The Oman exotics : a key to the understanding of the Neotethyan geodynamic evolution

The study of the exotic blocks of the Hawasina Nappes (Sultanate of Oman) leads to give apposit data that allow us to propose a new paleogeographic evolution of the Oman margin in time and space. A revised classification of exotic blocks into different paleogeographical units is presented. Two newly introduced stratigraphic groups, the Ramaq Group (Ordovician to Triassic) and the Al Buda'ah Group (upper Permian to Jurassic) are interpreted as tilted blocks related to the Oman continental margin. The Kawr Group (middle Triassic to Cretaceous) is redefined and interpreted as an atoll-type seamount. The paleogeography and paleoenvironments of these units are integrated into a new scheme of the Neotethyan rifting history. Brecciae and olisto¬liths of the Hawasina series are interpreted to have originated from tectonic movements affecting the Oman margin and the Neotethyan ocean floor. The breccias of late Permian age were generated by the extension processes affecting the margin, and by the creation of the Neotethyan oceanic floor. The breccias of mid-late Triassic age coincide in time with the collision of the Cimmerian continents with Eurasia. In constrast, the breccias of late Jurassic and Cretaceous age are interpreted as resulting to the creation of a new oceanic crust (Semail) off the Oman margin

Hazardous substances in frequently used professional cleaning products.

A growing number of studies have identified cleaners as a group at risk for adverse health effects of the skin and the respiratory tract. Chemical substances present in cleaning products could be responsible for these effects. Currently, only limited information is available about irritant and health hazardous chemical substances found in cleaning products. We hypothesized that chemical substances present in cleaning products are known health hazardous substances that might be involved in adverse health effects of the skin and the respiratory tract. We performed a systematic review of cleaning products used in the Swiss cleaning sector. We surveyed Swiss professional cleaning companies (n = 1476) to identify the most used products (n = 105) for inclusion. Safety data sheets (SDSs) were reviewed and hazardous substances present in cleaning products were tabulated with current European and global harmonized system hazard labels. Professional cleaning products are mixtures of substances (arithmetic mean 3.5 +/- 2.8), and more than 132 different chemical substances were identified in 105 products. The main groups of chemicals were fragrances, glycol ethers, surfactants, solvents; and to a lesser extent, phosphates, salts, detergents, pH-stabilizers, acids, and bases. Up to 75% of products contained irritant (Xi), 64% harmful (Xn) and 28% corrosive (C) labeled substances. Hazards for eyes (59%) and skin (50%), and hazards by ingestion (60%) were the most reported. Cleaning products potentially give rise to simultaneous exposures to different chemical substances. As professional cleaners represent a large workforce, and cleaning products are widely used, it is a major public health issue to better understand these exposures. The list of substances provided in this study contains important information for future occupational exposure assessment studies.

Biosphere/lithosphere interface : microbially-mediated CaCO3 precipitation in hypersaline and freshwater environments

