29 results on '"Caputo T"'
Search Results
2. Phase I trial of ixabepilone plus pegylated liposomal doxorubicin in patients with adenocarcinoma of breast or ovary
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Chuang, E., Wiener, N., Christos, P., Kessler, R., Cobham, M., Donovan, D., Goldberg, G.L., Caputo, T., Doyle, A., Vahdat, L., and Sparano, J.A.
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- 2010
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3. Punitiveness, Fear of Crime, and Perceptions of Violence
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Wanner, Richard A. and Caputo, T. C.
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- 1987
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4. The Young Offenders Act: Children's Rights, Children's Wrongs
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Caputo, T. C.
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- 1987
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5. Cascade testing für erbliche Tumorerkrankungen: Eine Meta-Analyse
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Lackner, A, additional, Li, X, additional, Kahn, R, additional, Baltich Nelson, B, additional, Krinsky, H, additional, Mei, E, additional, Badiner, N, additional, Caputo, T A, additional, Holcomb, K, additional, Chapman-Davis, E, additional, Nitecki, R, additional, Rauh-Hain, J A, additional, Sharaf, R, additional, and Frey, M K, additional
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- 2020
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6. Development of High-Loading Trastuzumab PLGA Nanoparticles: A Powerful Tool Against HER2 Positive Breast Cancer Cells
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Caputo TM, Barisciano G, Mulè C, Cusano AM, Aliberti A, Muccillo L, Colantuoni V, Sabatino L, and Cusano A
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plga nanoparticles ,double-emulsion method ,trastuzumab ,breast cancer ,signaling transduction. ,Medicine (General) ,R5-920 - Abstract
Tania Mariastella Caputo,1,* Giovannina Barisciano,2,* Chiara Mulè,1 Angela Maria Cusano,3 Anna Aliberti,1 Livio Muccillo,2 Vittorio Colantuoni,2 Lina Sabatino,2 Andrea Cusano1,3 1Optoelectronics Group, Department of Engineering, University of Sannio, Benevento, Italy; 2Department of Sciences and Technologies, University of Sannio, Benevento, Italy; 3CeRICTscrl Regional Center Information Communication Technology, Benevento, Italy*These authors contributed equally to this workCorrespondence: Anna Aliberti; Lina Sabatino, Email anna.aliberti@unisannio.it; sabatino@unisannio.itBackground: Trastuzumab, a therapeutic monoclonal antibody directed against HER2, is routinely used to treat HER2-positive breast cancer with a good response rate. However, concerns have arisen in the clinical practice due to adverse side effects. One way to overcome these limitations is to encapsulate trastuzumab in nanoparticles to improve cytotoxic activity, increase intracellular drug concentrations, escape the immune system and avoid systemic degradation of the drug in vivo.Methods: A double emulsion method was used to encapsulate trastuzumab into poly(lactic-co-glycolic) nanoparticles, effective for their biocompatibility and biodegradability. These nanocarriers, hereafter referred to as TZPs, were characterised in terms of size, homogeneity, zeta potential and tested for their stability and drug release kinetics. Finally, the TZPs cytotoxicity was assessed in vitro on the HER2 positive SKBR3 breast cancer cell line and compared to free trastuzumab.Results: The TZPs were stable, homogeneous in size, with a reduced zeta potential. They showed higher encapsulation efficiency and drug loading, a prolonged trastuzumab release kinetics that retained its physicochemical properties and functionality. TZPs showed a stronger cytotoxicity and increased apoptosis than similar doses of free trastuzumab in the cell line analysed. Confocal microscopy and flow cytometry assessed TZPs and trastuzumab cellular uptake while Western blot evaluated downstream signalling, overall HER2 content and shedding.Conclusion: TZPs exert more robust effects than free trastuzumab via a dual mode of action: TZPs are taken up by cells through an endocytosis mechanism and release the drug intracellularly for longer time. Additionally, the TZPs that remain in the extracellular space release trastuzumab which binds to the cognate receptor and impairs downstream signalling. This is the sole modality used by free trastuzumab. Remarkably, half dose of TZPs is as efficacious as the highest dose of free drug supporting their possible use for drug delivery in vivo. Keywords: PLGA nanoparticles, double-emulsion method, trastuzumab, breast cancer, signaling transduction
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- 2023
7. Visualization and normalization of drift effect across batches in metabolome-wide association studies
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Bararpour, N., Gilardi, F., Carmeli, C., Sidibe, J., Ivanisevic, J., Caputo, T., Augsburger, M., Grabherr, S., Desvergne, B., Guex, N., Bochud, M., Thomas, A., Bararpour, N., Gilardi, F., Carmeli, C., Sidibe, J., Ivanisevic, J., Caputo, T., Augsburger, M., Grabherr, S., Desvergne, B., Guex, N., Bochud, M., and Thomas, A.
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- 2020
8. Core/shell cellulose-based microspheres for oral administration of Ketoprofen Lysinate
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Guarino V., Caputo T., Calcagnile P., Altobelli R., Demitri C., Ambrosio L., Guarino, V., Caputo, T., Calcagnile, P., Altobelli, R., Demitri, C., and Ambrosio, L.
