Overcoming challenges in large-core SI-POF-based system-level modeling and simulation

The application areas for plastic optical fibers such as in-building or aircraft networks usually have tight power budgets and require multiple passive components. In addition, advanced modulation formats are being considered for transmission over plastic optical fibers (POFs) to increase spectral efficiency. In this scenario, there is a clear need for a flexible and dynamic system-level simulation framework for POFs that includes models of light propagation in POFs and the components that are needed to evaluate the entire system performance. Until recently, commercial simulation software either was designed specifically for single-mode glass fibers or modeled individual guided modes in multimode fibers with considerable detail, which is not adequate for large-core POFs where there are millions of propagation modes, strong mode coupling and high variability. These are some of the many challenges involved in the modeling and simulation of POF-based systems. Here, we describe how we are addressing these challenges with models based on an intensity-vs-angle representation of the multimode signal rather than one that attempts to model all the modes in the fiber. Furthermore, we present model approaches for the individual components that comprise the POF-based system and how the models have been incorporated into system-level simulations, including the commercial software packages SimulinkTM and ModeSYSTM

Dopamine and α-synuclein dysfunction in Smad3 null mice

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration in the substantia nigra (SN). Transforming growth factor-β1 (TGF-β1) levels increase in patients with PD, although the effects of this increment remain unclear. We have examined the mesostriatal system in adult mice deficient in Smad3, a molecule involved in the intracellular TGF-β1 signalling cascade.</p> <p>Results</p> <p>Striatal monoamine oxidase (MAO)-mediated dopamine (DA) catabolism to 3,4-dihydroxyphenylacetic acid (DOPAC) is strongly increased, promoting oxidative stress that is reflected by an increase in glutathione levels. Fewer astrocytes are detected in the ventral midbrain (VM) and striatal matrix, suggesting decreased trophic support to dopaminergic neurons. The SN of these mice has dopaminergic neuronal degeneration in its rostral portion, and the pro-survival Erk1/2 signalling is diminished in nigra dopaminergic neurons, not associated with alterations to p-JNK or p-p38. Furthermore, inclusions of α-synuclein are evident in selected brain areas, both in the perikaryon (SN and paralemniscal nucleus) or neurites (motor and cingulate cortices, striatum and spinal cord). Interestingly, these α-synuclein deposits are detected with ubiquitin and P^S129-α-synuclein in a core/halo cellular distribution, which resemble those observed in human Lewy bodies (LB).</p> <p>Conclusions</p> <p>Smad3 deficiency promotes strong catabolism of DA in the striatum (ST), decrease trophic and astrocytic support to dopaminergic neurons and may induce α-synuclein aggregation, which may be related to early parkinsonism. These data underline a role for Smad3 in α-synuclein and DA homeostasis, and suggest that modulatory molecules of this signalling pathway should be evaluated as possible neuroprotective agents.</p

Distinctive Expression and Amplification of Genes at 11q13 in Relation to HPV Status with Impact on Survival in Head and Neck Cancer Patients

Clear differences have been established between head and neck squamous cell carcinomas (HNSCC) depending on human papillomavirus (HPV) infection status. This study specifically investigated the status of the CTTN, CCND1 and ANO1 genes mapping at the 11q13 amplicon in relation to the HPV status in HNSCC patients. CTTN, CCND1 and ANO1 protein expression and gene amplification were respectively analyzed by immunohistochemistry and real-time PCR in a homogeneous cohort of 392 surgically treated HNSCC patients. The results were further confirmed using an independent cohort of 279 HNSCC patients from The Cancer Genome Atlas (TCGA). The impact on patient survival was also evaluated. CTTN, CCND1 and ANO1 gene amplification and protein expression were frequent in HPV-negative tumors, while absent or rare in HPV-positive tumors. Using an independent validation cohort of 279 HNSCC patients, we consistently found that these three genes were frequently co-amplified (28%) and overexpressed (39-46%) in HPV-negative tumors, whereas almost absent in HPV-positive tumors. Remarkably, these alterations (in particular CTTN and ANO1 overexpression) were associated with poor prognosis. Taken together, the distinctive expression and amplification of these genes could cooperatively contribute to the differences in prognosis and clinical outcome between HPV-positive and HPV-negative tumors. These findings could serve as the basis to design more personalized therapeutic strategies for HNSCC patients

