Understanding the Structure of Materials at the Intersection of Rationalisation, Prediction and Big Data

Theoretical materials science has a large and growing role to play in modern society thanks to its ability to deliver materials with new and interesting properties. The properties of any material are, on some level, a function of its internal structure. In this work we combine three important tools spanning the last 100 years of materials research, rationalisation, prediction and big data in an attempt to understand the factors that underpin the stability of ordered structures and to build an understanding of structure that is agnostic of a particular element or building block. We apply rationalisation to data mining of the Inorganic Crystal Structure Database, using various proposed structure descriptors to probe the factors affecting structure stability. Extensive prediction is performed on the Fe-Ni-Si system at inner earth core pressures to determine the phases most likely to be present, yielding a new, stable, Ni-Si structure. A new prediction technique for 2D grain boundaries is presented that doubles the size of system that can reasonably be studied at the ab initio level of theory. The structurally rich phosphorus and arsenic systems are investigated using structure prediction, producing new metastable structures. Finally, we use a simple model for particles that attract at long range and repel at short to probe all the possible binary structures over a wide range of stoichiometries. By carrying out prediction over a wide range of potential parameters we build a database of almost 20M entries. Contained within are a number of unreported structures including many in parts of parameter space that go beyond the periodic table in terms of size and bond energy ratios. Our work provides hints that these hypothetical structures could be realised in self assembling systems made up from constituents with tunable interactions opening the door to the possibility of new properties

Characterization of Navassa National Wildlife Refuge: A preliminary report for NF-06-05 (NOAA ship "Nancy Foster", April 18-30, 2006)

Navassa is a small, undeveloped island in the Windward Passage between Jamaica and Haiti. It was designated a National Wildlife Refuge under the jurisdiction of the U.S. Fish and Wildlife Service in 1999, but the remote location makes management and enforcement challenging, and the area is regularly fished by artisanal fishermen from Haiti. In April 2006, the NOAA Center for Coastal Fisheries and Habitat Research conducted a research cruise to Navassa. The cruise produced the first high-resolution multibeam bathymetry for the area, which will facilitate habitat mapping and assist in refuge management. A major emphasis of the cruise was to study the impact of Haitian fishing gear on benthic habitats and fish communities; however, in 10 days on station only one small boat was observed with five fishermen and seven traps. Fifteen monitoring stations were established to characterize fish and benthic communities along the deep (28-34 m) shelf, as these areas have been largely unstudied by previous cruises. The fish communities included numerous squirrelfishes, triggerfishes, and parrotfishes. Snappers and grouper were also present but no small individuals were observed. Similarly, conch surveys indicated the population was in low abundance and was heavily skewed towards adults. Analysis of the benthic photoquadrats is currently underway. Other cruise activities included installation of a temperature logger network, sample collection for stable isotope analyses to examine trophic structure, and drop camera surveys to ground-truth habitat maps and overhead imagery. (PDF contains 58 pages

Podoplanin Gene Disruption in Mice Promotes in vivo Neural Progenitor Cells Proliferation, Selectively Impairs Dentate Gyrus Synaptic Depression and Induces Anxiety-Like Behaviors.

Podoplanin (Pdpn), a brain-tumor-related glycoprotein identified in humans and animals, is endogenously expressed in several organs critical for life support such as kidney, lung, heart and brain. In the brain, Pdpn has been identified in proliferative nestin- positive adult neural progenitor cells and in neurons of the neurogenic hippocampal dentate gyrus (DG), a structure associated to anxiety, critical for learning and memory functions and severely damaged in people with Alzheimer’s Disease (AD). The in vivo role of Pdpn in adult neurogenesis and anxiety-like behavior remained however unexplored. Using mice with disrupted Pdpn gene as a model organism and applying combined behavioral, molecular biological and electrophysiological assays, we here show that the absence of Pdpn selectively impairs long-term synaptic depression in the neurogenic DG without affecting the CA3-Schaffer’s collateral-CA1 synapses. Pdpn deletion also enhanced the proliferative capacity of DG neural progenitor cells and diminished survival of differentiated neuronal cells in vitro. In addition, mice with podoplanin gene disruption showed increased anxiety-like behaviors in experimentally validated behavioral tests as compared to wild type littermate controls. Together, these findings broaden our knowledge on the molecular mechanisms influencing hippocampal synaptic plasticity and neurogenesis in vivo and reveal Pdpn as a novel molecular target for future studies addressing general anxiety disorder and synaptic depression-related memory dysfunctions

