84 research outputs found

    Detekcija polimorfizama jednog nukleotida (SNP-a) u HER2, MUC1, ESR1 i BRCA1 gena povezanih s tumorom mlijeńćne Ňĺlijezde kuja

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    Worldwide, canine mammary cancer (CMC) is the most frequent type of neoplasia in female dogs, and it is three times more frequent in dogs than in humans. In Colombia, CMC is the second most frequent type of cancer, after skin neoplasia. Genetics is one of the most important factors involved in any type of cancer, and the genetic basis of this disease is reflected through line breeding due to changes in allelic frequencies that are traceable using molecular markers. This study aimed to detect single nucleotide polymorphisms (SNPs) associated with CMC in blood samples collected from collected from healthy and CMC female dogs at Diego Villegas Toro Veterinary Hospital of Universidad de Caldas (Manizales, Colombia). We designed primers using Primer-BLAST and Primer3, and gene fragments from HER2, MUC1, ESR1, and BRCA1 were amplified to identify SNPs through genome mapping using the UCSC Genome Institute genome browser. We used the genome of Canis lupus familaris Boxer breed [GCF_000002285.3, (CanFam 3.1)] as a reference to compare the gene fragments and SNPs. We associated SNPs with the CMC and control groups by testing odds ratios (OR) through Fisher‚Äôs exact tests to determine an association or risk for CMC. We detected two SNPs for ESR1, three for MUC1, six for HER2, and one for BRCA1. MUC1 was the only gene to display an SNP in an exonic region that resulted in an amino acid substitution (Pro>Thr). No significant differences based on the OR were found, though the majority of SNPs, with the exception of four, were found in females with CMC. We report a novel molecular marker for HER2 that amplifies exons 25‚Äď26 and introns 24-25, and highlight the importance of conducting further studies on MUC1 and elucidating the role of introns and splicing in candidate genes associated with CMC.Diljem svijeta, tumor mlijeńćne Ňĺlijezde kuja (CMC) najńćeŇ°ńáa je skupina neoplazija kuja te je tri puta uńćestalija u pasa nego u ljudi. U Kolumbiji, CMC je bio druga najńćeŇ°ńáa vrsta tumora, nakon neoplazija na koŇĺi. Nadalje, genetika je jedan od najvaŇĺnijih ńćimbenika ukljuńćenih u bilo koju vrstu tumora, a genetska baza ove bolesti odrŇĺava se kroz linijski uzgoj uslijed promjena alelnih frekvencija, koje se mogu pratiti preko molekularnih markera. Ova studija imala je za cilj detektirati polimorfizme jednog nukleotida (SNP-e) povezane s CMC-om u uzorcima krvi prikupljenih od kuja s CMC-om i zdravih kuja u veterinarskoj bolnici Diego Villegas Toro SveuńćiliŇ°ta Caldas (Manizales, Kolumbija). Dizajnirali smo pońćetnice uporabom Primer-BLAST i Primer3 te su fragmenti gena HER2, MUC1, ESR1 i BRCA1 pojańćani za identifikaciju SNP-a preko mapiranja genoma uporabom preglednika genoma Instituta za genom SveuńćiliŇ°ta Santa Cruz u Kaliforniji (UCSC). Rabili smo genom Canis lupus familaris pasmine bokser [GCF_000002285.3, (CanFam 3.1)] kao referencu za usporedbu fragmenata gena i SNP-a. Povezali smo SNP-e s CMC-om i kontrolnim skupinama testiranjem omjera izgleda (OR) pomońáu Fisherovih egzaktnih testova za odreńĎivanje povezanosti ili rizika od CMC-a. Detektirali smo dva SNP-a za ESR1, tri za MUC1, Ň°est za HER2 i jedan za BRCA1. MUC1 je bio jedini gen koji je pokazao SNP u regiji egzona Ň°to je rezultiralo supstitucijom aminokiseline (Pro>Thr). Nismo pronaŇ°li znańćajne razlike na temelju OR-a, premda je veńáina SNP-a, izuzev ńćetiri, pronańĎena u kuja s CMC-om. Prijavljujemo novi molekularni marker za HER2 koji pojańćava egzone 25 - 26 i introne 24 - 25 te naglaŇ°avamo vaŇĺnost provońĎenja dodatnih studija na MUC1, kao i pojaŇ°njenja uloge introna i izrezivanja u gena kandidata poveznih s CMC-om

