Evolución cuaternaria del drenaje en un corredor intramontano: La Canal de Navarrés (Valencia, Spain)

[Resumen] Este artículo analiza la evolución actual y del Cuaternario reciente de la red de drenaje en una fosa intramontana del macizo del Caroig (Valencia). De la información bibliográfica, el análisis geomorfológico y el registro sedimentario obtenido por sondeo mecánico, acompañado de dataciones absolutas C14 y TL, se concluye que claros signos de precariedad en la organización de la red han perdurado, si bien a menor escala, hasta la actualidad[Abstract] This paper is about the drainage network evolution during the Holocene and Late Quaternary in the rift valley of the Caroig massif (Valencia). Geological and geomorphological studies showed halocinesis movements in this graben. Sorne other processes, for instance, aIluvial and coIluvial deposition, moreover lithochemical and biochemical sedimention occured at the same time. The core sediment analysis and C14 and TL datations, allow us to conclude that in this zone, the disruption of the quaternary drainage network persists at the present time, eventhough it is less evident.Dirección General de Investigación Científica y Técnica; PB91-089

City of dreams

Higher ability workers benefit more from bigger cities while housing costs there are higher for everyone, and yet there is little sorting on ability. A possible explanation is that young individuals have an imperfect assessment of their ability, and, when they learn about it, early decisions have had a lasting impact and reduce their incentives to move. We formalize this idea through an overlapping generations model of urban sorting by workers with heterogenous ability and self-confidence, with the latter defined as individuals’ assessment of their own ability. We then test the location patterns predicted by the model over the life cycle on panel data from the National Longitudinal Survey of Youth 1979. We find that the city-size choices of individuals at different stages vary with ability and self-confidence in a way that closely matches our theoretical predictions

Grain size effect on the thermal-induced martensitic transformation in polycrystalline Cu-based shape memory alloys

In Cu-based SMA alloys, the grain size (d) effect on the martensitic transformation temperature was investigated for a wide range of d. Specimens were prepared by different heat treatments in order to create a range of grain sizes, from about 500 nm (ribbons and tapes obtained by rapid solidification techniques) up to 6 mm diameter single-crystals (grown by the Bridgman method). Information obtained from the literature was also included in the set of analyzed experimental data. The reduction of grain size shifts the forward transformation temperature downwards. These grain-size effects are observed in specimens with d below ∼ 100 μm, and become more pronounced for d below ∼ 20 μm. An empirical expression was obtained that describes the grain-size effect over the whole temperature range. The obtained curve differs considerably from the Hall-Petch behaviour reported in the literature by some other investigators.Fil: la Roca, Paulo Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Física de Rosario (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura; ArgentinaFil: Isola, Lucio Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Física de Rosario (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura; ArgentinaFil: Sobrero, Cesar Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Física de Rosario (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura; ArgentinaFil: Vermaut, P.. Ecole Nationale Superieure de Chimie de Paris; FranciaFil: Malarria, Jorge Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Física de Rosario (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura; Argentin

Mesoscopic structure conditions the emergence of cooperation on social networks

We study the evolutionary Prisoner's Dilemma on two social networks obtained from actual relational data. We find very different cooperation levels on each of them that can not be easily understood in terms of global statistical properties of both networks. We claim that the result can be understood at the mesoscopic scale, by studying the community structure of the networks. We explain the dependence of the cooperation level on the temptation parameter in terms of the internal structure of the communities and their interconnections. We then test our results on community-structured, specifically designed artificial networks, finding perfect agreement with the observations in the real networks. Our results support the conclusion that studies of evolutionary games on model networks and their interpretation in terms of global properties may not be sufficient to study specific, real social systems. In addition, the community perspective may be helpful to interpret the origin and behavior of existing networks as well as to design structures that show resilient cooperative behavior.Comment: Largely improved version, includes an artificial network model that fully confirms the explanation of the results in terms of inter- and intra-community structur

NG2 antigen is a therapeutic target for MLL-rearranged B-cell acute lymphoblastic leukemia

Altres ajuts: This work has been supported by the Asociación Española Contra el Cáncer (AECC), Beca FERO, and OM are supported by postdoctoral fellowships from the AECC scientific foundation and the Catalunya Government (Beatriu de Pinos, BP00048), respectively. PM also acknowledges the financial support from the Obra Social La Caixa-Fundaciò Josep Carreras and "Premio Miguelín".B cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer, with cure rates of ∼80%. MLL-rearranged (MLLr) B-ALL (MLLr-B-ALL) has, however, an unfavorable prognosis with common therapy refractoriness and early relapse, and therefore new therapeutic targets are needed for relapsed/refractory MLLr-B-ALL. MLLr leukemias are characterized by the specific expression of chondroitin sulfate proteoglycan-4, also known as neuron-glial antigen-2 (NG2). NG2 was recently shown involved in leukemia invasiveness and central nervous system infiltration in MLLr-B-ALL, and correlated with lower event-free survival (EFS). We here hypothesized that blocking NG2 may synergize with established induction therapy for B-ALL based on vincristine, glucocorticoids, and l-asparaginase (VxL). Using robust patient-derived xenograft (PDX) models, we found that NG2 is crucial for MLLr-B-ALL engraftment upon intravenous (i.v.) transplantation. In vivo blockade of NG2 using either chondroitinase-ABC or an anti-NG2-specific monoclonal antibody (MoAb) resulted in a significant mobilization of MLLr-B-ALL blasts from bone marrow (BM) to peripheral blood (PB) as demonstrated by cytometric and 3D confocal imaging analysis. When combined with either NG2 antagonist, VxL treatment achieved higher rates of complete remission, and consequently higher EFS and delayed time to relapse. Mechanistically, anti-NG2 MoAb induces neither antibody-dependent cell-mediated not complement-dependent cytotoxicity. NG2 blockade rather overrides BM stroma-mediated chemoprotection through PB mobilization of MLLr-B-ALL blasts, thus becoming more accessible to chemotherapy. We provide a proof of concept for NG2 as a therapeutic target for MLLr-B-ALL

