Collaborative participatory research as a learning process: the case of CIP and CARE in Peru

Participatory research (PR) has been analyzed and documented from different points of view, but particularly taking into consideration the benefits that this process generates for farmers. Studies of the benefits of PR for other actors such as field staff, researchers and organizations have been limited, with organizational learning receiving the least attention. This paper analyzes the interaction between the International Potato Center (CIP) and CARE in Peru and makes the case that PR can also contribute to creating a collaborative learning environment that generates important lessons for the individuals and organizations involved. The paper describes the evolution of the collaborative environment of these two institutions for more than a decade. Three interactive learning periods are presented, namely the “information transfer period” (1993 –1996) the “action-learning period” (1997-2002), and the “social learning period” (on-going). Several lessons from each period, as well as changes in institutional contexts and perceptions, are described. The CIP-CARE case shows that research and developmentoriented organizations can interact fruitfully using PR as a mechanism to promote learning, as well as flexibility in interaction and innovativeness, and that a process of osmosis of information occurs between groups that use PR in a specific case to other groups within the organizations, influencing behavior. However, the paper also indicates that institutional learning should be promoted more specifically in order to extract guidelines from the lessons, which can influence the way organizations plan and implement their projects in a constantly changing environment

CSIndicators: Get tailored climate indicators for applications in your sector

CSIndicators is an R package that gathers generalised methods for the flexible computation of climate-related indicators. Each method represents a specific mathematical approach which is combined with the possibility of selecting a flexible time period to define the indicator. This enables a wide range of possibilities for tailoring indicators to sectorial climate service applications. This package is intended for sub-seasonal, seasonal and decadal climate predictions, but its methods are also applicable to other time scales. Additionally, this package is compatible with the CSTools R package for climate forecast post-processing.This package was developed in the context of H2020 MED-GOLD (776467), S2S4E (776787), VITIGEOSS (869565) projects and Horizon Europe ASPECT project (101081460).Peer ReviewedPostprint (published version

Scalable Multi-Agent Reinforcement Learning for Warehouse Logistics with Robotic and Human Co-Workers

We envision a warehouse in which dozens of mobile robots and human pickers work together to collect and deliver items within the warehouse. The fundamental problem we tackle, called the order-picking problem, is how these worker agents must coordinate their movement and actions in the warehouse to maximise performance (e.g. order throughput). Established industry methods using heuristic approaches require large engineering efforts to optimise for innately variable warehouse configurations. In contrast, multi-agent reinforcement learning (MARL) can be flexibly applied to diverse warehouse configurations (e.g. size, layout, number/types of workers, item replenishment frequency), as the agents learn through experience how to optimally cooperate with one another. We develop hierarchical MARL algorithms in which a manager assigns goals to worker agents, and the policies of the manager and workers are co-trained toward maximising a global objective (e.g. pick rate). Our hierarchical algorithms achieve significant gains in sample efficiency and overall pick rates over baseline MARL algorithms in diverse warehouse configurations, and substantially outperform two established industry heuristics for order-picking systems

A Recoding Method to Improve the Humoral Immune Response to an HIV DNA Vaccine

This manuscript describes a novel strategy to improve HIV DNA vaccine design. Employing a new information theory based bioinformatic algorithm, we identify a set of nucleotide motifs which are common in the coding region of HIV, but are under-represented in genes that are highly expressed in the human genome. We hypothesize that these motifs contribute to the poor protein expression of gag, pol, and env genes from the c-DNAs of HIV clinical isolates. Using this approach and beginning with a codon optimized consensus gag gene, we recode the nucleotide sequence so as to remove these motifs without modifying the amino acid sequence. Transfecting the recoded DNA sequence into a human kidney cell line results in doubling the gag protein expression level compared to the codon optimized version. We then turn both sequences into DNA vaccines and compare induced antibody response in a murine model. Our sequence, which has the motifs removed, induces a five-fold increase in gag antibody response compared to the codon optimized vaccine

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 clustering of galaxies at z~0.5 in the SDSS-III Data Release 9 BOSS-CMASS sample: a test for the LCDM cosmology

We present results on the clustering of 282,068 galaxies in the Baryon Oscillation Spectroscopic Survey (BOSS) sample of massive galaxies with redshifts 0.4<z<0.7 which is part of the Sloan Digital Sky Survey III project. Our results cover a large range of scales from ~0.5 to ~90 Mpc/h. We compare these estimates with the expectations of the flat LCDM cosmological model with parameters compatible with WMAP7 data. We use the MultiDark cosmological simulation together with a simple halo abundance matching technique, to estimate galaxy correlation functions, power spectra, abundance of subhaloes and galaxy biases. We find that the LCDM model gives a reasonable description to the observed correlation functions at z~0.5, which is a remarkably good agreement considering that the model, once matched to the observed abundance of BOSS galaxies, does not have any free parameters. However, we find a deviation (>~10%) in the correlation functions for scales less than ~1 Mpc/h and ~10-40 Mpc/h. A more realistic abundance matching model and better statistics from upcoming observations are needed to clarify the situation. We also estimate that about 12% of the "galaxies" in the abundance-matched sample are satellites inhabiting central haloes with mass M>~1e14 M_sun/h. Using the MultiDark simulation we also study the real space halo bias b(r) of the matched catalogue finding that b=2.00+/-0.07 at large scales, consistent with the one obtained using the measured BOSS projected correlation function. Furthermore, the linear large-scale bias depends on the number density n of the abundance-matched sample as b=-0.048-(0.594+/-0.02)*log(n/(h/Mpc)^3). Extrapolating these results to BAO scales we measure a scale-dependent damping of the acoustic signal produced by non-linear evolution that leads to ~2-4% dips at ~3 sigma level for wavenumbers k>~0.1 h/Mpc in the linear large-scale bias.Comment: Replaced to match published version. Typos corrected; 25 pages, 17 figures, 9 tables. To appear in MNRAS. Correlation functions (projected and redshift-space) and correlation matrices of CMASS presented in Appendix B. Correlation and covariance data for the combined CMASS sample can be downloaded from http://www.sdss3.org/science/boss_publications.ph

Enhanced hemato-endothelial specification during human embryonic differentiation through developmental cooperation between AF4-MLL and MLL-AF4 fusions.

