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Background and objectives: mRNA vaccines elicit a durable humoral response to SARS-CoV-2 in adults, whereas evidence in children is scarce. This study aimed to assess the early and long-term immune response to the mRNA vaccine in children with or without previous SARS-CoV-2 infection. Methods: In a multicentre prospective observational study, we profiled the immune response to the Pfizer BioNTech (BNT162b2) vaccine in 5-11-year-old children attending the University Pediatric Hospital of Padua and Bambino-Gesu Hospital in Rome (Italy) from December-2021 to February-2023. Blood samples were collected pre-, 1-, and 6-months after vaccination. Neutralizing antibodies (NAbs) and anti-spike-receptor-binding-domain (anti-S-RBD) IgG titers were analyzed through Plaque Reduction Neutralization Test (PRNT) and chemiluminescent immune-enzymatic assay (CLIA), respectively. Immune cell phenotypes were analyzed by flow cytometry. Results: Sixty children (26 [43 %] female, median age = 8 years [IQR = 7-10.7]) were enrolled in the study, including 46 children with a laboratory-confirmed previous COVID-19 (SARS-CoV-2-recovered) and 14 SARS CoV-2-naive participants defined as the absence of antigen-specific antibodies before vaccination. SARS-CoV-2recovered participants recorded higher anti-S-RBD IgG and Wild-type and Omicron BA.2 NAbs titers than SARSCoV-2-naive participants at both 1- and 6-months after vaccination. Antibody titers correlated with T (Tregs) and B (Bregs) regulatory cell frequencies in SARS-CoV-2-recovered children. Both SARS-CoV-2-recovered and SARSCoV-2-naive participants decreased antibody titers by approximately 100 to 250 % from 1 to 6 months. While children with immunocompromising underlying conditions developed immune responses comparable to those of healthy children, solid organ transplant recipients exhibited lower levels of NAbs and anti-S-RBD IgG titers, as well as reduced frequencies of Tregs and Bregs. Conclusions: mRNA vaccination triggered a higher pr

BACKGROUND: Recent evidence suggests that neutralizing antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 may persist over time; however, knowledge regarding pediatric subjects is limited. METHODS: A single-center, prospective observational study was conducted on 57 family clusters of coronavirus disease 2019, including children of neonatal and pediatric age attending the University Hospital of Padua (Italy). For each patient, blood samples were collected for both the quantification of nAbs through a plaque reduction neutralizing test and the detection of antinucleocapsid-spike protein immunoglobulin G and/or immunoglobulin M. RESULTS: We analyzed 283 blood samples collected from 152 confirmed coronavirus disease 2019 cases (82 parents and 70 children or older siblings of median age of 8 years, interquartile range: 4–13), presenting asymptomatic or with mildly symptomatic disease. Despite the decrease of immunoglobulin G over time, nAbs were found to persist up to 7 to 8 months in children, whereas adults recorded a modest declining trend. Interestingly, children aged <6 years, and, in particular, those aged <3 years, developed higher long-lasting levels of nAbs compared with older siblings and/or adults. CONCLUSIONS: Mild and asymptomatic severe acute respiratory syndrome coronavirus 2 infections in family clusters elicited higher nAbs among children.

Liver transplanted (LT) patients for hepatocellular carcinoma (LT-HCC) or for other causes (LT-no-HCC) may develop post-transplantation malignancies. Although immune activation and senescence are frequently implicated in cancer development, no data is available on their possible role as biomarkers predictive of tumor onset in this setting. A total of 116 patients were investigated: the 45 LT-HCC patients were older than the 71 LT-non-HCC (p=0.011), but comparable for sex, HCV, HBV infection and immunosuppressive treatment. At baseline, the numbers of activated and senescent-like circulating cells were significantly higher in LT-HCC patients than in LT-no-HCC ones. After a median follow-up of 26.8 months, 6 post-transplant malignancies (PTM) occurred: 4 in LT-HCC (8.9%) and 2 in LT-no-HCC (2.8%) patients. Overall, subjects with high percentages of activated and exhausted T and B cells at baseline were at higher risk of PTM. Notably, within the LT-HCC group, a higher percentage of senescence-like T cells was also associated with cancer development. Moreover, patients with PTM had higher telomere erosion and higher levels of circulating PAMPs (16S rDNA) and DAMPs (mtDNA) when compared with matched patients without PTM. Overall, these findings suggest that immune activation and exhaustion may be useful to predict the risk of PTM occurrence, regardless of the cause of transplantation. In LT-HCC, T-cell senescence represents an additional risk factor for tumor onset.

Importance: Understanding the long-term immune response against SARS-CoV-2 infection in children is crucial to optimize vaccination strategies. Although it is known that SARS-CoV-2 antibodies may persist in adults 12 months after infection, data are limited in the pediatric population. Objective: To examine long-term anti-SARS-CoV-2 spike receptor-binding domain (S-RBD) IgG kinetics in children after SARS-CoV-2 infection. Design, Setting, and Participants: In this single-center, prospective cohort study, patients were enrolled consecutively from April 1, 2020, to August 31, 2021, at the COVID-19 Family Cluster Follow-up Clinic, Department of Women's and Children's Health, University Hospital of Padua. A cohort of 252 COVID-19 family clusters underwent serologic follow-up at 1 to 4, 5 to 10, and more than 10 months after infection with quantification of anti-S-RBD IgG by chemiluminescent immunoassay. Exposures: SARS-CoV-2 infection. Results: Among 902 study participants, 697 had confirmed SARS-CoV-2 infection, including 351 children or older siblings (mean [SD] age, 8.6 [5.1] years) and 346 parents (mean [SD] age, 42.5 [7.1] years). Among 697 cases, 674 (96.7%) were asymptomatic or mild. Children had significantly higher S-RBD IgG titers than older patients across all follow-up time points, with an overall median S-RBD IgG titer in patients younger than 3 years 5-fold higher than adults (304.8 [IQR, 139.0-516.6] kBAU/L vs 55.6 [24.2-136.0] kBAU/L, P <.001). Longitudinal analysis of 56 study participants sampled at least twice during follow-up demonstrated the persistence of antibodies up to 10 months from infection in all age classes, despite a progressive decline over time. Conclusions and Relevance: In this cohort study of Italian children and adults following SARS-CoV-2 infection different kinetics of SARS-CoV-2 antibodies were found across several age classes of individuals with asymptomatic or mild COVID-19, which could help in optimizing COVID-19 vaccination

