1,064 research outputs found

    A multivariate analysis on non-nucleoside HIV-1 reverse transcriptase inhibitors and resistance induced by mutation

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    This paper describes the use of multivariate statistical procedure PCA as a tool to explore the inhibitory activity of classes of NNRTIs against HIV-1 viruses (wild type and more frequent mutants, Y181C, V106A, K103N, L100I) and against RT enzyme. The analysis of correlations between biological activity and molecular descriptors or similarity indexes allowed a reliable classification of the fifty five derivatives considered in this study. The best results were obtained in the case of L100I and K103N mutants for which the higher number of assignments was found when the principal components derived from the descriptors were used. On this basis this statistical approach is proposed as a reliable method for the prediction of the activity of NNRTIs, for which the data against mutant strains have not been reported

    Spatial analysis and heritage conservation. Leveraging 3-D data and GIS for monitoring earthen architecture

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    This paper discusses new advances in heritage site monitoring using a geo-spatial method for assessing the state of preservation of earthen architecture overtime as a preventive conservation measure. The proposed method leverages a comprehensive (quantitative–qualitative) approach that gathers multi-temporal data including environmental information collected by means of environmental loggers, qualitative vulnerability assessment of mud-brick walls, and surface change detection information obtained by comparing terrestrial laser scanning point cloud capturing the decay of building's wall features over time. Producing a detailed spatial understanding of the conservation issues that affect mud-brick walls in large earthen sites, this method can be used by conservators to rapidly identify which buildings require immediate intervention and lay the basis for future evaluation of the conservation actions undertaken. To test the effectiveness of the proposed geospatial model in producing a comprehensive view of the environmental risk and pattern of decay that affect mudbrick structures, this paper presents analyses and results obtained in a six-year study at Çatalhöyük, Turkey. Our results corroborate the effectiveness of the proposed method and prove that it can be successfully employed to create preventive conservation measures at other earthen sites inside and outside the Near East

    Dimensión urbana y percepción en la ciudad maya Clásica de Palenque

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    In this article I address two interrelated topics: space construction and the perception of the built environment at Palenque, Chiapas, during the Late Classic Period. Starting from the study of Palenque’s urban morphology and by using Geographic Information System’s tools, I aim at underlying intentionality in specific buildings’ position and to explore how people’s urbanity, that is their condition in the city and the experience of otherness, would have transformed their perception of the environment. To this end, I will consider some characteristics of the environment such as labor investment, infrastructure and resource access, land subdivision in architectural groups and their distribution. I argue that these elements, if considered in relation with circulation and visibility, suggest specific planning strategies and point to social status difference within city sectors and their inhabitants

    The Mausoleum Architectural Project: Reinterpreting Palenque's temple of the inscriptions through 3D data-driven architectural analysis

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    The Temple of the Inscriptions at Palenque, Mexico, is an outstanding example of Classic Maya architecture erected in the seventh century as the funerary building for ruler K'inich Janab Pakal. For decades, scholars have speculated on its construction sequence and the potential existence of hidden rooms on either side of Pakal's mortuary chamber. This article aims to advance understanding of the Temple's architectural context in light of new 3D data. After reviewing the application of drone-based photogrammetry and terrestrial Light Detection and Ranging in the Maya area, we argue that these techniques are capable of enhancing the architectural analysis of the Temple of the Inscriptions and showing that this structure was part of a larger architectural project, encompassing the adjacent Temple XIII, and the connecting stepped building platform. Our findings demonstrate that the basal platforms for the Temple of the Inscriptions and Temple XIII were erected contemporaneously and that the design of their mortuary chambers follows a tripartite layout we identified in Palenque's elite funerary architecture and associated mortuary practices. We conclude that these three buildings were part of a mausoleum architectural project, the construction of which was initiated by Pakal to reshape Palenque's site-core and enshrine the ruling family's power and ancestors

    Una proposta di lettura integrale della città Maya antica: la morfologia urbana di Chinikihá e Palenque (Chiapas, Messico) nel periodo classico

