271 research outputs found
Unique activities of two overlapping PAX6 retinal enhancers
Enhancers play a critical role in development by precisely modulating spatial, temporal, and cell type-specific gene expression. Sequence variants in enhancers have been implicated in diseases; however, establishing the functional consequences of these variants is challenging because of a lack of understanding of precise cell types and developmental stages where the enhancers are normally active. PAX6 is the master regulator of eye development, with a regulatory landscape containing multiple enhancers driving the expression in the eye. Whether these enhancers perform additive, redundant or distinct functions is unknown. Here, we describe the precise cell types and regulatory activity of two PAX6 retinal enhancers, HS5 and NRE. Using a unique combination of live imaging and single-cell RNA sequencing in dual enhancer-reporter zebrafish embryos, we uncover differences in the spatiotemporal activity of these enhancers. Our results show that although overlapping, these enhancers have distinct activities in different cell types and therefore likely nonredundant functions. This work demonstrates that unique cell type-specific activities can be uncovered for apparently similar enhancers when investigated at high resolution in vivo
Revealing the news: How online news changes without you noticing
This paper describes an ongoing design project relating to online news and how alterations to news stories are hidden from the reader. As the delivery and consumption of news content online continues to overtake other channels in reader numbers and market penetration, so methods of transparency and reliability developed over centuries continue also to be tested by digital media. We have conducted content analysis on existing stories and examined how news organisations and channels handle rapidly evolving news stories. We have proceeded to develop low-fidelity prototypes and an interaction model to test our design approach. The outcomes are in production and will result in a digital artifact that reveals editorial changes to news items (the News Inspector). These changes will be made visible within the browser. The implications of the project relate to the wider question of news truth-telling, trust and online news credibility
Search for rare and forbidden decays of charm and charmed-strange mesons to final states h^+- e^-+ e^+
We have searched for flavor-changing neutral current decays and
lepton-number-violating decays of D^+ and D^+_s mesons to final states of the
form h^+- e^-+ e^+, where h is either \pi or K. We use the complete samples of
CLEO-c open-charm data, corresponding to integrated luminosities of 818 pb^-1
at the center-of-mass energy E_CM = 3.774 GeV containing 2.4 x 10^6 D^+D^-
pairs and 602 pb^-1 at E_CM = 4.170 GeV containing 0.6 x 10^6 D^*+-_s D^-+_s
pairs. No signal is observed in any channel, and we obtain 90% confidence level
upper limits on branching fractions B(D^+ --> \pi^+ e^+ e^-) < 5.9 x 10^-6,
B(D^+ --> \pi^- e^+ e^+) K^+ e^+ e^-) < 3.0 x 10^-6,
B(D^+ --> K^- e^+ e^+) \pi^+ e^+ e^-) < 2.2 x 10^-5,
B(D^+_s --> \pi^- e^+ e^+) K^+ e^+ e^-) < 5.2 x
10^-5, and B(D^+_s --> K^- e^+ e^+) < 1.7 x 10^-5.Comment: 9 pages, available through http://www.lns.cornell.edu/public/CLNS
Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial
Background
Whole brain radiotherapy (WBRT) and dexamethasone are widely used to treat brain metastases from
non-small cell lung cancer (NSCLC), although there have been no randomised clinical trials showing that WBRT
improves either quality of life or overall survival. Even after treatment with WBRT, the prognosis of this patient group
is poor. We aimed to establish whether WBRT could be omitted without a signifi cant eff ect on survival or quality of life.
Methods
The Quality of Life after Treatment for Brain Metastases (QUARTZ) study is a non-inferiority, phase 3
randomised trial done at 69 UK and three Australian centres. NSCLC patients with brain metastases unsuitable for
surgical resection or stereotactic radiotherapy were randomly assigned (1:1) to optimal supportive care (OSC)
including dexamethasone plus WBRT (20 Gy in five daily fractions) or OSC alone (including dexamethasone). The
dose of dexamethasone was determined by the patients’ symptoms and titrated downwards if symptoms improved.
Allocation to treatment group was done by a phone call from the hospital to the Medical Research Council Clinical
Trials Unit at University College London using a minimisation programme with a random element and stratifi cation
by centre, Karnofsky Performance Status (KPS), gender, status of brain metastases, and the status of primary lung
cancer. The primary outcome measure was quality-adjusted life-years (QALYs). QALYs were generated from overall
survival and patients’ weekly completion of the EQ-5D questionnaire. Treatment with OSC alone was considered noninferior
if it was no more than 7 QALY days worse than treatment with WBRT plus OSC, which required 534 patients
(80% power, 5% [one-sided] signifi cance level). Analysis was done by intention to treat for all randomly assigned
patients. The trial is registered with ISRCTN, number ISRCTN3826061.