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cellulose acetate ,Chitosan ,electrofluidodynamics ,Lysine ,Administration, Oral ,electrofluidodynamic ,Hydrogen-Ion Concentration ,oral delivery ,Microspheres ,ketoprofen lysinate ,Ketoprofen ,Delayed-Action Preparation ,chitosan ,Cellulose - Abstract
Herein, we propose the fabrication of a new carrier with core/shell structure—inner core of cellulose acetate (CA) coated by a micrometric layer of chitosan (CS)—fabricated through an integrated process, which combines Electro Dynamic Atomization (EDA) and layer-by-layer (LbL) technique. We demonstrate that CA based microspheres possess a unique capability to relevantly retain the drugs—that is, Ketoprofen Lysinate (KL)—along the gastric tract, while providing a massive release along the intestine. CS shell slightly influences the morphology and water retention under different pH conditions, improving drug encapsulation without compromising drug release kinetics. In vitro studies in simulated gastric and intestine fluids (SGF, SIF) with physiological enzymes, show a moderate release of LSK during the first 2 h (ca. 20% at pH 2), followed by a sustained release during the next 6 h (ca. 80% at pH 7). The obtained results demonstrate that CA-based microspheres hold strong potential to be used as carriers for a delayed oral administration of anti-inflammatory drugs. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2636–2644, 2018.
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- 2018
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9. Sorafenib-Loaded PLGA Carriers for Enhanced Drug Delivery and Cellular Uptake in Liver Cancer Cells
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Caputo TM, Cusano AM, Principe S, Cicatiello P, Celetti G, Aliberti A, Micco A, Ruvo M, Tagliamonte M, Ragone C, Minopoli M, Carriero MV, Buonaguro L, and Cusano A
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poly(lactic-co-glycolic acid) ,sorafenib ,emulsion solvent evaporation technique ,hepatocellular carcinoma ,optical fiber ,microfluidics ,Medicine (General) ,R5-920 - Abstract
Tania Mariastella Caputo,1,* Angela Maria Cusano,2,* Sofia Principe,1 Paola Cicatiello,1 Giorgia Celetti,1 Anna Aliberti,1 Alberto Micco,2 Menotti Ruvo,3 Maria Tagliamonte,4 Concetta Ragone,4 Michele Minopoli,5 Maria Vincenza Carriero,5 Luigi Buonaguro,4 Andrea Cusano1,2 1Optoelectronics Group, Department of Engineering, University of Sannio, Palazzo Dell’ Aquila Bosco Lucarelli, Benevento, Italy; 2CeRICTscrl Regional Center Information Communication Technology, Palazzo Ex Poste, Benevento, Italy; 3Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy; 4Innovative Immunological Models Unit, Istituto Nazionale Tumori - IRCCS - “Fond G. Pascale”, Naples, Italy; 5Neoplastic Progression Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, Italy*These authors contributed equally to this workCorrespondence: Andrea Cusano; Anna Aliberti, Palazzo Dell’Aquila Bosco Lucarelli, Corso Garibaldi 107, Benevento, I-82100, Italy, Email a.cusano@unisannio.it; anna.aliberti@unisannio.itIntroduction: Currently, conventional treatments of hepatocellular carcinoma (HCC) are not selective enough for tumor tissue and lead to multidrug resistance and drug toxicity. Although sorafenib (SOR) is the standard first-line systemic therapy approved for the clinical treatment of HCC, its poor aqueous solubility and rapid clearance result in low absorption efficiency and severely limit its use for local treatment.Methods: Herein, we present the synthesis of biodegradable polymeric Poly (D, L-Lactide-co-glycolide) (PLGA) particles loaded with SOR (PS) by emulsion-solvent evaporation process. The particles are carefully characterized focusing on particle size, surface charge, morphology, drug loading content, encapsulation efficiency, in vitro stability, drug release behaviour and tested on HepG2 cells. Additionally, PLGA particles have been coupled on side emitting optical fibers (seOF) integrated in a microfluidic device for light-triggered local release.Results: PS have a size of 248 nm, tunable surface charge and a uniform and spherical shape without aggregation. PS shows encapsulation efficiency of 89.7% and the highest drug loading (8.9%) between the SOR-loaded PLGA formulations. Treating HepG2 cells with PS containing SOR at 7.5 μM their viability is dampened to 40%, 30% and 17% after 48, 129 and 168 hours of incubation, respectively.Conclusion: The high PS stability, their sustained release profile and the rapid cellular uptake corroborate the enhanced cytotoxicity effect on HepG2. With the prospect of developing biomedical tools to control the spatial and temporal release of drugs, we successfully demonstrated the potentiality of seOF for light-triggered local release of the carriers. Our prototypical system paves the way to new devices integrating microfluidics, optical fibers, and advanced carriers capable to deliver minimally invasive locoregional cancer treatments.Graphical Abstract: Keywords: poly(lactic-co-glycolic acid), sorafenib, emulsion solvent evaporation technique, hepatocellular carcinoma, optical fiber, microfluidics
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- 2023
10. Beyond crime rates and community surveys: A new approach to police accountability and performance measurement
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Hodgkinson, T. (Tarah), Caputo, T. (Tullio), McIntyre, M. (Michael L.), Hodgkinson, T. (Tarah), Caputo, T. (Tullio), and McIntyre, M. (Michael L.)
