Genotype x dose of artificial insemination interaction for buck fertility

Ponencia publicada en ITEA, vol.104El objetivo de este trabajo fue estimar los parámetros genéticos de la fertilidad tras la IA con 3 tipos de dosis obtenidas de eyaculados de machos de la línea Caldes: 1) tipo 10: con 10 x 106 espermatozoides/ml y 24h de conservación en un diluyente comercial tipo A. 2) tipo 40: con 40 x 106 espermatozoides/ml y las mismas condiciones de conservación que las del tipo 10. 3) tipo X: dosis preparadas tras diluir los eyaculados con un diluyente comercial tipo B (1:5) siendo desconocida la concentración y sin periodo de conservación. Se realizaron 3,628 IA con dosis del tipo 10 sobre hembras cruzadas, 3,027 con dosis del tipo 40 y la misma población de hembras, y 5,779 con dosis del tipo X sobre hembras puras de la línea Caldes. La fertilidad tras la IA con dosis del tipo 10 (F10), 40 (F40) y X (FX) fue considerada un carácter distinto en cada caso, de tipo binario. Los datos se analizaron utilizando un modelo umbral tri-carácter. La estima de la media de la distribución marginal posterior (DMP) de F10 menos F40 fue de -0.13. Este resultado indica un claro efecto de la concentración sobre la fertilidad, que podría no ser lineal. Las medias de la DMP de F10 menos FX y F40 menos FX fueron -0.37 y -0.23, respectivamente, lo que indica que el efecto de las condiciones de conservación sobre la fertilidad podría ser más importante que el de la concentración ya que FX fue muy próxima a la fertilidad tras la MN y la concentración del tipo de dosis X sería en promedio de unos 50 x 106 espermatozoides/ml. Las heredabilidades parecen ser similares para F10 y F40 y ambas mayores que las correspondientes a la fertilidad tras la MN y a FX. La interacción del genotipo x concentración de la dosis de IA es prácticamente despreciable debido a que las varianzas genéticas fueron similares para F10 y F40 y a que su correlación genética fue próxima a 1. Sin embargo, la interacción podría ser de mayor importancia entre el genotipo y las condiciones de conservación.The aim of this research was to estimate genetic parameters of male fertility after AI with three different types of AI doses obtained from ejaculates of bucks belonging to the Caldes line: 1) type 10: doses with 10 x 106 spermatozoa/ml and a period of 24 h of storage at 18ºC in a saline extender A. 2) type 40: doses with 40 x 106 spermatozoa/ml and the same storage conditions as type 10. 3) type X, doses prepared with semen diluted (1:5) with a saline extender B, but with unknown sperm dosage and no storage period. 3,628 AI were performed with the type 10 doses using crossbred females, 3,027 with the type 40 doses and the same population of females, and 5,779 with the type X doses, using purebred M. Piles et al. ITEA (2008), Vol. 104 (2), 160-168 16 females from the Caldes line in a different farm. Fertility after AI with type 10 doses (F10), type 40 doses (F40) and type X doses (FX) was considered as three different binary traits. Data were analyzed under a three-trait threshold model. The mean of the marginal posterior distribution (MPD) for F10 minus F40 was estimated to be -0.13. This result indicates a clear effect of the sperm dosage on fertility, which could be non-linear. The mean of the MPD of F10 minus FX and F40 minus FX were respectively, -0.37 and -0.23 which indicates that the effect of the storage conditions on fertility could be even more important on fertility than sperm dosage, since FX was very close to fertility after NM and sperm dosage of this type of doses was in average lower than 50 x 106 spermatozoa/ml. Heritabilities seem to be similar for F10 and F40 and both of them could be higher than heritability of male fertility after NM and FX. Variance of the genotype x sperm dosage interaction was almost negligible since additive variances were similar for F10 and F40 and their genetic correlation was close to 1. However, this interaction could be more important between the genotype and the storage conditions

Deep learning-based lung segmentation and automatic regional template in chest X-ray images for pediatric tuberculosis