The t(4;11)(q21;q23) translocation is associated with high-risk infant pro-B-cell acute lymphoblastic leukemia and arises prenatally during embryonic/fetal hematopoiesis. The developmental/pathogenic contribution of the t(4;11)-resulting MLL-AF4 (MA4) and AF4-MLL (A4M) fusions remains unclear; MA4 is always expressed in patients with t(4;11)+ B-cell acute lymphoblastic leukemia, but the reciprocal fusion A4M is expressed in only half of the patients. Because prenatal leukemogenesis manifests as impaired early hematopoietic differentiation, we took advantage of well-established human embryonic stem cell-based hematopoietic differentiation models to study whether the A4M fusion cooperates with MA4 during early human hematopoietic development. Co-expression of A4M and MA4 strongly promoted the emergence of hemato-endothelial precursors, both endothelial- and hemogenic-primed. Double fusion-expressing hemato-endothelial precursors specified into significantly higher numbers of both hematopoietic and endothelial-committed cells, irrespective of the differentiation protocol used and without hijacking survival/proliferation. Functional analysis of differentially expressed genes and differentially enriched H3K79me3 genomic regions by RNA-sequencing and H3K79me3 chromatin immunoprecipitation-sequencing, respectively, confirmed a hematopoietic/endothelial cell differentiation signature in double fusion-expressing hemato-endothelial precursors. Importantly, chromatin immunoprecipitation-sequencing analysis revealed a significant enrichment of H3K79 methylated regions specifically associated with HOX-A cluster genes in double fusion-expressing differentiating hematopoietic cells. Overall, these results establish a functional and molecular cooperation between MA4 and A4M fusions during human hematopoietic development.Wellcome Trust, CRUK, Bloodwise, ERC, Generalitat de Catalunya, Spanish Ministry of Economy and Competitiveness, Spanish Association Against cancer, Health Institute Carlos III, NIHR GOSH BRC, Great Ormond Steet Hospital Children's Charity, Deutsche José Carreras Leukämie Stiftung, Obra Social La Caixa-Fundaciò Josep Carreras, Spanish Association of Cancer Researc

Assessment of mechanical properties of human head tissues for trauma modelling

[EN] Many discrepancies are found in the literature regarding the damage and constitutive models for head tissues as well as the values of the constants involved in the constitutive equations. Their proper definition is required for consistent numerical model performance when predicting human head behaviour, and hence skull fracture and brain damage. The objective of this research is to perform a critical review of constitutive models and damage indicators describing human head tissue response under impact loading. A 3D finite element human head model has been generated by using computed tomography images, which has been validated through the comparison to experimental data in the literature. The threshold values of the skull and the scalp that lead to fracture have been analysed. We conclude that (1) compact bone properties are critical in skull fracture, (2) the elastic constants of the cerebrospinal fluid affect the intracranial pressure distribution, and (3) the consideration of brain tissue as a nearly incompressible solid with a high (but not complete) water content offers pressure responses consistent with the experimental data.Generalitat Valenciana, Grant/Award Number: PROMETEO 2016/007; Ministerio de Economia y Compatitividad and Fondo Europeo de Desarrollo Regional, Grant/Award Number: RTC-2015-3887-8Lozano-Mínguez, E.; Palomar-Toledano, M.; Infante, D.; Rupérez Moreno, MJ.; Giner Maravilla, E. (2018). Assessment of mechanical properties of human head tissues for trauma modelling. International Journal for Numerical Methods in Biomedical Engineering. 34(5):1-17. https://doi.org/10.1002/cnm.2962S117345Hyder, A. A., Wunderlich, C. A., Puvanachandra, P., Gururaj, G., & Kobusingye, O. C. (2007). 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Head injury prediction capability of the HIC, HIP, SIMon and ULP criteria. Accident Analysis & Prevention, 40(3), 1135-1148. doi:10.1016/j.aap.2007.12.006Bolander, R., Mathie, B., Bir, C., Ritzel, D., & VandeVord, P. (2011). Skull Flexure as a Contributing Factor in the Mechanism of Injury in the Rat when Exposed to a Shock Wave. Annals of Biomedical Engineering, 39(10), 2550-2559. doi:10.1007/s10439-011-0343-0Li, G., Zhang, J., Wang, K., Wang, M., Gao, C., & Ma, C. (2016). Experimental research of mechanical behavior of porcine brain tissue under rotational shear stress. Journal of the Mechanical Behavior of Biomedical Materials, 57, 224-234. doi:10.1016/j.jmbbm.2015.12.002YOGANANDAN, N., PINTAR, F. A., SANCES, A., WALSH, P. R., EWING, C. L., THOMAS, D. J., & SNYDER, R. G. (1995). Biomechanics of Skull Fracture. Journal of Neurotrauma, 12(4), 659-668. doi:10.1089/neu.1995.12.659Motherway, J. A., Verschueren, P., Van der Perre, G., Vander Sloten, J., & Gilchrist, M. D. (2009). 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