Abstract: Microbial mats very efficiently cycle elements, such as C, 0, N, S and H, which makes them key players of redox processes at the biosphere-lithosphere interface. They are characterized by high metabolic activities and high turnover rates (production and consumption) of biomass, which mainly consists of cell material and of extracellular organic matter (EOM). The EOM forms a matrix, embedding the microbial cells and fulfilling various functions within the microbial mat, including: mat attachment to surfaces; creation of micro-domains within the mat; physical stabilization under hy- drodynamic stress and the protection of the cells in multiple other stress conditions. EOM mainly consists of polysaccharides, amino acids, and a variety of chemical func-tional groups {e.g., -C00H, - SH -OH). These groups strongly bind cations such as Ca2+ and Mg2+ and thus exert a strong control on carbonate mineral formation within the microbial mat. A feedback mechanism between community metabolisms, their prod¬ucts, and the surrounding physicochemical microenvironment thus influences the de¬gree of carbonate saturation favoring either carbonate precipitation or dissolution. We investigated the driving forces and mechanisms of microbialite formation in the Sari ne River, FR, Switzerland, the hypersaline lake, Big Pond, Bahamas and in labo¬ratory experiments. The two fundamentally different natural systems allowed us to compare the geochemical conditions and microbial metabolisms, necessary for car¬bonate formation in microbial mats. Although carbonates are oversaturated in both environments, precipitation does not occur on physicochemical substrates (i.e. out¬side the microbial mats). In the Sarine a high crystal nucleation threshold exceeds the carbonate saturation, despite the high carbonate alkalinity in the water column. Cyanobacterial photosynthesis strongly locally enhances the carbonate alkalinity, whereas the EOM attract and immobilize calcium, which increases the saturation state and finally leads to carbonate precipitation within the EOM (in this case the cyanobacterial sheath) as nucleation template. In Big Pond, the presence of calcium- chelating anions (i.e. sulfate) and EOM, as well as the presence of magnesium, lowers the calcium activity in the water column and mat, and thus inhibits carbonate pre¬cipitation. Coupled with other heterotrophic metabolisms, sulfate reduction uses the EOM as carbon source, degrading it. The resulting EOM consumption creates alkalin¬ity, releases calcium and consumes sulfate in mat-micro domains, which leads to the formation of carbonate layers at the top of the microbial mat. Résumé: Interface biosphère/lithosphère: médiation microbienne de la précipitation de CaC03 dans des environnements en eaux douces et hypersalines Les tapis microbiens engendrent une circulation très efficace des éléments, tels que C, 0, N, S et H, ce qui en fait des acteurs clé pour les processus d'oxydoréduction à l'inter¬face biosphère-lithosphère. Ils sont caractérisés par des taux élevés d'activité méta¬bolique, ainsi que par la production et la consommation de biomasse, principalement constituée de cellules microbiennes et de matière organique extracellulaire (MOE). Dans un tapis microbien, les cellules microbiennes sont enveloppées par une matrice de MOE qui a différentes fonctions dont l'attachement du tapis aux surfaces, la créa¬tion de micro-domaines dans le tapis, la stabilisation physique en situation de stress hydrodynamique, et la protection des cellules dans de multiples autres conditions de stress. La MOE se compose principalement de polysaccharides, d'acides aminés, et d'une variété de groupes fonctionnels chimiques (par exemple, COOH, -SH et -OH). Ces groupes se lient fortement aux cations, tels que Ca2+ et Mg2+, et exercent ainsi un contrôle fort sur la formation de CaC03 dans le tapis microbien. Un mécanisme de rétroaction, entre les métabolismes de la communauté microbienne, leurs produits, et le microenvironnement physico-chimique, influence le degré de saturation de car¬bonate, favorisant soit leur précipitation, soit leur dissolution. Nous avons étudié le moteur et les mécanismes de minéralisation dans des tapis de la Sarine, FR, Suisse et du lac hypersalin, Big Pond, aux Bahamas, ainsi que durant des expériences en laboratoire. Les deux systèmes naturels, fondamentalement dif¬férents, nous ont permis de comparer les conditions géochimiques et les métabolis¬mes nécessaires à la formation des carbonates dans des tapis microbiens. Bien que les carbonates soient sursaturés dans les deux environnements, la précipitation ne se produit pas sur des substrats physico-chimiques (en dehors du tapis microbien). Dans la Sarine, malgré un taux d'alcalinité élevé, les valeurs de seuil pour la nucléa- tion de carbonates sont plus hautes que la saturation du carbonate. La photosynthèse cyanobactérienne augmente localement l'alcalinité, alors que la MOE attire et immo¬bilise le calcium, ce qui augmente l'état de saturation et conduit finalement à la pré¬cipitation des carbonates, en utilisant la MOE comme substrat de nucléation. À Big Pond, la présence de chélateurs de calcium, notamment les anions (p.ex. le sulfate) et la MOE, ainsi que la présence de magnésium, réduit l'activité du calcium et inhibe en conséquence la précipitation des carbonates. Couplée avec d'autres métabolismes hétérotrophes, la réduction des sulfates utilise la MOE comme source de carbone, en la dégradant. Cette consommation de MOE crée l'alcalinité, consomme des sulfates et libère du calcium dans des micro-domaines, conduisant à la formation de couches de carbonates dans le haut du tapis microbien.

