IODP Drilling of the "Shackleton Sites" on the Iberian Margin: A Plio-Pleistocene Marine Reference Section of Millennial-Scale Climate Change

Few marine sediment cores have played such a pivotal role in paleoclimate research as those recovered from the Portuguese Margin, including MD95-2039 to MD95-2042 (hereafter referred to as the “Shackleton sites”) (Fig. 1). These cores preserve a high-fidelity record of millennial-scale climate variability for the last several glacial cycles and can be readily correlated to Greenland ice cores. Moreover, the narrow continental shelf and proximity of the Tagus River results in rapid delivery of terrestrial material to the deep-sea environment, thereby permitting correlation of marine and ice-core records to European terrestrial sequences. Few places exist in the world’s ocean where such marine-ice-terrestrial linkages are possible. Consequently, the Iberian Margin cores have become de facto reference sections for the study of abrupt climate change

Étude et réalisation de sources photoniques intégrées sur InP pour les applications télécoms à hauts débits et à 1,55 m

Les formats de modulation avancés, codant l information sur la phase, la polarisation ou plusieurs niveaux d amplitude de la lumière reçoivent aujourd hui un intérêt croissant. En effet, ceux-ci permettent d atteindre une meilleure efficacité spectrale et par conséquent des débits plus élevés. Ces caractéristiques sont actuellement très recherchées dans les télécommunications pour répondre à la demande constante d augmentation de capacité des transmissions optiques fibrées. L essentiel du travail effectué porte sur la génération de tels signaux dans des sources photoniques monolithiques sur InP faisant appel à un concept nouveau de commutation de phases optiques préfixées avec des modulateurs électro-absorbants. Une comparaison de notre technologie intégrée avec la technologie actuelle de génération de formats de modulation avancés démontre des possibilités nouvelles de réduction de taille, de diminution de consommation énergétique et d évolution en vitesse de modulation jusqu à 56 GBauds. Suite à la validation, par simulations, d architectures de transmetteurs spécifiques pour la génération de formats de modulation avancés, nous réalisons en salle blanche les circuits photoniques intégrés d étude. Les caractérisations statiques confirment le fonctionnement de toutes les fonctions intégrées des circuits et soulignent l efficacité de la filière technologique. Pour une première démonstration de fonctionnalité nous choisissons un transmetteur BPSK capable de générer une modulation de phase à 12,4 GB. Ce résultat démontre la plus petite source intégrée BPSK à l heure actuelle. Un autre circuit capable de générer des formats de modulation plus complexes est aussi caractériséAdvanced modulation formats, encoding data on the phase, polarization or multi-level intensity of the light are currently a hot topic in the telecommunication domain. By using them, high spectral efficiency and therefore higher bit rate signals could be generated. Those characteristics are really attractive for the telecommunication systems manufacturers in order to answer to the constant need of increased bandwidth in fiber optic communications. The study of advanced modulation formats generation in Photonic Integrated Circuits (PICs) based on a new concept of preset phases switching by Electro-Absorption Modulators is the main task of the current work. Compared to the actual technology used for generate advanced modulations, our choice could allow a strong reduction of the dimensions and of the energy consumption of the transmitter as well as bit rate up to 56 GB. After validating specific transmitters architectures by simulations, we fabricated the studied photonic integrated circuits in clean room. Through static characterizations, we verify that all integrated functions of the transmitters are working and we show the efficiency of our technological choices. Using the available equipments at the lab, we prove the validity of our concept of EAM based phase switching by using a BPSK transmitter. A 12.4 GB BPSK modulation is obtained as well as a wide open eye diagram. This result demonstrates the smallest BPSK integrated photonic source at this time. Another photonic circuit able to generate more complex modulation formats is also measuredEVRY-INT (912282302) / SudocSudocFranceF

Golgi anti-apoptotic proteins are highly conserved ion channels that affect apoptosis and cell migration.

