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2. MA09.03 Plasma Proteomics-based Models for Predicting Immunotherapy- and Chemotherapy-Related Toxicity in NSCLC Patients

Author

Naidoo, J., Gandara, D.R., Sullivan, R.R., Chae, Y.K., Carbone, D., Christopoulos, P., Reinmuth, N., Koch, I., Puzanov, I., Bar, J., Kamer, I., Moskovitz, M., Levy-Barda, A., Agbarya, A., Zer, A., Gottfried, M., Abu Amna, M., Brown, S., Lotem, M., Price, G., Hassani, A., Harkovsky, T., Leibowitz, R., Sela, I., Lahav, C., Yellin, B., Harel, M., and Elon, Y.

Published
2024
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3. Giant valleyZeeman coupling in the surface layer of an intercalated transition metal dichalcogenide

Author

Edwards, B., Dowinton, O., Hall, A. E., Murgatroyd, P. A. E., Buchberger, S., Antonelli, T., Siemann, G.-R., Rajan, A., Morales, E. Abarca, Zivanovic, A., Bigi, C., Belosludov, R. V., Polley, C. M., Carbone, D., Mayoh, D. A., Balakrishnan, G., Bahramy, M. S., and King, P. D. C.

Abstract

Spin–valley locking is ubiquitous among transition metal dichalcogenides with local or global inversion asymmetry, in turn stabilizing properties such as Ising superconductivity, and opening routes towards ‘valleytronics’. The underlying valley–spin splitting is set by spin–orbit coupling but can be tuned via the application of external magnetic fields or through proximity coupling. However, only modest changes have been realized to date. Here, we investigate the electronic structure of the V-intercalated transition metal dichalcogenide V1/3NbS2using microscopic-area spatially resolved and angle-resolved photoemission spectroscopy. Our measurements and corresponding density functional theory calculations reveal that the bulk magnetic order induces a giant valley-selective Ising coupling exceeding 50 meV in the surface NbS2layer, equivalent to application of a ~250 T magnetic field. This energy scale is of comparable magnitude to the intrinsic spin–orbit splittings, and indicates how coupling of local magnetic moments to itinerant states of a transition metal dichalcogenide monolayer provides a powerful route to controlling their valley–spin splittings.

Published
2023
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7. Trends in particle and nuclei identification techniques in nuclear physics experiments

Author

Badalà, A., La Cognata, M., Nania, R., Osipenko, M., Piantelli, S., Turrisi, R., Barion, L., Capra, S., Carbone, D., Carnesecchi, F., Casula, E. A. R., Chatterjee, C., Ciani, G. F., Depalo, R., Di Nitto, A., Fantini, A., Goasduff, A., Guardo, G. L., Kraan, A. C., Manna, A., Marsicano, L., Martorana, N. S., Morales-Gallegos, L., Naselli, E., Scordo, A., Valdré, S., and Volpe, G.

Abstract

Particle identification techniques are fundamental tools in nuclear physics experiments. Discriminating particles or nuclei produced in nuclear interactions allows to better understand the underlying physics mechanisms. The energy interval of these reactions is very broad, from sub-eV up to TeV. For this reason, many different identification approaches have been developed, often combining two or more observables. This paper reviews several of these techniques with emphasis on the expertise gained within the current nuclear physics scientific program of the Italian Istituto Nazionale di Fisica Nucleare (INFN).

Published
2022
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9. Erratum to: Trends in particle and nuclei identification techniques in nuclear physics experiments

Author

Badalà, A., La Cognata, M., Nania, R., Osipenko, M., Piantelli, S., Turrisi, R., Barion, L., Capra, S., Carbone, D., Carnesecchi, F., Casula, E. A. R., Chatterjee, C., Ciani, G. F., Depalo, R., Di Nitto, A., Fantini, A., Goasduff, A., Guardo, G. L., Kraan, A. C., Manna, A., Marsicano, L., Martorana, N. S., Morales-Gallegos, L., Naselli, E., Scordo, A., Valdré, S., and Volpe, G.

Published
2022
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10. Identifying transient and variable sources in radio images

Author

Rowlinson, A., Stewart, A.J., Broderick, J.W., Swinbank, J.D., Wijers, R.A.M.J., Carbone, D., Cendes, Y., Fender, R., van der Horst, A., Molenaar, G., Scheers, B., Staley, T., Farrell, S., Grießmeier, J.-M., Bell, M., Eislöffel, J., Law, C.J., van Leeuwen, J., and Zarka, P.

Abstract

With the arrival of a number of wide-field snapshot image-plane radio transient surveys, there will be a huge influx of images in the coming years making it impossible to manually analyse the datasets. Automated pipelines to process the information stored in the images are being developed, such as the LOFAR Transients Pipeline, outputting light curves and various transient parameters. These pipelines have a number of tuneable parameters that require training to meet the survey requirements. This paper utilises both observed and simulated datasets to demonstrate different machine learning strategies that can be used to train these parameters. We use a simple anomaly detection algorithm and a penalised logistic regression algorithm. The datasets used are from LOFAR observations and we process the data using the LOFAR Transients Pipeline; however the strategies developed are applicable to any light curve datasets at different frequencies and can be adapted to different automated pipelines. These machine learning strategies are publicly available as Pythontools that can be downloaded and adapted to different datasets (https://github.com/AntoniaR/TraP_ML_tools).

Published
2019
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11. PS01.05 Surgical and Clinical Outcomes With Neoadjuvant Atezolizumab in Resectable Stage IB–IIIB NSCLC: LCMC3 Trial Primary Analysis

Author

Lee, J., Chaft, J., Nicholas, A., Patterson, A., Waqar, S., Toloza, E., Haura, E., Raz, D., Reckamp, K., Merritt, R., Owen, D., Finley, D., Mcnamee, C., Blasberg, J., Garon, E., Mitchell, J., Doebele, R., Baciewicz, F., Nagasaka, M., Pass, H., Schulze, K., Phan, S., Johnson, A., Bunn, P., Johnson, B., Kris, M., Kwiatkowski, D., Wistuba, I., Carbone, D., and Rusch, V.

