically and economically significant effect on public library development. The finding has implications for future interpretations of the history of the United States as a “nation of joiners”; local civic engagement and associational life was importantly influenced by larger scale civic and political action. JEL classifications: H40, H75, N31, N32, N41, N4

Public libraries and political participation, 1870-1940

The public library movement of the late 19th and early 20th centuries fostered a rapid increase in the number and quality of public libraries in cities and towns across the United States. One important argument for libraries was that they would enhance American democracy by promoting virtues of citizenship and enabling access to information. This paper examines how voter turnout was affected, in the short-term, by the establishment of public libraries, using a county-by-election year panel. Our empirical strategy exploits the founding dates of public libraries as discrete events that should have influenced subsequent voting behavior. Over the wide range of specifications considered, the vast majority of regression results suggest that libraries had no significant short term impact on voter turnout. We discuss potential reasons for this finding, and compare it with recent work finding a positive impact of newspapers on political participation. JEL classifications: H40, H75, N31, N32, N41, N4

From Quasi-Private to Quasi-Public: The Development of Local Libraries in the United States, 1870-1930

The period 1870-1930 witnessed the emergence of the local public library as a widespread and enduring American institution. During these years, access to free community-based library services spread to a much larger share of the U.S. population, while the institutional structure of local libraries underwent a transition from largely quasi-private, voluntary associations to the tax-supported public institutions familiar today. In this paper we describe this transition, and document the expansion of public libraries and library services in the United States over these years, using data drawn from library surveys conducted by the federal Bureau of Education. We then review some causal accounts for that expansion. Exploiting cross-state and temporal variation in the data, we estimate cross-section and panel regressions to assess plausible demand and supply factors affecting the pace of library development. We consider a number of the social and economic variables that have been found to correlate with the development of secondary educational institutions, which expanded during roughly the same historical period: these include, when available, income or wealth, urbanization, ethnic composition, and in some specifications average levels of education and literacy. We also examine the effect of legal and political factors that were specific to public libraries, such as state library commissions and associations

The Development of Public Libraries in the United States, 1870–1930: A Quantitative Assessment

The period 1870–1930 witnessed the emergence of the local public library as a widespread and enduring American institution. We document the expansion of public libraries in the United States using data drawn from library surveys conducted by the federal Bureau of Education. We then review causal accounts for that expansion. Exploiting cross-state and temporal variation in the data, we use statistical techniques to assess a number of plausible demand-and-supply factors affecting the pace of library development. Social and economic variables in the analysis include state income or wealth, urbanization, ethnic composition, and gender ratios. We also examine the effect of institutional innovations, such as state library commissions and library associations, that likely affected the establishment of public libraries. We confirm that library expansion was robustly related to urbanization and greater ethnic (immigrant) diversity and to institutional innovations and that it was greatly delayed in southern states

Expression, processing and transcriptional regulation of granulysin in short-term activated human lymphocytes

BACKGROUND: Granulysin, a cytotoxic protein expressed in human natural killer cells and activated T lymphocytes, exhibits cytolytic activity against a variety of intracellular microbes. Expression and transcription have been partially characterised in vitro and four transcripts (NKG5, 519, 520, and 522) were identified. However, only a single protein product of 15 kDa was found, which is subsequently processed to an active 9 kDa protein. RESULTS: In this study we investigated generation of granulysin in lymphokine activated killer (LAK) cells and antigen (Listeria) specific T-cells. Semiquantitative RT-PCR revealed NKG5 to be the most prominent transcript. It was found to be up-regulated in a time-dependent manner in LAK cells and antigen specific T-cells and their subsets. Two isoforms of 519 mRNA were up-regulated under IL-2 and antigen stimulation. Moreover, two novel transcripts, without any known function, comprising solely parts of the 5 prime region of the primary transcript, were detected. A significant increase of granulysin expressing LAK cells as well as antigen specific T-cells was shown by fluorescence microscopy. On the subset level, increase in CD4+ granulysin expressing cells was found only under antigen stimulation.Immunoblotting showed the 15 kDa form of granulysin to be present in the first week of stimulation either with IL-2 or with bacterial antigen. Substantial processing to the 9 kDa form was detected during the first week in LAK cells and in the second week in antigen specific T-cells. CONCLUSION: This first comprehensive study of granulysin gene regulation in primary cultured human lymphocytes shows that the regulation of granulysin synthesis in response to IL-2 or bacterial antigen stimulation occurs at several levels: RNA expression, extensive alternative splicing and posttranslational processing

Expression, processing and transcriptional regulation of granulysin in short-term activated human lymphocytes

