242 research outputs found
Pharmacological manipulation of L-carnitine transport into L6 cells with stable overexpression of human OCTN2
Abstract.: The high-affinity Na+-dependent carnitine transporter OCTN2 (SLC22A5) has a high renal expression and reabsorbs most filtered carnitine. To gain more insight into substrate specificity of OCTN2, we overexpressed hOCTN2 in L6 cells and characterized the structural requirements of substances acting as human OCTN2 (hOCTN2) inhibitors. A 1905-bp fragment containing the hOCTN2 complete coding sequence was introduced into the pWpiresGFP vector, and L6 cells were stably transduced using a lentiviral system. The transduced L6 cells revealed increased expression of hOCTN2 on the mRNA, protein and functional levels. Structural requirements for hOCTN2 inhibition were predicted in silico and investigated in vitro. Essential structural requirements for OCTN2 inhibition include a constantly positively charged nitrogen atom and a carboxyl, nitrile or ester group connected by a 2-4-atom linker. Our cell system is suitable for studying in vitro interactions with OCTN2, which can subsequently be investigated in viv
FACT - Long-term Monitoring of Bright TeV-Blazars
Since October 2011, the First G-APD Cherenkov Telescope (FACT) is operated
successfully on the Canary Island of La Palma. Apart from the proof of
principle for the use of G-APDs in Cherenkov telescopes, the major goal of the
project is the dedicated long-term monitoring of a small sample of bright TeV
blazars. The unique properties of G-APDs permit stable observations also during
strong moon light. Thus a superior sampling density is provided on time scales
at which the blazar variability amplitudes are expected to be largest, as
exemplified by the spectacular variations of Mrk 501 observed in June 2012.
While still in commissioning, FACT monitored bright blazars like Mrk 421 and
Mrk 501 during the past 1.5 years so far. Preliminary results including the Mrk
501 flare from June 2012 will be presented.Comment: 4 pages, 4 figures, presented at the 33rd ICRC (2013
FACT - Threshold prediction for higher duty cycle and improved scheduling
The First G-APD Cherenkov telescope (FACT) is the first telescope using
silicon photon detectors (G-APD aka. SiPM). The use of Silicon devices promise
a higher photon detection efficiency, more robustness and higher precision than
photo-multiplier tubes. Being operated during different light-conditions, the
threshold settings of a Cherenkov telescope have to be adapted to feature the
lowest possible threshold but also an efficient suppression of triggers from
night-sky background photons. Usually this threshold is set either by
experience or a mini-ratescan. Since the measured current through the sensors
is directly correlated with the noise level, the current can be used to set the
best threshold at any time. Due to the correlation between the physical
threshold and the final energy threshold, the current can also be used as a
measure for the energy threshold of any observation. This presentation
introduces a method which uses the properties of the moon and the source
position to predict the currents and the corresponding energy threshold for
every upcoming observation allowing to adapt the observation schedule
accordingly
FACT - Long-term stability and observations during strong Moon light
The First G-APD Cherenkov Telescope (FACT) is the first Cherenkov telescope
equipped with a camera made of silicon photon detectors (G-APD aka. SiPM).
Since October 2011, it is regularly taking data on the Canary Island of La
Palma. G-APDs are ideal detectors for Cherenkov telescopes as they are robust
and stable. Furthermore, the insensitivity of G-APDs towards strong ambient
light allows to conduct observations during bright Moon and twilight. This gain
in observation time is essential for the long-term monitoring of bright TeV
blazars. During the commissioning phase, hundreds of hours of data (including
data from the the Crab Nebula) were taken in order to understand the
performance and sensitivity of the instrument. The data cover a wide range of
observation conditions including different weather conditions, different zenith
angles and different light conditions (ranging from dark night to direct full
Moon). We use a new parmetrisation of the Moon light background to enhance our
scheduling and to monitor the atmosphere. With the data from 1.5 years, the
long-term stability and the performance of the camera during Moon light is
studied and compared to that achieved with photomultiplier tubes so far.Comment: 3 pages, 3 figures, FACT Contribution to the 33rd International
Cosmic Ray Conference (ICRC), Rio de Janeir
FACT - How stable are the silicon photon detectors?
The First G-APD Cherenkov telescope (FACT) is the first telescope using
silicon photon detectors (G-APD aka. SiPM). The use of Silicon devices promise
a higher photon detection efficiency, more robustness and higher precision than
photo-multiplier tubes. Since the properties of G-APDs depend on auxiliary
parameters like temperature, a feedback system adapting the applied voltage
accordingly is mandatory.
