910 research outputs found
Information Gains from Cosmological Probes
In light of the growing number of cosmological observations, it is important
to develop versatile tools to quantify the constraining power and consistency
of cosmological probes. Originally motivated from information theory, we use
the relative entropy to compute the information gained by Bayesian updates in
units of bits. This measure quantifies both the improvement in precision and
the 'surprise', i.e. the tension arising from shifts in central values. Our
starting point is a WMAP9 prior which we update with observations of the
distance ladder, supernovae (SNe), baryon acoustic oscillations (BAO), and weak
lensing as well as the 2015 Planck release. We consider the parameters of the
flat CDM concordance model and some of its extensions which include
curvature and Dark Energy equation of state parameter . We find that,
relative to WMAP9 and within these model spaces, the probes that have provided
the greatest gains are Planck (10 bits), followed by BAO surveys (5.1 bits) and
SNe experiments (3.1 bits). The other cosmological probes, including weak
lensing (1.7 bits) and {} measures (1.7 bits), have contributed
information but at a lower level. Furthermore, we do not find any significant
surprise when updating the constraints of WMAP9 with any of the other
experiments, meaning that they are consistent with WMAP9. However, when we
choose Planck15 as the prior, we find that, accounting for the full
multi-dimensionality of the parameter space, the weak lensing measurements of
CFHTLenS produce a large surprise of 4.4 bits which is statistically
significant at the 8 level. We discuss how the relative entropy
provides a versatile and robust framework to compare cosmological probes in the
context of current and future surveys.Comment: 26 pages, 5 figure
Quantifying Tensions between CMB and Distance Datasets in Models with Free Curvature or Lensing Amplitude
Recent measurements of the Cosmic Microwave Background (CMB) by the Planck
Collaboration have produced arguably the most powerful observational evidence
in support of the standard model of cosmology, i.e. the spatially flat
CDM paradigm. In this work, we perform model selection tests to
examine whether the base CMB temperature and large scale polarization
anisotropy data from Planck 2015 (P15) prefer any of eight commonly used
one-parameter model extensions with respect to flat CDM. We find a
clear preference for models with free curvature, , or free
amplitude of the CMB lensing potential, . We also further develop
statistical tools to measure tension between datasets. We use a Gaussianization
scheme to compute tensions directly from the posterior samples using an
entropy-based method, the surprise, as well as a calibrated evidence ratio
presented here for the first time. We then proceed to investigate the
consistency between the base P15~CMB data and six other CMB and distance
datasets. In flat CDM we find a tension between the base
P15~CMB data and a distance ladder measurement, whereas the former are
consistent with the other datasets. In the curved CDM model we find
significant tensions in most of the cases, arising from the well-known low
power of the low- multipoles of the CMB data. In the flat CDM
model, however, all datasets are consistent with the base
P15~CMB observations except for the CMB lensing measurement, which remains in
significant tension. This tension is driven by the increased power of the CMB
lensing potential derived from the base P15~CMB constraints in both models,
pointing at either potentially unresolved systematic effects or the need for
new physics beyond the standard flat CDM model.Comment: 16 pages, 8 figures, 6 table
Biochemical Properties of a Decoy Oligodeoxynucleotide Inhibitor of STAT3 Transcription Factor.
Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics a genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. CS3D competitively inhibits STAT3 binding to target gene promoters, resulting in decreased expression of proteins that promote cellular proliferation and survival. Previous studies have demonstrated antitumor activity of CS3D in preclinical models of solid tumors. However, prior to entering human clinical trials, the efficiency of generating the CS3D molecule and its stability in biological fluids should be determined. CS3D is synthesized as a single-stranded ODN and must have its free ends ligated to generate the final cyclic form. In this study, we report a ligation efficiency of nearly 95 percent. The ligated CS3D demonstrated a half-life of 7.9 h in human serum, indicating adequate stability for intravenous delivery. These results provide requisite biochemical characterization of CS3D that will inform upcoming clinical trials
Is regulatory innovation fit for purpose? A case study of adaptive regulation for advanced biotherapeutics
The need to better balance the promotion of scientific and technological innovation with risk management for consumer protection has inspired several recent reforms attempting to make regulations more flexible and adaptive. The pharmaceutical sector has a long, established regulatory tradition, as well as a long history of controversies around how to balance incentives for needed therapeutic innovations and protecting patient safety. The emergence of disruptive biotechnologies has provided the occasion for regulatory innovation in this sector. This article investigates the regulation of advanced biotherapeutics in the European Union and shows that it presents several defining features of an adaptive regulation regime, notably institutionalized processes of planned adaptation that allow regulators to gather, generate, and mobilize new scientific and risk evidence about innovative products. However, our in-depth case analysis highlights that more attention needs to be paid to the consequences of the introduction of adaptive regulations, especially for critical stakeholders involved in this new regulatory ecosystem, the capacity and resource requirements placed on them to adapt, and the new tradeoffs they face. In addition, our analysis highlights a deficit in how we currently evaluate the performance and public value proposition of adaptive regulations vis-Ã -vis their stated goals and objectives
Liquid-liquid coexistence in the phase diagram of a fluid confined in fractal porous materials
Multicanonical ensemble sampling simulations have been performed to calculate
the phase diagram of a Lennard-Jones fluid embedded in a fractal random matrix
generated through diffusion limited cluster aggregation. The study of the
system at increasing size and constant porosity shows that the results are
independent from the matrix realization but not from the size effects. A
gas-liquid transition shifted with respect to bulk is found. On growing the
size of the system on the high density side of the gas-liquid coexistence curve
it appears a second coexistence region between two liquid phases. These two
phases are characterized by a different behaviour of the local density inside
the interconnected porous structure at the same temperature and chemical
potential.Comment: 5 pages, 4 figures. To be published in Europhys. Letter
Analisis Sistem Tanggap Darurat Kebakaran Di Container Yard 02 Terminal Petikemas PT. Pelabuhan Indonesia III (Persero) Semarang Tahun 2016
Container Yard PT. Pelabuhan Indonesia III Semarang is large port giving services on manual handling container. A fire at the container terminal can cause a great deal of loss as it affects a high value of asset, work process and employment opportunities. One of the effort to decrease the risk and impact due to the fire is the emergency response system. One of efforts to reduce the risk and impact caused by the fires is require the application of non-structural mitigation in multi-storey office building. The purpose of the study is to analyze the emergency response system in the effort to prevent and control a fire disaster at terminal Container Yard 02. This research is a Descriptive Qualitative research with in-depth interviews and yard observation. The subjects of this study consists of 5 people as the main informants and 3 people as informant triangulation. The results show that the management has the commitment and written policy for Occupational Safety and Health, dated and certified by the highest leader atau level. Fire drills training are given to all staffs and the emergency response team. Container Yard 2 has all the facilities in active preventive fire such as APAR and hydrant and safety lives facilities that is the meeting point. The procedure taken in an emergency situation is the scenario in fire simulation. In emergency cases the communication system to inform and request help to the related parties is in place. The conclusion of this study is that in Terminal Container the emergency response is applied, such as fire simulation, socialization of the fire prevention policy and training on fire extinction and victim evacuation
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Epidermal growth factor receptor variant III mediates head and neck cancer cell invasion via STAT3 activation.
Epidermal growth factor receptor (EGFR) is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) where aberrant signaling downstream of this receptor contributes to tumor growth. EGFR variant III (EGFRvIII) is the most commonly altered form of EGFR and contains a truncated ligand-binding domain. We previously reported that EGFRvIII is expressed in up to 40% of HNSCC tumors where it is associated with increased proliferation, tumor growth and chemoresistance to antitumor drugs including the EGFR-targeting monoclonal antibody cetuximab. Cetuximab was FDA-approved in 2006 for HNSCC but has not been shown to prevent invasion or metastasis. This study was undertaken to evaluate the mechanisms of EGFRvIII-mediated cell motility and invasion in HNSCC. We found that EGFRvIII induced HNSCC cell migration and invasion in conjunction with increased signal transducer and activator of transcription 3 (STAT3) activation, which was not abrogated by cetuximab treatment. Further investigation showed that EGF-induced expression of the STAT3 target gene HIF1-α, was abolished by cetuximab in HNSCC cells expressing wild-type EGFR under hypoxic conditions, but not in EGFRvIII-expressing HNSCC cells. These results suggest that EGFRvIII mediates HNSCC cell migration and invasion by increased STAT3 activation and induction of HIF1-α, which contribute to cetuximab resistance in EGFRvIII-expressing HNSCC tumors
Modelling Magnetar Behaviour with 3D Magnetothermal Simulations
The observational properties of isolated NSs are shaped by their magnetic field and surface temperature. They evolve in a strongly coupled fashion, and modelling them is key in understanding the emission properties of NSs. Much effort was put in tackling this problem in the past but only recently a suitable 3D numerical framework was developed. We present a set of 3D simulations addressing both the long-Term evolution (≈ 104-106 yrs) and short-lived outbursts (â 1 yr). Not only a 3D approach allows one to test complex field geometries, but it is absolutely key to model magnetar outbursts, which observations associate to the appearance of small, inherently asymmetric hot regions. Even though the mechanism that triggers these phenomena is not completely understood, following the evolution of a localised heat injection in the crust serves as a model to study the unfolding of the event
Three-dimensional Modeling of the Magnetothermal Evolution of Neutron Stars: Method and Test Cases
Neutron stars harbor extremely strong magnetic fields within their solid outer crust. The topology of this field strongly influences the surface temperature distribution and, hence, the star's observational properties. In this work, we present the first realistic simulations of the coupled crustal magnetothermal evolution of isolated neutron stars in three dimensions accounting for neutrino emission, obtained with the pseudo-spectral code parody. We investigate both the secular evolution, especially in connection with the onset of instabilities during the Hall phase, and the short-term evolution following episodes of localized energy injection. Simulations show that a resistive tearing instability develops in about a Hall time if the initial toroidal field exceeds G. This leads to crustal failures because of the huge magnetic stresses coupled with the local temperature enhancement produced by dissipation. Localized heat deposition in the crust results in the appearance of hot spots on the star surface, which can exhibit a variety of patterns. Because the transport properties are strongly influenced by the magnetic field, the hot regions tend to drift away and get deformed following the magnetic field lines while cooling. The shapes obtained with our simulations are reminiscent of those recently derived from NICER X-ray observations of the millisecond pulsar PSR J0030+0451
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