Published
2021
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12. PySE: Software for extracting sources from radio images

Author

Carbone, D., Garsden, H., Spreeuw, H., Swinbank, J.D., van der Horst, A.J., Rowlinson, A., Broderick, J.W., Rol, E., Law, C., Molenaar, G., and Wijers, R.A.M.J.

Abstract

PySE is a Python software package for finding and measuring sources in radio telescope images. The software was designed to detect sources in the LOFAR telescope images, but can be used with images from other radio telescopes as well. We introduce the LOFAR Telescope, the context within which PySE was developed, the design of PySE, and describe how it is used. Detailed experiments on the validation and testing of PySE are then presented, along with results of performance testing. We discuss some of the current issues with the algorithms implemented in PySE and their interaction with LOFAR images, concluding with the current status of PySE and its future development.

Published
2018
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13. RFI flagging implications for short-duration transients

Author

Cendes, Y., Prasad, P., Rowlinson, A., Wijers, R.A.M.J., Swinbank, J.D., Law, C.J., van der Horst, A.J., Carbone, D., Broderick, J.W., Staley, T.D., Stewart, A.J., Huizinga, F., Molenaar, G., Alexov, A., Bell, M.E., Coenen, T., Corbel, S., Eislöffel, J., Fender, R., Grießmeier, J.-M., Jonker, P., Kramer, M., Kuniyoshi, M., Pietka, M., Stappers, B., Wise, M., and Zarka, P.

Abstract

With their wide fields of view and often relatively long coverage of any position in the sky in imaging survey mode, modern radio telescopes provide a data stream that is naturally suited to searching for rare transients. However, Radio Frequency Interference (RFI) can show up in the data stream in similar ways to such transients, and thus the normal pre-treatment of filtering RFI (flagging) may also remove astrophysical transients from the data stream before imaging. In this paper we investigate how standard flagging affects the detectability of such transients by examining the case of transient detection in an observing mode used for Low Frequency Array (LOFAR; van Haarlem et al., 2013) surveys. We quantify the fluence range of transients that would be detected, and the reduction of their SNR due to partial flagging. We find that transients with a duration close to the integration sampling time, as well as bright transients with durations on the order of tens of seconds, are completely flagged. For longer transients on the order of several tens of seconds to minutes, the flagging effects are not as severe, although part of the signal is lost. For these transients, we present a modified flagging strategy which mitigates the effect of flagging on transient signals. We also present a script which uses the differences between the two strategies, and known differences between transient RFI and astrophysical transients, to notify the observer when a potential transient is in the data stream.

Published
2018
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15. A new technique for probing the internal structure of volcanoes using cosmic-ray muons

Author

Del Santo, M., Catalano, O., Mineo, T., Cusumano, G., Maccarone, M.C., La Parola, V., La Rosa, G., Sottile, G., Vercellone, S., Pareschi, G., Carbone, D., and Zuccarello, L.

Abstract

Among the considerable number of studies that can be carried out using muons, we pay specific attention to the radiography of volcanoes based on the same principle of the X-ray radiography of human body. Thanks to their high penetration capability, cosmic-ray muons can be used to reconstruct the density distribution of the interior of huge structures by measuring the attenuation induced by the material on the muon flux. In particular, the quantitative understanding of the inner structure of volcanoes is a key-point to forecast the dangerous stages of activity and mitigate volcanic hazards. The instrumental approach is currently based on the detection of muons crossing hodoscopes made up of scintillator planes. Unfortunately, these detectors are affected by a strong background comprised by accidental coincidence of vertical shower particles, horizontal high-energy electrons and upward going particles. We propose an alternative technique based on the detection of the Cherenkov light produced by muons. This can be achieved with an imaging atmospheric Cherenkov telescope composed of a high reflectivity optical system that focus the Cherenkov light onto a multi-pixel focal camera with fast read-out electronics. The Cherenkov light emitted by a muon is imaged on the camera as an annular pattern which contains information to reconstruct the direction of the incident muon. We have estimated that using the Cherenkov imaging technique for muon radiography of volcanoes gives the advantage of a negligible background and improved spatial resolution, compared to the majority of the particle detectors. We present results of simulations based on a telescope with a positioning resolution of 13.5 m which corresponds to an acceptance of 9 cm2sr. The telescope is located 1500 m far from a toy-model volcano, namely, a cone with a base diameter of 500 m and a height of 240 m. We test the feasibility of the proposed method by estimating the minimum number of observation nights needed to resolve inner empty conduits of different diameter.

Published
2017
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16. PP01.25 Incidence and Timing of Immune-Related Adverse Events in Patients With Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitor as Monotherapy or in Combination With Chemotherapy

Author

Secor, A., Zhao, S., Wei, L., Das, P., Haddad, T., Miah, A., Spakowicz, D., Lopez, G., Husain, M., Grogan, M., Li, M., Schweitzer, C., Pilcher, C., Uribe, D., Cheng, G., Phelps, M., Guo, J., Shields, P., He, K., Bertino, E., Carbone, D., Otterson, G., Presley, C.J., and Owen, D.H.

Published
2023
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17. A large light-mass component of cosmic rays at 1017–1017.5electronvolts from radio observations

Author

Buitink, S., Corstanje, A., Falcke, H., Hörandel, J. R., Huege, T., Nelles, A., Rachen, J. P., Rossetto, L., Schellart, P., Scholten, O., ter Veen, S., Thoudam, S., Trinh, T. N. G., Anderson, J., Asgekar, A., Avruch, I. M., Bell, M. E., Bentum, M. J., Bernardi, G., Best, P., Bonafede, A., Breitling, F., Broderick, J. W., Brouw, W. N., Brüggen, M., Butcher, H. R., Carbone, D., Ciardi, B., Conway, J. E., de Gasperin, F., de Geus, E., Deller, A., Dettmar, R.-J., van Diepen, G., Duscha, S., Eislöffel, J., Engels, D., Enriquez, J. E., Fallows, R. A., Fender, R., Ferrari, C., Frieswijk, W., Garrett, M. A., Grießmeier, J. M., Gunst, A. W., van Haarlem, M. P., Hassall, T. E., Heald, G., Hessels, J. W. T., Hoeft, M., Horneffer, A., Iacobelli, M., Intema, H., Juette, E., Karastergiou, A., Kondratiev, V. I., Kramer, M., Kuniyoshi, M., Kuper, G., van Leeuwen, J., Loose, G. M., Maat, P., Mann, G., Markoff, S., McFadden, R., McKay-Bukowski, D., McKean, J. P., Mevius, M., Mulcahy, D. D., Munk, H., Norden, M. J., Orru, E., Paas, H., Pandey-Pommier, M., Pandey, V. N., Pietka, M., Pizzo, R., Polatidis, A. G., Reich, W., Röttgering, H. J. A., Scaife, A. M. M., Schwarz, D. J., Serylak, M., Sluman, J., Smirnov, O., Stappers, B. W., Steinmetz, M., Stewart, A., Swinbank, J., Tagger, M., Tang, Y., Tasse, C., Toribio, M. C., Vermeulen, R., Vocks, C., Vogt, C., van Weeren, R. J., Wijers, R. A. M. J., Wijnholds, S. J., Wise, M. W., Wucknitz, O., Yatawatta, S., Zarka, P., and Zensus, J. A.