Background: The immune response plays a pivotal role in dictating the clinical outcome in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected adults, but it is still poorly investigated in the pediatric population. Methods: Of 209 enrolled subjects, 155 patients were confirmed by PCR and/or serology as having coronavirus disease 2019 (COVID-19). Blood samples were obtained at a median of 2.8 (interquartile, 2.1–3.7) and 6.1 (5.3–7.2) months after baseline (symptom onset and/or first positive virus detection). The immune profiles of activation, senescence, exhaustion, and regulatory cells were analyzed by flow cytometry. Neutralizing antibodies (nAbs) were detected by a plaque reduction neutralization test. In available nasopharyngeal swabs at baseline, SARS-CoV-2 levels were quantified by digital droplet PCR (ddPCR). Results: Overall, COVID-19 patients had higher levels of immune activation, exhaustion, and regulatory cells compared to non-COVID-19 subjects. Within the COVID-19 group, activated and senescent cells were higher in adults than in children and inversely correlated with the nAbs levels. Conversely, Tregs and Bregs regulatory cells were higher in COVID-19 children compared to adults and positively correlated with nAbs. Higher immune activation still persisted in adults after 6 months of infection, while children maintained higher levels of regulatory cells. SARS-CoV-2 levels did not differ among age classes. Conclusions: Adults displayed higher immune activation and lower production of anti-SARS-CoV-2 nAbs than children. The different immune response was not related to different viral load. The higher expression of regulatory cells in children may contribute to reduce the immune activation, thus leading to a greater specific response against the virus.

Resumen Introducción: El Tumor inflamatorio de Pott es una complicación rara de una patología frecuente, como son los cuadros infecciosos sinusales, cada vez más inusual por el uso extendido de antibióticos de amplio espectro, es más frecuente en la población adolescente por la neumatización similar al adulto. Se presenta como un aumento de volumen blando a nivel frontal con una osteomielitis del hueso frontal y un absceso subperióstico. Materiales y métodos: En este trabajo, se presenta una revisión bibliográfica del tema y un caso de un paciente de 9 años, quien cursó con un cuadro infeccioso sinusal, que posterior desarrollo un aumento de volumen frontal, mostrando las imágenes perioperatorias e intraoperatorias. Discusión y conclusión: El absceso subperióstico secundario a la sinusitis, es una complicación rara. Sin embargo, se debe pensar en el diagnostico en pacientes de evolución tórpida y/o que presentan sintomatología neurológica, como convulsiones, se debe completar el estudio con neuroimagen contrastada.

Post-transplant lymphoproliferative disorders (PTLD) represent a severe complication in transplanted patients and Epstein-Barr Virus (EBV) is the main driver. Besides immunodepression, immune activation/chronic inflammation play an important role in both virus reactivation and expansion of EBV-positive B cells. The aim of this study was to assess the impact of immunosuppressive strategies on factors involved in the PTLD's pathogenesis. 124 kidney transplanted patients were enrolled in this study: 71 were treated with mycophenolic acid (MPA) and 53 treated with mTOR inhibitor (mTORi), both in combination with different doses of calcineurin inhibitor. At the time of the transplant (T0), profile of inflammation/immune activation and immune senescence didn't differ between the two groups, but after one year of treatment (T1) markers were significantly higher in MPA-treated patients; their immunosenescence process was supported by the greater erosion of telomeres despite their younger age. Percentages of activated B cells and levels of EBV-DNA significantly increased in MPA-treated patients, and at T1 were significantly higher in MPA- than in mTORi-treated patients. Overall, these findings indicate that mTOR inhibitors constrain the inflammation/immune activation and senescence status, thus reducing the expansion of EBV-infected B cells and the risk of virus-associated PTLD in kidney transplant recipients. © 2019 The Authors

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.

[Abstract] Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.

To characterize the urinary metabolomic fingerprint and multi-metabolite signature associated with type 2 diabetes (T2D), and to classify the population into metabotypes related to T2D.A metabolomics analysis using the 1H-NMR-based, non-targeted metabolomic approach was conducted to determine the urinary metabolomic fingerprint of T2D compared with non-T2D participants in the PREDIMED trial. The discriminant metabolite fingerprint was subjected to logistic regression analysis and ROC analyses to establish and to assess the multi-metabolite signature of T2D prevalence, respectively. Metabotypes associated with T2D were identified using the k-means algorithm.A total of 33 metabolites were significantly different (P<0.05) between T2D and non-T2D participants. The multi-metabolite signature of T2D comprised high levels of methylsuccinate, alanine, dimethylglycine and guanidoacetate, and reduced levels of glutamine, methylguanidine, 3-hydroxymandelate and hippurate, and had a 96.4% AUC, which was higher than the metabolites on their own and glucose. Amino-acid and carbohydrate metabolism were the main metabolic alterations in T2D, and various metabotypes were identified in the studied population. Among T2D participants, those with a metabotype of higher levels of phenylalanine, phenylacetylglutamine, p-cresol and acetoacetate had significantly higher levels of plasma glucose.The multi-metabolite signature of T2D highlights the altered metabolic fingerprint associated mainly with amino-acid, carbohydrate and microbiota metabolism. Metabotypes identified in this patient population could be related to higher risk of long-term cardiovascular events and therefore require further studies. Metabolomics is a useful tool for elucidating the metabolic complexity and interindividual va