New microdeletion and microduplication syndromes: a comprehensive review

Several new microdeletion and microduplication syndromes are emerging as disorders that have been proven to cause multisystem pathologies frequently associated with intellectual disability (ID), multiple congenital anomalies (MCA), autistic spectrum disorders (ASD) and other phenotypic findings. In this paper, we review the “new” and emergent microdeletion and microduplication syndromes that have been described and recognized in recent years with the aim of summarizing their main characteristics and chromosomal regions involved. We decided to group them by genomic region and within these groupings have classified them into those that include ID, MCA, ASD or other findings. This review does not intend to be exhaustive but is rather a quick guide to help pediatricians, clinical geneticists, cytogeneticists and/or molecular geneticists

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Trastorno de las habilidades académicas: Relación de las mismas con pautas de interacción familiar

En este trabajo se pretende evaluar algunas de las características de la estructura y perfil familiares en una muestra de 158 niños entre 7 y 13 años de edad que presentan algunos rasgos significativos de trastornos de las habilidades académicas. La finalidad de esta investigación es aislar los fenómenos de interacción propios de las familias de estos niños con el objetivo de plantear estrategias de intervención en las mismas. La información obtenida a través del Cuestionario Clínico Biográfico Infantil (C.C.B.I.) que se administra de forma sistemática en la Cátedra de Psiquiatría Infantil de la Facultad de Medicina de Sevilla, es analizada estadísticamente, lo cual permite extraer algunas conclusiones de interés y utilidad clínica.The authors of this present work seek to evaluate some characteristics of the family structure and outline, in a sample of 200 children aged between 7 and 13 years who present some significant signs of disturbance in academic abilities. The aim of this study is to isolate phenomenon with regard to interaction within the child family the objective of establishing intervention strategies. The information, obtained through the Child Biographical Clinical Questionnaire which is administered systematically in the Child Psychiatry Faculty of the Department of Medicine, Seville, will be used in the later process of statistical analyses of the data obtained and in the argument of the results, which finally allow the extraction of come interesting and useful conclusions

Resistance to the cereal cyst nematode (Heterodera avenae Woli.) transferred from the wild grass Aegilops ventricosa to hexaploid wheat by a "stepping-stone" procedure

7 páginas y 9 figurasTransfer of resistance to Heterodera avenae, the cereal cyst nematode (CCN), by a "stepping-stone" procedure from the wild grass Aegilops ventricosa to hexaploid wheat has been demonstrated. The number of nematodes per plant was lower, and reached a plateau much earlier, in the resistant introgression line H93-8 (1-2 nematodes per plant) than in the recipient H10-15 wheat (14-16 nematodes per plant). Necrosis (hypersensitive reaction) near the nematode, little cell fusion, and few, often degraded syncytia were observed in infested H93-8 roots, while abundant, well-formed syncytia were present in the susceptible H10-15 wheat. Line H93-8 was highly resistant to the two Spanish populations tested, as well as the four French races (Frl-Fr4), and the British pathotype Hall, but was susceptible to the Swedish pathotypes HgI and HgIII. Resistance was inherited as though determined by a single quasi-dominant factor in the F2 generations resulting from crosses of H93-8 with H10-15 and with Loros, a resistant wheat carrying the gene Crel (syn. Ccnl). The resistance gene in H93-8 (Cre2 or Ccn2) is not allelic with respect to that in Loros. RFLPs and other markers, together with the cytogenetical evidence, indicate that the Cre2 gene has been integrated into a wheat chromosome without affecting its meiotic pairing ability. Introduction of Cre2 by backcrossing into a commercial wheat backgroud increases grain yield when under challenge by the nematode and is not detrimental in the absence of infestation.AGR 89-0193-C03 Comisi6n Interministerial de Ciencia y Tenologia of SpainPeer reviewe

