Analysis of hepatitis C virus RNA dimerization and core–RNA interactions

The core protein of hepatitis C virus (HCV) has been shown previously to act as a potent nucleic acid chaperone in vitro, promoting the dimerization of the 3′-untranslated region (3′-UTR) of the HCV genomic RNA, a process probably mediated by a small, highly conserved palindromic RNA motif, named DLS (dimer linkage sequence) [G. Cristofari, R. Ivanyi-Nagy, C. Gabus, S. Boulant, J. P. Lavergne, F. Penin and J. L. Darlix (2004) Nucleic Acids Res., 32, 2623–2631]. To investigate in depth HCV RNA dimerization, we generated a series of point mutations in the DLS region. We find that both the plus-strand 3′-UTR and the complementary minus-strand RNA can dimerize in the presence of core protein, while mutations in the DLS (among them a single point mutation that abolished RNA replication in a HCV subgenomic replicon system) completely abrogate dimerization. Structural probing of plus- and minus-strand RNAs, in their monomeric and dimeric forms, indicate that the DLS is the major if not the sole determinant of UTR RNA dimerization. Furthermore, the N-terminal basic amino acid clusters of core protein were found to be sufficient to induce dimerization, suggesting that they retain full RNA chaperone activity. These findings may have important consequences for understanding the HCV replicative cycle and the genetic variability of the virus

Citizen Science Time Domain Astronomy with Astro-COLIBRI

Astro-COLIBRI is an innovative tool designed for professional astronomers to facilitate the study of transient astronomical events. Transient events - such as supernovae, gamma-ray bursts and stellar mergers - are fleeting cataclysmic phenomena that can offer profound insights into the most violent processes in the universe. Revealing their secrets requires rapid and precise observations: Astro-COLIBRI alerts its users of new transient discoveries from observatories all over the world in real-time. The platform also provides observers the details they need to make follow-up observations. Some of the transient phenomena available through Astro-COLIBRI are accessible by amateur astronomers and citizen scientists. A subset of the features dedicated to this growing group of users are highlighted here. They include the possibility of receiving only alerts on very bright events, the possibility of defining custom observer locations, as well as the calculation of optimized observation plans for searches for optical counterparts to gravitational wave events.Comment: Proceedings Atelier Pro-AM Gemini, Journ\'ees SF2A 2023. arXiv admin note: text overlap with arXiv:2308.0704

The seasonal cycle of ocean-atmosphere CO2 Flux in Ryder Bay, West Antarctic Peninsula

Approximately 15 million km2 of the Southern Ocean is seasonally ice covered, yet the processes affecting carbon cycling and gas exchange in this climatically important region remain inadequately understood. Here, 3 years of dissolved inorganic carbon (DIC) measurements and carbon dioxide (CO2) fluxes from Ryder Bay on the west Antarctic Peninsula (WAP) are presented. During spring and summer, primary production in the surface ocean promotes atmospheric CO2 uptake. In winter, higher DIC, caused by net heterotrophy and vertical mixing with Circumpolar Deep Water, results in outgassing of CO2 from the ocean. Ryder Bay is found to be a net sink of atmospheric CO2 of 0.59–0.94 mol C m−2 yr−1 (average of 3 years). Seasonal sea ice cover increases the net annual CO2 uptake, but its effect on gas exchange remains poorly constrained. A reduction in sea ice on the WAP shelf may reduce the strength of the oceanic CO2 sink in this region

Decision process in large-scale crisis management

International audienceThis paper deals with the decision-aiding process in large-scale crisis such as natural disasters. It consists in four phases: decision context characterization, system modelling, aggregation and integration. The elements of the context, such as crisis level, risk situation, decision-maker problem issue are defined through the characterization phase. At the feared event occurrence, these elements will interact on a target system. Through the model on this system, the consequences to stakes could be assessed or estimated. The presented aggregation approaches will allow taking the right decisions. The architecture of a Decision Support System is presented in the integration phase

Charge and current-sensitive preamplifiers for pulse shape discrimination techniques with silicon detectors

New charge and current-sensitive preamplifiers coupled to silicon detectors and devoted to studies in nuclear structure and dynamics have been developed and tested. For the first time shapes of current pulses from light charged particles and carbon ions are presented. Capabilities for pulse shape discrimination techniques are demonstrated.Comment: 14 pages, 12 figures, to be published in Nucl. Inst. Meth.