Findings
Between March 2, 2007, and Aug 29, 2014, 538 patients were recruited from 69 UK and three Australian
centres, and were randomly assigned to receive either OSC plus WBRT (269) or OSC alone (269). Baseline characteristics
were balanced between groups, and the median age of participants was 66 years (range 38–85). Signifi cantly more
episodes of drowsiness, hair loss, nausea, and dry or itchy scalp were reported while patients were receiving WBRT,
although there was no evidence of a difference in the rate of serious adverse events between the two groups. There was
no evidence of a diff erence in overall survival (hazard ratio 1·06, 95% CI 0·90–1·26), overall quality of life, or
dexamethasone use between the two groups. The diff erence between the mean QALYs was 4·7 days (46·4 QALY days
for the OSC plus WBRT group vs 41·7 QALY days for the OSC group), with two-sided 90% CI of –12·7 to 3·3.
Interpretation
Although the primary outcome measure result includes the prespecifi ed non-inferiority margin, the
combination of the small diff erence in QALYs and the absence of a diff erence in survival and quality of life between
the two groups suggests that WBRT provides little additional clinically signifi cant benefi t for this patient group
Higher-order multipole amplitudes in charmonium radiative transitions
Using 24 million decays in CLEO-c, we have searched
for higher multipole admixtures in electric-dipole-dominated radiative
transitions in charmonia. We find good agreement between our data and
theoretical predictions for magnetic quadrupole (M2) amplitudes in the
transitions and ,
in striking contrast to some previous measurements. Let and
denote the normalized M2 amplitudes in the respective aforementioned decays,
where the superscript refers to the angular momentum of the . By
performing unbinned maximum likelihood fits to full five-parameter angular
distributions, we determine the ratios and , where
the theoretical predictions are independent of the charmed quark magnetic
moment and are and .Comment: 32 pages, 7 figures, acceptance updat
Investigating Children’s Spiritual Experiences through the Health and Physical Education (HPE) Learning Area in Australian Schools
Impending Regeneration Failure of the IUCN Vulnerable Borneo Ironwood (Eusideroxylon zwageri)
The regeneration of many climax species in tropical forest critically depends on adequate seed dispersal and seedling establishment. Here, we report the decreased abundance and increased spatial aggregation of younger trees of the Borneo ironwood (Eusideroxylon zwageri) in a protected forest in Sabah Malaysia. We observed a high level of seedling herbivory with strong density dependence, likely exacerbated by local aggregation and contributing to the progressively shrinking size distribution. We also note the largely undocumented selective herbivory by sambar deer on E. zwageri seedlings. This study highlights the combined impact of altered megafauna community on a tree population through interlinked ecological processes and the need for targeted conservation intervention for this iconic tropical tree species
Fortified Settlements of the 9th and 10th Centuries ad in Central Europe: structure, function and symbolism
Open access article. © Society for Medieval Archaeology 2012.The structure, function(s)and symbolism of early medieval (9th-10th centuries ad) fortified settlements from central Europe, in particular today's Austria, Hungary, Czech Republic and Slovakia, are examined in this paper. It offers an overview of the current state of research together with new insights based on analysis of the site of Gars-Thunau in Lower Austria. Special emphasis is given to the position of the fortified sites in the landscape, to the elements of the built environment and their spatial organisation, as well as to graves within the fortified area. The region under study was situated on the SE border of the Carolingian (and later the Ottonian) Empire, with some of the discussed sites lying in the territory of the 'Great Moravian Empire' in the 9th and 10th centuries. These sites can therefore provide important comparative data for researchers working in other parts of the Carolingian Empire and neighbouring regions.Alexander von Humboldt
FoundationAustrian Science Fun
Search for CP violation in decays
A model-independent search for direct CP violation in the Cabibbo suppressed
decay in a sample of approximately 370,000 decays is
carried out. The data were collected by the LHCb experiment in 2010 and
correspond to an integrated luminosity of 35 pb. The normalized Dalitz
plot distributions for and are compared using four different
binning schemes that are sensitive to different manifestations of CP violation.
No evidence for CP asymmetry is found.Comment: 13 pages, 8 figures, submitted to Phys. Rev.
First observation of the decay and a measurement of the ratio of branching fractions
The first observation of the decay using
data collected by the LHCb detector at a centre-of-mass energy of 7 TeV,
corresponding to an integrated luminosity of 36 pb, is reported. A
signal of events is obtained and the absence of signal is
rejected with a statistical significance of more than nine standard deviations.
The branching fraction is measured relative to
that of : , where the first uncertainty is statistical, the second systematic and
the third is due to the uncertainty on the ratio of the and
hadronisation fractions.Comment: 10 pages, 3 figures, submitted to Phys. Lett. B; ISSN 0370-269
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