222 research outputs found
Down-Regulation of hsa-miR-10a in Chronic Myeloid Leukemia CD34+ Cells Increases USF2-Mediated Cell Growth
MicroRNAs (miRNA) are small noncoding,
single-stranded RNAs that inhibit gene expression at a
posttranscriptional level, whose abnormal expression
has been described in different tumors. The aim of our
study was to identify miRNAs potentially implicated
in chronic myeloid leukemia (CML). We detected an
abnormal miRNA expression profile in mononuclear and
CD34+ cells from patients with CML compared with
healthy controls. Of 157 miRNAs tested, hsa-miR-10a,
hsa-miR-150, and hsa-miR-151 were down-regulated,
whereas hsa-miR-96 was up-regulated in CML cells.
Down-regulation of hsa-miR-10a was not dependent
on BCR-ABL1 activity and contributed to the increased
cell growth of CML cells. We identified the upstream
stimulatory factor 2 (USF2) as a potential target of
hsa-miR-10a and showed that overexpression of USF2
also increases cell growth. The clinical relevance of
these findings was shown in a group of 85 newly
diagnosed patients with CML in which expression of
hsa-miR-10a was down-regulated in 71% of the patients,
whereas expression of USF2 was up-regulated in 60% of
the CML patients, with overexpression of USF2 being
significantly associated with decreased expression of
hsa-miR-10a (P = 0.004). Our results indicate that
down-regulation of hsa-miR-10a may increase USF2 and
contribute to the increase in cell proliferation of CML
implicating a miRNA in the abnormal behavior of CML
Neutralino dark matter in mSUGRA/CMSSM with a 125 GeV light Higgs scalar
The minimal supergravity (mSUGRA or CMSSM) model is an oft-used framework for
exhibiting the properties of neutralino (WIMP) cold dark matter (CDM). However,
the recent evidence from Atlas and CMS on a light Higgs scalar with mass
m_h\simeq 125 GeV highly constrains the superparticle mass spectrum, which in
turn constrains the neutralino annihilation mechanisms in the early universe.
We find that stau and stop co-annihilation mechanisms -- already highly
stressed by the latest Atlas/CMS results on SUSY searches -- are nearly
eliminated if indeed the light Higgs scalar has mass m_h\simeq 125 GeV.
Furthermore, neutralino annihilation via the A-resonance is essentially ruled
out in mSUGRA so that it is exceedingly difficult to generate
thermally-produced neutralino-only dark matter at the measured abundance. The
remaining possibility lies in the focus-point region which now moves out to
m_0\sim 10-20 TeV range due to the required large trilinear soft SUSY breaking
term A_0. The remaining HB/FP region is more fine-tuned than before owing to
the typically large top squark masses. We present updated direct and indirect
detection rates for neutralino dark matter, and show that ton scale noble
liquid detectors will either discover mixed higgsino CDM or essentially rule
out thermally-produced neutralino-only CDM in the mSUGRA model.Comment: 17 pages including 9 .eps figure
NOMAD spectrometer on the ExoMars trace gas orbiter mission: part 2—design, manufacturing, and testing of the ultraviolet and visible channel
NOMAD is a spectrometer suite on board the ESA/Roscosmos ExoMars Trace Gas Orbiter, which launched in March 2016. NOMAD consists of two infrared channels and one ultraviolet and visible channel, allowing the instrument to perform observations quasi-constantly, by taking nadir measurements at the day- and night-side, and during solar occultations. Here, in part 2 of a linked study, we describe the design, manufacturing, and testing of the ultraviolet and visible spectrometer channel called UVIS. We focus upon the optical design and working principle where two telescopes are coupled to a single grating spectrometer using a selector mechanism
Radiopurity control in the NEXT-100 double beta decay experiment: procedures and initial measurements
We have investigated the possibility of calibrating the PMTs of scintillation detectors, using the primary scintillation produced by X-rays to induce single photoelectron response of the PMT. The high-energy tail of this response, can be approximated to an exponential function, under some conditions. In these cases, it is possible to determine the average gain for each PMT biasing voltage from the inverse of the exponent of the exponential fit to the tail, which can be done even if the background and/or noise cover-up most of the distribution. We have compared our results with those obtained by the commonly used single electron response (SER) method, which uses a LED to induce a single photoelectron response of the PMT and determines the peak position of such response, relative to the pedestal peak (the electronic noise peak, which corresponds to 0 photoelectrons). The results of the exponential fit method agree with those obtained by the SER method when the average number of photoelectrons reaching the first dynode per light/scintillation pulse is around 1.0. The SER method has higher precision, while the exponential fit method has the advantage of being useful in situations where the PMT is already in situ, being difficult or even impossible to apply the SER method, e.g. in sealed scintillator/PMT devices
Accurate gamma and MeV-electron track reconstruction with an ultra-low diffusion Xenon/TMA TPC at 10 atm
We report the performance of a 10 atm Xenon/trimethylamine time projection chamber (TPC) for the detection of X-rays (30 keV) and gamma-rays (0.511-1.275 MeV) in conjunction with the accurate tracking of the associated electrons. When operated at such a high pressure and in similar to 1%-admixtures, trimethylamine (TMA) endows Xenon with an extremely low electron diffusion (1.3 +/- 0.13 mm-sigma (longitudinal), 0.95 +/- 0.20 mm-sigma (transverse) along 1 m drift) besides forming a convenient Penning-Fluorescent' mixture. The TPC, that houses 1.1 kg of gas in its fiducial volume, operated continuously for 100 live-days in charge amplification mode. The readout was performed through the recently introduced microbulk Micromegas technology and the AFTER chip, providing a 3D voxelization of 8 mm x 8 mm x 1.2 mm for approximately 10 cm/MeV-long electron tracks. Resolution in energy (epsilon) at full width half maximum (R) inside the fiducial volume ranged from R = 14.6% (30 keV) to R = 4.6% (1.275 MeV).
