257 research outputs found
Active roles for inhibitory B kinases and in nuclear factor- B-mediated chemoresistance to doxorubicin
Chemotherapy agents have been shown to induce the transcription factor NF-κB and subsequent chemoresistance in fibrosarcomas and other cancers. The mechanism of NF-κB-mediated chemoresistance remains unclear, with a previous report suggesting that doxorubicin induces this response independent of the inhibitory κB kinases (IKKs). Other studies have indicated that IKKβ, but not IKKα, is required. Mouse embryo fibroblasts (MEF) devoid of IKKα, IKKβ, or both subunits (DKO) were treated with doxorubicin. The absence of either IKKα or IKKβ or both kinases resulted in impaired induction of NF-κB DNA-binding activity in response to doxorubicin. To provide a valid clinical correlate, HT1080 human fibrosarcoma cells were transfected with small interference RNAs (siRNAs) specific for IKKα or IKKβ and then subsequently treated with doxorubicin. Knockdown of IKKα severely impaired the ability of doxorubicin to initiate NF-κB DNA-binding activity. However, a decrease in either IKKα or IKKβ resulted in decreased phosphorylation of p65 in response to doxorubicin. The inhibition of doxorubicin-induced NF-κB activation by the knockdown of either catalytic subunit resulted in increased cleaved caspase 3 and cleaved PARP, and increased apoptosis when compared to doxorubicin alone. The results of this study validate current approaches aimed at NF-κB inhibition to improve clinical therapies. Moreover, we demonstrate that IKKα plays a critical role in NF-κB-mediated chemoresistance in response to doxorubicin and may serve as a potential target in combinational strategies to improve chemotherapeutic response
A feasibility study of ortho-positronium decays measurement with the J-PET scanner based on plastic scintillators
We present a study of the application of the Jagiellonian Positron Emission
Tomograph (J-PET) for the registration of gamma quanta from decays of
ortho-positronium (o-Ps). The J-PET is the first positron emission tomography
scanner based on organic scintillators in contrast to all current PET scanners
based on inorganic crystals. Monte Carlo simulations show that the J-PET as an
axially symmetric and high acceptance scanner can be used as a multi-purpose
detector well suited to pursue research including e.g. tests of discrete
symmetries in decays of ortho-positronium in addition to the medical imaging.
The gamma quanta originating from o-Ps decay interact in the plastic
scintillators predominantly via the Compton effect, making the direct
measurement of their energy impossible. Nevertheless, it is shown in this paper
that the J-PET scanner will enable studies of the o-Ps decays with
angular and energy resolution equal to and
keV, respectively. An order of magnitude shorter decay
time of signals from plastic scintillators with respect to the inorganic
crystals results not only in better timing properties crucial for the reduction
of physical and instrumental background, but also suppresses significantly the
pileups, thus enabling compensation of the lower efficiency of the plastic
scintillators by performing measurements with higher positron source
activities
Processing optimization with parallel computing for the J-PET tomography scanner
The Jagiellonian-PET (J-PET) collaboration is developing a prototype TOF-PET
detector based on long polymer scintillators. This novel approach exploits the
excellent time properties of the plastic scintillators, which permit very
precise time measurements. The very fast, FPGA-based front-end electronics and
the data acquisition system, as well as, low- and high-level reconstruction
algorithms were specially developed to be used with the J-PET scanner. The
TOF-PET data processing and reconstruction are time and resource demanding
operations, especially in case of a large acceptance detector, which works in
triggerless data acquisition mode. In this article, we discuss the parallel
computing methods applied to optimize the data processing for the J-PET
detector. We begin with general concepts of parallel computing and then we
discuss several applications of those techniques in the J-PET data processing.Comment: 8 page
Calculation of time resolution of the J-PET tomograph using the Kernel Density Estimation
In this paper we estimate the time resolution of the J-PET scanner built from
plastic scintillators. We incorporate the method of signal processing using the
Tikhonov regularization framework and the Kernel Density Estimation method. We
obtain simple, closed-form analytical formulas for time resolutions. The
proposed method is validated using signals registered by means of the single
detection unit of the J-PET tomograph built out from 30 cm long plastic
scintillator strip. It is shown that the experimental and theoretical results,
obtained for the J-PET scanner equipped with vacuum tube photomultipliers, are
consistent.Comment: 25 pages, 11 figure
Multichannel FPGA based MVT system for high precision time (20~ps~RMS) and charge measurement
In this article it is presented an FPGA based ulti-oltage hreshold
(MVT) system which allows of sampling fast signals ( ns rising and falling
edge) in both voltage and time domain. It is possible to achieve a precision of
time measurement of ps RMS and reconstruct charge of signals, using a
simple approach, with deviation from real value smaller than 10.