BACKGROUND: Granulysin, a cytotoxic protein expressed in human natural killer cells and activated T lymphocytes, exhibits cytolytic activity against a variety of intracellular microbes. Expression and transcription have been partially characterised in vitro and four transcripts (NKG5, 519, 520, and 522) were identified. However, only a single protein product of 15 kDa was found, which is subsequently processed to an active 9 kDa protein. RESULTS: In this study we investigated generation of granulysin in lymphokine activated killer (LAK) cells and antigen (Listeria) specific T-cells. Semiquantitative RT-PCR revealed NKG5 to be the most prominent transcript. It was found to be up-regulated in a time-dependent manner in LAK cells and antigen specific T-cells and their subsets. Two isoforms of 519 mRNA were up-regulated under IL-2 and antigen stimulation. Moreover, two novel transcripts, without any known function, comprising solely parts of the 5 prime region of the primary transcript, were detected. A significant increase of granulysin expressing LAK cells as well as antigen specific T-cells was shown by fluorescence microscopy. On the subset level, increase in CD4+ granulysin expressing cells was found only under antigen stimulation.Immunoblotting showed the 15 kDa form of granulysin to be present in the first week of stimulation either with IL-2 or with bacterial antigen. Substantial processing to the 9 kDa form was detected during the first week in LAK cells and in the second week in antigen specific T-cells. CONCLUSION: This first comprehensive study of granulysin gene regulation in primary cultured human lymphocytes shows that the regulation of granulysin synthesis in response to IL-2 or bacterial antigen stimulation occurs at several levels: RNA expression, extensive alternative splicing and posttranslational processing

Perforin enhances the granulysin-induced lysis of Listeria innocua in human dendritic cells

Background: Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells play an essential role in the host defence against intracellular pathogens such as Listeria, and Mycobacteria. The key mediator of bacteria-directed cytotoxicity is granulysin, a 9 kDa protein stored in cytolytic granules together with perforin and granzymes. Granulysin binds to cell membranes and is subsequently taken up via a lipid raft-associated mechanism. In dendritic cells (DC) granulysin is further transferred via early endosomes to L. innocua-containing phagosomes were bacteriolysis is induced. In the present study we analysed the role of perforin in granulysin-induced intracellular bacteriolysis in DC. Results: We found granulysin-induced lysis of intracellular Listeria significantly increased when perforin was simultaneously present. In pulse-chase experiments enhanced bacteriolysis was observed when perforin was added up to 25 minutes after loading the cells with granulysin demonstrating no ultimate need for simultaneous uptake of granulysin and perforin. The perforin concentration sufficient to enhance granulysin-induced intracellular bacteriolysis did not cause permanent membrane pores in Listeria-challenged DC as shown by dye exclusion test and LDH release. This was in contrast to non challenged DC that were more susceptible to perforin lysis. For Listeria-challenged DC, there was clear evidence for an Ca2+ influx in response to sublytic perforin demonstrating a short-lived change in the plasma membrane permeability. Perforin treatment did not affect granulysin binding, initial uptake or intracellular trafficking to early endosomes. However, enhanced colocalization of granulysin with listerial DNA in presence of perforin was found by confocal laser scanning microscopy. Conclusion: The results provide evidence that perforin increases granulysin-mediated killing of intracellular Listeria by enhanced phagosome-endosome fusion triggered by a transient Ca2+ flux

Panarchy theory for convergence

Coping with surprise and uncertainty resulting from the emergence of undesired and unexpected novelty or the sudden reorganization of systems at multiple spatiotemporal scales requires both a scientific process that can incorporate diverse expertise and viewpoints, and a scientific framework that can account for the structure and dynamics of interacting social-ecological systems (SES) and the inherent uncertainty of what might emerge in the future. We argue that combining a convergence scientific process with a panarchy framework provides a pathway for improving our understanding of, and response to, emergence. Emergent phenomena are often unexpected (e.g., pandemics, regime shifts) and can be highly disruptive, so can pose a significant challenge to the development of sustainable and resilient SES. Convergence science is a new approach promoted by the U.S. National Science Foundation for tackling complex problems confronting humanity through the integration of multiple perspectives, expertise, methods, tools, and analytical approaches. Panarchy theory is a framework useful for studying emergence, because it characterizes complex systems of people and nature as dynamically organized and structured within and across scales of space and time. It accounts for the fundamental tenets of complex systems and explicitly grapples with emergence, including the emergence of novelty, and the emergent property of social-ecological resilience. We provide an overview of panarchy, convergence science, and emergence. We discuss the significant data and methodological challenges of using panarchy in a convergence approach to address emergent phenomena, as well as state-of-the-art methods for overcoming them. We present two examples that would benefit from such an approach: climate change and its impacts on social-ecological systems, and the relationships between infectious disease and social-ecological systems

FindFoci: a focus detection algorithm with automated parameter training that closely matches human assignments, reduces human inconsistencies and increases speed of analysis

Accurate and reproducible quantification of the accumulation of proteins into foci in cells is essential for data interpretation and for biological inferences. To improve reproducibility, much emphasis has been placed on the preparation of samples, but less attention has been given to reporting and standardizing the quantification of foci. The current standard to quantitate foci in open-source software is to manually determine a range of parameters based on the outcome of one or a few representative images and then apply the parameter combination to the analysis of a larger dataset. Here, we demonstrate the power and utility of using machine learning to train a new algorithm (FindFoci) to determine optimal parameters. FindFoci closely matches human assignments and allows rapid automated exploration of parameter space. Thus, individuals can train the algorithm to mirror their own assignments and then automate focus counting using the same parameters across a large number of images. Using the training algorithm to match human assignments of foci, we demonstrate that applying an optimal parameter combination from a single image is not broadly applicable to analysis of other images scored by the same experimenter or by other experimenters. Our analysis thus reveals wide variation in human assignment of foci and their quantification. To overcome this, we developed training on multiple images, which reduces the inconsistency of using a single or a few images to set parameters for focus detection. FindFoci is provided as an open-source plugin for ImageJ

Cellular shape reinforces niche to stem cell signaling in the small intestine

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