Crizotinib-induced antitumour activity in human alveolar rhabdomyosarcoma cells is not solely dependent on ALK and MET inhibition

BACKGROUND: Rhabdomyosarcoma (RMS) is the most commonly diagnosed malignant soft tissue tumour in children and adolescents. Aberrant expression of Anaplastic Lymphoma Kinase (ALK) and MET gene has been implicated in the malignant progression of RMS, especially in the alveolar subtype. This observation suggests that crizotinib (PF-02341066), a kinase inhibitor against ALK and MET, may have a therapeutic role in RMS, although its antitumour activity in this malignancy has not yet been studied. METHODS: RH4 and RH30 alveolar RMS (ARMS) cell lines were treated with crizotinib and then assessed by using proliferation, viability, migration and colony formation assays. Multiple approaches, including flow cytometry, immunofluorescence, western blotting and siRNA-based knock-down, were used in order to investigate possible molecular mechanisms linked to crizotinib activity. RESULTS: In vitro treatment with crizotinib inhibited ALK and MET proteins, as well as Insulin-like Growth Factor 1 Receptor (IGF1R), with a concomitant robust dephosphorylation of AKT and ERK, two downstream kinases involved in RMS cell proliferation and survival. Exposure to crizotinib impaired cell growth, and accumulation at G2/M phase was attributed to an altered expression and activation of checkpoint regulators, such as Cyclin B1 and Cdc2. Crizotinib was able to induce apoptosis and autophagy in a dose-dependent manner, as shown by caspase-3 activation/PARP proteolytic cleavage down-regulation and by LC3 activation/p62 down-regulation, respectively. The accumulation of reactive oxygen species (ROS) seemed to contribute to crizotinib effects in RH4 and RH30 cells. Moreover, crizotinib-treated RH4 and RH30 cells exhibited a decreased migratory/invasive capacity and clonogenic potential. CONCLUSIONS: These results provide a further insight into the molecular mechanisms affected by crizotinib in ARMS cells inferring that it could be a useful therapeutic tool in ARMS cancer treatment

Statistical assessment of feeding corn with higher oil content to piglets in the starter phase

The aim of this study was to assess the digestibility coefficients (DC) of corn [maize] with an oil content above 3.46% and its effects on the performance of piglets when fed as dry grain (DG) and as rehydrated corn grain silage (RCGS). In Experiment I, 15 piglets (22.51 + 2.39 kg) were allocated to a reference diet (RD) and to two test diets in which corn in the RD was replaced with DG or RCGS. There were five replications of each treatment. Experiment II involved 36 piglets (14.76 ± 2.72 kg), which were assigned to a control diet with common corn grain and to diets in which DG or RCGS replaced the common corn. There were six replications of each treatment. Data were analysed with four statistical models. Model 1 included only the effect of treatment. Model 2 was similar to Model 1 but included initial bodyweight as a covariate. Model 3 was similar to model 1 but included the interaction of diet and period. Model 4 was similar to Model 3 but included the covariate. The more complicated models were generally preferred to Model 1 as they controlled more of the nuisance variation. Feeding a diet that contained RCGS reduced feed intake and improved feed conversion ratio (FCR)

Avaliação bioeconômica de dietas para leitões no pós-desmame contendo milho naturalmente contaminado por micotoxinas.

Foi realizado um estudo para calcular os índices bioeconômicos de milho naturalmente contaminado por micotoxinas para leitões. Foram utilizados índices zootécnicos de um experimento prévio no qual foram avaliadas dietas com e sem micotoxinas, com três repetições e um animal por repetição. A partir dos resultados de ganho de peso e consumo de ração, foram calculados os bioíndices para estimar o preço máximo do milho. Posteriormente, foram aplicados os preços vigentes do período (junho/15, novembro/14, outubro/14, julho/12 e junho/11) para estimar o custo máximo do milho contaminado para ser economicamente igual às dietas com milho sem contaminação. Os bioíndices do leitão e do milho apresentaram maior efeito no preço do milho contaminado por micotoxinas e o seu uso foi economicamente inviável, na fase de creche, em todas as condições de mercado testadas

Marteletes desgastados afetam negativamente as características operacionais da moagem e físicas do milho processado em moinho do tipo martelo

