bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitrogen-Rich Carbon Nitrides as Novel High Energy Density Materials
Authors: Laniel Dominique , Sebastiao Elena , Cook Cyril , Murugesu Muralee , Desgreniers Serge
Published: November 2015

Nitrogen-rich carbon nitride materials hold the promise of constituting novel high density energetic materials if recoverable as metastable polymeric networks of single-bonded atoms at ambient conditions. Upon transition to a lowest-energy configuration, this high pressure synthesized nitrogen-heavy material would release a large amount of energy. In this work, two nitrogen-rich molecular precursors, namely, 5'-bis(1H-tetrazolyl)amine (BTA) and cyanuric triazide (CTA), were studied in their condensed states at elevated pressures and room temperature. Powder x-ray diffraction using synchrotron radiation and micro-Raman spectroscopy were carried out to pressures as high as 12.9 and 59.6 GPa, for BTA and CTA, respectively. In our study, dense BTA is shown to conserve its room condition crystalline structure, an orthorhombic unit cell (Pbca), up to the highest pressure. In the case of CTA, results of Raman spectroscopy and x-ray diffraction indicate structural changes between 29.6 and 33.4 GPa. From numerical simulations of dense CTA [1], a phase transition into either tritetrazole (hexagonal lattice, P-6) or the sought-after polymeric CTA (monoclinic lattice, P21) is expected to take place at a pressure close to 30 GPa. Preliminary results of x-ray diffraction data indicate a transition from a hexagonal to a monoclinic unit cell with parameters similar to those predicted. Moreover, theoretically calculated polymeric nitrogen Raman peaks [2] are well matched to those observed for the high-density phase of CTA [1]. Studies of BTA and CTA under extreme conditions provide a deeper understanding of the behaviour of dense nitrogen-rich materials and guidance for further developments of high energy density compounds.
Structure of methane and ethane at high pressure
Authors: Goncharov Alexander , Stavrou Elissaios , Lobanov Sergey , Oganov Artem , Roisen Valery , Chanyshev Artem , Litasov Konstantin , Konopkova Zuzana , Zhuravlev Kirill , Prakapenka Vitali
Published: November 2015

Methane is one of the most abundant hydrocarbon molecules in the universe and is expected to be a significant part of the icy giant planets (Uranus and Neptune) and their satellites. Ethane is one of the most predictable products of chemical reactivity of methane at extreme pressures and temperatures. In spite of numerous experimental and theoretical studies, the structure and relative stability of these materials even at room temperature remains controversial. We have performed a combined experimental and theoretical study of both methane and ethane up at high pressures up to 120 GPa at 300 K using x-ray diffraction and Raman spectroscopy and the ab-initio evolutionary algorithm, respectively. In the case of methane we have successfully solved the structure of phase B by determining the space group and the positional parameters of carbon atoms, and by completing these results for the hydrogen positions using the theoretical calculations. The general structural behavior under pressure and the relation between phase B and phases A and pre-B will be also discussed. For ethane we have determined the crystallization point, for room temperature, at 1.7 GPa and also the low pressure crystal structure (Phase A). This crystal structure is orientationally disordered (plastic phase) and deviates from the known crystal structures for ethane at low temperatures. Moreover, a pressure induced phase transition has been indentified, for the first time, at 18 GPa to a monoclinic phase III, the structure of which is solved based on a good agreement of the experimental results and theoretical predictions. We have determined the equations of state of methane and ethane, which provides a solid basis for the discussion of their relative stability at high pressures.
High pressure synthesis of BN and BCN crystals and their functionalization
Authors: Taniguchi Takashi
Published: November 2015

Hexagonal BN (hBN) and cubic BN (cBN) are known as the representative crystal structures of BN. The former is chemically and thermally stable, and has been widely used as an electrical insulator and heat-resistant materials. The latter, which is a high-density phase, is an ultra-hard material second only to diamond. Recently, some progresses in the synthesis of high purity BN crystals were achieved by using Ba-BN as a solvent material at high pressure crystal growth [1]. Band-edge natures (cBN Eg=6.2eV and hBN Eg=6eV) were characterized by their optical properties. The key issue to obtain high purity crystals is to reduce oxygen and carbon contamination in the growth circumstances. It should be emphasized that hBN exhibits attractive potential for deep ultraviolet (DUV) light emitter [2 ] and also superior properties as substrate of graphene devices [3]. In this study, the effect of carbon impurity in BN is investigated. Three types of experimental approaches were carried out; (1) synthesis of high purity hBN single crystals and its characterization with respect to residual carbon, (2) high temperature solid state diffusion of carbon into hBN and its characterization, and (3) high temperature annealing of turbostratic B-C-N(t-BCN) compound under high pressure. t-BCN flakes obtained by chemical vapour deposition process was annealed near 3000C and 2GPa so as to become well crystallized.At annealing near 3000C at 2GPa with graphite, carbon incorporation of 1E21/cm3 in hBN was achieved with exhibiting totally different Cathode Luminescence spectra feature with high purity hBN crystals. Since major carbon contribution may affect the crystal structure of the 2-D layers stacking in hBN system, phase stability of BCN ternary phase will be introduced by the experimental results of high temperature annealing. Furthermore, effect of carbon impurity upon the synthesis of wurtzite BN from highly crystalline hBN via martensitic phase transformation will also be introduced.
Simulation based approach to structure relaxation in oxides nanomaterials
Authors: Kuzmin Alexei , Anspoks Andris , Kalinko Aleksandr , Timoshenko Janis
Published: November 2015

