Synthesis of slow-wave structures based on capacitive-loaded lines through aggressive space mapping (ASM)

This article is focused on the automated synthesis of slow-wave structures based on microstrip lines loaded with patch capacitors. Thanks to the presence of the shunt capacitors, the effective capacitance of the line is enhanced, and the phase velocity of the structure can be made significantly smaller than the one of the unloaded line. The target is to achieve the layout of the slow-wave structure able to provide the required slow-wave ratio, characteristic (Bloch) impedance and electrical length (i.e., the usual specifications in the design of slow-wave transmission lines). To this end, a two-step synthesis method, based on the aggressive space mapping (ASM) algorithm, is proposed for the first time. Through the first ASM algorithm, the circuit schematic providing the target specifications is determined. Then, the second ASM optimizer is used to generate the layout of the structure. To illustrate the potential of the proposed synthesis method, three application examples are successfully reported. The two-step ASM algorithm is able to provide the layout of the considered structures from the required specifications, without the need of an external aid in the process.This work has been supported by MINECO-Spain (projects TEC2010-17512 METATRANSFER, TEC2010-21520-C04-01, TEC2013-47037-C5-1-R, CONSOLIDER EMET CSD2008-00066, TEC2013-40600-R and TEC2013-49221-EXP), Generalitat de Catalunya (project 2014SGR-157), Institucio Catalana de Recerca i Estudis Avancats (who has awarded Ferran Martin) and FEDER Funds. Marco Orellana acknowledges the support of the Universidad de Costa Rica, MICITT and CONICIT to study at the Univesitat Autonoma de Barcelona.Orellana, M.; Selga, J.; Sans, M.; Rodriguez Perez, AM.; Boria Esbert, VE.; Martín Antolín, JF. (2015). Synthesis of slow-wave structures based on capacitive-loaded lines through aggressive space mapping (ASM). 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Neuroinflammation and Neurotransmission Mechanisms Involved in Neuropsychiatric Disorders

Some classical psychiatric disorders, such as schizophrenia, autism, major depression, bipolar and obsessive‐compulsive disorders, have been related to neuroinflammatory process, immunological abnormalities, and neurotransmission impairment beyond genetic mutations. Neuroinflammation is mostly regulated by glial cells, which respond to physiological and pathological stimuli by anti‐ and pro‐inflammatory cytokine and chemokine signaling; moreover, recent studies have indicated that glial cells also respond to the neurotransmitters. Neurotransmitters regulate many biological processes, such as cell proliferation and synaptogenesis, which contribute to the formation of functional circuits. Alterations in the neurotransmission can lead to many pathological changes that occur in brain disorders. For example, studies have shown that neuroinflammation can alter the metabolism of glutamate as well as the function of its transporters, resulting in cognitive, behavioral, and psychiatric impairments. Cytokines as IL‐1β and IL‐6 appear to have an important influence in the dopaminergic and serotoninergic neurons. These data together suggest that glial cells via cytokines and abnormal regulation of neurotransmitters can influence psychiatric disorders. The present knowledge about this issue does not allow answering whether neuroinflammation is the cause or the consequence of neurotransmission imbalance and emphasizes the importance to improve in vivo imaging methods and models to elucidate this enigma