[EN] Evapotranspiration is the most important variable in the Pampas plain. Information provided by sensors onboard satellite missions allows represent the spatial and temporal variability of evapotranspiration, which cannot be achieved using only measurements of weather stations. In this work, the Priestley and Taylor (PT) and FAO Penman Monteith (FAO PM) equations were adapted to estimate the reference evapotranspiration, ET0 , using only CERES satellite products (SYN1 and CldTypHist). In order to evaluate the reference evapotranspiration from CERES, a comparison with in situ measurements was conducted. We used ET data provided by the Oficina de Riesgo Agropecuario, corresponding to 24 stations placed in the Pampean Region of Argentina (2001-2016). Results showed very good agreement between the estimates with CERES products and in situ values, with errors between ±0.8 and ±1.1 mm d–1 and r2 greater than 0.75 at daily scale, and errors between ±14 and ±19 mm month–1 and r2 greater than 0.9, at monthly scale better results were obtained with adapted model FAO PM than PT. Finally, ET0 monthly maps for the Pampean Region of Argentina were elaborated, which allowed knowing the temporal-spatial variation in the validation area. In conclusion, the methods presented here are a suitable alternative to estimate the reference evapotranspiration without requiring ground measurements., [ES] La evapotranspiración es la variable hidrológica de mayor relevancia en la llanura pampeana. La información provista por sensores a bordo de satélites permite representar la variabilidad espacio-temporal de la evapotranspiración, lo cual no es posible lograr utilizando únicamente datos de sitios puntuales de medida. En este trabajo se adaptaron las ecuaciones de Priestley y Taylor (PT) y FAO Penman-Monteith (FAO PM) para obtener la evapotranspiración del cultivo de referencia, ET0 , utilizando únicamente datos de los productos de satélite CERES (SYN1 y CldTypHist). Los resultados obtenidos con los datos CERES se compararon con valores de ET0 provistos por la Oficina de Riesgo Agropecuario de Argentina, a partir de información de 24 estaciones agro-meteorológicas distribuidas en la Región Pampeana de Argentina (2001-2016). Los resultados mostraron muy buena concordancia entre los valores generados con los métodos propuestos y aquellos obtenidos in situ, con errores de entre ±0,8 y ±1,1 mm d–1 y r2 superiores a 0,75 a escala diaria, y errores de entre ±14 y ±19 mm mes–1 y r2 superiores a 0,9, a escala mensual, siendo en general mejores los resultados con el método adaptado de FAO PM respecto al de PT. Finalmente, se elaboraron los mapas promedio mensual de la ET0 para la Región Pampeana de Argentina, los cuales permitieron conocer la variación espacio temporal en el área de validación. En conclusión, los métodos que aquí se presentan constituyen una buena alternativa para el cálculo de la evapotranspiración de referencia, sin necesidad de contar con medidas de terreno.

PTPN22 encodes a lymphoid-specific tyrosine phosphatase (LYP) that is a master regulator of the immune response. This gene is a major susceptibility factor for a wide range of autoimmune conditions, including rheumatoid arthritis (RA) for which it represents the strongest non-HLA contributor to disease risk. A missense PTPN22 allele (R620W) affecting the protein-protein interaction of LYP with other relevant players was described as the functional variant of the association. This review will focus on the role of PTPN22 in the pathogenic mechanisms underlying RA predisposition and discuss the possibility of developing LYP-based treatment strategies with a potential application in clinical practice. Areas covered: This review covers the literature showing how PTPN22 is implicated in signalling pathways involved in the autoimmune and autoinflammatory processes underlying RA. Insights obtained from studies aimed at developing novel selective LYP suppressors for treating RA are summarized. Expert opinion: Targeting key risk factors during the early steps of the disease may represent a good strategy to accomplish complete disease remission. As cumulating evidences suggest that PTPN22 R620W is a gain-of-function variant, a growing interest in developing LYP inhibitors has arisen. The potential efficacy and possible application of such compounds are discussed.

[EN] Evapotranspiration is the most important variable in the Pampas plain. Information provided by sensors onboard satellite missions allows represent the spatial and temporal variability of evapotranspiration, which cannot be achieved using only measurements of weather stations. In this work, the Priestley and Taylor (PT) and FAO Penman Monteith (FAO PM) equations were adapted to estimate the reference evapotranspiration, ET0 , using only CERES satellite products (SYN1 and CldTypHist). In order to evaluate the reference evapotranspiration from CERES, a comparison with in situ measurements was conducted. We used ET data provided by the Oficina de Riesgo Agropecuario, corresponding to 24 stations placed in the Pampean Region of Argentina (2001-2016). Results showed very good agreement between the estimates with CERES products and in situ values, with errors between ±0.8 and ±1.1 mm d–1 and r2 greater than 0.75 at daily scale, and errors between ±14 and ±19 mm month–1 and r2 greater than 0.9, at monthly scale better results were obtained with adapted model FAO PM than PT. Finally, ET0 monthly maps for the Pampean Region of Argentina were elaborated, which allowed knowing the temporal-spatial variation in the validation area. In conclusion, the methods presented here are a suitable alternative to estimate the reference evapotranspiration without requiring ground measurements., [ES] La evapotranspiración es la variable hidrológica de mayor relevancia en la llanura pampeana. La información provista por sensores a bordo de satélites permite representar la variabilidad espacio-temporal de la evapotranspiración, lo cual no es posible lograr utilizando únicamente datos de sitios puntuales de medida. En este trabajo se adaptaron las ecuaciones de Priestley y Taylor (PT) y FAO Penman-Monteith (FAO PM) para obtener la evapotranspiración del cultivo de referencia, ET0 , utilizando únicamente datos de los productos de satélite CERES (SYN1 y CldTypHist). Los resultados obtenidos con los datos CERES se compararon con valores de ET0 provistos por la Oficina de Riesgo Agropecuario de Argentina, a partir de información de 24 estaciones agro-meteorológicas distribuidas en la Región Pampeana de Argentina (2001-2016). Los resultados mostraron muy buena concordancia entre los valores generados con los métodos propuestos y aquellos obtenidos in situ, con errores de entre ±0,8 y ±1,1 mm d–1 y r2 superiores a 0,75 a escala diaria, y errores de entre ±14 y ±19 mm mes–1 y r2 superiores a 0,9, a escala mensual, siendo en general mejores los resultados con el método adaptado de FAO PM respecto al de PT. Finalmente, se elaboraron los mapas promedio mensual de la ET0 para la Región Pampeana de Argentina, los cuales permitieron conocer la variación espacio temporal en el área de validación. En conclusión, los métodos que aquí se presentan constituyen una buena alternativa para el cálculo de la evapotranspiración de referencia, sin necesidad de contar con medidas de terreno.