Physical properties of nanoparticles depend strongly on their structure, therefore an understanding of atomic structure relaxation at nanoscale is very important for properties tuning but is a challenging task. Upon crystallite size reduction below about 10 nm, the unit-cell volume expansion is observed in most nanooxides, opposite to metal nanoparticles. The detailed understanding of this phenomenon requires joint use of modern experimental and theoretical methods. In this study we will illustrate how the nanostructure problem can be addressed using classical molecular dynamics [1] and reverse Monte Carlo [2] simulation methods, employed to the analysis of synchrotron radiation x-ray absorption spectra. The two simulation based approaches allow us to obtain structural models which account for the nanoparticle size, thermal disorder and high-order correlation effects. Two examples of their use will be discussed in details: (i) the role of nickel vacancies in nickel oxide nanoparticles/thin films and (ii) the effect of transition metal type on tungstate nanoparticles.
Synthesis and Characterization of SPIONs for Biomedical applications
Authors: Britos Tatiane , Min Li , De Souza Li Lilia , Haddad Paula
Published: November 2015

This work reports the synthesis and characterization of superparamagnetic iron oxide nanoparticles (SPIONs), with great potential for biomedical applications. SPIONs were prepared through a decomposition of Fe(acac)3 in the presence of 1,2 hexadecanodiol (reducing agent), oleic acid and oleylamine (ligands) in a hot organic solvent. The mercaptosuccinic acid (MSA) and 2,3- dimercaptosuccinic acid (DMSA) were exchanged onto the nanocrystal surface making the particles stable in water. The thiolated nanoparticles (SH-NPs) were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and vibrating sample magnetometry (VSM). The as-prepared sample presented an amorphous partially oxidized iron structure. The results showed that the SH-NPs have a mean diameter of 6 nm and display superparamagnetic behavior at room temperature. Preliminary tests of incorporation of these systems were evaluated in Hela cells and stem cells. The results showed that the thiolated nanoparticles have no toxic effects for both cell types with good incorporation after 6 hours of transfection. Magnetic resonance image (MRI) were also carried and showed that the MNPs increase the contrast in systems investigated. Acknowledgements: FAPESP (2011/10125-0), CNPq, CAPES, UNICAMP
Formation dynamics of CoSi2thin nanoplates arrays studied by GISAXS in situ
Authors: Huck-Iriart Cristián , Giovanetti Lisandro , Dos Santos Claro Paula , Kellermann Guinther , Requejo Félix , Craievich Aldo
Published: November 2015

During the last decades an increasing demand for the development of new methods of preparation of nano-composite materials suited for technological applications has been observed [1]. The interest on these nanomaterials is related to the fact that many of their properties can be varied in a continuous way by changing size, shape and/or spatial ordering. Silicides of transition metals such as CoSi2 are of great interest because of the possibilities that they open to applications as a contact material for microelectronic devices [2]. A simple method for obtaining buried arrays of CoSi2 plates coherently embedded in a Si host lattice was described in a previous study [3]. Grazing-incidence small-angle X-ray "GISAXS" and transmission electron microscopy "TEM" results indicated that the nanoplates exhibit a hexagonal lateral shape and a remarkable uniform thickness. The lattice of each CoSi2 nanoplates was shown to be coherent with the host Si lattice, and parallel to one of the four planes belonging to the Si(111) crystallographic planes family. In this work we present a diffusion dynamics study of Co into Si single crystal lattice using in situ GISAXS setup designed ad-hoc. The Co atoms were initially embedded in a SiO2 thin film deposited on Si(001) substrates subjected to a isothermal treatment during 1 hour at several temperatures between 650-850 oC, The diffused Co react with Si atoms and form CoSi2 nanoplates. GISAXS intensity was modeled assuming that the total scattering intensity is the sum of the intensity produced by a set of spatially uncorrelated and spherical Co nanoparticles – embedded in the SiO2 layer - plus the intensity coming from the hexagonal nanoplates parallel to the different planes of the Si(111) family.
Atomic Structure and Mass-Production of Supported Size-Selected Nanoclusters
Authors: Palmer Richard
Published: November 2015

Deposition of size-selected nanoclusters assembled from atoms in the gas phase is a novel route to the fabrication of <10nm surface features. I will focus on the creation and atomic structure of monodispersed metal cluster arrays which enable new model catalysts and protein biochips. The atomic structure of the clusters – previously the province of theory - is revealed experimentally [1] by aberration-corrected scanning transmission electron microscopy (STEM) in the HAADF imaging regime; we can "count" atoms and obtain 3D information not just 2D projections. Results include mass spectrometry of thiolated Au clusters, adatom dynamics on Au923 magic-number nanoclusters [2], first atomic imaging results for Au55 and Au20 and a method to explore the potential energy landscape of (Au923) clusters via cluster transformations [3], presenting a reference system for theory. A new kind of cluster beam source, to allow super-abundant generation of size-selected nanoclusters, will also be demonstrated.
Microstructure and crystallographic texture of Ranella Olearia Shell
Authors: Ouhenia Salim , Chateigner Daniel , Belabbas Imad
Published: November 2015