Foi conduzido um trabalho para avaliar os efeitos dos níveis de desgaste de marteletes de moinho tipo martelo, sobre características físicas do milho e operacionais de moagem. Foram utilizados quatro diferentes lotes de milho, um moinho martelo com motor de 3.500 RPM, cinco conjuntos de marteletes com diferentes níveis de desgaste do vértice (0, 20, 43, 57 e 63%) e quatro diferentes peneiras com diâmetros de furos de 1, 3, 5 e 12 mm sob um esquema fatorial 5x4, com quatro repetições em um total de 80 unidades experimentais. O aumento no diâmetro dos furos das peneiras influenciou (P<0,05) com aumento na produção, nos decibéis, no diâmetro geométrico médio (DGM), no desvio padrão geométrico (DPG), na densidade e com redução no consumo de energia elétrica e no ângulo de repouso (AR). O maior desgaste do martelo aumentou (P<0,05) o consumo de energia elétrica, DGM, DPG, AR e com redução (P<0,05) na produtividade e densidade. A análise de Linear response plateau (LRP) indicou piora na produtividade do equipamento a partir dos 55,1% de desgaste. Neste contexto, o desgaste dos marteletes influenciou negativamente as características operacionais do equipamento e físicas do milho. Para favorecer as características físicas do milho moído e evitar perdas na produtividade do equipamento recomenda-se a moagem com martelos isentos de desgaste

Diferentes metodologias na determinação dos valores energéticos de rações fareladas e peletizadas para frangos de corte.

RESUMO: Para avaliar o efeito de diferentes métodos de coleta e uso de indicadores em ensaios de metabolismo com frangos de corte, foi realizado um experimento com delineamento inteiramente casualizado em um arranjo fatorial 4x2, sendo 4 métodos (coleta total, CIA, TiO2 e Cr2O3) x 2 formas físicas de ração (farelada e peletizada), com 10 repetições. Houve interação significativa entre as metodologias e a forma física das rações. Rações peletizadas tiveram maiores valores de EMAn (kcal/kg na MS e MN). O indicador CIA proporcionou valores de EMAn semelhantes à coleta total de excretas quando estes valores foram expressos na base seca, independente da forma física da ração. Contudo, quando expressos na base natural, a CIA proporcionou menores valores de EMAn em rações peletizadas e semelhantes a coleta total em fareladas. Conclui-se que o processo de peletização aumenta a EMAn de dietas, e a CIA é o indicador mais adequado para determinar os valores de EMAn (MS) de dietas. ABSTRACT: To evaluate the effect of different methods of collecting and using of markers in broiler metabolism tests, a completely randomized experiment was carried out in a 4x2 factorial arrangement, 4 methods (total collection, AIA, TiO2, and Cr2O3) x 2 physical forms of diets (mashed and pelleted), with 10 replicates. There was a significant interaction between the methodologies and the physical form of the diets. Pelleted diets with higher AMEn values (kcal/kg in DM and AS-IS). The AIA marker provided AMEn values similar to total excreta collection when these values were expressed in the dry matter basis, regardless of the physical form of the feed. However, when expressed as is the AIA provided lower values of AMEn in pelleted diets and similar to total collection in mashed diets. Pelleting process increases AMEn of diets, and AIA is the most adequate marker to determine the AMEn (DM) values of diets

Low-redshift quasars in the SDSS Stripe 82-II. Associated companion galaxies and signature of star formation

We present optical spectroscopy of the close companions of 22 low-redshift (z < 0.5) quasars (QSO) selected from a larger sample of QSO in the SDSS Stripe82 region for which both the host galaxy and the large-scale environments have been investigated in our previous work. The new observations extend the number of QSO studied in our previous paper on close companion galaxies of 12 quasars. Our analysis here covers all 34 quasars from both this work and the previously published paper. We find that half of them (15 QSO; similar to 44 per cent) have at least one associated galaxy. Many (12 galaxies; similar to 67 per cent) of the associated companions exhibit [O II] 3727 angstrom emission line as signature of recent star formation. The star formation rate (SFR) of these galaxies is modest (median SFR similar to 4.3 M-circle dot yr(-1)). For eight QSO, we are also able to detect the starlight of the host galaxy from which three have a typical spectrum of a post-starburst galaxy. Our results suggest that quasars do not have a strong influence on the star formation of their companion galaxies

Detection of very high energy gamma-ray emission from the gravitationally-lensed blazar QSO B0218+357 with the MAGIC telescopes