    Procjena gama-aktina, beta-aktina, gliceraldehid-3-fosfat dehidrogenaze i 18S kao referentnih gena za qRT-PCR uporabom uzoraka krvi u istraŇĺivanju mlijeńćnih Ňĺlijezda kujica

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    Mammary tumours are the most frequent group of neoplasia in female dogs. Tumorigenesis is associated with gene expression changes in a wide variety of genes. For this reason, real-time quantitative PCR (qRT-PCR) is used in routine diagnostic procedures in clinical practice due to its the specificity, sensitivity, simplicity, and high performance. qRT-PCR is also widely used to measure the expression of target genes compared to reference genes in several tissues. We collected blood samples from healthy female dogs and females with canine mammary cancer in Manizales, Colombia between June 2018 and January 2019, and mRNA was isolated from each sample for cDNA synthesis. qRT-PCR-based expression assays were performed using primers designed for gamma-actin, beta-actin, GAPDH, and 18S genes. We calculated the amplification efficiency, specificity, and stability using geNorm, NormFinder, BestKeeper, and the őĒCt comparative method. We obtained linear regressions to verify constant gene expression and conducted an ANOVA to detect expression differences regarding Ct values and healthy vs. ill conditions. We found stability for primers 18S-1, GAPDH-1, GAPDH-NM, and Gamma-actin-1 (in increasing order). Furthermore, these genes showed constant expression levels in patients (R2>0.80). We report novel primers for gamma-actin and GAPDH, which proved to be efficient endogenous control genes for qRT-PCR applications in blood tissue. These primers are useful for gene expression research in canine mammary cancer.Tumori mlijeńćnih Ňĺlijezda najńćeŇ°ńáa su skupina neoplazija u kujica. Tumorogeneza je povezana s promjenama u ekspresiji gena u Ň°irokom rasponu gena. Iz tog razloga se rabi kvantitativna lanńćana reakcija polimerazom u stvarnom vremenu (qRT-PCR) u rutinskim dijagnostińćkim postupcima u klinińćkoj praksi, uslijed specifińćnosti, osjetljivosti, jednostavnosti i visoke uńćinkovitosti ove tehnike. qRT-PCR se Ň°iroko rabi i za mjerenje ekspresije ciljanih gena u usporedbi s referentnim genima u viŇ°e vrsta tkiva. Prikupili smo uzorke krvi zdravih kujica i kujica s tumorom mlijeńćnih Ňĺlijezda u Manizalesu, Kolumbiji, od lipnja 2018. do sijeńćnja 2019. godine. Izolirali smo mRNK iz svakog uzorka za cDNK sintezu. Pokusi ekspresije na bazi qRT-PCR obavljeni su uporabom primera dizajniranih za gama-aktin, beta-aktin, gliceraldehid- 3-fosfat dehidrogenazu (GAPDH) i 18S gene. Izrańćunali smo pojańćanu uńćinkovitost, specifińćnost i stabilnost uporabom geNorm, NormFinder, BestKeeper i őĒCt komparativne metode. Dobili smo linearne regresije za potvrńĎivanje stalne ekspresije gena i proveli smo analizu varijance (ANOVA) za detekciju razlika u ekspresiji s obzirom na Ct vrijednosti te zdrava u usporedbi s bolesnim stanjima. Otkrili smo i stabilnost za primere 18S-1, GAPDH-1, GAPDH-NM i Gamma-actin-1 (rastuńáim redoslijedom). Nadalje, ovi geni su pokazali konstantne razine ekspresije u pacijenata (R2>0,80). IzvjeŇ°tavamo o novim primerima za gama-aktin i GAPDH, koji su se pokazali uńćinkovitim endogenim kontrolnim genima za qRT-PCR primjene u krvnom tkivu. Ti primeri su korisni za istraŇĺivanje ekspresije gena u tumora pseńáih mlijeńćnih Ňĺlijezda