Molluscs are soft-bodied animals, that why many of them invented complex strategies for protecting themselves [1]. One of these strategies consists in creating a rigid biomineral called mollusc shell. Mollusc shells are complex biocomposites of mineral and organic material (5% in volume) with high mechanical performances, compared to the geological mineral. Mollusc shells are mainly made of calcite and aragonite crystalline polymorphs of calcium carbonate. This organic part behaves as nanometer growth-control of the inorganic crystals. This has stimulated chemists and materials scientists to design materials with a microstructure similar to that of nacre. To achieve this, understanding the microstructure of the nacre at various scales is certainly the key [2]. In this work we made use of the Combined Analysis [3] to determine the structure and preferred orientations of constituting aragonite crystallites of the Ranella olerea shell (fig. 1a) layers using scanning electron microscopy and X-rays diffraction. SEM analyses (fig. 1b) show the presence of an inner layer composed of Radial Lamellar, an intermediate comarginal crossed lamellar layer and an outer crossed lamellar layer. The refinement of X-ray diffraction diagrams gives the textures of the three layers, their respective aragonite unit-cell distortions, and the macroscopic elastic tensor of their mineral parts. The textures of the three layers were found to be of high level, especially for the inner layer. Both intermediate and outer layers exhibit regular texture patterns for crossed lamellae with a split of the c-axis component around the normal to the shell. An anisotropic unit-cell distortion is quantified for the three layers which is attributed to the combined effects of inter- and intra-crystalline macromolecules. The simulation of the macroscopic elastic tensor shows that the strong orientations present in the successive layers give an optimisation in terms of rigidity and shear resistance.
Anisotropic resistivity tensor of melt-cast Bi2212 superconductors from QTA
Authors: Dellicour Aline , Pautrat Alain , Vertruyen Bénédicte , Rikel Mark , Lutterotti Luca , Chateigner Daniel
Published: November 2015

Bi2Sr2CaCu2O8+δ HTSC superconductor is characterized by a very strong normal-state resistivity anisotropy, with ρc/ρab typically above 10E4. The aim of this study is to use Quantitative Texture Analysis from x-ray diffraction measurements to estimate the orientation effect on the anisotropic macroscopic resistivity in melt-cast bulk Bi2Sr2CaCu2O8+δ superconductors. Our approach uses the geometric mean [1] of the single crystal resistivity tensor weighted by the Orientation Distribution Function (ODF) to quantitatively estimate the macroscopic resistivity tensor of the samples. The ODF is obtained from x-ray Combined Analysis [2], using the E-WIMV algorithm of the MAUD software. The GMA applies to the rank-two resistivity tensor of the orthorhombic space group considered tetragonal due to the small difference of a- and b-axes of the phase, with only two independent tensor components. We relate a relatively good agreement between measured and calculated macroscopic anisotropic resistivity ratios. Even with ρc/ρab between 10E4 and 10E5 for Bi2212 at room temperature in single crystals [3], we experiment macroscopic ratio in our bulk samples of around only 2. This small ratio is explained by the weak planar- or fiber-like (Figure) texture achieved in the melt-cast samples, characterized by maxima of orientation distributions not larger than 10 mrd. Calculated resistivities, based on homogeneous crystallites, perfect grain boundaries and no secondary phases, are 10 times larger than the observed ones. This suggests that the observed minor phases positively affect conductive pathways between grains. Calculated and measured anisotropic resistive ratios are coherent with one another, and Combined Analysis gives good predictions of these former.
Oriented hexagonal ferrite thin films prepared by chemical solution deposition
Authors: Bursik Josef , Kuzel Radomir , Knizek Karel , Drbohlav Ivo
Published: November 2015

Hexagonal ferrites (M, Y, Z-type) represent a new diverse class of magnetoelectric (ME) multiferroics, where ME effect is driven by complex magnetic order. Integration of ME materials with standard semiconductor technology is important for ultimate realization of ME functionalities. They have the potential to display ME coupling under low magnetic field bias and at temperatures close to room temperature. Methods based on sol–gel transition offer possibility of low cost and efficient way for the evaluation of new material system. The single phase, epitaxial thin films of Y-type hexagonal ferrite has been prepared and studied. Thin films of Ba2Zn2Fe12O22(Y) hexaferrite were prepared through the chemical solution deposition method on SrTiO3(111)(ST) single crystal substrates using epitaxial SrFe12O19(M) hexaferrite thin layer as a seed template layer. The process of crystallization was mainly investigated by means of X-ray diffraction and atomic force microscopy. A detailed inspection revealed that growth of seed layer starts through the break-up of initially continuous film into high density of well-oriented isolated grains with expressive shape anisotropy and hexagonal habit.The vital parameters of the seed layer, i.e. thickness, substrate coverage,crystallization conditions and temperature ramp were optimized with the aim to obtain epitaxially crystallized Y phase. By overcoating this seed layer, Y phase prepared under optimum deposition and heat treatment conditions presents a (001) orientation perpendicular to the substrate. Perfect parallel in-plane alignment of the hexagonal cells of SrTiO3substrate and both hexaferrite phases was proved by fast ω and φ scan measurements on sets of several diffraction planes at asymmetric orientations, and also by pole figures. The soft magnetic character and existence of pronounced magnetic anisotropy in Y films were confirmed by room temperature measurements of magnetization.
Characterization of βαβββ Resistance Proteins from Pseudomonas aeruginosa
Authors: Vit Allegra , Popp Monika , Kalawy-Fansa Eyad , Yu Shen , Blankenfeldt Wulf
Published: November 2015

