177 research outputs found
Multiscale Analysis of Metal Oxide Nanoparticles in Tissue: Insights into Biodistribution and Biotransformation
Metal oxide nanoparticles have emerged as exceptionally potent biomedical sensors and actuators due to their unique physicochemical features. Despite fascinating achievements, the current limited understanding of the molecular interplay between nanoparticles and the surrounding tissue remains a major obstacle in the rationalized development of nanomedicines, which is reflected in their poor clinical approval rate. This work reports on the nanoscopic characterization of inorganic nanoparticles in tissue by the example of complex metal oxide nanoparticle hybrids consisting of crystalline cerium oxide and the biodegradable ceramic bioglass. A validated analytical method based on semiquantitative Xâray fluorescence and inductively coupled plasma spectrometry is used to assess nanoparticle biodistribution following intravenous and topical application. Then, a correlative multiscale analytical cascade based on a combination of microscopy and spectroscopy techniques shows that the topically applied hybrid nanoparticles remain at the initial site and are preferentially taken up into macrophages, form apatite on their surface, and lead to increased accumulation of lipids in their surroundings. Taken together, this work displays how modern analytical techniques can be harnessed to gain unprecedented insights into the biodistribution and biotransformation of complex inorganic nanoparticles. Such nanoscopic characterization is imperative for the rationalized engineering of safe and efficacious nanoparticleâbased systems
Prevalence of contagious and environmental mastitis-causing bacteria in bulk tank milk and its relationships with milking practices of dairy cattle herds in SĂŁo Miguel Island (Azores)
This study aimed to assess the degree of contamination of bulk tank milk (BTM) by Staphylococcus spp. and coliform bacteria and to identify major milking practices that help perpetuate them in dairy cattle herds in SĂŁo Miguel Island. In July 2014, BTM was sampled and a survey concerning local milking practices was conducted on 100 herds. Semi quantitative multiplex polymerase chain reaction detected coagulase-negative staphylococci, Escherichia coli, Staphylococcus aureus, and other coliform bacteria (Klebsiella oxytoca, Klebsiella pneumoniae, andSerratia marcescens) in 100, 75, 59, and 35 % of BTM, respectively. According to multivariable univariate models, on herds not using hot water for cleaning the milking machine and teat liners, there was at least 3.4 more odds (P<0.01) to have S. aureus or coliform bacteria contamination in BTM. The likelihoodoffinding S.aureus inBTMwas higher(P<0.001)on herds without high hygiene during milking, when milking mastitic cows at the end, on abrupt cessation of milking at dry-off, and official milk control implementation. The glove use also favored (odds ratio (OR) 5.8; P<0.01)thedetection ofcoliformbacteriainBTM.Poormilkingpracticesidentified in this study should be avoided in order to decrease S. aureus and coliform bacteria contamination of BTM. Other factors
associated with milk quality in SĂŁo Miguel Island also should be further investigated
ReincidĂȘncia da violĂȘncia contra crianças no MunicĂpio de Curitiba: um olhar de gĂȘnero
Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector
The inclusive and dijet production cross-sections have been measured for jets
containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass
energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The
measurements use data corresponding to an integrated luminosity of 34 pb^-1.
