Correlation of ICME magnetic fields at radially aligned spacecraft

The magnetic field structures of two interplanetary coronal mass ejections (ICMEs), each observed by a pair of spacecraft close to radial alignment, have been analysed. The ICMEs were observed in situ by MESSENGER and STEREO-B in November 2010 and November 2011, while the spacecraft were separated by more than 0.6 AU in heliocentric distance, less than 4° in heliographic longitude, and less than 7° in heliographic latitude. Both ICMEs took approximately two days to travel between the spacecraft. The ICME magnetic field profiles observed at MESSENGER have been mapped to the heliocentric distance of STEREO-B and compared directly to the profiles observed by STEREO-B. Figures that result from this mapping allow for easy qualitative assessment of similarity in the profiles. Macroscale features in the profiles that varied on timescales of one hour, and which corresponded to the underlying flux rope structure of the ICMEs, were well correlated in the solar east–west and north–south directed components, with Pearson’s correlation coefficients of approximately 0.85 and 0.95, respectively; microscale features with timescales of one minute were uncorrelated. Overall correlation values in the profiles of one ICME were increased when an apparent change in the flux rope axis direction between the observing spacecraft was taken into account. The high degree of similarity seen in the magnetic field profiles may be interpreted in two ways. If the spacecraft sampled the same region of each ICME (i.e. if the spacecraft angular separations are neglected), the similarity indicates that there was little evolution in the underlying structure of the sampled region during propagation. Alternatively, if the spacecraft observed different, nearby regions within the ICMEs, it indicates that there was spatial homogeneity across those different regions. The field structure similarity observed in these ICMEs points to the value of placing in situ space weather monitors well upstream of the Earth

Quantum fields during black hole formation: how good an approximation is the Unruh state?

We study the quantum effects of a test Klein-Gordon field in a Vaidya space-time consisting of a collapsing null shell that forms a Schwazschild black hole, by explicitly obtaining, in a (1 + 1)-dimensional model, the Wightman function, the renormalised stress-energy tensor, and by analysing particle detector rates along stationary orbits in the exterior black hole region, and make a comparison with the folklore that the Unruh state is the state that emerges from black hole formation. In the causal future of the shell, we find a negative ingoing flux at the horizon that agrees precisely with the Unruh state calculation, and is the source of black hole radiation, while in the future null infinity we find that the radiation flux output in the Unruh state is an upper bound for the positive outgoing flux in the collapsing null shell spacetime. This indicates that back-reaction estimates based on Unruh state calculations over-estimate the energy output carried by so-called pre-Hawking radiation. The value of the output predicted by the Unruh state is however approached exponentially fast. Finally, we find that at late times, stationary observers in the exterior black hole region in the collapsing shell spacetime detect the local Hawking temperature, which is also well characterised by the Unruh state, coming from right-movers. Early-time discrepancies between the detector rates for the Unruh state and for the state in the collapsing shell spacetime are explored numerically

Fast 3D shape screening of large chemical databases through alignment-recycling

<p>Abstract</p> <p>Background</p> <p>Large chemical databases require fast, efficient, and simple ways of looking for similar structures. Although such tasks are now fairly well resolved for graph-based similarity queries, they remain an issue for 3D approaches, particularly for those based on 3D shape overlays. Inspired by a recent technique developed to compare molecular shapes, we designed a hybrid methodology, alignment-recycling, that enables efficient retrieval and alignment of structures with similar 3D shapes.</p> <p>Results</p> <p>Using a dataset of more than one million PubChem compounds of limited size (< 28 heavy atoms) and flexibility (< 6 rotatable bonds), we obtained a set of a few thousand diverse structures covering entirely the 3D shape space of the conformers of the dataset. Transformation matrices gathered from the overlays between these diverse structures and the 3D conformer dataset allowed us to drastically (100-fold) reduce the CPU time required for shape overlay. The alignment-recycling heuristic produces results consistent with <it>de novo </it>alignment calculation, with better than 80% hit list overlap on average.</p> <p>Conclusion</p> <p>Overlay-based 3D methods are computationally demanding when searching large databases. Alignment-recycling reduces the CPU time to perform shape similarity searches by breaking the alignment problem into three steps: selection of diverse shapes to describe the database shape-space; overlay of the database conformers to the diverse shapes; and non-optimized overlay of query and database conformers using common reference shapes. The precomputation, required by the first two steps, is a significant cost of the method; however, once performed, querying is two orders of magnitude faster. Extensions and variations of this methodology, for example, to handle more flexible and larger small-molecules are discussed.</p

A case study of bovine tuberculosis in an area of County Donegal, Ireland

A descriptive analysis, to investigate the potential risk factors that might have contributed to the increased incidence of bovine tuberculosis (BTB) herd-breakdowns in the reference area of Co. Donegal during the fifth year of the four-area project (FAP), was performed. Seventy two different herds were restricted for BTB during the FAP; 10 of these herds were restricted twice, resulting in a total of 82 BTB breakdowns. During the first four years of the FAP, the number of BTB herd breakdowns in the area varied from a lowest of nine to a maximum of 18 per year, and were geographically dispersed. In the fifth year of the study a considerable increase in the number of BTB breakdowns (n = 32) was observed, and there was a spatial 'cluster' of infected herds in the eastern part of the study area. The increased number of BTB breakdowns during the fifth year most likely occurred because of the recrudescence of infection, herd-to-herd transmission and, to a lesser extent, purchase of infected cattle. Infected badgers remain as a possible but less likely source of infection, especially as an explanation for the cluster of infected herds. The analysis supports the hypothesis that BTB in herds is a problem that cannot be addressed successfully by dedicating our efforts to the elimination of single risk factors. Neither is it a problem that needs to be investigated only at the herd level, but rather at the area level, including groups of contiguous herds

Translation invariant extensions of finite volume measures

We investigate the following questions: Given a measure μΛ on configurations on a subset Λ of a lattice L, where a configuration is an element of ΩΛ for some fixed set Ω, does there exist a measure μ on configurations on all of L, invariant under some specified symme- try group of L, such that μΛ is its marginal on configurations on Λ? When the answer is yes, what are the properties, e.g., the entropies, of such measures? Our primary focus is the case in which L = Zd and the symmetries are the translations. For the case in which Λ is an interval in Z we give a simple necessary and sufficient condition, local translation invariance (LTI), for extendibility. For LTI measures we construct extensions having maximal entropy, which we show are Gibbs measures; this construction extends to the case in which L is the Bethe lattice. On Z we also consider extensions supported on periodic configurations, which are analyzed using de Bruijn graphs and which include the extensions with minimal entropy. When Λ ⊂ Z is not an interval, or when Λ ⊂ Zd with d > 1, the LTI condition is necessary but not sufficient for extendibility. For Zd with d > 1, extendibility is in some sense undecidable

Optimal assignment methods for ligand-based virtual screening

<p>Abstract</p> <p>Background</p> <p>Ligand-based virtual screening experiments are an important task in the early drug discovery stage. An ambitious aim in each experiment is to disclose active structures based on new scaffolds. To perform these "scaffold-hoppings" for individual problems and targets, a plethora of different similarity methods based on diverse techniques were published in the last years. The optimal assignment approach on molecular graphs, a successful method in the field of quantitative structure-activity relationships, has not been tested as a ligand-based virtual screening method so far.</p> <p>Results</p> <p>We evaluated two already published and two new optimal assignment methods on various data sets. To emphasize the "scaffold-hopping" ability, we used the information of chemotype clustering analyses in our evaluation metrics. Comparisons with literature results show an improved early recognition performance and comparable results over the complete data set. A new method based on two different assignment steps shows an increased "scaffold-hopping" behavior together with a good early recognition performance.</p> <p>Conclusion</p> <p>The presented methods show a good combination of chemotype discovery and enrichment of active structures. Additionally, the optimal assignment on molecular graphs has the advantage to investigate and interpret the mappings, allowing precise modifications of internal parameters of the similarity measure for specific targets. All methods have low computation times which make them applicable to screen large data sets.</p

The emerging landscape of health research based on biobanks linked to electronic health records: Existing resources, statistical challenges, and potential opportunities

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154448/1/sim8445_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154448/2/sim8445.pd

Post-Translational Modifications Modulate Ligand Recognition by the Third PDZ Domain of the MAGUK Protein PSD-95

The relative promiscuity of hub proteins such as postsynaptic density protein-95 (PSD-95) can be achieved by alternative splicing, allosteric regulation, and post-translational modifications, the latter of which is the most efficient method of accelerating cellular responses to environmental changes in vivo. Here, a mutational approach was used to determine the impact of phosphorylation and succinimidation post-translational modifications on the binding affinity of the postsynaptic density protein-95/discs large/zonula occludens-1 (PDZ3) domain of PSD-95. Molecular dynamics simulations revealed that the binding affinity of this domain is influenced by an interplay between salt-bridges linking the α3 helix, the β2–β3 loop and the positively charged Lys residues in its high-affinity hexapeptide ligand KKETAV. The α3 helix is an extra structural element that is not present in other PDZ domains, which links PDZ3 with the following SH3 domain in the PSD-95 protein. This regulatory mechanism was confirmed experimentally via thermodynamic and NMR chemical shift perturbation analyses, discarding intra-domain long-range effects. Taken together, the results presented here reveal the molecular basis of the regulatory role of the α3 extra-element and the effects of post-translational modifications of PDZ3 on its binding affinity, both energetically and dynamically.This research was supported by grants CVI-05915, from the Andalusian Regional Government (http://www.juntadeandalucia.es), BIO2009-13261-C02 and BIO2012-39922-C02, from the Spanish Ministry of Science and Innovation (http://www.idi.mineco.gob.es/portal/site​/MICINN/) and FEDER. JMC received a postdoctoral contract from the Spanish Ministry of Science and Innovation. CCV was a recipient of a Formación de Personal Investigador fellowship from the Spanish Ministry of Science and Innovation

Defective Peripheral Nerve Development Is Linked to Abnormal Architecture and Metabolic Activity of Adipose Tissue in Nscl-2 Mutant Mice

BACKGROUND: In mammals the interplay between the peripheral nervous system (PNS) and adipose tissue is widely unexplored. We have employed mice, which develop an adult onset of obesity due to the lack the neuronal specific transcription factor Nscl-2 to investigate the interplay between the nervous system and white adipose tissue (WAT). METHODOLOGY: Changes in the architecture and innervation of WAT were compared between wildtype, Nscl2-/-, ob/ob and Nscl2-/-//ob/ob mice using morphological methods, immunohistochemistry and flow cytometry. Metabolic alterations in mutant mice and in isolated cells were investigated under basal and stimulated conditions. PRINCIPAL FINDINGS: We found that Nscl-2 mutant mice show a massive reduction of innervation of white epididymal and paired subcutaneous inguinal fat tissue including sensory and autonomic nerves as demonstrated by peripherin and neurofilament staining. Reduction of innervation went along with defects in the formation of the microvasculature, accumulation of cells of the macrophage/preadipocyte lineage, a bimodal distribution of the size of fat cells, and metabolic defects of isolated adipocytes. Despite a relative insulin resistance of white adipose tissue and isolated Nscl-2 mutant adipocytes the serum level of insulin in Nscl-2 mutant mice was only slightly increased. CONCLUSIONS: We conclude that the reduction of the innervation and vascularization of WAT in Nscl-2 mutant mice leads to the increase of preadipocyte/macrophage-like cells, a bimodal distribution of the size of adipocytes in WAT and an altered metabolic activity of adipocytes