The Twelve Apostles: Design, Construction, and Function of Late 16th-Century Spanish Galleons

The development of the Spanish galleon as a specialized warship took place in Spain during the 16th century. A series of prototypes built in Spain in that century incorporated concepts and technological solutions from both the Mediterranean and the Atlantic maritime traditions, and became the basis for this new type of vessel. The Spanish galleon was designed in response to changes in Atlantic trade routes at the beginning of the 16th century when, as a result of Spanish transoceanic expansion, new and more specialized vessels were needed for both the coastal defense of Spain and its overseas territories, as well as to escort the oceanic fleets. In November 1588, King Philip II of Spain ordered the construction of 12 new galleons of 500, 600, and 800 toneladas, four ships of each tonnage, specifically designed as warships. These galleons were to replace the losses that occurred after the failure of the Spanish Armada against England, since the chronic Spanish shortage of warships was aggravated by the loss of some of the best naval units. This decision marked the beginning of the largest shipbuilding program attempted in Spain until that moment. These galleons would became known as the Twelve Apostles. The present study focuses on the analysis of the design and construction of the Twelve Apostles based on original documents currently held at the Archive of Simancas in Spain, shipbuilding treatises and manuscripts, and archaeological evidence. The documents provide a realistic portrayal of the organizational requirements and challenges of a construction project of such magnitude in the context of a pre-industrial society. Moreover, the comparative analysis of 16th - and 17th -century Spanish designs and survey reports, shipbuilding treatises, manuscripts, ordinances, and shipbuilding contracts reveals the evolution of the ship design in Spain. Finally, the study confirms that the design of the midship sections of the vessels of this period, including those of the Twelve Apostles, was based on the use of a single arc. Therefore, a series of alternative interpretations for the reconstruction of the midship section of Iberian-built vessels is provided based on this method

Métodos de documentación arqueológica aplicados en arqueología subacuática: el modelo fotogramétrico y el fotomosaico del pecio fenicio Mazarrón-2 (Puerto de Mazarrón, Murcia)

In 2007, ARQVA – National Museum of Underwater Archaeology carried out an archaeological project at the Phoenician shipwreck Mazarron-2 (Port of Mazarron, Murcia, Spain). The aims of the project were to check the state of preservation of the hull remains of the ship as well as the metal structure that protects the site. Moreover, the available archaeological data on the shipwreck were updated for the purpose of creating a new digital archive of the site. A real scale photogrammetrical 3D model of the interior of the hull of the ship was created using the program Photomodeler. In addition, a high-resolution photomosaic of the ship was produced since this had not been done in the past. This article describes the methods employed in the realization of both the photogrammetrical model and the photomosaic. Finally, an evaluation is offered of the applications of these recording techniques for archaeological hull remains underwater

El arco urbano en la arquitectura maya

[EN] Urban arches are one of the most emblematic Mayan architecture elements, for their singularity and monumentality and also for their strategic urban location. They appear on its own or as a part of an ensemble, sometimes being part of the composition of a building façade, but always used in special settings, either generating access points to an enclosure or place, transitions between different urban spaces or emphasizing symbolically the access to relevant architectural ensembles. This paper presents the results of a documentation work of the urban arches identified in the Maya Lowlands, based on an in situ data gathering and the analysis of their features from the building technology, formal, functional and symbolic points of view.Las autoras agradecen el apoyo del Ministerio de Economía y Competitividad de España, a través de la financiación del proyecto de investigación Arquitectura maya. Sistemas constructivos, estética formal y nuevas tecnologías (BIA2014-53887-C2-1-P), así como el patrocinio del Ministerio de Educación, Cultura y Deportes a través de la financiación obtenida por el Proyecto Arqueológico La Blanca y su entorno, que han contribuido de forma determinante a hacer posibles las investigaciones que se exponen en esta publicación.Gilabert Sansalvador, L.; Peiró Vitoria, A.; Martínez Banaclocha, RA. (2017). El arco urbano en la arquitectura maya. Restauro Archeologico. XXV:48-65. https://doi.org/10.13128/RA-20526S4865XX

Early distant relapse after optimal local control in locally advanced rectal cancer

We present a case of locally advanced rectal cancer with initial optimal local control after neoadjuvant concurrent chemoradiotherapy followed by surgery; early liver recurrence then occurred and was treated again with curative intent with neoadjuvant combination chemotherapy followed by liver surgery. We reflect on this difficult problem and discuss relevant topics to this case report

Multicenter study of the seroprevalence of antibodies against covid-19 in patients with lymphoma: An analysis of the oncological group for the treatment and study of lymphomas (gotel)