This work was developed as part of the R&D program of the NEXT collaboration for future detector upgrades in the search of the neutrino-less double beta decay (beta beta 0 nu) in Xe-136, specifically those based on novel gas mixtures. Therefore we ultimately focus on the calorimetric and topological properties of the reconstructed MeV-electron tracks. In particular, the obtained energy resolution has been decomposed in its various contributions and improvements towards achieving the R =1.4%root MeV/epsilon levels obtained in small sensors are discussedThe NEXT collaboration acknowledges funding support from the following agencies and institutions: European Research Council under Advanced Grant 339787-NEXT and Starting Grant 240054-TREX, Spanish Ministerio de Economia y Competitividad under grants Consolider-Ingenio 2010 CSD2008-0037 (CUP) and CSD2007-00042 (CPAN), contracts FPA2008-03456 and FPA2009-13697; Portuguese Fundacao para a Ciencia e a Tecnologia; European FEDER under grant PPTDC/FIS/103860/2008; US Department Of Energy under contract DE-AC02-05CH11231.Gonzalez Diaz, D.; Álvarez Puerta, V.; Borges, FIG.; Camargo, M.; Carcel, S.; Cebrian, S.; Cervera, A.... (2015). Accurate gamma and MeV-electron track reconstruction with an ultra-low diffusion Xenon/TMA TPC at 10 atm. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. 804:8-24. https://doi.org/10.1016/j.nima.2015.08.033S82480
Physical Activity Patterns of the Spanish Population Are Mostly Determined by Sex and Age: Findings in the ANIBES Study
Background
Representative data for the Spanish population regarding physical activity (PA) behaviors
are scarce and seldom comparable due to methodological inconsistencies.
Aim
Our objectives were to describe the PA behavior by means of the standardized self-reported
International Physical Activity Questionnaire (IPAQ) and to know the proportion of the Spanish
population meeting and not meeting international PA recommendations.
Material and Methods
PA was assessed using the IPAQ in a representative sample of 2285 individuals (males,
50.4%) aged 9–75 years and living in municipalities of at least 2,000 inhabitants. Data were
analyzed according to: age groups 9–12, 13–17, 18–64, and 65–75 years; sex; geographical
distribution; locality size and educational levels.
Results
Mean total PA was 868.8±660.9 min/wk, mean vigorous PA 146.4±254.1 min/wk, and mean
moderate PA 398.1±408.0 min/wk, showing significant differences between sexes
(p<0.05). Children performed higher moderate-vigorous PA than adolescents and seniors
(p<0.05), and adults than adolescents and seniors (p<0.05). Compared to recommendations,
36.2%of adults performed <150 min/week of moderate PA, 65.4% <75 min/week of vigorous PA and 27.0%did not perform any PA at all, presenting significant differences
between sexes (p<0.05). A total of 55.4%of children and adolescents performed less than
420 min/week of MVPA, being higher in the later (62.6%) than in the former (48.4%). Highest
non-compliance was observed in adolescent females (86.5%).