Golgi anti-apoptotic proteins (GAAPs) are multitransmembrane proteins that are expressed in the Golgi apparatus and are able to homo-oligomerize. They are highly conserved throughout eukaryotes and are present in some prokaryotes and orthopoxviruses. Within eukaryotes, GAAPs regulate the Ca(2+) content of intracellular stores, inhibit apoptosis, and promote cell adhesion and migration. Data presented here demonstrate that purified viral GAAPs (vGAAPs) and human Bax inhibitor 1 form ion channels and that vGAAP from camelpox virus is selective for cations. Mutagenesis of vGAAP, including some residues conserved in the recently solved structure of a related bacterial protein, BsYetJ, altered the conductance (E207Q and D219N) and ion selectivity (E207Q) of the channel. Mutation of residue Glu-207 or -178 reduced the effects of GAAP on cell migration and adhesion without affecting protection from apoptosis. In contrast, mutation of Asp-219 abrogated the anti-apoptotic activity of GAAP but not its effects on cell migration and adhesion. These results demonstrate that GAAPs are ion channels and define residues that contribute to the ion-conducting pore and affect apoptosis, cell adhesion, and migration independently.This work was supported by the United Kingdom Medical Research Council, the Biotechnology and Biological Sciences Research Council, and the Wellcome TrustThis is the final published version. It first appeared at http://www.jbc.org/content/290/18/11785.long

Validación de productos MODIS relacionados con la estimación de flujos de carbono en un ecosistema de dehesa

En este trabajo se validan diferentes productos MODIS a partir de mediciones de campo. Se ha empleado una serie temporal de los productos de índice de vegetación de diferencia normalizada (NDVI, MOD/MYD13Q1), índice de área foliar (LAI, MOD/MYD/MCD15A2) y productividad primaria bruta (GPP, MOD/MY17A2) adquiridos entre los años 2009 y 2011 en una dehesa de Cáceres que dispone de una torre de medición de flujos incluida en la red internacional FLUXNET. Los resultados obtenidos muestran correlaciones significativas (P-valor<0,01) para NDVI (r2=0,91), LAI (r2=0,73) y GPP (r2=0,79). A pesar de que MODIS recoge bien las dinámicas temporales en el ecosistema, se observaron importantes diferencias, el error medio cuadrático relativo (RRMSE) fue menor para el NDVI (7,5%) que para los productos más complejos LAI (30,1%) y GPP (59,5%).Este trabajo ha sido financiado por el Ministerio de Economía y Competitividad a través de los proyecto Biospec (CGL2008-02301/CLI) y Fluxpec (CGL2012-34383) y por el CSIC a través del programa JAE-TECPeer reviewe

The spread of chloramphenicol-resistant Neisseria meningitidis in Southeast Asia.

OBJECTIVES: Invasive disease caused by Neisseria meningitidis is a significant health concern globally, but our knowledge of the prevailing serogroups, antimicrobial susceptibility patterns, and genetics of N. meningitidis in Southeast Asia is limited. Chloramphenicol resistance in N. meningitidis has rarely been reported, but was first described in isolates from Vietnam in 1998. We aimed to characterise eight chloramphenicol resistant meningococcal isolates collected between 2007 and 2018 from diagnostic microbiology laboratories in Cambodia, Thailand and the Lao People's Democratic Republic (Laos). METHODS: Whole-genome sequencing was used to generate genome sequences from 18 meningococcal isolates including the eight chloramphenicol resistant isolates. We identified antimicrobial resistance genes present in these strains, and examined the phylogenetic relationships between strains. RESULTS: The eight resistant strains all contain the same chloramphenicol resistance gene first described in 1998, and are closely related to each other. Strains resistant to penicillin, tetracycline, and ciprofloxacin were also observed, including a chloramphenicol-resistant strain which has acquired penicillin and ciprofloxacin resistance. CONCLUSIONS: This study suggests that chloramphenicol-resistant N. meningitidis is more widespread than previously thought, and that the previously-identified resistant lineage is now found in multiple countries in Southeast Asia

Design of a Trispecific Checkpoint Inhibitor and Natural Killer Cell Engager Based on a 2 + 1 Common Light Chain Antibody Architecture