In this presentation, the feedback system, developed and in operation for
FACT, is presented. Using the extraction of a single photon-equivalent (pe)
spectrum as a reference, it can be proven that the sensors can be operated with
very high precision. The extraction of the single-pe, its spectrum up to
10\,pe, its properties and their precision, as well as their long-term behavior
during operation are discussed. As a by product a single pulse template is
obtained. It is shown that with the presented method, an additional external
calibration device can be omitted. The presented method is essential for the
application of G-APDs in future projects in Cherenkov astronomy and is supposed
to result in a more stable and precise operation than possible with
photo-multiplier tubes
A novel camera type for very high energy gamma-ray astronomy based on Geiger-mode avalanche photodiodes
Geiger-mode avalanche photodiodes (G-APD) are promising new sensors for light
detection in atmospheric Cherenkov telescopes. In this paper, the design and
commissioning of a 36-pixel G-APD prototype camera is presented. The data
acquisition is based on the Domino Ring Sampling (DRS2) chip. A sub-nanosecond
time resolution has been achieved. Cosmic-ray induced air showers have been
recorded using an imaging mirror setup, in a self-triggered mode. This is the
first time that such measurements have been carried out with a complete G-APD
camera.Comment: 9 pages with 11 figure
FACT -- the First Cherenkov Telescope using a G-APD Camera for TeV Gamma-ray Astronomy (HEAD 2010)
Geiger-mode Avalanche Photodiodes (G-APD) bear the potential to significantly
improve the sensitivity of Imaging Air Cherenkov Telescopes (IACT). We are
currently building the First G-APD Cherenkov Telescope (FACT) by refurbishing
an old IACT with a mirror area of 9.5 square meters and construct a new, fine
pixelized camera using novel G-APDs. The main goal is to evaluate the
performance of a complete system by observing very high energy gamma-rays from
the Crab Nebula. This is an important field test to check the feasibility of
G-APD-based cameras to replace at some time the PMT-based cameras of planned
future IACTs like AGIS and CTA. In this article, we present the basic design of
such a camera as well as some important details to be taken into account.Comment: Poster shown at HEAD 2010, Big Island, Hawaii, March 1-4, 201
Calibration and performance of the photon sensor response of FACT -- The First G-APD Cherenkov telescope
The First G-APD Cherenkov Telescope (FACT) is the first in-operation test of
the performance of silicon photo detectors in Cherenkov Astronomy. For more
than two years it is operated on La Palma, Canary Islands (Spain), for the
purpose of long-term monitoring of astrophysical sources. For this, the
performance of the photo detectors is crucial and therefore has been studied in
great detail. Special care has been taken for their temperature and voltage
dependence implementing a correction method to keep their properties stable.
Several measurements have been carried out to monitor the performance. The
measurements and their results are shown, demonstrating the stability of the
gain below the percent level. The resulting stability of the whole system is
discussed, nicely demonstrating that silicon photo detectors are perfectly
suited for the usage in Cherenkov telescopes, especially for long-term
monitoring purpose
Methotrexate area under the curve is an important outcome predictor in patients with primary CNS lymphoma: A pharmacokinetic–pharmacodynamic analysis from the IELSG no. 20 trial
This analysis was initiated to define the predictive value of the area under the curve of high-dose methotrexate (AUC(HD-MTX)) in patients with primary central nervous system lymphoma (PCNSL).; We included 55 patients with PCNSL and available pharmacokinetic (PK) data from the International Extranodal Lymphoma Study Group (IELSG) no. 20 trial, randomised to HD-MTX (n=30) or HD-MTX and high-dose cytarabine (HD-AraC) (n=25). Individual AUC(HD-MTX) from population PK analysis was tested on drug toxicity and clinical outcome using multivariate logistic regression analysis and Cox hazards modelling.; AUC(HD-MTX), the IELSG score and treatment group were significant predictors for treatment response (complete or partial) in the adjusted model. The AUC(HD-MTX) did not predict toxicity, with the exception of liver toxicity and neutropaenia. A high AUC(HD-MTX) was associated with better event-free survival (EFS) (P=0.01) and overall survival (OAS) (P=0.02). Both the AUC(HD-MTX) and the IELSG score were significant predictors of EFS and OAS in the adjusted model, with a hazard ratio of 0.82 and 0.73, respectively, per 100 micromol l(-1) h(-1) increase in AUC(HD-MTX).; Individualised dosing of HD-MTX might have the potential to improve clinical outcome in patients with PCNSL, even when administered concurrently with HD-AraC. In the future, this could be carried out by using first-cycle PK modelling with determination of potential dose adaptations for later cycles using Bayesian analysis
FACT -- Operation of the First G-APD Cherenkov Telescope
Since more than two years, the First G-APD Cherenkov Telescope (FACT) is
operating successfully at the Canary Island of La Palma. Apart from its purpose
to serve as a monitoring facility for the brightest TeV blazars, it was built
as a major step to establish solid state photon counters as detectors in
Cherenkov astronomy.
The camera of the First G-APD Cherenkov Telesope comprises 1440 Geiger-mode
avalanche photo diodes (G-APD aka. MPPC or SiPM) for photon detection. Since
properties as the gain of G-APDs depend on temperature and the applied voltage,
a real-time feedback system has been developed and implemented. To correct for
the change introduced by temperature, several sensors have been placed close to
the photon detectors. Their read out is used to calculate a corresponding
voltage offset. In addition to temperature changes, changing current introduces
a voltage drop in the supporting resistor network. To correct changes in the
voltage drop introduced by varying photon flux from the night-sky background,
the current is measured and the voltage drop calculated. To check the stability
of the G-APD properties, dark count spectra with high statistics have been
taken under different environmental conditions and been evaluated.
The maximum data rate delivered by the camera is about 240 MB/s. The recorded
data, which can exceed 1 TB in a moonless night, is compressed in real-time
with a proprietary loss-less algorithm. The performance is better than gzip by
almost a factor of two in compression ratio and speed. In total, two to three
CPU cores are needed for data taking. In parallel, a quick-look analysis of the
recently recorded data is executed on a second machine. Its result is publicly
available within a few minutes after the data were taken.
[...]Comment: 19th IEEE Real-Time Conference, Nara, Japan (2014
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