- Abstract
In this conceptual piece, we argue that the current approach to police performance measurement typically based on the use of traditional police metrics has failed to achieve the desired results and that a different strategy is required. Traditional police metrics have a narrow focus on crime and the police response to it. They provide little information on how well police organizations are performing. Importantly, traditional police metrics do not incorporate input from police stakeholders in goal identification, nor do they use specifically designed indicators to assess progress towards achieving these goals. Following an analysis of the criticisms levelled at the use of traditional police metrics, and subsequent attempts to address these issues, we argue that a networked governance approach represents a more promising foundation for undertaking police organizational performance assessment. Such an approach would engage stakeholders more directly in goal identification and performance assessment, and potentially lead to more successful, responsive and accountable policing.
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- 2019
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11. ER Stress Sensor XBP1 Controls Anti-tumor Immunity by Disrupting Dendritic Cell Homeostasis
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Cubillos-Ruiz JR, Silberman PC, Rutkowski MR, Chopra S, Perales-Puchalt A, Song M, Zhang S, Bettigole SE, Gupta D, Holcomb K, Ellenson LH, Caputo T, Lee AH, Conejo-Garcia JR, and Glimcher LH
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Dendritic cells (DCs) are required to initiate and sustain T cell-dependent anti-cancer immunity. However, tumors often evade immune control by crippling normal DC function. The endoplasmic reticulum (ER) stress response factor XBP1 promotes intrinsic tumor growth directly, but whether it also regulates the host anti-tumor immune response is not known. Here we show that constitutive activation of XBP1 in tumor-associated DCs (tDCs) drives ovarian cancer (OvCa) progression by blunting antitumor immunity. XBP1 activation, fueled by lipid peroxidation byproducts, induced a triglyceride biosynthetic program in tDCs leading to abnormal lipid accumulation and subsequent inhibition of tDC capacity to support anti-tumor T cells. Accordingly, DC-specific XBP1 deletion or selective nanoparticle-mediated XBP1 silencing in tDCs restored their immunostimulatory activity in situ and extended survival by evoking protective type 1 anti-tumor responses. Targeting the ER stress response should concomitantly inhibit tumor growth and enhance anti-cancer immunity, thus offering a unique approach to cancer immunotherapy.
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- 2015
12. Infrared spectroscopy of exfoliated human cervical cells: evidence of extensive structural changes during carcinogenesis.
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Wong, P T, primary, Wong, R K, additional, Caputo, T A, additional, Godwin, T A, additional, and Rigas, B, additional
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- 1991
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13. DBnorm as an R package for the comparison and selection of appropriate statistical methods for batch effect correction in metabolomic studies
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Bararpour, N., Gilardi, F., Carmeli, C., Sidibe, J., Ivanisevic, J., Caputo, T., Augsburger, M., Grabherr, S., Desvergne, B., Guex, N., Bochud, M., and Thomas, A.
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Data processing ,Multidisciplinary ,Statistical methods ,Science ,Medicine ,Metabolomics ,Article - Abstract
As a powerful phenotyping technology, metabolomics provides new opportunities in biomarker discovery through metabolome-wide association studies (MWAS) and the identification of metabolites having a regulatory effect in various biological processes. While mass spectrometry-based (MS) metabolomics assays are endowed with high throughput and sensitivity, MWAS are doomed to long-term data acquisition generating an overtime-analytical signal drift that can hinder the uncovering of real biologically relevant changes. We developed “dbnorm”, a package in the R environment, which allows for an easy comparison of the model performance of advanced statistical tools commonly used in metabolomics to remove batch effects from large metabolomics datasets. “dbnorm” integrates advanced statistical tools to inspect the dataset structure not only at the macroscopic (sample batches) scale, but also at the microscopic (metabolic features) level. To compare the model performance on data correction, “dbnorm” assigns a score that help users identify the best fitting model for each dataset. In this study, we applied “dbnorm” to two large-scale metabolomics datasets as a proof of concept. We demonstrate that “dbnorm” allows for the accurate selection of the most appropriate statistical tool to efficiently remove the overtime signal drift and to focus on the relevant biological components of complex datasets.
14. Small Oligonucleotides Detection in Three-Dimensional Polymer Network of DNA-PEG Hydrogels
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Alessia Mazzarotta, Paolo A. Netti, Edmondo Battista, Tania Mariastella Caputo, Luca Raiola, Filippo Causa, Mazzarotta, A., Caputo, T. M., Raiola, L., Battista, E., Netti, P. A., and Causa, F.