Tuberculosis (TB) is still considered a leading cause of death and a substantial threat to global child health. Both TB infection and disease are curable using antibiotics. However, most children who die of TB are never diagnosed or treated. In clinical practice, experienced physicians assess TB by examining chest X-rays (CXR). Pediatric CXR has specific challenges compared to adult CXR, which makes TB diagnosis in children more difficult. Computer-aided diagnosis systems supported by Artificial Intelligence have shown performance comparable to experienced radiologist TB readings, which could ease mass TB screening and reduce clinical burden. We propose a multi-view deep learning-based solution which, by following a proposed template, aims to automatically regionalize and extract lung and mediastinal regions of interest from pediatric CXR images where key TB findings may be present. Experimental results have shown accurate region extraction, which can be used for further analysis to confirm TB finding presence and severity assessment. Code publicly available at https://github.com/dani-capellan/pTB_LungRegionExtractor.Comment: This work has been accepted at the SPIE Medical Imaging 2023, Image Processing conferenc

Consensus of experts from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines

5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines

YKT6 expression, exosome release, and survival in non-small cell lung cancer

BACKGROUND: Cancer-derived exosomes are involved in metastasis. YKT6 is a SNARE protein that participates in the regulation of exosome production and release, but its role in non-small cell lung cancer (NSCLC) has not been examined. MATERIALS AND METHODS: Ultracentrifugation-purified exosomes from the A549 cell line were studied by CRYO-TEM, nanoparticle tracking analysis and western blot (TSG101 marker). YKT6 was inhibited using a DsiRNA and selected pre-microRNAs. MicroRNAs targeting YKT6 were validated by Renilla/Luciferase assay and western blot. YKT6 expression and its prognostic impact were analyzed in 98 tissue specimens from resected NSCLC patients. RESULTS: Membranous nanosized vesicles (mode size: 128nm) with TSG101 protein were purified from A549 cells. YKT6 inhibition reduced exosome release by 80.9%. We validated miR-134 and miR-135b as miRNAs targeting YKT6, and transfection with the pre-miRNAs also produced a significant reduction in exosome release. The analysis of YKT6 in tumor samples showed that patients with high levels had shorter disease-free and overall survival. CONCLUSIONS: YKT6 is a key molecule in the regulation of exosome release in lung cancer cells and is in turn precisely regulated by miR-134 and miR-135b. Moreover, YKT6 levels impact prognosis of resected NSCLC patients

Discovery of Very High Energy gamma-rays from 1ES 1011+496 at z=0.212

We report on the discovery of Very High Energy (VHE) gamma-ray emission from the BL Lacertae object 1ES1011+496. The observation was triggered by an optical outburst in March 2007 and the source was observed with the MAGIC telescope from March to May 2007. Observing for 18.7 hr we find an excess of 6.2 sigma with an integrated flux above 200 GeV of (1.58$\pm0.32) 10^{-11}$ photons cm$^{-2}$ s$^{-1}$. The VHE gamma-ray flux is >40% higher than in March-April 2006 (reported elsewhere), indicating that the VHE emission state may be related to the optical emission state. We have also determined the redshift of 1ES1011+496 based on an optical spectrum that reveals the absorption lines of the host galaxy. The redshift of z=0.212 makes 1ES1011+496 the most distant source observed to emit VHE gamma-rays up to date.Comment: 4 pages, 6 figures, minor changes to fit the ApJ versio

Unfolding of differential energy spectra in the MAGIC experiment

The paper describes the different methods, used in the MAGIC experiment, to unfold experimental energy distributions of cosmic ray particles (gamma-rays). Questions and problems related to the unfolding are discussed. Various procedures are proposed which can help to make the unfolding robust and reliable. The different methods and procedures are implemented in the MAGIC software and are used in most of the analyses.Comment: Submitted to NIM

Implementation of the Random Forest Method for the Imaging Atmospheric Cherenkov Telescope MAGIC