Context. QSO B0218+357 is a gravitationally lensed blazar located at a redshift of 0.944. The gravitational lensing splits the emitted radiation into two components, spatially indistinguishable by gamma-ray instruments, but separated by a 10-12 day delay. In July 2014, QSO B0218+357 experienced a violent flare observed by the Fermi-LAT and followed by the MAGIC telescopes. Aims. The spectral energy distribution of QSO B0218+357 can give information on the energetics of z ~ 1 very high energy gamma- ray sources. Moreover the gamma-ray emission can also be used as a probe of the extragalactic background light at z ~ 1. Methods. MAGIC performed observations of QSO B0218+357 during the expected arrival time of the delayed component of the emission. The MAGIC and Fermi-LAT observations were accompanied by quasi-simultaneous optical data from the KVA telescope and X-ray observations by Swift-XRT. We construct a multiwavelength spectral energy distribution of QSO B0218+357 and use it to model the source. The GeV and sub-TeV data, obtained by Fermi-LAT and MAGIC, are used to set constraints on the extragalactic background light. Results. Very high energy gamma-ray emission was detected from the direction of QSO B0218+357 by the MAGIC telescopes during the expected time of arrival of the trailing component of the flare, making it the farthest very high energy gamma-ray sources detected to date. The observed emission spans the energy range from 65 to 175 GeV. The combined MAGIC and Fermi-LAT spectral energy distribution of QSO B0218+357 is consistent with current extragalactic background light models. The broad band emission can be modeled in the framework of a two zone external Compton scenario, where the GeV emission comes from an emission region in the jet, located outside the broad line region.Comment: 11 pages, 6 figures, accepted for publication in A&

The major upgrade of the MAGIC telescopes, Part II: A performance study using observations of the Crab Nebula

MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes located in the Canary island of La Palma, Spain. During summer 2011 and 2012 it underwent a series of upgrades, involving the exchange of the MAGIC-I camera and its trigger system, as well as the upgrade of the readout system of both telescopes. We use observations of the Crab Nebula taken at low and medium zenith angles to assess the key performance parameters of the MAGIC stereo system. For low zenith angle observations, the standard trigger threshold of the MAGIC telescopes is ~50GeV. The integral sensitivity for point-like sources with Crab Nebula-like spectrum above 220GeV is (0.66+/-0.03)% of Crab Nebula flux in 50 h of observations. The angular resolution, defined as the sigma of a 2-dimensional Gaussian distribution, at those energies is < 0.07 degree, while the energy resolution is 16%. We also re-evaluate the effect of the systematic uncertainty on the data taken with the MAGIC telescopes after the upgrade. We estimate that the systematic uncertainties can be divided in the following components: < 15% in energy scale, 11-18% in flux normalization and +/-0.15 for the energy spectrum power-law slope.Comment: 21 pages, 25 figures, accepted for publication in Astroparticle Physic

Measurement of the Crab Nebula spectrum over three decades in energy with the MAGIC telescopes

The MAGIC stereoscopic system collected 69 hours of Crab Nebula data between October 2009 and April 2011. Analysis of this data sample using the latest improvements in the MAGIC stereoscopic software provided an unprecedented precision of spectral and night-by-night light curve determination at gamma rays. We derived a differential spectrum with a single instrument from 50 GeV up to almost 30 TeV with 5 bins per energy decade. At low energies, MAGIC results, combined with Fermi-LAT data, show a flat and broad Inverse Compton peak. The overall fit to the data between 1 GeV and 30 TeV is not well described by a log-parabola function. We find that a modified log-parabola function with an exponent of 2.5 instead of 2 provides a good description of the data ($\chi^2=35/26$). Using systematic uncertainties of red the MAGIC and Fermi-LAT measurements we determine the position of the Inverse Compton peak to be at (53 $\pm$ 3stat + 31syst -13syst) GeV, which is the most precise estimation up to date and is dominated by the systematic effects. There is no hint of the integral flux variability on daily scales at energies above 300 GeV when systematic uncertainties are included in the flux measurement. We consider three state- of-the-art theoretical models to describe the overall spectral energy distribution of the Crab Nebula. The constant B-field model cannot satisfactorily reproduce the VHE spectral measurements presented in this work, having particular difficulty reproducing the broadness of the observed IC peak. Most probably this implies that the assumption of the homogeneity of the magnetic field inside the nebula is incorrect. On the other hand, the time-dependent 1D spectral model provides a good fit of the new VHE results when considering a 80 {\mu}G magnetic field. However, it fails to match the data when including the morphology of the nebula at lower wavelengths.Comment: accepted by JHEAp, 9 pages, 6 figure