Historical and archaeological contributions to the study of the standardization process in the anchor industry of the 18th century European maritime powers

Las anclas fueron un elemento de capital importancia a lo largo de la historia de la navegación. En el siglo XVIII, los barcos de guerra europeos utilizaban varios tipos y dependían de ellas para fondear y realizar otras maniobras. La industria ancorera constituyó en aquel entonces una de las expresiones más complejas de la tecnología de forjado del hierro y, en el marco de un proceso de industrialización creciente, estuvo sujeta a varios cambios. En este artículo examinamos las características de las anclas, en materia de diseño y manufactura, de las principales potencias marítimas. A la luz de las fuentes documentales y materiales disponibles, discutimos aspectos relativos al proceso de estandarización y cambio tecnológico en la industria ancorera. Complementariamente, presentamos algunos lineamientos para el estudio de anclas de procedencia arqueológica.Anchors were an element of major importance throughout the history of navigation. In the 18th century, European warships used various types and relied on them to anchor and perform other maneuvers. The anchor industry was at that time one of the most complex expressions of iron forging technology and, under a process of increasing industrialization, it was subject to several changes. In this article, we examine the characteristics of the anchors of the main Maritime powers in terms of design and manufacturing. In light of the available documentary and material sources, we discuss aspects related to the process of standardization and technological change in the anchor industry. Complementarily, we present some guidelines for the study of anchors of archaeological provenance

Impact of the microbial derived short chain fatty acid propionate on host susceptibility to bacterial and fungal infections in vivo.

Short chain fatty acids (SCFAs) produced by intestinal microbes mediate anti-inflammatory effects, but whether they impact on antimicrobial host defenses remains largely unknown. This is of particular concern in light of the attractiveness of developing SCFA-mediated therapies and considering that SCFAs work as inhibitors of histone deacetylases which are known to interfere with host defenses. Here we show that propionate, one of the main SCFAs, dampens the response of innate immune cells to microbial stimulation, inhibiting cytokine and NO production by mouse or human monocytes/macrophages, splenocytes, whole blood and, less efficiently, dendritic cells. In proof of concept studies, propionate neither improved nor worsened morbidity and mortality parameters in models of endotoxemia and infections induced by gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae), gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae) and Candida albicans. Moreover, propionate did not impair the efficacy of passive immunization and natural immunization. Therefore, propionate has no significant impact on host susceptibility to infections and the establishment of protective anti-bacterial responses. These data support the safety of propionate-based therapies, either via direct supplementation or via the diet/microbiota, to treat non-infectious inflammation-related disorders, without increasing the risk of infection

Trained Immunity Confers Broad-Spectrum Protection Against Bacterial Infections.

The innate immune system recalls a challenge to adapt to a secondary challenge, a phenomenon called trained immunity. Training involves cellular metabolic, epigenetic and functional reprogramming, but how broadly trained immunity protects from infections is unknown. For the first time, we addressed whether trained immunity provides protection in a large panel of preclinical models of infections. Mice were trained and subjected to systemic infections, peritonitis, enteritis, and pneumonia induced by Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, Citrobacter rodentium, and Pseudomonas aeruginosa. Bacteria, cytokines, leukocytes, and hematopoietic precursors were quantified in blood, bone marrow, and organs. The role of monocytes/macrophages, granulocytes, and interleukin 1 signaling was investigated using depletion or blocking approaches. Induction of trained immunity protected mice in all preclinical models, including when training and infection were initiated in distant organs. Trained immunity increased bone marrow hematopoietic progenitors, blood Ly6Chigh inflammatory monocytes and granulocytes, and sustained blood antimicrobial responses. Monocytes/macrophages and interleukin 1 signaling were required to protect trained mice from listeriosis. Trained mice were efficiently protected from peritonitis and listeriosis for up to 5 weeks. Trained immunity confers broad-spectrum protection against lethal bacterial infections. These observations support the development of trained immunity-based strategies to improve host defenses

En busca de un horizonte común para la Biblioteca digital de arqueología náutica (NADL). Reflexiones sobre ciencia, método, teoría y plantillas