    Present Status and Future Programs of the n_TOF Experiment

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    This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial License 3.0, which permits unrestricted use, distribution, and reproduction in any noncommercial medium, provided the original work is properly citedThe neutron time-of-flight facility n_TOF at CERN, Switzerland, operational since 2001, delivers neutrons using the Proton Synchrotron (PS) 20 GeV/c proton beam impinging on a lead spallation target. The facility combines a very high instantaneous neutron flux, an excellent time of flight resolution due to the distance between the experimental area and the production target (185 meters), a low intrinsic background and a wide range of neutron energies, from thermal to GeV neutrons. These characteristics provide a unique possibility to perform neutron-induced capture and fission cross-section measurements for applications in nuclear astrophysics and in nuclear reactor technology.The most relevant measurements performed up to now and foreseen for the future will be presented in this contribution. The overall efficiency of the experimental program and the range of possible measurements achievable with the construction of a second experimental area (EAR-2), vertically located 20 m on top of the n_TOF spallation target, might offer a substantial improvement in measurement sensitivities. A feasibility study of the possible realisation of the installation extension will be also presented

    Cross section measurements of 155,157Gd(n, ő≥) induced by thermal and epithermal neutrons

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    © SIF, Springer-Verlag GmbH Germany, part of Springer Nature 2019Neutron capture cross section measurements on 155Gd and 157Gd were performed using the time-of-flight technique at the n_TOF facility at CERN on isotopically enriched samples. The measurements were carried out in the n_TOF experimental area EAR1, at 185 m from the neutron source, with an array of 4 C6D6 liquid scintillation detectors. At a neutron kinetic energy of 0.0253 eV, capture cross sections of 62.2(2.2) and 239.8(8.4) kilobarn have been derived for 155Gd and 157Gd, respectively, with up to 6% deviation relative to values presently reported in nuclear data libraries, but consistent with those values within 1.6 standard deviations. A resonance shape analysis has been performed in the resolved resonance region up to 181 eV and 307 eV, respectively for 155Gd and 157Gd, where on average, resonance parameters have been found in good agreement with evaluations. Above these energies and up to 1 keV, the observed resonance-like structure of the cross section has been analysed and characterised. From a statistical analysis of the observed neutron resonances we deduced: neutron strength function of 2. 01 (28) × 10 - 4 and 2. 17 (41) × 10 - 4; average total radiative width of 106.8(14) meV and 101.1(20) meV and s-wave resonance spacing 1.6(2) eV and 4.8(5) eV for n + 155Gd and n + 157Gd systems, respectively.Peer reviewedFinal Accepted Versio

    Ni-62(n,gamma) and Ni-63(n,gamma) cross sections measured at the n_TOF facility at CERN

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    The cross section of the Ni-62(n,gamma) reaction was measured with the time-of-flight technique at the neutron time-of-flight facility n_TOF at CERN. Capture kernels of 42 resonances were analyzed up to 200 keV neutron energy and Maxwellian averaged cross sections (MACS) from kT = 5-100 keV were calculated. With a total uncertainty of 4.5%, the stellar cross section is in excellent agreement with the the KADoNiS compilation at kT = 30 keV, while being systematically lower up to a factor of 1.6 at higher stellar temperatures. The cross section of the Ni-63(n,gamma) reaction was measured for the first time at n_TOF. We determined unresolved cross sections from 10 to 270 keV with a systematic uncertainty of 17%. These results provide fundamental constraints on s-process production of heavier species, especially the production of Cu in massive stars, which serve as the dominant source of Cu in the solar system.Peer reviewedFinal Accepted Versio

