469 research outputs found
Synthesis and biological evaluation of new simple indolic non peptidic HIV Protease inhibitors: The effect of different substitution patterns
New structurally simple indolic non peptidic HIV Protease inhibitors were synthesized from (S)-
glycidol by regioselective methods. Following the concept of targeting the protein backbone,
different substitution patterns were introduced onto the common stereodefined
isopropanolamine core modifying the type of functional group on the indole, the position of the
functional group on the indole and the type of the nitrogen containing group (sulfonamides or
perhydroisoquinoline), alternatively. The systematic study on in vitro inhibition activity of such
compounds confirmed the general beneficial effect of the 5-indolyl substituents in presence of
arylsulfonamide moieties, which furnished activities in the micromolar range. Preliminary docking
analysis allowed to identify several key features of the binding mode of such compounds to the
protease
The obesity and inflammatory marker haptoglobin attracts monocytes via interaction with chemokine (C-C motif) receptor 2 (CCR2)
<p>Abstract</p> <p>Background</p> <p>Obesity is a chronic low inflammatory state. In the obesity condition the white adipose tissue (WAT) is massively infiltrated with monocytes/macrophages, and the nature of the signals recruiting these inflammatory cells has yet to be fully elucidated. Haptoglobin (Hp) is an inflammatory marker and its expression is induced in the WAT of obese subjects. In an effort to elucidate the biological significance of Hp presence in the WAT and of its upregulation in obesity we formulated the hypothesis that Hp may serve as a macrophage chemoattractant.</p> <p>Results</p> <p>We demonstrated by chemotaxis assay that Hp is able to attract chemokine (C-C motif) receptor 2 (CCR2)-transfected pre-B lymphocytes and monocytes in a dose-dependent manner. Moreover, Hp-mediated migration of monocytes is impaired by CCR2-specific inhibition or previous cell exposure to monocyte chemoattractant protein 1 (MCP1) (also known as CCR2 ligand or chemokine (C-C motif) ligand 2 (CCL2)). Downstream effects of Hp/CCR2 interaction were also investigated: flow cytometry proved that monocytes treated with Hp show reduced CCR2 expression on their surface; Hp interaction induces calcium release that is reduced upon pretreatment with CCR2 antagonist; extracellular signal-regulated kinase (ERK)1/2, a signal transducer activated by CCR2, is phosphorylated following Hp treatment and this phosphorylation is reduced when cells are pretreated with a specific CCR2 inhibitor. Consistently, blocking the ERK1/2 pathway with U0126, the selective inhibitor of the ERK upstream mitogen-activated protein (MAP)-ERK kinase (MEK), results in a dramatic reduction (by almost 100%) of the capability of Hp to induce monocyte migration.</p> <p>Conclusions</p> <p>Our data show that Hp is a novel monocyte chemoattractant and that its chemotactic potential is mediated, at least in part. by its interaction with CCR2.</p
Monomeric Tartrate Resistant Acid Phosphatase Induces Insulin Sensitive Obesity
Obesity is associated with macrophage infiltration of adipose tissue, which may link adipose inflammation to insulin resistance. However, the impact of inflammatory cells in the pathophysiology of obesity remains unclear
Study of cosmogenic activation above ground for the DarkSide-20k experiment
The activation of materials due to exposure to cosmic rays may become an important background source for experiments investigating rare event phenomena. DarkSide-20k, currently under construction at the Laboratori Nazionali del Gran Sasso, is a direct detection experiment for galactic dark matter particles, using a two-phase liquid-argon Time Projection Chamber (TPC) filled with 49.7 tonnes (active mass) of Underground Argon (UAr) depleted in 39Ar. Despite the outstanding capability of discriminating
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background in argon TPCs, this background must be considered because of induced dead time or accidental coincidences mimicking dark-matter signals and it is relevant for low-threshold electron-counting measurements. Here, the cosmogenic activity of relevant long-lived radioisotopes induced in the experiment has been estimated to set requirements and procedures during preparation of the experiment and to check that it is not dominant over primordial radioactivity; particular attention has been paid to the activation of the 120 t of UAr used in DarkSide-20k. Expected exposures above ground and production rates, either measured or calculated, have been considered in detail. From the simulated counting rates in the detector due to cosmogenic isotopes, it is concluded that activation in copper and stainless steel is not problematic. The activity of 39Ar induced during extraction, purification and transport on surface is evaluated to be 2.8% of the activity measured in UAr by DarkSide-50 experiment, which used the same underground source, and thus considered acceptable. Other isotopes in the UAr such as 37Ar and 3H are shown not to be relevant due to short half-life and assumed purification methods
Measurement of isotopic separation of argon with the prototype of the cryogenic distillation plant Aria for dark matter searches
The Aria cryogenic distillation plant, located in Sardinia, Italy, is a key component of the DarkSide-20k experimental program for WIMP dark matter searches at the INFN Laboratori Nazionali del Gran Sasso, Italy. Aria is designed to purify the argon, extracted from underground wells in Colorado, USA, and used as the DarkSide-20k target material, to detector-grade quality. In this paper, we report the first measurement of argon isotopic separation by distillation with the 26 m tall Aria prototype. We discuss the measurement of the operating parameters of the column and the observation of the simultaneous separation of the three stable argon isotopes: 36Ar , 38Ar , and 40Ar . We also provide a detailed comparison of the experimental results with commercial process simulation software. This measurement of isotopic separation of argon is a significant achievement for the project, building on the success of the initial demonstration of isotopic separation of nitrogen using the same equipment in 2019