The paper describes an application of the tree classification method Random Forest (RF), as used in the analysis of data from the ground-based gamma telescope MAGIC. In such telescopes, cosmic gamma-rays are observed and have to be discriminated against a dominating background of hadronic cosmic-ray particles. We describe the application of RF for this gamma/hadron separation. The RF method often shows superior performance in comparison with traditional semi-empirical techniques. Critical issues of the method and its implementation are discussed. An application of the RF method for estimation of a continuous parameter from related variables, rather than discrete classes, is also discussed.Comment: 16 pages, 8 figure

MAGIC Upper Limits for two Milagro-detected, Bright Fermi Sources in the Region of SNR G65.1+0.6

We report on the observation of the region around supernova remnant G65.1+0.6 with the stand-alone MAGIC-I telescope. This region hosts the two bright GeV gamma-ray sources 1FGL J1954.3+2836 and 1FGL J1958.6+2845. They are identified as GeV pulsars and both have a possible counterpart detected at about 35 TeV by the Milagro observatory. MAGIC collected 25.5 hours of good quality data, and found no significant emission in the range around 1 TeV. We therefore report differential flux upper limits, assuming the emission to be point-like (<0.1 deg) or within a radius of 0.3 deg. In the point-like scenario, the flux limits around 1 TeV are at the level of 3 % and 2 % of the Crab Nebula flux, for the two sources respectively. This implies that the Milagro emission is either extended over a much larger area than our point spread function, or it must be peaked at energies beyond 1 TeV, resulting in a photon index harder than 2.2 in the TeV band.Comment: 8 pages, 3 figures, 1 tabl

Systematic search for VHE gamma-ray emission from X-ray bright high-frequency BL Lac objects

All but three (M87, BL Lac and 3C 279) extragalactic sources detected so far at very high energy (VHE) gamma-rays belong to the class of high-frequency peaked BL Lac (HBL) objects. This suggested to us a systematic scan of candidate sources with the MAGIC telescope, based on the compilation of X-ray blazars by Donato et al. (2001). The observations took place from December 2004 to March 2006 and cover sources on the northern sky visible under small zenith distances zd < 30 degrees at culmination. The sensitivity of the search was planned for detecting X-ray bright F(1 keV) > 2 uJy) sources emitting at least the same energy flux at 200 GeV as at 1 keV. In order to avoid strong gamma-ray attenuation close to the energy threshold, the redshift of the sources was constrained to values z<0.3. Of the fourteen sources observed, 1ES 1218+304 and 1ES 2344+514 have been detected in addition to the known bright TeV blazars Mrk 421 and Mrk 501. A marginal excess of 3.5 sigma from the position of 1ES 1011+496 was observed and has been confirmed as a source of VHE gamma-rays by a second MAGIC observation triggered by a high optical state (Albert et al. 2007). For the remaining sources, we present here the 99% confidence level upper limits on the integral flux above ~200 GeV. We characterize the sample of HBLs (including all HBLs detected at VHE so far) by looking for correlations between their multi-frequency spectral indices determined from simultaneous optical, archival X-ray, and radio luminosities, finding that the VHE emitting HBLs do not seem to constitute a unique subclass. The absorption corrected gamma-ray luminosities at 200 GeV of the HBLs are generally not higher than their X-ray luminosities at 1 keV.Comment: 15 pages, 7 figures, 5 tables, submitted to ApJ (revised version

Upper limit for gamma-ray emission above 140 GeV from the dwarf spheroidal galaxy Draco

The nearby dwarf spheroidal galaxy Draco with its high mass to light ratio is one of the most auspicious targets for indirect dark matter searches. Annihilation of hypothetical DM particles can result in high-energy gamma-rays, e.g. from neutralino annihilation in the supersymmetric framework. With the MAGIC telescope a search for a possible DM signal originating from Draco was performed during 2007. The analysis of the data results in a flux upper limit of 1.1x10^-11 photons cm^-2 sec^-1 for photon energies above 140 GeV, assuming a point like source. Furthermore, a comparison with predictions from supersymmetric models is given. While our results do not constrain the mSUGRA phase parameter space, a very high flux enhancement can be ruled out.Comment: Accepted for publication by Astrophysical Journa