1,569 research outputs found
Joint Load Balancing and Interference Management for Small-Cell Heterogeneous Networks with Limited Backhaul Capacity
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Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity.
Developmental enhancers integrate graded concentrations of transcription factors (TFs) to create sharp gene expression boundaries. Here we examine the hunchback P2 (HbP2) enhancer which drives a sharp expression pattern in the Drosophila blastoderm embryo in response to the transcriptional activator Bicoid (Bcd). We systematically interrogate cis and trans factors that influence the shape and position of expression driven by HbP2, and find that the prevailing model, based on pairwise cooperative binding of Bcd to HbP2 is not adequate. We demonstrate that other proteins, such as pioneer factors, Mediator and histone modifiers influence the shape and position of the HbP2 expression pattern. Comparing our results to theory reveals how higher-order cooperativity and energy expenditure impact boundary location and sharpness. Our results emphasize that the bacterial view of transcription regulation, where pairwise interactions between regulatory proteins dominate, must be reexamined in animals, where multiple molecular mechanisms collaborate to shape the gene regulatory function
Clinical translation of positive metastases identified on prostate-specific membrane antigen positron emission tomography/computed tomography imaging in the management of de novo synchronous oligometastatic prostate cancer
Recent randomised evidence supports the diagnostic superiority of prostate-specific membrane antigen (PSMA) PET/CT, over conventional imaging, in the detection of distant occult metastasis in men with newly diagnosed high-risk prostate cancer. This may result in a rise in the detection of de novo synchronous hormone-sensitive âoligometastaticâ prostate cancer. We outline the evidence supporting PSMA PET/CT imaging in primary staging. We also discuss the translation of positive areas, with a high probability of distant metastasis, into clinical therapeutic targets for metastasis-directed interventions. Finally, we highlight the role of PSMA PET/CT as an imaging biomarker. This may have future utility in disease monitoring and prediction of response to systemic, local cytoreductive and metastasis-directed interventions. Patient Summary: A new whole-body scan can accurately detect cancer deposits, in men in whom distant prostate cancer spread is suspected. This may be useful to monitor and predict response to drug therapy, treatments to the prostate and cancer deposits
Artificial intelligence and ambient intelligence
Ambient intelligence (AmI) is intrinsically and thoroughly connected with artificial intelligence (AI). Some even say that it is, in essence, AI in the environment. AI, on the other hand, owes its success to the phenomenal development of the information and communication technologies (ICTs), based on principles such as Mooreâs law. In this paper we give an overview of the progress in AI and AmI interconnected with ICT through information-society laws, superintelligence, and several related disciplines, such as multi-agent systems and the Semantic Web, ambient assisted living and e-healthcare, AmI for assisting medical diagnosis, ambient intelligence for e-learning and ambient intelligence for smart cities. Besides a short history and a description of the current state, the frontiers and the future of AmI and AI are also considered in the paper
Implication of Genetic Variants Near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in Type 2 Diabetes and Obesity in 6,719 Asians
OBJECTIVEâ Recent genome-wide association studies have identified six novel genes for type 2 diabetes and obesity and confirmed TCF7L2 as the major type 2 diabetes gene to date in Europeans. However, the implications of these genes in Asians are unclear
Surveillance of emerging drugs of abuse in Hong Kong: Validation of an analytical tool
