The L3+C detector, a unique tool-set to study cosmic rays Adriani, O.; van den Akker, M.; Banerjee, S. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
08/2002, Letnik:
488, Številka:
1
Journal Article
Recenzirano
The L3 detector at the CERN electron–positron collider, LEP, has been employed for the study of cosmic ray muons. The muon spectrometer of L3 consists of a set of high-precision drift chambers ...installed inside a magnet with a volume of about
1000
m
3
and a field of
0.5
T
. Muon momenta are measured with a resolution of a few percent at
50
GeV
. The detector is located under
30
m
of overburden. A scintillator air shower array of
54
m
by
30
m
is installed on the roof of the surface hall above L3 in order to estimate the energy and the core position of the shower associated with a sample of detected muons. Thanks to the unique properties of the L3+C detector, muon research topics relevant to various current problems in cosmic ray and particle astrophysics can be studied.
The p53 upregulated modulator of apoptosis (PUMA) is known as an essential apoptosis inducer. Here, we report the seemingly paradoxical finding that PUMA is a proangiogenic factor critically required ...for the proliferation and survival of vascular and microglia cells. Strikingly, Puma deficiency by genetic deletion or small hairpin RNA knockdown inhibited developmental and pathological angiogenesis and reduced microglia numbers in vivo, whereas Puma gene delivery increased angiogenesis and cell survival. Mechanistically, we revealed that PUMA plays a critical role in regulating autophagy by modulating Erk activation and intracellular calcium level. Our findings revealed an unexpected function of PUMA in promoting angiogenesis and warrant more careful investigations into the therapeutic potential of PUMA in treating cancer and degenerative diseases.
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► PUMA is abundantly expressed in vascular and microglia cells ► PUMA promotes vascular/microglia cell proliferation/survival and angiogenesis ► Puma deficiency reduces angiogenesis and microglia density ► PUMA regulates autophagy, Erk activation, and intracellular calcium level
Even though the p53 upregulated modulator of apoptosis (PUMA) gene has been known as an essential apoptosis inducer for many years, its effect on vascular and microglia cells is largely unknown. Now, Zhang and colleagues report their surprising finding that PUMA is a proangiogenic factor critically required for the proliferation and survival of vascular and microglia cells. Mechanistically, the authors reveal that PUMA plays a critical role in regulating autophagy by modulating Erk activation and intracellular calcium level.
The data collected by the L3+C muon spectrometer at the CERN Large Electron–Positron collider, LEP, have been used to search for short duration signals emitted by cosmic point sources. A sky survey ...performed from July to November 1999 and from April to November 2000 has revealed one single flux enhancement
(
chance probability
=
2.6
×
10
-
3
)
between the 17th and 20th of August 2000 from a direction with a galactic longitude of (265.02
±
0.42)° and latitude of (55.58
±
0.24)°. The energy of the detected muons was above 15
GeV.
Context. Primary cosmic rays experience multiple deflections in the non-uniform galactic and heliospheric magnetic fields which may generate anisotropies. Aims. A study of anisotropies in the energy ...range between 100 and 500 GeV is performed. This energy range is not yet well explored. Methods. The L3 detector at the CERN electron-positron collider, LEP, is used for a study of the angular distribution of atmospheric muons with energies above 20 GeV. This distribution is used to investigate the isotropy of the time-dependent intensity of the primary cosmic-ray flux with a Fourier analysis. Results. A small deviation from isotropy at energies around 200 GeV is observed for the second harmonics at the solar frequency. No sidereal anisotropy is found at a level above 10-4. The measurements were performed in the years 1999 and 2000.
RNA interference (RNAi)-mediated gene silencing has become a valuable tool for functional studies, reverse genomics, and drug discoveries. One major challenge of using RNAi is to identify the most ...effective short interfering RNAs (siRNAs) sites of a given gene. Although several published bioinformatic prediction models have proven useful, the process to select and validate optimal siRNA sites for a given gene remains empirical and laborious. Here, we developed a fluorescence-based selection system using a retroviral vector backbone, namely pSOS, which was based on the premise that candidate siRNAs would knockdown the chimeric transcript between GFP and target gene. The expression of siRNA was driven by the opposing convergent H1 and U6 promoters. This configuration simplifies the cloning of duplex siRNA oligonucleotide cassettes. We demonstrated that GFP signal reduction was closely correlated with siRNA knockdown efficiency of human β-catenin, as well as with the inhibition of β-catenin/Tcf4 signaling activity. The pSOS should not only facilitate the selection and validation of candidate siRNA sites, but also provide efficient delivery tools of siRNAs via viral vectors in mammalian cells. Thus, the pSOS system represents an efficient and user-friendly strategy to select and validate siRNA target sites.