Information security and the enforcement of secrecy : the practical application of quantum key distribution

There is no doubt about the necessity of protecting digital communication: Citizens are entrusting their most confidential and sensitive data to digital processing and communication, and so do governments, corporations, and armed forces. Digital communication networks are also an integral component of many critical infrastructures we are seriously depending on in our daily lives. Transportation services, financial services, energy grids, food production and distribution networks are only a few examples of such infrastructures. Protecting digital communication means protecting confidentiality and integrity by encrypting and authenticating its contents. But most digital communication is not secure today. Nevertheless, some of the most ardent problems could be solved with a more stringent use of current cryptographic technologies. Quite surprisingly, a new cryptographic primitive emerges from the ap-plication of quantum mechanics to information and communication theory: Quantum Key Distribution. QKD is difficult to understand, it is complex, technically challenging, and costly-yet it enables two parties to share a secret key for use in any subsequent cryptographic task, with an unprecedented long-term security. It is disputed, whether technically and economically fea-sible applications can be found. Our vision is, that despite technical difficulty and inherent limitations, Quantum Key Distribution has a great potential and fits well with other cryptographic primitives, enabling the development of highly secure new applications and services. In this thesis we take a structured approach to analyze the practical applicability of QKD and display several use cases of different complexity, for which it can be a technology of choice, either because of its unique forward security features, or because of its practicability.

A Novel Acute Retroviral Syndrome Severity Score Predicts the Key Surrogate Markers for HIV-1 Disease Progression.

OBJECTIVE: Best long-term practice in primary HIV-1 infection (PHI) remains unknown for the individual. A risk-based scoring system associated with surrogate markers of HIV-1 disease progression could be helpful to stratify patients with PHI at highest risk for HIV-1 disease progression. METHODS: We prospectively enrolled 290 individuals with well-documented PHI in the Zurich Primary HIV-1 Infection Study, an open-label, non-randomized, observational, single-center study. Patients could choose to undergo early antiretroviral treatment (eART) and stop it after one year of undetectable viremia, to go on with treatment indefinitely, or to defer treatment. For each patient we calculated an a priori defined "Acute Retroviral Syndrome Severity Score" (ARSSS), consisting of clinical and basic laboratory variables, ranging from zero to ten points. We used linear regression models to assess the association between ARSSS and log baseline viral load (VL), baseline CD4+ cell count, and log viral setpoint (sVL) (i.e. VL measured ≥90 days after infection or treatment interruption). RESULTS: Mean ARSSS was 2.89. CD4+ cell count at baseline was negatively correlated with ARSSS (p = 0.03, n = 289), whereas HIV-RNA levels at baseline showed a strong positive correlation with ARSSS (p<0.001, n = 290). In the regression models, a 1-point increase in the score corresponded to a 0.10 log increase in baseline VL and a CD4+cell count decline of 12/µl, respectively. In patients with PHI and not undergoing eART, higher ARSSS were significantly associated with higher sVL (p = 0.029, n = 64). In contrast, in patients undergoing eART with subsequent structured treatment interruption, no correlation was found between sVL and ARSSS (p = 0.28, n = 40). CONCLUSION: The ARSSS is a simple clinical score that correlates with the best-validated surrogate markers of HIV-1 disease progression. In regions where ART is not universally available and eART is not standard this score may help identifying patients who will profit the most from early antiretroviral therapy.

Entry and transcription as key determinants of differences in CD4 T-cell permissiveness to human immunodeficiency virus type 1 infection.

Isolated primary human cells from different donors vary in their permissiveness-the ability of cells to be infected and sustain the replication of human immunodeficiency virus type 1 (HIV-1). We used replicating HIV-1 and single-cycle lentivirus vectors in a population approach to identify polymorphic steps during viral replication. We found that phytohemagglutinin-stimulated CD4(+) CD45RO(+) CD57(-) T cells from healthy blood donors (n = 128) exhibited a 5.2-log-unit range in virus production. For 20 selected donors representing the spectrum of CD4 T-cell permissiveness, we could attribute up to 42% of the total variance in virus production to entry factors and 48% to postentry steps. Efficacy at key intracellular steps of the replicative cycle (reverse transcription, integration, transcription and splicing, translation, and budding and release) varied from 0.71 to 1.45 log units among donors. However, interindividual differences in transcription efficiency alone accounted for 64 to 83% of the total variance in virus production that was attributable to postentry factors. While vesicular stomatitis virus G protein-mediated fusion was more efficacious than CCR5/CD4 entry, the latter resulted in greater transcriptional activity per proviral copy. The phenotype of provirus transcription was stable over time, indicating that it represents a genetic trait.