Robustness of dead Cas9 activators in human pluripotent and mesenchymal stem cells

Human pluripotent stem cells (hPSCs) and mesenchymal stromal/stem cells (hMSCs) are clinically relevant sources for cellular therapies and for modeling human development and disease. Many stem cell-based applications rely on the ability to activate several endogenous genes simultaneously to modify cell fate. However, genetic intervention of these cells remains challenging. Several catalytically dead Cas9 (dCas9) proteins fused to distinct activation domains can modulate gene expression when directed to their regulatory regions by a specific single-guide RNA (sgRNA). In this study, we have compared the ability of the first-generation dCas9-VP64 activator and the second-generation systems, dCas9-SAM and dCas9-SunTag, to induce gene expression in hPSCs and hMSCs. Several stem cell lines were tested for single and multiplexed gene activation. When the activation of several genes was compared, all three systems induced specific and potent gene expression in both single and multiplexed settings, but the dCas9-SAM and dCas9-SunTag systems resulted in the highest and most consistent level of gene expression. Simultaneous targeting of the same gene with multiple sgRNAs did not result in additive levels of gene expression in hPSCs nor hMSCs. We demonstrate the robustness and specificity of second-generation dCas9 activators as tools to simultaneously activate several endogenous genes in clinically relevant human stem cells.We thank CERCA/Generalitat de Catalunya and Fundació Josep Carreras-Obra Social la Caixa for their institutional support. We thank Jose Luis Sardina (IJC, Barcelona) for technical assistance with the teratoma assays. Financial support for this work was obtained from the Catalunya Goverment (SGR330 and PERIS 2017-2019), the Spanish Ministry of Economy and Competitiveness (SAF2016-80481-R), the European Research Council (CoG-2014-646903), and the Fundación Leo Messi to P.M.; the Spanish Association against Cancer (AECC-CI-2015) and the Health Institute Carlos III (ISCIII/FEDER, PI17/01028) to C.B.; the Biotechnology and Biological Sciences Research Council (BBRSC) to L.M.F. and A.F.; and the Spanish National Research and Development Plan (ISCIII/FEDER, PI17/02303) and the AEI/MICIU EXPLORA Project (BIO2017-91272-EXP) to S.R.-P. P.M. is an investigator of the Spanish Cell Therapy Cooperative Network (TERCEL). R.T.-R. is supported by a postdoctoral fellowship from the Asociación Española Contra el Cáncer (AECC).S

The Roles of the S3MPC: Monitoring, Validation and Evolution of Sentinel-3 Altimetry Observations

The Sentinel-3 Mission Performance Centre (S3MPC) is tasked by the European Space Agency (ESA) to monitor the health of the Copernicus Sentinel-3 satellites and ensure a high data quality to the users. This paper deals exclusively with the effort devoted to the altimeter and microwave radiometer, both components of the Surface Topography Mission (STM). The altimeters on Sentinel-3A and -3B are the first to operate in delay-Doppler or SAR mode over all Earth surfaces, which enables better spatial resolution of the signal in the along-track direction and improved noise reduction through multi-looking, whilst the radiometer is a two-channel nadir-viewing system. There are regular routine assessments of the instruments through investigation of telemetered housekeeping data, calibrations over selected sites and comparisons of geophysical retrievals with models, in situ data and other satellite systems. These are performed both to monitor the daily production, assessing the uncertainties and errors on the estimates, and also to characterize the long-term performance for climate science applications. This is critical because an undetected drift in performance could be misconstrued as a climate variation. As the data are used by the Copernicus Services (e.g., CMEMS, Global Land Monitoring Services) and by the research community over open ocean, coastal waters, sea ice, land ice, rivers and lakes, the validation activities encompass all these domains, with regular reports openly available. The S3MPC is also in charge of preparing improvements to the processing, and of the development and tuning of algorithms to improve their accuracy. This paper is thus the first refereed publication to bring together the analysis of SAR altimetry across all these different domains to highlight the benefits and existing challenges

Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures

Generosity Pays in the Presence of Direct Reciprocity: A Comprehensive Study of 2×2 Repeated Games

By applying a technique previously developed to study ecosystem assembly [Capitán et al., Phys. Rev. Lett. 103, 168101 (2009)] we study the evolutionary stable strategies of iterated 22 games. We focus on memory-one strategies, whose probability to play a given action depends on the actions of both players in the previous time step. We find the asymptotically stable populations resulting from all possible invasions of any known stable population. The results of this invasion process are interpreted as transitions between different populations that occur with a certain probability. Thus the whole process can be described as a Markov chain whose states are the different stable populations. With this approach we are able to study the whole space of symmetric 22 games, characterizing the most probable results of evolution for the different classes of games. Our analysis includes quasi-stationary mixed equilibria that are relevant as very long-lived metastable states and is compared to the predictions of a fixation probability analysis. We confirm earlier results on the success of the Pavlov strategy in a wide range of parameters for the iterated Prisoner's Dilemma, but find that as the temptation to defect grows there are many other possible successful strategies. Other regions of the diagram reflect the equilibria structure of the underlying one-shot game, albeit often some non-expected strategies arise as well. We thus provide a thorough analysis of iterated 22 games from which we are able to extract some general conclusions. Our most relevant finding is that a great deal of the payoff parameter range can still be understood by focusing on win-stay, lose-shift strategies, and that very ambitious ones, aspiring to obtaining always a high payoff, are never evolutionary stable