Landscape Transformation During Ceramic Age and Colonial Occupations of Barbuda, West Indies

This research documented the history of landscape transformation on the island of Barbuda in the Lesser Antilles, Caribbean through cross-disciplinary research approaches. Excavations confirmed a human presence for the seasonal exploitation of conch meat and other mollusks during the Archaic Age (c.3000–500 BC), but more substantial impacts to terrestrial ecosystems likely began during the Ceramic Age (c.500 BC–AD 1500). Our combined sedimentary and charcoal records revealed that human-induced environmental transformations began with Ceramic Age peoples as they cleared vegetation for settlements and gardens with intentional burning. Sedimentary charcoal indicated a dramatic decline in fire during post-Ceramic Age abandonment, continuing through the Colonial Period, as the dominant human activities shifted to herding, farming, and selective wood harvesting. Historical sources showed that during the Colonial Period (post-1492), the island was intermittently settled until the mid-seventeenth century, while the Codrington family of Antigua held the lease to the island from 1681 to 1870. They used the island for farming and stock-rearing, exporting meat and draught animals along with lime, timber, and subsistence crops. Macrocharcoal recovered from Colonial Period archaeological sites reflect the use of a variety of local species and wood imported to the island or harvested from shipwrecks

Interopérabilité des systèmes d'information : approches dirigées par les modèles

National audienceInformation systems are more and more often based on aggregation of other systems that must be maintained and evolved in an agile way and with no entropy creation. This is not without interoperability problems! Among others, the aim of Model-Driven Engineering (MDE) is to provide solutions for interoperability issues between systems. This paper summarizes thoughts that have come up from the specific action "Interoper- ability of information systems and model-driven engineering: What challenges? What solutions?" supported by inforsid. We propose a summary of approaches that are based on MDE and knowledge engineering and that tackle interoperability issues in the industry. Open questions and limitations that raised during the meetings are also reported

Catalytic ozonation with γ-Al2O3 to enhance the degradation of refractory organics in water

Nowadays, heterogeneous catalytic ozonation appears as a promising way to treat industrial wastewaters containing refractory pollutants, which resist to biological treatments. Several oxides and minerals have been used and their behavior is subject to controversy with particularly the role of Lewis acid sites and/or basic sites and the effect of salts. In this study, millimetric mesoporous γ-Al2O3 particles suitable for industrial processes were used for enhancing the ozonation efficiency of petrochemical effluents without pH adjustment. A phenol (2,4-dimethylphenol (2,4-DMP)) was first chosen as petrochemical refractory molecule to evaluate the influence of alumina in ozonation. Single ozonation and ozonation in presence of γ-Al2O3 led to the disappearance of 2,4-DMP in 25 min and a decrease in pH from 4.5 to 2.5. No adsorption of 2,4-DMP occurred on γ-Al2O3. Adding γ-Al2O3 in the process resulted in an increase of the 2,4–DMP oxidation level. Indeed, the total organic carbon (TOC) removal was 14% for a single ozonation and 46% for ozonation with γ-Al2O3. Similarly, chemical oxygen demand (COD) removal increases from 35 to 75%, respectively. Various oxidized by-products were produced during the degradation of 2,4-DMP, but after 5 h ozonation 90% of organic by-products were acetic acid > formic acid ≫ oxalic acid. Some of the carboxylic acids were adsorbed on γ-Al2O3. The use of radical scavengers (tert-butanol) highlighted the involvement of hydroxyl radicals during catalytic ozonation with γ-Al2O3 in contrary to single ozonation, which mainly involved direct ozone reaction. γ-Al2O3 is an amphoteric solid with Lewis acid AlOH(H+) sites and basicAl-OH sites. After ozonation the amount of basic sites decreased due to carboxylates adsorption, while the Lewis acid sites remained constant as evidenced by FTIR. Several ozonation runs with γ-Al2O3 reported a progressive decrease of its catalytic activity due to the cumulative sorption of carboxylates on the basic sites. After 80 h of ozonation, a calcination at 550 °C allowed to recover allAl-OH basic sites and the initial activity of γ-Al2O3. A synthetic petrochemical effluent containing various petrochemicals (phenol, acetic acid, naphtenic acid, pyrene, naphtalene) was then treated with γ-Al2O3 with and without NaCl. Sodium ions prevented carboxylates adsorption on γ-Al2O3 leading to a higher efficiency of γ-Al2O3 in presence of NaCl and allowed to decrease the toxicity of the petrochemical effluent

