Long-term planning versus short-term planning in the asymptotical location problem

Given the probability measure $\nu$ over the given region $\Omega\subset \R^n$, we consider the optimal location of a set $\Sigma$ composed by $n$ points \Om in order to minimize the average distance \Sigma\mapsto \int_\Om \dist(x,\Sigma) d\nu (the classical optimal facility location problem). The paper compares two strategies to find optimal configurations: the long-term one which consists in placing all $n$ points at once in an optimal position, and the short-term one which consists in placing the points one by one adding at each step at most one point and preserving the configuration built at previous steps. We show that the respective optimization problems exhibit qualitatively different asymptotic behavior as $n\to\infty$, although the optimization costs in both cases have the same asymptotic orders of vanishing.Comment: for more pictures and some movies as well, see http://www.sissa.it/~brancoli

Optimization of Pyro-gasification of Carbon Fiber Reinforced Polymers (CFRPs)

This work focuses on the optimization of pyro-gasification process of carbon fiber reinforced polymers (CFRPs) with the aim of recovering carbon fibers (CFs) with properties suitable for the production of new more sustainable composites with high performances. In particular, the pyro-gasification process is carried out on cured CFRPs panels based on both epoxy (EC) and vinyl ester (VC) matrices, which are the two most used resins for CFRPs. The matrix degradation is evaluated via sample's weight loss measurement and the recovered CFs obtained after different time of treatment are analyzed to identify convenient pyro-gasification conditions to avoid damaging of the recovered CFs. The obtained results highlight the importance of the thickness of the composites to be treated for the identification of the more suitable pyro-gasification conditions

Mega debris flow deposits on the western Wilkes Land margin, East Antarctica

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Enhancing proteotoxic stress in leiomyosarcoma cells triggers mitochondrial dysfunctions, cell death, and antitumor activity in vivo

Leiomyosarcomas are rare and aggressive tumors characterized by a complex karyotype. Surgical resection with or without radiotherapy and chemotherapy is the standard curative treatment. Unfortunately, a high percentage of leiomyosarcomas recurs and metastasizes. In these cases, doxorubicin and ifosfamide represent the standard treatment but with low response rates. Here, we evaluated the induction of proteotoxic stress as a possible strategy to kill leiomyosarcoma cells in a therapeutic perspective. We show that aggressive leiomyosarcomas coexist with high levels of proteotoxic stress. As a consequence, we hypothesized that leiomyosarcoma cells are vulnerable to further increases of proteotoxic stress. The small compound 2c is a strong inducer of proteotoxic stress. In leiomyosarcoma cells, it triggers cell death coupled to a profound reorganization of the mitochondrial network. By using stimulated emission depletion microscopy, we have unveiled the existence of DIABLO/SMAC clusters that are modulated by 2c. Finally, we have engineered a new version of 2c linked to polyethylene glycol though a short peptide, named 2cPP. This new prodrug is specifically activated by proteases present in the tumor microenvironment. 2cPP shows a strong antitumor activity in vivo against leiomyosarcomas and no toxicity against normal cells

Synchronous oceanic spreading and continental rifting in West Antarctica

Magnetic anomalies associated with new ocean crust formation in the Adare Basin off north-western Ross Sea (43 – 26 Ma) can be traced directly into the Northern Basin that underlies the adjacent morphological continental shelf, implying a continuity in the emplacement of oceanic crust. Steep gravity gradients along the margins of the Northern Basin, particularly in the east, suggest that little extension and thinning of continental crust occurred before it ruptured and the new oceanic crust formed, unlike most other continental rifts and the Victoria Land Basin further south. A pre-existing weak crust and localisation of strain by strike slip faulting are proposed as the factors allowing the rapid rupture of continental crust

A user's guide to optimal transport

This text is an expanded version of the lectures given by the first author in the 2009 CIME summer school of Cetraro. It provides a quick and reasonably account of the classical theory of optimal mass transportation and of its more recent developments, including the metric theory of gradient flows, geometric and functional inequalities related to optimal transportation, the first and second order differential calculus in the Wasserstein space and the synthetic theory of metric measure spaces with Ricci curvature bounded from below

Protein-Binding Microarray Analysis of Tumor Suppressor AP2α Target Gene Specificity

Cheap and massively parallel methods to assess the DNA-binding specificity of transcription factors are actively sought, given their prominent regulatory role in cellular processes and diseases. Here we evaluated the use of protein-binding microarrays (PBM) to probe the association of the tumor suppressor AP2α with 6000 human genomic DNA regulatory sequences. We show that the PBM provides accurate relative binding affinities when compared to quantitative surface plasmon resonance assays. A PBM-based study of human healthy and breast tumor tissue extracts allowed the identification of previously unknown AP2α target genes and it revealed genes whose direct or indirect interactions with AP2α are affected in the diseased tissues. AP2α binding and regulation was confirmed experimentally in human carcinoma cells for novel target genes involved in tumor progression and resistance to chemotherapeutics, providing a molecular interpretation of AP2α role in cancer chemoresistance. Overall, we conclude that this approach provides quantitative and accurate assays of the specificity and activity of tumor suppressor and oncogenic proteins in clinical samples, interfacing genomic and proteomic assays

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field