Pseudomonas aeruginosa is a multiresistant pathogen that can cause infection in immuno-compromized patients, for example in people suffering from cystic fibrosis. [1] It has complex patho-physiology and produces a large number of exoproducts, among which the phenazines are especially prominent. In P. aeruginosa, the blue phenazine derivative pyocyanin plays a crucial role in infection of the host. [2] This phenazine can generate reactive oxygen species and is thought to act as respiratory pigment and as a virulence factor at the same time. P. aeruginosa has to protect itself from its own phenazines because of the antibiotic action of these substances. Inspired by the fact that the phenazine biosynthesis operon of several bacteria contains a phenazine resistance factor of the βαβββ module protein family, we have searched the genome of P. aeruginosa for proteins of this fold. [3] In P. aeruginosa we could identify 22 of these genes, most without previous functional characterization. A structure-based sequence alignment made it possible to assign these proteins to two classes with two subgroups each, based on the conserved residues in the active site. Using X-ray crystallography and biophysical methods, we further demonstrate that several of these proteins indeed bind phenazines and possibly other antibiotics that contain aromatic moieties. Currently, we are working on the structural characterization and physiological function assignment of all of these βαβββ-module-containing proteins. Ultimately, these data may lead to novel anti-infective strategies.
Developing an antibiotic effective against multi-drug resistant bacteria.
Authors: Steussy Calvin , Stauffacher Cynthia , Lipton Mark , Seleem Mohamed
Published: November 2015

The emergence of multi-drug resistant pathogenic bacteria is one of the great challenges to modern medicine. The gram positive cocci Methicillin Resistant Staphylococcus aureus (MRSA) and Vancomycin Resistant Enterococcus faecalis (VRE) are two particularly virulent examples. In vivo studies have shown that the eukaryotic like 'mevalonate' isoprenoid pathway used by these pathogenic cocci is essential to their growth and virulence [1]. Our structures of HMG-CoA reductase (HMGR) from P. mevalonii demonstrated that the bacterial enzymes are structurally distinct from the human enzymes allowing for specific antibacterial activity [2]. High throughput in vitro screening against bacterial HMGR at the Southern Research Center, Birmingham, AL uncovered a lead compound with an IC50 of 80 µM with a competitive mode of action. Our x-ray crystal structures of HMGR from E. faecalis complexed with the lead compound and its variations have informed the synthesis of new inhibitors that have improved the IC50 to 5 µM [3]. Studies of this compound show it to be active against both MRSA and VRE in culture, effective against these bacteria in biofilms, and efficacious in a model system of eukaryotic infection. Structures and kinetics of these compounds will be presented and future directions discussed.
Structural studies of proteins involved in the activity of novel antibiotics
Authors: Moynie Lucile , Ferrara Luana , Tortajada Antoni , Naismith James
Published: November 2015

The emergence of multidrug-resistant Gram-negative bacteria such as P. aeruginosa has become a growing challenge for developing new drugs. One of the strategies recently used to improve the efficacy of the antibiotics is to increase their uptake by exploiting bacterial transport systems such as the siderophore-mediated iron acquisition system. BAL30072, a new monosulfactam conjugated to a siderophore moiety has been shown to have potent activity against many Gram-negative bacteria [1]. Several proteins affecting susceptibility to this antibiotic have been identified in Pseudomonas aeruginosa [2]. As part of the Translocation project (Innovative Medicines Initiative), we have undertaken structural studies of these proteins and have solved the three dimensional structures of two of these targets. The structure of PiuA, a TonB-dependent siderophore transporter involved in the uptake of siderophore antibiotics across the outer membrane [2,3] has been solved to a resolution of 1.9 Å. The structure of PiuC, an Fe(II)/α-ketoglutarate-dependent dioxygenase, has been solved to a resolution of 2.6 Å. The structural and biochemical studies of these proteins will help us to understand the mode of action of these novel antibiotics and subsequently help to design new drugs acting against multidrug-resistant bacteria.
X-ray crystallographic analysis of a MATE multidrug transporter from V. cholerae
Authors: Kusakizako Tsukasa , Tanaka Yoshiki , Maturana Andrés , Hipolito Christopher , Kuroda Teruo , Ishitani Ryuichiro , Suga Hiroaki , Nureki Osamu
Published: November 2015