Occupational respiratory exposures to irritating and sensitizing volatile compounds deriving from cleaning products

Recent findings suggest an association between exposure to cleaning products and respiratory dysfunctions including asthma. However, little information is available about quantitative airborne exposures of professional cleaners to volatile organic compounds deriving from cleaning products. During the first phases of the study, a systematic review of cleaning products was performed. Safety data sheets were reviewed to assess the most frequently added volatile organic compounds. It was found that professional cleaning products are complex mixtures of different components (compounds in cleaning products: 3.5 ± 2.8), and more than 130 chemical substances listed in the safety data sheets were identified in 105 products. The main groups of chemicals were fragrances, glycol ethers, surfactants, solvents; and to a lesser extent phosphates, salts, detergents, pH-stabilizers, acids, and bases. Up to 75% of products contained irritant (Xi), 64% harmful (Xn) and 28% corrosive (C) labeled substances. Hazards for eyes (59%), skin (50%) and by ingestion (60%) were the most reported. Monoethanolamine, a strong irritant and known to be involved in sensitizing mechanisms as well as allergic reactions, is frequently added to cleaning products. Monoethanolamine determination in air has traditionally been difficult and air sampling and analysis methods available were little adapted for personal occupational air concentration assessments. A convenient method was developed with air sampling on impregnated glass fiber filters followed by one step desorption, gas chromatography and nitrogen phosphorous selective detection. An exposure assessment was conducted in the cleaning sector, to determine airborne concentrations of monoethanolamine, glycol ethers, and benzyl alcohol during different cleaning tasks performed by professional cleaning workers in different companies, and to determine background air concentrations of formaldehyde, a known indoor air contaminant. The occupational exposure study was carried out in 12 cleaning companies, and personal air samples were collected for monoethanolamine (n=68), glycol ethers (n=79), benzyl alcohol (n=15) and formaldehyde (n=45). All but ethylene glycol mono-n-butyl ether air concentrations measured were far below (<1/10) of the Swiss eight hours occupational exposure limits, except for butoxypropanol and benzyl alcohol, where no occupational exposure limits were available. Although only detected once, ethylene glycol mono-n-butyl ether air concentrations (n=4) were high (49.5 mg/m3 to 58.7 mg/m3), hovering at the Swiss occupational exposure limit (49 mg/m3). Background air concentrations showed no presence of monoethanolamine, while the glycol ethers were often present, and formaldehyde was universally detected. Exposures were influenced by the amount of monoethanolamine in the cleaning product, cross ventilation and spraying. The collected data was used to test an already existing exposure modeling tool during the last phases of the study. The exposure estimation of the so called Bayesian tool converged with the measured range of exposure the more air concentrations of measured exposure were added. This was best described by an inverse 2nd order equation. The results suggest that the Bayesian tool is not adapted to predict low exposures. The Bayesian tool should be tested also with other datasets describing higher exposures. Low exposures to different chemical sensitizers and irritants should be further investigated to better understand the development of respiratory disorders in cleaning workers. Prevention measures should especially focus on incorrect use of cleaning products, to avoid high air concentrations at the exposure limits. - De récentes études montrent l'existence d'un lien entre l'exposition aux produits de nettoyages et les maladies respiratoires telles que l'asthme. En revanche, encore peu d'informations sont disponibles concernant la quantité d'exposition des professionnels du secteur du nettoyage aux composants organiques volatiles provenant des produits qu'ils utilisent. Pendant la première phase de cette étude, un recueil systématique des produits professionnels utilisés dans le secteur du nettoyage a été effectué. Les