Ab initio tensile experiment on a model of an intergranular glassy film in β-Si3N4 with prismatic surfaces

NASA Astrophysics Data System (ADS)

Ching, W. Y.; Rulis, Paul; Ouyang, Lizhi; Misra, A.

2009-02-01

We report the results of a large-scale ab initio simulation of an intergranular glassy film (IGF) model in β-Si3N4. It is shown that the stress-strain behavior under uniaxial load in the model with prismatic surfaces and few defective bonds is very different from an earlier IGF model with basal planes. The results are explained by the fundamental electronic structure of the model.

Serious Gaming for Test & Evaluation of Clean-Slate (Ab Initio) National Airspace System (NAS) Designs

NASA Technical Reports Server (NTRS)

Allen, B. Danette; Alexandrov, Natalia

2016-01-01

Incremental approaches to air transportation system development inherit current architectural constraints, which, in turn, place hard bounds on system capacity, efficiency of performance, and complexity. To enable airspace operations of the future, a clean-slate (ab initio) airspace design(s) must be considered. This ab initio National Airspace System (NAS) must be capable of accommodating increased traffic density, a broader diversity of aircraft, and on-demand mobility. System and subsystem designs should scale to accommodate the inevitable demand for airspace services that include large numbers of autonomous Unmanned Aerial Vehicles and a paradigm shift in general aviation (e.g., personal air vehicles) in addition to more traditional aerial vehicles such as commercial jetliners and weather balloons. The complex and adaptive nature of ab initio designs for the future NAS requires new approaches to validation, adding a significant physical experimentation component to analytical and simulation tools. In addition to software modeling and simulation, the ability to exercise system solutions in a flight environment will be an essential aspect of validation. The NASA Langley Research Center (LaRC) Autonomy Incubator seeks to develop a flight simulation infrastructure for ab initio modeling and simulation that assumes no specific NAS architecture and models vehicle-to-vehicle behavior to examine interactions and emergent behaviors among hundreds of intelligent aerial agents exhibiting collaborative, cooperative, coordinative, selfish, and malicious behaviors. The air transportation system of the future will be a complex adaptive system (CAS) characterized by complex and sometimes unpredictable (or unpredicted) behaviors that result from temporal and spatial interactions among large numbers of participants. A CAS not only evolves with a changing environment and adapts to it, it is closely coupled to all systems that constitute the environment. Thus, the ecosystem that contains the system and other systems evolves with the CAS as well. The effects of the emerging adaptation and co-evolution are difficult to capture with only combined mathematical and computational experimentation. Therefore, an ab initio flight simulation environment must accommodate individual vehicles, groups of self-organizing vehicles, and large-scale infrastructure behavior. Inspired by Massively Multiplayer Online Role Playing Games (MMORPG) and Serious Gaming, the proposed ab initio simulation environment is similar to online gaming environments in which player participants interact with each other, affect their environment, and expect the simulation to persist and change regardless of any individual player's active participation.

Large haematoxylin-stainable keratohyaline granules in solar keratoses: immunohistochemical comparison using anti-Ted-H-1 antibody and antiloricrin antibody.

PubMed

Takahashi, M; Horiuchi, Y; Tezuka, T

2005-11-01

Our previous study showed that large keratohyaline granules (KHG) in molluscum contagiosum that stained with haematoxylin also reacted with anti-Ted-H-1 monoclonal antibody (mAb), but not with antifilaggrin mAb or antiloricrin polyclonal antibody (pAb). This finding indicated that the Ted-H-1 antigenic protein is a haematoxylin-stainable protein in KHG. To clarify the identity of the major component protein of the large KHG in solar keratosis, another disorder in which large KHG are observed. An enzyme immunohistochemical study was performed using antifilaggrin mAb, anti-Ted-H-1 mAb and antiloricrin pAb. Immunofluorescent double staining and immunoelectron microscopic analyses were performed using anti-Ted-H-1 mAb and antiloricrin pAb. Antifilaggrin mAb, anti-Ted-H-1 mAb and antiloricrin pAb reacted with normal KHG in nonlesional skin of solar keratosis, while only anti-Ted-H-1 mAb reacted with the large KHG in the lesions of solar keratosis. Antifilaggrin mAb did not react with large KHG. Antiloricrin pAb reacted with the cell membrane of the stratum granulosum, but not with large KHG. These findings suggest that the haematoxylin-stainable protein in the large KHG would be a Ted-H-1 antigen protein which was neither filaggrin nor loricrin.

Multiscale modeling of current-induced switching in magnetic tunnel junctions using ab initio spin-transfer torques

NASA Astrophysics Data System (ADS)

Ellis, Matthew O. A.; Stamenova, Maria; Sanvito, Stefano

2017-12-01

There exists a significant challenge in developing efficient magnetic tunnel junctions with low write currents for nonvolatile memory devices. With the aim of analyzing potential materials for efficient current-operated magnetic junctions, we have developed a multi-scale methodology combining ab initio calculations of spin-transfer torque with large-scale time-dependent simulations using atomistic spin dynamics. In this work we introduce our multiscale approach, including a discussion on a number of possible schemes for mapping the ab initio spin torques into the spin dynamics. We demonstrate this methodology on a prototype Co/MgO/Co/Cu tunnel junction showing that the spin torques are primarily acting at the interface between the Co free layer and MgO. Using spin dynamics we then calculate the reversal switching times for the free layer and the critical voltages and currents required for such switching. Our work provides an efficient, accurate, and versatile framework for designing novel current-operated magnetic devices, where all the materials details are taken into account.

Characterization of the Atacama B-mode Search

NASA Astrophysics Data System (ADS)

Simon, S. M.; Raghunathan, S.; Appel, J. W.; Becker, D. T.; Campusano, L. E.; Cho, H. M.; Essinger-Hileman, T.; Ho, S. P.; Irwin, K. D.; Jarosik, N.; Kusaka, A.; Niemack, M. D.; Nixon, G. W.; Nolta, M. R.; Page, L. A.; Palma, G. A.; Parker, L. P.; Sievers, J. L.; Staggs, S. T.; Visnjic, K.

2014-07-01

The Atacama B-mode Search (ABS), which began observations in February of 2012, is a crossed-Dragone telescope located at an elevation of 5190 m in the Atacama Desert in Chile. ABS is searching for the B-mode polarization spectrum of the cosmic microwave background (CMB) at large angular scales from multipole moments of ` ~ 50 ~ 500, a range that includes the primor- dial B-mode peak from inflationary gravity waves at ~ 100. The ABS focal plane consists of 240 pixels sensitive to 145 GHz, each containing two transition-edge sensor bolometers coupled to orthogonal polarizations with a planar ortho-mode transducer. An ambient-temperature con- tinuously rotating half-wave plate and 4 K optics make the ABS instrument unique. We discuss the characterization of the detector spectral responses with a Fourier transform spectrometer and demonstrate that the pointing model is adequate. We also present measurements of the beam from point sources and compare them with simulations.

Retaining large and adjustable elastic strains of kilogram-scale Nb nanowires [Better Superconductor by Elastic Strain Engineering: Kilogram-scale Free-Standing Niobium Metal Composite with Large Retained Elastic Strains

DOE PAGES

Hao, Shijie; Cui, Lishan; Wang, Hua; ...

2016-02-10

Crystals held at ultrahigh elastic strains and stresses may exhibit exceptional physical and chemical properties. Individual metallic nanowires can sustain ultra-large elastic strains of 4-7%. However, retaining elastic strains of such magnitude in kilogram-scale nanowires is challenging. Here, we find that under active load, ~5.6% elastic strain can be achieved in Nb nanowires in a composite material. Moreover, large tensile (2.8%) and compressive (-2.4%) elastic strains can be retained in kilogram-scale Nb nanowires when the composite is unloaded to a free-standing condition. It is then demonstrated that the retained tensile elastic strains of Nb nanowires significantly increase their superconducting transitionmore » temperature and critical magnetic fields, corroborating ab initio calculations based on BCS theory. This free-standing nanocomposite design paradigm opens new avenues for retaining ultra-large elastic strains in great quantities of nanowires and elastic-strain-engineering at industrial scale.« less

Relating Ab Initio Mechanical Behavior of Intergranular Glassy Films in Γ-Si3N4 to Continuum Scales

NASA Astrophysics Data System (ADS)

Ouyang, L.; Chen, J.; Ching, W.; Misra, A.

2006-05-01

Nanometer thin intergranular glassy films (IGFs) form in polycrystalline ceramics during sintering at high temperatures. The structure and properties of these IGFs are significantly changed by doping with rare earth elements. We have performed highly accurate large-scale ab initio calculations of the mechanical properties of both undoped and Yittria doped (Y-IGF) model by theoretical uniaxial tensile experiments. Uniaxial strain was applied by incrementally stretching the super cell in one direction, while the other two dimensions were kept constant. At each strain, all atoms in the model were fully relaxed using Vienna Ab initio Simulation Package VASP. The relaxed model at a given strain serves as the starting position for the next increment of strain. This process is carried on until the total energy (TE) and stress data show that the "sample" is fully fractured. Interesting differences are seen between the stress-strain response of undoped and Y-doped models. For the undoped model, the stress-strain behavior indicates that the initial atomic structure of the IGF is such that there is negligible coupling between the x- and the y-z directions. However, once the behavior becomes non- linear the lateral stresses increase, indicating that the atomic structure evolves with loading [1]. To relate the ab initio calculations to the continuum scales we analyze the atomic-scale deformation field under this uniaxial loading [1]. The applied strain in the x-direction is mostly accommodated by the IGF part of the model and the crystalline part experiences almost negligible strain. As the overall strain on the sample is incrementally increased, the local strain field evolves such that locations proximal to the softer spots attract higher strains. As the load progresses, the strain concentration spots coalesce and eventually form persistent strain localization zone across the IGF. The deformation pattern obtained through ab initio calculations indicates that it is possible to construct discrete grain-scale models that may be used to bridge these calculations to the continuum scale for finite element analysis. Reference: 1. J. Chen, L. Ouyang, P. Rulis, A. Misra, W. Y. Ching, Phys. Rev. Lett. 95, 256103 (2005)

MULTISPECIES REACTIVE TRACER TEST IN A SAND AND GRAVEL AQUIFER, CAPE COD, MASSACHUSETTS: PART 1: EXPERIMENTAL DESIGN AND TRANSPORT OF BROMIDE AND NICKEL-EDTA TRACERS

EPA Science Inventory

In this report, we summarize a portion of the results of a large-scale tracer test conducted at the U. S. Geological Survey research site on Cape Cod, Massachusetts. The site is located on a large sand and gravel glacial outwash plain in an unconfined aquifer. In April 1993, ab...

Silicate Melts of the Protolunar Disk and the Formation of the Magma Ocean from AB Initio Simulations

NASA Astrophysics Data System (ADS)

Caracas, R.; Stewart, S. T.

2018-05-01

We employ large-scale first-principles molecular dynamics simulations to understand the physical and chemical behavior of the evolution of the molten protolunar disk from its formation all the way to the crystallization of the magma ocean.

Large scale Full QM-MD investigation of small peptides and insulin adsorption on ideal and defective TiO2 (1 0 0) surfaces. Influence of peptide size on interfacial bonds

NASA Astrophysics Data System (ADS)

Dubot, Pierre; Boisseau, Nicolas; Cenedese, Pierre

2018-05-01

Large biomolecule interaction with oxide surface has attracted a lot of attention because it drives behavior of implanted devices in the living body. To investigate the role of TiO2 surface structure on a large polypeptide (insulin) adsorption, we use a homemade mixed Molecular Dynamics-Full large scale Quantum Mechanics code. A specific re-parameterized (Ti) and globally convergent NDDO method fitted on high level ab initio method (coupled cluster CCSD(T) and DFT) allows us to safely describe the electronic structure of the whole insulin-TiO2 surface system (up to 4000 atoms). Looking specifically at carboxylate residues, we demonstrate in this work that specific interfacial bonds are obtained from the insulin/TiO2 system that are not observed in the case of smaller peptides (tripeptides, insulin segment chains with different configurations). We also demonstrate that a large part of the adsorption energy is compensated by insulin conformational energy changes and surface defects enhanced this trend. Large slab dimensions allow us to take into account surface defects that are actually beyond ab initio capabilities owing to size effect. These results highlight the influence of the surface structure on the conformation and therefore of the possible inactivity of an adsorbed polypeptides.

Manufacturing of High-Concentration Monoclonal Antibody Formulations via Spray Drying-the Road to Manufacturing Scale.

PubMed

Gikanga, Benson; Turok, Robert; Hui, Ada; Bowen, Mayumi; Stauch, Oliver B; Maa, Yuh-Fun

2015-01-01

Spray-dried monoclonal antibody (mAb) powders may offer applications more versatile than the freeze-dried cake, including preparing high-concentration formulations for subcutaneous administration. Published studies on this topic, however, are generally scarce. This study evaluates a pilot-scale spray dryer against a laboratory-scale dryer to spray-dry multiple mAbs in consideration of scale-up, impact on mAb stability, and feasibility of a high-concentration preparation. Under similar conditions, both dryers produced powders of similar properties-for example, water content, particle size and morphology, and mAb stability profile-despite a 4-fold faster output by the pilot-scale unit. All formulations containing arginine salt or a combination of arginine salt and trehalose were able to be spray-dried with high powder collection efficiency (>95%), but yield was adversely affected in formulations with high trehalose content due to powder sticking to the drying chamber. Spray-drying production output was dictated by the size of the dryer operated at an optimal liquid feed rate. Spray-dried powders could be reconstituted to high-viscosity liquids, >300 cP, substantially beyond what an ultrafiltration process can achieve. The molar ratio of trehalose to mAb needed to be reduced to 50:1 in consideration of isotonicity of the formulation with mAb concentration at 250 mg/mL. Even with this low level of sugar protection, long-term stability of spray-dried formulations remained superior to their liquid counterparts based on size variant and potency data. This study offers a commercially viable spray-drying process for biological bulk storage and an option for high-concentration mAb manufacturing. This study evaluates a pilot-scale spray dryer against a laboratory-scale dryer to spray-dry multiple monoclonal antibodies (mAbs) from the perspective of scale-up, impact on mAb stability, and feasibility of a high-concentration preparation. The data demonstrated that there is no process limitation in solution viscosity when high-concentration mAb formulations are prepared from spray-dried powder reconstitution compared with concentration via the conventional ultrafiltration process. This study offers a commercially viable spray-drying process for biological bulk storage and a high-concentration mAb manufacturing option for subcutaneous administration. The outcomes of this study will benefit scientists and engineers who develop high-concentration mAb products by providing a viable manufacturing alternative. © PDA, Inc. 2015.

