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1. Defining signal thresholds in DNA microarrays: exemplary application for invasive cancer

Author

Head S, Buehler LK, Bilban M, Desoye G, and Quaranta V

Subjects
Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Genome-wide or application-targeted microarrays containing a subset of genes of interest have become widely used as a research tool with the prospect of diagnostic application. Intrinsic variability of microarray measurements poses a major problem in defining signal thresholds for absent/present or differentially expressed genes. Most strategies have used fold-change threshold values, but variability at low signal intensities may invalidate this approach and it does not provide information about false-positives and false negatives. Results We introduce a method to filter false-positives and false-negatives from DNA microarray experiments. This is achieved by evaluating a set of positive and negative controls by receiver operating characteristic (ROC) analysis. As an advantage of this approach, users may define thresholds on the basis of sensitivity and specificity considerations. The area under the ROC curve allows quality control of microarray hybridizations. This method has been applied to custom made microarrays developed for the analysis of invasive melanoma derived tumor cells. It demonstrated that ROC analysis yields a threshold with reduced missclassified genes in microarray experiments. Conclusions Provided that a set of appropriate positive and negative controls is included on the microarray, ROC analysis obviates the inherent problem of arbitrarily selecting threshold levels in microarray experiments. The proposed method is applicable to both custom made and commercially available DNA microarrays and will help to improve the reliability of predictions from DNA microarray experiments.

Published
2002
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6. Expression and function of alpha(v)beta(3) and alpha(v)beta(5) integrins in the developing pancreas: roles in the adhesion and migration of putative endocrine progenitor cells.

Author

Cirulli, V, Beattie, GM, Klier, G, Ellisman, M, Ricordi, C, Quaranta, V, Frasier, F, Ishii, JK, Hayek, A, and Salomon, DR

Subjects
Islets of Langerhans, Pancreatic Ducts, Epithelial Cells, Stem Cells, Animals, Humans, Mice, Mice, SCID, Oligopeptides, Integrins, Receptors, Vitronectin, Extracellular Matrix Proteins, Fluorescent Antibody Technique, Pancreas Transplantation, Stem Cell Transplantation, Fetal Tissue Transplantation, Age Factors, Cell Adhesion, Cell Movement, Gene Expression Regulation, Developmental, Adult, pancreatic islets, endocrine progenitors, alpha(v)beta(3), integrins, cell migration, Gene Expression Regulation, Developmental, SCID, Receptors, Vitronectin, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

Cell-cell and cell-matrix interactions play a critical role in tissue morphogenesis and in homeostasis of adult tissues. The integrin family of adhesion receptors regulates cellular interactions with the extracellular matrix, which provides three-dimensional information for tissue organization. It is currently thought that pancreatic islet cells develop from undifferentiated progenitors residing within the ductal epithelium of the fetal pancreas. This process involves cell budding from the duct, migration into the surrounding mesenchyme, differentiation, and clustering into the highly organized islet of Langerhans. Here we report that alpha(v)beta(3) and alpha(v)beta(5), two integrins known to coordinate epithelial cell adhesion and movement, are expressed in pancreatic ductal cells and clusters of undifferentiated cells emerging from the ductal epithelium. We show that expression and function of alpha(v)beta(3) and alpha(v)beta(5) integrins are developmentally regulated during pancreatic islet ontogeny, and mediate adhesion and migration of putative endocrine progenitor cells both in vitro and in vivo in a model of pancreatic islet development. Moreover, we demonstrate the expression of fibronectin and collagen IV in the basal membrane of pancreatic ducts and of cell clusters budding from the ductal epithelium. Conversely, expression of vitronectin marks a population of epithelial cells adjacent to, or emerging from, pancreatic ducts. Thus, these data provide the first evidence for the contribution of integrins alpha(v)beta(3) and alpha(v)beta(5) and their ligands to morphogenetic events in the human endocrine pancreas.