fiches de données de sécurité de ces produits ont ensuite été analysées, afin de répertorier les composés organiques volatiles les plus souvent utilisés. Il a été mis en évidence que les produits de nettoyage professionnels sont des mélanges complexes de composants chimiques (composants chimiques dans les produits de nettoyage : 3.5 ± 2.8). Ainsi, plus de 130 substances listées dans les fiches de données de sécurité ont été retrouvées dans les 105 produits répertoriés. Les principales classes de substances chimiques identifiées étaient les parfums, les éthers de glycol, les agents de surface et les solvants; dans une moindre mesure, les phosphates, les sels, les détergents, les régulateurs de pH, les acides et les bases ont été identifiés. Plus de 75% des produits répertoriés contenaient des substances décrites comme irritantes (Xi), 64% nuisibles (Xn) et 28% corrosives (C). Les risques pour les yeux (59%), la peau (50%) et par ingestion (60%) était les plus mentionnés. La monoéthanolamine, un fort irritant connu pour être impliqué dans les mécanismes de sensibilisation tels que les réactions allergiques, est fréquemment ajouté aux produits de nettoyage. L'analyse de la monoéthanolamine dans l'air a été habituellement difficile et les échantillons d'air ainsi que les méthodes d'analyse déjà disponibles étaient peu adaptées à l'évaluation de la concentration individuelle d'air aux postes de travail. Une nouvelle méthode plus efficace a donc été développée en captant les échantillons d'air sur des filtres de fibre de verre imprégnés, suivi par une étape de désorption, puis une Chromatographie des gaz et enfin une détection sélective des composants d'azote. Une évaluation de l'exposition des professionnels a été réalisée dans le secteur du nettoyage afin de déterminer la concentration atmosphérique en monoéthanolamine, en éthers de glycol et en alcool benzylique au cours des différentes tâches de nettoyage effectuées par les professionnels du nettoyage dans différentes entreprises, ainsi que pour déterminer les concentrations atmosphériques de fond en formaldéhyde, un polluant de l'air intérieur bien connu. L'étude de l'exposition professionnelle a été effectuée dans 12 compagnies de nettoyage et les échantillons d'air individuels ont été collectés pour l'éthanolamine (n=68), les éthers de glycol (n=79), l'alcool benzylique (n=15) et le formaldéhyde (n=45). Toutes les substances mesurées dans l'air, excepté le 2-butoxyéthanol, étaient en-dessous (<1/10) de la valeur moyenne d'exposition aux postes de travail en Suisse (8 heures), excepté pour le butoxypropanol et l'alcool benzylique, pour lesquels aucune valeur limite d'exposition n'était disponible. Bien que détecté qu'une seule fois, les concentrations d'air de 2-butoxyéthanol (n=4) étaient élevées (49,5 mg/m3 à 58,7 mg/m3), se situant au-dessus de la frontière des valeurs limites d'exposition aux postes de travail en Suisse (49 mg/m3). Les concentrations d'air de fond n'ont montré aucune présence de monoéthanolamine, alors que les éthers de glycol étaient souvent présents et les formaldéhydes quasiment toujours détectés. L'exposition des professionnels a été influencée par la quantité de monoéthanolamine présente dans les produits de nettoyage utilisés, par la ventilation extérieure et par l'emploie de sprays. Durant la dernière phase de l'étude, les informations collectées ont été utilisées pour tester un outil de modélisation de l'exposition déjà existant, l'outil de Bayesian. L'estimation de l'exposition de cet outil convergeait avec l'exposition mesurée. Cela a été le mieux décrit par une équation du second degré inversée. Les résultats suggèrent que l'outil de Bayesian n'est pas adapté pour mettre en évidence les taux d'expositions faibles. Cet outil devrait également être testé avec d'autres ensembles de données décrivant des taux d'expositions plus élevés. L'exposition répétée à des substances chimiques ayant des propriétés irritatives et sensibilisantes devrait être investiguée d'avantage, afin de mieux comprendre l'apparition de maladies respiratoires chez les professionnels du nettoyage. Des mesures de prévention devraient tout particulièrement être orientées sur l'utilisation correcte des produits de nettoyage, afin d'éviter les concentrations d'air élevées se situant à la valeur limite d'exposition acceptée.

