7 research outputs found
Modeling of GERDA Phase II data
The GERmanium Detector Array (GERDA) experiment at the Gran Sasso underground
laboratory (LNGS) of INFN is searching for neutrinoless double-beta
() decay of Ge. The technological challenge of GERDA is
to operate in a "background-free" regime in the region of interest (ROI) after
analysis cuts for the full 100kgyr target exposure of the
experiment. A careful modeling and decomposition of the full-range energy
spectrum is essential to predict the shape and composition of events in the ROI
around for the search, to extract a precise
measurement of the half-life of the double-beta decay mode with neutrinos
() and in order to identify the location of residual
impurities. The latter will permit future experiments to build strategies in
order to further lower the background and achieve even better sensitivities. In
this article the background decomposition prior to analysis cuts is presented
for GERDA Phase II. The background model fit yields a flat spectrum in the ROI
with a background index (BI) of cts/(kgkeVyr) for the enriched BEGe data set and
cts/(kgkeVyr) for the
enriched coaxial data set. These values are similar to the one of Gerda Phase I
despite a much larger number of detectors and hence radioactive hardware
components
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Modeling of GERDA Phase II data
The GERmanium Detector Array (Gerda) experiment at the Gran Sasso underground laboratory (LNGS) of INFN is searching for neutrinoless double-beta (0νββ) decay of 76Ge. The technological challenge of Gerda is to operate in a “background-free” regime in the region of interest (ROI) after analysis cuts for the full 100 kg·yr target exposure of the experiment. A careful modeling and decomposition of the full-range energy spectrum is essential to predict the shape and composition of events in the ROI around Qββ for the 0νββ search, to extract a precise measurement of the half-life of the double-beta decay mode with neutrinos (2νββ) and in order to identify the location of residual impurities. The latter will permit future experiments to build strategies in order to further lower the background and achieve even better sensitivities. In this article the background decomposition prior to analysis cuts is presented for Gerda Phase II. The background model fit yields a flat spectrum in the ROI with a background index (BI) of 16.04+0.78−0.85⋅10−3 cts/(keV·kg·yr) for the enriched BEGe data set and 14.68+0.47−0.52⋅10−3 cts/(keV·kg·yr) for the enriched coaxial data set. These values are similar to the one of Phase I despite a much larger number of detectors and hence radioactive hardware components
Osmolytes and Macromolecular Crowders Diversely Affect the Aggregation of the Cancerrelated L106R Mutant of the Axin RGS Domain
Protein aggregation is involved in a variety
of diseases, including neurodegenerative diseases and cancer. The cellular
environment is crowded by a plethora of cosolutes comprising small molecules
and biomacromolecules at high concentrations, which may influence the
aggregation of proteins in vivo. To account for the effect of cosolutes
on cancer-related protein aggregation, we studied their effect on the
aggregation of the cancer-related L106R mutant of the Axin protein. Axin is a
key player in the Wnt signaling pathway, and the L106R mutation in its RGS
domain results in a native molten globule that tends to form native-like
aggregates. This results in uncontrolled activation of the Wnt signaling
pathway, leading to cancer. We monitored the aggregation process of Axin RGS
L106Rin vitro in the presence of a wide ensemble of cosolutes including
polyols, amino acids, betaine and polyethylene glycol (PEG) crowders. Except myo-inositol,
all polyols decreased RGS L106R aggregation, with carbohydrates exerting the
strongest inhibition. Conversely, betaine and PEGs enhanced aggregation. These
results are consistent with the reported effects of osmolytes and crowders on
the stability of molten globular proteins and with both amorphous and amyloid
aggregation mechanisms. We suggest a model of Axin L106R aggregation in vivo, whereby molecularly small
osmolytes keep the protein as a free solublemolecule but the increased crowding
of the bound state by macromolecules induces its aggregation at the nano-scale.
Our study sheds light on the potential contribution of cosolutes to the onset
of cancer as a protein misfolding disease, and on the relevance of aggregation
in the molecular aetiology of cancer.</p
International comparability in spectroscopic measurements of protein structure by circular dichroism: CCQM-P59.1
Circular dichroism (CD) is a spectroscopic technique that is widely used to obtain information about protein structure, and hence is an important tool with many applications, including the characterization of biopharmaceuticals. A previous inter-laboratory study, CCQM-P59, showed that there was a poor level of comparability between laboratories in CD spectroscopy. In a follow-up study reported here, we achieved our goal of demonstrating improved comparability and data quality, primarily by addressing the problems identified in the previous study, which included cell path-length measurement, instrument calibration and good practice in general. Multivariate analysis techniques (principal component analysis and soft independent modelling of class analogies) were shown to be useful in comparing large spectral data sets and in classifying spectra. However, our results also show that there is more work to be done to improve confidence in the technique as the discrepancies observed were partially due to systematic effects, which the statistical approaches do not consider. We therefore conclude that there is a need for an improved understanding of the uncertainties in CD measurement
Rapid oligomer formation of human muscle acylphosphatase induced by heparan sulfate
Many human diseases are caused by the conversion of proteins from their native state into amyloid fibrils that deposit in the extracellular space. Heparan sulfate, a component of the extracellular matrix, is universally associated with amyloid deposits and promotes fibril formation. The formation of cytotoxic prefibrillar oligomers is challenging to study because of its rapidity, transient appearance and the heterogeneity of species generated. The process is even more complex with agents such as heparan sulfate. Here we have used a stopped-flow device coupled to turbidometry detection to monitor the rapid conversion of human muscle acylphosphatase into oligomers with varying heparan sulfate and protein concentrations. We also analyzed mutants of the 15 basic amino acids of acylphosphatase, identifying the residues primarily involved in heparan sulfate-induced oligomerization of this protein and tracing the process with unprecedented molecular detail