Published
2000

8. Laminin receptors in the retina: sequence analysis of the chick integrin alpha 6 subunit. Evidence for transcriptional and posttranslational regulation.

Author

de Curtis, I, Quaranta, V, Tamura, RN, and Reichardt, LF

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Genetics, Neurosciences, Eye Disease and Disorders of Vision, Neurodegenerative, 1.1 Normal biological development and functioning, Underpinning research, Eye, Amino Acid Sequence, Animals, Base Sequence, Chick Embryo, Cloning, Molecular, DNA, Gene Expression Regulation, Humans, Integrins, Molecular Sequence Data, Precipitin Tests, Protein Biosynthesis, Receptors, Immunologic, Receptors, Laminin, Restriction Mapping, Retina, Retinal Ganglion Cells, Sequence Homology, Nucleic Acid, Transcription, Genetic, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

The integrin alpha 6 beta 1 is a prominent laminin receptor used by many cell types. In the present work, we isolate clones and determine the primary sequence of the chick integrin alpha 6 subunit. We show that alpha 6 beta 1 is a prominent integrin expressed by cells in the developing chick retina. Between embryonic days 6 and 12, both retinal ganglion cells and other retinal neurons lose selected integrin functions, including the ability to attach and extend neurites on laminin. In retinal ganglion cells, we show that this is correlated with a dramatic decrease in alpha 6 mRNA and protein, suggesting that changes in gene expression account for the developmental regulation of the interactions of these neurons with laminin. In other retinal neurons the expression of alpha 6 mRNA and protein remains high while function is lost, suggesting that the function of the alpha 6 beta 1 heterodimer in these cells is regulated by posttranslational mechanisms.

Published
1991

9. Epithelial integrin alpha 6 beta 4: complete primary structure of alpha 6 and variant forms of beta 4.

Author

Tamura, RN, Rozzo, C, Starr, L, Chambers, J, Reichardt, LF, Cooper, HM, and Quaranta, V

Subjects
Biochemistry and Cell Biology, Biological Sciences, Amino Acid Sequence, Base Sequence, Cell Compartmentation, Cloning, Molecular, Fluorescent Antibody Technique, Humans, Integrins, Macromolecular Substances, Molecular Sequence Data, Poly A, Polymerase Chain Reaction, RNA, Messenger, Sequence Alignment, Sequence Homology, Nucleic Acid, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

The integrin alpha 6 beta 4 is a heterodimer predominantly expressed by epithelia. While no definite receptor function has yet been assigned to it, this integrin may mediate adhesive and/or migratory functions of epithelial cells. We have determined the complete primary structure of both the alpha 6 and beta 4 subunits from cDNA clones isolated from pancreatic carcinoma cell line libraries. The deduced amino acid sequence of alpha 6 is homologous to other integrin alpha chains (18-26% identity). Antibodies to an alpha 6 carboxy terminus peptide immunoprecipitated alpha 6 beta 4 complexes from carcinoma cells and alpha 6 beta 1 complexes from platelets, providing further evidence for the association of alpha 6 with more than one beta subunit. The deduced amino acid sequence of beta 4 predicts an extracellular portion homologous to other integrin beta chains, and a unique cytoplasmic domain comprised of greater than 1,000 residues. This agrees with the structures of the beta 4 cDNAs from normal epithelial cells (Suzuki, S., and Y. Naitoh. 1990. EMBO [Eur. Mol. Biol. Organ.] J. 9:757-763; Hogervost, F., I. Kuikman, A. E. G. Kr. von dem Borne, and A. Sonnenberg. 1990. EMBO [Eur. Mol. Biol. Organ.] J. 9:765-770). Compared to these structures, however, the beta 4 cDNAs that we have cloned from carcinoma cells contain extra sequences. One of these is located in the 5'-untranslated region, and may encode regulatory sequences. Another specifies a segment of 70 amino acids in the cytoplasmic tail. Amplification by reverse transcription-polymerase chain reaction of mRNA indicated that multiple forms of beta 4 may exist, possibly due to cell-type specific alternative splicing. The unique structure of beta 4 suggests its involvement in novel cytoskeletal interactions. Consistent with this possibility, alpha 6 beta 4 is mostly concentrated on the basal surface of epithelial cells, but does not colocalize with components of adhesion plaques.