MATE (Multidrug And Toxic compound Extrusion) family transporters are highly conserved from Bacteria to Eukarya including human, and export a broad range of xenobiotics using either a proton or a sodium ion gradient across the membrane. Especially in bacterial pathogens, MATE transporters contribute to their multiple drug resistance (MDR). To understand how MATE transporters export various substrates such as drugs and thus how pathogens acquire MDR, structural analyses are essential. The crystal structures of several MATE transporters from pathogens have been reported. However, because of the limited resolution and the lack of drug-MATE transporters complex structures, the recognition mechanism of various substrates and the coupling mechanism of the cation influx and the drug efflux have been poorly understood. Although the high-resolution structures of MATE transporters from non-pathogenic archaeal P. furiosus (PfMATE) have been reported, PfMATE shares low sequence identity with MATE transporters from pathogens such as V. cholerae. Therefore, further findings of the structural mechanism of MDR caused by MATE transporters from pathogens have been needed. To understand the substrate recognition and transport mechanism of MATE transporters from pathogens, we determined the crystal structures of one of MATE transporters from V. cholerae (VcMATE) at 2.5-2.7 Å resolutions using in meso crystallization method. The high-resolution structures of VcMATE show two distinct conformations, as observed in the structures of PfMATE, and reveal the large movement of transmembrane helix 1 and the putative substrate-binding site. The structures suggest that the bending of transmembrane helix 1 and the sequential collapse of the putative substrate-binding site induce the release of the bound substrate. This conformational change during the substrate transport may be a common mechanism among MATE transporters from pathogens to non-pathogens.
Analysis of bacterial cell-wall synthesis to combat antibiotic resistance
Authors: King Dustin , Strynadka Natalie
Published: November 2015

The peptidoglycan biosynthetic pathway is one of the most important processes in the bacterial cell to be exploited as a target for the design of antimicrobial drugs to combat infection and pathogenesis. This pathway, unique to bacteria, utilizes over twenty enzymes, likely in concert, with reactions that proceed from the cytoplasm, across the membrane and into the periplasmic space culminating in the production of the mesh-like structure composed of polymerized glycan and cross-linked peptide components that form the major structural component of the essential bacterial protective barrier known as the cell wall. Work in our group has aimed at understanding the structural and kinetic properties of several of these enzymes including the glycosyltransferase/transpeptidase activity of a family of enzymes known historically as the penicillin binding proteins (PBPs). As the name implies, these enzymes are also the target of beta-lactam antibiotics, and molecular modifications to transpeptidase variants have been shown to be linked to increased antibiotic resistance in superbugs such as Methicillin Resistant Staphlococcal aureus (MRSA). In parallel, highly disseminated plasmid-encoded beta-lactamase enzymes, with structural and mechanistic ties to the transpeptidases, have also arisen in many of the clinically important bacterial pathogens, leading to further widespread beta-lactam antibiotic resistance. The molecular details of these critical enzymatic reactions in bacterial viability and drug resistance will be presented.
Structural Insights into Mechanism of Antibiotic Regulation in Streptomyces
Authors: Anand Ruchi , Bhukya Hussain
Published: November 2015

Streptomyces species are well-known for their wide variety of biologically active secondary metabolites and contribute to two-third of naturally occurring antibiotics. Production of antibiotics and resistance pathways in these species are dictated by interplay of transcriptional regulatory proteins that trigger downstream responses to either small diffusible molecules (autoinducers) or by binding to the antibiotic intermediates. These regulators have a ligand binding site and a DNA binding site and they carry out their transcription regulation via conformational changes induced upon ligand or DNA binding. To decipher the structural mechanism of action here we present the crystal structure of CprB in complex with its consensus DNA element to a resolution of 3.2 Å. The structure revealed that CprB belongs to the tetracycline family of antibiotic resistance efflux pumps regulators. CprB binds to the DNA as a tetramer via the helix-turn-helix (HTH) motif with the mode of DNA binding is most analogous to that observed for the broad spectrum multidrug resistance regulator QacR from Staphylococcus aureus. The binding of the DNA induces the restructuring of the CprB dimeric interface, thereby inducing a pendulum like motion of the HTH motif that inserts into the major grove of the DNA. A genome wide search for the cognate DNA element revealed that CprB serves as an autoregulatory protein and binds to its own promoter sequence. Our studies suggest that CprB is a part of a network of proteins that regulate the antibiotic production and resistance pathways in Streptomyces. Fluorescence anisotropy lifetime studies performed with both consensus and CprB promoter helped in concluding that both the sequence have an analogous mode of binding with the CprB DNA exhibiting a stronger binding profile as supported by ITC studies. A sequential binding mode, similar to a clamp and click model of binding was proposed.
Structure-based Vaccine Development (Structural Vaccinology)
Authors: Malito Enrico
Published: November 2015