The MOLDY short-range molecular dynamics package

We describe a parallelised version of the MOLDY molecular dynamics program. This Fortran code is aimed at systems which may be described by short-range potentials and specifically those which may be addressed with the embedded atom method. This includes a wide range of transition metals and alloys. MOLDY provides a range of options in terms of the molecular dynamics ensemble used and the boundary conditions which may be applied. A number of standard potentials are provided, and the modular structure of the code allows new potentials to be added easily. The code is parallelised using OpenMP and can therefore be run on shared memory systems, including modern multicore processors. Particular attention is paid to the updates required in the main force loop, where synchronisation is often required in OpenMP implementations of molecular dynamics. We examine the performance of the parallel code in detail and give some examples of applications to realistic problems, including the dynamic compression of copper and carbon migration in an iron-carbon alloy

Expression patterns of protein C inhibitor in mouse development

Proteolysis of extracellular matrix is an important requirement for embryonic development and is instrumental in processes such as morphogenesis, angiogenesis, and cell migration. Efficient remodeling requires controlled spatio-temporal expression of both the proteases and their inhibitors. Protein C inhibitor (PCI) effectively blocks a range of serine proteases, and recently has been suggested to play a role in cell differentiation and angiogenesis. In this study, we mapped the expression pattern of PCI throughout mouse development using in situ hybridization and immunohistochemistry. We detected a wide-spread, yet distinct expression pattern with prominent PCI levels in skin including vibrissae, and in fore- and hindgut. Further sites of PCI expression were choroid plexus of brain ventricles, heart, skeletal muscles, urogenital tract, and cartilages. A strong and stage-dependent PCI expression was observed in the developing lung. In the pseudoglandular stage, PCI expression was present in distal branching tubules whereas proximal tubules did not express PCI. Later in development, in the saccular stage, PCI expression was restricted to distal bronchioli whereas sacculi did not express PCI. PCI expression declined in postnatal stages and was not detected in adult lungs. In general, embryonic PCI expression indicates multifunctional roles of PCI during mouse development. The expression pattern of PCI during lung development suggests its possible involvement in lung morphogenesis and angiogenesis

Ongoing monitoring of Tortugas Ecological Reserve: Assessing the consequences of reserve designation

Over the past five years, a biogeographic characterization of Tortugas Ecological Reserve(TER) has been carried out to measure the post-implementation effects of TER as a refuge for exploited species. Our results demonstrate that there is substantial microalgal biomass at depths between 10 and 30 m in the soft sediments at the coral reef interface, and that this community may play an important role in the food web supporting reef organisms. In addition, preliminary stable isotope data, in conjunction with prior results from the west Florida shelf, suggest that the shallow water benthic habitats surrounding the coral reefs of TER will prove to be an important source of the primary production ultimately fueling fish production throughout TER. The majority of the fish analyzed so far have exhibited a C isotope signature consistent with a food web which relies heavily on benthic primary production. Fish counts indicate a marked increase in the abundance of large fish (>20 cm) within the Reserve relative to the Out and Park strata, across years. Faunal collections from open and protected soft bottom habitat near the northern boundary of Tortugas North strongly suggest that relaxation of trawling pressure has increased benthic biomass and diversity in this area of TER. These data, employing an integrated Before - After Control Impact (BACI) design at multiple spatial scales, will allow us to continue to document and quantify the post-implementation effects of TER. (PDF contains 58 pages

De novo Vessel Formation Through Cross-Talk of Blood-Derived Cells and Mesenchymal Stromal Cells in the Absence of Pre-existing Vascular Structures

