Increased tumour necrosis factor-α levels have been observed in bronchial biopsies and induced sputum from subjects with severe asthma. We investigated etanercept (ETN) as a therapeutic option for ...treating moderate-to-severe persistent asthma. In this 12-week, randomised, double-blind, placebo-controlled, phase 2 trial, subjects (n=132) with moderate-to-severe persistent asthma received subcutaneous injections of 25 mg ETN or placebo twice weekly, and were evaluated at baseline, and at weeks 2, 4, 8 and 12. The primary end-point was the change from baseline to week 12 in pre-bronchodilator forced expiratory volume in 1 s (FEV1)% predicted. Secondary end-points included morning peak expiratory flow, FEV1% pred, Asthma Control Questionnaire (5-item version), asthma exacerbations, provocative concentration of methacholine causing a 20% decrease in FEV1, and the Asthma Quality of Life Questionnaire. No significant differences were observed between ETN and placebo for any of the efficacy end-points. ETN treatment was well tolerated, with no unexpected safety findings observed during the study. Clinical efficacy of ETN was not shown in subjects with moderate-to-severe persistent asthma over 12 weeks. However, ETN treatment was a well-tolerated therapy. Studies in specific subsets of patients with asthma with longer-term follow-up may be needed to fully evaluate the clinical efficacy of ETN in this population.
A monolithic pixelated silicon detector designed for high time resolution has been produced in the SG13G2 130 nm SiGe BiCMOS technology of IHP. This proof-of-concept chip contains hexagonal pixels of ...65 μm and 130 μm side. The SiGe front-end electronics implemented provides an equivalent noise charge of 90 and 160 e− for a pixel capacitance of 70 and 220 fF, respectively, and a total time walk of less than 1 ns. Lab measurements with a 90Sr source show a time resolution of the order of 50 ps. This result is competitive with silicon technologies that integrate an avalanche gain mechanism.
The Picosecond Avalanche Detector is a multi-junction silicon pixel detector devised to enable charged-particle tracking with high spatial resolution and picosecond time-stamping capability. A ...proof-of-concept prototype of the PicoAD sensor has been produced by IHP microelectronics. Measurements with a 55Fe X-ray radioactive source show that the prototype is functional with an avalanche gain up to a maximum electron gain of 23.
A crystal (diamond) particle detector has been developed and tested, whose constitute elements are a multi-layer polycrystalline diamond and a pick-up system capable of collecting in parallel the ...charge produced in the layers. The charge is read with a charge-to-voltage amplifier (5–6mV/fC) realized with bipolar junction transistors in order to minimize the effect of the detector capacitance. The tests performed with cosmic rays and at the beam test facility of Frascati with 500MeV electrons in single electron mode operation have shown that a detector with 4–5 layers of 250μm thickness each and 9mm2 active area exhibits an upper limit of 150ps time resolution for minimum ionizing particles at an operating voltage of about 350V.
Abstract
A 33.6 ps LSB Time-to-Digital converter was designed in 130 nm BiCMOS technology. The core of the converter is a differential
9-stage ring oscillator, based on a multi-path architecture. A ...novel
version of this design is proposed, along with an analytical model
of linearity. The model allowed us to understand the source of the
performance superiority (in terms of linearity) of our design and to
predict further improvements. The oscillator is integrated in a
event-by-event self-calibration system that allows avoiding any
PLL-based synchronization. For this reason and for the compactness
and simplicity of the architecture, the proposed TDC is suitable for
applications in which a large number of converters and a massive
parallelization are required such as High-Energy Physics and medical
imaging detector systems. A test chip for the TDC has been
fabricated and tested. The TDC shows a DNL≤1.3 LSB, an
INL≤2 LSB and a single-shot precision of 19.5 ps (0.58
LSB). The chip dissipates a power of 5.4 mW overall.
The ability of each of the nine Escherichia coli division proteins (FtsZ, FtsA, ZipA, FtsK, FtsQ, FtsL, FtsW, FtsI, FtsN) to interact with itself and with each of the remaining eight proteins was ...studied in 43 possible combinations of protein pairs by the two-hybrid system previously developed by the authors' group. Once the presumed interactions between the division proteins were determined, a model showing their temporal sequence of assembly was developed. This model agrees with that developed by other authors, based on the co-localization sequence in the septum of the division proteins fused with GFP. In addition, this paper shows that the authors' assay, which has already proved to be very versatile in the study of prokaryotic and eukaryotic protein interaction, is also a powerful instrument for an in vivo study of the interaction and assembly of proteins, as in the case of septum division formation.
Abstract
This paper presents a small-area monolithic pixel detector
ASIC designed in 130 nm SiGe BiCMOS technology for the upgrade of
the pre-shower detector of the FASER experiment at CERN. The ...purpose
of this prototype is to study the integration of fast front-end
electronics inside the sensitive area of the pixels and to identify
the configuration that could satisfy at best the specifications of
the experiment. Self-induced noise, instabilities and cross-talk
were minimised to cope with the several challenges associated to the
integration of pre-amplifiers and discriminators inside the pixels.
The methodology used in the characterisation and the design choices
will also be described. Two of the variants studied here will be
implemented in the pre-production ASIC of the FASER experiment
pre-shower for further tests.
Abstract
A monolithic silicon pixel detector prototype has been
produced in the SiGe BiCMOS SG13G2 130 nm node technology by
IHP. The ASIC contains a matrix of hexagonal pixels with pitch of
...approximately 100 μm. Three analog pixels were calibrated in
laboratory with radioactive sources and tested in a 180 GeV/c pion
beamline at the CERN SPS. A detection efficiency of
(99.9
-0.2
+0.1
)% was measured together with a time
resolution of (36.4 ± 0.8) ps at the highest preamplifier bias
current working point of 150 μA and at a sensor bias voltage
of 160 V. The ASIC was also characterized at lower bias voltage and
preamplifier current.
Abstract
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.
Summary
The Escherichia coli division protein FtsQ, which plays a central role in the septosome assembly, interacts with several protein partners of the division machinery. Its interaction with FtsB ...and FtsL allows the formation of the trimeric complex connecting the early cytoplasmic cell division proteins with the late, essentially periplasmic, ones. Little is known about the interactions that FtsQ contracts with other divisome components, besides the fact that all are localized in its periplasmic domain. In this domain, two independent subdomains, both involved in FtsQ, FtsI and FtsN interactions, were also identified. The study of FtsQ interaction‐defective mutants constituted a basis to investigate the biological significance of its interactions. However, in the case of interactions where two independent sites are involved, mutation(s) in one domain can be suppressed by the presence of the still‐functional second interaction region. To ascertain the biological role of these interactions, it is therefore necessary to select double mutants, where both sites are impaired. This paper describes the behaviour of FtsQ double mutants that have lost the ability to interact with FtsN, which is the last component in the hierarchy of divisome assembly, and is necessary to guarantee its stability and function.
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