Structural biology is playing an increasingly important role in vaccine development, as it can facilitate the rational design of vaccines by allowing an atomic-level control of their antigenic and immunogenic properties. Several cases are now available that demonstrate the potential of structure-based methods for vaccine development. Here, I will present an overview of the insights we gained at Novartis Vaccines from studying two protein antigens of the recently approved vaccine against serogroup B meningococcus (MenB), and their impact for vaccine design and development. MenB causes severe sepsis and invasive meningococcal disease (IMD), particularly affecting young children and adolescents. In 2013, the first genome-derived vaccine, which targets MenB (4CMenB), was approved for use in Europe, and it is expected to become widely implemented in Europe beginning in 2014. The vaccine contains 3 previously unknown recombinant proteins discovered by genome mining. For one of the antigens, Factor H Binding Protein (FHBP), we recently generated a broadly protective chimera by a structure-based approach that consisted in grafting multiple immunodominant regions onto a single scaffold. Also, co-crystal structures of FHBP with Fabs from monoclonal antibodies provided insights into the molecular bases of the immune recognition and bactericidal activity. The structure of a second antigen, Neisserial adhesin A (NadA), a member of the Trimeric Autotransporter Adhesins (TAA), revealed a novel fold, while epitope mapping by Hydrogen-Deuterium Exchange Mass Spectrometry showed that in addition to being the receptor-binding domain, the head domain of NadA is also the target of a bactericidal monoclonal antibody. Overall, the structural information on the MenB antigens presented here provides important details on the pathogenesis and vaccine-induced immunity against meningococcus, and especially informs the engineering of improved immunogens by structure-based design.
Smart Sensitivity Control with Agilent's New Range of S2 CCD Detectors
Authors: Skarzynski Tadeusz , Meyer Mathias , Stec Przemyslaw , Baker Daniel , White Fraser , Gal Zoltan
Published: November 2015

With the recent improvements in the brightness of laboratory X-ray sources, high-quality data can be collected from a wider range of crystal samples on in-house diffractometers. To cope with the resulting increase in workload it is important to be able to collect highest-quality data as quickly and efficiently as possible. Agilent Technologies develop and supply X-ray systems for small-molecule and macromolecular crystallography, which include SuperNova line of diffractometers utilizing the latest generation sealed-tube micro-focus X-ray sources, as well as the new range of Atlas S2, Eos S2 and Titan S2 CCD detectors. Technological improvements allow us to make use of the high brilliance of the sources and the large dynamic range and low signal-to-noise of the new detectors to shift the boundaries of what crystal samples can be successfully measured in the home laboratory. The new S2 detectors incorporate an Intelligent Measurement System, where the exposure time, binning mode, and gain settings are automatically or manually set for each sample. High binning and gain modes are chosen to boost signal detectivity for weakly-diffracting data, whereas low binning and gain modes are selected to increase the dynamic range for well-diffracting samples. This flexibility makes it very easy to collect high-quality datasets for a very large range of samples. In conjunction, our innovative, user-friendly CrysAlisPro software is constantly being updated to make use of all new hardware improvements, as well as making it as easy as possible for the user to effectively screen their samples, gather enough preliminary information quickly, and run the experiments in the most effective way. Key aspects of the detectors, including the notions of absolute detectivity, processing overheads, readout speed, minimizing systematic errors and optimizing data collection protocols will be discussed. To illustrate the benefits of the newly developed technology, a number of protein and small-molecule data collection experiments will be presented and different modes of detector operation compared.
Integration and first data with a Pilatus3 6M at APS beamline 23ID-D
Authors: Sanishvili Ruslan , Makarov Oleg , Hilgart Mark , Pothineni Sudhir-Babu , Stepanov Sergey , Nagarajan Venugopalan , Ogata Craig , Schulze-Briese Clemens , Fischetti Robert , Smith Janet
Published: November 2015

GM/CA@APS operates two insertion-device beamlines, 23ID-B and 23ID-D, and one bending magnet beamline, 23BM-B, in sector 23 of the Advanced Photon Source. We recently integrated a Pilatus3 6M detector - a new generation of large sensitive area detectors based on pixel array detector technology and marketed by Dectris. The sensitive area of the device is 423.6 mm × 434.6 mm. The Pilatus3 features the newly implemented re-triggering mechanism that increases the count-rate capabilities by almost an order of magnitude compared to previous generation Pilatus detectors. The detector installed on beamline 23ID-D is the first Pilatus3 6M with a 1000-micron thick sensor, offering higher efficiency at energies above 12 keV. The fast read-out (0.95 ms) and high speed (up to 100 Hz) of the detector allow shutterless data collection. The detector has been fully integrated into the JBluIce user interface and data processing pipeline at GM/CA. Systematic studies with protein crystals were carried out in order to optimize data collection parameters. Overall data collection speed (frame rate), oscillation width per frame, spindle axis speed, and re-triggering have been studied. Different sets of optimal parameters have been established for crystallographic data collection and for crystal screening with the raster feature (grid scanning). The results of these studies and of performance measurements will be presented. This project and GM/CA @ APS are supported by the National Institute of General Medical Sciences and Cancer Institute of NIH.
A new energy-dispersive position sensitive detector
Authors: Kern Arnt
Published: November 2015

