Artists before Columbus: A multi-method characterization of the materials and practices of Caribbean cave art

This study represents the first positive identification of plant gum binding media in pre-Columbian art, and the first dates from indigenous cave art in the Caribbean. Mona Island reveals an extensive and well-preserved pre-Columbian and early colonial subterranean cultural landscape with dense concentrations of newly-discovered cave art in up to 30 caves. A multi-method approach to the research of pigments and binding media, charcoal, and cave sediments was used to elucidate the technologies, chronologies and processes of indigenous art and artists. Analyses included on-site use of a portable X-ray fluorescence (P-XRF) device to inform sample selection, scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDX) on paint and charcoal samples, polarized light microscopy (PLM) for material characterizations, and gas chromatography - mass spectrometry (GC-MS) and X-ray diffraction (XRD) for detailed chemical analysis of paint structures and composition. In addition direct dates of cave art using radiocarbon (C14) and Uranium-thorium (U-Th) dating methods are discussed. Results demonstrate multiple centuries of cave use during indigenous occupation and multiple phases and techniques of mark-making in dark zone locations within extensive cave systems. Visitors set out on pre-meditated journeys underground, making rock art using pigments from the cave floors, which they mixed into complex paints with the addition of plant gums from outside. This study is the first of its kind in the Caribbean providing insight into native paint recipes, material choices, and mark-making techniques. The methods have scope for widespread application and advance the integration of cave art research in archaeology

Regulation of pituitary MT1 melatonin receptor expression by gonadotrophin-releasing hormone (GnRH) and early growth response factor-1 (Egr-1) : in vivo and in vitro studies

Copyright: © 2014 Bae et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC; grant BB/F020309/1; http://www.bbsrc.ac.uk/home/home.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

New taxa of Neosartorya and Aspergillus in Aspergillus section Fumigati

Three new species of Neosartorya and one new Aspergillus of section Fumigati are proposed using a polyphasic approach based on morphology, extrolite production and partial β-tubulin, calmodulin, and actin gene sequences. The phylogenetic analyses using the three genes clearly show that the taxa grouped separately from the known species and confirmed the phenotypic differences. Neosartorya denticulata is characterized by its unique denticulate ascospores with a prominent equatorial furrow; N. assulata by well developed flaps on the convex surface of the ascospores which in addition have two distinct equatorial crests and N. galapagensis by a funiculose colony morphology, short and narrow conidiophores and ascospores with two wide equatorial crests with a microtuberculate convex surface. Aspergillus turcosus can be distinguished by velvety, gray turquoise colonies and short, loosely columnar conidial heads. The four new taxa also have unique extrolite profiles, which contain the mycotoxins gliotoxin and viriditoxin in N. denticulate; apolar compounds provisionally named NEPS in N. assulata and gregatins in N. galapagensis. A. turcosus produced kotanins. N.denticulata sp. nov., N. assulata sp. nov., N. galapagensis sp. nov., and A. turcosus sp. nov. are described and illustrated

Plasmacytoid dendritic cells orchestrate innate and adaptive anti-tumor immunity induced by oncolytic coxsackievirus A21

Background: The oncolytic virus, coxsackievirus A21 (CVA21), has shown promise as a single agent in several clinical trials and is now being tested in combination with immune checkpoint blockade. Combination therapies offer the best chance of disease control; however, the design of successful combination strategies requires a deeper understanding of the mechanisms underpinning CVA21 efficacy, in particular, the role of CVA21 anti-tumor immunity. Therefore, this study aimed to examine the ability of CVA21 to induce human anti-tumor immunity, and identify the cellular mechanism responsible. Methods: This study utilized peripheral blood mononuclear cells from i) healthy donors, ii) Acute Myeloid Leukemia (AML) patients, and iii) patients taking part in the STORM clinical trial, who received intravenous CVA21; patients receiving intravenous CVA21 were consented separately in accordance with local institutional ethics review and approval. Collectively, these blood samples were used to characterize the development of innate and adaptive anti-tumor immune responses following CVA21 treatment. Results: An Initial characterization of peripheral blood mononuclear cells, collected from cancer patients following intravenous infusion of CVA21, confirmed that CVA21 activated immune effector cells in patients. Next, using hematological disease models which were sensitive (Multiple Myeloma; MM) or resistant (AML) to CVA21-direct oncolysis, we demonstrated that CVA21 stimulated potent anti-tumor immune responses, including: 1) cytokine-mediated bystander killing; 2) enhanced natural killer cell-mediated cellular cytotoxicity; and 3) priming of tumor-specific cytotoxic T lymphocytes, with specificity towards known tumor-associated antigens. Importantly, immune-mediated killing of both MM and AML, despite AML cells being resistant to CVA21-direct oncolysis, was observed. Upon further examination of the cellular mechanisms responsible for CVA21-induced anti-tumor immunity we have identified the importance of type I IFN for NK cell activation, and demonstrated that both ICAM-1 and plasmacytoid dendritic cells were key mediators of this response. Conclusion: This work supports the development of CVA21 as an immunotherapeutic agent for the treatment of both AML and MM. Additionally, the data presented provides an important insight into the mechanisms of CVA21-mediated immunotherapy to aid the development of clinical biomarkers to predict response and rationalize future drug combinations