Utilization of the differential inputs of an FPGA chip as comparators together
with an implementation of a TDC inside an FPGA allowed us to achieve a compact
multi-channel system characterized by low power consumption and low production
costs. This paper describes realization and functioning of the system
comprising 192-channel TDC board and a four mezzanine cards which split
incoming signals and discriminate them. The boards have been used to validate a
newly developed Time-of-Flight Positron Emission Tomography system based on
plastic scintillators. The achieved full system time resolution of
(TOF) ps is by factor of two better with respect to the
current TOF-PET systems.Comment: Accepted for publication in JINST, 10 pages, 8 figure
Search for the eta-mesic 4He with WASA-at-COSY detector
An exclusive measurement of the excitation function for the dd->3Heppi-
reaction was performed at the Cooler Synchrotron COSY-Juelich with the
WASA-at-COSY detection system. The data were taken during a slow acceleration
of the beam from 2.185 GeV/c to 2.400 GeV/c crossing the kinematic threshold
for the eta meson production in the dd->4He-eta reaction at 2.336 GeV/c. The
corresponding excess energy with respect to the 4He-eta system varied from
-51.4MeV to 22MeV. The integrated luminosity in the experiment was determined
using the dd->3Hen reaction. The shape of the excitation function for the
dd->3Heppi- was examined. No signal of the 4He-eta bound state was observed. An
upper limit for the cross-section for the bound state formation and decay in
the process dd->(4He-eta)bound->3Heppi- was determined on the 90% confidence
level and it varies from 20nb to 27nb for the bound state width ranging from
5MeV to 35MeV, respectively.Comment: 8 pages, 9 figure
Radiation Sterilization of Anthracycline Antibiotics in Solid State
The impact of ionizing radiation generated by a beam of electrons of 25–400 kGy on the stability of such analogs of anthracycline antibiotics as daunorubicin (DAU), doxorubicin (DOX), and epidoxorubicin (EPI) was studied. Based on EPR results, it was established that unstable free radicals decay exponentially with the half-time of 4 days in DAU and DOX and 7 days in EPI after irradiation. Radiation-induced structural changes were analyzed with the use of spectrophotometric methods (UV-Vis and IR) and electron microscope imaging (SEM). A chromatographic method (HPLC-DAD) was applied to assess changes in the contents of the analogs in the presence of their impurities. The study showed that the structures of the analogs did not demonstrate any significant alterations at the end of the period necessary for the elimination of unstable free radicals. The separation of main substances and related substances (impurities and potential degradation products) allowed determining that no statistically significant changes in the content of particular active substances occurred and that their conversion due to the presence of free radicals resulting from exposure to an irradiation of 25 kGy (prescribed to ensure sterility) was not observed
Time resolution of the plastic scintillator strips with matrix photomultiplier readout for J-PET tomograph
Recent tests of a single module of the Jagiellonian Positron Emission
Tomography system (J-PET) consisting of 30 cm long plastic scintillator strips
have proven its applicability for the detection of annihilation quanta (0.511
MeV) with a coincidence resolving time (CRT) of 0.266 ns. The achieved
resolution is almost by a factor of two better with respect to the current
TOF-PET detectors and it can still be improved since, as it is shown in this
article, the intrinsic limit of time resolution for the determination of time
of the interaction of 0.511 MeV gamma quanta in plastic scintillators is much
lower. As the major point of the article, a method allowing to record
timestamps of several photons, at two ends of the scintillator strip, by means
of matrix of silicon photomultipliers (SiPM) is introduced. As a result of
simulations, conducted with the number of SiPM varying from 4 to 42, it is
shown that the improvement of timing resolution saturates with the growing
number of photomultipliers, and that the 2 x 5 configuration at two ends
allowing to read twenty timestamps, constitutes an optimal solution. The
conducted simulations accounted for the emission time distribution, photon
transport and absorption inside the scintillator, as well as quantum efficiency
and transit time spread of photosensors, and were checked based on the
experimental results. Application of the 2 x 5 matrix of SiPM allows for
achieving the coincidence resolving time in positron emission tomography of
0.170 ns for 15 cm axial field-of-view (AFOV) and 0.365 ns
for 100 cm AFOV. The results open perspectives for construction of a
cost-effective TOF-PET scanner with significantly better TOF resolution and
larger AFOV with respect to the current TOF-PET modalities.Comment: To be published in Phys. Med. Biol. (26 pages, 17 figures
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