The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) coronavirus has generated a pandemic, in which there are population groups at higher risk and who are potentially fatal victims of the disease. Cancer patients have been considered a group with special susceptibility, particularly patients with lung tumour involvement and haematological neoplasms. The Spanish Lymphoma Oncology Group (GOTEL) carried out a multicenter study of SARS-CoV-2 seroprevalence in patients with lymphoma. Results: A total of 150 patients were included between 22 May and 11 June 2020. The mean age was 65 years (range 17–89), 70 women (46.5%) and 80 men (53, 5%). At the time of diagnosis of lymphoma, 13 cases were stage I (9%), 27 (18%) stage II, 37 (24.5%) stage III, and 73 (48.5%) stage IV, while 6.6% had a primary extranodal origin. A total of 10 cases with positive serology for SARS-CoV-2 were identified, which is a prevalence of 6% in this population. None of the patients required intensive care unit management and all fully recovered from the infection. Conclusion: IgG antibody seroprevalence in lymphoma patients appears similar to that of the general population and does not show greater aggressivenessThis study was supported by the European Union Horizon 2020 research and innovation programme under grant agreement number 87516

Electroencephalographic field influence on calcium momentum waves

Macroscopic EEG fields can be an explicit top-down neocortical mechanism that directly drives bottom-up processes that describe memory, attention, and other neuronal processes. The top-down mechanism considered are macrocolumnar EEG firings in neocortex, as described by a statistical mechanics of neocortical interactions (SMNI), developed as a magnetic vector potential $\mathbf{A}$. The bottom-up process considered are $\mathrm{Ca}^{2+}$ waves prominent in synaptic and extracellular processes that are considered to greatly influence neuronal firings. Here, the complimentary effects are considered, i.e., the influence of $\mathbf{A}$ on $\mathrm{Ca}^{2+}$ momentum, $\mathbf{p}$. The canonical momentum of a charged particle in an electromagnetic field, $\mathbf{\Pi} = \mathbf{p} + q \mathbf{A}$ (SI units), is calculated, where the charge of $\mathrm{Ca}^{2+}$ is $q = - 2 e$, $e$ is the magnitude of the charge of an electron. Calculations demonstrate that macroscopic EEG $\mathbf{A}$ can be quite influential on the momentum $\mathbf{p}$ of $\mathrm{Ca}^{2+}$ ions, in both classical and quantum mechanics. Molecular scales of $\mathrm{Ca}^{2+}$ wave dynamics are coupled with $\mathbf{A}$ fields developed at macroscopic regional scales measured by coherent neuronal firing activity measured by scalp EEG. The project has three main aspects: fitting $\mathbf{A}$ models to EEG data as reported here, building tripartite models to develop $\mathbf{A}$ models, and studying long coherence times of $\mathrm{Ca}^{2+}$ waves in the presence of $\mathbf{A}$ due to coherent neuronal firings measured by scalp EEG. The SMNI model supports a mechanism wherein the $\mathbf{p} + q \mathbf{A}$ interaction at tripartite synapses, via a dynamic centering mechanism (DCM) to control background synaptic activity, acts to maintain short-term memory (STM) during states of selective attention.Comment: Final draft. http://ingber.com/smni14_eeg_ca.pdf may be updated more frequentl

A high concentration of TGF-β correlates with opportunistic infection in liver and kidney transplantation

Transforming growth factor-β (TGF-β) has been associated with numerous human infections, but its role in the occurrence of opportunistic infection (OI) after solid organ transplantation remains unexplored. This study aimed to assess the utility of the TGF-β following in vitro stimulation of whole peripheral blood (WPB) as a surrogate biomarker of post-transplant OI in a cohort of liver and kidney recipients. Thirty liver and thirty-one kidney transplant recipients were recruited to be prospectively monitored for one-year post-transplantation. Enzyme-linked immunosorbent assay (ELISA) was performed to calculate IFN-γ, IL-17, IL-10 and TGF-β concentration in the supernatant from the activated WPB. Recipients showed higher TGF-β concentrations compared to IFN-γ, IL-17, IL-10 at baseline, although these differences were not significant between INF and NoINF. However, recipients who developed an OI within the first sixth months had a higher concentration of TGF-β than those without OI. A concentration of TGF-β > 363.25 pg/ml in liver and TGF-β > 808.51 pg/ml in kidney recipients were able to stratify patients at high risk of OI with a sensitivity and specificity above 70% in both types of solid organ transplantations. TGF-β could provide valuable information for the management of liver and kidney recipients at risk of post-transplant infection.Our work was possible thanks to the support and funding obtained from the “Instituto de Salud Carlos III (ISCIII)”, Spanish Ministry of Health (Grant Number PI15/01370 and P19/01194); and co-funding by the European Union from the European Regional Development Fund (ERDF) with the principle of “A manner to build Europe”

N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson\u27s Disease: Preliminary Clinical and Cell Line Data.