Physicochemical conditions and timing of rodingite formation: evidence from rodingite-hosted fluid inclusions in the JM Asbestos mine, Asbestos, Québec

Fluid inclusions and geological relationships indicate that rodingite formation in the Asbestos ophiolite, Québec, occurred in two, or possibly three, separate episodes during thrusting of the ophiolite onto the Laurentian margin, and that it involved three fluids. The first episode of rodingitization, which affected diorite, occurred at temperatures of between 290 and 360°C and pressures of 2.5 to 4.5 kbar, and the second episode, which affected granite and slate, occurred at temperatures of between 325 and 400°C and pressures less than 3 kbar. The fluids responsible for these episodes of alteration were moderately to strongly saline (~1.5 to 6.3 m eq. NaCl), rich in divalent cations and contained appreciable methane. A possible third episode of alteration is suggested by primary fluid inclusions in vesuvianite-rich bodies and secondary inclusions in other types of rodingite, with significantly lower trapping temperatures, salinity and methane content. The association of the aqueous fluids with hydrocarbon-rich fluids containing CH4 and higher order alkanes, but no CO2, suggests strongly that the former originated from the serpentinites. The similarities in the composition of the fluids in all rock types indicate that the ophiolite had already been thrust onto the slates when rodingitization occurred

Conceptual Framework for Managing Uncertainty in a Collaborative Agri-Food Supply Chain Context

[EN] Agri-food supply chains are subjected to many sources of uncertainty. If these uncertainties are not managed properly, they can have a negative impact on the agri-food supply chain (AFSC) performance, its customers, and the environment. In this sense, collaboration is proposed as a possible solution to reduce it. For that, a conceptual framework (CF) for managing uncertainty in a collaborative context is proposed. In this context, this paper seeks to answer the following research questions: What are the existing uncertainty sources in the AFSCs? Can collaboration be used to reduce the uncertainty of AFSCs? Which elements can integrate a CF for managing uncertainty in a collaborative AFSC? The CF proposal is applied to the weather source of uncertainty in order to show its applicability.The first author acknowledges the partial support of the Program of Formation of University Professors of the Spanish Ministry of Education, Culture, and Sport (FPU15/03595). The other authors acknowledge the partial support of the Project 691249, RUC-APS: Enhancing and implementing Knowledge based ICT solutions within high Risk and Uncertain Conditions for Agriculture Production Systems, funded by the EU under its funding scheme H2020-MSCA-RISE-2015.Esteso-Álvarez, A.; Alemany Díaz, MDM.; Ortiz Bas, Á. (2017). Conceptual Framework for Managing Uncertainty in a Collaborative Agri-Food Supply Chain Context. IFIP Advances in Information and Communication Technology. 506:715-724. https://doi.org/10.1007/978-3-319-65151-4_64S715724506Taylor, D.H., Fearne, A.: Towards a framework for improvement in the management of demand in agri-food supply chains. Supply Chain Manag. Int. J. 11, 379–384 (2006)Matopoulos, A., Vlachopoulou, M., Manthou, V., Manos, B.: A conceptual framework for supply chain collaboration: empirical evidence from the agri-food industry. Supply Chain Manag. Int. 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The use of the SAEM algorithm in MONOLIX software for estimation of population pharmacokinetic-pharmacodynamic-viral dynamics parameters of maraviroc in asymptomatic HIV subjects

Using simulated viral load data for a given maraviroc monotherapy study design, the feasibility of different algorithms to perform parameter estimation for a pharmacokinetic-pharmacodynamic-viral dynamics (PKPD-VD) model was assessed. The assessed algorithms are the first-order conditional estimation method with interaction (FOCEI) implemented in NONMEM VI and the SAEM algorithm implemented in MONOLIX version 2.4. Simulated data were also used to test if an effect compartment and/or a lag time could be distinguished to describe an observed delay in onset of viral inhibition using SAEM. The preferred model was then used to describe the observed maraviroc monotherapy plasma concentration and viral load data using SAEM. In this last step, three modelling approaches were compared; (i) sequential PKPD-VD with fixed individual Empirical Bayesian Estimates (EBE) for PK, (ii) sequential PKPD-VD with fixed population PK parameters and including concentrations, and (iii) simultaneous PKPD-VD. Using FOCEI, many convergence problems (56%) were experienced with fitting the sequential PKPD-VD model to the simulated data. For the sequential modelling approach, SAEM (with default settings) took less time to generate population and individual estimates including diagnostics than with FOCEI without diagnostics. For the given maraviroc monotherapy sampling design, it was difficult to separate the viral dynamics system delay from a pharmacokinetic distributional delay or delay due to receptor binding and subsequent cellular signalling. The preferred model included a viral load lag time without inter-individual variability. Parameter estimates from the SAEM analysis of observed data were comparable among the three modelling approaches. For the sequential methods, computation time is approximately 25% less when fixing individual EBE of PK parameters with omission of the concentration data compared with fixed population PK parameters and retention of concentration data in the PD-VD estimation step. Computation times were similar for the sequential method with fixed population PK parameters and the simultaneous PKPD-VD modelling approach. The current analysis demonstrated that the SAEM algorithm in MONOLIX is useful for fitting complex mechanistic models requiring multiple differential equations. The SAEM algorithm allowed simultaneous estimation of PKPD and viral dynamics parameters, as well as investigation of different model sub-components during the model building process. This was not possible with the FOCEI method (NONMEM version VI or below). SAEM provides a more feasible alternative to FOCEI when facing lengthy computation times and convergence problems with complex models

Dynamic 3D shape of the plantar surface of the foot using coded structured light:a technical report

The foot provides a crucial contribution to the balance and stability of the musculoskeletal system, and accurate foot measurements are important in applications such as designing custom insoles/footwear. With better understanding of the dynamic behavior of the foot, dynamic foot reconstruction techniques are surfacing as useful ways to properly measure the shape of the foot. This paper presents a novel design and implementation of a structured-light prototype system providing dense three dimensional (3D) measurements of the foot in motion. The input to the system is a video sequence of a foot during a single step; the output is a 3D reconstruction of the plantar surface of the foot for each frame of the input. Methods Engineering and clinical tests were carried out to test the accuracy and repeatability of the system. Accuracy experiments involved imaging a planar surface from different orientations and elevations and measuring the fitting errors of the data to a plane. Repeatability experiments were done using reconstructions from 27 different subjects, where for each one both right and left feet were reconstructed in static and dynamic conditions over two different days. Results The static accuracy of the system was found to be 0.3 mm with planar test objects. In tests with real feet, the system proved repeatable, with reconstruction differences between trials one week apart averaging 2.4 mm (static case) and 2.8 mm (dynamic case). Conclusion The results obtained in the experiments show positive accuracy and repeatability results when compared to current literature. The design also shows to be superior to the systems available in the literature in several factors. Further studies need to be done to quantify the reliability of the system in clinical environment

Growth in Children with Cerebral Palsy during five years after Selective Dorsal Rhizotomy: a practice-based study

Background: Overweight is reported as a side effect of SDR. The aims were to study the development of weight, height and body mass index (BMI) during five years after SDR. Methods: This prospective, longitudinal and practice-based study included all 56 children with CP spastic diplegia undergoing SDR from the start in March 1993 to April 2003 in our hospital. The preoperative Gross Motor Function Classification System (GMFCS) levels were I-II in 17, III in 15, IV-V in 24 children. Median age at SDR was 4.3 years (range 2.4-7.4 years). Weight and height/recumbent length were measured. Swedish growth charts for typically developing children generated weight, height and BMI z-scores for age and gender. Results: The preoperative median z-scores were for height-1.92 and for body mass index (BMI)-0.22. Five years later, the median BMI z-score was increased by + 0.57 (p + 2 SD) increased (p < 0.05). Baseline BMI and age at the start of follow-up influenced the BMI change during the five years (p < 0.001 and p < 0.05 respectively). The individual growth was highly variable, but a tendency towards increasing stunting with age was seen in severe gross motor dysfunction (GMFCS levels IV-V) and the opposite, a slight catch-up of height in children with walking ability (GMFCS levels I-III). Conclusions: These are the first available subtype-and GMFCS-specific longitudinal growth data for children with CP spastic diplegia. Their growth potential according to these data should be regarded as a minimum, as some children were undernourished. It is unknown whether the spasticity reduction through SDR increased the weight gain velocity, or if the relative weight increase was part of the general "obesity epidemic". For some children the weight increase was highly desirable. In others, it resulted in overweight and obesity with risk of negative health effects. Weight and height should be monitored to enable early prevention of weight aberrations also causing problems with mobility, activity and participation