In-column ATR-FTIR spectroscopy to monitor affinity chromatography purification of monoclonal antibodies

NASA Astrophysics Data System (ADS)

Boulet-Audet, Maxime; Kazarian, Sergei G.; Byrne, Bernadette

2016-07-01

In recent years many monoclonal antibodies (mAb) have entered the biotherapeutics market, offering new treatments for chronic and life-threatening diseases. Protein A resin captures monoclonal antibody (mAb) effectively, but the binding capacity decays over repeated purification cycles. On an industrial scale, replacing fouled Protein A affinity chromatography resin accounts for a large proportion of the raw material cost. Cleaning-in-place (CIP) procedures were developed to extend Protein A resin lifespan, but chromatograms cannot reliably quantify any remaining contaminants over repeated cycles. To study resin fouling in situ, we coupled affinity chromatography and Fourier transform infrared (FTIR) spectroscopy for the first time, by embedding an attenuated total reflection (ATR) sensor inside a micro-scale column while measuring the UV 280 nm and conductivity. Our approach quantified the in-column protein concentration in the resin bed and determined protein conformation. Our results show that Protein A ligand leached during CIP. We also found that host cell proteins bound to the Protein A resin even more strongly than mAbs and that typical CIP conditions do not remove all fouling contaminants. The insights derived from in-column ATR-FTIR spectroscopic monitoring could contribute to mAb purification quality assurance as well as guide the development of more effective CIP conditions to optimise resin lifespan.

In-column ATR-FTIR spectroscopy to monitor affinity chromatography purification of monoclonal antibodies

PubMed Central

Boulet-Audet, Maxime; Kazarian, Sergei G.; Byrne, Bernadette

2016-01-01

In recent years many monoclonal antibodies (mAb) have entered the biotherapeutics market, offering new treatments for chronic and life-threatening diseases. Protein A resin captures monoclonal antibody (mAb) effectively, but the binding capacity decays over repeated purification cycles. On an industrial scale, replacing fouled Protein A affinity chromatography resin accounts for a large proportion of the raw material cost. Cleaning-in-place (CIP) procedures were developed to extend Protein A resin lifespan, but chromatograms cannot reliably quantify any remaining contaminants over repeated cycles. To study resin fouling in situ, we coupled affinity chromatography and Fourier transform infrared (FTIR) spectroscopy for the first time, by embedding an attenuated total reflection (ATR) sensor inside a micro-scale column while measuring the UV 280 nm and conductivity. Our approach quantified the in-column protein concentration in the resin bed and determined protein conformation. Our results show that Protein A ligand leached during CIP. We also found that host cell proteins bound to the Protein A resin even more strongly than mAbs and that typical CIP conditions do not remove all fouling contaminants. The insights derived from in-column ATR-FTIR spectroscopic monitoring could contribute to mAb purification quality assurance as well as guide the development of more effective CIP conditions to optimise resin lifespan. PMID:27470880

Impact of incomplete metal coverage on the electrical properties of metal-CNT contacts: A large-scale ab initio study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fediai, Artem, E-mail: artem.fediai@nano.tu-dresden.de; Ryndyk, Dmitry A.; Center for Advancing Electronics Dresden, TU Dresden, 01062 Dresden

2016-09-05

Using a dedicated combination of the non-equilibrium Green function formalism and large-scale density functional theory calculations, we investigated how incomplete metal coverage influences two of the most important electrical properties of carbon nanotube (CNT)-based transistors: contact resistance and its scaling with contact length, and maximum current. These quantities have been derived from parameter-free simulations of atomic systems that are as close as possible to experimental geometries. Physical mechanisms that govern these dependences have been identified for various metals, representing different CNT-metal interaction strengths from chemisorption to physisorption. Our results pave the way for an application-oriented design of CNT-metal contacts.

A high-throughput shotgun mutagenesis approach to mapping B-cell antibody epitopes.

PubMed

Davidson, Edgar; Doranz, Benjamin J

2014-09-01

Characterizing the binding sites of monoclonal antibodies (mAbs) on protein targets, their 'epitopes', can aid in the discovery and development of new therapeutics, diagnostics and vaccines. However, the speed of epitope mapping techniques has not kept pace with the increasingly large numbers of mAbs being isolated. Obtaining detailed epitope maps for functionally relevant antibodies can be challenging, particularly for conformational epitopes on structurally complex proteins. To enable rapid epitope mapping, we developed a high-throughput strategy, shotgun mutagenesis, that enables the identification of both linear and conformational epitopes in a fraction of the time required by conventional approaches. Shotgun mutagenesis epitope mapping is based on large-scale mutagenesis and rapid cellular testing of natively folded proteins. Hundreds of mutant plasmids are individually cloned, arrayed in 384-well microplates, expressed within human cells, and tested for mAb reactivity. Residues are identified as a component of a mAb epitope if their mutation (e.g. to alanine) does not support candidate mAb binding but does support that of other conformational mAbs or allows full protein function. Shotgun mutagenesis is particularly suited for studying structurally complex proteins because targets are expressed in their native form directly within human cells. Shotgun mutagenesis has been used to delineate hundreds of epitopes on a variety of proteins, including G protein-coupled receptor and viral envelope proteins. The epitopes mapped on dengue virus prM/E represent one of the largest collections of epitope information for any viral protein, and results are being used to design better vaccines and drugs. © 2014 John Wiley & Sons Ltd.

Density-matrix based determination of low-energy model Hamiltonians from ab initio wavefunctions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Changlani, Hitesh J.; Zheng, Huihuo; Wagner, Lucas K.

2015-09-14

We propose a way of obtaining effective low energy Hubbard-like model Hamiltonians from ab initio quantum Monte Carlo calculations for molecular and extended systems. The Hamiltonian parameters are fit to best match the ab initio two-body density matrices and energies of the ground and excited states, and thus we refer to the method as ab initio density matrix based downfolding. For benzene (a finite system), we find good agreement with experimentally available energy gaps without using any experimental inputs. For graphene, a two dimensional solid (extended system) with periodic boundary conditions, we find the effective on-site Hubbard U{sup ∗}/t tomore » be 1.3 ± 0.2, comparable to a recent estimate based on the constrained random phase approximation. For molecules, such parameterizations enable calculation of excited states that are usually not accessible within ground state approaches. For solids, the effective Hamiltonian enables large-scale calculations using techniques designed for lattice models.« less

Electron transport in extended carbon-nanotube/metal contacts: Ab initio based Green function method

NASA Astrophysics Data System (ADS)

Fediai, Artem; Ryndyk, Dmitry A.; Cuniberti, Gianaurelio

2015-04-01

We have developed a new method that is able to predict the electrical properties of the source and drain contacts in realistic carbon nanotube field effect transistors (CNTFETs). It is based on large-scale ab initio calculations combined with a Green function approach. For the first time, both internal and external parts of a realistic CNT-metal contact are taken into account at the ab initio level. We have developed the procedure allowing direct calculation of the self-energy for an extended contact. Within the method, it is possible to calculate the transmission coefficient through a contact of both finite and infinite length; the local density of states can be determined in both free and embedded CNT segments. We found perfect agreement with the experimental data for Pd and Al contacts. We have explained why CNTFETs with Pd electrodes are p -type FETs with ohmic contacts, which can carry current close to the ballistic limit (provided contact length is large enough), whereas in CNT-Al contacts transmission is suppressed to a significant extent, especially for holes.

Preface: Introductory Remarks: Linear Scaling Methods

NASA Astrophysics Data System (ADS)

Bowler, D. R.; Fattebert, J.-L.; Gillan, M. J.; Haynes, P. D.; Skylaris, C.-K.

2008-07-01

It has been just over twenty years since the publication of the seminal paper on molecular dynamics with ab initio methods by Car and Parrinello [1], and the contribution of density functional theory (DFT) and the related techniques to physics, chemistry, materials science, earth science and biochemistry has been huge. Nevertheless, significant improvements are still being made to the performance of these standard techniques; recent work suggests that speed improvements of one or even two orders of magnitude are possible [2]. One of the areas where major progress has long been expected is in O(N), or linear scaling, DFT, in which the computer effort is proportional to the number of atoms. Linear scaling DFT methods have been in development for over ten years [3] but we are now in an exciting period where more and more research groups are working on these methods. Naturally there is a strong and continuing effort to improve the efficiency of the methods and to make them more robust. But there is also a growing ambition to apply them to challenging real-life problems. This special issue contains papers submitted following the CECAM Workshop 'Linear-scaling ab initio calculations: applications and future directions', held in Lyon from 3-6 September 2007. A noteworthy feature of the workshop is that it included a significant number of presentations involving real applications of O(N) methods, as well as work to extend O(N) methods into areas of greater accuracy (correlated wavefunction methods, quantum Monte Carlo, TDDFT) and large scale computer architectures. As well as explicitly linear scaling methods, the conference included presentations on techniques designed to accelerate and improve the efficiency of standard (that is non-linear-scaling) methods; this highlights the important question of crossover—that is, at what size of system does it become more efficient to use a linear-scaling method? As well as fundamental algorithmic questions, this brings up implementation questions relating to parallelization (particularly with multi-core processors starting to dominate the market) and inherent scaling and basis sets (in both normal and linear scaling codes). For now, the answer seems to lie between 100-1,000 atoms, though this depends on the type of simulation used among other factors. Basis sets are still a problematic question in the area of electronic structure calculations. The linear scaling community has largely split into two camps: those using relatively small basis sets based on local atomic-like functions (where systematic convergence to the full basis set limit is hard to achieve); and those that use necessarily larger basis sets which allow convergence systematically and therefore are the localised equivalent of plane waves. Related to basis sets is the study of Wannier functions, on which some linear scaling methods are based and which give a good point of contact with traditional techniques; they are particularly interesting for modelling unoccupied states with linear scaling methods. There are, of course, as many approaches to linear scaling solution for the density matrix as there are groups in the area, though there are various broad areas: McWeeny-based methods, fragment-based methods, recursion methods, and combinations of these. While many ideas have been in development for several years, there are still improvements emerging, as shown by the rich variety of the talks below. Applications using O(N) DFT methods are now starting to emerge, though they are still clearly not trivial. Once systems to be simulated cross the 10,000 atom barrier, only linear scaling methods can be applied, even with the most efficient standard techniques. One of the most challenging problems remaining, now that ab initio methods can be applied to large systems, is the long timescale problem. Although much of the work presented was concerned with improving the performance of the codes, and applying them to scientificallyimportant problems, there was another important theme: extending functionality. The search for greater accuracy has given an implementation of density functional designed to model van der Waals interactions accurately as well as local correlation, TDDFT and QMC and GW methods which, while not explicitly O(N), take advantage of localisation. All speakers at the workshop were invited to contribute to this issue, but not all were able to do this. Hence it is useful to give a complete list of the talks presented, with the names of the sessions; however, many talks fell within more than one area. This is an exciting time for linear scaling methods, which are already starting to contribute significantly to important scientific problems. Applications to nanostructures and biomolecules A DFT study on the structural stability of Ge 3D nanostructures on Si(001) using CONQUEST Tsuyoshi Miyazaki, D R Bowler, M J Gillan, T Otsuka and T Ohno Large scale electronic structure calculation theory and several applications Takeo Fujiwara and Takeo Hoshi ONETEP:Linear-scaling DFT with plane waves Chris-Kriton Skylaris, Peter D Haynes, Arash A Mostofi, Mike C Payne Maximally-localised Wannier functions as building blocks for large-scale electronic structure calculations Arash A Mostofi and Nicola Marzari A linear scaling three dimensional fragment method for ab initio calculations Lin-Wang Wang, Zhengji Zhao, Juan Meza Peta-scalable reactive Molecular dynamics simulation of mechanochemical processes Aiichiro Nakano, Rajiv K. Kalia, Ken-ichi Nomura, Fuyuki Shimojo and Priya Vashishta Recent developments and applications of the real-space multigrid (RMG) method Jerzy Bernholc, M Hodak, W Lu, and F Ribeiro Energy minimisation functionals and algorithms CONQUEST: A linear scaling DFT Code David R Bowler, Tsuyoshi Miyazaki, Antonio Torralba, Veronika Brazdova, Milica Todorovic, Takao Otsuka and Mike Gillan Kernel optimisation and the physical significance of optimised local orbitals in the ONETEP code Peter Haynes, Chris-Kriton Skylaris, Arash Mostofi and Mike Payne A miscellaneous overview of SIESTA algorithms Jose M Soler Wavelets as a basis set for electronic structure calculations and electrostatic problems Stefan Goedecker Wavelets as a basis set for linear scaling electronic structure calculationsMark Rayson O(N) Krylov subspace method for large-scale ab initio electronic structure calculations Taisuke Ozaki Linear scaling calculations with the divide-and-conquer approach and with non-orthogonal localized orbitals Weitao Yang Toward efficient wavefunction based linear scaling energy minimization Valery Weber Accurate O(N) first-principles DFT calculations using finite differences and confined orbitals Jean-Luc Fattebert Linear-scaling methods in dynamics simulations or beyond DFT and ground state properties An O(N) time-domain algorithm for TDDFT Guan Hua Chen Local correlation theory and electronic delocalization Joseph Subotnik Ab initio molecular dynamics with linear scaling: foundations and applications Eiji Tsuchida Towards a linear scaling Car-Parrinello-like approach to Born-Oppenheimer molecular dynamics Thomas Kühne, Michele Ceriotti, Matthias Krack and Michele Parrinello Partial linear scaling for quantum Monte Carlo calculations on condensed matter Mike Gillan Exact embedding of local defects in crystals using maximally localized Wannier functions Eric Cancès Faster GW calculations in larger model structures using ultralocalized nonorthogonal Wannier functions Paolo Umari Other approaches for linear-scaling, including methods formetals Partition-of-unity finite element method for large, accurate electronic-structure calculations of metals John E Pask and Natarajan Sukumar Semiclassical approach to density functional theory Kieron Burke Ab initio transport calculations in defected carbon nanotubes using O(N) techniques Blanca Biel, F J Garcia-Vidal, A Rubio and F Flores Large-scale calculations with the tight-binding (screened) KKR method Rudolf Zeller Acknowledgments We gratefully acknowledge funding for the workshop from the UK CCP9 network, CECAM and the ESF through the PsiK network. DRB, PDH and CKS are funded by the Royal Society. References [1] Car R and Parrinello M 1985 Phys. Rev. Lett. 55 2471 [2] Kühne T D, Krack M, Mohamed F R and Parrinello M 2007 Phys. Rev. Lett. 98 066401 [3] Goedecker S 1999 Rev. Mod. Phys. 71 1085

A novel bicistronic gene design couples stable cell line selection with a fucose switch in a designer CHO host to produce native and afucosylated glycoform antibodies.