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    Research on urban and architectonical contexts in Mesoamerica have generally concentrated on the study and excavation of settlements’ civic-ceremonial core. Nevertheless, in recent years, several projects aim to understand the real extension of Mesoamerican cities and their territorial and political integration. The Palenque Regional Project, directed by Dr. Rodrigo Liendo Stuardo, has concentrated its efforts on the register and documentation of the archaeological sites within the area controlled by the Palenque kingdom in the Classic period. In this regional context, Chinikihá and Palenque are the only settlements that we can define as capitals of a large territory, because of their public architecture as temples, ball games, big central plazas and the hieroglyphic inscriptions, which testify the presence of a ruling dynasty. The urban complexity they manifest, with respect to the other 600 registered sites, confirm their predominant role and their capacity to concentrate people and activities. In this paper, in order to understand the functioning of the city as a response to people´s movement, differential accessibility, buildings hierarchy and association, I propose a methodology to study the ancient Maya urban morphology. This is composed of two topics: a first typological categorization of architectural compounds and groups, and the adoption of the five formal categories proposed by the American urbanist Kevin Lynch which, in my opinion, help outlying the perception that the users could have had of their surrounding built environment. The methodological proposal here formulated is a first approach to understand the urban morphology of ancient Maya cities: I consider that, from an architectonic point of view, it is a fundamental task to complement archaeological investigations with the study of the urban context, in order to better comprehend and propose how space was used and how it would have been to live in a planned city and in a symbolic environment

    Broad inhibition of plasmodium falciparum cytoadherence by (+)-epigallocatechin gallate

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    <p>Abstract</p> <p>Background</p> <p>The surface antigen P<it>f</it>EMP-1 is a key virulence factor of the human malaria parasite implicated in the cytoadherence of <it>Plasmodium falciparum </it>infected erythrocytes to a range of receptors on host endothelium. Among these host receptors, binding to ICAM-1 is related to cerebral malaria. The majority of the mortality in children with cerebral malaria is seen within 24 h of hospital admission despite the use of effective anti-parasite drugs, therefore, the development of adjunctive therapies is urgently needed.</p> <p>The polyphenolic compound (+)-epigallocatechin gallate ((+)-EGCG) has been previously evaluated for anti-adhesive properties using a small number of laboratory parasite isolates. Here, this property is further explored using a new panel of ICAM-1-binding patient isolates of <it>P. falciparum </it>to ascertain if (+)-EGCG might be effective as a broad spectrum inhibitor of ICAM-1-based cytoadherence.</p> <p>Methods</p> <p><it>Plasmodium falciparum </it>lines, including A4 and ItG as positive controls and nine new ICAM-1 binding patient isolates, were allowed to bind with ICAM-1-Fc protein under static assay conditions in the presence and absence of 50 μM (+)-EGCG. Adhesion levels of all the parasite strains were quantified by microscopy as the mean number of infected erythrocyte (IE) bound per mm<sup>2 </sup>of surface area and statistical comparisons were made to demonstrate the effect of (+)-EGCG on the binding of various parasite variants to human ICAM-1.</p> <p>Results</p> <p>This study revealed that binding of patient isolates to ICAM-1 was reduced significantly with inhibition levels of 37% in patient isolate BC-12 up to a maximum of 80% in patient isolate 8146 at 50 μM (+)-EGCG.</p> <p>Conclusion</p> <p>Evaluation of the anti-adhesive property of (+)-EGCG against a new panel of ICAM-1-binding patient isolates of <it>P. falciparum </it>showed that this inhibitor, identified as potential mimic of the L43 loop of human ICAM-1, was effective at blocking cytoadherence.</p

    Expression, Purification, Structural and Functional Characterization of Recombinant Human Parvulin 17

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    Parvulins, peptidyl-prolyl isomerase enzymes (PPIase), catalyze the cis-trans isomerization of prolyl bonds in polypeptides, contributing to folding and function regulation of many proteins. Among Parvulins, Par17, exclusively expressed in hominids, is the least examined in terms of structure, catalytic function and cellular activity. Setting the conditions for the preparation of recombinant active Par17 may therefore significantly foster future studies. Here, we comparatively evaluated the impact of several parameters, including host strains, culture media, isopropyl ss-D-1-thiogalactopyranoside concentration, post-induction incubation time and temperature, on the overexpression of Par17 in E. coli cells. A similar approach was also comparatively adopted for the preparation of the recombinant full-length Pin1 protein, the most representative Parvulin, and the catalytic domains of both enzymes. Proteins were efficiently expressed and purified to homogeneity and were subjected to a structural characterization by Size Exclusion Chromatography and Circular Dichroism. Moreover, a single-step homogeneous protease-based fluorimetric assay, potentially scalable in HTS format, has been developed for determining the peptidyl-prolyl cis-trans isomerase activity of recombinant Parvulins. Results obtained show that proteins are folded and active. These new data mark an important milestone for progressing the investigation of Parvulins
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