International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients

A century after its discovery, Chagas disease, caused by the parasite Trypanosoma cruzi, still represents a major neglected tropical threat. Accurate diagnostics tools as well as surrogate markers of parasitological response to treatment are research priorities in the field. The polymerase chain reaction (PCR) has been proposed as a sensitive laboratory tool for detection of T. cruzi infection and monitoring of parasitological treatment outcome. However, high variation in accuracy and lack of international quality controls has precluded reliable applications in the clinical practice and comparisons of data among cohorts and geographical regions. In an effort towards harmonization of PCR strategies, 26 expert laboratories from 16 countries evaluated their current PCR procedures against sets of control samples, composed by serial dilutions of T.cruzi DNA from culture stocks belonging to different lineages, human blood spiked with parasite cells and blood samples from Chagas disease patients. A high variability in sensitivities and specificities was found among the 48 reported PCR tests. Out of them, four tests with best performance were selected and further evaluated. This study represents a crucial first step towards device of a standardized operative procedure for T. cruzi PCR.Fil: Schijman, Alejandro G. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI-CONICET). Laboratorio de Biología Molecular de la Enfermedad de Chagas (LabMECh); Argentina.Fil: Bisio, Margarita. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI-CONICET). Laboratorio de Biología Molecular de la Enfermedad de Chagas (LabMECh); Argentina.Fil: Orellana, Liliana. Universidad de Buenos Aires. Instituto de Cálculo; Argentina.Fil: Sued, Mariela. Universidad de Buenos Aires. Instituto de Cálculo; Argentina.Fil: Duffy, Tomás. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI-CONICET). Laboratorio de Biología Molecular de la Enfermedad de Chagas (LabMECh); Argentina.Fil: Mejia Jaramillo, Ana M. Universidad de Antioquia. Grupo Chagas; Colombia.Fil: Cura, Carolina. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI-CONICET). Laboratorio de Biología Molecular de la Enfermedad de Chagas (LabMECh); Argentina.Fil: Auter, Frederic. French Blood Services; Francia.Fil: Veron, Vincent. Universidad de Parasitología. Laboratorio Hospitalario; Guayana Francesa.Fil: Qvarnstrom, Yvonne. Centers for Disease Control. Department of Parasitic Diseases; Estados Unidos.Fil: Deborggraeve, Stijn. Institute of Tropical Medicine; Bélgica.Fil: Hijar, Gisely. Instituto Nacional de Salud; Perú.Fil: Zulantay, Inés. Facultad de Medicina; Chile.Fil: Lucero, Raúl Horacio. Universidad Nacional del Nordeste; Argentina.Fil: Velázquez, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología Dr. Mario Fatala Chaben; Argentina.Fil: Tellez, Tatiana. Universidad Mayor de San Simon. Centro Universitario de Medicina Tropical; Bolivia.Fil: Sanchez Leon, Zunilda. Universidad Nacional de Asunción. Instituto de Investigaciones en Ciencias de la Salud; Paraguay.Fil: Galvão, Lucia. Faculdade de Farmácia; Brasil.Fil: Nolder, Debbie. Hospital for Tropical Diseases. London School of Tropical Medicine and Hygiene Department of Clinical Parasitology; Reino Unido.Fil: Monje Rumi, María. Universidad Nacional de Salta. Laboratorio de Patología Experimental; Argentina.Fil: Levi, José E. Hospital Sirio Libanês. Blood Bank; Brasil.Fil: Ramirez, Juan D. Universidad de los Andes. Centro de Investigaciones en Microbiología y Parasitología Tropical; Colombia.Fil: Zorrilla, Pilar. Instituto Pasteur; Uruguay.Fil: Flores, María. Instituto de Salud Carlos III. Centro de Mahahonda; España.Fil: Jercic, Maria I. Instituto Nacional De Salud. Sección Parasitología; Chile.Fil: Crisante, Gladys. Universidad de los Andes. Centro de Investigaciones Parasitológicas J.F. Torrealba; Venezuela.Fil: Añez, Néstor. Universidad de los Andes. Centro de Investigaciones Parasitológicas J.F. Torrealba; Venezuela.Fil: De Castro, Ana M. Universidade Federal de Goiás. Instituto de Patologia Tropical e Saúde Pública (IPTSP); Brasil.Fil: Gonzalez, Clara I. Universidad Industrial de Santander. Grupo de Inmunología y Epidemiología Molecular (GIEM); Colombia.Fil: Acosta Viana, Karla. Universidad Autónoma de Yucatán. Departamento de Biomedicina de Enfermedades Infecciosas y Parasitarias Laboratorio de Biología Celular; México.Fil: Yachelini, Pedro. Universidad Católica de Santiago del Estero. Instituto de Biomedicina; Argentina.Fil: Torrico, Faustino. Universidad Mayor de San Simon. Centro Universitario de Medicina Tropical; Bolivia.Fil: Robello, Carlos. Instituto Pasteur; Uruguay.Fil: Diosque, Patricio. Universidad Nacional de Salta. Laboratorio de Patología Experimental; Argentina.Fil: Triana Chavez, Omar. Universidad de Antioquia. Grupo Chagas; Colombia.Fil: Aznar, Christine. Universidad de Parasitología. Laboratorio Hospitalario; Guayana Francesa.Fil: Russomando, Graciela. Universidad Nacional de Asunción. Instituto de Investigaciones en Ciencias de la Salud; Paraguay.Fil: Büscher, Philippe. Institute of Tropical Medicine; Bélgica.Fil: Assal, Azzedine. French Blood Services; Francia.Fil: Guhl, Felipe. Universidad de los Andes. Centro de Investigaciones en Microbiología y Parasitología Tropical; Colombia.Fil: Sosa Estani, Sergio. ANLIS Dr.C.G.Malbrán. Centro Nacional de Diagnóstico e Investigación en Endemo-Epidemias; Argentina.Fil: DaSilva, Alexandre. Centers for Disease Control. Department of Parasitic Diseases; Estados Unidos.Fil: Britto, Constança. Instituto Oswaldo Cruz/FIOCRUZ. Laboratório de Biologia Molecular e Doenças Endêmicas; Brasil.Fil: Luquetti, Alejandro. Laboratório de Pesquisa de Doença de Chagas; Brasil.Fil: Ladzins, Janis. World Health Organization (WHO). Special Programme for Research and Training in Tropical Diseases (TDR); Suiza