PubMed

Roy, Gargi; Martin, Tom; Barnes, Arnita; Wang, Jihong; Jimenez, Rod Brian; Rice, Megan; Li, Lina; Feng, Hui; Zhang, Shu; Chaerkady, Raghothama; Wu, Herren; Marelli, Marcello; Hatton, Diane; Zhu, Jie; Bowen, Michael A

2018-04-01

The conserved glycosylation site Asn 297 of a monoclonal antibody (mAb) can be decorated with a variety of sugars that can alter mAb pharmacokinetics and recruitment of effector proteins. Antibodies lacking the core fucose at Asn 297 (afucosylated mAbs) show enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and increased efficacy. Here, we describe the development of a robust platform for the manufacture of afucosylated therapeutic mAbs by engineering a Chinese hamster ovary (CHO) host cell line to co-express a mAb with GDP-6-deoxy-D-lyxo-4-hexulose reductase (RMD), a prokaryotic enzyme that deflects an intermediate in the de novo synthesis of fucose to a dead-end product, resulting in the production of afucosylated mAb (GlymaxX™ Technology, ProBioGen). Expression of the mAb and RMD genes was coordinated by co-transfection of separate mAb and RMD vectors or use of an internal ribosome entry site (IRES) element to link the translation of RMD with either the glutamine synthase selection marker or the mAb light chain. The GS-IRES-RMD vector format was more suitable for the rapid generation of high yielding cell lines, secreting afucosylated mAb with titers exceeding 6.0 g/L. These cell lines maintained production of afucosylated mAb over 60 generations, ensuring their suitability for use in large-scale manufacturing. The afucosylated mAbs purified from these RMD-engineered cell lines showed increased binding in a CD16 cellular assay, demonstrating enhancement of ADCC compared to fucosylated control mAb. Furthermore, the afucosylation in these mAbs could be controlled by simple addition of L-fucose in the culture medium, thereby allowing the use of a single cell line for production of the same mAb in fucosylated and afucosylated formats for multiple therapeutic indications.

Exploring the Validity of the Affect Balance Scale With a Sample of Family Caregivers

PubMed Central

Perkinson, Margaret A.; Albert, Steven M.; Luborsky, Mark; Moss, Miriam; Glicksman, Allen

2014-01-01

Open-ended responses of caregiving daughters and daughters-in-law were generated by a modified random probe technique to investigate the construct validity of the two subscales of the Affect Balance Scale (ABS), i.e., the 5-item Positive Affect Scale (PAS) and the 5-item Negative Affect Scale (NAS). A set of criteria were developed to distinguish between responses that did and did not correspond to Bradburn’s assumptions concerning affect. While most responses met at least one of the criteria, very few met all. In exploring the nature of affect, we found that positive affect was based to a large extent on personal accomplishments and the recognition of others. The assessment of negative affect was a more interior, or self-focused process. For a significant subset of the sample, a negative response to a closed-ended PAS or NAS item implied disagreement or discontent with the wording or the implications of the item itself, rather than an absence of affect. Not all of the ABS items were equally valid measures of affect. PMID:8056955

An optimum A-B scale of psychotherapist effectiveness.

PubMed

Stephens, J H; Shaffer, J W; Zlotowitz, H I

1975-04-01

On the basis of the original Whitehorn-Betz data collected over a 16-year period, it is shown that all previously derived A-B scales of psychotherapist effectiveness using Strong Vocational Interest Blank (SVIB) items are deficient in terms of correlation with the original criterion and, frequently, in terms of reliability as well. The reasons for these deficiencies are discussed, and a new experimental A-B scale is formulated and tested for adequacy. This scale is shown to possess substantial internal consistency reliability and to have a high degree of correlation with the criterion even after the removal of possible contaminating factors such as use ofancillary teatments, differences in patient prognosis, and changing practices and interest over time. It is further shown that none of the A-B scales has any validity with respect to female therapists in the original data pool. Exploration of the factor-analytic structure of this new scale and two other widely used A-B measures in terms of the occupationa scales of the SVIB reveals differential loadings on four dimensions labeled verbal/comceptual vs. manual/practical, scientific vs. sales, social concern, and artistic vs. business-oriented. It is concluded that although male therapists' scores on the best of the A-B scales may , under certain circumstances,be related to short term judged improvement in patients treated, there is little evidence that high scoring therapists are more likey than low scoring ones to have a favorable, long range impact on diagnosed schizophrenics.

Hydrogen diffusion in liquid aluminum from ab initio molecular dynamics

NASA Astrophysics Data System (ADS)

Jakse, N.; Pasturel, A.

2014-05-01

Ab initio molecular dynamics simulations are used to describe the diffusion of hydrogen in liquid aluminum at different temperatures. Quasi-instantaneous jumps separating periods of localized vibrations around a mean position are found to characterize the hydrogen motion at the microscopic scale. The hydrogen motion is furthermore analyzed using the van Hove function. We highlight a non-Fickian behavior for the hydrogen diffusion due to a large spatial distribution of hydrogen jumps. We show that a generalized continuous time random walk (CTRW) model describes the experimental diffusion coefficients in a satisfactory manner. Finally, the impact of impurities and alloying elements on hydrogen diffusion in aluminum is discussed.

Monoclonal antibody proteomics: use of antibody mimotope displaying phages and the relevant synthetic peptides for mAb scouting.

PubMed

Hajdú, István; Flachner, Beáta; Bognár, Melinda; Végh, Barbara M; Dobi, Krisztina; Lőrincz, Zsolt; Lázár, József; Cseh, Sándor; Takács, László; Kurucz, István

2014-08-01

Monoclonal antibody proteomics uses nascent libraries or cloned (Plasmascan™, QuantiPlasma™) libraries of mAbs that react with individual epitopes of proteins in the human plasma. At the initial phase of library creation, cognate protein antigen and the epitope interacting with the antibodies are not known. Scouting for monoclonal antibodies (mAbs) with the best binding characteristics is of high importance for mAb based biomarker assay development. However, in the absence of the identity of the cognate antigen the task represents a challenge. We combined phage display, and surface plasmon resonance (Biacore) experiments to test whether specific phages and the respective mimotope peptides obtained from large scale studies are applicable to determine key features of antibodies for scouting. We show here that mAb captured phage-mimotope heterogeneity that is the diversity of the selected peptide sequences, is inversely correlated with an important binding descriptor; the off-rate of the antibodies and that represents clues for driving the selection of useful mAbs for biomarker assay development. Carefully chosen synthetic mimotope peptides are suitable for specificity testing in competitive assays using the target proteome, in our case the human plasma. Copyright © 2014 Elsevier B.V. All rights reserved.

Scaling and memory in volatility return intervals in financial markets

NASA Astrophysics Data System (ADS)

Yamasaki, Kazuko; Muchnik, Lev; Havlin, Shlomo; Bunde, Armin; Stanley, H. Eugene

2005-06-01

For both stock and currency markets, we study the return intervals τ between the daily volatilities of the price changes that are above a certain threshold q. We find that the distribution function Pq(τ) scales with the mean return interval [Formula] as [Formula]. The scaling function f(x) is similar in form for all seven stocks and for all seven currency databases analyzed, and f(x) is consistent with a power-law form, f(x) ˜ x-γ with γ ≈ 2. We also quantify how the conditional distribution Pq(τ|τ0) depends on the previous return interval τ0 and find that small (or large) return intervals are more likely to be followed by small (or large) return intervals. This “clustering” of the volatility return intervals is a previously unrecognized phenomenon that we relate to the long-term correlations known to be present in the volatility. Author contributions: S.H. and H.E.S. designed research; K.Y., L.M., S.H., and H.E.S. performed research; A.B. contributed new reagents/analytic tools; A.B. analyzed data; and S.H. wrote the paper.Abbreviations: pdf, probability density function; S&P 500, Standard and Poor's 500 Index; USD, U.S. dollar; JPY, Japanese yen; SEK, Swedish krona.

Chemically intuited, large-scale screening of MOFs by machine learning techniques

NASA Astrophysics Data System (ADS)

Borboudakis, Giorgos; Stergiannakos, Taxiarchis; Frysali, Maria; Klontzas, Emmanuel; Tsamardinos, Ioannis; Froudakis, George E.

2017-10-01

A novel computational methodology for large-scale screening of MOFs is applied to gas storage with the use of machine learning technologies. This approach is a promising trade-off between the accuracy of ab initio methods and the speed of classical approaches, strategically combined with chemical intuition. The results demonstrate that the chemical properties of MOFs are indeed predictable (stochastically, not deterministically) using machine learning methods and automated analysis protocols, with the accuracy of predictions increasing with sample size. Our initial results indicate that this methodology is promising to apply not only to gas storage in MOFs but in many other material science projects.

Two-Level Chebyshev Filter Based Complementary Subspace Method: Pushing the Envelope of Large-Scale Electronic Structure Calculations.

PubMed

Banerjee, Amartya S; Lin, Lin; Suryanarayana, Phanish; Yang, Chao; Pask, John E

2018-06-12

We describe a novel iterative strategy for Kohn-Sham density functional theory calculations aimed at large systems (>1,000 electrons), applicable to metals and insulators alike. In lieu of explicit diagonalization of the Kohn-Sham Hamiltonian on every self-consistent field (SCF) iteration, we employ a two-level Chebyshev polynomial filter based complementary subspace strategy to (1) compute a set of vectors that span the occupied subspace of the Hamiltonian; (2) reduce subspace diagonalization to just partially occupied states; and (3) obtain those states in an efficient, scalable manner via an inner Chebyshev filter iteration. By reducing the necessary computation to just partially occupied states and obtaining these through an inner Chebyshev iteration, our approach reduces the cost of large metallic calculations significantly, while eliminating subspace diagonalization for insulating systems altogether. We describe the implementation of the method within the framework of the discontinuous Galerkin (DG) electronic structure method and show that this results in a computational scheme that can effectively tackle bulk and nano systems containing tens of thousands of electrons, with chemical accuracy, within a few minutes or less of wall clock time per SCF iteration on large-scale computing platforms. We anticipate that our method will be instrumental in pushing the envelope of large-scale ab initio molecular dynamics. As a demonstration of this, we simulate a bulk silicon system containing 8,000 atoms at finite temperature, and obtain an average SCF step wall time of 51 s on 34,560 processors; thus allowing us to carry out 1.0 ps of ab initio molecular dynamics in approximately 28 h (of wall time).

Solving large scale unit dilemma in electricity system by applying commutative law

NASA Astrophysics Data System (ADS)

Legino, Supriadi; Arianto, Rakhmat

2018-03-01

The conventional system, pooling resources with large centralized power plant interconnected as a network. provides a lot of advantages compare to the isolated one include optimizing efficiency and reliability. However, such a large plant need a huge capital. In addition, more problems emerged to hinder the construction of big power plant as well as its associated transmission lines. By applying commutative law of math, ab = ba, for all a,b €-R, the problem associated with conventional system as depicted above, can be reduced. The idea of having small unit but many power plants, namely “Listrik Kerakyatan,” abbreviated as LK provides both social and environmental benefit that could be capitalized by using proper assumption. This study compares the cost and benefit of LK to those of conventional system, using simulation method to prove that LK offers alternative solution to answer many problems associated with the large system. Commutative Law of Algebra can be used as a simple mathematical model to analyze whether the LK system as an eco-friendly distributed generation can be applied to solve various problems associated with a large scale conventional system. The result of simulation shows that LK provides more value if its plants operate in less than 11 hours as peaker power plant or load follower power plant to improve load curve balance of the power system. The result of simulation indicates that the investment cost of LK plant should be optimized in order to minimize the plant investment cost. This study indicates that the benefit of economies of scale principle does not always apply to every condition, particularly if the portion of intangible cost and benefit is relatively high.

Entanglement and area law with a fractal boundary in a topologically ordered phase

NASA Astrophysics Data System (ADS)

Hamma, Alioscia; Lidar, Daniel A.; Severini, Simone

2010-01-01

Quantum systems with short-range interactions are known to respect an area law for the entanglement entropy: The von Neumann entropy S associated to a bipartition scales with the boundary p between the two parts. Here we study the case in which the boundary is a fractal. We consider the topologically ordered phase of the toric code with a magnetic field. When the field vanishes it is possible to analytically compute the entanglement entropy for both regular and fractal bipartitions (A,B) of the system and this yields an upper bound for the entire topological phase. When the A-B boundary is regular we have S/p=1 for large p. When the boundary is a fractal of the Hausdorff dimension D, we show that the entanglement between the two parts scales as S/p=γ⩽1/D, and γ depends on the fractal considered.

Large-Scale Hybrid Density Functional Theory Calculations in the Condensed-Phase: Ab Initio Molecular Dynamics in the Isobaric-Isothermal Ensemble

NASA Astrophysics Data System (ADS)

Ko, Hsin-Yu; Santra, Biswajit; Distasio, Robert A., Jr.; Wu, Xifan; Car, Roberto

Hybrid functionals are known to alleviate the self-interaction error in density functional theory (DFT) and provide a more accurate description of the electronic structure of molecules and materials. However, hybrid DFT in the condensed-phase has a prohibitively high associated computational cost which limits their applicability to large systems of interest. In this work, we present a general-purpose order(N) implementation of hybrid DFT in the condensed-phase using Maximally localized Wannier function; this implementation is optimized for massively parallel computing architectures. This algorithm is used to perform large-scale ab initio molecular dynamics simulations of liquid water, ice, and aqueous ionic solutions. We have performed simulations in the isothermal-isobaric ensemble to quantify the effects of exact exchange on the equilibrium density properties of water at different thermodynamic conditions. We find that the anomalous density difference between ice I h and liquid water at ambient conditions as well as the enthalpy differences between ice I h, II, and III phases at the experimental triple point (238 K and 20 Kbar) are significantly improved using hybrid DFT over previous estimates using the lower rungs of DFT This work has been supported by the Department of Energy under Grants No. DE-FG02-05ER46201 and DE-SC0008626.

Is there a place for nutrition-sensitive agriculture?