Published
1990

12. CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth

Author

Yang, J, primary, Bergdorf, K, additional, Yan, C, additional, Luo, W, additional, Chen, SC, additional, Ayers, D, additional, Liu, Q, additional, Liu, X, additional, Boothby, M, additional, Groves, SM, additional, Oleskie, AN, additional, Zhang, X, additional, Maeda, DY, additional, Zebala, JA, additional, Quaranta, V, additional, and Richmond, A, additional

Published
2023
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15. CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth.

Author

Yang, J., Bergdorf, K., Yan, C., Luo, W., Chen, S. C., Ayers, G.D., Liu, Q., Liu, X., Boothby, M., Weiss, V.L., Groves, S. M., Oleskie, A. N., Zhang, X., Maeda, D. Y., Zebala, J. A., Quaranta, V., and Richmond, A.

Subjects
GENE expression, TUMOR growth, NEOPLASTIC cell transformation, PROGENITOR cells, REGULATION of growth, MELANOMA
Abstract

Background: Though the CXCR2 chemokine receptor is known to play a key role in cancer growth and response to therapy, a direct link between expression of CXCR2 in tumor progenitor cells during induction of tumorigenesis has not been established. Methods: To characterize the role of CXCR2 during melanoma tumorigenesis, we generated tamoxifen-inducible tyrosinase-promoter driven BrafV600E/Pten−/−/Cxcr2−/− and NRasQ61R/INK4a−/−/Cxcr2−/− melanoma models. In addition, the effects of a CXCR1/CXCR2 antagonist, SX-682, on melanoma tumorigenesis were evaluated in BrafV600E/Pten−/− and NRasQ61R/INK4a−/− mice and in melanoma cell lines. Potential mechanisms by which Cxcr2 affects melanoma tumorigenesis in these murine models were explored using RNAseq, mMCP-counter, ChIPseq, and qRT-PCR; flow cytometry, and reverse phosphoprotein analysis (RPPA). Results: Genetic loss of Cxcr2 or pharmacological inhibition of CXCR1/CXCR2 during melanoma tumor induction resulted in key changes in gene expression that reduced tumor incidence/growth and increased anti-tumor immunity. Interestingly, after Cxcr2 ablation, Tfcp2l1, a key tumor suppressive transcription factor, was the only gene significantly induced with a log2 fold-change greater than 2 in these three different melanoma models. Conclusions: Here, we provide novel mechanistic insight revealing how loss of Cxcr2 expression/activity in melanoma tumor progenitor cells results in reduced tumor burden and creation of an anti-tumor immune microenvironment. This mechanism entails an increase in expression of the tumor suppressive transcription factor, Tfcp2l1, along with alteration in the expression of genes involved in growth regulation, tumor suppression, stemness, differentiation, and immune modulation. These gene expression changes are coincident with reduction in the activation of key growth regulatory pathways, including AKT and mTOR. [ABSTRACT FROM AUTHOR]

Published
2023
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16. ACDC: Automated Cell Detection and Counting for time-lapse fluorescence microscopy

Author

Rundo, L, Tangherloni, A, Tyson, D, Betta, R, Militello, C, Spolaor, S, Nobile, M, Besozzi, D, Lubbock, A, Quaranta, V, Mauri, G, Lopez, C, Cazzaniga, P, Rundo L., Tangherloni A., Tyson D. R., Betta R., Militello C., Spolaor S., Nobile M. S., Besozzi D., Lubbock A. L. R., Quaranta V., Mauri G., Lopez C. F., Cazzaniga P., Rundo, L, Tangherloni, A, Tyson, D, Betta, R, Militello, C, Spolaor, S, Nobile, M, Besozzi, D, Lubbock, A, Quaranta, V, Mauri, G, Lopez, C, Cazzaniga, P, Rundo L., Tangherloni A., Tyson D. R., Betta R., Militello C., Spolaor S., Nobile M. S., Besozzi D., Lubbock A. L. R., Quaranta V., Mauri G., Lopez C. F., and Cazzaniga P.