    Report on G4‚ÄźMed, a Geant4 benchmarking system for medical physics applications developed by the Geant4 Medical Simulation Benchmarking Group

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    Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro‚Äź and nano‚Äź dosimetry, imaging, radiation protection and nuclear medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing. To respond to these needs, we developed G4‚ÄźMed, a benchmarking and regression testing system of Geant4 for medical physics, that currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the pre‚Äźbuilt, Geant4 physics lists are tested. The tests included in G4‚ÄźMed are executed on the CERN computing infrastructure via the use of the geant‚Äźval web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes. This paper describes the tests included in G4‚ÄźMed and shows the results derived from the benchmarking of Geant4 10.5 against reference data. The results presented and discussed in this paper will aid users in tailoring physics lists to their particular application.D. Bolst acknowledges the support of the Australian Government Research Training Program Scholarship. M. A. Cort ŐĀes-Giraldo, A. Perales, and J. M. Quesada acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness under grant FPA2016-77689-C2-1-R. B. Faddegon and J. Ramos-M ŐĀendez acknowledge partial financial support from the NIH grant U24CA215123. D. Bolst, S. Guatelli, D. Sakata, S.Incerti, and I. Kyriakou acknowledge financial support from the Australian Research Council, ARC DP170100967. S. Incerti acknowledges the financial support of CNRS through the IN2P3/MOVI Master Project and through the France-Greece PICS 8235 funding scheme. I. Kyriakou acknowledges additional financial support from the European Space Agency (Contract No. 4000126645/19/NL/BW). E. C. Simpson acknowledges financial support from the Australian Research Council under grant DP170102423. I. Sechopoulos and C. Fedon acknowledge financial support from the Susan G Komen Foundation for the Cure grant IIR13262248. S. Guatelli and D. Bolst acknowlege the use of computing resources of the Aus-tralian National Computing Infrastructure (NCI), through the NCMAS 2020 grant scheme

    Colombian consensus on the diagnosis, treatment, and prevention of candida Spp. disease in children and adults

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    La Candidiasis Invasora (CI) y la candidemia, como su manifestaci√≥n m√°s frecuente, se ha convertido en la principal causa de micosis oportunista a nivel hospitalario. Este manuscrito realizado por miembros de la Asociaci√≥n Colombiana de Infectolog√≠a (ACIN), tuvo como objetivo proporcionar un conjunto de recomendaciones para manejo, seguimiento y prevenci√≥n de la CI/candidemia y de la infecci√≥n candidi√°sica de mucosas, en poblaci√≥n adulta, pedi√°trica y neonatal, en un entorno hospitalario, incluyendo las unidades hemato-oncol√≥gicas y unidades de cuidado cr√≠tico. Todos los datos obtenidos mediante una b√ļsqueda exhaustiva, fueron revisados y analizados de manera amplia por todos los miembros del grupo, y las recomendaciones emitidas se elaboraron luego de la evaluaci√≥n de la literatura cient√≠fica disponible, y el consenso de todos los especialistas involucrados, reconociendo el problema de la emergencia de las infecciones por Candida Spp. y brindando una correcta orientaci√≥n a los profesionales de la salud sobre el manejo de pacientes con enfermedad candidi√°sica, de una forma racional y pr√°ctica, enfatizando en la evaluaci√≥n del paciente, estrategias de diagn√≥stico, profilaxis, tratamiento emp√≠rico, tratamiento dirigido y terapia preventiva.Invasive Candidiasis (IC) and candidemia (as its most frequent manifestation) have become the main cause of opportunistic mycosis at hospital settings. This study, made by members of the Colombian Association of Infectious Diseases (ACIN), was aimed at providing a set of recommendations for the management, follow-up and prevention of IC / candidemia and mucous membrane candida infection in adult, pediatric and neonatal patients in a hospital setting, including the hemato-oncological and critical care units. All the data obtained through an exhaustive search were reviewed and analyzed in a comprehensive manner by all the members of the group, and the recommendations issued are being made after a careful review of the scientific literature available and the consensus of all specialists involved; the emergence of Candida Spp. problem is highlighted and a correct orientation to health professionals regarding the management of patients with candidiasis is provided in a rational and practical way, emphasizing patient evaluation, diagnostic strategies, prophylaxis, empirical treatment, directed treatment and preventative therap