[EN] Data sharing is a fundamental process for the advancement of both natural and social sciences. Starting from the idea that computers and the internet have drastically changed the world in the last decades, this paper advocates for the creation of a space where archaeologists from around the world can share information about maritime history and exchange data with colleagues. Following the principles of open access, we argue that raw data publication is necessary and significant for the development and democratization of the discipline. This study explains the fundamental aspects of the Nautical Archaeology Digital Library (NADL) and its efforts to standardize information collection for shipwrecks and related sites, so that scholars can create a community to disseminate both raw data and complete information in the field of maritime archaeology. To achieve this, our purpose is to facilitate the development of common-ground methodology and terminology that promotes an intelligible dialogue within the global community of nautical archaeologists. This paper addresses some considerations on terminology and systematization in scientific disciplines and discusses the theoretical and methodological issues linked to the process of making a template for recording shipwrecks. Furthermore, this article analyses some of the problems related to the standardization of description processes and the necessity to create a flexible system that accounts for data diversity. The third section discusses how science is greatly enhanced by publishing information in open access platforms.Highlights:Standardization of data allows robust comparative and inter-subjective analysis of coastal and maritime projects, shipwrecks and nautical technology.Research is strongly benefited by sharing information underlying publications and raw data generated within a project in open source platforms.Digital databases such as NADL enhance cooperative research, as well as teaching and outreach strategies.[ES] Compartir información es un proceso fundamental para el desarrollo de las ciencias naturales y sociales. Partiendo de la idea de que las computadoras e Internet han cambiado drásticamente el mundo en las últimas décadas, este trabajo aboga por la creación de un espacio en el que arqueólogos de alrededor del mundo puedan compartir información sobre historia marítima e intercambiar datos con otros colegas. Siguiendo los principios del libre acceso, sostenemos que la publicación de datos en bruto es necesaria y significativa para el desarrollo y democratización de la disciplina. Este artículo explica los fundamentos de la Biblioteca Digital de Arqueología Náutica (NADL: https://nadl.tamu.edu/) y sus esfuerzos por estandarizar el registro de la información sobre naufragios y sitios relacionados, para que los investigadores puedan crear una comunidad de divulgación, tanto de datos primarios como de información completa en el campo de la arqueología marítima. Para lograrlo, nuestro propósito es contribuir al desarrollo de una metodología y terminología común que promueva un diálogo inteligible entre la comunidad global de arqueólogos náuticos. En este artículo presentamos algunas consideraciones sobre la terminología y la sistematización en las disciplinas científicas y discutimos los problemas teóricos y metodológicos vinculados al proceso de creación de una plantilla para el registro de naufragios. Además, reflexionamos sobre algunos de los problemas relacionados con la estandarización de los procesos descriptivos y la necesidad de crear un sistema flexible que refleje la diversidad de los datos. Finalmente, discutimos cómo la ciencia se ve enormemente favorecida por la publicación de información en plataformas de libre acceso.This paper is a result of a T3 Texas A&M University grant. We want to thank the NADL community for their input. This paper is based on extensive discussions among the community. 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Trained Immunity Confers Prolonged Protection From Listeriosis.

Trained immunity refers to the ability of the innate immune system exposed to a first challenge to provide an enhanced response to a secondary homologous or heterologous challenge. We reported that training induced with β-glucan one week before infection confers protection against a broad-spectrum of lethal bacterial infections. Whether this protection persists over time is unknown. To tackle this question, we analyzed the immune status and the response to Listeria monocytogenes (L. monocytogenes) of mice trained 9 weeks before analysis. The induction of trained immunity increased bone marrow myelopoiesis and blood counts of Ly6C <sup>high</sup> inflammatory monocytes and polymorphonuclear neutrophils (PMNs). Ex vivo, whole blood, PMNs and monocytes from trained mice produced increased levels of cytokines in response to microbial products and limited the growth of L. monocytogenes. In vivo, following challenge with L. monocytogenes, peripheral blood leukocytes were massively depleted in control mice but largely preserved in trained mice. PMNs were reduced also in the spleen from control mice, and increased in the spleen of trained mice. In transwell experiments, PMNs from trained mice showed increased spontaneous migration and CXCL2/MIP2α-induced chemotaxis, suggesting that training promotes the migration of PMNs in peripheral organs targeted by L. monocytogenes. Trained PMNs and monocytes had higher glycolytic activity and mitochondrial respiration than control cells when exposed to L. monocytogenes. Bacterial burden and dissemination in blood, spleen and liver as well as systemic cytokines and inflammation (multiplex bead assay and bioluminescence imaging) were reduced in trained mice. In full agreement with these results, mice trained 9 weeks before infection were powerfully protected from lethal listeriosis. Altogether, these data suggest that training increases the generation and the antimicrobial activity of PMNs and monocytes, which may confer prolonged protection from lethal bacterial infection