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Materials science ,Polymers and Plastics ,Science ,Diffusion ,General. Including alchemy ,Bioengineering ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Article ,Biomaterials ,chemistry.chemical_compound ,QD1-65 ,3D recognition ,Molecule ,strand displacement assay ,QD1-999 ,QD146-197 ,chemistry.chemical_classification ,Oligonucleotide ,Biomolecule ,Organic Chemistry ,diffusion ,021001 nanoscience & nanotechnology ,PEGDA hydrogel ,0104 chemical sciences ,Chemistry ,Photopolymer ,chemistry ,PEGDA hydrogels ,Self-healing hydrogels ,0210 nano-technology ,Biosensor ,Inorganic chemistry ,DNA ,biomaterials - Abstract
The control of the three-dimensional (3D) polymer network structure is important for permselective materials when specific biomolecule detection is needed. Here we investigate conditions to obtain a tailored hydrogel network that combines both molecular filtering and molecular capture capabilities for biosensing applications. Along this line, short oligonucleotide detection in a displacement assay is set within PEGDA hydrogels synthetized by UV radical photopolymerization. To provide insights on the molecular filter capability, diffusion studies of several probes (sulforhodamine G and dextrans) with different hydrodynamic radii were carried out using NMR technique. Moreover, fluorometric analyses of hybridization of DNA oligonucleotides inside PEGDA hydrogels shed light on the mechanisms of recognition in 3D, highlighting that mesh size and crowding effect greatly impact the hybridization mechanism on a polymer network. Finally, we found the best probe density and diffusion transport conditions to allow the specific oligonucleotide capture and detection inside PEGDA hydrogels for oligonucleotide detection and the filtering out of higher molecular weight molecules.
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- 2021
15. On the role of redox properties of CuO/CeO2 catalysts in the preferential oxidation of CO in H2-rich gases
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Luciana Lisi, Tiziana Caputo, Raffaele Pirone, Gennaro Russo, Caputo, T., Lisi, L., Pirone, R., and Russo, Gennaro
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H2 purification ,Chemistry ,Process Chemistry and Technology ,PROX ,Inorganic chemistry ,selectivity ,chemistry.chemical_element ,TPR ,fuel cells ,Heterogeneous catalysis ,CO oxidation ,Redox ,Copper ,Catalysis ,ceria ,CO PROX ,redox ,CO ,Transition metal ,Oxidation state ,Hydrogen ,BET theory - Abstract
CuO/CeO 2 catalysts with CuO content ranging from 0.5 wt.% to 8 wt.%, prepared by wet impregnation of commercial ceria, have been tested for the preferential oxidation of CO (CO-PROX) under H 2 -rich conditions at 70–210 °C. Catalytic activity increases up to 4 wt.% CuO content, with less concentrated catalysts showing higher intrinsic activity. Catalysts have been characterized by means of XRD, BET analysis and UV spectroscopy. Formation of segregated CuO clusters has been detected for Cu richest CuO/CeO 2 sample. Redox properties have been deeply investigated using TP analysis (H 2 TPR, CO TPR, TPO) of fresh or pre-treated samples. Participation of surface ceria, induced by the strong interaction with copper, to reduction/oxidation reactions in the temperature range explored (up to 430 °C) has been demonstrated. Different copper species and their reactivity towards H 2 and CO have been individuated by comparing TPR of fully oxidized catalysts with those of partially oxidized catalysts. Active species have been identified as copper-ceria sites able to oxidize CO even at room temperature and to be re-oxidized by O 2 at the same temperature. Transient experiments have been carried out at different temperature using a diluted mixture starting from oxidized or reduced catalysts and followed by a H 2 TPR of the used samples. The results of these tests have showed that active centres for CO oxidation contain copper in the +2 oxidation state. At T > 100 °C some reduced copper sites are stabilized which promote H 2 oxidation thus lowering the selectivity of the CO-PROX process.
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- 2008
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16. Geostructure of Coroglio tuff cliff, Naples (Italy) derived from terrestrial laser scanner data
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Antonio Pignalosa, Fabio Matano, Claudia Troise, Flavia Molisso, S. Iuliano, Marco Sacchi, Giuseppe Maria Grimaldi, Teresa Caputo, Ermanno Marino, Umberto del Vecchio, Germana Scepi, Renato Somma, Giuseppe Esposito, Giuseppe De Natale, Matano, Fabio, Iuliano, Sabato, Somma, R., Marino, E., del Vecchio, U., Esposito, G., Molisso, F., Scepi, Germana, Grimaldi, G. M., Pignalosa, A., Caputo, T., Troise, C., De Natale, G., and Sacchi, M.