Gyrokinetic particle simulation of fusion plasmas for studying turbulent transport on state-of-theart computers has a long history of important scientific discoveries. The primary examples are: (i) ...the identification of ion temperature gradient (ITG) drift turbulence as the most plausible process responsible for the thermal transport observed in tokamak experiments; (ii) the reduction of such transport due to the presence of zonal flows; (iii) the confinement scaling trends associated with size of the plasma and also with the ionic isotope species. With the availability of terascale computers in recent years, we have also been able to carry out simulations with improved physics fidelity using experimentally relevant parameters. Computationally, we have demonstrated that our lead Particle-in- Cell (PIC) code, the Gyrokinetic Turbulence Code (GTC), is portable, efficient, and scalable on various MPP platforms. Convergence studies with unprecedented phase-space resolution have also been carried out. Since petascale resources are expected to be available in the near future, we have also engaged in developing better physics models and more efficient numerical algorithms to take advantage of this exciting opportunity. For the near term, we are interested in understanding some basic physics issues related to burning plasmas experiments in International Thermonuclear Experimental Reactor (ITER) - a multi-billion dollar device to be constructed over the next decade. Our long range goal is to carry out integrated simulations for ITER plasmas for a wide range of temporal and spatial scales, including high-frequency short-wavelength wave heating, low-frequency meso-scale transport, and low-frequency large scale magnetohydrodynamic (MHD) physics on these computers.
Identification of key drivers and new therapeutic targets is important given the poor prognosis for hepatocellular carcinoma (HCC) patients, particularly those ineligible for surgical resection or ...liver transplant. However, the approach to identify such driver genes is facing significant challenges due to the genomically heterogenous nature of HCC. Here we tested whether the integrative genomic profiling of a well-defined HCC subset that is classified by an extreme EpCAM super(+) AFP super(+) gene expression signature and associated with poor prognosis, all attributes of a stem cell-like phenotype, could uncover survival-related driver genes in HCC. Following transcriptomic analysis of the well-defined HCC cases, a Gene Set Enrichment Analysis coupled with genomic copy number alteration assessment revealed that YY1-associated protein 1 (YY1AP1) is a critical oncoprotein specifically activated in EpCAM super(+) AFP super(+) HCC. YY1AP1 silencing eliminates oncogene addiction by altering the chromatin landscape and triggering massive apoptosis in vitro and tumor suppression in vivo. YY1AP1 expression promotes HCC proliferation and is required for the maintenance of stem cell features. We revealed that YY1AP1 cooperates with YY1 to alter the chromatin landscape and activate transcription of stemness regulators. Thus YY1AP1 may serve as a key molecular target for EpCAM super(+) AFP super(+) HCC subtype. Our results demonstrate the feasibility and power of a new strategy by utilizing well-defined patient samples and integrative genomics to uncover critical pathways linked to HCC subtypes with prognostic impact.
Two novel metal−organic frameworks (MOFs) Zn(TITMB)(OAc)(OH)·8.5H2O (1) and Ag(TITMB)N3·H2O (2) TITMB = 1,3,5-tris(imidazol-1-ylmethyl)-2,4,6-trimethylbenzene, OAc = acetate anion were synthesized ...and their structures were determined by X-ray crystallography. Complex 1 crystallizes in tetragonal space group P4̄ with a = 23.2664(7) and c = 11.9890(3) Å and Z = 8. 1 has a one-dimensional tubelike structure with large inner pore size of ∼17 Å. Complex 2 crystallizes in monoclinic space group C2 with a = 20.7193(10), b = 11.5677(8), and c = 12.2944(6) Å, β = 125.5770(10)°, and Z = 4. 2 consists of two-dimensional honeycomb networks that interpenetrate each other to generate a polycatenated structure. In these two complexes, both zinc(II) and silver(I) atoms are four-coordinated with the same tetrahedral coordination geometry. The topologies of 1 and 2 are predominated by the conformations of TITMB, which are cis, trans, trans in 1 and cis, cis, cis in 2, respectively.
To investigate the pathological characteristics and the clinical significance of novel coronavirus (2019-nCoV)-infected pneumonia (termed by WHO as coronavirus disease 2019, COVID-19).
Minimally ...invasive autopsies from lung, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, intestine, thyroid and skin were performed on three patients died of novel coronavirus pneumonia in Chongqing, China. Hematoxylin and eosin staining (HE), transmission electron microcopy, and histochemical staining were performed to investigate the pathological changes of indicated organs or tissues. Immunohistochemical staining was conducted to evaluate the infiltration of immune cells as well as the expression of 2019-nCoV proteins. Real time PCR was carried out to detect the RNA of 2019-nCoV.
Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. Hyaline membrane formation was observed in some alveoli. The infiltrated immune cells in alveoli were majorly macrophages and monocytes. Moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed. Most of infiltrated lymphocytes were CD4-positive T cells. Significant proliferation of type Ⅱ alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. Hyaline thrombi were found in a minority of microvessels. Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosis were observed. Part of the bronchial epithelia were exfoliated. Coronavirus particles in bronchial mucosal epithelia and type Ⅱ alveolar epithelia were observed under electron microscope. Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. Real time PCR analyses identified positive signals for 2019-nCoV nucleic acid. Decreased numbers of lymphocyte, cell degeneration and necrosis were observed in spleen. Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs.
The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation. While the 2019-nCoV is mainly distributed in lung, the infection also involves in the damages of heart, vessels, liver, kidney and other organs. Further studies are warranted to investigate the mechanism underlying pathological changes of this disease.
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