30 research outputs found
Automated Selection of the Optimal Cardiac Phase for Single-Beat Coronary CT Angiography Reconstruction
No full textThis thesis investigates an automated algorithm for selecting the optimal cardiac phase for CCTA reconstruction. Reconstructing a low-motion cardiac phase improves coronary artery visualization in coronary CT angiography (CCTA) exams. Currently, standard end-systole and/or mid-diastole default phases are prescribed or alternatively, quiescent phases are determined by the user. As manual selection may be time-consuming and standard locations may be suboptimal due to patient variability, an automated method is investigated. An automated algorithm was developed to select the optimal phase based on quantitative image quality (IQ) metrics. For each reconstructed slice at each reconstructed phase, an image quality metric was calculated based on measures of circularity and edge strength of through-plane vessels. The image quality metric was aggregated across slices, while a metric of vessel-location consistency was used to ignore slices that did not contain through-plane vessels. A binary metric based on the edge strength of in-plane vessels was calculated to determine if IQ of in-plane vessels was acceptable. The algorithm performance was evaluated using two observer studies. Fourteen single-beat CCTA exams (Revolution CT, GE Healthcare) reconstructed at 2% intervals were evaluated for best systolic (1), diastolic (6), or systolic and diastolic phases (7) by three readers and the algorithm. Inter-reader (RR) and reader-algorithm (RA) agreement was calculated using the mean absolute difference (MAD) and concordance correlation coefficient (CCC). A reader-consensus best phase was determined and compared to the algorithm selected phase. In cases where the algorithm and consensus best phases differed by more than 2%, IQ was scored by three readers using a 5pt Likert scale. There was no significant difference between RR and RA agreement for either MAD or CCC metrics (p\u3e0.2). The algorithm phase was within 2% of the consensus phase in 71% of cases. There was no significant difference (p\u3e0.2) between the IQ of the algorithm phase (4.06±0.73) and the consensus phase (4.11±0.76). The proposed algorithm was statistically equivalent to a reader in selecting an optimal cardiac phase for CCTA exams. When reader and algorithm phases differed by \u3e2%, IQ was statistically equivalent
PI3K-driven HER2 expression is a potential therapeutic target in colorectal cancer stem cells
No full textObjective: Cancer stem cells are responsible for tumour spreading and relapse. Human epidermal growth factor receptor 2 (HER2) expression is a negative prognostic factor in colorectal cancer (CRC) and a potential target in tumours carrying the gene amplification. Our aim was to define the expression of HER2 in colorectal cancer stem cells (CR-CSCs) and its possible role as therapeutic target in CRC resistant to anti-epidermal growth factor receptor (EGFR) therapy. Design: A collection of primary sphere cell cultures obtained from 60 CRC specimens was used to generate CR-CSC mouse avatars to preclinically validate therapeutic options. We also made use of the ChIP-seq analysis for transcriptional evaluation of HER2 activation and global RNA-seq to identify the mechanisms underlying therapy resistance. Results: Here we show that in CD44v6-positive CR-CSCs, high HER2 expression levels are associated with an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, which promotes the acetylation at the regulatory elements of the Erbb2 gene. HER2 targeting in combination with phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MEK) inhibitors induces CR-CSC death and regression of tumour xenografts, including those carrying Kras and Pik3ca mutation. Requirement for the triple targeting is due to the presence of cancer-associated fibroblasts, which release cytokines able to confer CR-CSC resistance to PI3K/AKT inhibitors. In contrast, targeting of PI3K/AKT as monotherapy is sufficient to kill liver-disseminating CR-CSCs in a model of adjuvant therapy. Conclusions: While PI3K targeting kills liver-colonising CR-CSCs, the concomitant inhibition of PI3K, HER2 and MEK is required to induce regression of tumours resistant to anti-EGFR therapies. These data may provide a rationale for designing clinical trials in the adjuvant and metastatic setting
Modulation of the cytotoxic activity of Vγ9Vδ2 T cells by blocking the TCR or NKG2D interactions.