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landslide monitoring ,010504 meteorology & atmospheric sciences ,Laser scanning ,Geography, Planning and Development ,Classification of discontinuities ,010502 geochemistry & geophysics ,Spatial distribution ,01 natural sciences ,Discontinuity (geotechnical engineering) ,Data acquisition ,Earth and Planetary Sciences (miscellaneous) ,Cliff ,Geomorphology ,Spatial analysis ,terrestrial laser scanner ,0105 earth and related environmental sciences ,geography ,Data processing ,GIS processing ,geography.geographical_feature_category ,vertical geostructural map, terrestrial laser scanner, GIS processing, tuff cliff, landslide monitoring, Campi Flegrei caldera, Naples ,vertical geostructural map ,Campi Flegrei caldera ,tuff cliff ,Naples ,Geology ,Seismology - Abstract
We present a long-range terrestrial laser scanner application for the geostructural mapping of Coroglio cliff, a tuff rock face exposed along the coastal zone of Campi Flegrei, Napoli. The procedure includes several phases (geomorphological analysis, structural field survey, laser scanner data acquisition and data processing, 3-D model development and analysis, geostructural classification of discontinuity orientation data and 2-D vertical cartographic production). Field data were processed with specific software dedicated to geostructural and geometric analysis. Spatial data were managed with a geographical information system and have been used for the construction of 2-D and 3-D geometric models of the rock cliff surface and geostructural interpretation. The main product of this study is a vertical geostructural map of the Coroglio cliff at 1:500 scale that illustrates the spatial distribution and orientation of the major families of structural discontinuities detected along the exposed surface of the cliff. The cartographic product includes base information useful to identify the main rock failure mechanisms along the cliff and represents a first step for the zonation of areas susceptible to block failures and the planning of monitoring activities.
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- 2016
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17. Modeling ethane oxy-dehydrogenation over monolithic combustion catalysts
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DONSI FRANCESCO, CAPUTO TIZIANA, DI BENEDETTO ALMERINDA, PIRONE RAFFAELE, RUSSO, GENNARO, Donsi, Francesco, Caputo, Tiziana, Russo, Gennaro, DI BENEDETTO, Almerinda, Pirone, Raffaele, Caputo, T., Donsì, F., Russo, G., and Pirone, R.
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Environmental Engineering ,Ethylene ,Oxy ,General Chemical Engineering ,Thermodynamics ,catalysi ,carbon dioxide, ethane ,Combustion ,ODH ,modelling ,ethylene ,short contact time ,Monolith ,Catalysis ,chemistry.chemical_compound ,Catalyst activity, Combustion, Ethylene, Heat transfer, Hydrogenation, Navier Stokes equation ,Dehydrogenation ,Energy equations, Monolithic combustion ,geography ,geography.geographical_feature_category ,ethane ,chemistry ,Catalytic oxidation ,Chemical engineering ,Heat transfer ,article, catalyst, combustion, dehydrogenation, heat transfer, mathematical analysis, mathematical model, process model, reaction analysis, simulation, thermogenesi ,Selectivity ,catalyst ,Biotechnology - Abstract
A numerical approach is used to investigate the role of a combustion catalyst in the oxidative dehydrogenation of ethane at short contact times for ethylene production. A two-dimensional (2-D) model, with mass and energy equations coupled with the Navier-Stokes equations, is applied to show that an oxidation catalyst can beneficially affect the formation of ethylene, by optimizing the sacrifice of ethane for producing heat with a larger selectivity to CO2 than a purely homogeneous process. Simulations also showed that for exceedingly high catalyst activity hot spots are formed on the catalyst walls, as the characteristic times of heat production become comparable with those of heat transfer. This may result into the formation of byproducts that reduce ethylene selectivity. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2233–2245, 2004
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- 2004
18. Exercise training and cold exposure trigger distinct molecular adaptations to inguinal white adipose tissue.
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Vamvini M, Nigro P, Caputo T, Stanford KI, Hirshman MF, Middelbeek RJW, and Goodyear LJ
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- Animals, Mice, Male, Proteome metabolism, Thermogenesis physiology, Glucose metabolism, Adipose Tissue, White metabolism, Physical Conditioning, Animal, Cold Temperature, Adaptation, Physiological, Mice, Inbred C57BL
- Abstract
Exercise training and cold exposure both improve systemic metabolism, but the mechanisms are not well established. Here, we tested the hypothesis that inguinal white adipose tissue (iWAT) adaptations are critical for these beneficial effects and determined the impact of exercise-trained and cold-exposed iWAT on systemic glucose metabolism and the iWAT proteome and secretome. Transplanting trained iWAT into sedentary mice improves glucose tolerance, while cold-exposed iWAT transplantation shows no such benefit. Compared to training, cold leads to more pronounced alterations in the iWAT proteome and secretome, downregulating >2,000 proteins but also boosting the thermogenic capacity of iWAT. In contrast, only training increases extracellular space and vesicle transport proteins, and only training upregulates proteins that correlate with favorable fasting glucose, suggesting fundamental changes in trained iWAT that mediate tissue-to-tissue communication. This study defines the unique exercise training- and cold exposure-induced iWAT proteomes, revealing distinct mechanisms for the beneficial effects of these interventions on metabolic health., Competing Interests: Declaration of interests R.J.W.M. and L.J.G. have received research support from Novo Nordisk, which is unrelated to the present study., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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19. The Arduous Path Toward Equitable Access to Endocrinology Care.
