The convergence of radiation and immunogenic cell death signaling pathways.

Ionizing radiation (IR) triggers programmed cell death in tumor cells through a variety of highly regulated processes. Radiation-induced tumor cell death has been studied extensively in vitro and is widely attributed to multiple distinct mechanisms, including apoptosis, necrosis, mitotic catastrophe (MC), autophagy, and senescence, which may occur concurrently. When considering tumor cell death in the context of an organism, an emerging body of evidence suggests there is a reciprocal relationship in which radiation stimulates the immune system, which in turn contributes to tumor cell kill. As a result, traditional measurements of radiation-induced tumor cell death, in vitro, fail to represent the extent of clinically observed responses, including reductions in loco-regional failure rates and improvements in metastases free and overall survival. Hence, understanding the immunological responses to the type of radiation-induced cell death is critical. In this review, the mechanisms of radiation-induced tumor cell death are described, with particular focus on immunogenic cell death (ICD). Strategies combining radiotherapy with specific chemotherapies or immunotherapies capable of inducing a repertoire of cancer specific immunogens might potentiate tumor control not only by enhancing cell kill but also through the induction of a successful anti-tumor vaccination that improves patient survival

On the complete digraphs which are simply disconnected

Homotopic methods are employed for the characterization of the complete digraphs which are the composition of non-trivial highly regular tournaments

È VIVO: Virtual eruptions at Vesuvius; A multimedia tool to illustrate numerical modeling to a general public

Dissemination of scientific results to the general public has become increasingly important in our society. When science deals with natural hazards, public outreach is even more important: on the one hand, it contributes to hazard perception and it is a necessary step toward preparedness and risk mitigation; on the other hand, it contributes to establish a positive link of mutual confidence between scientific community and the population living at risk. The existence of such a link plays a relevant role in hazard communication, which in turn is essential to mitigate the risk. In this work, we present a tool that we have developed to illustrate our scientific results on pyroclastic flow propagation at Vesuvius. This tool, a CD-ROM that we developed joining scientific data with appropriate knowledge in communication sciences is meant to be a first prototype that will be used to test the validity of this approach to public outreach. The multimedia guide contains figures, images of real volcanoes and computer animations obtained through numerical modeling of pyroclastic density currents. Explanatory text, kept as short and simple as possible, illustrates both the process and the methodology applied to study this very dangerous natural phenomenon. In this first version, the CD-ROM will be distributed among selected categories of end-users together with a short questionnaire that we have drawn to test its readability. Future releases will include feedback from the users, further advancement of scientific results as well as a higher degree of interactivity

Political Dramas e drammi della politica in tempi di crisi. House of Cards e dintorni.

How do the imaginary and the narrative frames underlying TV political dramas influence the audience\u2019s perception of politics, of the political field, and of the quest for power and its management? What do they tell us of the ways in which a narrative of, and on, politics involve \u2013 as spy and crime stories have done since the end of the 19th century \u2013 a meditation on the consistency and on the very endurance of \u201creality\u201d, on the reality of reality? After an introduction devoted to clarifying the possible intertwining between the concepts of imaginary, TV Series and the representation of the political field, the essay focuses on the analysis of House of Cards (Netflix, 2013-) in comparison to other previous political dramas, such as The West Wing (NBC, 1999-2006). Through the lenses of four of the main narrative frames that characterize narratives of politics (the quest, the soap, the beaurocracy and the conspiracy), the attempt is to demonstrate how this show presents a view of politics and the quest for power that undermines not only any positive imaginary about the state and who governs it, but also any faith in the reality of reality

Spaces of Memory

In the last decade, museums, memorials and monuments have become the battlefield for competing and conflicting visions of the past and the hegemonic or counter memories of the so-called “difficult heritage” or “traumatic heritage”. Far from being mere spaces of musealization that freeze and fix dominant narratives of the past, spaces of memory are increasingly turning into sites of negotiations and reconfigurations of meaning in which social and political identities are debated, strengthened, or weakened in reference to the traumatic experiences of the past which they “represent”. Yet, what does it mean to spatially represent a (traumatic) memory, and what is a space of memory? In expanding and, simultaneously, problematizing Pierre Nora’s (Nora 1996) category of lieu de mémoire, the way we think of spaces of memory aims at an in-depth examination of the peculiar yet specific ways of re-thinking the nexus between space and memory: how do we elaborate, activate, and make visible spaces for memory? This question points to the dynamic construction that underlines the production and connection of spatiality and memory, as well as to the coexistence of a plurality of meanings and experiences that characterize spaces of memory

Exploring the feasibility of electric vehicle travel for remote communities in Australia

