Variability and power enhancement of current controlled resistive switching devices

Producción CientíficaIn this work, the unipolar resistive switching behaviour of Ni/HfO2/Si(n+) devices is studied. The structures are characterized using both current and voltage sweeps, with the device resistance and its cycle-to-cycle variability being analysed in each case. Experimental measurements indicate a clear improvement on resistance states stability when using current sweeps to induce both set and reset processes. Moreover, it has been found that using current to induce these transitions is more efficient than using voltage sweeps, as seen when analysing the device power consumption. The same results are obtained for devices with a Ni top electrode and a bilayer or pentalayer of HfO2/Al2O3 as dielectric. Finally, kinetic Monte Carlo and compact modelling simulation studies are performed to shed light on the experimental results.Junta de Andalucía - FEDER (B-TIC-624-UGR20)Consejo Superior de Investigaciones Científicas (CSIC) (project 20225AT012)Ramón y Cajal (grant RYC2020-030150-I

Strategies for GHG mitigation in Mediterranean cropping systems. A review

In this review we aimed to synthetize and analyze the most promising GHGs mitigation strategies for Mediterranean cropping systems. A description of most relevant measures, based on the best crop choice and management by farmers (i.e., agronomical practices), was firstly carried out. Many of these measures can be also efficient in other climatic regions, but here we provide particular results and discussion of their efficiencies for Mediterranean cropping systems. An integrated assessment of management practices on mitigating each component of the global warming potential (N2O and CH4 emissions and C sequestration) of production systems considering potential side-effects of their implementation allowed us to propose the best strategies to abate GHG emissions, while sustaining crop yields and mitigating other sources of environmental pollution (e.g. nitrate leaching and ammonia volatilization)

Strategies for greenhouse gas emissions mitigation in Mediterranean agriculture: A review

[EN] An integrated assessment of the potential of different management practices for mitigating specific components of the total GHG budget (N2O and CH4 emissions and C sequestration) of Mediterranean agrosystems was performed in this study. Their suitability regarding both yield and environmental (e.g. nitrate leaching and ammonia volatilization) sustainability, and regional barriers and opportunities for their implementation were also considered. Based on its results best strategies to abate GHG emissions in Mediterranean agro-systems were proposed. Adjusting N fertilization to crop needs in both irrigated and rain-fed systems could reduce N2O emissions up to 50% compared with a non-adjusted practice. Substitution of N synthetic fertilizers by solid manure can be also implemented in those systems, and may abate N2O emissions by about 20% under Mediterranean conditions, with additional indirect benefits associated to energy savings and positive effects in crop yields. The use of urease and nitrification inhibitors enhances N use efficiency of the cropping systems and may mitigate N2O emissions up to 80% and 50%, respectively. The type of irrigation may also have a great mitigation potential in the Mediterranean region. Drip-irrigated systems have on average 80% lower N2O emissions than sprinkler systems and drip-irrigation combined with optimized fertilization showed a reduction in direct N2O emissions up to 50%. Methane fluxes have a relatively small contribution to the total GHG budget of Mediterranean crops, which can mostly be controlled by careful management of the water table and organic inputs in paddies. Reduced soil tillage, improved management of crop residues and agro-industry by-products, and cover cropping in orchards, are the most suitable interventions to enhance organic C stocks in Mediterranean agricultural soils. The adoption of the proposed agricultural practices will require farmers training. The global analysis of life cycle emissions associated to irrigation type (drip, sprinkle and furrow) and N fertilization rate (100 and 300 kg N ha(-1) yr(-1)) revealed that these factors may outweigh the reduction in GHG emissions beyond the plot scale. The analysis of the impact of some structural changes on top-down mitigation of GHG emissions revealed that 3-15% of N2O emissions could be suppressed by avoiding food waste at the end-consumer level. A 40% reduction in meat and dairy consumption could reduce GHG emissions by 20-30%. Reintroducing the Mediterranean diet (i.e. similar to 35% intake of animal protein) would therefore result in a significant decrease of GHG emissions from agricultural production systems under Mediterranean conditions. (C) 2016 Elsevier B.V. All rights reserved.The authors would like to thank the Spanish National R+D+i Plan (AGL2012-37815-C05-01, AGL2012-37815-C05-04) and very specifically the workshop held in December 2016 in Butron (Bizkaia) to synthesize the most promising measures to reduce N2O emissions from Spanish agricultural soils. BC3 is sponsored by the Basque Government. M. L. Cayuela thanks Fundacion Seneca for financing the project 19281/PI/14.Sanz-Cobeña, A.; Lassaletta, L.; Aguilera, E.; Del Prado, A.; Garnier, J.; Billen, G.; Iglesias, A.... (2017). Strategies for greenhouse gas emissions mitigation in Mediterranean agriculture: A review. Agriculture Ecosystems & Environment. 238:5-24. https://doi.org/10.1016/j.agee.2016.09.038S52423

B-cell regeneration profile and minimal residual disease status in bone marrow of treated multiple myeloma patients

