Identification and Characterization of AES-135, a Hydroxamic Acid-Based HDAC Inhibitor That Prolongs Survival in an Orthotopic Mouse Model of Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, incurable cancer with a 20% 1 year survival rate. While standard-of-care therapy can prolong life in a small fraction of cases, PDAC is inherently resistant to current treatments, and novel therapies are urgently required. Histone deacetylase (HDAC) inhibitors are effective in killing pancreatic cancer cells in in vitro PDAC studies, and although there are a few clinical studies investigating combination therapy including HDAC inhibitors, no HDAC drug or combination therapy with an HDAC drug has been approved for the treatment of PDAC. We developed an inhibitor of HDACs, AES-135, that exhibits nanomolar inhibitory activity against HDAC3, HDAC6, and HDAC11 in biochemical assays. In a three-dimensional coculture model, AES-135 kills low-passage patient-derived tumor spheroids selectively over surrounding cancer-associated fibroblasts and has excellent pharmacokinetic properties in vivo. In an orthotopic murine model of pancreatic cancer, AES-135 prolongs survival significantly, therefore representing a candidate for further preclinical testing

Gesture analysis for physics education researchers

Systematic observations of student gestures can not only fill in gaps in students' verbal expressions, but can also offer valuable information about student ideas, including their source, their novelty to the speaker, and their construction in real time. This paper provides a review of the research in gesture analysis that is most relevant to physics education researchers and illustrates gesture analysis for the purpose of better understanding student thinking about physics.Comment: 14 page

The CERN n_TOF facility: a unique tool for nuclear data measurement

The study of the resonant structures in neutron-nucleus cross-sections, and therefore of the compoundnucleus reaction mechanism, requires spectroscopic measurements to determine with high accuracy the energy of the neutron interacting with the material under study. To this purpose, the neutron time-of-flight facility n_TOF has been operating since 2001 at CERN. Its characteristics, such as the high intensity instantaneous neutron flux, the wide energy range from thermal to few GeV, and the very good energy resolution, are perfectly suited to perform highquality measurements of neutron-induced reaction cross sections. The precise and accurate knowledge of these cross sections plays a fundamental role in nuclear technologies, nuclear astrophysics and nuclear physics. Two different measuring stations are available at the n_TOF facility, called EAR1 and EAR2, with different characteristics of intensity of the neutron flux and energy resolution. These experimental areas, combined with advanced detection systems lead to a great flexibility in performing challenging measurement of high precision and accuracy, and allow the investigation isotopes with very low cross sections, or available only in small quantities, or with very high specific activity. The characteristics and performances of the two experimental areas of the n_TOF facility will be presented, together with the most important measurements performed to date and their physics case. In addition, the significant upcoming measurements will be introduced.Postprint (published version

Pulse shape analysis of signals from BaF2 and CeF3 scintillators for neutron capture experiments

The scope of this work is to study the characteristics of BaF2 and CeF3 signals using fast digitizers, which allow the sampling of the signal at very high frequencies and the application of the fitting method for analysis of the recorded pulses. By this procedure particle identification and the reconstruction of pile-up events can be improved, while maintaining the energy and time-of-flight resolution as compared to traditional methods. The reliability of the technique and problems connected with data acquisition are discussed with respect to accurate measurements of neutron capture cross-sections

Level densities and γ\gamma-strength functions in 148,149^{148,149}Sm

The level densities and $\gamma$-strength functions of the weakly deformed $^{148}$Sm and $^{149}$Sm nuclei have been extracted. The temperature versus excitation energy curve, derived within the framework of the micro canonical ensemble, shows structures, which we associate with the break up of Cooper pairs. The nuclear heat capacity is deduced within the framework of both the micro canonical and the canonical ensemble. We observe negative heat capacity in the micro canonical ensemble whereas the canonical heat capacity exhibits an S-shape as function of temperature, both signals of a phase transition. The structures in the $\gamma$-strength functions are discussed in terms of the pygmy resonance and the scissors mode built on exited states. The samarium results are compared with data for the well deformed $^{161,162}$Dy, $^{166,167}$Er and $^{171,172}$Yb isotopes and with data from (n,$\gamma$)-experiments and giant dipole resonance studies.Comment: 12 figure