Abstract

Advances in microscopy imaging technologies have enabled the visualization of live-cell dynamic processes using time-lapse microscopy imaging. However, modern methods exhibit several limitations related to the training phases and to time constraints, hindering their application in the laboratory practice. In this work, we present a novel method, named Automated Cell Detection and Counting (ACDC), designed for activity detection of fluorescent labeled cell nuclei in time-lapse microscopy. ACDC overcomes the limitations of the literature methods, by first applying bilateral filtering on the original image to smooth the input cell images while preserving edge sharpness, and then by exploiting the watershed transform and morphological filtering. Moreover, ACDC represents a feasible solution for the laboratory practice, as it can leverage multi-core architectures in computer clusters to efficiently handle large-scale imaging datasets. Indeed, our Parent-Workers implementation of ACDC allows to obtain up to a 3.7× speed-up compared to the sequential counterpart. ACDC was tested on two distinct cell imaging datasets to assess its accuracy and effectiveness on images with different characteristics. We achieved an accurate cell-count and nuclei segmentation without relying on large-scale annotated datasets, a result confirmed by the average Dice Similarity Coefficients of 76.84 and 88.64 and the Pearson coefficients of 0.99 and 0.96, calculated against the manual cell counting, on the two tested datasets.

Published
2020

18. Chronic rhinosinusitis with nasal polyps: how to identify eligible patients for biologics in clinical practice

Author

Gelardi, M., Bocciolini, C., Notargiacomo, M., Schiavetti, I., Lingua, C., Pecoraro, P., Iannuzzi, L., Quaranta, V. A., Giancaspro, R., Ronca, G., Cassano, M., Ciprandi, G., Luca, Amorosa, Flavio, Arnone, Paolo, Luperto, Pasqua Irene Sciancalepore, Luigi, Alonzi, Marilena, Tomaiuolo, Alessandro Maselli Del Giudice, Anna, Miglietta, Veronica, Seccia, Giovanni Giulio Sulis, Cristiano, Caruso, Valentina, Rossi, Ciofalo, Andrea, Consagra, Calogera, Antonio, Palma, and Michela, Mancini

Subjects
Adult, Biological Products, nasal polyp score, chronic rhinosinusitis with nasal polyps, biological therapy, CCG, SNOT-22, adult, humans, quality of life, biological products, nasal polyps, rhinitis, sinusitis, General Energy, Nasal Polyps, Otorhinolaryngology, Quality of Life, Humans, Sinusitis, Rhinitis
Abstract