In this paper a new energy-dispersive position-sensitive line detector with an energy resolution better than 500eV will be introduced. This detector is based on the well known silicon strip technology and thus offers the same advantages in terms of intensity gain / measurement speed and angular resolution as its currently available predecessors. It can be operated both as a traditional line detector to acquire one-dimensional diffraction data, but also turned 900(perpendicular to the diffractometer plane) to acquire two-dimensional diffraction images (e.g. He, 2009). Its remarkable energy resolution allows to effectively filter Kß radiation and specimen fluorescense, eliminating the need for any Kß-filters or secondary monochromators and related intensity losses in both one- and two-dimensional X-ray diffraction. The detector technology as well as application examples will be discussed.
Data collection strategies for the Rayonix MX300HS 10 Hz CCD Detector
Authors: Jin Zhongmin , Chrzas John , Fait James , Fu Zheng-Qing , Salazar Rod , Gonczy John , Chinte Unmesh , Kandavelu Palani , Rose John , Wang Bi-Cheng
Published: November 2015

Investigating Data Collection Strategies for the Rayonix MX300HS 10 Hz CCD Detector Zhongmin Jin, John Chrzas, James Fait, Zheng-Qing Fu, Rod Salazar, John Gonczy, Unmesh Chinte, Palani Kandavelu, John P. Rose and Bi-Cheng Wang SERCAT, APS, Argonne National Lab, Argonne, IL 60439 and Department of Biochemistry & Molecular Biology, University of Georgia, Athens, GA 30602, USA. Earlier this year SER-CAT received its Rayonix MX300HS high-speed area detector purchased with funds awarded from an NIH grant. The detector is CCD based (4X4 taper/chip array) with a 1-2 millisecond readout speed and 8e-/pixel (78 micron/pixel) readout noise providing 10Hz data collection capabilities. In its slower readout mode, the readout noise can be further reduced to about 4e-/pixel, which is less than 1 ADU. The detector was installed in late January on beamline 22BM for integration with SER-CAT's beamline control system and commissioning. This detector is the first of its kind and its fast readout time will allow us to collect data in the traditional shuttered mode with both normal and low noise readout; or in shutter-less mode using 0.1 second exposures with constant rotation of crystal. Importantly, the shutter-less mode may enhance system precision and improve the quality of the resulting data since it should eliminate mechanical errors associated with shutter jitter, shutter synchronization and goniometer backlash during data collection. Based on our preliminary tests, shutter-less mode data collection has confirmed the expectation of being capable for providing better quality data than that from shuttered mode. Shutter-less data collection also offers the ability to efficiently collect fine slice data, which will further improve the signal to noise in the data. We will present the results from systematic tests of the detector in terms of frame width (rotation angle per frame), rotation speed, exposure time, dynamic range etc. Work supported in part by NIH NCRR (S10RR028976), SER-CAT, The University of Georgia and the Advanced Photon Source.
Detector Development Status and Outlook of the SACLA/SPring-8 Site
Authors: Hatsui Takaki , Ono Shun , Kudo Togo , Kobayashi Kazuo , Kameshima Takashi , Ozaki Kyosuke , Kirihara Yoichi , Omodani Motohiko , Teranishi Nobukazu
Published: November 2015

X-ray Free-Electron Laser facility, SACLA has been operational for more than 2 years. During the user runs, multi-port charge coupled device (MPCCD) detectors has been extensively used to deliver novel scientific results. In order to strengthen the facility capability, we are developing new variants of the MPCCD detectors[1]. Because some of the features such as high peak signal detection cannot be implemented by CCD technology, novel monolithic process based on silicon-on-insulator (SOI) sensor technology is under development. By employing the novel process, we are developing SOPHIAS sensor targeting the peak signal of 40000 photons at 7 keV within 100 micrometer square[2]. The SPring-8 site has proposed an upgrade of the storage ring to SPring-8 II. After the upgrades, we will obtain brighter x-rays, for example, 10^13 photons/second within a diameter of 100 nanometer. With this kind of bright X-ray sources, X-ray imaging detector with higher count rate, higher frame rate, and higher quantum efficiency up to 20-30 keV region is required. Detector development plan toward these targets are also discussed.
Fast and Wide Dynamic Range X-ray Detectors Enable Novel Science
Authors: Philipp Hugh , Shanks Katherine , Tate Mark , Weiss Joel , Gruner Sol
Published: November 2015

New and improved synchrotron radiation sources enable experiments that demand the ability to acquire successive hard (e.g., 10 keV) x-ray images at sub-microsecond rates or to quickly acquire x-ray patterns encompassing intensities that vary by 10^6 or more across single images. We describe two novel integrating Pixel Array Detectors (PADs) developed at Cornell University that accomplish these objectives. The Mixed-Mode PAD (MM-PAD) frames at > 1 KHz and can readily detect signals within a single image ranging from single x-rays to over 107 x-rays/pixel/frame. The Keck-PAD can acquire 8-12 successive images at frame rates approaching 10 MHz with a range of single x-rays up to about 10^4 x-rays/pixel/frame. The operating principles of the MM-PAD and Keck-PAD, respectively, are described. We also describe examples of experiments that have been performed at various synchrotron radiation sources.
Detector program for the LCLS complex
Authors: Kenney Chris , Blaj Gabriel , Caragiulo Pietro , Carini Gabriella , Dragone Angelo , Hart Philip , Hasi Jasmine , Herrmann Sven , Markovic Bojan , Osier Shawn , Segal Julie , Tomada Astrid , Haller Gunther
Published: November 2015