Abstract

High-resolution radio measurements of air showers—cascades of secondary particles in the atmosphere initiated by cosmic rays—reveal that cosmic rays with energies of 1017–1017.5electronvolts have a mixed composition, with light elements (protons and helium nuclei) making up 80 per cent of their mass.

Published
2016
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18. LKB1 deficiency enhances sensitivity to energetic stress induced by erlotinib treatment in non-small-cell lung cancer (NSCLC) cells

Author

Whang, Y M, Park, S I, Trenary, I A, Egnatchik, R A, Fessel, J P, Kaufman, J M, Carbone, D P, and Young, J D

Abstract

The tumor suppressor serine/threonine kinase 11 (STK11or LKB1) is mutated in 20–30% of patients with non-small-cell lung cancer (NSCLC). Loss of LKB1-adenosine monophosphate-activated protein kinase (AMPK) signaling confers sensitivity to metabolic inhibition or stress-induced mitochondrial insults. We tested the hypothesis that loss of LKB1 sensitizes NSCLC cells to energetic stress induced by treatment with erlotinib. LKB1-deficient cells exhibited enhanced sensitivity to erlotinib in vitroand in vivothat was associated with alterations in energy metabolism and mitochondrial dysfunction. Loss of LKB1 expression altered the cellular response to erlotinib treatment, resulting in impaired ATP homeostasis and an increase in reactive oxygen species. Furthermore, erlotinib selectively blocked mammalian target of rapamycin signaling, inhibited cell growth and activated apoptosis in LKB1-deficient cells. Erlotinib treatment also induced AMPK activation despite loss of LKB1 expression, which was partially reduced by the application of a calcium/calmodulin-dependent protein kinase kinase 2 inhibitor (STO-609) or calcium chelator (BAPTA-AM). These findings may have significant implications for the design of novel NSCLC treatments that target dysregulated metabolic and signaling pathways in LKB1-deficient tumors.

Published
2016
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20. OA06.04 Constructing a Global Molecular Database for Thoracic Malignancies: The IASLC Molecular Subcommittee Lung Cancer Dataset

Author

Osarogiagbon, R., Nishimura, K., Porta, R. Rami, Montuenga, L., Giroux, D., Suda, K., Araujo, L., Detterbeck, F., Gautschi, O., Kerr, K., Kneuertz, P., Mack, P., Matilla, J., Nicholson, A., Pass, H., Presley, C., Terra, R., Wistuba, I., Yang, D., Yatabe, Y., Travis, W., Tsao, M., Asamura, H., Rusch, V., Hirsch, F., and Carbone, D.

Published
2021
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23. EP08.01-062 Body Mass Index, Immune Related Adverse Events, and Survival in Patients with Metastatic Non-small Cell Lung Cancer Treated with Immunotherapy

Author

Li, M., Zhao, S., Guo, J., Gauntner, T., Schafer, J., Chakravarthy, K., Lopez, G., Secor, A., Das, P., Surya, N., Husain, M., Patel, S., Grogan, M., Spakowicz, D., Miah, A., Wei, L., He, K., Bertino, E., Alahmadi, A., Memmott, R., Kaufman, J., Presley, C., Shields, P., Carbone, D., Otterson, G., and Owen, D.

Published
2022
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25. Transient simulations for radio surveys

Author

Chastain, S.I., van der Horst, A.J., and Carbone, D.

Abstract

Several new radio facilities have a field of view and sensitivity well suited for transient searches. This makes it more important than ever to accurately determine transient rates in radio surveys. The work presented here seeks to do this task by using Monte-Carlo simulations. In particular, the user inputs either a real or simulated observational setup, and the simulations code calculates transient rate as a function of transient duration and peak flux. These simulations allow for simulating a wide variety of scenarios including observations with varying sensitivities and durations, multiple overlapping telescope pointings, and a wide variety of light curve shapes with the user having the ability to easily add more. While the current scientific focus is on the radio regime, with examples given here from the MeerKAT telescope in South Africa, the simulations code can be easily adapted to other wavelength regimes.

Published
2022
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29. OA06.06 Clinical/Biomarker Data for Neoadjuvant Atezolizumab in Resectable Stage IB-IIIB NSCLC: Primary Analysis in the LCMC3 Study

Author

Carbone, D., Lee, J., Kris, M., Wistuba, I., Kwiatkowski, D., Owen, D., Bunn, P., Johnson, B., Oezkan, F., Tang, Y., Parra, E.R., Lozanski, G., Rivard, C., Schulze, K., Nicholas, A., Johnson, A., Grindheim, J., Shames, D., Phan, S., Toloza, E., Haura, E., Mcnamee, C., Gainor, J., Patterson, A., Waqar, S., Raz, D., Reckamp, K., Finley, D., Rusch, V., Chaft, J., and Abel, J.

Published
2021
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33. Evidence-based Medicine Update on Testosterone Replacement Therapy (TRT) in Male Hypogonadism: Focus on New Formulations

Author

A. Giagulli, V., Triggiani, V., Corona, G., Carbone, D., Licchelli, B., Tafaro, E., Resta, F., Sabba, C., Maggi, M., and Guastamacchia, E.