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Romeo GR, Caputo T, Stanescu IW, and Alkhaddo JB
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Multiple factors contribute to the widening gap between supply and demand of endocrinology services. In addition to the inadequate growth of the workforce, the inefficient utilization of endocrinologists' expertise coupled with the rising prevalence of endocrine conditions has generated a crisis in access to specialty care. This mismatch is magnified in underserved communities and among certain racial/ethnic groups that carry a disproportionate burden of chronic diseases, like diabetes and osteoporosis, thus perpetuating the cycle of health disparities in vulnerable populations. Reorienting the framework of endocrine care toward more effective and equitable access will require comprehensive changes in operational processes, system-based policies, and in the diversity of our workforce. Specifically, the progressive transition to outcome-driven, team-based models of care can extend endocrinology services beyond the traditional boundaries of in-office referrals and promote job satisfaction. Further, the implementation of policies that directly tackle structural determinants of health is a prerequisite to a more precise and equitable deployment of specialty care. In this view, the recruitment and professional growth of clinicians underrepresented in medicine along the career ladder, including leadership roles, is a key conduit to revitalize our field and to innovate the delivery of endocrine care across all communities., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2024
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20. Exercise Training and Cold Exposure Trigger Distinct Molecular Adaptations to Inguinal White Adipose Tissue.
- Author
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Vamvini M, Nigro P, Caputo T, Stanford KI, Hirshman MF, Middelbeek RJW, and Goodyear LJ
- Abstract
Exercise training and cold exposure both improve systemic metabolism, but the mechanisms are not well-established. We tested the hypothesis that adaptations to inguinal white adipose tissue (iWAT) are critical for these beneficial effects by determining the impact of exercise-trained and cold-exposed iWAT on systemic glucose metabolism and the iWAT proteome and secretome. Transplanting trained iWAT into sedentary mice improved glucose tolerance, while cold-exposed iWAT transplantation showed no such benefit. Compared to training, cold led to more pronounced alterations in the iWAT proteome and secretome, downregulating >2,000 proteins but also boosting iWAT's thermogenic capacity. In contrast, only training increased extracellular space and vesicle transport proteins, and only training upregulated proteins that correlate with favorable fasting glucose, suggesting fundamental changes in trained iWAT that mediate tissue-to-tissue communication. This study defines the unique exercise training- and cold exposure-induced iWAT proteomes, revealing distinct mechanisms for the beneficial effects of these interventions on metabolic health., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests. R.J.W.M. and L.J.G. have received research support from Novo Nordisk, which is unrelated to this work.
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- 2023
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21. Exercise training remodels inguinal white adipose tissue through adaptations in innervation, vascularization, and the extracellular matrix.
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Nigro P, Vamvini M, Yang J, Caputo T, Ho LL, Carbone NP, Papadopoulos D, Conlin R, He J, Hirshman MF, White JD, Robidoux J, Hickner RC, Nielsen S, Pedersen BK, Kellis M, Middelbeek RJW, and Goodyear LJ
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- Male, Mice, Animals, Adaptation, Physiological physiology, Acclimatization physiology, Transcription Factors metabolism, Adipose Tissue, Brown metabolism, Adipose Tissue metabolism, Mice, Inbred C57BL, Cell Adhesion Molecules, Neuronal metabolism, Motor Activity, Adipose Tissue, White metabolism
- Abstract
Inguinal white adipose tissue (iWAT) is essential for the beneficial effects of exercise training on metabolic health. The underlying mechanisms for these effects are not fully understood, and here, we test the hypothesis that exercise training results in a more favorable iWAT structural phenotype. Using biochemical, imaging, and multi-omics analyses, we find that 11 days of wheel running in male mice causes profound iWAT remodeling including decreased extracellular matrix (ECM) deposition and increased vascularization and innervation. We identify adipose stem cells as one of the main contributors to training-induced ECM remodeling, show that the PRDM16 transcriptional complex is necessary for iWAT remodeling and beiging, and discover neuronal growth regulator 1 (NEGR1) as a link between PRDM16 and neuritogenesis. Moreover, we find that training causes a shift from hypertrophic to insulin-sensitive adipocyte subpopulations. Exercise training leads to remarkable adaptations to iWAT structure and cell-type composition that can confer beneficial changes in tissue metabolism., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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22. Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue.
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Many GM, Sanford JA, Sagendorf TJ, Hou Z, Nigro P, Whytock K, Amar D, Caputo T, Gay NR, Gaul DA, Hirshman M, Jimenez-Morales D, Lindholm ME, Muehlbauer MJ, Vamvini M, Bergman B, Fern Ndez FM, Goodyear LJ, Ortlund EA, Sparks LM, Xia A, Adkins JN, Bodine SC, Newgard CB, and Schenk S
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Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training and sex on its molecular landscape has not been fully established. Utilizing an integrative multi-omics approach with data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we identified profound sexual dimorphism in the dynamic response of rat scWAT to endurance exercise training. Despite similar cardiorespiratory improvements, only male rats reduced whole-body adiposity, scWAT adipocyte size, and total scWAT triglyceride abundance with training. Multi-omic analyses of adipose tissue integrated with phenotypic measures identified sex-specific training responses including enrichment of mTOR signaling in females, while males displayed enhanced mitochondrial ribosome biogenesis and oxidative metabolism. Overall, this study reinforces our understanding that sex impacts scWAT biology and provides a rich resource to interrogate responses of scWAT to endurance training.