PubMed

Wambugu, Florence; Obukosia, Silas; Gaffney, Jim; Kamanga, Daniel; Che, Ping; Albertsen, Marc C; Zhao, Zuo-Yu; Ragland, Lonnetta; Yeye, Mary; Kimani, Esther; Aba, Daniel; Gidado, Rose; Solomon, B O; Njuguna, Michael

2015-11-01

The focus of the review paper is to discuss how biotechnological innovations are opening new frontiers to mitigate nutrition in key agricultural crops with potential for large-scale health impact to people in Africa. The general objective of the Africa Biofortified Sorghum (ABS) project is to develop and deploy sorghum with enhanced pro-vitamin A to farmers and end-users in Africa to alleviate vitamin A-related micronutrient deficiency diseases. To achieve this objective the project technology development team has developed several promising high pro-vitamin A sorghum events. ABS 203 events are so far the most advanced and well-characterised lead events with about 12 μg β-carotene/g tissue which would supply about 40-50 % of the daily recommended vitamin A at harvest. Through gene expression optimisation other events with higher amounts of pro-vitamin A, including ABS 214, ABS 235, ABS 239 with 25, 30-40, 40-50 μg β-carotene/g tissue, respectively, have been developed. ABS 239 would provide twice recommended pro-vitamin A at harvest, 50-90 % after 3 months storage and 13-45 % after 6 months storage for children. Preliminary results of introgression of ABS pro-vitamin A traits into local sorghum varieties in target countries Nigeria and Kenya show stable introgression of ABS vitamin A into local farmer-preferred sorghums varieties. ABS gene Intellectual Property Rights and Freedom to Operate have been donated for use royalty free for Africa. Prior to the focus on the current target countries, the project was implemented by fourteen institutions in Africa and the USA. For the next 5 years, the project will complete ABS product development, complete regulatory science data package and apply for product deregulation in target African countries.

IgY Antibodies Protect against Human Rotavirus Induced Diarrhea in the Neonatal Gnotobiotic Piglet Disease Model

PubMed Central

Vega, Celina G.; Bok, Marina; Vlasova, Anastasia N.; Chattha, Kuldeep S.; Fernández, Fernando M.; Wigdorovitz, Andrés; Parreño, Viviana G.; Saif, Linda J.

2012-01-01

Group A Rotaviruses are the most common cause of severe, dehydrating diarrhea in children worldwide. The aim of the present work was to evaluate protection against rotavirus (RV) diarrhea conferred by the prophylactic administration of specific IgY antibodies (Ab) to gnotobiotic piglets experimentally inoculated with virulent Wa G1P[8] human rotavirus (HRV). Chicken egg yolk IgY Ab generated from Wa HRV hyperimmunized hens specifically recognized (ELISA) and neutralized Wa HRV in vitro. Supplementation of the RV Ab free cow milk diet with Wa HRV-specific egg yolk IgY Ab at a final ELISA Ab titer of 4096 (virus neutralization –VN- titer = 256) for 9 days conferred full protection against Wa HRV associated diarrhea and significantly reduced virus shedding. This protection was dose-dependent. The oral administration of semi-purified passive IgY Abs from chickens did not affect the isotype profile of the pig Ab secreting cell (ASC) responses to Wa HRV infection, but it was associated with significantly fewer numbers of HRV–specific IgA ASC in the duodenum. We further analyzed the pigś immune responses to the passive IgY treatment. The oral administration of IgY Abs induced IgG Ab responses to chicken IgY in serum and local IgA and IgG Ab responses to IgY in the intestinal contents of neonatal piglets in a dose dependent manner. To our knowledge, this is the first study to show that IgY Abs administered orally as a milk supplement passively protect neonatal pigs against an enteric viral pathogen (HRV). Piglets are an animal model with a gastrointestinal physiology and an immune system that closely mimic human infants. This strategy can be scaled-up to inexpensively produce large amounts of polyclonal IgY Abs from egg yolks to be applied as a preventive and therapeutic passive Ab treatment to control RV diarrhea. PMID:22880110

The American Association on Mental Deficiency-Adaptive Behavior Scale: Allowing Credit for Alternative Means of Communication.

ERIC Educational Resources Information Center

Suess, James F.; And Others

1983-01-01

Compared were the Adaptive Behavior Scale (ABS) and a modified version of the ABS (which allowed alternative methods of communication such as sign language) with 134 deaf-blind persons, three to 30 years old. Among results were that alternative communication methods had no effect on nine of 10 ABS domains. (Author/MC)

Evaluation of immobilized metal membrane affinity chromatography for purification of an immunoglobulin G1 monoclonal antibody.

PubMed

Serpa, Gisele; Augusto, Elisabeth Fátima Pires; Tamashiro, Wirla Maria Silva Cunha; Ribeiro, Mariana Borçoe; Miranda, Everson Alves; Bueno, Sônia Maria Alves

2005-02-25

The large scale production of monoclonal antibodies (McAbs) has gaining increased relevance with the development of the hybridoma cell culture in bioreactors creating a need for specific efficient bioseparation techniques. Conventional fixed bead affinity adsorption commonly applied for McAbs purification has the drawback of low flow rates and colmatage. We developed and evaluated a immobilized metal affinity chromatographies (IMAC) affinity membrane for the purification of anti-TNP IgG(1) mouse McAbs. We immobilized metal ions on a poly(ethylene vinyl alcohol) hollow fiber membrane (Me(2+)-IDA-PEVA) and applied it for the purification of this McAbs from cell culture supernatant after precipitation with 50% saturation of ammonium sulphate. The purity of IgG(1) in the eluate fractions was high when eluted from Zn(2+) complex. The anti-TNP antibody could be eluted under conditions causing no loss of antigen binding capacity. The purification procedure can be considered as an alternative to the biospecific adsorbent commonly applied for mouse IgG(1) purification, the protein G-Sepharose.

Study of Higgs effective couplings at electron-proton colliders

NASA Astrophysics Data System (ADS)

Hesari, Hoda; Khanpour, Hamzeh; Najafabadi, Mojtaba Mohammadi

2018-05-01

We perform a search for beyond-the-Standard-Model (BSM) dimension-six operators relevant to the Higgs boson at the Large Hadron Electron Collider (LHeC) and the Future Circular Hadron Electron Collider (FCC-he). With a large amount of data (few ab-1 ) and collisions at the TeV scale, both LHeC and FCC-he provide excellent opportunities to search for the BSM effects. The study is done through the process e-p →h j νe , where the Higgs boson decays into a pair of b b ¯, and we consider the main sources of background processes, including a realistic simulation of detector effects. For the FCC-he case, in some signal scenarios, to obtain an efficient event reconstruction and to have a good background rejection, jet substructure techniques are employed to reconstruct the boosted Higgs boson in the final state. In order to assess the sensitivity to the dimension-six operators, a shape analysis on the differential cross sections is performed. Stringent bounds are found on the Wilson coefficients of dimension-six operators with the integrated luminosities of 1 ab-1 and 10 ab-1 , which in some cases show improvements with respect to the high-luminosity LHC results.

Ab Initio Potential Energy Surfaces and the Calculation of Accurate Vibrational Frequencies

NASA Technical Reports Server (NTRS)

Lee, Timothy J.; Dateo, Christopher E.; Martin, Jan M. L.; Taylor, Peter R.; Langhoff, Stephen R. (Technical Monitor)

1995-01-01

Due to advances in quantum mechanical methods over the last few years, it is now possible to determine ab initio potential energy surfaces in which fundamental vibrational frequencies are accurate to within plus or minus 8 cm(exp -1) on average, and molecular bond distances are accurate to within plus or minus 0.001-0.003 Angstroms, depending on the nature of the bond. That is, the potential energy surfaces have not been scaled or empirically adjusted in any way, showing that theoretical methods have progressed to the point of being useful in analyzing spectra that are not from a tightly controlled laboratory environment, such as vibrational spectra from the interstellar medium. Some recent examples demonstrating this accuracy will be presented and discussed. These include the HNO, CH4, C2H4, and ClCN molecules. The HNO molecule is interesting due to the very large H-N anharmonicity, while ClCN has a very large Fermi resonance. The ab initio studies for the CH4 and C2H4 molecules present the first accurate full quartic force fields of any kind (i.e., whether theoretical or empirical) for a five-atom and six-atom system, respectively.

Ab Initio Calculation of Accurate Vibrational Frequencies for Molecules of Interest in Atmospheric Chemistry

NASA Technical Reports Server (NTRS)

Lee, Timothy J.; Langhoff, Stephen R. (Technical Monitor)

1996-01-01

Due to advances in quantum mechanical methods over the last few years, it is now possible to determine ab initio potential energy surfaces in which fundamental vibrational frequencies are accurate to within +/- 8 cm(sup -1) on average, and molecular bond distances are accurate to within +/- 0.001-0.003 A, depending on the nature of the bond. That is, the potential energy surfaces have not been scaled or empirically adjusted in any way, showing that theoretical methods have progressed to the point of being useful in analyzing spectra that are not from a tightly controlled laboratory environment, such as rovibrational spectra from the interstellar medium. Some recent examples demonstrating this accuracy win be presented and discussed. These include the HNO, CH4, C2H4, and ClCN molecules. The HNO molecule is interesting due to the very large H-N anharmonicity, while ClCN has a very large Fermi resonance. The ab initio studies for the CH4 and C2H4 molecules present the first accurate full quartic force fields of any kind (i.e., whether theoretical or empirical) for a five-atom and six-atom system, respectively.

The fate and transport of the Cry1Ab protein in an agricultural field and laboratory aquatic microcosms.

PubMed

Strain, Katherine E; Lydy, Michael J

2015-08-01

Genetically engineered crops expressing insecticidal crystalline proteins derived from Bacillus thuringiensis (Bt), were commercialized almost two decades ago as a means to manage agricultural pests. The Bt proteins are highly specific and only lethal upon ingestion, limiting the scope of toxicity to target insects. However, concern of exposure to non-target organisms and negative public perceptions regarding Bt crops has caused controversy surrounding their use. The objective of this research was to monitor the fate and transport of a Bt protein, Cry1Ab, in a large-scale agricultural field containing maize expressing the Cry1Ab protein and a non-Bt near isoline, and in aquatic microcosms. The highest environmental concentrations of the Cry1Ab protein were found in runoff water and sediment, up to 130ngL(-1) and 143ngg(-1) dry weight, respectively, with the Cry1Ab protein detected in both Bt and non-Bt maize fields. As surface runoff and residual crop debris can transport Bt proteins to waterways adjacent to agricultural fields, a series of laboratory experiments were conducted to determine the potential fate of the Cry1Ab protein under different conditions. The results showed that sediment type and temperature can influence the degradation of the Cry1Ab protein in an aquatic system and that the Cry1Ab protein can persist for up to two months. Although Cry1Ab protein concentrations measured in the field soil indicate little exposure to terrestrial organisms, the consistent input of Bt-contaminated runoff and crop debris into agricultural waterways is relevant to understanding potential consequences to aquatic species. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fractionation of equine antivenom using caprylic acid precipitation in combination with cationic ion-exchange chromatography.

PubMed

Raweerith, Rutai; Ratanabanangkoon, Kavi

2003-11-01

A combined process of caprylic acid (CA) precipitation and ion-exchange chromatography on SP-Sepharose was studied as a means to fractionate pepsin-digested horse antivenom F(ab')(2) antibody. In the CA precipitation, the optimal concentration for fractionation of F(ab')(2) from pepsin-digested horse plasma was 2%, in which 89.61% of F(ab')(2) antibody activity was recovered in the supernatant with 1.5-fold purification. A significant amount of pepsin was not precipitated and remained active under these conditions. An analytical cation exchanger Protein-Pak SP 8HR HPLC column was tested to establish optimal conditions for the effective separation of IgG, albumin, pepsin and CA from the F(ab')(2) product. From these results, the supernatant from CA precipitation of pepsin-digested plasma was subjected to a SP-Sepharose column chromatography using a linear salt gradient. With stepwise elution, a peak containing F(ab')(2) antibody could be obtained by elution with 0.25 M NaCl. The total recovery of antibody was 65.56% with 2.91-fold purification, which was higher than that achieved by ammonium sulfate precipitation. This process simultaneously and effectively removed residual pepsin, high molecular weight aggregates and CA in the final F(ab')(2) product, and should be suitable for large-scale fractionation of therapeutic equine antivenoms.

Fast detection of atrazine in corn using thermometric biosensors.

PubMed

Qie, Zhiwei; Ning, Baoan; Liu, Ming; Bai, Jialei; Peng, Yuan; Song, Nan; Lv, Zhiqiang; Wang, Ying; Sun, Siming; Su, Xuan; Zhang, Yihong; Gao, Zhixian

2013-09-07

Fast detection is important in screening large-scale samples. This study establishes a direct competitive ELISA method (dcTELISA) based on an enzyme thermistor for fast atrazine (ATZ) detection. ATZ competes with β-lactamase-labeled ATZ (ATZ-E) for the binding sites on anti-ATZ monoclonal antibody (mAb). The mAb are covalently bound to Controlled Pore Glass (CPG) in an immunoreactor to form immunocomplexes with ATZ and ATZ-E. Several parameters of biosensor performance were optimized, such as the ATZ-E concentration, concentration and nature of the substrate, flow rate, and effect of temperature on the sensor response. After optimization, the assay time for a single sample was 12 min. The work process and result were compared with those of high-performance liquid chromatography (HPLC). The detection results exhibited a recovery rate of 88% to 107% in ATZ-spiked fresh cut corn stalks and silage samples. The results obtained via dcTELISA had good correlation with that of HPLC, and the biosensor response was reproducible and stable even when used continuously for over 4 months. All these properties suggested that the fast detection method, dcTELISA, may be used to detect pesticide residue in large-scale samples.

SPACE: the SPectroscopic, All-Sky Cosmic Explorer

NASA Technical Reports Server (NTRS)

Cimatti, A.; Robberto, M.; Baugh, C.; Beckwith, S. W. V.; Content, R.; Daddi, E.; deLucia, G.; Garilli, B.; Guzzo, L.; Kauffmann, G.;

Fast Crystallization of the Phase Change Compound GeTe by Large-Scale Molecular Dynamics Simulations.

PubMed

Sosso, Gabriele C; Miceli, Giacomo; Caravati, Sebastiano; Giberti, Federico; Behler, Jörg; Bernasconi, Marco

2013-12-19

Phase change materials are of great interest as active layers in rewritable optical disks and novel electronic nonvolatile memories. These applications rest on a fast and reversible transformation between the amorphous and crystalline phases upon heating, taking place on the nanosecond time scale. In this work, we investigate the microscopic origin of the fast crystallization process by means of large-scale molecular dynamics simulations of the phase change compound GeTe. To this end, we use an interatomic potential generated from a Neural Network fitting of a large database of ab initio energies. We demonstrate that in the temperature range of the programming protocols of the electronic memories (500-700 K), nucleation of the crystal in the supercooled liquid is not rate-limiting. In this temperature range, the growth of supercritical nuclei is very fast because of a large atomic mobility, which is, in turn, the consequence of the high fragility of the supercooled liquid and the associated breakdown of the Stokes-Einstein relation between viscosity and diffusivity.