Uncertainty information in climate data records from Earth observation

Climate data records (CDRs) derived from Earth observation (EO) should include rigorous uncertainty information, to support application of the data in policy, climate modelling and numerical weather prediction reanalysis. Uncertainty, error and quality are distinct concepts, and CDR products should follow international norms for presenting quantified uncertainty. Ideally, uncertainty should be quantified per datum in a CDR, and the uncertainty estimates should be able to discriminate more and less certain data with confidence. In this case, flags for data quality should not duplicate uncertainty information, but instead describe complementary information (such as the confidence held in the uncertainty estimate provided, or indicators of conditions violating retrieval assumptions). Errors have many sources and some are correlated across a wide range of time and space scales. Error effects that contribute negligibly to the total uncertainty in a single satellite measurement can be the dominant sources of uncertainty in a CDR on large space and long time scales that are highly relevant for some climate applications. For this reason, identifying and characterizing the relevant sources of uncertainty for CDRs is particularly challenging. Characterisation of uncertainty caused by a given error effect involves assessing the magnitude of the effect, the shape of the error distribution, and the propagation of the uncertainty to the geophysical variable in the CDR accounting for its error correlation properties. Uncertainty estimates can and should be validated as part of CDR validation, where possible. These principles are quite general, but the form of uncertainty information appropriate to different essential climate variables (ECVs) is highly variable, as confirmed by a quick review of the different approaches to uncertainty taken across different ECVs in the European Space Agency’s Climate Change Initiative. User requirements for uncertainty information can conflict with each other, and again a variety of solutions and compromises are possible. The concept of an ensemble CDR as a simple means of communicating rigorous uncertainty information to users is discussed. Our review concludes by providing eight recommendations for good practice in providing and communicating uncertainty in EO-based climate data records

Changes in global ocean bottom properties and volume transports in CMIP5 models under climate change scenarios

Changes in bottom temperature, salinity and density in the global ocean by 2100 for CMIP5 climate models are investigated for the climate change scenarios RCP4.5 and RCP8.5. The mean of 24 models shows a decrease in density in all deep basins except the North Atlantic which becomes denser. The individual model responses to climate change forcing are more complex: regarding temperature, the 24 models predict a warming of the bottom layer of the global ocean; in salinity, there is less agreement regarding the sign of the change, especially in the Southern Ocean. The magnitude and equatorward extent of these changes also vary strongly among models. The changes in properties can be linked with changes in the mean transport of key water masses. The Atlantic Meridional Overturning Circulation weakens in most models and is directly linked to changes in bottom density in the North Atlantic. These changes are due to the intrusion of modified Antarctic Bottom Water, made possible by the decrease in North Atlantic Deep Water formation. In the Indian, Pacific and South Atlantic, changes in bottom density are congruent with the weakening in Antarctic Bottom Water transport through these basins. We argue that the greater the 1986-2005 meridional transports, the more changes have propagated equatorwards by 2100. However, strong decreases in density over 100 years of climate change cause a weakening of the transports. The speed at which these property changes reach the deep basins is critical for a correct assessment of the heat storage capacity of the oceans as well as for predictions of future sea level rise

The programming of sequences of saccades

Saccadic eye movements move the high-resolution fovea to point at regions of interest. Saccades can only be generated serially (i.e., one at a time). However, what remains unclear is the extent to which saccades are programmed in parallel (i.e., a series of such moments can be planned together) and how far ahead such planning occurs. In the current experiment, we investigate this issue with a saccade contingent preview paradigm. Participants were asked to execute saccadic eye movements in response to seven small circles presented on a screen. The extent to which participants were given prior information about target locations was varied on a trial-by-trial basis: participants were aware of the location of the next target only, the next three, five, or all seven targets. The addition of new targets to the display was made during the saccade to the next target in the sequence. The overall time taken to complete the sequence was decreased as more targets were available up to all seven targets. This was a result of a reduction in the number of saccades being executed and a reduction in their saccade latencies. Surprisingly, these results suggest that, when faced with a demand to saccade to a large number of target locations, saccade preparation about all target locations is carried out in paralle

Measurement of CD4+ and CD8+ T-Lymphocyte Cytokine Secretion and Gene Expression Changes in p-Phenylenediamine Allergic Patients and Tolerant Individuals

Factors predisposing to individual susceptibility to contact allergic dermatitis are ill defined. This study was designed to characterize the response of allergic and tolerant individuals’ T-lymphocytes after exposure to p-phenylenediamine (PPD). Peripheral blood mononuclear cells (PBMCs) from allergic patients proliferated when treated with PPD and Bandrowski's base (BB) and secreted IL-1α, -1β, -4, -5, -6, -8, -10, and -13; IFN-γ; tumor necrosis factor-α; MIP-1α/β; MCP-1 (monocyte chemotactic protein-1); and RANTES. PBMCs from tolerant individuals were stimulated to proliferate only with BB, and they secreted significantly lower levels of Th2 cytokines. Principal component analysis showed that genes are differentially expressed between the patient groups. A network-based analysis of microarray data showed upregulation of T helper type 2 (Th2) gene pathways, including IL-9, in allergic patients, but a regulatory gene profile in tolerant individuals. Real-time PCR confirmed the observed increase in Th2 cytokine gene transcription in allergic patients. Purified CD4+ and CD8+ T cells from allergic patients were stimulated to proliferate and secrete Th2 cytokines following antigen exposure. Only CD4+ T cells from tolerant individuals were stimulated by BB, and levels of Th2 cytokines were 80% lower. The nature of the antigenic determinant stimulating PBMCs and levels of Th2 cytokines, including IL-9, was confirmed in a validation cohort. These studies show increased activity of Th2 cytokines in CD4+ and CD8+ T cells from individuals with allergic contact dermatitis