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- 2023
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23. DBnorm as an R package for the comparison and selection of appropriate statistical methods for batch effect correction in metabolomic studies.
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Bararpour N, Gilardi F, Carmeli C, Sidibe J, Ivanisevic J, Caputo T, Augsburger M, Grabherr S, Desvergne B, Guex N, Bochud M, and Thomas A
- Abstract
As a powerful phenotyping technology, metabolomics provides new opportunities in biomarker discovery through metabolome-wide association studies (MWAS) and the identification of metabolites having a regulatory effect in various biological processes. While mass spectrometry-based (MS) metabolomics assays are endowed with high throughput and sensitivity, MWAS are doomed to long-term data acquisition generating an overtime-analytical signal drift that can hinder the uncovering of real biologically relevant changes. We developed "dbnorm", a package in the R environment, which allows for an easy comparison of the model performance of advanced statistical tools commonly used in metabolomics to remove batch effects from large metabolomics datasets. "dbnorm" integrates advanced statistical tools to inspect the dataset structure not only at the macroscopic (sample batches) scale, but also at the microscopic (metabolic features) level. To compare the model performance on data correction, "dbnorm" assigns a score that help users identify the best fitting model for each dataset. In this study, we applied "dbnorm" to two large-scale metabolomics datasets as a proof of concept. We demonstrate that "dbnorm" allows for the accurate selection of the most appropriate statistical tool to efficiently remove the overtime signal drift and to focus on the relevant biological components of complex datasets.
- Published
- 2021
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24. Anti-adipogenic signals at the onset of obesity-related inflammation in white adipose tissue.
- Author
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Caputo T, Tran VDT, Bararpour N, Winkler C, Aguileta G, Trang KB, Giordano Attianese GMP, Wilson A, Thomas A, Pagni M, Guex N, Desvergne B, and Gilardi F
- Subjects
- Adipose Tissue, White cytology, Adipose Tissue, White pathology, Animals, Diet, High-Fat, Fatty Acid-Binding Proteins genetics, Fatty Acid-Binding Proteins metabolism, Gene Expression Regulation, Inflammation etiology, Inflammation metabolism, Interleukin-1beta genetics, Interleukin-1beta metabolism, Intra-Abdominal Fat cytology, Intra-Abdominal Fat metabolism, Intra-Abdominal Fat pathology, Lipid Metabolism, Male, Mice, Mice, Inbred C57BL, Obesity complications, Signal Transduction genetics, Stem Cells cytology, Stem Cells metabolism, Subcutaneous Fat cytology, Subcutaneous Fat metabolism, Subcutaneous Fat pathology, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha metabolism, Wnt Proteins metabolism, Adipogenesis, Adipose Tissue, White metabolism, Cell Differentiation, Inflammation pathology, Obesity pathology
- Abstract
Chronic inflammation that affects primarily metabolic organs, such as white adipose tissue (WAT), is considered as a major cause of human obesity-associated co-morbidities. However, the molecular mechanisms initiating this inflammation in WAT are poorly understood. By combining transcriptomics, ChIP-seq and modeling approaches, we studied the global early and late responses to a high-fat diet (HFD) in visceral (vWAT) and subcutaneous (scWAT) AT, the first being more prone to obesity-induced inflammation. HFD rapidly triggers proliferation of adipocyte precursors within vWAT. However, concomitant antiadipogenic signals limit vWAT hyperplastic expansion by interfering with the differentiation of proliferating adipocyte precursors. Conversely, in scWAT, residing beige adipocytes lose their oxidizing properties and allow storage of excessive fatty acids. This phase is followed by tissue hyperplastic growth and increased angiogenic signals, which further enable scWAT expansion without generating inflammation. Our data indicate that scWAT and vWAT differential ability to modulate adipocyte number and differentiation in response to obesogenic stimuli has a crucial impact on the different susceptibility to obesity-related inflammation of these adipose tissue depots.
- Published
- 2021
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25. Mono- and Bi-Phasic Cellulose Acetate Micro-Vectors for Anti-Inflammatory Drug Delivery.
- Author
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Guarino V, Altobelli R, Caputo T, Ambrosio L, Caserta S, Calcagnile P, and Demitri C
- Abstract
In recent years, different processing technologies have been engineered to fabricate capsules or particles with peculiar properties (e.g., swelling, pH-sensitive response) at the micro and sub-micrometric size scale, to be used as carriers for controlled drug and molecular release. Herein, the development of cellulose acetate (CA) micro-carriers with mono- (MC) or bi-phasic (BC) composition is proposed, fabricated via electrohydrodynamic atomization (EHDA)-an electro-dropping technology able to micro-size polymer solution by the application of high voltage electrostatic forces. Image analysis allows identification of the process parameters to optimize morphology, in terms of size distribution and shape. Meanwhile, an accurate rheological study has enabled investigating the interface between CA solutions with different viscosities to optimize BC systems. Release tests have confirmed that BC carriers can retain the drug more efficiently in acidic conditions, also providing a more gradual and sustained release until six days, with respect to MC carriers. Hence, all these results have proven that biphasic architecture significantly improves the capability of CA microcarriers to release ketoprofen lysinate, thus suggesting a new route to design core/shell systems for the retarded oral administration of anti-inflammatory drugs.