Identification of GPx8 as a novel cellular substrate of the hepatitis C virus NS3-4A protease

Background: The hepatitis C virus (HCV) NS3-4A protease is not only an essential component of the viral replication complex and a prime target for antiviral intervention but also a key player in the persistence and pathogenesis of HCV. It cleaves and thereby inactivates two crucial adaptor proteins in viral RNA sensing and innate immunity (MAVS and TRIF) as well as a phosphatase involved in growth factor signaling (TC-PTP). The aim of this study was to identify novel cellular substrates of the NS3-4A protease and to investigate their role in the life cycle and pathogenesis of HCV. Methods: Cell lines inducibly expressing the NS3-4A protease were analyzed in basal as well as interferon- α -stimulated states by stable isotopic labeling using amino acids in cell culture (SILAC) coupled with protein separation and mass spectrometry. Candidates fulfilling strin- gent criteria for potential substrates or products of the NS3-4A protease were further investigated in different experimental sys- tems as well as in liver biopsies from patients with chronic hep- atitis C. Results: SILAC coupled with protein separation and mass spectrometry yielded > 5000 proteins of which 21 can- didates were selected for further analyses. These allowed us to identify GPx8, a membrane-associated peroxidase involved in disulfide bond formation in the endoplasmic reticulum, as a novel cellular substrate of the HCV NS3-4A protease. Cleavage occurs at cysteine in position 11, removing the cytosolic tip of GPx8, and was observed in different experimental systems as well as in liver biopsies from patients with chronic hepatitis C. Further functional studies, involving overexpression and RNA silencing, revealed that GPx8 is a proviral factor involved in viral particle production but not in HCV entry or RNA replica- tion. Conclusions: GPx8 is a proviral host factor cleaved by the HCV NS3-4A protease. Studies investigating the consequences of cleavage for GPx8 function are underway. The identification of novel cellular substrates of the HCV NS3-4A protease should yield new insights into the HCV life cycle and the pathogenesis of hepatitis C and may reveal novel angles for therapeutic inter- vention.

Loss of the thyroid hormone-binding protein Crym renders striatal neurons more vulnerable to mutant huntingtin in Huntington's disease.

The mechanisms underlying preferential atrophy of the striatum in Huntington's disease (HD) are unknown. One hypothesis is that a set of gene products preferentially expressed in the striatum could determine the particular vulnerability of this brain region to mutant huntingtin (mHtt). Here, we studied the striatal protein µ-crystallin (Crym). Crym is the NADPH-dependent p38 cytosolic T3-binding protein (p38CTBP), a key regulator of thyroid hormone (TH) T3 (3,5,3'-triiodo-l-thyronine) transportation. It has been also recently identified as the enzyme that reduces the sulfur-containing cyclic ketimines, which are potential neurotransmitters. Here, we confirm the preferential expression of the Crym protein in the rodent and macaque striatum. Crym expression was found to be higher in the macaque caudate than in the putamen. Expression of Crym was reduced in the BACHD and Knock-in 140CAG mouse models of HD before onset of striatal atrophy. We show that overexpression of Crym in striatal medium-size spiny neurons using a lentiviral-based strategy in mice is neuroprotective against the neurotoxicity of an N-terminal fragment of mHtt in vivo. Thus, reduction of Crym expression in HD could render striatal neurons more susceptible to mHtt suggesting that Crym may be a key determinant of the vulnerability of the striatum. In addition our work points to Crym as a potential molecular link between striatal degeneration and the THs deregulation reported in HD patients.

Functionally and phylogenetically diverse plant communities key to soil biota

Recent studies assessing the role of biological diversity for ecosystem functioning indicate that the diversity of functional traits and the evolutionary history of species in a community, not the number of taxonomic units, ultimately drives the biodiversity-ecosystem-function relationship. Here, we simultaneously assessed the importance of plant functional trait and phylogenetic diversity as predictors of major trophic groups of soil biota (abundance and diversity), six years from the onset of a grassland biodiversity experiment. Plant functional and phylogenetic diversity were generally better predictors of soil biota than the traditionally used species or functional group richness. Functional diversity was a reliable predictor for most biota, with the exception of soil microorganisms, which were better predicted by phylogenetic diversity. These results provide empirical support for the idea that the diversity of plant functional traits and the diversity of evolutionary lineages in a community are important for maintaining higher abundances and diversity of soil communities.