The b-jets are identified using either a lifetime-based method, where secondary
decay vertices of b-hadrons in jets are reconstructed using information from
the tracking detectors, or a muon-based method where the presence of a muon is
used to identify semileptonic decays of b-hadrons inside jets. The inclusive
b-jet cross-section is measured as a function of transverse momentum in the
range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet
cross-section is measured as a function of the dijet invariant mass in the
range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets
and the angular variable chi in two dijet mass regions. The results are
compared with next-to-leading-order QCD predictions. Good agreement is observed
between the measured cross-sections and the predictions obtained using POWHEG +
Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet
cross-section. However, it does not reproduce the measured inclusive
cross-section well, particularly for central b-jets with large transverse
momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final
version published in European Physical Journal
Inhibition of the Intrinsic but Not the Extrinsic Apoptosis Pathway Accelerates and Drives Myc-Driven Tumorigenesis Towards Acute Myeloid Leukemia
Myc plays an important role in tumor development, including acute myeloid leukemia (AML). However, MYC is also a powerful inducer of apoptosis, which is one of the major failsafe programs to prevent cancer development. To clarify the relative importance of the extrinsic (death receptor-mediated) versus the intrinsic (mitochondrial) pathway of apoptosis in MYC-driven AML, we coexpressed MYC together with anti-apoptotic proteins of relevance for AML; BCL-XL/BCL-2 (inhibiting the intrinsic pathway) or FLIPL (inhibiting the extrinsic pathway), in hematopoietic stems cells (HSCs). Transplantation of HSCs expressing MYC into syngeneic recipient mice resulted in development of AML and T-cell lymphomas within 7â9 weeks as expected. Importantly, coexpression of MYC together with BCL-XL/BCL-2 resulted in strongly accelerated kinetics and favored tumor development towards aggressive AML. In contrast, coexpression of MYC and FLIPL did neither accelerate tumorigenesis nor change the ratio of AML versus T-cell lymphoma. However, a change in distribution of immature CD4+CD8+ versus mature CD4+ T-cell lymphoma was observed in MYC/FLIPL mice, possibly as a result of increased survival of the CD4+ population, but this did not significantly affect the outcome of the disease. In conclusion, our findings provide direct evidence that BCL-XL and BCL-2 but not FLIPL acts in synergy with MYC to drive AML development
Limits on active to sterile neutrino oscillations from disappearance searches in the MINOS, Daya Bay, and bugey-3 experiments
Searches for a light sterile neutrino have been performed independently by the MINOS and the Daya Bay experiments using the muon (anti)neutrino and electron antineutrino disappearance channels, respectively. In this Letter, results from both experiments are combined with those from the Bugey-3 reactor neutrino experiment to constrain oscillations into light sterile neutrinos. The three experiments are sensitive to complementary regions of parameter space, enabling the combined analysis to probe regions allowed by the Liquid Scintillator Neutrino Detector (LSND) and MiniBooNE experiments in a minimally extended four-neutrino flavor framework. Stringent limits on sin^2 2ΞΌe are set over 6 orders of magnitude in the sterile mass-squared splitting Îm^2 41. The sterile-neutrino mixing phase space allowed by the LSND and MiniBooNE experiments is excluded for Îm^2 41 < 0.8 eV^2 at 95% CLs
Rare and low-frequency coding variants alter human adult height
Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways
Observation of B(s)0âJ/ÏppÂŻ decays and precision measurements of the B(s)0 masses
The first observation of the decays
B
0
(
s
)
â
J
/
Ï
p
ÂŻ
p
is reported, using proton-proton collision data corresponding to an integrated luminosity of
5.2
â
â
fb
â
1
, collected with the LHCb detector. These decays are suppressed due to limited available phase space, as well as due to Okubo-Zweig-Iizuka or Cabibbo suppression. The measured branching fractions are
B
(
B
0
â
J
/
Ï
p
ÂŻ
p
)
=
[
4.51
±
0.40
(
stat
)
±
0.44
(
syst
)
]
Ă
10
â
7
,
B
(
B
0
s
â
J
/
Ï
p
ÂŻ
p
)
=
[
3.58
±
0.19
(
stat
)
±
0.39
(
syst
)
]
Ă
10
â
6
. For the
B
0
s
meson, the result is much higher than the expected value of
O
(
10
â
9
)
. The small available phase space in these decays also allows for the most precise single measurement of both the
B
0
mass as
5279.74
±
0.30
(
stat
)
±
0.10
(
syst
)
â
â
MeV
and the
B
0
s
mass as
5366.85
±
0.19
(
stat
)
±
0.13
(
syst
)
â
â
MeV
Measurement of D s <sup>±</sup> production asymmetry in pp collisions at âs=7 and 8 TeV
The inclusive production asymmetry is measured in collisions
collected by the LHCb experiment at centre-of-mass energies of
and 8 TeV. Promptly produced mesons are used, which decay as
, with . The measurement is
performed in bins of transverse momentum, , and rapidity, ,
covering the range GeV and . No kinematic
dependence is observed. Evidence of nonzero production asymmetry is
found with a significance of 3.3 standard deviations.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2018-010.htm
Observation of the decay Î <sub>b</sub> <sup>0</sup> âââÏ(2S)pÏ<sup>â</sup>
International audienceThe Cabibbo-suppressed decay Î âââÏ(2S)pÏ is observed for the first time using a data sample collected by the LHCb experiment in proton-proton collisions corresponding to 1.0, 2.0 and 1.9 fb of integrated luminosity at centre-of-mass energies of 7, 8 and 13 TeV, respectively. The Ï(2S) mesons are reconstructed in the ΌΌ final state. The branching fraction with respect to that of the Î âââÏ(2S)pK decay mode is measured to b
- âŠ