A review of the different techniques for solid surface acid-base characterization.

PubMed

Sun, Chenhang; Berg, John C

2003-09-18

In this work, various techniques for solid surface acid-base (AB) characterization are reviewed. Different techniques employ different scales to rank acid-base properties. Based on the results from literature and the authors' own investigations for mineral oxides, these scales are compared. The comparison shows that Isoelectric Point (IEP), the most commonly used AB scale, is not a description of the absolute basicity or acidity of a surface, but a description of their relative strength. That is, a high IEP surface shows more basic functionality comparing with its acidic functionality, whereas a low IEP surface shows less basic functionality comparing with its acidic functionality. The choice of technique and scale for AB characterization depends on the specific application. For the cases in which the overall AB property is of interest, IEP (by electrokinetic titration) and H(0,max) (by indicator dye adsorption) are appropriate. For the cases in which the absolute AB property is of interest such as in the study of adhesion, it is more pertinent to use chemical shift (by XPS) and the heat of adsorption of probe gases (by calorimetry or IGC).

The new allelic variant of the subtilase cytotoxin (subAB2) is common among Shiga toxin-producing Escherichia coli strains from large game animals and their meat and meat products.

PubMed

Sánchez, Sergio; Díaz-Sánchez, Sandra; Martínez, Remigio; Llorente, María Teresa; Herrera-León, Silvia; Vidal, Dolors

2013-10-25

Subtilase cytotoxin (SubAB) is an AB5 toxin produced by Shiga toxin (Stx)-producing Escherichia coli (STEC) strains usually lacking the eae gene product intimin. Two allelic variants of SubAB encoding genes have been described: subAB1, located on a plasmid, and subAB2, located on a pathogenicity island (PAI) together with tia gene. While subAB1 has been reported to be more frequent among bovine strains, subAB2 has been mainly associated with strains from small ruminants. We investigated the presence of the two variants of subAB among 59 eae-negative STEC from large game animals (deer and wild boar) and their meat and meat products in order to assess the role of other species in the epidemiology of subAB-positive, eae-negative STEC. For this approach, the strains were PCR-screened for the presence of subAB, including the specific detection of both allelic variants, for the presence of saa, tia and sab, and for stx subtyping. Overall, subAB genes were detected in 71.2% of the strains: 84.1% of the strains from deer and 33.3% of the strains from wild boar. Most of them (97.6%) possessed subAB2 and most of these subAB2-positive strains (92.7%) were also positive for tia and negative for saa, suggesting the presence of the subAB2-harbouring PAI. Subtype stx2b was present in most of the strains (67.8%) and a statistically significant association could be established between subAB2 and stx2b. Our results suggest that large game animals, mainly deer, may represent an important animal reservoir of subAB2-positive, eae-negative STEC, and also highlight the risk of human infection posed by the consumption of large game meat and meat products. Copyright © 2013 Elsevier B.V. All rights reserved.

Critical Problems in Very Large Scale Computer Systems

DTIC Science & Technology

1989-09-30

N Massachusetts Institute of Technology Cambridge, Massachusetts 02139 Anant Agarwal (617) 253-1448 William J. Dally (617) 253-6043 Srinivas Devadas ...rapidly switched between the ports. Labelling the terminal voltages ab.c. d. this attempts to enforce a constraint a - b = c - d. This is a reciprocal...Srinivas Devadas and his students have been focusing on the optimization ofcomibinational and sequen- tial circuits specified at the register

The Atacama B-mode Search: An Experiment to Probe Inflation by Measuring the Cosmic Microwave Background Polarization

NASA Astrophysics Data System (ADS)

Niemack, Michael; Appel, J.; Cho, H. M.; Essinger-Hileman, T.; Fowler, J.; Halpern, M.; Irwin, K. D.; Marriage, T. A.; Page, L.; Parker, L. P.; Pufu, S.; Staggs, S. T.; Visnjic, K.; Yoon, K. W.; Zhao, Y.

2009-12-01

The Atacama B-mode Seach (ABS) is a new experiment to test the prediction that inflation during the early universe resulted in stochastic gravitational waves. The predicted signature of these inflationary gravitational waves is the introduction of a B-mode, or curl, component into the primordial cosmic microwave background (CMB) polarization field, which is dominated by curl-free E-modes. ABS is designed to measure the CMB polarization on large angular scales over a wide frequency band centered at 145 GHz. ABS comprises a 60 cm diameter telescope in the crossed Mizuguchi-Dragone configuration, which illuminates a large focal plane of 200 feedhorns coupled to polarization sensitive bolometric detectors. The detectors are fabricated at NIST and include planar ortho-mode transducers, band defining filters, microstrip tranmission lines and two transition-edge sensors (TES) to provide measurements of the polarization and total power from each feed simultaneously. The telescope mirrors are cooled to 4 K to control systematic effects, and the bolometers are cooled to 0.3 K to achieve sufficiently high saturation power while maintaining low detector noise. The polarization signals are modulated by a 33 cm diameter rotating half-wave plate (HWP) in front of the telescope. The HWP limits the mirror illumination, resulting in 0.5 degree angular resolution over a 20 degree field of view. ABS will begin observing at a high-altitude site in the Atacama Desert, Chile in 2009.

Microorganisms with Novel Dissimilatory (Bi)Sulfite Reductase Genes Are Widespread and Part of the Core Microbiota in Low-Sulfate Peatlands ▿ †

PubMed Central

Steger, Doris; Wentrup, Cecilia; Braunegger, Christina; Deevong, Pinsurang; Hofer, Manuel; Richter, Andreas; Baranyi, Christian; Pester, Michael; Wagner, Michael; Loy, Alexander

2011-01-01

Peatlands of the Lehstenbach catchment (Germany) house as-yet-unidentified microorganisms with phylogenetically novel variants of the dissimilatory (bi)sulfite reductase genes dsrAB. These genes are characteristic of microorganisms that reduce sulfate, sulfite, or some organosulfonates for energy conservation but can also be present in anaerobic syntrophs. However, nothing is currently known regarding the abundance, community dynamics, and biogeography of these dsrAB-carrying microorganisms in peatlands. To tackle these issues, soils from a Lehstenbach catchment site (Schlöppnerbrunnen II fen) from different depths were sampled at three time points over a 6-year period to analyze the diversity and distribution of dsrAB-containing microorganisms by a newly developed functional gene microarray and quantitative PCR assays. Members of novel, uncultivated dsrAB lineages (approximately representing species-level groups) (i) dominated a temporally stable but spatially structured dsrAB community and (ii) represented “core” members (up to 1% to 1.7% relative abundance) of the autochthonous microbial community in this fen. In addition, denaturing gradient gel electrophoresis (DGGE)- and clone library-based comparisons of the dsrAB diversity in soils from a wet meadow, three bogs, and five fens of various geographic locations (distance of ∼1 to 400 km) identified that one Syntrophobacter-related and nine novel dsrAB lineages are widespread in low-sulfate peatlands. Signatures of biogeography in dsrB-based DGGE data were not correlated with geographic distance but could be explained largely by soil pH and wetland type, implying that the distribution of dsrAB-carrying microorganisms in wetlands on the scale of a few hundred kilometers is not limited by dispersal but determined by local environmental conditions. PMID:21169452

Data and Analysis of the Double Stars STFA 10AB and STFA 1744AB

NASA Astrophysics Data System (ADS)

Arcilla, Marisa; Bowden, Sam; DeBlase, Jacqueline; Hall, Anthony; Hall, Corielyn; Hernandez, Alyssa; Renna, Danielle; Rodriguez, Fatima; Salazar, Cassandra; Sanchez, Andres; Teeter, Dayton; Brewer, Mark; Funk, Benjamin; Gillette, Travis; Sharpe, Scott

2017-04-01

Eighth grade students at Vanguard Preparatory School measured the double stars STFA 10AB and STFA 1744AB. A 22-inch Newtonian Alt/Az telescope and a 14-inch Celestron Schmidt Cassegrain telescope were used. The star Bellatrix was used as the calibration star to determine the scale constant of the 22-inch telescope to be 7.8 “/tick marks. The double star STFA 1744AB was used as the calibration star to determine the scale constant of the 14-inch telescope to be 5.1 “/tick marks. The separation and position angle of STFA 10AB was determined by the 22-inch telescope to be 347.9” and 339.3°. The separation and position angle of STFA 1744AB was determined by the 14-inch telescope to be 3.6” and 158.1°. The measurements that were calculated were compared to the most recent measurements listed in the Washington Double Star Catalog.

Development of the Systems Thinking Scale for Adolescent Behavior Change.

PubMed

Moore, Shirley M; Komton, Vilailert; Adegbite-Adeniyi, Clara; Dolansky, Mary A; Hardin, Heather K; Borawski, Elaine A

2018-03-01

This report describes the development and psychometric testing of the Systems Thinking Scale for Adolescent Behavior Change (STS-AB). Following item development, initial assessments of understandability and stability of the STS-AB were conducted in a sample of nine adolescents enrolled in a weight management program. Exploratory factor analysis of the 16-item STS-AB and internal consistency assessments were then done with 359 adolescents enrolled in a weight management program. Test-retest reliability of the STS-AB was .71, p = .03; internal consistency reliability was .87. Factor analysis of the 16-item STS-AB indicated a one-factor solution with good factor loadings, ranging from .40 to .67. Evidence of construct validity was supported by significant correlations with established measures of variables associated with health behavior change. We provide beginning evidence of the reliability and validity of the STS-AB to measure systems thinking for health behavior change in young adolescents.

Development of the Systems Thinking Scale for Adolescent Behavior Change

PubMed Central

Moore, Shirley M.; Komton, Vilailert; Adegbite-Adeniyi, Clara; Dolansky, Mary A.; Hardin, Heather K.; Borawski, Elaine A.

2017-01-01

This report describes the development and psychometric testing of the Systems Thinking Scale for Adolescent Behavior Change (STS-AB). Following item development, initial assessments of understandability and stability of the STS-AB were conducted in a sample of nine adolescents enrolled in a weight management program. Exploratory factor analysis of the 16-item STS-AB and internal consistency assessments were then done with 359 adolescents enrolled in a weight management program. Test–retest reliability of the STS-AB was .71, p = .03; internal consistency reliability was .87. Factor analysis of the 16-item STS-AB indicated a one-factor solution with good factor loadings, ranging from .40 to .67. Evidence of construct validity was supported by significant correlations with established measures of variables associated with health behavior change. We provide beginning evidence of the reliability and validity of the STS-AB to measure systems thinking for health behavior change in young adolescents. PMID:28303755

Approximate Quantum Dynamics using Ab Initio Classical Separable Potentials: Spectroscopic Applications.

PubMed

Hirshberg, Barak; Sagiv, Lior; Gerber, R Benny

2017-03-14

Algorithms for quantum molecular dynamics simulations that directly use ab initio methods have many potential applications. In this article, the ab initio classical separable potentials (AICSP) method is proposed as the basis for approximate algorithms of this type. The AICSP method assumes separability of the total time-dependent wave function of the nuclei and employs mean-field potentials that govern the dynamics of each degree of freedom. In the proposed approach, the mean-field potentials are determined by classical ab initio molecular dynamics simulations. The nuclear wave function can thus be propagated in time using the effective potentials generated "on the fly". As a test of the method for realistic systems, calculations of the stationary anharmonic frequencies of hydrogen stretching modes were carried out for several polyatomic systems, including three amino acids and the guanine-cytosine pair of nucleobases. Good agreement with experiments was found. The method scales very favorably with the number of vibrational modes and should be applicable for very large molecules, e.g., peptides. The method should also be applicable for properties such as vibrational line widths and line shapes. Work in these directions is underway.

Kinetics of Electrocatalytic Reactions from First-Principles: A Critical Comparison with the Ab Initio Thermodynamics Approach.

PubMed

Exner, Kai S; Over, Herbert

2017-05-16

Multielectron processes in electrochemistry require the stabilization of reaction intermediates (RI) at the electrode surface after every elementary reaction step. Accordingly, the bond strengths of these intermediates are important for assessing the catalytic performance of an electrode material. Current understanding of microscopic processes in modern electrocatalysis research is largely driven by theory, mostly based on ab initio thermodynamics considerations, where stable reaction intermediates at the electrode surface are identified, while the actual free energy barriers (or activation barriers) are ignored. This simple approach is popular in electrochemistry in that the researcher has a simple tool at hand in successfully searching for promising electrode materials. The ab initio TD approach allows for a rough but fast screening of the parameter space with low computational cost. However, ab initio thermodynamics is also frequently employed (often, even based on a single binding energy only) to comprehend on the activity and on the mechanism of an electrochemical reaction. The basic idea is that the activation barrier of an endergonic reaction step consists of a thermodynamic part and an additional kinetically determined barrier. Assuming that the activation barrier scales with thermodynamics (so-called Brønsted-Polanyi-Evans (BEP) relation) and the kinetic part of the barrier is small, ab initio thermodynamics may provide molecular insights into the electrochemical reaction kinetics. However, for many electrocatalytic reactions, these tacit assumptions are violated so that ab initio thermodynamics will lead to contradictions with both experimental data and ab initio kinetics. In this Account, we will discuss several electrochemical key reactions, including chlorine evolution (CER), oxygen evolution reaction (OER), and oxygen reduction (ORR), where ab initio kinetics data are available in order to critically compare the results with those derived from a simple ab initio thermodynamics treatment. We show that ab initio thermodynamics leads to erroneous conclusions about kinetic and mechanistic aspects for the CER over RuO 2 (110), while the kinetics of the OER over RuO 2 (110) and ORR over Pt(111) are reasonably well described. Microkinetics of an electrocatalyzed reaction is largely simplified by the quasi-equilibria of the RI preceding the rate-determining step (rds) with the reactants. Therefore, in ab initio kinetics the rate of an electrocatalyzed reaction is governed by the transition state (TS) with the highest free energy G rds # , defining also the rate-determining step (rds). Ab initio thermodynamics may be even more powerful, when using the highest free energy of an reaction intermediate G max (RI) rather than the highest free energy difference between consecutive reaction intermediates, ΔG loss , as a descriptor for the kinetics.

Quantum Fragment Based ab Initio Molecular Dynamics for Proteins.