Directionality of nuclear recoils in a liquid argon time projection chamber
The direct search for dark matter in the form of weakly interacting massive
particles (WIMP) is performed by detecting nuclear recoils (NR) produced in a
target material from the WIMP elastic scattering. A promising experimental
strategy for direct dark matter search employs argon dual-phase time projection
chambers (TPC). One of the advantages of the TPC is the capability to detect
both the scintillation and charge signals produced by NRs. Furthermore, the
existence of a drift electric field in the TPC breaks the rotational symmetry:
the angle between the drift field and the momentum of the recoiling nucleus can
potentially affect the charge recombination probability in liquid argon and
then the relative balance between the two signal channels. This fact could make
the detector sensitive to the directionality of the WIMP-induced signal,
enabling unmistakable annual and daily modulation signatures for future
searches aiming for discovery. The Recoil Directionality (ReD) experiment was
designed to probe for such directional sensitivity. The TPC of ReD was
irradiated with neutrons at the INFN Laboratori Nazionali del Sud, and data
were taken with 72 keV NRs of known recoil directions. The direction-dependent
liquid argon charge recombination model by Cataudella et al. was adopted and a
likelihood statistical analysis was performed, which gave no indications of
significant dependence of the detector response to the recoil direction. The
aspect ratio R of the initial ionization cloud is estimated to be 1.037 +/-
0.027 and the upper limit is R < 1.072 with 90% confidence levelComment: 20 pages, 10 figures, submitted to Eur. Phys. J.
Sensitivity projections for a dual-phase argon TPC optimized for light dark matter searches through the ionization channel
Dark matter lighter than 10 GeV/c2 encompasses a promising range of candidates. A conceptual design for a new detector, DarkSide-LowMass, is presented, based on the DarkSide-50 detector and progress toward DarkSide-20k, optimized for a low-threshold electron-counting measurement. Sensitivity to light dark matter is explored for various potential energy thresholds and background rates. These studies show that DarkSide-LowMass can achieve sensitivity to light dark matter down to the solar neutrino fog for GeV-scale masses and significant sensitivity down to 10 MeV/c2 considering the Migdal effect or interactions with electrons. Requirements for optimizing the detector’s sensitivity are explored, as are potential sensitivity gains from modeling and mitigating spurious electron backgrounds that may dominate the signal at the lowest energies
Study on cosmogenic activation above ground for the DarkSide-20k project
The activation of materials due to the exposure to cosmic rays may become an
important background source for experiments investigating rare event phenomena.
DarkSide-20k is a direct detection experiment for galactic dark matter
particles, using a two-phase liquid argon time projection chamber filled with
49.7 tonnes (active mass) of Underground Argon (UAr) depleted in 39Ar. Here,
the cosmogenic activity of relevant long-lived radioisotopes induced in the
argon and other massive components of the set-up has been estimated; production
of 120 t of radiopure UAr is foreseen. The expected exposure above ground and
production rates, either measured or calculated, have been considered. From the
simulated counting rates in the detector due to cosmogenic isotopes, it is
concluded that activation in copper and stainless steel is not problematic.
Activation of titanium, considered in early designs but not used in the final
design, is discussed. The activity of 39Ar induced during extraction,
purification and transport on surface, in baseline conditions, is evaluated to
be 2.8% of the activity measured in UAr from the same source, and thus
considered acceptable. Other products in the UAr such as 37Ar and 3H are shown
to not be relevant due to short half-life and assumed purification methods
Sensitivity projections for a dual-phase argon TPC optimized for light dark matter searches through the ionization channel
Dark matter lighter than 10 GeV/c encompasses a promising range of
candidates. A conceptual design for a new detector, DarkSide-LowMass, is
presented, based on the DarkSide-50 detector and progress toward DarkSide-20k,
optimized for a low-threshold electron-counting measurement. Sensitivity to
light dark matter is explored for various potential energy thresholds and
background rates. These studies show that DarkSide-LowMass can achieve
sensitivity to light dark matter down to the solar neutrino floor for GeV-scale
masses and significant sensitivity down to 10 MeV/c considering the Migdal
effect or interactions with electrons. Requirements for optimizing the
detector's sensitivity are explored, as are potential sensitivity gains from
modeling and mitigating spurious electron backgrounds that may dominate the
signal at the lowest energies
Hypertriton Production in p-Pb Collisions at √sNN = 5.02 TeV
The study of nuclei and antinuclei production has proven to be a powerful
tool to investigate the formation mechanism of loosely bound states in
high-energy hadronic collisions. The first measurement of the production of
in p-Pb collisions at = 5.02
TeV is presented in this Letter. Its production yield measured in the rapidity
interval -1 < y < 0 for the 40% highest multiplicity p-Pb collisions is . The measurement is compared with the expectations of statistical
hadronisation and coalescence models, which describe the nucleosynthesis in
hadronic collisions. These two models predict very different yields of the
hypertriton in small collision systems such as p-Pb and therefore the
measurement of is crucial to distinguish between them.
The precision of this measurement leads to the exclusion with a significance
larger than 6 of some configurations of the statistical hadronisation,
thus constraining the production mechanism of loosely bound states
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