[EN] Evapotranspiration is the most important variable in the Pampas plain. Information provided by sensors onboard satellite missions allows represent the spatial and temporal variability of evapotranspiration, which cannot be achieved using only measurements of weather stations. In this work, the Priestley and Taylor (PT) and FAO Penman Monteith (FAO PM) equations were adapted to estimate the reference evapotranspiration, ET0 , using only CERES satellite products (SYN1 and CldTypHist). In order to evaluate the reference evapotranspiration from CERES, a comparison with in situ measurements was conducted. We used ET data provided by the Oficina de Riesgo Agropecuario, corresponding to 24 stations placed in the Pampean Region of Argentina (2001-2016). Results showed very good agreement between the estimates with CERES products and in situ values, with errors between ±0.8 and ±1.1 mm d–1 and r2 greater than 0.75 at daily scale, and errors between ±14 and ±19 mm month–1 and r2 greater than 0.9, at monthly scale better results were obtained with adapted model FAO PM than PT. Finally, ET0 monthly maps for the Pampean Region of Argentina were elaborated, which allowed knowing the temporal-spatial variation in the validation area. In conclusion, the methods presented here are a suitable alternative to estimate the reference evapotranspiration without requiring ground measurements., [ES] La evapotranspiración es la variable hidrológica de mayor relevancia en la llanura pampeana. La información provista por sensores a bordo de satélites permite representar la variabilidad espacio-temporal de la evapotranspiración, lo cual no es posible lograr utilizando únicamente datos de sitios puntuales de medida. En este trabajo se adaptaron las ecuaciones de Priestley y Taylor (PT) y FAO Penman-Monteith (FAO PM) para obtener la evapotranspiración del cultivo de referencia, ET0 , utilizando únicamente datos de los productos de satélite CERES (SYN1 y CldTypHist). Los resultados obtenidos con los datos CERES se compararon con valores de ET0 provistos por la Oficina de Riesgo Agropecuario de Argentina, a partir de información de 24 estaciones agro-meteorológicas distribuidas en la Región Pampeana de Argentina (2001-2016). Los resultados mostraron muy buena concordancia entre los valores generados con los métodos propuestos y aquellos obtenidos in situ, con errores de entre ±0,8 y ±1,1 mm d–1 y r2 superiores a 0,75 a escala diaria, y errores de entre ±14 y ±19 mm mes–1 y r2 superiores a 0,9, a escala mensual, siendo en general mejores los resultados con el método adaptado de FAO PM respecto al de PT. Finalmente, se elaboraron los mapas promedio mensual de la ET0 para la Región Pampeana de Argentina, los cuales permitieron conocer la variación espacio temporal en el área de validación. En conclusión, los métodos que aquí se presentan constituyen una buena alternativa para el cálculo de la evapotranspiración de referencia, sin necesidad de contar con medidas de terreno.

[EN] Evapotranspiration is the most important variable in the Pampas plain. Information provided by sensors onboard satellite missions allows represent the spatial and temporal variability of evapotranspiration, which cannot be achieved using only measurements of weather stations. In this work, the Priestley and Taylor (PT) and FAO Penman Monteith (FAO PM) equations were adapted to estimate the reference evapotranspiration, ET0 , using only CERES satellite products (SYN1 and CldTypHist). In order to evaluate the reference evapotranspiration from CERES, a comparison with in situ measurements was conducted. We used ET data provided by the Oficina de Riesgo Agropecuario, corresponding to 24 stations placed in the Pampean Region of Argentina (2001-2016). Results showed very good agreement between the estimates with CERES products and in situ values, with errors between ±0.8 and ±1.1 mm d–1 and r2 greater than 0.75 at daily scale, and errors between ±14 and ±19 mm month–1 and r2 greater than 0.9, at monthly scale better results were obtained with adapted model FAO PM than PT. Finally, ET0 monthly maps for the Pampean Region of Argentina were elaborated, which allowed knowing the temporal-spatial variation in the validation area. In conclusion, the methods presented here are a suitable alternative to estimate the reference evapotranspiration without requiring ground measurements., [ES] La evapotranspiración es la variable hidrológica de mayor relevancia en la llanura pampeana. La información provista por sensores a bordo de satélites permite representar la variabilidad espacio-temporal de la evapotranspiración, lo cual no es posible lograr utilizando únicamente datos de sitios puntuales de medida. En este trabajo se adaptaron las ecuaciones de Priestley y Taylor (PT) y FAO Penman-Monteith (FAO PM) para obtener la evapotranspiración del cultivo de referencia, ET0 , utilizando únicamente datos de los productos de satélite CERES (SYN1 y CldTypHist). Los resultados obtenidos con los datos CERES se compararon con valores de ET0 provistos por la Oficina de Riesgo Agropecuario de Argentina, a partir de información de 24 estaciones agro-meteorológicas distribuidas en la Región Pampeana de Argentina (2001-2016). Los resultados mostraron muy buena concordancia entre los valores generados con los métodos propuestos y aquellos obtenidos in situ, con errores de entre ±0,8 y ±1,1 mm d–1 y r2 superiores a 0,75 a escala diaria, y errores de entre ±14 y ±19 mm mes–1 y r2 superiores a 0,9, a escala mensual, siendo en general mejores los resultados con el método adaptado de FAO PM respecto al de PT. Finalmente, se elaboraron los mapas promedio mensual de la ET0 para la Región Pampeana de Argentina, los cuales permitieron conocer la variación espacio temporal en el área de validación. En conclusión, los métodos que aquí se presentan constituyen una buena alternativa para el cálculo de la evapotranspiración de referencia, sin necesidad de contar con medidas de terreno.