PubMed

Liu, Jinfeng; Zhu, Tong; Wang, Xianwei; He, Xiao; Zhang, John Z H

2015-12-08

Developing ab initio molecular dynamics (AIMD) methods for practical application in protein dynamics is of significant interest. Due to the large size of biomolecules, applying standard quantum chemical methods to compute energies for dynamic simulation is computationally prohibitive. In this work, a fragment based ab initio molecular dynamics approach is presented for practical application in protein dynamics study. In this approach, the energy and forces of the protein are calculated by a recently developed electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) method. For simulation in explicit solvent, mechanical embedding is introduced to treat protein interaction with explicit water molecules. This AIMD approach has been applied to MD simulations of a small benchmark protein Trpcage (with 20 residues and 304 atoms) in both the gas phase and in solution. Comparison to the simulation result using the AMBER force field shows that the AIMD gives a more stable protein structure in the simulation, indicating that quantum chemical energy is more reliable. Importantly, the present fragment-based AIMD simulation captures quantum effects including electrostatic polarization and charge transfer that are missing in standard classical MD simulations. The current approach is linear-scaling, trivially parallel, and applicable to performing the AIMD simulation of proteins with a large size.

On the energy scale involved in the metal to insulator transition of quadruple perovskite EuCu3Fe4O12: infrared spectroscopy and ab-initio calculations.

PubMed

Brière, B; Kalinko, A; Yamada, I; Roy, P; Brubach, J B; Sopracase, R; Zaghrioui, M; Phuoc, V Ta

2016-06-27

Optical measurements were carried out by infrared spectroscopy on AA'3B4O12 A-site ordered quadruple perovskite EuCu3Fe4O12 (microscopic sample) as function of temperature. At 240 K (=TMI), EuCu3Fe4O12 undergoes a very abrupt metal to insulator transition, a paramagnetic to antiferromagnetic transition and an isostructural transformation with an abrupt large volume expansion. Above TMI, optical conductivity reveals a bad metal behavior and below TMI, an insulating phase with an optical gap of 125 meV is observed. As temperature is decreased, a large and abrupt spectral weight transfer toward an energy scale larger than 1 eV is detected. Concurrently, electronic structure calculations for both high and low temperature phases were compared to the optical conductivity results giving a precise pattern of the transition. Density of states and computed optical conductivity analysis identified Cu3dxy, Fe3d and O2p orbitals as principal actors of the spectral weight transfer. The present work constitutes a first step to shed light on EuCu3Fe4O12 electronic properties with optical measurements and ab-initio calculations.

On the energy scale involved in the metal to insulator transition of quadruple perovskite EuCu3Fe4O12: infrared spectroscopy and ab-initio calculations

PubMed Central

Brière, B.; Kalinko, A.; Yamada, I.; Roy, P.; Brubach, J. B.; Sopracase, R.; Zaghrioui, M.; Phuoc, V. Ta

2016-01-01

Optical measurements were carried out by infrared spectroscopy on AA′3B4O12 A-site ordered quadruple perovskite EuCu3Fe4O12 (microscopic sample) as function of temperature. At 240 K (=TMI), EuCu3Fe4O12 undergoes a very abrupt metal to insulator transition, a paramagnetic to antiferromagnetic transition and an isostructural transformation with an abrupt large volume expansion. Above TMI, optical conductivity reveals a bad metal behavior and below TMI, an insulating phase with an optical gap of 125 meV is observed. As temperature is decreased, a large and abrupt spectral weight transfer toward an energy scale larger than 1 eV is detected. Concurrently, electronic structure calculations for both high and low temperature phases were compared to the optical conductivity results giving a precise pattern of the transition. Density of states and computed optical conductivity analysis identified Cu3dxy, Fe3d and O2p orbitals as principal actors of the spectral weight transfer. The present work constitutes a first step to shed light on EuCu3Fe4O12 electronic properties with optical measurements and ab-initio calculations. PMID:27346212

Temperature scaling method for Markov chains.

PubMed

Crosby, Lonnie D; Windus, Theresa L

2009-01-22

The use of ab initio potentials in Monte Carlo simulations aimed at investigating the nucleation kinetics of water clusters is complicated by the computational expense of the potential energy determinations. Furthermore, the common desire to investigate the temperature dependence of kinetic properties leads to an urgent need to reduce the expense of performing simulations at many different temperatures. A method is detailed that allows a Markov chain (obtained via Monte Carlo) at one temperature to be scaled to other temperatures of interest without the need to perform additional large simulations. This Markov chain temperature-scaling (TeS) can be generally applied to simulations geared for numerous applications. This paper shows the quality of results which can be obtained by TeS and the possible quantities which may be extracted from scaled Markov chains. Results are obtained for a 1-D analytical potential for which the exact solutions are known. Also, this method is applied to water clusters consisting of between 2 and 5 monomers, using Dynamical Nucleation Theory to determine the evaporation rate constant for monomer loss. Although ab initio potentials are not utilized in this paper, the benefit of this method is made apparent by using the Dang-Chang polarizable classical potential for water to obtain statistical properties at various temperatures.

Blocking monocyte transmigration in in vitro system by a human antibody scFv anti-CD99. Efficient large scale purification from periplasmic inclusion bodies in E. coli expression system.

PubMed

Moricoli, Diego; Muller, William Anthony; Carbonella, Damiano Cosimo; Balducci, Maria Cristina; Dominici, Sabrina; Watson, Richard; Fiori, Valentina; Weber, Evan; Cianfriglia, Maurizio; Scotlandi, Katia; Magnani, Mauro

2014-06-01

Migration of leukocytes into site of inflammation involves several steps mediated by various families of adhesion molecules. CD99 play a significant role in transendothelial migration (TEM) of leukocytes. Inhibition of TEM by specific monoclonal antibody (mAb) can provide a potent therapeutic approach to treating inflammatory conditions. However, the therapeutic utilization of whole IgG can lead to an inappropriate activation of Fc receptor-expressing cells, inducing serious adverse side effects due to cytokine release. In this regard, specific recombinant antibody in single chain variable fragments (scFvs) originated by phage library may offer a solution by affecting TEM function in a safe clinical context. However, this consideration requires large scale production of functional scFv antibodies and the absence of toxic reagents utilized for solubilization and refolding step of inclusion bodies that may discourage industrial application of these antibody fragments. In order to apply the scFv anti-CD99 named C7A in a clinical setting, we herein describe an efficient and large scale production of the antibody fragments expressed in E. coli as periplasmic insoluble protein avoiding gel filtration chromatography approach, and laborious refolding step pre- and post-purification. Using differential salt elution which is a simple, reproducible and effective procedure we are able to separate scFv in monomer format from aggregates. The purified scFv antibody C7A exhibits inhibitory activity comparable to an antagonistic conventional mAb, thus providing an excellent agent for blocking CD99 signaling. This protocol can be useful for the successful purification of other monomeric scFvs which are expressed as periplasmic inclusion bodies in bacterial systems. Copyright © 2014 Elsevier B.V. All rights reserved.

Adaptation of the ABS-S:2 for Use in Spain with Children with Intellectual Disabilities

ERIC Educational Resources Information Center

Garcia Alonso, Isabel; De La Fuente Anuncibay, Raquel; Fernandez Hawrylak, Maria

2010-01-01

As there is a dearth of Spanish-language standardized scales that assess adaptive behavior in children and adolescents with intellectual disabilities (ID), the authors adapted one of the most widely used and studied scales of adaptive behavior in the U.S., the ABS-S:2 (Adaptive Behavior Scale-School, 2nd Edition), and validated it for use in…

The seroprevalence of antithyroid peroxidase antibodies in bipolar families and bipolar twins: results from two longitudinal studies.

PubMed

Snijders, G; de Witte, L; Mesman, E; Kemner, S; Vonk, R; Brouwer, R; Nolen, W A; Drexhage, H A; Hillegers, M H J

2017-12-01

Previous studies of our group among bipolar offspring and bipolar twins showed significant higher prevalence's and levels of antithyroid peroxidase antibodies (TPO-Abs) in offspring and co-twins (without a mood disorder) compared to controls, suggesting that TPO-Abs might be considered as vulnerability factor (trait marker) for BD development. Here we elucidate, in the same cohorts, but now after 12- and 6-year follow-up, whether TPO-abs should be considered as a 'trait' marker for BD. The present study aims to investigate whether TPO-Abs (1) are stable over time, (2) are associated with lithium-exposure, (3) share a common genetic background with BD and are related to psychopathology. In bipolar offspring and twins, the prevalence of TPO-Abs is stable over time (r s  = .72 p < .001 resp. r s  = .82, p < .001) and not associated with lithium use. At follow-up, an increased prevalence of TPO-abs was again observed in bipolar offspring (10,4% versus 4%) and higher TPO-abs titers were still present in co-twins of bipolar cases compared to control twins [mean 1.06 IU/ml (SD .82) versus mean .82 IU/ml (SD .67)], although statistical significance was lost. Although our results show a trend toward an increased inherited risk of the co-occurrence of BD and thyroid autoimmunity, large-scale studies can only draw final conclusions. Nationwide epidemiological and GWAS studies reach such numbers and support the view of a possible common (autoimmune) etiology of severe mood disorders and chronic recurrent infections and autoimmunity, including thyroid autoimmunity.

Microphase separation of comb copolymers with two different lengths of side chains

NASA Astrophysics Data System (ADS)

Aliev, M. A.; Kuzminyh, N. Yu.

2009-10-01

The phase behavior of the monodisperse AB comb copolymer melt contained the macromolecules of special architecture is discussed. Each macromolecule is assumed to be composed of two comb blocks which differ in numbers of side chains and numbers of monomer units in these chains. It is shown (by analysis of the structure factor of the melt) that microphase separation at two different length scales in the melt is possible. The large and small length scales correspond to separation between comb blocks and separation between monomer units in repeating fragments of blocks, respectively. The classification diagrams indicated which length scale is favored for a given parameters of chemical structure of macromolecules are constructed.

Low frequency of broadly neutralizing HIV antibodies during chronic infection even in quaternary epitope targeting antibodies containing large numbers of somatic mutations.

PubMed

Hicar, Mark D; Chen, Xuemin; Kalams, Spyros A; Sojar, Hakimuddin; Landucci, Gary; Forthal, Donald N; Spearman, Paul; Crowe, James E

2016-02-01

Neutralizing antibodies (Abs) are thought to be a critical component of an appropriate HIV vaccine response. It has been proposed that Abs recognizing conformationally dependent quaternary epitopes on the HIV envelope (Env) trimer may be necessary to neutralize diverse HIV strains. A number of recently described broadly neutralizing monoclonal Abs (mAbs) recognize complex and quaternary epitopes. Generally, many such Abs exhibit extensive numbers of somatic mutations and unique structural characteristics. We sought to characterize the native antibody (Ab) response against circulating HIV focusing on such conformational responses, without a prior selection based on neutralization. Using a capture system based on VLPs incorporating cleaved envelope protein, we identified a selection of B cells that produce quaternary epitope targeting Abs (QtAbs). Similar to a number of broadly neutralizing Abs, the Ab genes encoding these QtAbs showed extensive numbers of somatic mutations. However, when expressed as recombinant molecules, these Abs failed to neutralize virus or mediate ADCVI activity. Molecular analysis showed unusually high numbers of mutations in the Ab heavy chain framework 3 region of the variable genes. The analysis suggests that large numbers of somatic mutations occur in Ab genes encoding HIV Abs in chronically infected individuals in a non-directed, stochastic, manner. Copyright © 2015 Elsevier Ltd. All rights reserved.

Radiator-induced erythema ab igne in 8-year-old girl.

PubMed

Brzezinski, Piotr; Ismail, Samir; Chiriac, Anca

2014-04-01

The cutaneous lesion of erythema ab Igne are characterized by a reticulate erythema, hyperpigmentation, fine scaling, epidermal atrophy and telangiectasias, and reticulated erythema. We report a case of erythema ab igne on the hands of a 8-year-old girl, induced by classic homemade radiator.

Introducing ab initio based neural networks for transition-rate prediction in kinetic Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Messina, Luca; Castin, Nicolas; Domain, Christophe; Olsson, Pär

2017-02-01

The quality of kinetic Monte Carlo (KMC) simulations of microstructure evolution in alloys relies on the parametrization of point-defect migration rates, which are complex functions of the local chemical composition and can be calculated accurately with ab initio methods. However, constructing reliable models that ensure the best possible transfer of physical information from ab initio to KMC is a challenging task. This work presents an innovative approach, where the transition rates are predicted by artificial neural networks trained on a database of 2000 migration barriers, obtained with density functional theory (DFT) in place of interatomic potentials. The method is tested on copper precipitation in thermally aged iron alloys, by means of a hybrid atomistic-object KMC model. For the object part of the model, the stability and mobility properties of copper-vacancy clusters are analyzed by means of independent atomistic KMC simulations, driven by the same neural networks. The cluster diffusion coefficients and mean free paths are found to increase with size, confirming the dominant role of coarsening of medium- and large-sized clusters in the precipitation kinetics. The evolution under thermal aging is in better agreement with experiments with respect to a previous interatomic-potential model, especially concerning the experiment time scales. However, the model underestimates the solubility of copper in iron due to the excessively high solution energy predicted by the chosen DFT method. Nevertheless, this work proves the capability of neural networks to transfer complex ab initio physical properties to higher-scale models, and facilitates the extension to systems with increasing chemical complexity, setting the ground for reliable microstructure evolution simulations in a wide range of alloys and applications.

Separation and purification of both tea seed polysaccharide and saponin from camellia cake extract using macroporous resin.