Over five years of operation the Linac Coherent Light Source has helped established free-electron lasers as a radically new paradigm for x-ray-based science. Part of this has been the demonstration of novel experimental techniques and the qualification of established methods in the LCLS environment. To take full advantage of this machine, a complimentary suite of detectors must be made available to scientists. Progress towards this goal will be described along with experience gained from operating within the LCLS environment. The status of currently installed detectors as well as future plans will be presented.
Guest Inclusion Crystal structures of Macrocyclic Boronic Esters
Authors: Toyoshima Ryosuke , Fujii Kotaro , Johmoto Kohei , Uekusa Hidehiro , Kikuchi Yuji , Takahagi Hiroki , Ono Kosuke , Iwasawa Nobuharu
Published: November 2015

Macrocyclic compound has been attracting increasing attention because of their application for guest absorption and storage, guest selectivity, and reaction environment, which would utilize void space in the compound. Recently, such macrocyclic compound, boronic esters, has found to be formed as dynamic self-assembly of organic molecules through solvent dependent dynamic covalent bond formation between racemic polyol and planar 1,4-benzen(boronic acid)[1]. Thus, it is important to determine the crystal structure of the macrocyclic boronic esters with incorporated guest molecule to reveal the features of the compounds. In this study, structures of boronic ester of 1,4- naphthalene(boronic acid) (1) are presented and compared. The boronic ester with toluene guest molecule crystalized in monoclinic system, C2/c, Z=4, V=5099.7(6) Å3. As expected, toluene molecule was accommodated within a ring sandwiched by two naphthalene rings suggesting π-π interaction (ca. 3.6 Å separations). It is interesting that other structures of 1 with 1,4-dicyanobenzene, chloroform, and THF also have isomorphic structures to 1 with toluene. It clearly shows the guest inclusion ability of this boronic ester by weak intermolecular interactions. In the crystal structures, the boronic ester aligned along b-axis forming one-dimensional stacking with channel structure filled with guest molecules. Also, 1 with chloroform has a pseudo-polymorph phase (P21/c, V=5780.8(13) Å3) that has two additional chloroform molecules inside and outside of the ring; however, it also shows similar one-dimensional stacking structure with channel, implying this boronic ester has an easily stacking molecular shape. Although, the molecules have similar [2+2] ring structure, dihedral angle between two facing naphthalene rings is different in 1 with toluene, which is smaller as 14.10than 22 to 240in other structures. It may indicate a flexibility of the macrocyclic ring.
Crystallographic studies of novel aryl heavy Group 14/15 halides and hydrides
Authors: Torvisco Ana , Binder Judith , Wolf Melanie , Zeppek Cathrin , Stammler Hans-Georg , Mitzel Norbert , Uhlig Frank
Published: November 2015

A series of novel aryl (phenyl, tolyl, xylyl, mesityl, naphthyl, anthracenyl) heavy Group 14 and 15 halides (Cl, Br) and hydrides have been synthesized and structurally characterized via X-ray diffraction. Depending on the nature of the aryl substituent, these compounds display a range of non-covalent intermolecular interactions in the form of edge to face, π-π stacking and C-H···π interactions resulting in discrete arrangements in the solid state. The strength of these interactions as well as halide or hydride substituent effects and their consequences on resulting structural parameters will be highlighted and discussed. In addition, in situ crystallization techniques were employed to elucidate the structures of highly air sensitive novel aryl tin and silicon hydride species.
Polymorphic Behaviour of 3-Chloromandelic acid
Authors: Tizzard Graham , Coles Simon , Ellis Amy , Hylton Rebecca , Price Sarah , Threlfall Terry
Published: November 2015

For several years we have been making detailed comparisons of the crystal structures of large sets of related compounds in an attempt to understand the factors determining the adoption of particular molecular arrangements within crystal structures. In all these projects, the XPac program [1] was used to identify similarity between structures in 0-dimensions (0D) (discrete molecular arrangements e.g. dimers, trimers etc),1D (chains or stacks), 2D (sheets or planes) and 3D (frameworks or full isostructurality) as a preliminary to the detailed comparison of the similarities so identified. As part of a larger crystallographic project to investigate the relationship between structure and chirality, we have synthesized and determined crystal structures of families of monosubstituted racemic mandelic acids with fluoro, chloro, bromo, iodo, trifluoromethyl, methyl and methoxy substituents at the ortho, meta and para positions. The substituted mandelic acids are polymorphically prolific and with the inclusion of unsubstituted mandelic acid, 28 structures have been compared. Of special interest has been 3-chloromandelic acid (3-ClMA), for which so far five polymorphs have been discovered: three racemic, two of which are isostructural [2], and two enantiopure. A crystal structure prediction (CSP) study of 3-ClMA has been carried out using the CrystalPredictor [3] and CrystalOptimizer [3] algorithms to generate the crystal energy landscape which is exceptionally dense with 3050 structures within 20 kJ mol-1. Many of these are more stable than the known forms, which is consistent with the complex crystallisation behaviour observed. From our observations of the crystallisation behaviour of substituted chloromandelic acids in general and the CSP study of 3-ClMA, we expect to discover further polymorphs of 3-ClMA and to this end cross-seeding experiments using crystals from differently substituted mandelic acids and a comprehensive polymorph screen are at present being undertaken.