Conclusion
Sex and age are the main influencing factors on PA in the Spanish population. Males
engage in more vigorous and light PA overall, whereas females perform more moderate
PA. PA behavior differs between age groups and no clear lineal increase with age could be
observed. Twenty-seven percent of adults and 55.4% of children and adolescents do not
meet international PA recommendations. Identified target groups should be addressed to
increase PA in the Spanish populationCoca-Cola Iberia through Spanish Nutrition Foundation (FEN)Coca-Cola Iberi
Initial results of NEXT-DEMO, a large-scale prototype of the NEXT-100 experiment
NEXT-DEMO is a large scale prototype and demonstrator of the NEXT-100 High Pressure Xenon Gas TPC, which will search for the neutrinoless double beta decay of Xe-136 using 100-150 kg of enriched xenon gas. The apparatus was built to prove the expected performance of NEXT-100, namely, energy resolution better than 1% FWHM at 2.5 MeV and event topological reconstruction. In this paper we describe the operation and initial results of the detector. A resolution of 1.7% FWHM at 511 keV (0.77% FWHM at 2.5 MeV) is obtained in the full fiducial volume of the detector. A topological analysis shows that electrons are identified by the characteristic blob energy deposit associated to the Bragg peak in 98.5% of the cases, with a rate of misidentification (two blobs) of 0.14%
Management and outcomes of gastrointestinal congenital anomalies in low, middle and high income countries: Protocol for a multicentre, international, prospective cohort study
Introduction
Congenital anomalies are the fifth leading cause of death in children <5 years of age globally, contributing an estimated half a million deaths per year. Very limited literature exists from low and middle income countries (LMICs) where most of these deaths occur. The Global PaedSurg Research Collaboration aims to undertake the first multicentre, international, prospective cohort study of a selection of common congenital anomalies comparing management and outcomes between low, middle and high income countries (HICs) globally.
Methods and analysis
The Global PaedSurg Research Collaboration consists of surgeons, paediatricians, anaesthetists and allied healthcare professionals involved in the surgical care of children globally. Collaborators will prospectively collect observational data on consecutive patients presenting for the first time, with one of seven common congenital anomalies (oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation and Hirschsprung''s disease). Patient recruitment will be for a minimum of 1 month from October 2018 to April 2019 with a 30-day post-primary intervention follow-up period. Anonymous data will be collected on patient demographics, clinical status, interventions and outcomes using REDCap. Collaborators will complete a survey regarding the resources and facilities for neonatal and paediatric surgery at their centre. The primary outcome is all-cause in-hospital mortality. Secondary outcomes include the occurrence of postoperative complications. Chi-squared analysis will be used to compare mortality between LMICs and HICs. Multilevel, multivariate logistic regression analysis will be undertaken to identify patient-level and hospital-level factors affecting outcomes with adjustment for confounding factors.
Ethics and dissemination
At the host centre, this study is classified as an audit not requiring ethical approval. All participating collaborators have gained local approval in accordance with their institutional ethical regulations. Collaborators will be encouraged to present the results locally, nationally and internationally. The results will be submitted for open access publication in a peer reviewed journal
Microglia Are Mediators of Borrelia burgdorferi–Induced Apoptosis in SH-SY5Y Neuronal Cells
Inflammation has long been implicated as a contributor to pathogenesis in many CNS illnesses, including Lyme neuroborreliosis. Borrelia burgdorferi is the spirochete that causes Lyme disease and it is known to potently induce the production of inflammatory mediators in a variety of cells. In experiments where B. burgdorferi was co-cultured in vitro with primary microglia, we observed robust expression and release of IL-6 and IL-8, CCL2 (MCP-1), CCL3 (MIP-1α), CCL4 (MIP-1β) and CCL5 (RANTES), but we detected no induction of microglial apoptosis. In contrast, SH-SY5Y (SY) neuroblastoma cells co-cultured with B. burgdorferi expressed negligible amounts of inflammatory mediators and also remained resistant to apoptosis. When SY cells were co-cultured with microglia and B. burgdorferi, significant neuronal apoptosis consistently occurred. Confocal microscopy imaging of these cell cultures stained for apoptosis and with cell type-specific markers confirmed that it was predominantly the SY cells that were dying. Microarray analysis demonstrated an intense microglia-mediated inflammatory response to B. burgdorferi including up-regulation in gene transcripts for TLR-2 and NFκβ. Surprisingly, a pathway that exhibited profound changes in regard to inflammatory signaling was triggering receptor expressed on myeloid cells-1 (TREM1). Significant transcript alterations in essential p53 pathway genes also occurred in SY cells cultured in the presence of microglia and B. burgdorferi, which indicated a shift from cell survival to preparation for apoptosis when compared to SY cells cultured in the presence of B. burgdorferi alone. Taken together, these findings indicate that B. burgdorferi is not directly toxic to SY cells; rather, these cells become distressed and die in the inflammatory surroundings generated by microglia through a bystander effect. If, as we hypothesized, neuronal apoptosis is the key pathogenic event in Lyme neuroborreliosis, then targeting microglial responses may be a significant therapeutic approach for the treatment of this form of Lyme disease
- …