© 2021 by the authors.B-cell regeneration during therapy has been considered as a strong prognostic factor in multiple myeloma (MM). However, the effects of therapy and hemodilution in bone marrow (BM) B-cell recovery have not been systematically evaluated during follow-up. MM (n = 177) and adult (≥50y) healthy donor (HD; n = 14) BM samples were studied by next-generation flow (NGF) to simultaneously assess measurable residual disease (MRD) and residual normal B-cell populations. BM hemodilution was detected in 41 out of 177 (23%) patient samples, leading to lower total B-cell, B-cell precursor (BCP) and normal plasma cell (nPC) counts. Among MM BM, decreased percentages (vs. HD) of BCP, transitional/naïve B-cell (TBC/NBC) and nPC populations were observed at diagnosis. BM BCP increased after induction therapy, whereas TBC/NBC counts remained abnormally low. At day+100 postautologous stem cell transplantation, a greater increase in BCP with recovered TBC/NBC cell numbers but persistently low memory B-cell and nPC counts were found. At the end of therapy, complete response (CR) BM samples showed higher CD19− nPC counts vs. non-CR specimens. MRD positivity was associated with higher BCP and nPC percentages. Hemodilution showed a negative impact on BM B-cell distribution. Different BM B-cell regeneration profiles are present in MM at diagnosis and after therapy with no significant association with patient outcome.This work has been supported by the International Myeloma Foundation-Black Swan Research Initiative, the EuroFlow Consortium (grant LSHB-CT-2006-018708); Centro de Investigación Biomédica en Red de Cáncer (CIBER-ONC; Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER), numbers: CB16/12/00400, CB16/12/00233, CB16/12/00369, CB16/12/00489 and CB16/12/00480; grant from Bilateral Cooperation Program between Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES (Brasília/Brazil) and Dirección General de Políticas Universitárias (DGPU)-Ministério de Educación, Cultura y Deportes (Madrid/Spain) number DGPU 311/15; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro of Brazil (FAPERJ) numbers: E26/110.105/2014 and E26/102.191/2013; grant from Conselho Nacional de Desenvolvimento Científico e Tecnológico of Brazil (CNPQ), number: 400194/2014-7. R.M.d.P. was supported by a grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/DGPU), number: 000281/2016-06 and CAPES/PROEX 641/2018, Brazil; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro of Brazil (FAPERJ) number: E01/200/537/2018

Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

[EN]Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾107 cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.This work has been supported by the International Myeloma Foundation-Black Swan Research Initiative, the Red Temática de Investigación Cooperativa en Cáncer (RTICC); grant SA079U14 from the Consejería de Educación, Junta de Castilla y León, Valladolid, Spain and; grant DTS15/00119 from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain

Differential transcriptional profiling of damaged and intact adjacent dorsal root ganglia neurons in neuropathic pain

Neuropathic pain, caused by a lesion in the somatosensory system, is a severely impairing mostly chronic disease. While its underlying molecular mechanisms are not thoroughly understood, neuroimmune interactions as well as changes in the pain pathway such as sensitization of nociceptors have been implicated. It has been shown that not only are different cell types involved in generation and maintenance of neuropathic pain, like neurons, immune and glial cells, but, also, intact adjacent neurons are relevant to the process. Here, we describe an experimental approach to discriminate damaged from intact adjacent neurons in the same dorsal root ganglion (DRG) using differential fluorescent neuronal labelling and fluorescence-activated cell sorting (FACS). Two fluorescent tracers, Fluoroemerald (FE) and 1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate (DiI), were used, whose properties allow us to distinguish between damaged and intact neurons. Subsequent sorting permitted transcriptional analysis of both groups. Results and qPCR validation show a strong regulation in damaged neurons versus contralateral controls as well as a moderate regulation in adjacent neurons. Data for damaged neurons reveal an mRNA expression pattern consistent with established upregulated genes like galanin, which supports our approach. Moreover, novel genes were found strongly regulated such as corticotropinreleasing hormone (CRH), providing novel targets for further research. Differential fluorescent neuronal labelling and sorting allows for a clear distinction between primarily damaged neuropathic neurons and "bystanders," thereby facilitating a more detailed understanding of their respective roles in neuropathic processes in the DRG

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Inhibition of Specific NF-κB Activity Contributes to the Tumor Suppressor Function of 14-3-3σ in Breast Cancer

14-3-3σ is frequently lost in human breast cancers by genetic deletion or promoter methylation. We have now investigated the involvement of 14-3-3σ in the termination of NF-κB signal in mammary cells and its putative role in cancer relapse and metastasis. Our results show that 14-3-3σ regulates nuclear export of p65-NF-κB following chronic TNFα stimulation. Restoration of 14-3-3σ in breast cancer cells reduces migration capacity and metastatic abilities in vivo. By microarray analysis, we have identified a genetic signature that responds to TNFα in a 14-3-3σ-dependent manner and significantly associates with different breast and other types of cancer. By interrogating public databases, we have found that over-expression of this signature correlates with poor relapse-free survival in breast cancer patients. Finally, screening of 96 human breast tumors showed that NF-κB activation strictly correlates with the absence of 14-3-3σ and it is significantly associated with worse prognosis in the multivariate analysis. Our findings identify a genetic signature that is important for breast cancer prognosis and for future personalized treatments based on NF-κB targeting