AGC1-malate aspartate shuttle activity is critical for dopamine handling in the nigrostriatal pathway

The mitochondrial transporter of aspartate-glutamate Aralar/AGC1 is a regulatory component of the malate-aspartate shuttle. Aralar deficiency in mouse and human causes a shutdown of brain shuttle activity and global cerebral hypomyelination. A lack of neurofilament-labeled processes is detected in the cerebral cortex, but whether different types of neurons are differentially affected by Aralar deficiency is still unknown. We have now found that Aralar-knockout (Aralar-KO) post-natal mice show hyperactivity, anxiety-like behavior, and hyperreactivity with a decrease of dopamine (DA) in terminal-rich regions. The striatum is the brain region most affected in terms of size, amino acid and monoamine content. We find a decline in vesicular monoamine transporter-2 (VMAT2) levels associated with increased DA metabolism through MAO activity (DOPAC/DA ratio) in Aralar-KO striatum. However, no decrease in DA or in the number of nigral tyrosine hydroxylase-positive cells was detected in Aralar-KO brainstem. Adult Aralar-hemizygous mice presented also increased DOPAC/DA ratio in striatum and enhanced sensitivity to amphetamine. Our results suggest that Aralar deficiency causes a fall in GSH/GSSG ratio and VMAT2 in striatum that might be related to a failure to produce mitochondrial NADH and to an increase of reactive oxygen species (ROS) in the cytosol. The results indicate that the nigrostriatal dopaminergic system is a target of Aralar deficiency. © 2012 International Society for Neurochemistry.Ministerio de Educacion y Ciencia BFU2008-04084/BMC; Ministerio de Ciencia e Innovacion (SAF2010-16427); Comunidad de Madrid SGEN-0269-2006 MITOLAB-CM; European Union LSHM-CT-2006-518153; CureFXS E-Rare; EU/FIS PS09102673; Spanish Ministry of Health (PI 082038 to MD); Marato TV3, Jerome Lejeune (JMLM/AC/08-044); Fundacion Medica Mutua Madrileña; Fundacion Ramon ArecesPeer Reviewe

EFECTIVIDAD CLÍNICA DEL MÉTODO MUCOTÉRMICO PARA REGULAR LA FERTILIDAD: RESULTADOS DE UN PROGRAMA APLICADO EN LA COMUNA DE SAN BERNARDO

Antecedentes: Los métodos naturales modernos para la regulación de la fertilidad (MNMRF) son un sistema estandarizado de instrucciones que, aplicadas correctamente por la usuaria, le permiten diagnosticar con precisión los días de infertilidad y de fertilidad presentes en un ciclo menstrual. Su aplicabilidad clínica como método para regular la fertilidad ha sido ampliamente documentada. Los MNMRF permiten, a su vez, evaluar el funcionamiento endocrino gonadal de la usuaria. Objetivos: El objetivo principal fue determinar la efectividad clínica para espaciar los embarazos de los MNMRF en un programa aplicado en la comuna de San Bernardo. El objetivo secundario fue describir las características socio demográficas de las usuarias de los MNMRF. Método: Estudio de cohorte prospectivo. La intervención consistió en la instrucción modular de un método mucotérmico. Resultados: Se reportan los resultados de todas las pacientes consecutivas ingresadas al programa entre el 1° de enero de 1996 hasta el 31 de diciembre de 2003 que hayan finalizado la instrucción. Contactaron el programa 600 pacientes, de las que 389 (64,8%) comenzaron efectivamente el proceso de instrucción completándolo a la fecha de cierre de este análisis el 67,6% de ellas (263/389). La efectividad clínica, calculada con tabla de sobrevida, fue de 94,3% (IC: 86,8-97,6). Conclusiones: El método natural enseñado es altamente efectivo para espaciar o limitar los nacimiento