4,946 research outputs found
The cell cycle checkpoint inhibitors in the treatment of leukemias
open3noThe study was funded by the University of Bologna and by the Italian Association for Cancer Research (AIRC).The inhibition of the DNA damage response (DDR) pathway in the treatment of cancers has recently reached an exciting stage with several cell cycle checkpoint inhibitors that are now being tested in several clinical trials in cancer patients. Although the great amount of pre-clinical and clinical data are from the solid tumor experience, only few studies have been done on leukemias using specific cell cycle checkpoint inhibitors. This review aims to summarize the most recent data found on the biological mechanisms of the response to DNA damages highlighting the role of the different elements of the DDR pathway in normal and cancer cells and focusing on the main genetic alteration or aberrant gene expression that has been found on acute and chronic leukemias. This review, for the first time, outlines the most important pre-clinical and clinical data available on the efficacy of cell cycle checkpoint inhibitors in single agent and in combination with different agents normally used for the treatment of acute and chronic leukemias.openGhelli Luserna di Rora', A; Iacobucci, I; Martinelli, GGhelli Luserna di Rora', A; Iacobucci, I; Martinelli,
Characterisation of AMS H35 HV-CMOS monolithic active pixel sensor prototypes for HEP applications
Monolithic active pixel sensors produced in High Voltage CMOS (HV-CMOS)
technology are being considered for High Energy Physics applications due to the
ease of production and the reduced costs. Such technology is especially
appealing when large areas to be covered and material budget are concerned.
This is the case of the outermost pixel layers of the future ATLAS tracking
detector for the HL-LHC. For experiments at hadron colliders, radiation
hardness is a key requirement which is not fulfilled by standard CMOS sensor
designs that collect charge by diffusion. This issue has been addressed by
depleted active pixel sensors in which electronics are embedded into a large
deep implantation ensuring uniform charge collection by drift. Very first small
prototypes of hybrid depleted active pixel sensors have already shown a
radiation hardness compatible with the ATLAS requirements. Nevertheless, to
compete with the present hybrid solutions a further reduction in costs
achievable by a fully monolithic design is desirable. The H35DEMO is a large
electrode full reticle demonstrator chip produced in AMS 350 nm HV-CMOS
technology by the collaboration of Karlsruher Institut f\"ur Technologie (KIT),
Institut de F\'isica d'Altes Energies (IFAE), University of Liverpool and
University of Geneva. It includes two large monolithic pixel matrices which can
be operated standalone. One of these two matrices has been characterised at
beam test before and after irradiation with protons and neutrons. Results
demonstrated the feasibility of producing radiation hard large area fully
monolithic pixel sensors in HV-CMOS technology. H35DEMO chips with a substrate
resistivity of 200 cm irradiated with neutrons showed a radiation
hardness up to a fluence of ncm with a hit efficiency of
about 99% and a noise occupancy lower than hits in a LHC bunch
crossing of 25ns at 150V
Modulation of amyloidogenic peptide aggregation by photoactivatable co-releasing ruthenium(II) complexes
Three Ru(II)-based CO-releasing molecules featuring bidentate benzimidazole and terpyridine derivatives as ligands were investigated for their ability to modulate the aggregation process of the second helix of the C-terminal domain of nucleophosmin 1, namely nucleophosmin 1 (NPM1)264–277, a model amyloidogenic system, before and after irradiation at 365 nm. Thioflavin T (ThT) binding assays and UV/Vis absorption spectra indicate that binding of the compounds to the peptide inhibits its aggregation and that the inhibitory effect increases upon irradiation (half maximal effective concentration (EC50) values in the high micromolar range). Electrospray ionization mass spectrometry data of the peptide in the presence of one of these compounds confirm that the modulation of amyloid aggregation relies on the formation of adducts obtained when the Ru compounds react with the peptide upon releasing of labile ligands, like chloride and carbon monoxide. This mechanism of action explains the subtle different behavior of the three compounds observed in ThT experiments. Overall, data support the hypothesis that metal-based CO releasing molecules can be used to develop metal-based drugs with potential application as anti-amyloidogenic agents
Persistence of Nonceliac Wheat Sensitivity, Based on Long-term Follow-up
We investigated how many patients with a diagnosis of nonceliac wheat sensitivity (NCWS) still experienced wheat sensitivity after a median follow-up time of 99 months. We collected data from 200 participants from a previous study of NCWS, performed between July and December 2016 in Italy; 148 of these individuals were still on a strict wheat- free diet. In total, 175 patients (88%) improved (had fewer symptoms) after a diagnosis of NCWS; 145 of 148 patients who adhered strictly to a gluten-free diet (98%) had reduced symptoms, compared with 30 of 52 patients who did not adhere to a gluten-free diet (58%) (P < .0001). Of the 22 patients who repeated the double-blind, placebo- controlled challenge, 20 reacted to wheat. We conclude that NCWS is a persistent condition. Clinicaltrials.gov registration number: NCT02823522