Abstract

Until the 2000s Testosterone (T) Replacement Therapy (TRT) was not very satisfactory for male hypogonadic patients because the available T formulations were not able to reproduce the physiological pattern of T secretion in man. In fact, oral formulations (oral undecanoate T) showed very short half-life (<24 hours), requiring the administration of several daily doses, whereas the old injection products (T esters) were characterized by very long half-life (>7 days) because of their adipose tissue storage, requiring to be administered every 2-3 weeks but determining remarkable and quick fluctuations (in 2-3 weeks) of the testosteronemia with variations in a few days from over-physiological levels (> 2000 ng/dl) to very low levels (< 200 ng/dl). Nowadays, several compounds can attain the standards of suitability and effectiveness of TRT in hypogonadal men. Both transcutaneous (gel) T and long-acting injectable formulations are the most modern preparations that can satisfy the criteria of an ideal chronic replacement therapy. In fact, they keep the serum T levels in the physiological range imitating its circadian rhythm, leading to the development and/or the preservation of male sexual characteristics and, finally, positively influencing bone mass, skeletal muscle and adipose tissue distribution. In particular, the availability and use of long-acting injectable undecanoate T can really improve the patients compliance as requested for a life-long treatment. However, definitive and conclusive evidence regarding the main end-points, such as the diminished recurrence of falls in elderly men, the decrease in fractures in osteoporotic subjects, the reduction in disabling conditions and the extension of life, have not been reached so far. Therefore, the aim of this review is to sum up the most important evidence that has been collected regarding TRT, highlighting in particular those concerning both transcutaneous and long-acting injectable T compounds.

Published
2011

34. Does Calprotectin Represent a Regulatory Factor in Host Defense or a Drug Target in Inflammatory Disease?

Author

Baldassarre, M. E., Altomare, M. A., Fanelli, M., Carbone, D., Di Bitonto, G., Mautone, A., and Laforgia, N.

Abstract

Calprotectin, a protein composed by two subunits of 8 and 14 kD respectively, is released by neutrophils in the biological fluids under inflammatory states. For instance, detection of calprotectin in faeces represents a diagnostic tool in the case of inflammatory bowel disease. Quite interestingly, calprotectin is increased in the stool of healthy newborns from day three up to day thirty and, physiologically, this increase may be interpreted as a defense mechanism against yeast and fungi. Therapeutic attempts at inhibiting the deleterious effect of calprotectin have been experimentally made by using lycoricinidol. This natural compound is able to hamper the calprotectin-induced apoptosis on the one hand. On the other hand, the same compound plays a prophylactic role in the course of experimental arthritis in rats.

Published
2007

35. Hormonal control of inhibin B in men

Author

Giagulli, V. and Carbone, D.

Abstract

Serum inhibin B (IB) and testosterone (T) levels, secreted by Sertoli cells (SC) and Leydig cells (LC), respectively, are parameters of the functional state of these cells. Whereas LC activity and, consequently, T secretion are regulated by serum LH, factors regulating IB secretion by SC are still partially unknown. There is evidence that under certain conditions such as puberty, aging or some spermatogenesis defects, LH levels or Gn-independent factors might contribute to regulating SC activity and IB secretion. Among these factors, GH and IGF-I as well as PRL might have a role. Therefore, in order to explore the possible effects of either LH alone and FSH alone or a combination of both Gn, respectively, on SC function, IB plasma levels and spermatogenesis, we studied their effects in 6 patients with hypogonadotropic hypogonadism (HH), whereas the effects of GH on these parameters were studied in 6 men with panhypopituitarism (PH). Finally, the possible effects of PRL on SC function and spermatogenesis were studied in 6 patients with hyperprolactinemia (HPRL); 24 normal, fertile adults served as control group. In men with HH, neither human chorionic Gn (hCG) nor FSH, respectively, were able to increase serum IB after 3 months of therapy, whereas combined Gn therapy for 24 months increased IB plasma levels and stimulated spermatogenesis in 4 out of 6 hypogonadal men. In panhypopituitaric men, GH added to the classical Gn therapy did not have an additional effect on serum IB levels or spermatogenesis. Surprisingly, in our hyperprolactemic men, IB plasma levels were increased and positively correlated (p<0.01) with serum PRL levels, whereas normalization of the latter by cabergoline treatment caused a decrease of IB levels and a moderate increase in T, LH and FSH. In conclusion, the lack of SC response to FSH therapy alone, as opposed to the response to combined Gn therapy, might indicate that normalization of serum T by hCG is required to obtain IB secretion by SC. Addition of GH did not affect SC function, serum IB levels or spermatogenesis. Finally, our data suggest that PRL plasma levels might have a direct role on IB secretion, suggesting that the hypogonadism found in patients with HPRL might be a consequence of both central (inhibition of Gn secretion) and peripheral (stimulation of IB secretion) origin.

Published
2006
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36. Cysteine Modification by Lipid Peroxidation Products Inhibits Protein Disulfide Isomerase

Author

Carbone, D. L., Doorn, J. A., Kiebler, Z., and Petersen, D. R.

Abstract

A proteomic approach was applied to mitochondrial protein isolated from the livers of rats fed a combination high-fat and ethanol diet to identify proteins modified by 4-hydroxynonenal (4-HNE). Using this approach, the endoplasmic reticulum chaperone, protein disulfide isomerase (PDI), which participates in the maturation of newly synthesized proteins through promoting correct disulfide formation, was consistently found to be modified by 4-HNE. Further mass spectral analysis of PDI isolated from the animals revealed modification of an active site Cys residue thought to be involved in client protein binding. To test the hypothesis that 4-HNE inhibits the chaperone, purified bovine PDI was treated with concentrations of 4-HNE ranging from 20 to 200 μM (10−100-fold molar excess aldehyde), resulting in 14−56% inhibition, respectively. Similar treatments with the lipid peroxidation products acrolein (ACR) and 4-oxononenal (4-ONE) resulted in 60 and 100% inhibition, respectively, suggesting inactivation of the chaperone via Cys modification. Thiol sensitivity was confirmed through concentration-dependent inhibition of PDI by the Cys modifier N-ethylmaleimide (NEM). While some degree of sensitivity to these lipid aldehydes is suggested by the data, when compared to inactivation of other proteins by 4-HNE, PDI has demonstrated a relative resistance. It was also observed that physiologic (e.g., 4 mM) concentrations of GSH were capable of removing the 4-HNE adducts, likely serving as a protective mechanism against inactivation by 4-HNE and other lipid peroxidation products. However, because an active site Cys was found to be modified by 4-HNE on PDI in vivo, it is possible that the protective effect of GSH on the chaperone decreases under conditions of sustained oxidative stress, such as during chronic alcohol consumption, as GSH is depleted. The data presented here thus suggest potential impairment of an important molecular chaperone during oxidative stress.