This study compared three severity measures for chronic rhinosinusitis with nasal polyps (CRSwNP). The outcome was to identify patients who are eligible for biological therapy.330 adult patients with CRSwNP were examined. Nasal polyp score (NPS), sinonasal outcome test (SNOT-22) and clinical-cytological grading (CCG) were compared. Clinical history, past surgery and asthma control test were also considered.Only 45 (13.6%) patients had a contextual positivity to the three severity measures. The concordance among tests was slight/fair. Patients with severe disease (all tests positive) had more impaired parameters. The mixed cytotype (OR = 4.07), nasal obstruction (OR = 10.06), post-nasal drip (OR = 1.98), embarrassment (OR = 2.53) and difficulty falling asleep (OR = 1.92) were significantly associated with severe CRSwNP.To identify candidates for biological therapy, the contextual use of NPS, SNOT-22 and CCG is preferable. In this way, global assessment of CRSwNP, including morphology, inflammation, comorbidity, symptoms and quality of life is possible.Rinosinusite cronica con poliposi nasale: come individuare i candidati alla terapia biologica nella pratica clinica.Questo studio confrontava 3 differenti indici di gravità della rinosinusite cronica con poliposi nasale (RSCcPN). L’obbiettivo era individuare i pazienti eleggibili al trattamento con farmaci biologici.330 pazienti adulti con RSCcPN erano arruolati. Tutti i pazienti venivano valutati mediante nasal polyp score (NPS), sinonasal outcome test (SNOT-22) e clinical-cytological grading (CCG). Inoltre erano considerati la storia clinica, i pregressi interventi chirurgici ed il controllo dell’asma.Solamente 45 (13,6%) pazienti avevano i 3 indici positivi. La concordanza tra i 3 indici era bassa/modesta. I pazienti con la malattia grave (contestuale positività a tutti i test) avevano peggiori parametri. Il citotipo misto (OR = 4,07), l’ostruzione nasale (OR = 10,06), il post-nasal drip (OR = 1,98), il disagio (OR = 2,53), e la difficoltà ad addormentarsi (OR = 1,92) erano significativamente associati con la malattia grave.È preferibile utilizzare contemporaneamente i 3 test per individuare i pazienti candidati alla terapia biologica. In questo modo si può avere un quadro generale della malattia, comprendente la morfologia dei polipi, lo stato di infiammazione, le comorbidità, i sintomi e la qualità della vita.

Published
2021

21. Clinical-Cytological-Grading and phenotyping in patients with chronic rhinosinusitis with nasal polyps: the relevance in clinical practice

Author

Gelardi, M., Porro, G., Quaranta, V., Quaranta, N., Cassano, M., Ciprandi, G., Luigi, Alonzi, Arturo Arnone Caruso, Francesco, Barbara, Michele, Barbara, Paolo, Castelnuovo, Giovanna, Ciancio, Ciofalo, Andrea, Michele, Curatolo, Nicola De Candia, Carlo De Luca, Valentina De Robertis, Valentina Di Benedetto, Valeria, Fiore, Lucia, Iannuzzi, Clara, Imperatore, Cristiano, Lingua, Giuseppe, Lombardo, Alberto, Macchi, Michela, Mancini, Alessandro Maselli del Giudice, Patrizia, Mola, Mario, Notargiacomo, Antonio, Palma, Piero, Pecoraro, Giuseppe, Pellitteri, Krizia, Piccininni, Massimo, Rinaldi, and Valentina, Rossi. Study Group On CRSwNP I.

Subjects
Pulmonary and Respiratory Medicine, Adult, Male, Allergy, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, real-world, cytological phenotype, Chronic rhinosinusitis, lcsh:Medicine, Comorbidity, chronic rhinosinusitis with nasal polyps, Nasal Polyps, Internal medicine, clinical-cytological-grading, Eosinophilic, Outcome Assessment, Health Care, medicine, Hypersensitivity, Prevalence, Humans, Nasal polyps, Sinusitis, Grading (tumors), Asthma, Retrospective Studies, Aspirin, business.industry, lcsh:R, Cell Biology, Middle Aged, medicine.disease, asthma, comorbidity, Clinical Practice, Cross-Sectional Studies, Phenotype, Italy, Chronic Disease, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Chronic rhinosinusitis (CRS) includes two main phenotypes: without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP). CRSwNP may be associated with comorbidity, mainly concerning asthma, aspirin intolerance, and allergy. CRSwNP patients may also be evaluated by clinical-cytological grading (CCG). The current study investigated the prevalence and characteristics of the different CCG and phenotypes in CRSwNP outpatients examined in clinical practice. This retrospective cross-sectional study enrolled 791 consecutive CRSwNP outpatients (424 males, mean age 48.8 years). In the total population, asthma was a common comorbidity (30.8%) as well as aspirin intolerance (24.8%), and allergy (50.8%). As concerns CCG-grading, 210 (26.5%) outpatients had low-grade, 366 (46.3%) medium, and 215 (27.2%) high. As regards cytological phenotypes, 87 (11%) had neutrophilic type, 371 (46.3%) eosinophilic, 112 (14.2%) mast cell, and 221 (27.9%) mixed. High-grade CCG was significantly associated with more frequent asthma, aspirin intolerance, allergy, recurrent surgery, and mixed cytological phenotype. Low-grade CCG was characterized by fewer comorbidities and operations, and neutrophilic phenotype. Therefore, the present study confirmed that CCG is a useful tool in the management of outpatients with CRSwNP. CRSwNP is frequently associated with asthma, aspirin intolerance, and allergy comorbidity. High-grade CCG is frequently characterized by a mixed cytological phenotype, thus, by more severe progress. These real-world outcomes underline that CRSwNP deserves adequate attention for careful management and optimal identification of the best-tailored therapy; CCG and cytological phenotyping could be fruitful tools in clinical practice. Asthma and aspirin intolerance should be adequately investigated in all CRS patients.