PubMed

Yang, Pengjie; Zhou, Mingda; Zhou, Chengyun; Wang, Qian; Zhang, Fangfang; Chen, Jian

2015-02-01

A novel method to separate and purify tea seed polysaccharide and tea seed saponin from camellia cake extract by macroporous resin was developed. Among four kinds of resins (AB-8, NKA-9, XDA-6, and D4020) tested, AB-8 macroporous resin possessed optimal separating capacity for the two substances and thus was selected for the separation, in which deionized water was used to elute tea seed polysaccharide, 0.25% NaOH solution to remove the undesired pigments, and 90% ethanol to elute tea seed saponin. Further dynamic adsorption/desorption experiments on AB-8 resin-based column chromatography were conducted to obtain the optimal parameters. Under optimal dynamic adsorption and desorption conditions, 18.7 and 11.8% yield of tea seed polysaccharide and tea seed saponin were obtained with purities of 89.2 and 96.0%, respectively. The developed method provides a potential approach for the large-scale production of tea seed polysaccharide and tea seed saponin from camellia cake. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Contrasting patterns in lichen diversity in the continental and maritime Antarctic

NASA Astrophysics Data System (ADS)

Singh, Shiv Mohan; Olech, Maria; Cannone, Nicoletta; Convey, Peter

2015-09-01

Systematic surveys of the lichen floras of Schirmacher Oasis (Queen Maud Land, continental Antarctic), Victoria Land (Ross Sector, continental Antarctic) and Admiralty Bay (South Shetland Islands, maritime Antarctic) were compared to help infer the major factors influencing patterns of diversity and biogeography in the three areas. Biogeographic patterns were determined using a variety of multivariate statistical tools. A total of 54 lichen species were documented from Schirmacher Oasis (SO), 48 from Victoria Land (VL) and 244 from Admiralty Bay (AB). Of these, 21 species were common to all areas. Most lichens from the SO and VL areas were microlichens, the dominant genus being Buellia. In AB, in contrast, many macrolichens were also present and the dominant genus was Caloplaca. In SO and VL large areas lacked any visible lichen cover, even where the ground was snow-free in summer. Small-scale diversity patterns were present in AB, where the number of species and genera was greater close to the coast. Most species recorded were rare in the study areas in which they were present and endemic to Antarctica.

Density functional calculations on structural materials for nuclear energy applications and functional materials for photovoltaic energy applications (abstract only).

PubMed

Domain, C; Olsson, P; Becquart, C S; Legris, A; Guillemoles, J F

2008-02-13

Ab initio density functional theory calculations are carried out in order to predict the evolution of structural materials under aggressive working conditions such as cases with exposure to corrosion and irradiation, as well as to predict and investigate the properties of functional materials for photovoltaic energy applications. Structural metallic materials used in nuclear facilities are subjected to irradiation which induces the creation of large amounts of point defects. These defects interact with each other as well as with the different elements constituting the alloys, which leads to modifications of the microstructure and the mechanical properties. VASP (Vienna Ab initio Simulation Package) has been used to determine the properties of point defect clusters and also those of extended defects such as dislocations. The resulting quantities, such as interaction energies and migration energies, are used in larger scale simulation methods in order to build predictive tools. For photovoltaic energy applications, ab initio calculations are used in order to search for new semiconductors and possible element substitutions for existing ones in order to improve their efficiency.

Effect of structure variation of the aptamer-DNA duplex probe on the performance of displacement-based electrochemical aptamer sensors.

PubMed

Pang, Jie; Zhang, Ziping; Jin, Haizhu

2016-03-15

Electrochemical aptamer-based (E-AB) sensors employing electrode-immobilized, redox-tagged aptamer probes have emerged as a promising platform for the sensitive and quick detection of target analytes ranging from small molecules to proteins. Signal generation in this class of sensor is linked to change in electron transfer efficiency upon binding-induced change in flexibility/conformation of the aptamer probe. Because of this signaling mechanism, signal gains of these sensors can be improved by employing a displacement-based recognition system, which links target binding with a large-scale flexibility/conformation shift from the aptamer-DNA duplex to the single-stranded DNA or the native aptamer. Despite the relatively large number of displacement-based E-AB sensor samples, little attention has been paid to the structure variation of the aptamer-DNA duplex probe. Here we detail the effects of complementary length and position of the aptamer-DNA duplex probe on the performance of a model displacement-based E-AB sensor for ATP. We find that, greater background suppression and signal gain are observed with longer complementary length of the aptamer-DNA duplex probe. However, sensor equilibration time slows monotonically with increasing complementary length; and with too many target binding sites in aptamer sequence being occupied by the complementary DNA, the aptamer-target binding does not occur and no signal gain observed. We also demonstrate that signal gain of the displacement-based E-AB sensor is strongly dependent on the complementary position of the aptamer-DNA duplex probe, with complementary position located at the electrode-attached or redox-tagged end of the duplex probe, larger background suppression and signal increase than that of the middle position are observed. These results highlight the importance of rational structure design of the aptamer-DNA duplex probe and provide new insights into the optimization of displacement-based E-AB sensors. Copyright © 2015 Elsevier B.V. All rights reserved.

Mass-Production and Characterization of Anti-CD20 Monoclonal Antibody in Peritoneum of Balb/c Mice

PubMed Central

Sineh sepehr, Koushan; Baradaran, Behzad; Majidi, Jafar; Abdolalizadeh, Jalal; Aghebati, leili; Zare Shahneh, Fatemeh

2013-01-01

Purpose: Monoclonal antibodies are important tools are used in basic research as well as, in diagnosis, imaging and treatment of immunodeficiency diseases, infections and cancers. The purpose of this study was to produce large scale of monoclonal antibody against CD20 in order to diagnostic application in leukemia and lymphomas disorders. Methods: Hybridoma cells that produce monoclonal antibody against human CD20 were administered into the peritoneum of the Balb/c mice which have previously been primed with 0.5 ml Pristane. After twelve days, approximately 7 ml ascetic fluid was harvested from the peritoneum of each mouse. Evaluation of mAb titration was assessed by ELISA method. In the present study, we describe a protocol for large scale production of MAbs. Results: We prepared monoclonal antibodies (mAbs) with high specificity and sensitivity against human CD20 by hybridoma method and characterized them by ELISA. The subclass of antibody was IgG2a and its light chain was kappa. Ascetic fluid was purified by Protein-A Sepharose affinity chromatography and the purified monoclonal antibody was conjugated with FITC and Immunofluorescence was done for confirming the specific binding. Conclusion: The conjugated monoclonal antibody could have application in diagnosis B-cell lymphomas, hairy cell leukemia, B-cell chronic lymphocytic leukemia, and melanoma cancer stem cells. PMID:24312821

reaxFF Reactive Force Field for Disulfide Mechanochemistry, Fitted to Multireference ab Initio Data.

PubMed

Müller, Julian; Hartke, Bernd

2016-08-09

Mechanochemistry, in particular in the form of single-molecule atomic force microscopy experiments, is difficult to model theoretically, for two reasons: Covalent bond breaking is not captured accurately by single-determinant, single-reference quantum chemistry methods, and experimental times of milliseconds or longer are hard to simulate with any approach. Reactive force fields have the potential to alleviate both problems, as demonstrated in this work: Using nondeterministic global parameter optimization by evolutionary algorithms, we have fitted a reaxFF force field to high-level multireference ab initio data for disulfides. The resulting force field can be used to reliably model large, multifunctional mechanochemistry units with disulfide bonds as designed breaking points. Explorative calculations show that a significant part of the time scale gap between AFM experiments and dynamical simulations can be bridged with this approach.

Machine-learned and codified synthesis parameters of oxide materials

NASA Astrophysics Data System (ADS)

Kim, Edward; Huang, Kevin; Tomala, Alex; Matthews, Sara; Strubell, Emma; Saunders, Adam; McCallum, Andrew; Olivetti, Elsa

2017-09-01

Predictive materials design has rapidly accelerated in recent years with the advent of large-scale resources, such as materials structure and property databases generated by ab initio computations. In the absence of analogous ab initio frameworks for materials synthesis, high-throughput and machine learning techniques have recently been harnessed to generate synthesis strategies for select materials of interest. Still, a community-accessible, autonomously-compiled synthesis planning resource which spans across materials systems has not yet been developed. In this work, we present a collection of aggregated synthesis parameters computed using the text contained within over 640,000 journal articles using state-of-the-art natural language processing and machine learning techniques. We provide a dataset of synthesis parameters, compiled autonomously across 30 different oxide systems, in a format optimized for planning novel syntheses of materials.

Treatment of artificial wastewater containing two azo textile dyes by vertical-flow constructed wetlands.

PubMed

Hussein, Amjad; Scholz, Miklas

2018-03-01

The release of untreated dye textile wastewater into receiving streams is unacceptable not only for aesthetic reasons and its negative impacts on aquatic life but also because numerous dyes are toxic and carcinogenic to humans. Strategies, as of now, used for treating textile wastewaters have technical and economical restrictions. The greater part of the physico-chemical methods, which are used to treat this kind of wastewater, are costly, produce large amounts of sludge and are wasteful concerning some soluble dyes. In contrast, biological treatments such as constructed wetlands are cheaper than the traditional methods, environmental friendly and do not produce large amounts of sludge. Synthetic wastewater containing Acid Blue 113 (AB113) and Basic Red 46 (BR46) has been added to laboratory-scale vertical-flow construction wetland systems, which have been planted with Phragmites australis (Cav.) Trin. ex Steud. (common reed). The concentrations 7 and 208 mg/l were applied for each dye at the hydraulic contact times of 48 and 96 h. Concerning the low concentrations of BR46 and AB113, the unplanted wetlands are associated with significant (ρ < 0.05) reduction performances, if compared with planted wetlands concerning the removal of dyes. For the high concentrations of AB113, BR46 and a mixture of both of them, wetlands with long contact times were significantly (ρ < 0.05) better than wetlands that had short contact times in terms of dye, colour and chemical oxygen demand reductions. Regarding nitrate nitrogen (NO 3 -N), the reduction percentage rates of AB113, BR46 and a mixture dye of both of them were between 85 and 100%. For low and high inflow dye concentrations, best removals were generally recorded for spring and summer, respectively.

Single pass tangential flow filtration to debottleneck downstream processing for therapeutic antibody production.

PubMed

Dizon-Maspat, Jemelle; Bourret, Justin; D'Agostini, Anna; Li, Feng

2012-04-01

As the therapeutic monoclonal antibody (mAb) market continues to grow, optimizing production processes is becoming more critical in improving efficiencies and reducing cost-of-goods in large-scale production. With the recent trends of increasing cell culture titers from upstream process improvements, downstream capacity has become the bottleneck in many existing manufacturing facilities. Single Pass Tangential Flow Filtration (SPTFF) is an emerging technology, which is potentially useful in debottlenecking downstream capacity, especially when the pool tank size is a limiting factor. It can be integrated as part of an existing purification process, after a column chromatography step or a filtration step, without introducing a new unit operation. In this study, SPTFF technology was systematically evaluated for reducing process intermediate volumes from 2× to 10× with multiple mAbs and the impact of SPTFF on product quality, and process yield was analyzed. Finally, the potential fit into the typical 3-column industry platform antibody purification process and its implementation in a commercial scale manufacturing facility were also evaluated. Our data indicate that using SPTFF to concentrate protein pools is a simple, flexible, and robust operation, which can be implemented at various scales to improve antibody purification process capacity. Copyright © 2011 Wiley Periodicals, Inc.

NHLBI-AbDesigner: an online tool for design of peptide-directed antibodies.

PubMed

Pisitkun, Trairak; Hoffert, Jason D; Saeed, Fahad; Knepper, Mark A

2012-01-01

Investigation of physiological mechanisms at a cellular level often requires production of high-quality antibodies, frequently using synthetic peptides as immunogens. Here we describe a new, web-based software tool called NHLBI-AbDesigner that allows the user to visualize the information needed to choose optimal peptide sequences for peptide-directed antibody production (http://helixweb.nih.gov/AbDesigner/). The choice of an immunizing peptide is generally based on a need to optimize immunogenicity, antibody specificity, multispecies conservation, and robustness in the face of posttranslational modifications (PTMs). AbDesigner displays information relevant to these criteria as follows: 1) "Immunogenicity Score," based on hydropathy and secondary structure prediction; 2) "Uniqueness Score," a predictor of specificity of an antibody against all proteins expressed in the same species; 3) "Conservation Score," a predictor of ability of the antibody to recognize orthologs in other animal species; and 4) "Protein Features" that show structural domains, variable regions, and annotated PTMs that may affect antibody performance. AbDesigner displays the information online in an interactive graphical user interface, which allows the user to recognize the trade-offs that exist for alternative synthetic peptide choices and to choose the one that is best for a proposed application. Several examples of the use of AbDesigner for the display of such trade-offs are presented, including production of a new antibody to Slc9a3. We also used the program in large-scale mode to create a database listing the 15-amino acid peptides with the highest Immunogenicity Scores for all known proteins in five animal species, one plant species (Arabidopsis thaliana), and Saccharomyces cerevisiae.

Perspective: Ab initio force field methods derived from quantum mechanics

NASA Astrophysics Data System (ADS)

Xu, Peng; Guidez, Emilie B.; Bertoni, Colleen; Gordon, Mark S.

2018-03-01

It is often desirable to accurately and efficiently model the behavior of large molecular systems in the condensed phase (thousands to tens of thousands of atoms) over long time scales (from nanoseconds to milliseconds). In these cases, ab initio methods are difficult due to the increasing computational cost with the number of electrons. A more computationally attractive alternative is to perform the simulations at the atomic level using a parameterized function to model the electronic energy. Many empirical force fields have been developed for this purpose. However, the functions that are used to model interatomic and intermolecular interactions contain many fitted parameters obtained from selected model systems, and such classical force fields cannot properly simulate important electronic effects. Furthermore, while such force fields are computationally affordable, they are not reliable when applied to systems that differ significantly from those used in their parameterization. They also cannot provide the information necessary to analyze the interactions that occur in the system, making the systematic improvement of the functional forms that are used difficult. Ab initio force field methods aim to combine the merits of both types of methods. The ideal ab initio force fields are built on first principles and require no fitted parameters. Ab initio force field methods surveyed in this perspective are based on fragmentation approaches and intermolecular perturbation theory. This perspective summarizes their theoretical foundation, key components in their formulation, and discusses key aspects of these methods such as accuracy and formal computational cost. The ab initio force fields considered here were developed for different targets, and this perspective also aims to provide a balanced presentation of their strengths and shortcomings. Finally, this perspective suggests some future directions for this actively developing area.

Ankle Block vs Single-Shot Popliteal Fossa Block as Primary Anesthesia for Forefoot Operative Procedures: Prospective, Randomized Comparison.