Published
2005

37. Inhibition of Hsp72-Mediated Protein Refolding by 4-Hydroxy-2-nonenal

Author

Carbone, D. L., Doorn, J. A., Kiebler, Z., Sampey, B. P., and Petersen, D. R.

Abstract

A proteomic approach was applied to liver cytosol from rats fed a diet consisting of high fat and ethanol to identify 4-hydroxy-2-nonenal (4-HNE)-modified proteins in vivo. Cytosolic Hsp72, the inducible variant of the Hsp70 heat shock protein family, was consistently among the proteins modified by 4-HNE. Despite 1.3-fold induction of Hsp72 in the livers of ethanol-fed animals, no increase in Hsp70-mediated luciferase refolding in isolated heptocytes was observed, suggesting inhibition of this process by 4-HNE. A 50% and 75% reduction in luciferase refolding efficiency was observed in rabbit reticulocyte lysate (RRL) supplemented with recombinant Hsp72 which had been modified in vitro with 10 and 100 μM 4-HNE, respectively. This observation was accompanied by a 25% and 50% decrease in substrate binding by the chaperone following the same treatment; however, no effect on complex formation between Hsp72 and its co-chaperone Hsp40 was observed. Trypsin digest and mass spectral analysis of Hsp72 treated with 10 and 100 μM 4-HNE consistently identified adduct formation at Cys267 in the ATPase domain of the chaperone. The role of this residue in the observed inhibition was demonstrated through the use of DnaK, a bacterial Hsp70 variant lacking Cys267. DnaK was resistant to 4-HNE inactivation. Additionally, Hsp72 was resistant to inactivation by the thiol-unreactive aldehyde malondialdehyde (MDA), further supporting a role for Cys in Hsp72 inhibition by 4-HNE. Finally, the affinity of Hsp72 for ATP was decreased 32% and 72% following treatment of the chaperone with 10 and 100 μM 4-HNE, respectively. In a model of chronic alcoholic liver injury, induction of Hsp72 was not accompanied by an increase in protein refolding ability. This is likely the result of 4-HNE modification of the Hsp72 ATPase domain.

Published
2004

39. COMPLICATION RATE OF MICROSURGICAL VARICOCELE LIGATION WITHOUT DELIVERY OF THE TESTIS

Author

Carbone, D. J. and MERHOFF, Jr.

Abstract

It is commonly assumed that the complication rate of microsurgical varicocele repair is lower than that of nonmicrosurgical techniques, particularly since magnification allows for preservation of lymphatic vessels and, thus, a theoretically lower incidence of hydrocele. However, review of the literature reveals relatively few papers on this subject. The authors reviewed their experience to determine the incidence of complications following microsurgical varicocele repair without delivery of the testicle in the adult population. From 1 July 1997 to 1 September 2001 139 men underwent microsurgical varicocele ligation without delivery of the testicle, with a mean follow-up of 22 months. Of the 139 men, 4 (2.9%) had complications. One (0.7%) had a recurrence, 1 (0.7%) had a wound infection, 1 (0.7%) had epididymitis, and 1 (0.7%) had an unintentional injury of the testicular artery. None of the men developed a hydrocele. The published complication rate for nonmicrosurgical varicocle ligation ranges from 5.4 to 7.2%, with the most common complication being hydrocele formation. In the authors' series, the overall complication rate was 2.9%, with no patient developing a hydrocele. Thus, microsurgical varicocele ligation without delivery of the testicle results in a lower complication rate and a lower incidence of hydrocele than nonmicrosurgical techniques.

Published
2003
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40. Heavy Ions Double Charge Exchange reactions: towards the 0νββNuclear Matrix Element determination

Author

Agodi, C., Cappuzzello, F., Cavallaro, M., Bondì, M., Carbone, D., Cunsolo, A., and Foti, A.

Abstract

First experimental results, obtained at the INFN-LNS laboratory in Catania, for the 40Ca(18O,18Ne)40Ar reaction at 270 MeV are shown. The data give encouraging indication on the capability to access quantitative information towards the determination of the Nuclear Matrix Elements for 0νββdecay. The idea is to use an innovative technique to access the nuclear matrix elements entering the expression of the life time of the double beta decay by cross sections measurements of double charge exchange reactions. The basic point is the coincidence of the initial and final state wave-functions in the two classes of processes and the similarity of the transition operators, which in both cases present a superposition of Fermi-like, Gamow-Teller-like and rank-two tensor components with a relevant implicit momentum available in the intermediate channel.

Published
2015
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42. Temporal variations in gravity at Mt. Etna (Italy) associated with the 1989 and 1991 eruptions

Author

Budetta, G. and Carbone, D.

Abstract

Abstract:  Results are presented from 11 microgravity surveys on Mt. Etna between 1987 and 1993, a period including the major 1989 and 1991–1993 flank eruptions and subordinate 1990 activity. Measurements were made with LaCoste and Romberg D-62 and D-157 gravity meters along a network around the volcano between 1000 and 1900 m a.s.l. and, since 1992, a N–S summit profile. Gravity changes of as much as 200 μGal were observed at scales from the size of the summit region to that of the volcano. None was associated with significant changes in ground elevation. The data show an increase in gravity for 2 years before the 1989 eruption. The increase is attributed to the accumulation of magma (0.25–1.7×109 m3) in an elongate zone, oriented NNW–SSE, between 2.5 and 6 km below sea level. Part of this magma was injected into the volcanic pile to supply the 1989 and 1990 eruptions. It also probably fed the start of the 1991–1993 eruption, since this event was not preceded by significant gravity changes. A large gravity increase (up to 140 μGal) detected across the volcano between June and September 1992 is consistent with the arrival in the accumulation zone of 0.32–2.2×109 m3 of new magma, thus favoring continued flank effusion until 1993. A large gravity decrease (200 μGal) in the summit region marked the closing stages of the 1991–1993 event and is associated with magma drainage from the upper levels of Etna's central feeding system.