Published
2020

22. Experimental training and validation of a system for aircraft acoustic signature identification

Author

Quaranta, V. and Dimino, I.

Subjects
Neural networks -- Usage, Airplanes -- Noise, Airplanes -- Acoustic properties, Airplanes -- Measurement, Airplanes -- Comparative analysis, Neural network, Aerospace and defense industries, Business, Science and technology
Abstract

This paper deals with the experimental validation of an innovative system for the aircraft acoustic signature identification which has been developed by the vibration and acoustics laboratory of the Italian Aerospace Research Center. The system is composed of an algorithm for the acoustic signature identification and a dedicated neural network classifier, trained with a set of experimental aircraft noise data. The algorithm test and validation has been performed for different airplanes during takeoff and landing maneuvers. The experimental activity of ground noise measurements has been carried out at the Naples airport of Capodichino. More than 200 aircraft noise events of five aircraft types (Airbus A320, Boeing B737, McDonnel Douglas MD80, Fokker F100, Aerospatiale/Alenia ATR721, during both takeoff and landing maneuver, have been measured. This paper demonstrates the feasibility of developing a suitable artificial neural network to establish if a time signal, elaborated through a wavelet process, is or is not similar to others, having been recognized as originated from a defined type of aircraft. The artificial neural network was trained by the use of a subset of experimental data and then validated through a comparison with another subset of data from the same experimental campaign. The developed software demonstrated to give more than satisfactory results for each of the acquired spectra, with the maximum error always being under (10)%.

Published
2007

25. OC11.10: Diagnostic cytogenetics and cytogenomics confirmations following a cfDNA test with a high‐risk or inconclusive result

Author

De Siero, D., primary, Malvestiti, B., additional, Marcato, L., additional, Ferreira, J., additional, Crippa, S., additional, Quaranta, V., additional, Saragozza, S., additional, Grimi, B., additional, Zanatta, V., additional, Agrati, C., additional, Repetti, E., additional, Malvestiti, F., additional, and Grati, F., additional

Published
2020
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27. VP29.06: Cell‐free DNA screening for fetal aneuploidy by targeted method based on microarray quantitation as primary test in the average risk population: results from a single European laboratory

Author

Malvestiti, B., primary, Crippa, S., additional, Marcato, L., additional, Saragozza, S., additional, Quaranta, V., additional, Grimi, B., additional, Ruggeri, A., additional, Dulcetti, F., additional, De Toffol, S., additional, Malvestiti, F., additional, and Grati, F., additional

Published
2020
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35. The integrin alpha6/beta4 in epithelial and carcinoma cells

Author

Quaranta, V, Collo, Luigia Rinalda, Rozzo, C, Starr, L, Gaietta, G, and Tamura, Rn

Subjects
Integrins, cell migration, cell adhesion, epithelial cells
Abstract

This book represents the most current, comprehensive, and authoritative study of integrins on the market today. It provides an overview of the diverse biological functions of integrins, including: The structure and functions of integrin cytoplasmic domains, the role of b2 integrins in leukocyte adhesion, the role of platelet membrane fibrinogen receptor glycoprotein IIb-IIIa (aIIbb3) in thrombosis and hemostasis, the functions of aV integrin family, the role of integrins in signal transduction, the role of integrins in carcinoma cells, the role of integrins in internalization of microbial pathogens through the binding of Yersinia pseudotuberculosis invasin protein, the role of integrins in the skin, the integrin function in early vertebrate development using amphibian embryos.