Present Status and Future Programs of the n_TOF Experiment

This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial License 3.0, which permits unrestricted use, distribution, and reproduction in any noncommercial medium, provided the original work is properly citedThe neutron time-of-flight facility n_TOF at CERN, Switzerland, operational since 2001, delivers neutrons using the Proton Synchrotron (PS) 20 GeV/c proton beam impinging on a lead spallation target. The facility combines a very high instantaneous neutron flux, an excellent time of flight resolution due to the distance between the experimental area and the production target (185 meters), a low intrinsic background and a wide range of neutron energies, from thermal to GeV neutrons. These characteristics provide a unique possibility to perform neutron-induced capture and fission cross-section measurements for applications in nuclear astrophysics and in nuclear reactor technology.The most relevant measurements performed up to now and foreseen for the future will be presented in this contribution. The overall efficiency of the experimental program and the range of possible measurements achievable with the construction of a second experimental area (EAR-2), vertically located 20 m on top of the n_TOF spallation target, might offer a substantial improvement in measurement sensitivities. A feasibility study of the possible realisation of the installation extension will be also presented

Measurement of the (90,91,92,93,94,96)Zr(n,gamma) and (139)La(n,gamma) cross sections at n_TOF

Open AccessNeutron capture cross sections of Zr and La isotopes have important implications in the field of nuclear astrophysics as well as in the nuclear technology. In particular the Zr isotopes play a key role for the determination of the neutron density in the He burning zone of the Red Giant star, while the (139)La is important to monitor the s-process abundances from Ba up to Ph. Zr is also largely used as structural materials of traditional and advanced nuclear reactors. The nuclear resonance parameters and the cross section of (90,91,92,93,94,96)Zr and (139)La have been measured at the n_TOF facility at CERN. Based on these data the capture resonance strength and the Maxwellian-averaged cross section were calculated

Radiative neutron capture cross-section measurement of ge isotopes at n_TOF CERN facility and its importance for stellar nucleosynthesis

This manuscript summarizes the results of radiative neutron capture cross-section measurements on two stable germanium isotopes, 70Ge and 73Ge. Experiments were performed at the n_TOF facility at CERN via the time-of-flight technique, over a wide neutron energy range, for all stable germanium isotopes (70,72,73,74, and 76). Results for 70Ge [Phys. Rev. C 100, 045804 (2019)] and 73Ge [Phys. Lett. B 790, 458 (2019)] are already published. In the field of nuclear structure, such measurements allow to study excited levels close to the neutron binding energy and to obtain information on nuclear properties. In stellar nucleosynthesis research, neutron induced reactions on germanium are of importance for nucleosynthesis in the weak component of the slow neutron capture processes.Peer ReviewedArticle signat per 134 autors/autores: A. Gawlik, C. Lederer-Woods, J. Andrzejewski, J. Perkowski, U. Battino, P. Ferreira, F. Gunsing, S. Heinitz, M. Krtička, C. Massimi, F. Mingrone, R. Reifarth, A. Tattersall, S. Valenta, C. Weiss, O. Aberle, L. Audouin, M. Bacak, J. Balibrea, M. Barbagallo, S. Barros, V. Bécares, F. Bečvář, C. Beinrucker, E. Berthoumieux, J. Billowes, D. Bosnar, M. Brugger, M. Caamaño, F. Calviño, M. Calviani, D. Cano-Ott, R. Cardella, A. Casanovas, D.M. Castelluccio, F. Cerutti, Y.H. Chen, E. Chiaveri, N. Colonna, G. Cortés, M.A. Cortés-Giraldo, L. Cosentino, L.A. Damone, M. Diakaki, M. Dietz, C. Domingo-Pardo, R. Dressler, E. Dupont, I. Durán, B. Fernández-Domínguez, A. Ferrari, P. Finocchiaro, V. Furman, K. Göbel, A.R. García, T. Glodariu, I.F. Gonçalves, E. González-Romero, A. Goverdovski, E. Griesmayer, C. Guerrero, H. Harada, T. Heftrich, J. Heyse, D.G. Jenkins, E. Jericha, F. Käppeler, Y. Kadi, T. Katabuchi, P. Kavrigin, V. Ketlerov, V. Khryachkov, A. Kimura, N. Kivel, I. Knapova, M. Kokkoris, E. Leal-Cidoncha, H. Leeb, J. Lerendegui-Marco, S. Lo Meo, S.J. Lonsdale, R. Losito, D. Macina, T. Martínez, P. Mastinu, M. Mastromarco, F. Matteucci, E.A. Maugeri, E. Mendoza, A. Mengoni, P.M. Milazzo, M. Mirea, S. Montesano, A. Musumarra, R. Nolte, A. Oprea, N. Patronis, A. Pavlik, J.I. Porras, J. Praena, J.M. Quesada, K. Rajeev, T. Rauscher, A. Riego-Perez, P.C. Rout, C. Rubbia, J.A. Ryan, M. Sabaté-Gilarte, A. Saxena, P. Schillebeeckx, S. Schmidt, D. Schumann, P. Sedyshev, A.G. Smith, A. Stamatopoulos, G. Tagliente, J.L. Tain, A. Tarifeño-Saldivia, L. Tassan-Got, A. Tsinganis, G. Vannini, V. Variale, P. Vaz, A. Ventura, V. Vlachoudis, R. Vlastou, A. Wallner, S. Warren, M. Weigand, C. Wolf, P.J. Woods, T. Wright, P. ŽugecObjectius de Desenvolupament Sostenible::7 - Energia Assequible i No ContaminantPostprint (author's final draft