Published
1998
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44. Radium Needles Implant in the Treatment of Extensive Vaginal Involvement from Cervical Carcinoma a Dosimetry Appraisal

Author

Sewchand, W., Prempree, T., Patanaphan, V., Carbone, D., and Salazar, O. M.

Abstract

An appraisal of the dosimetry of a modified brachytherapy approach is presented for improving the local control of extensive vaginal involvement from carcinoma of the cervix. This approach incorporates radium needles implant to the vaginal disease in conjunction with the usual routine intracavitary radium application. The aim of the interstitial implant is specifically to supplement the dose to the vaginal disease from the intracavitary application. Our procedure for accomplishing this boost in the dose to the vagina depends on the location, extent and thickness of the vaginal lesion following external beam irradiation of the whole pelvis. An increase of greater than 50 per cent in the dose to the vaginal disease is gained by this combination intracavitary/implant approach which has been used in a variety of cases covering virtually all pertinent stages of cervical carcinoma. Discussion of the dosimetry of example cases is presented to demonstrate the value of combining interstitial and intracavitary therapy for this specific clinical application.

Published
1984
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47. Abstract

Author

Mache, Ch., Urban, Ch., Sauer, H., Brandesky, G., Meßner, H., Grienberger, H., Becker, H., Slave, I., Hauer, Ch., Pakisch, B., Oberbauer, R., Mokry, M., Ebner, F., Kleinert, R., Schiller, D., Kasparu, H., Schneider, G., Sega, W., Lutz, D., Mader, R. M., Steger, G. G., Sieder, A. E., Ovissi, L., Roth, E., Hamilton, G., Jakesz, R., Rainer, H., Schenk, T., Kornek, G., Schulz, F., Depisch, D., Rosen, H., Sebesta, Ch., Scheithauer, W., Locker, G. J., Czernin, J., Derfler, K., Gnant, M., Schiessel, R., Petru, E., Pickel, H., Heydarfadai, M., Lahousen, M., Haas, J., Sagaster, P., Flamm, J., Umek, H., Essl, R., Teich, G., Micksche, M., Ludwig, H., Ambros, P. F., Lestou, V., Strehl, S., Mann, G., Gadner, H., Eibl, B., Greiter, E., Grünewald, K., Gastl, G., Thaler, J., Aulitzky, W., Lion, T., Henn, T., Gaiger, A., Hofmann, J., Wolf, A., Spitaler, M., Ludescher, Christof, Grunicke, H., Mitterbauer, G., Stangl, E., Geissler, K., Jäger, U., Lechner, K., Mannhalter, C., Haas, Oskar A., Tirita, Anthi, Kahls, P., Haas, O., Hinterberger, W., Linkesch, W., Pober, Michael, Fae, Ingrid, Kyrle, Alexander, Neumeister, Andrea, Panzer, Simon, Kandioler, D., End, A., Grill, R., Karlic, H., Inhauser, T., Chott, A., Pirc-Danoewinata, H., Klepetko, W., Heinz, R., Hopfinger-Limberger, G., Koller, E., Schneider, B., Pittermann, E., Lorber, C., Eichinger, S., Neumann, E., Weidinger, J., Gisslinger, H., Bedford, P., Jones, D., Cawley, J., Catovsky, D., Bevan, P., Scherrer, R., Bettelheim, P., Knöbl, P., Kyrie, P. A., Lazcika, K., Schwarzinger, I., Sillaber, C., Watzke, H., Dávid, M., Losonczy, H., Matolcsy, A., Papp, M., Prischl, F. C., Schwarzmeier, J. D., Zoubek, Andreas, Harbott, Jochen, Ritterbach, Jutta, Ritter, Jörg, Sillaber, Ch., Agis, H., Spanblöchl, E., Sperr, W. R., Valent, P., Czerwenka, K., Virgolini, I., Li, S. R., Müller, M., Wrann, M., Gaggl, S., Fasching, B., Herold, M., Geissler, D., Nachbaur, D., Huber, Ch., Schwaighofer, H., Pichl, M., Niederwieser, D., Gilly, B., Weissel, H., Lorber, Ch., Schwarzmeier, J., Gasché, C., Reinisch, W., Hilgarth, M., Keil, F., Thomssen, C., Kolb, H. J., Holler, E., Wilmanns, W., Tilg, H., Gächter, A., Panzer-Grümayer, E. R., Majdic, O., Kersey, J. H., Petzer, A. L., Bilgeri, R., Zilian, U., Geisen, F. H., Haun, M., Konwalinka, G., Fuchs, D., Zangerle, R., Artner-Dworzak, E., Weiss, G., Fritsch, P., Tilz, G. P., Dierich, M. P., Wachter, H., Schüller, J., Czejka, M. 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K., Ploner, F., Stoeger, H., Moser, R., Leikauf, W., Klemm, F., Pfeffel, F., Niessner, H., Poschauko, H., Pojer, E., Locker, G. J., Braun, J., Gnant, M. F. X., Michl, I., Pirker, R., Liebhard, A., Zielinski, C., Dittrich, C., Bernát, S. I., Pongrácz, E., Kastner, J., Raderer, M., Jorbenyi, Z., Yilmaz, A., Suardet, L., Lahm, H., Odartchenko, N., Varga, Gy., Sréter, L. A., Oberberg, D., Berdel, W. E., Budiman, R., Brand, C., Berkessy, S., Radványi, G., Pauker, Zs., Nagy, Zs., Karádi, Å., Serti, S., Hainz, R., Kirchweger, P., Prager, C., Prada, J., Neifer, S., Bienzle, U., Kremsner, P., Kämmerer, B., Vetterlein, M., Pohl, W., Letnansky, K., Imre, S. 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E., Huhn, D., Bergmann, L., Dönner, H., Hartlapp, J. H., Kreiter, H., Schuhmacher, K., Schalk, T., Sparwasser, C., Peschel, U., Fraaß, C. Huber, HIadik, F., Kolbe, K., Irschick, E., Bajko, G., Wozny, T., Hansz, J., Bares, R., Buell, U., Baumann, I., Harms, H., Kuse, R., Wilms, K., Müller-Hermelink, H. K., Baurmann, H., Cherif, D., Berger, R., Becker, K., Zeller, W., Helmchen, U., Hossfeld, D. K., Bentrup, I., Plusczyk, T., Kemkes-Matthes, B., Matthes, K., Bentz, M., Speicher, M., Schröder, M., Moos, M., Döhner, H., Lichter, P., Stilgenbauer, S., Korfel, A., Harnoss, B. -M., Boese-Landgraf, J., May, E., Kreuser, E. -D., Thiel, E., Karacas, T., Jahn, B., Lautenschläger, G., Szepes, S., Fenchel, K., Mitrou, P. S., Hoelzer, D., Heil, G., Lengfelder, E., Puzicha, E., Martin, H., Beyer, J., Kleiner, S., Strohscheer, I., Schwerdtfeger, R., Schwella, N., Schmidt-Wolf, I., Siegert, W., Weyer, C., arzen, G., Risse, G., Miksits, K., Farshidfar, G., Birken, R., Schilling, C. v., Brugger, W., Holldack, J., Mertelsmann, R., Kanz, L., Blanz, J., Mewes, K., Ehninger, G., Zeller, K. -P., Böhme., A., Just, G., Bergmann., L., Shah, P., Hoelzer, D., Stille, W., Bohlen, H., Hopff, T., Kapp, U., Wolf, J., Engert, A., Diehl, V., Tesch, H., Schrader, A., van Rhee, J., Köhne-Wömpner, H., Bokemeyer', C., Gonnermann, D., Harstrick, A., Schöffski, P., van