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- 2019
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26. From chronic overnutrition to metaflammation and insulin resistance: adipose tissue and liver contributions.
- Author
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Caputo T, Gilardi F, and Desvergne B
- Subjects
- Animals, Chronic Disease, Humans, Models, Biological, Adipose Tissue pathology, Inflammation pathology, Insulin Resistance, Liver pathology, Overnutrition pathology
- Abstract
The close association of obesity with an increased risk of metabolic diseases, such as insulin resistance, type 2 diabetes, and nonalcoholic fatty liver disease, is now well established. In this review, we aim first to describe the inflammatory process activated in response to overnutrition, especially in the liver and the adipose tissue. We then discuss the systemic effects of low-grade inflammation on the onset of insulin resistance. Particular attention is given to a series of very recent reports that identify not only processes but also molecules (lipids and metabolites) that interfere with the normal insulin signaling. Finally, special notes concerning the roles of peroxisome proliferator-activated receptors in the various processes will be made., (© 2017 Federation of European Biochemical Societies.)
- Published
- 2017
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27. A case of mesothelioma masquerading pre-operatively as ovarian cancer and brief review of the literature.
- Author
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Hancock KL, Clinton CM, Dinkelspiel HE, Saab J, Schneider B, and Caputo TA
- Abstract
Background: Malignant peritoneal mesothelioma (MPM) can masquerade as an ovarian epithelial neoplasm, with very similar presenting clinical symptoms and imaging findings. The gold standard in differentiating between these two diagnoses lies in tissue pathology., Case Report: This is a case of MPM that was initially misdiagnosed as ovarian cancer based on family history, imaging, and surgical findings. Tissue diagnosis preoperatively would have changed the planned procedure. Retrospectively, after the diagnosis of MPM, the patient was found to have had an indirect exposure to asbestos through her father., Conclusions: This case highlights the importance of keeping a broad differential when diagnosing ovarian malignancies, collecting both family and social histories (including screening for exposure to asbestos), and the benefit of obtaining tissue diagnosis when MPM is suspected.
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- 2016
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28. In situ transient FTIR and XANES studies of the evolution of surface species in CO oxidation on Au/TiO2.
- Author
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Henao JD, Caputo T, Yang JH, Kung MC, and Kung HH
- Subjects
- Adsorption, Oxidation-Reduction, Sensitivity and Specificity, Spectroscopy, Fourier Transform Infrared methods, Spectrum Analysis methods, Surface Properties, Time Factors, X-Rays, Carbon Monoxide chemistry, Gold chemistry, Titanium chemistry
- Abstract
The adsorption of CO and its reaction with oxygen were investigated using a combination of in situ Fourier transform infrared spectroscopy, step response measurements in a microreactor, (18)O isotopic labeling, and X-ray absorption near edge structure spectroscopy. An as-prepared sample in which Au is present as a surface oxyhydroxy complex does not adsorb CO. On an activated sample in which only metallic Au is detected, 0.18 +/- 0.03 mol CO/(mol Au) are adsorbed on Au at -60 degrees C, which shows an IR band at 2090 cm(-1). When oxygen is present in the gas phase, this species reacts with a turnover rate of 1.4 +/- 0.2 mol CO(mol Au min)(-1), which is close to the steady-state turnover rate. In contrast, there is a very small quantity of adsorbed oxygen on Au. A small IR peak at 1242 cm(-1) appears when an activated sample is exposed to CO. It reacts rapidly with oxygen and is shifted to 1236 cm(-1) if (18)O is used. It is assigned to the possible intermediate hydroxycarbonyl.
- Published
- 2006
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29. Activation of Au/TiO2 catalyst for CO oxidation.
- Author
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Yang JH, Henao JD, Raphulu MC, Wang Y, Caputo T, Groszek AJ, Kung MC, Scurrell MS, Miller JT, and Kung HH
- Abstract
Changes in a Au/TiO(2) catalyst during the activation process from an as-prepared state, consisting of supported AuO(x)(OH)(4-2x)(-) species, were monitored with X-ray absorption spectroscopy and FTIR spectroscopy, complemented with XPS, microcalorimetry, and TEM characterization. When the catalyst was activated with H(2) pulses at 298 K, there was an induction period when little changes were detected. This was followed by a period of increasing rate of reduction of Au(3+) to Au(0), before the reduction rate decreased until the sample was fully reduced. A similar trend in the activation process was observed if CO pulses at 273 K or a steady flow of CO at about 240 K was used to activate the sample. With both activation procedures, the CO oxidation activity of the catalyst at 195 K increased with the degree of reduction up to 70% reduction, and decreased slightly beyond 80% reduction. The results were consistent with metallic Au being necessary for catalytic activity.
- Published
- 2005
- Full Text
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