Published
2017

40. Mycotoxin contamination in foodstuffs: decontamination of aflatoxin M1 in bovine milk by clay materials

Author

Carraro A.(1), De Giacomo A.(2), Giannossi M.L.(3), Medici L.(3), Muscarella M.(4), Palazzo L.(2), Quaranta V.(2), Summa V.(3), and Tateo F.(1)

Subjects
food and beverages
Abstract

Mycotoxines are widespread toxic substances produced by moulds in human and animal foodstuffs. Some of them, such as aflatoxin B1 (AFB1), are very toxic even in small amounts, but the modern approach to the problem (and the link with public health) started only in the 60s. The presence of aflatoxin M1 (AFM1), in milk and dairy products is also a problem of crucial interest. AFM1 is resistant to thermal and chemical treatments, so mineral sorbents are highly advisable. Clay minerals are suitable, but only a few data are available, as most studies deal with AFB1 (absent in milk). The capacity of clay materials to remove or attenuate the contamination of AFM1 in bovine milk was studied, also considering the effects of these clays on the nutritional properties of milk (in terms of protein, fat and lactose). In order to make the experiments transferable for practical use, only clays available from the market were tested, as well a very simple clay-milk interaction procedure was used. Some bentonites and a kaolin were selected for the experimental work. In particular, different bentonites were selected in order to partially accomplish the wide crystal-chemical features of smectite. Kaolin was less effective than bentonites, but was still able to detoxify contaminated milk, even using a little amount of kaolin (2.4% of the milk suspension). The detoxification role of the bentonites used was variable, but still very efficient: contaminated bovine milk (up to about 80 ng/L) was purified to safe levels (50ng/L for adults and 25ng/L for lactants), with moderate alteration of the nutritional properties of milk; moreover, the bentonite residue in the purified milk was very low (0.4%). The protein was more sensitive to clay adsorption compared to fat and lactose, and the decrease of protein in the treated milk increased with the clay-milk ratio. Among bentonites (beidellite-montmorillonite, ferruginous and saponite types), a saponite clay showed the highest sorbent capacity, in agreement with theoretical consideration about its higher cell surface (available for AFM1) and higher hydrophobicity. Isothermal adsorption procedures for the two more effective bentonites were also carried out in water. The collected data show an effective and safe use of clays in the detoxification of milk (and dairy products) contaminated by AFM1. The climatic changes observed in the last decades point to a wider diffusion of mycotoxines and health effects, and push toward the search for safe, cheap and accessible food treatments.

Published
2013

44. Ground Vibration Test and Aeroelastic Analyses of the CIRA Unmanned Space Vehicle

Author

Belardo, M., Ignazio Dimino, Quaranta, V., Belardo, Marika, I., Dimino, and V., Quaranta

Subjects
modal analysi, space vehicle, ground vibration test
Abstract

This paper deals with the numerical and experimental activities performed by CIRA for the Aeroelastic flutter predictions and the numerical structural model validation of the CIRA Unmanned Space Vehicle in the first phase of the Dropped Transonic Test campaign. Starting from the FE model, the numerical results have been used in order to plan the test strategy and to find the optimal location for sensors and shakers, allowing the optimal control and observation of the structural modes in the frequency range of interest. A dedicated suspension system has been designed and realized in order to achieve the test article free free boundary conditions. The Ground Vibration test has been carried out in order to characterize the experimental dynamic model of the vehicle by using both the Phase Resonance (Normal Mode) and the Phase Separation techniques. A correlation analysis between the experimental modal data and the numerical results has been performed. The aeroelastic model has been updated on the basis of experimental FRFs and modal parameters, by minimizing the discrepancies between the FE model predictions and experimental data. Finally the validated numerical model has been used to investigate the aeroelastic phenomena. The interactions of elastic, inertial and aerodynamic forces have been predicted and the flutter speeds have been calculated.