Rhee, J., Schuppert, F., Freund, M., Boos, J., Göring, M., Blaschke, G., Borstel, A., Franke, A., Hüller, G., Uhle, R., Weise, W., Brach, Marion A., Gruss, Hans-Jürgen, Herrmann, Friedhelm, deVos, Sven, Brennscheidt, Ulrich, Riedel, Detlev, Klch, Walter, Bonlfer, Renate, Mertelsmann, Roland, Brieaer, J., Appelhans, H., Brückner, S., Siemens, HJ., Wagner, T., Moecklin, W., Mertelsmann, R., Bertz, H., Hecht, T., Mertelsmann, R., Bühl, K., Eichelbaum, M. G., Ladda, E., Schumacher, K., Weimer, A., Bühling, F., Kunz, D., Lendeckel, U., Reinhold, D., Ulmer, A. J., Flad, H. -D., Ansorge, S., Bühring, Hans-Jörg, Broudy¶, Virginia C., Ashman§, Leonie K., Burk, M., Kunecke, H., Dumont, C., Meckenstock, G., Volmer, M., Bucher, M., Manegold, C., Krenpien, B., Fischer, J. R., Drings, P., Bückner, U., Donhuijsen-Ant, R., Eberhardt, B., Westerhausen, M., Busch, F. W., Jaschonek, K., Steinke, B., Calavrezos, A., Hausmann, K., Solbach, M., Woitowitz, H. -P., Hilierdal, G., Heilmann, H. -P., Chen, Z. J., Frickhofen, N., Ellbrück, D., Schwarz, T. F., Körner, K., Wiest, C., Kubanek, B., Seifried, E., Claudé, R., Brücher, J., Clemens, M. R., Bublitz, K., Bieger, O., Schmid, B., Clemetson, K. J., Clemm, Ch., Bamberg, M., Gerl, A., Weißbach, L., Danhauser-Riedl, S., Schick, H. D., Bender, R., Reuter, M., Dietzfelbinger, H., Rastetter, J., Hanauske, A. -R., Decker, Hans-Jochen, Klauck, Sabine, Seizinger, Bernd, Denfeld, Ralf, Pohl, Christoph, Renner, Christoph, Hombach, Andreas, Jung, Wolfram, Schwonzen, Martin, Pfreundschuh, Michael, Derigs, H. Günter, Boswell, H. Scott, Kühn, D., Zafferani, M., Ehrhardt, R., Fischer, K., Schmitt, M., Witt, B., Ho, A. D., Haas, R., Hunstein, W., Dölken, G., Finke, J., Lange, W., Held, M., Schalipp, E., Fauser, A. A., Mertelsmann, R., Donhuijsen, K., Nabavi, D., Leder, L. D., Haedicke, Ch., Freund, H., Hattenberger, S., Dreger, Peter, Grelle, Karen, Schmitz, Norbert, Suttorp, Meinolf, Müller-Ruchholtz, Wolfgang, Löffler, Helmut, Dumoulin, F. L., Jakschies, D., Walther, M., Hunger, P., Deicher, H., von Wussow, P., Dutcher, J. P., Ebell, W., Bender-Götze, C., Bettoni, C., Niethammer, D., Reiter, A., Sauter, S., Schrappe, M., Riehm, H., Niederle, N., Heidersdorf, H., Müller, M. 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M., Ternes, P., Mertelsmann, R., Dölken, G., Fischbach, W., Zidianakis, Z., Lüke, G., Kirchner, Th., Mössner, J., Fischer, Thomas, Haque, Saikh J., Kumar, Aseem, Rutherford, Michael N., Williams, Bryan R. G., Flohr, T., Decker, T., Thews, A., Hild, F., Dohmen, M., von Wussow, P., Grote-Metke, A., Otremba, B., Fonatsch, C., Binder, T., Imhof, C., Feller, A. C., Fruehauf, S., Moehle, R., Hiddemann, Th., Büchner, M. Unterhalt, Wörmann, B., Ottmann, O. G., Verbeek, G. W., Seipelt, A. Maurer, Geissler, G., Schardt, C., Reutzel, R., Hiddemann, W., Maurer, A., Hess, U., Lindemann, A., Frisch, J., Schulz, G., Mertelsmann, R., Hoelzer, P., Gassmann, W., Sperling, C., Uharek, L., Becher, R., Weh, H. J., Tirier, C., Hagemann, F. G., Fuhr, H. G., Wandt, H., Sauerland, M. C., Gause, A., Spickermann, D., Klein, S., Pfreund-schuh, M., Gebauer, W., Fallgren-Gebauer, E., Geissler, R. G., Mentzel, U., Kleiner, K., Rossol, R., Guba, P., Kojouharoff, G., Gerdau, St., Körholz, D., Klein-Vehne, A., Burdach, St., Gerdemann, M., Maurer, J., Gerhartz, H. H., Schmetzer, H., Mayer, P., Clemm, C., Hentrich, M., Hartenstein, R., Kohl, P., Gieseler, F., Boege, F., Enttmann, R., Meyer, P., Glass, B., Zeis, M., Loeffler, H., Mueller-Ruchholtz, W., Görg, C., Schwerk, W. B., Köppler, H., Havemann, K., Goldschmitt, J., Goldschmidt, H., Nicolai, M., Richter, Th., Blau, W., Hahn, U., Kappe, R., Leithäuser, F., Gottstein, Claudia, Schön, Gisela, Dünnebacke, Markus, Berthold, Frank, Gramatzki, M., Eger, G., Geiger, M., Burger, R., Zölch, A., Bair, H. J., Becker, W., Griesinger, F., Elfers, H., Griesser, H., Grundner-Culemann, E., Neubauer, V., Fricke, D., Shalitin, C., Benter, T., Mertelsmann, R., Dölken, Gottfried, Mertelsmann, Roland, Günther, W., Schunmm, M., Rieber, P., Thierfelder, S., Gunsilius, E., Kirstein, O., Bommer, M., Serve, H., Hülser, P. -J., Del Valle, F., Fischer, J. Th., Huberts, H., Kaplan, E., Haase, D., Halbmayer, W. -M., Feichtinger, Ch., Rubi, K., Fischer, M., Hallek, M., Lepislo, E. M., Griffin, J. D., Emst, T. J., Druker, B., Eder, M., Okuda, K., D.Griffin, J., Kozłowska-Skrzypczak, K., Meyer, B., Reile, D., Scharnofske, M., Hapke, G., Aulenbacher, P., Havemann, K., Becker, N., Scheller, S., Zugmaier, G., Pralle, H., Wahrendorf, J., Heide, Immo, Thiede, Christian, de Kant, Eric, Neubauer, Andreas, Herrmann, Richard, Rochlitz, Christoph, Heiden, B., Depenbrock, H., Block, T., Vogelsang, H., Schneider, P., Fellbaum, Ch., Heidtmann, H. -H., Blings, B., Havemann, K., Fackler-Schwalbe, E., Schlimok, G., Lösch, A., Queißer, W., Löffler, B., Kurrle, E., Chadid, L., Lindemann, A., Mertelsmann, R., Nicolay, U., Gaus, W., Heinemann, V., Jehn, U., Gleixner, B., Wachholz, W., Scholz, P., Plunkett, W., Heinze, B., Novotny, J., Hess, Georg, Gamm, Heinold, Seliger, Barbara, Heuft, H. G., Oettle, H., Zeiler, T., Eckstein, R., Heymanns, J., Havemann, K., Hladik, F., Hoang-Vu, C., Horn, R., Cetin, Y., Scheumann, G., Dralle, H., Köhrle, J., von zur Mühlen, A., Brabant, G., Hochhaus, A., Mende, S., Simon, M., Fonatsch, Ch., Heinze, B., Georgii, A., Hötzl, Ch., Hintermeier-Knabe, R., Kempeni, J., Kaul, M., Hoetzl, Ch., Clemm, Ch., Lauter, H., Hoffknecht, M. M., Eckardt, N., Hoffmann-Fezer, G., Gall, C., Kranz, B., Zengerle, U., Pfoersich, M., Birkenstock, U., Pittenann, E., Heinz, B., Hosten, N., Schörner, W., Kirsch, A., Neumann, K., Felix, R., Humpe, A., Kiss, T., Trümper, L. H., Messner, H. A., Hundt, M., Zielinska-Skowronek, M., Schubert, J., Schmidt, R. E., Huss, R., Storb, R., Deeg, H. J., Issels, R. 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Published
1992
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49. Dipole Moments and Configurations of Triaryl Acrilonitriles