No full text<p>The Vγ9Vδ2 T cell line COLD2-1 was cultured with two chemotherapy-treated colon CICs (CIC#3 and CIC#5) at an E:T ratio of 20∶1, in the presence of blocking antibodies to the γδ TCR, CD3, NKG2D, or in the presence of mevastatin. Specific cytotoxicity levels achieved by the Vγ9Vδ2 T cell line COLD2-1 were 65±11 for CIC#3 and 71±9 for CIC#5. Data are mean ± SD of two experiments carried out in triplicate. Percent inhibition with anti-NKG2D mAb was significantly different than values in all other groups (*p<0.001).</p
Multifunctional role of PED/PEA15 in cell death and cell motility in human non small cell lung cancer (NSCLC)
No full textPED (phosphoprotein enriched in diabetes) is a 15 KDa protein involved in many cellular pathways and human diseases, including type II diabetes and cancer. We recently reported its overexpression in breast and lung cancers, and B-cell chronic lymphocytic leukemia (B-CLL). Furthermore, PED mediated resistance to chemotherapic agents in breast cancer cell lines and TRAIL (TNF-Related Apoptosis Inducing Ligand) treatment in primary B-CLL cells and lung cancer cell lines. Then, we show that PED function and expression are reguated by vitamin D3. To better understand its role in cancer, we focused on PED interactome characterization in non small cell lung cancer (NSCLC) cell line, A459. By the Tandem Affinity Purification (TAP), we have identified Rac1, member of mammalian Rho GTPase proteins family, as a PED-interacting protein, which is involved in many cellular processes, such as migration and invasion. Here we show that PED stimulates migration and invasion in Rac1-dependent manner in non small cell lung cancer. In conclusion, this is teh first report showing that PED and Rac1 interact and that this interaction regulates cell migration/invasion process through ERK1/2 pathway
Lack of correlation of stem cell markers in breast cancer stem cells
No full textBackground:Various markers are used to identify the unique sub-population of breast cancer cells with stem cell properties. Whether these markers are expressed in all breast cancers, identify the same population of cells, or equate to therapeutic response is controversial.Methods:We investigated the expression of multiple cancer stem cell markers in human breast cancer samples and cell lines in vitro and in vivo, comparing across and within samples and relating expression with growth and therapeutic response to doxorubicin, docetaxol and radiotherapy.Results:CD24, CD44, ALDH and SOX2 expression, the ability to form mammospheres and side-population cells are variably present in human cancers and cell lines. Each marker identifies a unique rather than common population of cancer cells. In vivo, cells expressing these markers are not specifically localized to the presumptive stem cell niche at the tumour/stroma interface. Repeated therapy does not consistently enrich cells expressing these markers, although ER-negative cells accumulate.Conclusions:Commonly employed methods identify different cancer cell sub-populations with no consistent therapeutic implications, rather than a single population of cells. The relationships of breast cancer stem cells to clinical parameters will require identification of specific markers or panels for the individual cancer.British Journal of Cancer advance online publication, 27 February 2014; doi:10.1038/bjc.2014.105 www.bjcancer.com
SIRIO : Integrated Forest Firesmonitoring, detection and decision supportsystem with low cost commercial sensorssuited for complex orography
No full textForest Fires in our society cause a lot of damage, in particular regarding the economic and environmental landscape. In order to monitor a large portion of territory automatically, with a good cost/performances trade-off, it is necessary to develop new early warning systems. We propose a ground-based system with modular architecture, equipped with low cost commercial sensor. The idea is to develop the software able to manage the forest fires monitoring. The technique is based on Static and Dynamic analysis of chromatic changes between images, tailored for our case of study in a large scale monitoring of vegetation and using different sensors to reduce or eliminate the false alarm rate. Concerning the image geo-referencing tool, the present work describes an innovative projective geo-referencing algorithm able to geo-reference complex orography regions using fixed ground station images. Besides, it does not need the collection of Ground Control Points, which is a very hard task in complex orography environments. In order to make a user oriented product and to help the operator during extinguishing activities, a decision support tool has been developed as well. This work presents the results of one year monitoring campaign conducted in cooperation with the Civil Protection Offices in Sanremo (IM), Ital
Erratum: Search for photons with energies above 1018 eV using the hybrid detector of the Pierre Auger Observatory (Journal of Cosmology and Astroparticle Physics (2017) 4 (9) DOI: 10.1088/1475-7516/2017/04/009)
No full text1 Exposure calculation Due to a mistake in the numerical integration following eq. (6.2) of the original article [1], the exposure shown in figure 5 of the original article was incorrect. The correct exposure is shown in figure 1. 2 Upper limits on the integral photon flux and fraction The incorrect exposure affects the calculation of the upper limits on the integral photon flux following eq. (6.1) of the original article. The correct values for the upper limits are 0.038, 0.010, 0.009, 0.008 and 0.007 km−2 sr−1 yr−1 for threshold energies of 1, 2, 3, 5 and 10 EeV. The correct values for the upper limits on the integral photon fraction subsequently derived are 0.14 %, 0.17 %, 0.42 %, 0.86 % and 2.9 % for the same threshold energies. 3 Author list The author list of this erratum also corrects a mistake made in the original article, where F. Zuccarello was missing and Z. Zong was listed twice