Natural killer cell engagers gained enormous interest in recent years due to their potent anti-tumor activity and favorable safety profile. Simultaneously, chicken-derived antibodies entered clinical studies paving the way for avian-derived therapeutics. In this study, we describe the affinity maturation of a common light chain (cLC)-based, chickenderived antibody targeting EGFR, followed by utilization of the same light chain for the isolation of CD16a- and PD-L1-specific monoclonal antibodies. The resulting binders target their respective antigen with single-digit nanomolar affinity while blocking the ligand binding of all three respective receptors. Following library-based humanization, bispecific and trispecific variants in a standard 1 + 1 or a 2 + 1 common light chain format were generated, simultaneously targeting EGFR, CD16a, and PD-L1. The trispecific antibody mediated an elevated antibody-dependent cellular cytotoxicity (ADCC) in comparison to the EGFR×CD16a bispecific variant by effectively bridging EGFR/PD-L1 double-positive cancer cells with CD16a-positive effector cells. These findings represent, to our knowledge, the first detailed report on the generation of a trispecific 2 + 1 antibodies exhibiting a common light chain and illustrate synergistic effects of trispecific antigen binding. Overall, this generic procedure paves the way for the engineering of tri- and oligospecific therapeutic antibodies derived from avian immunizations

Exploring pathways of solar PV learning-by-doing in Integrated Assessment Models

International audienc

Heatwave breaks down the linearity between sun-induced fluorescence and gross primary production

Sun-induced fluorescence in the far-red region (SIF) is increasingly used as a remote and proximal-sensing tool capable of tracking vegetation gross primary production (GPP). However, the use of SIF to probe changes in GPP is challenged during extreme climatic events, such as heatwaves. Here, we examined how the 2018 European heatwave (HW) affected the GPP-SIF relationship in evergreen broadleaved trees with a relatively invariant canopy structure. To do so, we combined canopy-scale SIF measurements, GPP estimated from an eddy covariance tower, and active pulse amplitude modulation fluorescence. The HW caused an inversion of the photosynthesis-fluorescence relationship at both the canopy and leaf scales. The highly nonlinear relationship was strongly shaped by nonphotochemical quenching (NPQ), that is, a dissipation mechanism to protect from the adverse effects of high light intensity. During the extreme heat stress, plants experienced a saturation of NPQ, causing a change in the allocation of energy dissipation pathways towards SIF. Our results show the complex modulation of the NPQ-SIF-GPP relationship at an extreme level of heat stress, which is not completely represented in state-of-the-art coupled radiative transfer and photosynthesis models.Peer reviewe

Artesunate-mefloquine combination therapy in acute Plasmodium falciparum malaria in young children: a field study regarding neurological and neuropsychiatric safety

BACKGROUND: Mefloquine-artesunate combination therapy for uncomplicated falciparum malaria is one of the treatments used in African children. Data concerning neurological safety in adults and children treated with mefloquine and artesunate combination therapy is well documented in Asia. Safety data for neurological and neuropsychiatric side effects of mefloquine and artesunate combination therapy in African children are scarce, although WHO recommends this therapy in Africa. METHODS: A phase IV, open label, single arm study was conducted among African children between 10 and 20 kg with acute uncomplicated falciparum malaria. They were treated over three consecutive days with a paediatric fixed-dose combination of artesunate (50 mg/d) and mefloquine (125 mg/d). Parasitological, clinical and neurological examinations and standardized questions about neuropsychiatric symptoms were carried out on days 0, 4, 7, 28 and 63. The primary objective was to assess the neurological and neuropsychiatric safety of artesunate-mefloquine combination therapy in young children. RESULTS: From December 2007 to March 2009, 220 children with uncomplicated Plasmodium falciparum malaria were treated with artesunate and mefloquine. 213 children were analysed according to study protocol. 50 neurological and neuropsychiatric adverse events occurred in 28 patients. Eleven drug-related neurological and neuropsychiatric adverse events occurred in eight patients. Sleeping disorders were present in 2.3%, neurological disorders in 1.4%, neuropsychiatric disorders in 1% and eating disorders in 0.5% of the patients. Adverse events were of mild to moderate intensity and resolved spontaneously. CONCLUSION: African children showed a low percentage of self-limited neurological and neuropsychiatric adverse events, confirming studies on neurological safety in Asian children treated with artesunate and mefloquine. Sleeping disorders were most frequently observed