    Measurement of the Ge 70 (n,ő≥) cross section up to 300 keV at the CERN n-TOF facility

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    ¬©2019 American Physical Society.Neutron capture data on intermediate mass nuclei are of key importance to nucleosynthesis in the weak component of the slow neutron capture processes, which occurs in massive stars. The (n,ő≥) cross section on Ge70, which is mainly produced in the s process, was measured at the neutron time-of-flight facility n-TOF at CERN. Resonance capture kernels were determined up to 40 keV neutron energy and average cross sections up to 300 keV. Stellar cross sections were calculated from kT=5 keV to kT=100 keV and are in very good agreement with a previous measurement by Walter and Beer (1985) and recent evaluations. Average cross sections are in agreement with Walter and Beer (1985) over most of the neutron energy range covered, while they are systematically smaller for neutron energies above 150 keV. We have calculated isotopic abundances produced in s-process environments in a 25 solar mass star for two initial metallicities (below solar and close to solar). While the low metallicity model reproduces best the solar system germanium isotopic abundances, the close to solar model shows a good global match to solar system abundances in the range of mass numbers A=60-80.Peer reviewedFinal Published versio

    Towards the high-accuracy determination of the 238U fission cross section at the threshold region at CERN - N-TOF

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    The 238U fission cross section is an international standard beyond 2 MeV where the fission plateau starts. However, due to its importance in fission reactors, this cross-section should be very accurately known also in the threshold region below 2 MeV. The 238U fission cross section has been measured relative to the 235U fission cross section at CERN - n-TOF with different detection systems. These datasets have been collected and suitably combined to increase the counting statistics in the threshold region from about 300 keV up to 3 MeV. The results are compared with other experimental data, evaluated libraries, and the IAEA standards

    Support vector machine versus logistic regression modeling for prediction of hospital mortality in critically ill patients with haematological malignancies

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    Background: Several models for mortality prediction have been constructed for critically ill patients with haematological malignancies in recent years. These models have proven to be equally or more accurate in predicting hospital mortality in patients with haematological malignancies than ICU severity of illness scores such as the APACHE II or SAPS II [1]. The objective of this study is to compare the accuracy of predicting hospital mortality in patients with haematological malignancies admitted to the ICU between models based on multiple logistic regression (MLR) and support vector machine (SVM) based models. Methods: 352 patients with haematological malignancies admitted to the ICU between 1997 and 2006 for a life-threatening complication were included. 252 patient records were used for training of the models and 100 were used for validation. In a first model 12 input variables were included for comparison between MLR and SVM. In a second more complex model 17 input variables were used. MLR and SVM analysis were performed independently from each other. Discrimination was evaluated using the area under the receiver operating characteristic (ROC) curves (+/- SE). Results: The area under ROC curve for the MLR and SVM in the validation data set were 0.768 (+/- 0.04) vs. 0.802 (+/- 0.04) in the first model (p = 0.19) and 0.781 (+/- 0.05) vs. 0.808 (+/- 0.04) in the second more complex model (p = 0.44). SVM needed only 4 variables to make its prediction in both models, whereas MLR needed 7 and 8 variables in the first and second model respectively. Conclusion: The discriminative power of both the MLR and SVM models was good. No statistically significant differences were found in discriminative power between MLR and SVM for prediction of hospital mortality in critically ill patients with haematological malignancies
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