Distinct Effects of Two HIV-1 Capsid Assembly Inhibitor Families That Bind the Same Site within the N-Terminal Domain of the Viral CA Protein

The emergence of resistance to existing classes of antiretroviral drugs necessitates finding new HIV-1 targets for drug discovery. The viral capsid (CA) protein represents one such potential new target. CA is sufficient to form mature HIV-1 capsids in vitro, and extensive structure-function and mutational analyses of CA have shown that the proper assembly, morphology, and stability of the mature capsid core are essential for the infectivity of HIV-1 virions. Here we describe the development of an in vitro capsid assembly assay based on the association of CA-NC subunits on immobilized oligonucleotides. This assay was used to screen a compound library, yielding several different families of compounds that inhibited capsid assembly. Optimization of two chemical series, termed the benzodiazepines (BD) and the benzimidazoles (BM), resulted in compounds with potent antiviral activity against wild-type and drug-resistant HIV-1. Nuclear magnetic resonance (NMR) spectroscopic and X-ray crystallographic analyses showed that both series of inhibitors bound to the N-terminal domain of CA. These inhibitors induce the formation of a pocket that overlaps with the binding site for the previously reported CAP inhibitors but is expanded significantly by these new, more potent CA inhibitors. Virus release and electron microscopic (EM) studies showed that the BD compounds prevented virion release, whereas the BM compounds inhibited the formation of the mature capsid. Passage of virus in the presence of the inhibitors selected for resistance mutations that mapped to highly conserved residues surrounding the inhibitor binding pocket, but also to the C-terminal domain of CA. The resistance mutations selected by the two series differed, consistent with differences in their interactions within the pocket, and most also impaired virus replicative capacity. Resistance mutations had two modes of action, either directly impacting inhibitor binding affinity or apparently increasing the overall stability of the viral capsid without affecting inhibitor binding. These studies demonstrate that CA is a viable antiviral target and demonstrate that inhibitors that bind within the same site on CA can have distinct binding modes and mechanisms of action

Relations anthropo-environnementales depuis la période archaïque jusqu'au XIXe siècle à Barbuda : multidisciplinarité archéobotanique

Cette recherche doctorale a comme but principal l’étude de la dynamique anthropo-environnementale à Barbuda grâce à une approche archéobotanique multidisciplinaire. À la base de ce projet se trouve une démarche méthodologique, celle de combiner l’analyse des graines, du charbon de bois, des grains d’amidon et des phytolithes pour rendre compte de l’évolution des relations anthropo-environnementale. Cette thèse repose sur l’analyse de six sites archéologiques datant des premières occupations humaines sur l’île en couvrant la période archaïque jusqu’au XIXe siècle. Les analyses archéobotaniques sont peu nombreuses dans la région caribéenne, surtout celles combinant plusieurs types de restes. Ainsi, il a d’abord fallu évaluer le potentiel de préservation des macro-et microrestes botaniques sur l’île calcaire de Barbuda. Les données ont révélé un potentiel d’analyse variable selon les sites et les types de restes. Les graines recueillies sont peu nombreuses, alors que les charbons de bois sont omniprésents sur l’ensemble des sites. La principale découverte est la présence de phytolithes et de grains d’amidon autant dans les résidus prélevés sur les artéfacts que dans les échantillons de sédiments. Au cours des années, les populations archaïques, saladoïdes, post-saladoïdes et britanniques, en plus des esclaves, se sont succédéessur l’île. Chacune d’entre elles possédait un mode de vie spécifique et des besoins particuliers, ce qui a laissé une succession d’empruntes sur la végétation. Les données recueillies démontrent leur tentative degestion de la ressource végétale, l’introduction et la culture d’espèces botaniques pour l’alimentation, ainsi que le changement progressif du couvert végétal initial vers une végétation secondaire. L’arrivée des Britanniques, sous la direction de la famille Codrington, a joué un rôle clé dans la création du paysage environnemental actuel de l’île. Ce projet est un premier pas vers une compréhension rigoureuse de la dynamique anthropo-environnementale à Barbuda et à travers les îles caribéennes.The primary goal of this doctoral research is to examine human-plant dynamics on the island of Barbuda using multiple methods of archaeobotanical analyses. This research is thus a methodological contribution combining the analysis of seeds, charcoal, starch grains and phytolithes in order to study the evolution of human-plant relationships. Six archaeological sites were analysed dating from the first human occupation on the island by Archaic populations until the 19th century. Archaeobotanical analyses are scare throughout the Caribbean region, especially those that combine the study of several types of botanical remains. The analytical potential of botanical macro-and microremains on the limestone island of Barbuda was evaluated for all sites. The ensuing results varied greatly depending on the site and the type of remains analysed. Seeds were very few in number, while charcoal is omnipresent on all sites. The most important discovery was the preservation of phytoliths and starch grains on artefact residues and in soil samples. Over 2000 years, Archaic, Saladoid, post-Saladoid, British, and enslaved peoples lived on the island. Each population had varying needs for subsistence resulting in different vegetation signatures. Data recovered suggests attempts at vegetation management, the introduction of new plant species for cultivation and consumption, as well as a progressive transition from the initial vegetation cover to a secondary forest. The British arrival on the island, under the management of the Codrington Family played a key role in the creation of the island’s current landscape. This research project is thus a first step towards a more rigorous and comprehensive understanding of human-plant dynamicson Barbuda and in the region