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Carbon nanotube - Based cold cathodes: Field emission angular properties and temporal stability
The field emission (FE) properties of carbon nanotube (CNT)-based cathodes have been investigated on nanostructured surfaces grown by plasma enhanced chemical vapor deposition. The FE angular properties and temporal stability of the emergent electron beam have been determined using a dedicated apparatus for cathodes of various architectures and geometries, characterized by scanning electron microscopy and I-V measurements. The angular electron beam divergence and time instability at the extraction stage, which are crucial parameters in order to obtain high brilliance of FE-based-cathode electron sources, have been measured for electrons emitted by several regular architectures of vertically aligned arrays and critically compared to conventional disordered cathodes. The measured divergences strongly depend on the grid mesh. For regular arrays of individual CNT, divergences from 2° to 5° have been obtained; in this specific case, measurements together with ray-tracing simulations suggest that the maximum emission angle is of the order of ±30° about the tube main axis. Larger divergences have been measured for electron beams emitted from honeycomb-structured cathodes (6°) and significantly broader angle distributions (10°) from disordered CNT surfaces. Emission current instabilities of the order of 1% for temporal stability studies conducted across a medium time scale (hours) have been noted for all cathodes consisting of a high number (10 and larger) of aligned CNTs, with the degree of stability being largely independent of the architecture.The European AXIS project (FP7-SME-1-2007) is acknowledged for financial support
Test beam measurement of the first prototype of the fast silicon pixel monolithic detector for the TT-PET project
The TT-PET collaboration is developing a PET scanner for small animals with
30 ps time-of-flight resolution and sub-millimetre 3D detection granularity.
The sensitive element of the scanner is a monolithic silicon pixel detector
based on state-of-the-art SiGe BiCMOS technology. The first ASIC prototype for
the TT-PET was produced and tested in the laboratory and with minimum ionizing
particles. The electronics exhibit an equivalent noise charge below 600 e- RMS
and a pulse rise time of less than 2 ns, in accordance with the simulations.
The pixels with a capacitance of 0.8 pF were measured to have a detection
efficiency greater than 99% and, although in the absence of the
post-processing, a time resolution of approximately 200 ps
Unexpectedly large electron correlation measured in Auger spectra of ferromagnetic iron thin films: orbital-selected Coulomb and exchange contributions
A set of electron-correlation energies as large as 10 eV have been measured
for a magnetic 2ML Fefilm deposited on Ag(001). By exploiting the spin
selectivity in angle-resolved Auger-photoelectroncoincidence spectroscopy and
the Cini-Sawatzky theory, the core-valence-valence Auger spectrumof a
spin-polarized system have been resolved: correlation energies have been
determined for eachindividual combination of the two holes created in the four
sub-bands involved in the decay: majorityand minority spin, as well asegandt2g.
The energy difference between final states with paralleland antiparallel spin
of the two emitted electrons is ascribed to the spin-flip energy for the final
ionstate, thus disentangling the contributions of Coulomb and exchange
interactions.Comment: 5 pages, 2 figures, 1 tabl
Thermal conductivity of the Toda lattice with conservative noise
We study the thermal conductivity of the one dimensional Toda lattice
perturbed by a stochastic dynamics preserving energy and momentum. The strength
of the stochastic noise is controlled by a parameter . We show that
heat transport is anomalous, and that the thermal conductivity diverges with
the length of the chain according to , with . In particular, the ballistic heat conduction of the
unperturbed Toda chain is destroyed. Besides, the exponent of the
divergence depends on
Novel high-speed monolithic silicon detector for particle physics
This contribution presents simulation results, implementation, and first tests of a monolithic detector developed at KIT. It consists of a sensor diode tightly integrated with an analogue front-end based on SiGe (Silicon-Germanium) SG13G2 130 nm BiCMOS technology produced at the Leibniz Institute for High Performance Microelectronics (IHP). The pixel size is 100 μm × 100 μm, and the nwell charge collection node dimensions were reduced to 10 μm × 10 μm. We investigate the influence of this approach on sensor performance, spatial resolution via charge sharing and timing behaviour
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