Author

Carbone, D., Chisari, A., Montoneri, E., Pappalardo, G. C., and Scarlata, G.

Abstract

The electric dipole moments of trans-1,2 diaryl acrilonitrile 1 and of a series of triaryl acrilonitriles 2-14 were measured in benzene solution at 25 °C. A mesomeric moment of 0.4 D was found to act between the phenyl-and the nitrile groups through the vinylic bond in triaryl acrilonitrile 2. For this molecule the direction of action of the total molecular moment was calculated and used to evaluate theoretical moments for the possible E and Z configurations of some unsymmetrical derivative compounds of the series. The configuration was settled for each com-pound on the basis of comparison between experimental and calculated dipole moment values.

Published
1983
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50. Oncogenic mutations in ras create HLA-A2.1 binding peptides but affect their extracellular antigen processing.

Author

Smith, M C, Pendleton, C D, Maher, V E, Kelley, M J, Carbone, D P, and Berzofsky, J A

Abstract

Point mutations in oncogene products such as ras may create neoantigenic determinants recognizable by T lymphocytes as tumor antigens, that could be marshalled to eliminate a tumor by inducing specific cytotoxic T lymphocytes (CTL) with an appropriate vaccine. Peptide-pulsed dendritic cells are a promising new approach to cancer vaccines. For such an approach to work, the determinant must be appropriately processed to the right size fragment and be presented by an appropriate HLA molecule. We have investigated both of these issues for a series of ras codon 12 and 13 point mutations that contain sequences predicted to bind to HLA-A2.1, the most common class I HLA molecule. We find that not only do the different mutations affect binding to HLA-A2.1, but also they affect extracellular antigen processing in two ways: by influencing the trimming of flanking residues from the longer sequence and by influencing the susceptibility of the optimal decamer to further proteolytic degradation. The influence of internal residues on cleavage of flanking residues downstream demonstrates the importance of distant interactions between separated amino acid side chains and/or conformational effects in determining antigen processing. These results may be important in designing an effective vaccine to induce mutant ras-specific tumor immunity.

Published
1997
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