Biphenylsulfonacetic Acid Inhibitors of the Human Papillomavirus Type 6 E1 Helicase Inhibit ATP Hydrolysis by an Allosteric Mechanism Involving Tyrosine 486

Human papillomaviruses (HPVs) are the causative agents of benign and malignant lesions of the epithelium. Despite their high prevalence, there is currently no antiviral drug for the treatment of HPV-induced lesions. The ATPase and helicase activities of the highly conserved E1 protein of HPV are essential for viral DNA replication and pathogenesis and hence are considered valid antiviral targets. We recently described novel biphenylsulfonacetic acid inhibitors of the ATPase activity of E1 from HPV type 6 (HPV6). Based on kinetics and mutagenesis studies, we now report that these compounds act by an allosteric mechanism. They are hyperbolic competitive inhibitors of the ATPase activity of HPV6 E1 and also inhibit its helicase activity. Compounds in this series can also inhibit the ATPase activity of the closely related enzyme from HPV11; however, the most potent inhibitors of HPV6 E1 are significantly less active against the type 11 protein. We identified a single critical residue in HPV6 E1, Tyr-486, substituted by a cysteine in HPV11, which is primarily responsible for this difference in inhibitor potency. Interestingly, HPV18 E1, which also has a tyrosine at this position, could be inhibited by biphenylsulfonacetic acid derivatives, thereby raising the possibility that this class of inhibitors could be optimized as antiviral agents against multiple HPV types. These studies implicate Tyr-486 as a key residue for inhibitor binding and define an allosteric pocket on HPV E1 that can be exploited for future drug discovery efforts

Oral Bioavailability and In Vivo Efficacy of the Helicase-Primase Inhibitor BILS 45 BS against Acyclovir-Resistant Herpes Simplex Virus Type 1

This study investigated the oral bioavailability and efficacy of BILS 45 BS, a selective herpes simplex virus (HSV) helicase-primase inhibitor, against acyclovir (ACV)-resistant (ACV(r)) infections mediated by the HSV type 1 (HSV-1) dlsptk and PAA(r)5 mutant strains. In vitro, the compound was more potent than ACV against wild-type clinical and laboratory HSV-1 strains and ACV(r) HSV isolates, as determined by a standard plaque reduction assay, with a mean 50% effective concentration of about 0.15 μM. The oral bioavailability of BILS 45 BS in hairless mice was 49%, with a peak concentration in plasma of 31.5 μM after administration of a single dose of 25 mg/kg. Following cutaneous infection of nude mice, both the HSV-1 dlsptk and PAA(r)5 mutant strains induced significant, reproducible, and persistent cutaneous lesions that lasted for more than 2 weeks. Oral treatment with ACV (100 or 125 mg/kg/day, three times a day by gavage) did not affect either mutant-induced infection. In contrast, BILS 45 BS at an oral dose of 100 mg/kg/day almost completely abolished cutaneous lesions mediated by both ACV(r) HSV-1 mutants. The 50% effective doses of BILS 45 BS were 56.7 and 61 mg/kg/day against dlsptk- and PAA(r)5-induced infections, respectively. Taken together, our results demonstrate very effective oral therapy of experimental ACV(r) HSV-1 infections in nude mice and support the potential use of HSV helicase-primase inhibitors for the treatment of nucleoside-resistant HSV disease in humans