Remote communities in Australia face unique mobility challenges that stand to be further complicated by the transition from Internal Combustion Engine (ICE) vehicles to Electric Vehicles (EVs). EVs offer a range of advantages that include lower maintenance requirements and independence from costly, dangerous and polluting petroleum imports that have long been burdensome for remote communities. Yet the adoption of electric vehicles in Australia has been slow by international standards, and what policy strategies do exist tend to focus on incentivizing uptake among urban residents with the means to afford new technologies, potentially leaving remote communities in the 'too hard basket'. In this study we assess the feasibility of EVs for a sample of communities in remote Australia using Geographic Information System analysis of travel distances between communities and service hub towns utilizing present-day EV specifications and charging technologies. We show that while EV travel is often not currently feasible for trips to large service hub towns using low-range vehicles, over 99% of communities and residents considered would be able to travel to their nearest small service hub town with existing long-range EVs. This finding suggests that while the barriers to the electrification of transport in remote communities are significant, they are not insurmountable and are deserving of consideration in national and state policy developments in the deployment of charging infrastructure

Baseline T cell dysfunction by single cell network profiling in metastatic breast cancer patients.

BackgroundWe previously reported the results of a multicentric prospective randomized trial of chemo-refractory metastatic breast cancer patients testing the efficacy of two doses of TGFβ blockade during radiotherapy. Despite a lack of objective responses to the combination, patients who received a higher dose of TGFβ blocking antibody fresolimumab had a better overall survival when compared to those assigned to lower dose (hazard ratio of 2.73, p = 0.039). They also demonstrated an improved peripheral blood mononuclear cell (PBMC) counts and increase in the CD8 central memory pool. We performed additional analysis on residual PBMC using single cell network profiling (SCNP).MethodsThe original trial randomized metastatic breast cancer patients to either 1 or 10 mg/kg of fresolimumab, every 3 weeks for 5 cycles, combined with radiotherapy to a metastatic site at week 1 and 7 (22.5 Gy given in 3 doses of 7.5 Gy). Trial immune monitoring results were previously reported. In 15 patients with available residual blood samples, additional functional studies were performed, and compared with data obtained in parallel from seven healthy female donors (HD): SCNP was applied to analyze T cell receptor (TCR) modulated signaling via CD3 and CD28 crosslinking and measurement of evoked phosphorylation of AKT and ERK in CD4 and CD8 T cell subsets defined by PD-1 expression.ResultsAt baseline, a significantly higher level of expression (p < 0.05) of PD-L1 was identified in patient monocytes compared to HD. TCR modulation revealed dysfunction of circulating T-cells in patient baseline samples as compared to HD, and this was more pronounced in PD-1+ cells. Treatment with radiotherapy and fresolimumab did not resolve this dyfunctional signaling. However, in vitro PD-1 blockade enhanced TCR signaling in patient PD-1+ T cells and not in PD-1- T cells or in PD-1+ T cells from HD.ConclusionsFunctional T cell analysis suggests that baseline T cell functionality is hampered in metastatic breast cancer patients, at least in part mediated by the PD-1 signaling pathway. These preliminary data support the rationale for investigating the possible beneficial effects of adding PD-1 blockade to improve responses to TGFβ blockade and radiotherapy.Trial registrationNCT01401062

The Effects of Climate Change on Seasonal Snowpack and the Hydrology of the Northeastern and Upper Midwest United States

Permission to use figures, tables, and brief excerpts from this work in scientific and educational works is hereby granted provided that the source is acknowledged. Any use of material in this work that is determined to be “fair use” under Section 107 of the U.S. Copyright Act or that satisfies the conditions specified in Section 108 of the U.S. Copyright Act (17 USC §108) does not require the AMS’s permission. Republication, systematic reproduction, posting in electronic form, such as on a website or in a searchable database, or other uses of this material, except as exempted by the above statement, requires written permission or a license from the AMS. All AMS journals and monograph publications are registered with the Copyright Clearance Center (http://www.copyright.com). Questions about permission to use materials for which AMS holds the copyright can also be directed to the AMS Permissions Officer at [email protected]. Additional details are provided in the AMS Copyright Policy statement, available on the AMS website (http://www.ametsoc.org/CopyrightInformation).The potential effects of climate change on the snowpack of the northeastern and upper Midwest United States are assessed using statistically downscaled climate projections from an ensemble of 10 climate models and a macroscale hydrological model. Climate simulations for the region indicate warmer-than-normal temperatures and wetter conditions for the snow season (November–April) during the twenty-first century. However, despite projected increases in seasonal precipitation, statistically significant negative trends in snow water equivalent (SWE) are found for the region. Snow cover is likely to migrate northward in the future as a result of warmer-than-present air temperatures, with higher loss rates in northern latitudes and at high elevation. Decreases in future (2041–95) snow cover in early spring will likely affect the timing of maximum spring peak streamflow, with earlier peaks predicted in more than 80% of the 124 basins studied