[EN] Evapotranspiration is the most important variable in the Pampas plain. Information provided by sensors onboard satellite missions allows represent the spatial and temporal variability of evapotranspiration, which cannot be achieved using only measurements of weather stations. In this work, the Priestley and Taylor (PT) and FAO Penman Monteith (FAO PM) equations were adapted to estimate the reference evapotranspiration, ET0 , using only CERES satellite products (SYN1 and CldTypHist). In order to evaluate the reference evapotranspiration from CERES, a comparison with in situ measurements was conducted. We used ET data provided by the Oficina de Riesgo Agropecuario, corresponding to 24 stations placed in the Pampean Region of Argentina (2001-2016). Results showed very good agreement between the estimates with CERES products and in situ values, with errors between ±0.8 and ±1.1 mm d–1 and r2 greater than 0.75 at daily scale, and errors between ±14 and ±19 mm month–1 and r2 greater than 0.9, at monthly scale better results were obtained with adapted model FAO PM than PT. Finally, ET0 monthly maps for the Pampean Region of Argentina were elaborated, which allowed knowing the temporal-spatial variation in the validation area. In conclusion, the methods presented here are a suitable alternative to estimate the reference evapotranspiration without requiring ground measurements., [ES] La evapotranspiración es la variable hidrológica de mayor relevancia en la llanura pampeana. La información provista por sensores a bordo de satélites permite representar la variabilidad espacio-temporal de la evapotranspiración, lo cual no es posible lograr utilizando únicamente datos de sitios puntuales de medida. En este trabajo se adaptaron las ecuaciones de Priestley y Taylor (PT) y FAO Penman-Monteith (FAO PM) para obtener la evapotranspiración del cultivo de referencia, ET0 , utilizando únicamente datos de los productos de satélite CERES (SYN1 y CldTypHist). Los resultados obtenidos con los datos CERES se compararon con valores de ET0 provistos por la Oficina de Riesgo Agropecuario de Argentina, a partir de información de 24 estaciones agro-meteorológicas distribuidas en la Región Pampeana de Argentina (2001-2016). Los resultados mostraron muy buena concordancia entre los valores generados con los métodos propuestos y aquellos obtenidos in situ, con errores de entre ±0,8 y ±1,1 mm d–1 y r2 superiores a 0,75 a escala diaria, y errores de entre ±14 y ±19 mm mes–1 y r2 superiores a 0,9, a escala mensual, siendo en general mejores los resultados con el método adaptado de FAO PM respecto al de PT. Finalmente, se elaboraron los mapas promedio mensual de la ET0 para la Región Pampeana de Argentina, los cuales permitieron conocer la variación espacio temporal en el área de validación. En conclusión, los métodos que aquí se presentan constituyen una buena alternativa para el cálculo de la evapotranspiración de referencia, sin necesidad de contar con medidas de terreno.

[EN] Evapotranspiration is the most important variable in the Pampas plain. Information provided by sensors onboard satellite missions allows represent the spatial and temporal variability of evapotranspiration, which cannot be achieved using only measurements of weather stations. In this work, the Priestley and Taylor (PT) and FAO Penman Monteith (FAO PM) equations were adapted to estimate the reference evapotranspiration, ET0 , using only CERES satellite products (SYN1 and CldTypHist). In order to evaluate the reference evapotranspiration from CERES, a comparison with in situ measurements was conducted. We used ET data provided by the Oficina de Riesgo Agropecuario, corresponding to 24 stations placed in the Pampean Region of Argentina (2001-2016). Results showed very good agreement between the estimates with CERES products and in situ values, with errors between ±0.8 and ±1.1 mm d–1 and r2 greater than 0.75 at daily scale, and errors between ±14 and ±19 mm month–1 and r2 greater than 0.9, at monthly scale better results were obtained with adapted model FAO PM than PT. Finally, ET0 monthly maps for the Pampean Region of Argentina were elaborated, which allowed knowing the temporal-spatial variation in the validation area. In conclusion, the methods presented here are a suitable alternative to estimate the reference evapotranspiration without requiring ground measurements., [ES] La evapotranspiración es la variable hidrológica de mayor relevancia en la llanura pampeana. La información provista por sensores a bordo de satélites permite representar la variabilidad espacio-temporal de la evapotranspiración, lo cual no es posible lograr utilizando únicamente datos de sitios puntuales de medida. En este trabajo se adaptaron las ecuaciones de Priestley y Taylor (PT) y FAO Penman-Monteith (FAO PM) para obtener la evapotranspiración del cultivo de referencia, ET0 , utilizando únicamente datos de los productos de satélite CERES (SYN1 y CldTypHist). Los resultados obtenidos con los datos CERES se compararon con valores de ET0 provistos por la Oficina de Riesgo Agropecuario de Argentina, a partir de información de 24 estaciones agro-meteorológicas distribuidas en la Región Pampeana de Argentina (2001-2016). Los resultados mostraron muy buena concordancia entre los valores generados con los métodos propuestos y aquellos obtenidos in situ, con errores de entre ±0,8 y ±1,1 mm d–1 y r2 superiores a 0,75 a escala diaria, y errores de entre ±14 y ±19 mm mes–1 y r2 superiores a 0,9, a escala mensual, siendo en general mejores los resultados con el método adaptado de FAO PM respecto al de PT. Finalmente, se elaboraron los mapas promedio mensual de la ET0 para la Región Pampeana de Argentina, los cuales permitieron conocer la variación espacio temporal en el área de validación. En conclusión, los métodos que aquí se presentan constituyen una buena alternativa para el cálculo de la evapotranspiración de referencia, sin necesidad de contar con medidas de terreno.