International Study to Evaluate PCR Methods for Detection of Trypanosoma cruzi DNA in Blood Samples from Chagas Disease Patients

A century after its discovery, Chagas disease, caused by the parasite Trypanosoma cruzi, still represents a major neglected tropical threat. Accurate diagnostics tools as well as surrogate markers of parasitological response to treatment are research priorities in the field. The polymerase chain reaction (PCR) has been proposed as a sensitive laboratory tool for detection of T. cruzi infection and monitoring of parasitological treatment outcome. However, high variation in accuracy and lack of international quality controls has precluded reliable applications in the clinical practice and comparisons of data among cohorts and geographical regions. In an effort towards harmonization of PCR strategies, 26 expert laboratories from 16 countries evaluated their current PCR procedures against sets of control samples, composed by serial dilutions of T.cruzi DNA from culture stocks belonging to different lineages, human blood spiked with parasite cells and blood samples from Chagas disease patients. A high variability in sensitivities and specificities was found among the 48 reported PCR tests. Out of them, four tests with best performance were selected and further evaluated. This study represents a crucial first step towards device of a standardized operative procedure for T. cruzi PCR

Infection of Anopheles aquasalis from symptomatic and asymptomatic Plasmodium vivax infections in Manaus, western Brazilian Amazon

BACKGROUND: Asymptomatic individuals are one of the major challenges for malaria elimination programs in endemic areas. In the absence of clinical symptoms and with a lower parasite density they constitute silent reservoirs considered important for maintaining transmission of human malaria. Studies from Brazil have shown that infected individuals may carry these parasites for long periods. RESULTS: Patients were selected from three periurban endemic areas of the city of Manaus, in the western Brazilian Amazon. Symptomatic and asymptomatic patients with positive thick blood smear and quantitative real-time PCR (qPCR) positive for Plasmodium vivax were invited to participate in the study. A standardised pvs25 gene amplification by qPCR was used for P. vivax gametocytes detection. Anopheles aquasalis were fed using membrane feeding assays (MFA) containing blood from malaria patients. Parasitemia of 42 symptomatic and 25 asymptomatic individuals was determined by microscopic examination of blood smears and qPCR. Parasitemia density and gametocyte density were assessed as determinants of infection rates and oocysts densities. A strong correlation between gametocyte densities (microscopy and molecular techniques) and mosquito infectivity (P < 0.001) and oocysts median numbers (P < 0.05) was found in both groups. The ability to infect mosquitoes was higher in the symptomatic group (41%), but infectivity in the asymptomatic group was also seen (1.42%). CONCLUSIONS: Although their infectivity to mosquitoes is relatively low, given the high prevalence of P. vivax asymptomatic carriers they are likely to play and important role in malaria transmission in the city of Manaus. The role of asymptomatic infections therefore needs to be considered in future malaria elimination programs in Brazil

Characterization in vitro and in vivo of a pandemic H1N1 influenza virus from a fatal case

Pandemic 2009 H1N1 (pH1N1) influenza viruses caused mild symptoms in most infected patients. However, a greater rate of severe disease was observed in healthy young adults and children without co-morbid conditions. Here we tested whether influenza strains displaying differential virulence could be present among circulating pH1N1 viruses. The biological properties and the genotype of viruses isolated from a patient showing mild disease (M) or from a fatal case (F), both without known co-morbid conditions were compared in vitro and in vivo. The F virus presented faster growth kinetics and stronger induction of cytokines than M virus in human alveolar lung epithelial cells. In the murine model in vivo, the F virus showed a stronger morbidity and mortality than M virus. Remarkably, a higher proportion of mice presenting infectious virus in the hearts, was found in F virus-infected animals. Altogether, the data indicate that strains of pH1N1 virus with enhanced pathogenicity circulated during the 2009 pandemic. In addition, examination of chemokine receptor 5 (CCR5) genotype, recently reported as involved in severe influenza virus disease, revealed that the F virus-infected patient was homozygous for the deleted form of CCR5 receptor (CCR5Δ32).Funding Statement: This work was supported by Instituto de Salud Carlos III (Programa especial de investigación sobre la gripe pándemica GR09/0023, GR09/0040, GR09/0039) and Ciber de Enfermedades Respiratorias. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers

Amyloid-beta 42 (A beta 42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for A beta 42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple A beta 42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.Peer reviewe

Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage

Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use meta-genomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.Peer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele