Immune response to functionalized mesoporous silica nanoparticles for targeted drug delivery

Multifunctional mesoporous silica nanoparticles (MSN) have attracted substantial attention with regard to their high potential for targeted drug delivery. For future clinical applications it is crucial to address safety concerns and understand the potential immunotoxicity of these nanoparticles. In this study, we assess the biocompatibility and functionality of multifunctional MSN in freshly isolated, primary murine immune cells. We show that the functionalized silica nanoparticles are rapidly and efficiently taken up into the endosomal compartment by specialized antigen-presenting cells such as dendritic cells. The silica nanoparticles showed a favorable toxicity profile and did not affect the viability of primary immune cells from the spleen in relevant concentrations. Cargo-free MSN induced only very low immune responses in primary cells as determined by surface expression of activation markers and release of pro-inflammatory cytokines such as Interleukin-6, -12 and -1β. In contrast, when surface-functionalized MSN with a pH-responsive polymer capping were loaded with an immune-activating drug, the synthetic Toll-like receptor 7 agonist R848, a strong immune response was provoked. We thus demonstrate that MSN represent an efficient drug delivery vehicle to primary immune cells that is both non-toxic and non-inflammagenic, which is a prerequisite for the use of these particles in biomedical applications

The conditions of peak empiricism in big data and interaction design

An influx of mechanisms for the collection of large sets of data has prompted widespread consideration of the impact that data analytic methods can have on a number of disciplines. Having an established record of the use of a unique mixture of empirical methods, the work of understanding and designing for user behavior is well situated to take advantage of the advances claimed by “big data” methods. Beyond any straightforward benefit of the use of large sets of data, such an increase in the scale of empirical evidence has far-reaching implications for the work of empirically guided design. We develop the concept of “peak empiricism” to explain the new role that large-scale data comes to play in design, one in which data become more than a simple empirical tool. In providing such an expansive empirical setting for design, big data weakens the subjective conditions necessary for empirical insight, pointing to a more performative approach to the relationship between a designer and his or her work. In this, the work of design is characterized as “thinking with” the data in a partnership that weakens not only any sense of empiricism but also the agentive foundations of a classical view of design work

In the Shadow of Akimbo Corporatism: Arched Athleticism and the 'Becoming-Human' of a People.

The importance of Deleuze and Deleuze and Guattari’s development of ‘encounter’ is brought into sharp relief as key to the notion of ‘athleticism’. Here, both are developed as indispensable to each other, forming an a-radical/ana-material groundless ground to power, politics, literary sensibility, indeed sense itself – though all played in a minor key. It is a nuanced encounter which, at one and the same time, if working as encounter, produces an acephaletic knowledge, a body-knowledge, without the Ego-I. This, in itself would have been enough. But in an age of massifying systems, drone warfare and horrific migrations, where corporate tentacles bend the rules akimbo, one finds that this turn to a Deleuzean athleticism offers a different kind of political analysis, a radical difference, which, despite (or because of) the odds, enables a politics of hope and indeed, of a ‘becoming-human’

Interleukin-22 Is Frequently Expressed in Small- and Large-Cell Lung Cancer and Promotes Growth in Chemotherapy-Resistant Cancer Cells

Introduction: In lung cancer, interleukin-22 (IL-22) expression within primary tissue has been demonstrated, but the frequency and the functional consequence of IL-22 signaling have not been addressed. This study aims at analyzing the cellular effects of IL-22 on lung carcinoma cell lines and the prognostic impact of IL-22 tissue expression in lung cancer patients. Methods: Biological effects of IL-22 signaling were investigated in seven lung cancer cell lines by Western blot, flow cytometry, real-time polymerase chain reaction, and proliferation assays. Tumor tissue specimens of two cohorts with a total of 2300 lung cancer patients were tested for IL-22 expression by immunohistochemistry. IL-22 serum concentrations were analyzed in 103 additional patients by enzyme-linked immunosorbent assay. Results: We found the IL-22 receptor 1 (IL-22-R1) to be expressed in six of seven lung cancer cell lines. However IL-22 signaling was functional in only four cell lines, where IL-22 induced signal transducer activator of transcription 3 phosphorylation and increased cell proliferation. Furthermore, IL-22 induced the expression of antiapoptotic B-cell lymphoma 2, but did not rescue tumor cells from carboplatin-induced apoptosis. Cisplatin-resistant cell lines showed a significant up-regulation of IL-22-R1 along with a stronger proliferative response to IL-22 stimulation. IL-22 was preferentially expressed in small- and large-cell lung carcinoma (58% and 46% of cases, respectively). However, no correlation between IL-22 expression by immunohistochemistry and prognosis was observed. Conclusion: IL-22 is frequently expressed in lung cancer tissue. Enhanced IL-22-R1 expression and signaling in chemotherapy-refractory cell lines are indicative of a protumorigenic function of IL-22 and may contribute to a more aggressive phenotype

Materiality in the future of history: things, practices, and politics

Frank Trentmann is professor of history at Birkbeck College, University of London. From 2002 to 2007, he was director of the £5 million Cultures of Consumption research program, cofunded by the Arts and Humanities Research Council and the Economic and Social Research Council (ESRC). He is working on a book for Penguin, The Consuming Passion: How Things Came to Seduce, Enrich, and Define Our Lives, from the Seventeenth Century to the Twenty‐First. This article is one of a pair seeking to facilitate greater exchange between history and the social sciences. Its twin—“Crossing Divides: Globalization and Consumption in History” (forthcoming in the Handbook of Globalization Studies, ed. Bryan Turner)—shows what social scientists (and contemporary historians) might learn from earlier histories. The piece here follows the flow in the other direction. Many thanks to the ESRC for grant number RES‐052‐27‐002 and, for their comments, to Heather Chappells, Steve Pincus, Elizabeth Shove, and the editor and the reviewer

Static Single Information Form for Abstract Compilation

In previous work we have shown that more precise type analysis can be achieved by exploiting union types and static single assignment (SSA) intermediate representation (IR) of code. In this paper we exploit static single information (SSI), an extension of SSA proposed in literature and adopted by some compilers, to allow assignments of more precise types to variables in conditional branches. In particular, SSI can be exploited rather easily and effectively to infer more precise types in dynamic object-oriented languages, where explicit runtime typechecking is frequently used. We show how the use of SSI form can be smoothly integrated with abstract compilation, our approach to static type analysis. In particular, we define abstract compilation based on union and nominal types for a simple dynamic object-oriented language in SSI form with a runtime typechecking operator, to show how precise type inference can be