Ă© 2015, Hong Kong Academy of Medicine Press. All rights reserved. Objective: To validate a locally developed chromatography-based method to monitor emerging drugs of abuse whilst performing regular drug testing in abusers. Design: Cross-sectional study. Setting: Eleven regional hospitals, seven social service units, and a tertiary level clinical toxicology laboratory in Hong Kong. Participants: A total of 972 drug abusers and high-risk individuals were recruited from acute, rehabilitation, and high-risk settings between 1 November 2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity. In total, 2000 urine or hair specimens were collected. Main outcome measures: Proof of concept that surveillance of emerging drugs of abuse can be performed whilst conducting routine drug of abuse testing in patients. Results: The method was successfully applied to 2000 samples with three emerging drugs of abuse detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3-trifluoromethylphenyl)piperazine], and methcathinone. The method also detected conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine, and ketamine being the most frequently detected drugs. Other findings included the observation that South Asians had significantly higher rates of using opiates such as heroin, methadone, and codeine; and that ketamine and cocaine had significantly higher detection rates in acute subjects compared with the rehabilitation population. Conclusions: This locally developed analytical method is a valid tool for simultaneous surveillance of emerging drugs of abuse and routine drug monitoring of patients at minimal additional cost and effort. Continued, proactive surveillance and early identification of emerging drugs will facilitate prompt clinical, social, and legislative management.Link_to_subscribed_fulltex
Generating Robust and Informative Nonclinical In Vitro and In Vivo Bacterial Infection Model Efficacy Data To Support Translation to Humans
H.E.S.S. observations of gamma-ray bursts in 2003-2007
Very-high-energy (VHE; >~100 GeV) gamma-rays are expected from gamma-ray
bursts (GRBs) in some scenarios. Exploring this photon energy regime is
necessary for understanding the energetics and properties of GRBs. GRBs have
been one of the prime targets for the H.E.S.S. experiment, which makes use of
four Imaging Atmospheric Cherenkov Telescopes (IACTs) to detect VHE gamma-rays.
Dedicated observations of 32 GRB positions were made in the years 2003-2007 and
a search for VHE gamma-ray counterparts of these GRBs was made. Depending on
the visibility and observing conditions, the observations mostly start minutes
to hours after the burst and typically last two hours. Results from
observations of 22 GRB positions are presented and evidence of a VHE signal was
found neither in observations of any individual GRBs, nor from stacking data
from subsets of GRBs with higher expected VHE flux according to a
model-independent ranking scheme. Upper limits for the VHE gamma-ray flux from
the GRB positions were derived. For those GRBs with measured redshifts,
differential upper limits at the energy threshold after correcting for
absorption due to extra-galactic background light are also presented.Comment: 9 pages, 4 tables, 3 figure
Discovery of VHE gamma-rays from the high-frequency-peaked BL Lac object RGB J0152+017
Aims: The BL Lac object RGB J0152+017 (z=0.080) was predicted to be a very
high-energy (VHE; > 100 GeV) gamma-ray source, due to its high X-ray and radio
fluxes. Our aim is to understand the radiative processes by investigating the
observed emission and its production mechanism using the High Energy
Stereoscopic System (H.E.S.S.) experiment. Methods: We report recent
observations of the BL Lac source RGB J0152+017 made in late October and
November 2007 with the H.E.S.S. array consisting of four imaging atmospheric
Cherenkov telescopes. Contemporaneous observations were made in X-rays by the
Swift and RXTE satellites, in the optical band with the ATOM telescope, and in
the radio band with the Nancay Radio Telescope. Results: A signal of 173
gamma-ray photons corresponding to a statistical significance of 6.6 sigma was
found in the data. The energy spectrum of the source can be described by a
powerlaw with a spectral index of 2.95+/-0.36stat+/-0.20syst. The integral flux
above 300 GeV corresponds to ~2% of the flux of the Crab nebula. The source
spectral energy distribution (SED) can be described using a two-component
non-thermal synchrotron self-Compton (SSC) leptonic model, except in the
optical band, which is dominated by a thermal host galaxy component. The
parameters that are found are very close to those found in similar SSC studies
in TeV blazars. Conclusions: RGB J0152+017 is discovered as a source of VHE
gamma-rays by H.E.S.S. The location of its synchrotron peak, as derived from
the SED in Swift data, allows clearly classification it as a
high-frequency-peaked BL Lac (HBL).Comment: Accepted for publication in A&A Letters (5 pages, 4 figures
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