9,953 research outputs found
Determining rotational dynamics of the guanidino group of arginine side chains in proteins by carbon-detected NMR
Arginine residues are imperative for many active sites and protein-interaction interfaces. A new NMR-based method is presented to determine the rotational dynamics around the Nε-Cζ bond of arginine side chains. An application to a 19 kDa protein shows that the strengths of interactions involving arginine side chains can be characterised
A framework for the simulation of regional decadal variability for agricultural and other applications
The SimGen software, including ancillary files and scripts, can be found at http://iri.columbia.edu/~amg/CCAFS/simgen/Climate prediction on decadal time scales is currently an active area of research. Although there are indications that predictions from dynamical models may have skill in some regions, assessment of this skill is still underway, and reliable model-based predictions of regional ‘near-term’ climate change, particularly for terrestrial regions, have not yet been demonstrated. Given the absence of such forecasts, synthetic data sequences that capture the statistical properties of observed near-term climate variability have potential value. Incorporation of a climate change component in such sequences can aid in estimating likelihoods for a range of climatic stresses, perhaps lying outside the range of past experience. Such simulations can be used to drive agricultural, hydrological or other application models, enabling resilience testing of adaptation or decision systems. The use of statistically-based methods enables the efficient generation of a large ensemble of synthetic sequences as well as the creation of well-defined probabilistic risk estimates. In this report we discuss procedures for the generation of synthetic climate sequences that incorporate both the statistics of observed variability and expectations regarding future regional climate change. Model fitting and simulation are conditioned by requirements particular to the decadal climate problem. A method for downscaling annualized simulations to the daily time step while preserving both spatial and temporal subannual statistical properties is presented and other possible methods discussed. A ‘case-study’ realization of the proposed framework is described
Sustainability performance measurement : a preliminary classification framework of models and indicators
In this position paper we focus on the diversity of sustainability measurements. Based on existing research on performance measurement, we propose a preliminary classification framework summarizing sustainability models and indicators. By describing illustrative examples, we claim that several models and indicators can be distinguished with their own peculiarities. Having such a framework is interesting for both academia and business to structure the range of models and indicators and to ultimately select the appropriate sustainability measurement approach. The proposed framework should be validated by further research
Symmetries of degenerate center singularities of plane vector fields
Let be a closed unit -disk on the plane centered at the origin ,
and be a smooth vector field such that is a unique singular point of
and all other orbits of are simple closed curves wrapping once around
. Thus topologically is a "center" singularity. Let also
be the group of all diffeomorphisms of which preserve
orientation and orbits of . In arXiv:0907.0359 the author described the
homotopy type of under assumption that the -jet of at
is non-degenerate. In this paper degenerate case is considered. Under
additional "non-degeneracy assumptions" on the path components of
with respect to distinct weak topologies are described.Comment: 21 page, 3 figure
The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer
The significance of the inter-relationship between tumour and host local/systemic inflammatory responses in primary operable invasive breast cancer is limited. The inter-relationship between the systemic inflammatory response (pre-operative white cell count, C-reactive protein and albumin concentrations), standard clinicopathological factors, tumour T-lymphocytic (CD4+ and CD8+) and macrophage (CD68+) infiltration, proliferative (Ki-67) index and microvessel density (CD34+) was examined using immunohistochemistry and slide-counting techniques, and their prognostic values were examined in 168 patients with potentially curative resection of early-stage invasive breast cancer. Increased tumour grade and proliferative activity were associated with greater tumour T-lymphocyte (P<0.05) and macrophage (P<0.05) infiltration and microvessel density (P<0.01). The median follow-up of survivors was 72 months. During this period, 31 patients died; 18 died of their cancer. On univariate analysis, increased lymph-node involvement (P<0.01), negative hormonal receptor (P<0.10), lower albumin concentrations (P<0.01), increased tumour proliferation (P<0.05), increased tumour microvessel density (P<0.05), the extent of locoregional control (P<0.0001) and limited systemic treatment (Pless than or equal to0.01) were associated with cancer-specific survival. On multivariate analysis of these significant covariates, albumin (HR 4.77, 95% CI 1.35–16.85, P=0.015), locoregional treatment (HR 3.64, 95% CI 1.04–12.72, P=0.043) and systemic treatment (HR 2.29, 95% CI 1.23–4.27, P=0.009) were significant independent predictors of cancer-specific survival. Among tumour-based inflammatory factors, only tumour microvessel density (P<0.05) was independently associated with poorer cancer-specific survival. The host inflammatory responses are closely associated with poor tumour differentiation, proliferation and malignant disease progression in breast cancer
Three Dimensional Electrical Impedance Tomography
The electrical resistivity of mammalian tissues varies widely and is correlated with physiological
function. Electrical impedance tomography (EIT) can be used to probe such variations in vivo, and offers a
non-invasive means of imaging the internal conductivity distribution of the human body. But the
computational complexity of EIT has severe practical limitations, and previous work has been restricted to
considering image reconstruction as an essentially two-dimensional problem. This simplification can limit
significantly the imaging capabilities of EIT, as the electric currents used to determine the conductivity variations will not in general be confined to a two-dimensional plane. A few studies have attempted three-dimensional EIT image reconstruction, but have not yet succeeded in generating images of a quality suitable for clinical applications. Here we report the development of a three-dimensional EIT system with greatly improved imaging capabilities, which combines our 64-electrode data-collection apparatus with customized matrix inversion techniques. Our results demonstrate the practical potential of EIT for clinical applications, such as lung or brain imaging and diagnostic screening
Regulation of caspase-3 processing by cIAP2 controls the switch between pro-inflammatory activation and cell death in microglia.
Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material.The activation of microglia, resident immune cells of the central nervous system, and inflammation-mediated neurotoxicity are typical features of neurodegenerative diseases, for example, Alzheimer's and Parkinson's diseases. An unexpected role of caspase-3, commonly known to have executioner role for apoptosis, was uncovered in the microglia activation process. A central question emerging from this finding is what prevents caspase-3 during the microglia activation from killing those cells? Caspase-3 activation occurs as a two-step process, where the zymogen is first cleaved by upstream caspases, such as caspase-8, to form intermediate, yet still active, p19/p12 complex; thereafter, autocatalytic processing generates the fully mature p17/p12 form of the enzyme. Here, we show that the induction of cellular inhibitor of apoptosis protein 2 (cIAP2) expression upon microglia activation prevents the conversion of caspase-3 p19 subunit to p17 subunit and is responsible for restraining caspase-3 in terms of activity and subcellular localization. We demonstrate that counteracting the repressive effect of cIAP2 on caspase-3 activation, using small interfering RNA targeting cIAP2 or a SMAC mimetic such as the BV6 compound, reduced the pro-inflammatory activation of microglia cells and promoted their death. We propose that the different caspase-3 functions in microglia, and potentially other cell types, reside in the active caspase-3 complexes formed. These results also could indicate cIAP2 as a possible therapeutic target to modulate microglia pro-inflammatory activation and associated neurotoxicity observed in neurodegenerative disorders
Combustion in thermonuclear supernova explosions
Type Ia supernovae are associated with thermonuclear explosions of white
dwarf stars. Combustion processes convert material in nuclear reactions and
release the energy required to explode the stars. At the same time, they
produce the radioactive species that power radiation and give rise to the
formation of the observables. Therefore, the physical mechanism of the
combustion processes, as reviewed here, is the key to understand these
astrophysical events. Theory establishes two distinct modes of propagation for
combustion fronts: subsonic deflagrations and supersonic detonations. Both are
assumed to play an important role in thermonuclear supernovae. The physical
nature and theoretical models of deflagrations and detonations are discussed
together with numerical implementations. A particular challenge arises due to
the wide range of spatial scales involved in these phenomena. Neither the
combustion waves nor their interaction with fluid flow and instabilities can be
directly resolved in simulations. Substantial modeling effort is required to
consistently capture such effects and the corresponding techniques are
discussed in detail. They form the basis of modern multidimensional
hydrodynamical simulations of thermonuclear supernova explosions. The problem
of deflagration-to-detonation transitions in thermonuclear supernova explosions
is briefly mentioned.Comment: Author version of chapter for 'Handbook of Supernovae,' edited by A.
Alsabti and P. Murdin, Springer. 24 pages, 4 figure
- …