Published
2009

48. Tissue remodelling in liver diseases

Author

Gianluigi Giannelli, Quaranta, V., and Antonaci, S.

Subjects
Integrins, 6 - Ciencias aplicadas::61 - Medicina [CDU], Liver fibrosis
Abstract

Tissue remodelling is a dynamic process that occurs during fetal or adult life and involves a modification of the original organization and function of a tissue. Tissue remodelling is observed in physiological and pathological conditions such as during wound healing or in the mammary gland during the course of pregnancy. In this review we will discuss the remodelling occurring in the liver as a consequence of chronic inflammation, as observed in chronic hepatitis, or as a consequence of hepatocellular carcinoma (HCC) progression in more detail. We will consider how altered deposition and turn-over of extracellular matrix (ECM) proteins could lead to development of liver fibrosis, and how the exacerbation of fibrosis could underlie the development of cirrhosis. The involvement of inflammatory and anti-inflammatory cytokines commonly used as therapeutic agents, such as Interferon-a, is then evaluated with a particular focus on modulation of ECM proteolysis. Finally, we analyze the role of alterations of the surrounding microenvironment including ECM, growth factors, cytokines and membrane receptors for ECM ligands in the development of HCC and in its invasive behaviour.

Published
2003

49. DNA copy number aberrations in small-cell lung cancer reveal activation of the focal adhesion pathway

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de pneumologie, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Ocak, Sebahat, Yamashita, H, Udyavar, A R, Miller, A N, Gonzalez, A L, Zou, Y, Jiang, A, Yi, Y, Shyr, Y, Estrada, L, Quaranta, V, Massion, P P, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de pneumologie, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Ocak, Sebahat, Yamashita, H, Udyavar, A R, Miller, A N, Gonzalez, A L, Zou, Y, Jiang, A, Yi, Y, Shyr, Y, Estrada, L, Quaranta, V, and Massion, P P

Abstract

Small-cell lung cancer (SCLC) is the most aggressive subtype of lung cancer in its clinical behavior, with a 5-year overall survival as low as 5%. Despite years of research in the field, molecular determinants of SCLC behavior are still poorly understood, and this deficiency has translated into an absence of specific diagnostics and targeted therapeutics. We hypothesized that tumor DNA copy number alterations would allow the identification of molecular pathways involved in SCLC progression. Array comparative genomic hybridization was performed on DNA extracted from 46 formalin-fixed paraffin-embedded SCLC tissue specimens. Genomic profiling of tumor and sex-matched control DNA allowed the identification of 70 regions of copy number gain and 55 regions of copy number loss. Using molecular pathway analysis, we found a strong enrichment in these regions of copy number alterations for 11 genes associated with the focal adhesion pathway. We verified these findings at the genomic, gene expression and protein level. Focal Adhesion Kinase (FAK), one of the central genes represented in this pathway, was commonly expressed in SCLC tumors and constitutively phosphorylated in SCLC cell lines. Those were poorly adherent to most substrates but not to laminin-322. Inhibition of FAK phosphorylation at Tyr(397) by a small-molecule inhibitor, PF-573,228, induced a dose-dependent decrease of adhesion and an increase of spreading in SCLC cell lines on laminin-322. Cells that tended to spread also showed a decrease in focal adhesions, as demonstrated by a decreased vinculin expression. These results support the concept that pathway analysis of genes in regions of copy number alterations may uncover molecular mechanisms of disease progression and demonstrate a new role of FAK and associated adhesion pathways in SCLC. Further investigations of FAK at the functional level may lead to a better understanding of SCLC progression and may have therapeutic implications.

Published
2010

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