Erratum: Search for photons with energies above 1018 eV using the hybrid detector of the Pierre Auger Observatory
No full textExposure calculation Due to a mistake in the numerical integration following eq. (6.2) of the original article [1], the exposure shown in figure 5 of the original article was incorrect. The correct exposure is shown in figure 1. 2 Upper limits on the integral photon flux and fraction The incorrect exposure affects the calculation of the upper limits on the integral photon flux following eq. (6.1) of the original article. The correct values for the upper limits are 0.038, 0.010, 0.009, 0.008 and 0.007 km−2 sr−1 yr−1 for threshold energies of 1, 2, 3, 5 and 10 EeV. The correct values for the upper limits on the integral photon fraction subsequently derived are 0.14 %, 0.17 %, 0.42 %, 0.86 % and 2.9 % for the same threshold energies. 3 Author list The author list of this erratum also corrects a mistake made in the original article, where F. Zuccarello was missing and Z. Zong was listed twice
Extração e encapsulamento de compostos com importância tecnológica e biológica proveniente do resíduo de processamento de camarão
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Engenharia de AlimentosO processamento de camarão gera um resíduo formado pela cabeça e carapaça do crustáceo. Este resíduo apresenta um grande potencial para agregação de valor mediante a extração da fração carotenoídica da matéria-prima. O método de extração usado para a obtenção de compostos a partir de uma matéria-prima natural é crítico para a definição da qualidade do produto final. Desta forma, o objetivo deste trabalho é estudar o aproveitamento do resíduo de processamento de camarão rosa (P. brasiliensis e P. paulensis) para a obtenção de extratos de alto valor agregado, avaliando a técnica de extração, atividade biológica dos extratos e o seu encapsulamento. A matéria-prima, obtida no mercado público de Florianópolis/SC/Brasil, foi submetida a diferentes pré-tratamentos como tratamento térmico, secagem e moagem, sendo que estes métodos combinados apresentaram a melhor recuperação da fração carotenoídica da matéria-prima. Subsequentemente, foi estudada a eficiência de extração de carotenóides de sistemas a baixa pressão. Como tecnologia alternativa de extração de carotenóides foi aplicada a extração supercrítica (ESC) nas condições de 313.15 e 333.15 K e de 100 a 300 bar, empregando CO2 puro como solvente. Como modificadores do CO2 foram utilizados hexano:isopropanol (50:50) e óleo de girassol (2 % e 5 %, m/m). A cinética e a modelagem da ESC foram avaliadas com diferentes vazões de CO2 e umidades da matéria-prima. Os resultados foram avaliados quanto ao rendimento de extração, o perfil quali/quantitativo de carotenóides, o rendimento em astaxantina, o perfil espectrofotométrico UV-Visível e no infravermelho médio (FTIR), o perfil de ácidos graxos e as atividades antioxidante, anti-obesidade e hipolipemiante dos diferentes extratos. Finalmente, foi realizada a co-precipitação de astaxantina em polímeros por tecnologia supercrítica utilizando CO2 como anti-solvente pelos métodos Anti-Solvente Supercrítico (SAS), onde foi investigado o efeito de variáveis do processo no tamanho, distribuição do tamanho e morfologia das partículas precipitadas, e SAS de emulsão (SFEE). A composição dos extratos obtidos a baixa pressão indicou a acetona e a solução hexano:isopropanol como os solventes de maior eficiência na extração de carotenóides. A eficiência da ESC de carotenóides aumentou com o aumento da massa específica do CO2 e o maior rendimento em astaxantina foi a 333.15 K/300 bar, usando CO2 puro. A análise de custos do processo sugere o emprego de um equipamento de 2 x 400 L e tempo de 25 min para um processo mais lucrativo. Maiores atividades antioxidantes foram obtidas para os extratos alcoólico e cetônico, dentre os sistemas a baixa pressão. Os extratos apresentaram alto conteúdo de ácidos graxos poli-insaturados, especialmente ?-3 EPA e DHA, e de compostos fenólicos. O extrato ESC (333.15 K/300 bar) a 50 mg/kg.d apresentou os melhores efeitos anti-obesidade (79-84 %) e hipotrigliceremiante. Os extratos Soxhlet promoveram as maiores reduções nos níveis de colesterol sérico. A eficiência do encapsulamento do extrato em Pluronic F127 através de SAS foi de até 74 %. Nano-emulsões processadas por SFEE apresentaram o melhor desempenho de encapsulamento e o menor tamanho de partícula. Todas as partículas produzidas por SAS e SFEE apresentaram melhor preservação de cor quando comparadas com o extrato não processado
Features of the Energy Spectrum of Cosmic Rays above 2.5×10 eV Using the Pierre Auger Observatory
No full textInternational audienceWe report a measurement of the energy spectrum of cosmic rays above 2.5×1018 eV based on 215 030 events. New results are presented: at about 1.3×1019 eV, the spectral index changes from 2.51±0.03(stat)±0.05(syst) to 3.05±0.05(stat)±0.10(syst), evolving to 5.1±0.3(stat)±0.1(syst) beyond 5×1019 eV, while no significant dependence of spectral features on the declination is seen in the accessible range. These features of the spectrum can be reproduced in models with energy-dependent mass composition. The energy density in cosmic rays above 5×1018 eV is [5.66±0.03(stat)±1.40(syst)]×1053 erg Mpc-3