Cross section measurements of 155,157Gd(n, γ) induced by thermal and epithermal neutrons

© SIF, Springer-Verlag GmbH Germany, part of Springer Nature 2019Neutron capture cross section measurements on 155Gd and 157Gd were performed using the time-of-flight technique at the n_TOF facility at CERN on isotopically enriched samples. The measurements were carried out in the n_TOF experimental area EAR1, at 185 m from the neutron source, with an array of 4 C6D6 liquid scintillation detectors. At a neutron kinetic energy of 0.0253 eV, capture cross sections of 62.2(2.2) and 239.8(8.4) kilobarn have been derived for 155Gd and 157Gd, respectively, with up to 6% deviation relative to values presently reported in nuclear data libraries, but consistent with those values within 1.6 standard deviations. A resonance shape analysis has been performed in the resolved resonance region up to 181 eV and 307 eV, respectively for 155Gd and 157Gd, where on average, resonance parameters have been found in good agreement with evaluations. Above these energies and up to 1 keV, the observed resonance-like structure of the cross section has been analysed and characterised. From a statistical analysis of the observed neutron resonances we deduced: neutron strength function of 2. 01 (28) × 10 - 4 and 2. 17 (41) × 10 - 4; average total radiative width of 106.8(14) meV and 101.1(20) meV and s-wave resonance spacing 1.6(2) eV and 4.8(5) eV for n + 155Gd and n + 157Gd systems, respectively.Peer reviewedFinal Accepted Versio

Measurement of the Ge 70 (n,γ) cross section up to 300 keV at the CERN n-TOF facility

©2019 American Physical Society.Neutron capture data on intermediate mass nuclei are of key importance to nucleosynthesis in the weak component of the slow neutron capture processes, which occurs in massive stars. The (n,γ) cross section on Ge70, which is mainly produced in the s process, was measured at the neutron time-of-flight facility n-TOF at CERN. Resonance capture kernels were determined up to 40 keV neutron energy and average cross sections up to 300 keV. Stellar cross sections were calculated from kT=5 keV to kT=100 keV and are in very good agreement with a previous measurement by Walter and Beer (1985) and recent evaluations. Average cross sections are in agreement with Walter and Beer (1985) over most of the neutron energy range covered, while they are systematically smaller for neutron energies above 150 keV. We have calculated isotopic abundances produced in s-process environments in a 25 solar mass star for two initial metallicities (below solar and close to solar). While the low metallicity model reproduces best the solar system germanium isotopic abundances, the close to solar model shows a good global match to solar system abundances in the range of mass numbers A=60-80.Peer reviewedFinal Published versio