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1 / HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; OR = 1.19, OR = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (P = 5.52E-04, OR = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus

A straightforward and atom-economical enantioselective approach to highly substituted tetrahydropyrans is reported. The process, which consists of an intermolecular gold-catalyzed [2+2+2] cycloaddition between allenamides, alkenes, and aldehydes, is efficiently catalyzed by both phosphoramidite- and chiral N-heterocyclic carbene-gold catalysts, occurs with complete chemoselectivity and regioselectivity, moderate diastereoselectivity, and moderate to very good enantioselectivities.

STUDY QUESTION Which essential items should be recorded before, during and after endometriosis surgery and in clinical outcome based surgical trials in patients with deep endometriosis (DE)? SUMMARY ANSWER A DE surgical sheet (DESS) was developed for standardized reporting of the surgical treatment of DE and an international expert consensus proposal on relevant items that should be recorded in surgical outcome trials in women with DE. WHAT IS KNOWN ALREADY Surgery is an important treatment for symptomatic DE. So far, data have been reported in such a way that comparison of different surgical techniques is impossible. Therefore, we present an international expert proposal for standardized reporting of surgical treatment and surgical outcome trials in women with DE. STUDY DESIGN, SIZE, DURATION International expert consensus based on a systematic review of literature. PARTICIPANTS/MATERIALS, SETTING, METHODS Taking into account recommendations from Consolidated Standards of Reporting Trials (CONSORT), the Innovation Development Exploration Assessment and Long-term Study (IDEAL), the Initiative on Methods, Measurement and Pain Assessment in Clinical trials (IMMPACT) and the World Endometriosis Research Foundation Phenome and Biobanking Harmonisation Project (WERF EPHect), a systematic literature review on surgical treatment of DE was performed and resulted in a proposal for standardized reporting, adapted by contributions from eight members of the multidisciplinary Leuven University Hospitals Endometriosis Care Program, from 18 international experts and from audience feedback during three international meetings. MAIN RESULTS AND THE ROLE OF CHANCE We have developed the DESS to record in detail the surgical procedures for DE, and an international consensus on pre-, intra- and post-operative data that should be recorded in surgical outcome trials on DE. LIMITATIONS, REASONS FOR CAUTION The recommendations in this paper represent a consensus among international experts b

STUDY QUESTION Which essential items should be recorded before, during and after endometriosis surgery and in clinical outcome based surgical trials in patients with deep endometriosis (DE)? SUMMARY ANSWER A DE surgical sheet (DESS) was developed for standardized reporting of the surgical treatment of DE and an international expert consensus proposal on relevant items that should be recorded in surgical outcome trials in women with DE. WHAT IS KNOWN ALREADY Surgery is an important treatment for symptomatic DE. So far, data have been reported in such a way that comparison of different surgical techniques is impossible. Therefore, we present an international expert proposal for standardized reporting of surgical treatment and surgical outcome trials in women with DE. STUDY DESIGN, SIZE, DURATION International expert consensus based on a systematic review of literature. PARTICIPANTS/MATERIALS, SETTING, METHODS Taking into account recommendations from Consolidated Standards of Reporting Trials (CONSORT), the Innovation Development Exploration Assessment and Long-term Study (IDEAL), the Initiative on Methods, Measurement and Pain Assessment in Clinical trials (IMMPACT) and the World Endometriosis Research Foundation Phenome and Biobanking Harmonisation Project (WERF EPHect), a systematic literature review on surgical treatment of DE was performed and resulted in a proposal for standardized reporting, adapted by contributions from eight members of the multidisciplinary Leuven University Hospitals Endometriosis Care Program, from 18 international experts and from audience feedback during three international meetings. MAIN RESULTS AND THE ROLE OF CHANCE We have developed the DESS to record in detail the surgical procedures for DE, and an international consensus on pre-, intra- and post-operative data that should be recorded in surgical outcome trials on DE. LIMITATIONS, REASONS FOR CAUTION The recommendations in this paper represent a consensus among international experts b

There is growing interest in defining the aberrant molecular differences between normal and tumor-associated fibroblasts (TAFs) that support tumor progression. For this purpose, we recently conducted a genome-wide DNA methylation profiling of TAFs and paired control fibroblasts (CFs) from non-small cell lung cancer (NSCLC) patients, and reported a widespread hypomethylation concomitantly with focal gain of DNA methylation; in addition, we found evidence that a fraction of lung TAFs are fibrocytes in origin. Of note, the aberrant epigenome of lung TAFs had a global impact in gene expression and a selective impact on the TGF-ß pathway. To get insights on the functional implications of the latter impact, we analyzed the response of lung TAFs to exogenous TGF-ß1 in terms of activation and contractility. We found a larger expression of a panel of activation markers including a-SMA and collagen-I in TAFs compared to control fibroblasts. Likewise, TGF-ß1 elicited a larger contractility in TAFs than in CFs as assessed by traction force microscopy. These findings reveal that lung TAFs are hyperresponsive to TGF-ß1, which may underlie the expansion and/or maintenance of the tumor-promoting desmoplastic stroma in lung cancer., Postprint (author's final draft)

Metastasis is responsible for most cancer-related deaths, and, among common tumor types, melanoma is one with great potential to metastasize. Here we study the contribution of epigenetic changes to the dissemination process by analyzing the changes that occur at the DNA methylation level between primary cancer cells and metastases. We found a hypomethylation event that reactivates a cryptic transcript of the Rab GTPase activating protein TBC1D16 (TBC1D16-47 kDa; referred to hereafter as TBC1D16-47KD) to be a characteristic feature of the metastatic cascade. This short isoform of TBC1D16 exacerbates melanoma growth and metastasis both in vitro and in vivo. By combining immunoprecipitation and mass spectrometry, we identified RAB5C as a new TBC1D16 target and showed that it regulates EGFR in melanoma cells. We also found that epigenetic reactivation of TBC1D16-47KD is associated with poor clinical outcome in melanoma, while conferring greater sensitivity to BRAF and MEK inhibitors.