Background: The generation of functional blood vessels remains a key challenge for regenerative medicine. Optimized in vitro culture set-ups mimicking the in vivo perivascular niche environment during tissue repair may provide information about the biological function and contribution of progenitor cells to postnatal vasculogenesis, thereby enhancing their therapeutic potential. Aim: We established a fibrin-based xeno-free human 3D in vitro vascular niche model to study the interaction of mesenchymal stromal cells (MSC) with peripheral blood mononuclear cells (PBMC) including circulating progenitor cells in the absence of endothelial cells (EC), and to investigate the contribution of this cross-talk to neo-vessel formation. Materials and Methods: Bone marrow-derived MSC were co-cultured with whole PBMC, enriched monocytes (Mo), enriched T cells, and Mo together with T cells, respectively, obtained from leukocyte reduction chambers generated during the process of single-donor platelet apheresis. Cells were embedded in 3D fibrin matrices, using exclusively human-derived culture components without external growth factors. Cytokine secretion was analyzed in supernatants of 3D cultures by cytokine array, vascular endothelial growth factor (VEGF) secretion was quantified by ELISA. Cellular and structural re-arrangements were characterized by immunofluorescence and confocal laser-scanning microscopy of topographically intact 3D fibrin gels. Results: 3D co-cultures of MSC with PBMC, and enriched Mo together with enriched T cells, respectively, generated, within 2 weeks, complex CD31C /CD34C vascular structures, surrounded by basement membrane collagen type-IVC cells and matrix, in association with increased VEGF secretion. PBMC contained CD31C CD34CCD45dimCD14 progenitor-type cells, and EC of neo-vessels were PBMC-derived. Vascular structures showed intraluminal CD45C cells that underwent apoptosis thereby creating a lumen. Cross-talk of MSC with enriched Mo provided a proangiogenic paracrine environment. MSC co-cultured with enriched T cells formed "cellin-cell" structures generated through internalization of T cells by CD31C CD45dim = cells. No vascular structures were detected in co-cultures of MSC with either Mo or T cells. Conclusion: Our xeno-free 3D in vitro vascular niche model demonstrates that a complex synergistic network of cellular, extracellular and paracrine cross-talk can contribute to de novo vascular development through self-organization via co-operation of immune cells with blood-derived progenitor cells and MSC, and thereby may open a new perspective for advanced vascular tissue engineering in regenerative medicine

Residual dipolar coupling investigation of a heparin tetrasaccharide confirms the limited effect of flexibility of the iduronic acid on the molecular shape of heparin

The solution conformation of a fully sulfated heparin-derived tetrasaccharide, I, was studied in the presence of a 4-fold excess of Ca2+. Proton–proton and proton–carbon residual dipolar couplings (RDCs) were measured in a neutral aligning medium. The order parameters of two rigid hexosamine rings of I were determined separately using singular value decomposition and ab initio structures of disaccharide fragments of I. The order parameters were very similar implying that a common order tensor can be used to analyze the structure of I. Using one order tensor, RDCs of both hexosamine rings were used as restraints in molecular dynamics simulations. RDCs of the inner iduronic acid were calculated for every point of the molecular dynamics trajectory. The fitting of the calculated RDCs of the two forms of the iduronic acid to the experimental values yielded a population of 1C4 and 2So conformers of iduronic acid that agreed well with the analysis based on proton–proton scalar coupling constants. The glycosidic linkage torsion angles in RDC-restrained molecular dynamics (MD) structures of I are consistent with the interglycosidic three-bond proton–carbon coupling constants. These structures also show that the shape of heparin is not affected dramatically by the conformational flexibility of the iduronic acid ring. This is in line with conclusions of previous studies based on MD simulations and the analysis of 1H-1H NOEs. Our work therefore demonstrates the effectiveness of RDCs in the conformational analysis of glycosaminoglycans

Increasing Incidence of Geomyces destructans Fungus in Bats from the Czech Republic and Slovakia

BACKGROUND: White-nose syndrome is a disease of hibernating insectivorous bats associated with the fungus Geomyces destructans. It first appeared in North America in 2006, where over a million bats died since then. In Europe, G. destructans was first identified in France in 2009. Its distribution, infection dynamics, and effects on hibernating bats in Europe are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We screened hibernacula in the Czech Republic and Slovakia for the presence of the fungus during the winter seasons of 2008/2009 and 2009/2010. In winter 2009/2010, we found infected bats in 76 out of 98 surveyed sites, in which the majority had been previously negative. A photographic record of over 6000 hibernating bats, taken since 1994, revealed bats with fungal growths since 1995; however, the incidence of such bats increased in Myotis myotis from 2% in 2007 to 14% by 2010. Microscopic, cultivation and molecular genetic evaluations confirmed the identity of the recently sampled fungus as G. destructans, and demonstrated its continuous distribution in the studied area. At the end of the hibernation season we recorded pathologic changes in the skin of the affected bats, from which the fungus was isolated. We registered no mass mortality caused by the fungus, and the recorded population decline in the last two years of the most affected species, M. myotis, is within the population trend prediction interval. CONCLUSIONS/SIGNIFICANCE: G. destructans was found to be widespread in the Czech Republic and Slovakia, with an epizootic incidence in bats during the most recent years. Further development of the situation urgently requires a detailed pan-European monitoring scheme