Activity and safety of RAD001 (everolimus) in patients affected by biliary tract cancer progressing after prior chemotherapy: a phase II ITMO study.

BACKGROUND: Biliary tract cancer (BTC) is a highly lethal disease for which the best available therapy remains undetermined. The mammalian target of rapamycin (mTOR) pathway is up-regulated in several cancers, including BTC, and preclinical evidence indicates that mTOR inhibition may be effective in the treatment of BTC. We sought to evaluate the activity and tolerability of the mTOR inhibitor RAD001-everolimus-in patients with BTC progressing after prior chemotherapy. PATIENTS AND METHODS: This was an open-label, single-arm, phase II study (EUDRACT 2008-007152-94) conducted in eight sites in Italy. Patients with locally advanced, metastatic or recurrent BTC progressing despite previous chemotherapy received a daily oral dose of everolimus 10 mg administered continuously in 28-day cycles. The two primary end points were disease control rate (DCR) and objective response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival (OS) and time-to-progression (TTP). RESULTS: Thirty-nine patients were enrolled. The DCR was 44.7%, and the ORR was 5.1%. One patient showed a partial response at 2 months and one patient showed a complete response sustained up to 8 months. The median (95% confidence interval) PFS was 3.2 (1.8-4.0) months, and the median OS was 7.7 (5.5-13.2) months. The median TTP was 2.0 (1.7-3.7) months. Most common toxicities were asthenia (43.6%), thrombocytopenia (35.9%), pyrexia (30.8%) and erythema, mainly of mild-to-moderate severity. Two patients required dose reduction due to adverse events. CONCLUSION: Everolimus demonstrated a favourable toxicity profile and encouraging anti-tumour activity. Further trials are needed to establish the role of everolimus in the treatment of BTC. EUDRACT 2008-007152-94

Sirtuin 5 Deficiency Does Not Compromise Innate Immune Responses to Bacterial Infections.

Sirtuin 5 (SIRT5) is a member of the family of NAD <sup>+</sup> -dependent lysine/histone deacetylases. SIRT5 resides mainly in the mitochondria where it catalyzes deacetylation, demalonylation, desuccinylation, and deglutarylation of lysine to regulate metabolic and oxidative stress response pathways. Pharmacologic inhibitors of SIRT5 are under development for oncologic conditions, but nothing is known about the impact of SIRT5 on antimicrobial innate immune defenses. Using SIRT5 knockout mice, we show that SIRT5 deficiency does not affect immune cell development, cytokine production and proliferation by macrophages and splenocytes exposed to microbial and immunological stimuli. Moreover, preclinical models suggest that SIRT5 deficiency does not worsen endotoxemia, Klebsiella pneumoniae and Streptococcus pneumoniae pneumonia, Escherichia coli peritonitis, listeriosis, and staphylococcal infection. Altogether, these data support the safety profile in terms of susceptibility to infections of SIRT5 inhibitors under development

Measuring Program Outcome

The Progress Evaluation Scales (PES) provide an efficient measuring devicefor evaluating current functioning, setting treatment goals, and assessing change over time in clinically relevant aspects of personal, social, and community adjustment. The PES can be completed by patients, significant others, and therapists, making it possible to obtain various points of view of the outcome of mental health services. This article describes the seven domains measured by the PES and the underlying dimensions they were designed to tap, and presents the generalizability, validity, and usefulness of the scales as applied to an adult mental health center population.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67322/2/10.1177_0193841X8100500402.pd

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies