Exact Site Percolation Thresholds Using the Site-to-Bond and Star-Triangle Transformations

I construct a two-dimensional lattice on which the inhomogeneous site percolation threshold is exactly calculable and use this result to find two more lattices on which the site thresholds can be determined. The primary lattice studied here, the ``martini lattice'', is a hexagonal lattice with every second site transformed into a triangle. The site threshold of this lattice is found to be $0.764826...$, while the others have $0.618034...$ and $1/\sqrt{2}$. This last solution suggests a possible approach to establishing the bound for the hexagonal site threshold, $p_c<1/\sqrt{2}$. To derive these results, I solve a correlated bond problem on the hexagonal lattice by use of the star-triangle transformation and then, by a particular choice of correlations, solve the site problem on the martini lattice.Comment: 12 pages, 10 figures. Submitted to Physical Review

Crystal structures of PI3K-C2α PX domain indicate conformational change associated with ligand binding

<p>Abstract</p> <p>Background</p> <p>PX domains have specialized protein structures involved in binding of phosphoinositides (PIs). Through binding to the various PIs PX domains provide site-specific membrane signals to modulate the intracellular localisation and biological activity of effector proteins. Several crystal structures of these domains are now available from a variety of proteins. All PX domains contain a canonical core structure with main differences exhibited within the loop regions forming the phosphoinositide binding pockets. It is within these areas that the molecular basis for ligand specificity originates.</p> <p>Results</p> <p>We now report two new structures of PI3K-C2α PX domain that crystallised in a P3₁21 space group. The two structures, refined to 2.1 Å and 2.5 Å, exhibit significantly different conformations of the phosphoinositide-binding loops. Unexpectedly, in one of the structures, we have detected a putative-ligand trapped in the binding site during the process of protein purification and crystallisation.</p> <p>Conclusion</p> <p>The two structures reported here provide a more complete description of the phosphoinositide binding region compared to the previously reported 2.6 Å crystal structure of human PI3K-C2α PX where this region was highly disordered. The structures enabled us to further analyse PI specificity and to postulate that the observed conformational change could be related to ligand-binding.</p

Extracellular DNA release from the genome-reduced pathogen Mycoplasma hyopneumoniae is essential for biofilm formation on abiotic surfaces

© 2018 The Author(s). Mycoplasma hyopneumoniae is an economically devastating, globally disseminated pathogen that can maintain a chronic infectious state within its host, swine. Here, we depict the events underpinning M. hyopneumoniae biofilm formation on an abiotic surface and demonstrate for the first time, biofilms forming on porcine epithelial cell monolayers and in the lungs of pigs, experimentally infected with M. hyopneumoniae. Nuclease treatment prevents biofilms forming on glass but not on porcine epithelial cells indicating that extracellular DNA (eDNA), which localises at the base of biofilms, is critical in the formation of these structures on abiotic surfaces. Subpopulations of M. hyopneumoniae cells, denoted by their ability to take up the dye TOTO-1 and release eDNA, were identified. A visually distinct sub-population of pleomorphic cells, that we refer to here as large cell variants (LCVs), rapidly transition from phase dark to translucent "ghost" cells. The translucent cells accumulate the membrane-impermeable dye TOTO-1, forming readily discernible membrane breaches immediately prior to lysis and the possible release of eDNA and other intracellular content (public goods) into the extracellular environment. Our novel observations expand knowledge of the lifestyles adopted by this wall-less, genome-reduced pathogen and provide further insights to its survival within farm environments and swine

The effect of inclusion of inlets in dual drainage modelling

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.In coupled sewer and surface flood modelling approaches, the flow process in gullies is often ignored although the overland flow is drained to sewer network via inlets and gullies. Therefore, the flow entering inlets is transferred to the sewer network immediately, which may lead to a different flood estimation than the reality. In this paper, we compared two modelling approach with and without considering the flow processes in gullies in the coupled sewer and surface modelling. Three historical flood events were adopted for model calibration and validation. The results showed that the inclusion of flow process in gullies can further improve the accuracy of urban flood modelling.The research is partially funded by the SINATRA project which is supported by the United Kingdom NERC Flooding from Intense Rainfall programme (grant NE/K008765/1)

Charm Quark Energy Loss in QCD Matter

The energy loss of heavy quarks in a quark-gluon plasma of finite size is studied within the light-cone integral approach. A simple analytical formulation of the radiative energy loss of heavy quarks is derived. This provides a convenient way to quantitatively estimate the quark energy loss. Our results show that if the energy of a heavy quark is much larger than its mass, the radiative energy loss approaches the radiative energy loss of light quarks.Comment: 4 pages, 2 figures. Accepted for publication in European Physical Journal

Predictive risk modelling of real-world wastewater network incidents

Due to growing pressure on wastewater network operators to deliver improved serviceability and lower costs to customers, there is a real need for greater understanding of the factors which influence incident rates, enabling effective prioritisation of proactive maintenance. This paper applies decision trees to investigate both static factors, such as sewer material and diameter, and derived factors, such as sewer velocity, for the prediction of blockages on the network of Dŵr Cymru Welsh Water. The results obtained illustrate the effectiveness of the proposed approach when identifying important explanatory factors and predicting sewers that are likely to block.Innovate UKDŵr Cymru Welsh Water (DCWW)University of Exeter’s Centre for Water Systems (CWS

An integrated framework for high-resolution urban flood modelling considering multiple information sources and urban features

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.High accuracy models are required for informed decision making in urban flood management. This paper develops a new holistic framework for using information collected from multiple sources for setting parameters of a 2D flood model. This illustrates the importance of identifying key urban features from the terrain data for capturing high resolution flood processes. A Cellular Automata based model CADDIES was used to simulate surface water flood inundation. Existing reports and flood photos obtained via social media were used to set model parameters and investigate different approaches for representing infiltration and drainage system capacity in urban flood modelling. The results of different approaches to processing terrain datasets indicate that the representation of urban micro-features is critical to the accuracy of modelling results. The constant infiltration approach is better than the rainfall reduction approach in representing soil infiltration and drainage capacity, as it describes the flood recession process better. This study provides an in-depth insight into high resolution flood modelling.This research was partially funded by the British Council through the Global Innovation Initiative (GII206), the UK Engineering and Physical Sciences Research Council under the Building Resilience into Risk Management project (EP/N010329/1), and the SINATRA project of the NERC Flooding From Intense Rainfall programme (NE/K008765/1). The first author was funded by the China Scholarship Council. The authors would also like to thank the UK Environment Agency for the LIDAR datasets, UK Met Office (BADC) for the Radar rainfall data, Ordnance Survey for the Master Maps, and NVIDIA Corporation for the Tesla K20c GPU used in this research

Identification of a major IP5 kinase in Cryptococcus neoformans confirms that PP-IP5/IP7, not IP6, is essential for virulence

Fungal inositol polyphosphate (IP) kinases catalyse phosphorylation of IP3 to inositol pyrophosphate, PP-IP5/IP7, which is essential for virulence of Cryptococcus neoformans. Cryptococcal Kcs1 converts IP6 to PP-IP5/IP7, but the kinase converting IP5 to IP6 is unknown. Deletion of a putative IP5 kinase-encoding gene (IPK1) alone (ipk1Δ), and in combination with KCS1 (ipk1Δkcs1Δ), profoundly reduced virulence in mice. However, deletion of KCS1 and IPK1 had a greater impact on virulence attenuation than that of IPK1 alone. ipk1Δkcs1Δ and kcs1Δ lung burdens were also lower than those of ipk1Δ. Unlike ipk1Δ, ipk1Δkcs1Δ and kcs1Δ failed to disseminate to the brain. IP profiling confirmed Ipk1 as the major IP5 kinase in C. neoformans: ipk1Δ produced no IP6 or PP-IP5/IP7 and, in contrast to ipk1Δkcs1Δ, accumulated IP5 and its pyrophosphorylated PP-IP4 derivative. Kcs1 is therefore a dual specificity (IP5 and IP6) kinase producing PP-IP4 and PP-IP5/IP7. All mutants were similarly attenuated in virulence phenotypes including laccase, urease and growth under oxidative/nitrosative stress. Alternative carbon source utilisation was also reduced significantly in all mutants except ipk1Δ, suggesting that PP-IP4 partially compensates for absent PP-IP5/IP7 in ipk1Δ grown under this condition. In conclusion, PP-IP5/IP7, not IP6, is essential for fungal virulence

VEGFA, B, C: Implications of the C-Terminal Sequence Variations for the Interaction with Neuropilins

Vascular endothelial growth factors (VEGFs) are the key regulators of blood and lymphatic vessels’ formation and function. Each of the proteins from the homologous family VEGFA, VEGFB, VEGFC and VEGFD employs a core cysteine-knot structural domain for the specific interaction with one or more of the cognate tyrosine kinase receptors. Additional diversity is exhibited by the involvement of neuropilins–transmembrane co-receptors, whose b1 domain contains the binding site for the C-terminal sequence of VEGFs. Although all relevant isoforms of VEGFs that interact with neuropilins contain the required C-terminal Arg residue, there is selectivity of neuropilins and VEGF receptors for the VEGF proteins, which is reflected in the physiological roles that they mediate. To decipher the contribution made by the C-terminal sequences of the individual VEGF proteins to that functional differentiation, we determined structures of molecular complexes of neuropilins and VEGFderived peptides and examined binding interactions for all neuropilin-VEGF pairs experimentally and computationally. While X-ray crystal structures and ligand-binding experiments highlighted similarities between the ligands, the molecular dynamics simulations uncovered conformational preferences of VEGF-derived peptides beyond the C-terminal arginine that contribute to the ligand selectivity of neuropilins. The implications for the design of the selective antagonists of neuropilins’ functions are discussed

Dietary fat intake as a risk factor for the development of diabetes. Multinational, multicenter study of the Mediterranean Group for the Study of Diabetes (MGDS)

In the context of the Multinational MGSD Nutrition Study, three groups of subjects were studied: 204 subjects with recently diagnosed diabetes(RDM),42subjectswithundiagnoseddiabetes(UDM)(AmericanDiabetesAssociation criteria—fasting plasma glucose [FPG] 126 mg/dl), and 55 subjects with impaired fasting glucose(IFG)(FPG 110and126mg/dl).Eachgroupwascomparedwithacontrolgroupof nondiabetic subjects, matched one by one for center, sex, age, and BMI. Nutritional habits were evaluated by a dietary history method, validated against the 3-day diet diary. In RDM, the questionnaire referred to the nutritional habits before the diagnosis of diabetes. Demographic data were collected, and anthropometrical and biochemical measurements were taken. RESULTS— Compared with control subjects, RDM more frequently had a family history of diabetes(49.0vs.14.2%;P0.001),exercisedless(exerciseindex53.5vs.64.4;P0.01),and more frequently had sedentary professions (47.5 vs. 27.4%; P 0.001). Carbohydrates contributed less to their energy intake (53.5 vs. 55.1%; P 0.05), whereas total fat (30.2 0.5 vs. 27.8 0.5%; P 0.001) and animal fat (12.2 0.3 vs. 10.8 0.3%; P 0.01) contributed moreandtheplant-to-animalfatratiowaslower(1.50.1vs.1.80.1;P0.01).UDMmore frequentlyhadafamilyhistoryofdiabetes(38.1vs.19.0%;P0.05)andsedentaryprofessions (58.5vs.34.1%;P0.05),carbohydratescontributedlesstotheirenergyintake(47.61.7vs. 52.81.4%;P0.05),totalfat(34.71.5vs.30.41.2%;P0.05)andanimalfat(14.2 0.9 vs. 10.6 0.7%; P 0.05) contributed more, and the plant-to-animal fat ratio was lower (1.6 0.2 vs. 2.3 0.4; P 0.05). IFG differed only in the prevalence of family history of diabetes (32.7 vs. 16.4%; P 0.05). CONCLUSIONS— Our data support the view that increased animal fat intake is associated with the presence of diabetes