STUDY QUESTION: Are the levels of biologically active and the most toxic dioxin-like substances in adipose tissue of patients with deep infiltrating endometriosis (DIE) higher than in a control group without endometriosis? SUMMARY ANSWER: DIE patients have higher levels of dioxins and polychlorinated biphenyls (PCBs) in adipose tissue compared with controls without endometriosis. WHAT IS KNOWN ALREADY: Some studies have investigated the levels of dioxin-like substances, in serum samples, in patients with endometriosis, with inconsistent results. STUDY DESIGN, SIZE, DURATION: Case-control study including two groups of patients. The study group (DIE group) consisted of 30 patients undergoing laparoscopic surgery because of DIE. In all patients, an extensive preoperative work-up was performed including clinical exploration, magnetic resonance imaging (MRI) and transvaginal sonography. All patients with DIE underwent a confirmatory histological study for DIE after surgery. The non-endometriosis control group (control group), included the next consecutive patient undergoing laparoscopic surgery in our center due to adnexal benign gynecological disease (ovarian or tubal procedures other than endometriosis) after each DIE patient, and who did not present any type of endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: During the surgical procedure 1-2 g of adipose tissue from the omentum were obtained. Dioxin-like substances were analyzed in adipose tissue in DIE patients and controls without endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE: The total toxic equivalence and concentrations of both dioxins and PCBs were significantly higher in patients with DIE in comparison with the control group (P < 0.05), mainly due to the significantly higher values of the two most toxic dioxins (2,3,7,8-tetrachlorodibenzo-p-dioxin [2,3,7,8-TCDD] and 1,2,3,7,8-pentachlorodibenzo-p-dioxin [1,2,3,7,8-PeCDD]) (P < 0.01 for each compound). The levels of furan 2,3,4,7,8-PeCDF were

Objective To evaluate whether the systemic sclerosis (SSc)-associated IRAK1 non-synonymous single-nucleotide polymorphism rs1059702 is responsible for the Xq28 association with SSc or whether there are other independent signals in the nearby methyl-CpG-binding protein 2 gene (MECP2). Methods We analysed a total of 3065 women with SSc and 2630 unaffected controls from five independent Caucasian cohorts. Four tag single-nucleotide polymorphisms of MECP2 (rs3027935, rs17435, rs5987201 and rs5945175) and the IRAK1 variant rs1059702 were genotyped using TaqMan predesigned assays. A meta-analysis including all cohorts was performed to test the overall effect of these Xq28 polymorphisms on SSc. ResultsIRAK1 rs1059702 and MECP2 rs17435 were associated specifically with diffuse cutaneous SSc (P-FDR=4.12x10(-3), OR=1.27, 95% CI 1.09 to 1.47, and P-FDR=5.26x10(-4), OR=1.30, 95% CI 1.14 to 1.48, respectively), but conditional logistic regression analysis showed that the association of IRAK1 rs1059702 with this subtype was explained by that of MECP2 rs17435. On the other hand, IRAK1 rs1059702 was consistently associated with presence of pulmonary fibrosis (PF), because statistical significance was observed when comparing SSc patients PF+ versus controls (P-FDR=0.039, OR=1.30, 95% CI 1.07 to 1.58) and SSc patients PF+ versus SSc patients PF- (p=0.025, OR=1.26, 95% CI 1.03 to 1.55). Conclusions Our data clearly suggest the existence of two independent signals within the Xq28 region, one located in IRAK1 related to PF and another in MECP2 related to diffuse cutaneous SSc, indicating that both genes may have an impact on the clinical outcome of the disease.

Objective To evaluate whether the systemic sclerosis (SSc)-associated IRAK1 non-synonymous single-nucleotide polymorphism rs1059702 is responsible for the Xq28 association with SSc or whether there are other independent signals in the nearby methyl-CpG-binding protein 2 gene (MECP2). Methods We analysed a total of 3065 women with SSc and 2630 unaffected controls from five independent Caucasian cohorts. Four tag single-nucleotide polymorphisms of MECP2 (rs3027935, rs17435, rs5987201 and rs5945175) and the IRAK1 variant rs1059702 were genotyped using TaqMan predesigned assays. A meta-analysis including all cohorts was performed to test the overall effect of these Xq28 polymorphisms on SSc. ResultsIRAK1 rs1059702 and MECP2 rs17435 were associated specifically with diffuse cutaneous SSc (P-FDR=4.12x10(-3), OR=1.27, 95% CI 1.09 to 1.47, and P-FDR=5.26x10(-4), OR=1.30, 95% CI 1.14 to 1.48, respectively), but conditional logistic regression analysis showed that the association of IRAK1 rs1059702 with this subtype was explained by that of MECP2 rs17435. On the other hand, IRAK1 rs1059702 was consistently associated with presence of pulmonary fibrosis (PF), because statistical significance was observed when comparing SSc patients PF+ versus controls (P-FDR=0.039, OR=1.30, 95% CI 1.07 to 1.58) and SSc patients PF+ versus SSc patients PF- (p=0.025, OR=1.26, 95% CI 1.03 to 1.55). Conclusions Our data clearly suggest the existence of two independent signals within the Xq28 region, one located in IRAK1 related to PF and another in MECP2 related to diffuse cutaneous SSc, indicating that both genes may have an impact on the clinical outcome of the disease.

Human aging cannot be fully understood in terms of the constrained genetic setting. Epigenetic drift is an alternative means of explaining age-associated alterations. To address this issue, we performed whole-genome bisulfite sequencing (WGBS) of newborn and centenarian genomes. The centenarian DNA had a lower DNA methylation content and a reduced correlation in the methylation status of neighboring cytosine--phosphate--guanine (CpGs) throughout the genome in comparison with the more homogeneously methylated newborn DNA. The more hypomethylated CpGs observed in the centenarian DNA compared with the neonate covered all genomic compartments, such as promoters, exonic, intronic, and intergenic regions. For regulatory regions, the most hypomethylated sequences in the centenarian DNA were present mainly at CpG-poor promoters and in tissue-specific genes, whereas a greater level of DNA methylation was observed in CpG island promoters. We extended the study to a larger cohort of newborn and nonagenarian samples using a 450,000 CpG-site DNA methylation microarray that reinforced the observation of more hypomethylated DNA sequences in the advanced age group. WGBS and 450,000 analyses of middle-age individuals demonstrated DNA methylomes in the crossroad between the newborn and the nonagenarian/centenarian groups. Our study constitutes a unique DNA methylation analysis of the extreme points of human life at a single-nucleotide resolution level.

The first highly enantioselective intermolecular (4 + 2) cycloaddition between allenes and dienes is reported. The reaction provides good yields of optically active cyclohexenes featuring diverse substitution patterns and up to three stereocenters. Key to the success of the process is the use of newly designed axially chiral N-heterocyclic carbene-gold catalysts. © 2012 American Chemical Society.

Human aging cannot be fully understood in terms of the constrained genetic setting. Epigenetic drift is an alternative means of explaining age-associated alterations. To address this issue, we performed whole-genome bisulfite sequencing (WGBS) of newborn and centenarian genomes. The centenarian DNA had a lower DNA methylation content and a reduced correlation in the methylation status of neighboring cytosine--phosphate--guanine (CpGs) throughout the genome in comparison with the more homogeneously methylated newborn DNA. The more hypomethylated CpGs observed in the centenarian DNA compared with the neonate covered all genomic compartments, such as promoters, exonic, intronic, and intergenic regions. For regulatory regions, the most hypomethylated sequences in the centenarian DNA were present mainly at CpG-poor promoters and in tissue-specific genes, whereas a greater level of DNA methylation was observed in CpG island promoters. We extended the study to a larger cohort of newborn and nonagenarian samples using a 450,000 CpG-site DNA methylation microarray that reinforced the observation of more hypomethylated DNA sequences in the advanced age group. WGBS and 450,000 analyses of middle-age individuals demonstrated DNA methylomes in the crossroad between the newborn and the nonagenarian/centenarian groups. Our study constitutes a unique DNA methylation analysis of the extreme points of human life at a single-nucleotide resolution level.

Mammalian sex determination is the genetic process that commits the undifferentiated bipotential gonads to develop as either testes or ovaries. The differentiation of SOX9-expressing Sertoli cells is assumed to be necessary to initiate testis development. Insectivorous moles of the genus Talpa represent a unique case of generalized true hermaphroditism, as XX female moles constitutively develop two ovotestes instead of normal ovaries. In this work, we have investigated the expression patterns of a number of genes known to play key roles in gonad organogenesis, throughout the entire process of ovotestis development in female moles. Molecular and morphological evidence are provided that these ovotestes contain primary medullary testis-like cords, Leydig cells, peritubular myoid cells, and a testis-specific vasculature, but no Sertoli cells. Our results show for the first time that SOX9 is not required for the formation of the primary testis cords, but it is necessary for the maintenance and subsequent development of these cords. In addition, the expression pattern of WNT4 in male and female moles indicates that this gene inhibits Leydig cell differentiation and, contrary to the proposed scenario in the mouse, it is not required for the colonization and survival of primordial germ cells. According to our data, mole ovotestes result from a process of PDGFRalpha-mediated mesonephric cell migration, which occurs simultaneously in both sexes. The fact that FST remains inactive during the critical stages of female gonad development, explains the lack of migration inhibition, and may be a consequence of improper WNT4 signalling in the mole.

Current-voltage characteristics, critical current density and thermal conductivity measurements have been performed on YBaCuO/Ag composites. From current-voltage characteristics and critical current density measurements, it is shown that the YBaCuO/Ag composites can be viewed as superconducting link networks. Current-voltage characteristics and critical current density seem to obey a universal law. It has also been demonstrated that the thermal conductivity of the composites is dominated by the electronic contribution of silver.

In the industrial obtention of D-a-p-hydroxyphenylglycine the separation of the amino acid is carried out by precipitation and during this process, a mother liquor is produced with a high salt content (phosphates and sulphates) and an amino acid concentration of approximately 120-150 mol.m-3. The disposal of this mother liquor not only suppose an environmental problem for its high salinity and COD (Chemical Oxygen Demand) content but also an economic lost due to the high price of the unrecoved amino acid. To avoid this problem an electrodialytic process has been developped that allow the recovery of 85% of the amino acid in the form of a low salinity stream with a salt content a 70% lower than that the initial mother liquor. This low salinity stream can beincorporated to the main process and in this way the amino acid can be recover.

In the industrial obtention of D-a-p-hydroxyphenylglycine the separation of the amino acid is carried out by precipitation and during this process, a mother liquor is produced with a high salt content (phosphates and sulphates) and an amino acid concentration of approximately 120-150 mol.m-3. The disposal of this mother liquor not only suppose an environmental problem for its high salinity and COD (Chemical Oxygen Demand) content but also an economic lost due to the high price of the unrecoved amino acid. To avoid this problem an electrodialytic process has been developped that allow the recovery of 85% of the amino acid in the form of a low salinity stream with a salt content a 70% lower than that the initial mother liquor. This low salinity stream can beincorporated to the main process and in this way the amino acid can be recover.

info:eu-repo/semantics/published, Comm. 31st Annual Meeting of the European Association for the Study of Diabetes - Stockholm (Sweden), 13.09.1995

info:eu-repo/semantics/published, Comm. 31st Annual Meeting of the European Association for the Study of Diabetes - Stockholm (Sweden), 13.09.1995