BACKGOUND: The purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine (NAC) in Parkinson\u27s disease (PD). METHODS: The overarching goal of this pilot study was to generate additional data about potentially protective properties of NAC in PD, using an in vitro and in vivo approach. In preparation for the clinical study we performed a cell tissue culture study with human embryonic stem cell (hESC)-derived midbrain dopamine (mDA) neurons that were treated with rotenone as a model for PD. The primary outcome in the cell tissue cultures was the number of cells that survived the insult with the neurotoxin rotenone. In the clinical study, patients continued their standard of care and were randomized to receive either daily NAC or were a waitlist control. Patients were evaluated before and after 3 months of receiving the NAC with DaTscan to measure dopamine transporter (DAT) binding and the Unified Parkinson\u27s Disease Rating Scale (UPDRS) to measure clinical symptoms. RESULTS: The cell line study showed that NAC exposure resulted in significantly more mDA neurons surviving after exposure to rotenone compared to no NAC, consistent with the protective effects of NAC previously observed. The clinical study showed significantly increased DAT binding in the caudate and putamen (mean increase ranging from 4.4% to 7.8%; p CONCLUSIONS: The results of this preliminary study demonstrate for the first time a potential direct effect of NAC on the dopamine system in PD patients, and this observation may be associated with positive clinical effects. A large-scale clinical trial to test the therapeutic efficacy of NAC in this population and to better elucidate the mechanism of action is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02445651

Saturation of acyl chains converts cardiolipin from an antagonist to an activator of Toll-like receptor-4

Abstract: Cardiolipins (CLs) are tetra-acylated diphosphatidylglycerols found in bacteria, yeast, plants, and animals. In healthy mammals, CLs are unsaturated, whereas saturated CLs are found in blood cells from Barth syndrome patients and in some Gram-positive bacteria. Here, we show that unsaturated but not saturated CLs block LPS-induced NF-κB activation, TNF-α and IP-10 secretion in human and murine macrophages, as well as LPS-induced TNF-α and IL-1β release in human blood mononuclear cells. Using HEK293 cells transfected with Toll-like receptor 4 (TLR4) and its co-receptor Myeloid Differentiation 2 (MD2), we demonstrate that unsaturated CLs compete with LPS for binding TLR4/MD2 preventing its activation, whereas saturated CLs are TLR4/MD2 agonists. As a consequence, saturated CLs induce a pro-inflammatory response in macrophages characterized by TNF-α and IP-10 secretion, and activate the alternative NLRP3 inflammasome pathway in human blood-derived monocytes. Thus, we identify that double bonds discriminate between anti- and pro-inflammatory properties of tetra-acylated molecules, providing a rationale for the development of TLR4 activators and inhibitors for use as vaccine adjuvants or in the treatment of TLR4-related diseases. Graphical abstract

Prospective Exploratory Analysis of Angiogenic Biomarkers in Peripheral Blood in Advanced NSCLC Patients Treated With Bevacizumab Plus Chemotherapy: The ANGIOMET Study

Finding angiogenic prognostic markers in advanced non-small-cell lung cancer is still an unmet medical need. We explored a set of genetic variants in the VEGF-pathway as potential biomarkers to predict clinical outcomes of patients with non-small-cell lung cancer treated with chemotherapy plus bevacizumab. We prospectively analyzed the relationship between VEGF-pathway components with both pathological and prognostic variables in response to chemotherapy plus bevacizumab in 168 patients with non-squamous non-small-cell lung cancer. Circulating levels of VEGF and VEGFR2 and expression of specific endothelial surface markers and single-nucleotide polymorphisms in VEGF-pathway genes were analyzed. The primary clinical endpoint was progression-free survival. Secondary endpoints included overall survival and objective tumor response. VEGFR-1 rs9582036 variants AA/AC were associated with increased progression-free survival (p = 0.012 and p = 0.035, respectively), and with improved overall survival (p = 0.019) with respect to CC allele. Patients with VEGF-A rs3025039 harboring allele TT had also reduced mortality risk (p = 0.049) compared with the CC allele. The VEGF-A rs833061 variant was found to be related with response to treatment, with 61.1% of patients harboring the CC allele achieving partial treatment response. High pre-treatment circulating levels of VEGF-A were associated with shorter progression-free survival (p = 0.036). In conclusion, in this prospective study, genetic variants in VEGFR-1 and VEGF-A and plasma levels of VEGF-A were associated with clinical benefit, progression-free survival, or overall survival in a cohort of advanced non-squamous non-small-cell lung cancer patients receiving chemotherapy plus antiangiogenic therapy