PubMed

Schipper, Oliver N; Hunt, Kenneth J; Anderson, Robert B; Davis, W Hodges; Jones, Carroll P; Cohen, Bruce E

2017-11-01

Postoperative pain is often difficult to control with oral medications, requiring large doses of opioid analgesia. Regional anesthesia may be used for primary anesthesia, reducing the need for general anesthetic and postoperative pain medication requirements in the immediate postoperative period. The purpose of this study was to compare the analgesic effects of an ankle block (AB) to a single-shot popliteal fossa block (PFB) for patients undergoing orthopedic forefoot procedures. All patients having elective outpatient orthopedic forefoot procedures were invited to participate in the study. Patients were prospectively randomized to receive either an ultrasound-guided AB or PFB by a board-certified anesthesiologist prior to their procedure. Intraoperative conversion to general anesthesia and postanesthesia care unit (PACU) opioid requirements were recorded. Postoperative pain was assessed using the visual analog scale (VAS) at regular time intervals until 8 am on postoperative day (POD) 2. Patients rated the effectiveness of the block on a 1 to 5 scale, with 5 being very effective. A total of 167 patients participated in the study with 88 patients (53%) receiving an AB and 79 (47%) receiving a single-shot PFB. There was no significant difference in the rate of conversion to general anesthesia between the 2 groups (13.6% [12/88] AB vs 12.7% [10/79] PFB). PACU morphine requirements and doses were significantly reduced in the PFB group ( P = .004) when compared to the AB group. The VAS was also significantly lower for the PFB patients at 10 pm on POD 0 (4.6 vs 1.6, P < .001), 8 am on POD 1 (5.9 vs 4.2, P = .003), and 12 pm on POD 1 (5.4 vs 4.1, P = .01). Overall complication rates were similar between the groups (AB 9% vs PFB 10.1%, P = .51) and there were no significant differences in residual sensory paresthesias (AB 2.3% [2/88] vs PFB 5.1% [4/79], P = .29), motor loss (0% vs 0%), or block site pain and/or erythema (AB 6.9% [6/88] vs PFB 5.1% [4/79], P = .44). The analgesic effect of the PFB lasted significantly longer when compared to the ankle block (AB 14.5 hours vs PFB 20.9 hours, P < .001). There was no significant difference in patient-perceived effectiveness of the block between the 2 groups, with both blocks being highly effective (AB 4.79/5 vs PFB 4.82/5, P = .68). Regional anesthesia was a safe and reliable adjunct to perioperative pain management and highly effective in patients undergoing elective orthopedic forefoot procedures. However, patients who received a PFB had significantly better pain management and decreased opioid requirements in the immediate perioperative period than patients who received an ankle block. Level I, prospective randomized study.

Investigations of suprathreshold color-difference tolerances with different visual scales and different perceptual correlates using CRT colors.

PubMed

Wang, Zhehong; Xu, Haisong

2008-12-01

In order to investigate the performance of suprathreshold color-difference tolerances with different visual scales and different perceptual correlates, a psychophysical experiment was carried out by the method of constant stimuli using CRT colors. Five hue circles at three lightness (L*=30, 50, and 70) and chroma (C*ab=10, 20, and 30) levels were selected to ensure that the color-difference tolerances did not exceed the color gamut of the CRT display. Twelve color centers distributed evenly every 30 degrees along each hue circle were assessed by a panel of eight observers, and the corresponding color-difference tolerances were obtained. The hue circle with L*=50 and C*ab=20 was assessed with three different visual scales (DeltaV=3.06, 5.92, and 8.87 CIELAB units), which ranged from small to large visual scales, while the remaining hue circles were observed only with the small visual scale. The lightness tolerances had no significant correlation with the hue angles, while chroma and hue tolerances showed considerable hue angle dependences. The color-difference tolerances were linearly proportional to the visual scales but with different slopes. The lightness tolerances with different lightness levels but the same chroma showed the crispening effect to some extent, while the chroma and hue tolerances decreased with the increment of the lightness. For the color-difference tolerances with different chroma levels but the same lightness, there was no correlation between the lightness tolerances and the chroma levels, while the chroma and hue tolerances were nearly linearly proportional to the chroma levels.

German version, inter- and intrarater reliability and internal consistency of the "Agitated Behavior Scale" (ABS-G) in patients with moderate to severe traumatic brain injury.

PubMed

Hellweg, Stephanie; Schuster-Amft, Corina

2016-07-19

Agitation is frequently observed during early recovery after traumatic brain injury (TBI). Agitated behaviour often interferes with a goal-orientated rehabilitation and can be a substantial hindrance to therapy. Despite the relatively high occurance of agitation in TBI population there is no objective assessement in German (G) available. An existing scale with excellent psychometric properties is the "Agitated Behavior Scale (ABS)" developed by Corrigan in 1989. The aim of the study was to translate the Agitated Behavior Scale (ABS) into German (ABS-G) and investigate the inter- and intrarater reliability and internal consistency in patients with moderate to severe TBI. A formal nine-step translation and cross-cultural adaptation procedure (TCCA) was applied. Subsequently a prospective observational patient study was conducted. To examine the interrater reliability and internal consistency, two therapists rated 20 patients independently after a therapy session. This procedure was repeated twice on a weekly basis. The intrarater reliability was assessed through video recordings from three patients. Nine raters scored the demonstrated behaviour on the videotape with the ABS-G independently twice within one month. The inter- and intrarater reliability were evaluated with the Spearman rank correlation coefficient and the quadratic weighted kappa. The internal consistency was tested with Cronbach's alpha. Behaviour of 20 patients (18 males; mean age 41 ± 20.7; mean Functional Independence Measure (FIM) cognitive score on admission 7.1 ± 4.04; mean ABS-G score at first observation 17.3 ± 2.83) was assessed threefold. Interrater reliability yielded a correlation coefficient for ABS-G total score of all 60 paired observations of r s 0.845 and a weighted Kappa of 0.738. Intrarater reliability for ABS-G total score ranged between r s 0.719 and 0.953 and showed a weighted Kappa between 0.871 and 0.953. Cronbach's alpha indicated moderate internal consistency with 0.661. This study demonstrates that the ABS-G is a reliable instrument for evaluating agitation in patients with moderate to severe TBI. Hereby it would be possible to monitor agitation objectively and optimise the management of agitated patients according to international recommendations.

Efficient preconditioning of the electronic structure problem in large scale ab initio molecular dynamics simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schiffmann, Florian; VandeVondele, Joost, E-mail: Joost.VandeVondele@mat.ethz.ch

2015-06-28

We present an improved preconditioning scheme for electronic structure calculations based on the orbital transformation method. First, a preconditioner is developed which includes information from the full Kohn-Sham matrix but avoids computationally demanding diagonalisation steps in its construction. This reduces the computational cost of its construction, eliminating a bottleneck in large scale simulations, while maintaining rapid convergence. In addition, a modified form of Hotelling’s iterative inversion is introduced to replace the exact inversion of the preconditioner matrix. This method is highly effective during molecular dynamics (MD), as the solution obtained in earlier MD steps is a suitable initial guess. Filteringmore » small elements during sparse matrix multiplication leads to linear scaling inversion, while retaining robustness, already for relatively small systems. For system sizes ranging from a few hundred to a few thousand atoms, which are typical for many practical applications, the improvements to the algorithm lead to a 2-5 fold speedup per MD step.« less

Hydrogen bond basicity of ionic liquids and molar entropy of hydration of salts as major descriptors in the formation of aqueous biphasic systems.

PubMed

Passos, Helena; Dinis, Teresa B V; Cláudio, Ana Filipa M; Freire, Mara G; Coutinho, João A P

2018-05-23

Aqueous biphasic systems (ABS) composed of ionic liquids (ILs) and conventional salts have been largely investigated and successfully used in separation processes, for which the determination of the corresponding ternary phase diagrams is a prerequisite. However, due the large number of ILs that can be prepared and their high structural versatility, it is impossible to experimentally cover and characterize all possible combinations of ILs and salts that may form ABS. The development of tools for the prediction and design of IL-based ABS is thus a crucial requirement. Based on a large compilation of experimental data, a correlation describing the formation of IL-based ABS is shown here, based on the hydrogen-bonding interaction energies of ILs (EHB) obtained by the COnductor-like Screening MOdel for Real Solvents (COSMO-RS) and the molar entropy of hydration of the salt ions. The ability of the proposed model to predict the formation of novel IL-based ABS is further ascertained.

Discovering charge density functionals and structure-property relationships with PROPhet: A general framework for coupling machine learning and first-principles methods

DOE PAGES

Kolb, Brian; Lentz, Levi C.; Kolpak, Alexie M.

2017-04-26

Modern ab initio methods have rapidly increased our understanding of solid state materials properties, chemical reactions, and the quantum interactions between atoms. However, poor scaling often renders direct ab initio calculations intractable for large or complex systems. There are two obvious avenues through which to remedy this problem: (i) develop new, less expensive methods to calculate system properties, or (ii) make existing methods faster. This paper describes an open source framework designed to pursue both of these avenues. PROPhet (short for PROPerty Prophet) utilizes machine learning techniques to find complex, non-linear mappings between sets of material or system properties. Themore » result is a single code capable of learning analytical potentials, non-linear density functionals, and other structure-property or property-property relationships. These capabilities enable highly accurate mesoscopic simulations, facilitate computation of expensive properties, and enable the development of predictive models for systematic materials design and optimization. Here, this work explores the coupling of machine learning to ab initio methods through means both familiar (e.g., the creation of various potentials and energy functionals) and less familiar (e.g., the creation of density functionals for arbitrary properties), serving both to demonstrate PROPhet’s ability to create exciting post-processing analysis tools and to open the door to improving ab initio methods themselves with these powerful machine learning techniques.« less

Discovering charge density functionals and structure-property relationships with PROPhet: A general framework for coupling machine learning and first-principles methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kolb, Brian; Lentz, Levi C.; Kolpak, Alexie M.

Modern ab initio methods have rapidly increased our understanding of solid state materials properties, chemical reactions, and the quantum interactions between atoms. However, poor scaling often renders direct ab initio calculations intractable for large or complex systems. There are two obvious avenues through which to remedy this problem: (i) develop new, less expensive methods to calculate system properties, or (ii) make existing methods faster. This paper describes an open source framework designed to pursue both of these avenues. PROPhet (short for PROPerty Prophet) utilizes machine learning techniques to find complex, non-linear mappings between sets of material or system properties. Themore » result is a single code capable of learning analytical potentials, non-linear density functionals, and other structure-property or property-property relationships. These capabilities enable highly accurate mesoscopic simulations, facilitate computation of expensive properties, and enable the development of predictive models for systematic materials design and optimization. Here, this work explores the coupling of machine learning to ab initio methods through means both familiar (e.g., the creation of various potentials and energy functionals) and less familiar (e.g., the creation of density functionals for arbitrary properties), serving both to demonstrate PROPhet’s ability to create exciting post-processing analysis tools and to open the door to improving ab initio methods themselves with these powerful machine learning techniques.« less

Improved Soluble ScFv ELISA Screening Approach for Antibody Discovery Using Phage Display Technology.

PubMed

Tohidkia, Mohammad R; Sepehri, Maryam; Khajeh, Shirin; Barar, Jaleh; Omidi, Yadollah

2017-09-01

Phage display technology (PDT) is a powerful tool for the isolation of recombinant antibody (Ab) fragments. Using PDT, target molecule-specific phage-Ab clones are enriched through the "biopanning" process. The individual specific binders are screened by the monoclonal scFv enzyme-linked immunosorbent assay (ELISA) that may associate with inevitable false-negative results. Thus, in this study, three strategies were investigated for optimization of the scFvs screening using Tomlinson I and J libraries, including (1) optimizing the expression of functional scFvs, (2) improving the sensitivity of ELISA, and (3) preparing different samples containing scFvs. The expression of all scFv Abs was significantly enhanced when scFv clones were cultivated in the terrific broth (TB) medium at the optimum temperature of 30 °C. The protein A-conjugated with horseradish peroxidase (HRP) was found to be a well-suited reagent for the detection of Ag-bound scFvs in comparison with either anti-c-myc Ab or the mixing procedure. Based on our findings, it seems there is no universal media supplement for an improved expression of all scFvs derived from both Tomlinson I and J libraries. We thus propose that expression of scFv fragments in a microplate scale is largely dependent on a variety of parameters, in particular the scFv clones and relevant sequences.

A fitting empirical potential for NiTi alloy and its application

NASA Astrophysics Data System (ADS)

Ren, Guowu; Tang, Tiegang; Sehitoglu, Huseyin

Due to its superelastic behavior, NiTi shape memory alloy receives considerable attentions over a wide range of industrial and commercial applications. Limited to its complex structural transformation and multiple variants, semiempirical potentials for performing large-scale molecular dynamics simulations to investigate the atomistic mechanical process, are very few. In this work, we construct a new interatomic potential for the NiTi alloy by fitting to experimental or ab initio data. The fitting potential correctly predicts the lattice parameter, structural stability, equation of state for cubic B2(austenite) and monoclinic B19'(martensite) phases. In particular the elastic properties(three elastic constants for B2 and thirteen ones for B19') are in satisfactory agreement with the experiments or ab initio calculations. Furthermore, we apply this potential to conduct the molecular dynamics simulations of the mechanical behavior for NiTi alloy and the results capture its reversible transformation.

Physical conditions in star-forming regions around S235

NASA Astrophysics Data System (ADS)

Kirsanova, M. S.; Wiebe, D. S.; Sobolev, A. M.; Henkel, C.; Tsivilev, A. P.

2014-01-01

Gas density and temperature in star-forming regions around Sh2-235 are derived from ammonia line observations. This information is used to evaluate formation scenarios and to determine evolutionary stages of the young embedded clusters S235 East 1, S235 East 2 and S235 Central. We also estimate the gas mass in the embedded clusters and its ratio to the stellar mass. S235 East 1 appears to be less evolved than S235 East 2 and S235 Central. In S235 East 1 the molecular gas mass exceeds that in the other clusters. Also, this cluster is more embedded in the parent gas cloud than the other two. Comparison with a theoretical model shows that the formation of these three clusters could have been stimulated by the expansion of the Sh2-235 H II region (hereafter S235) via a collect-and-collapse process, provided the density in the surrounding gas exceeds 3 × 103 cm-3, or via collapse of pre-existing clumps. The expansion of S235 cannot be responsible for star formation in the southern S235 A-B region. However, formation of the massive stars in this region might have been triggered by a large-scale supernova shock. Thus, triggered star formation in the studied region may come in three varieties, namely collect-and-collapse and collapse of pre-existing clumps, both initiated by expansion of the local H II regions, and triggered by an external large-scale shock. We argue that the S235 A H II region expands into a highly non-uniform medium with increasing density. It is too young to trigger star formation in its vicinity by a collect-and-collapse process. There is an age spread inside the S235 A-B region. Massive stars in the S235 A-B region are considerably younger than lower mass stars in the same area. This follows from the estimates of their ages and the ages of associated H II regions.

Modification of the Rappaport rapid test in large-scale testing for syphilis. Evaluation of the rapid plate and rapid card tests.

PubMed

Ghinsberg, R; Meir, E; Blumstein, G; Kafeman, R

1975-11-01

The Rappaport rapid (RR) plate and card tests were developed as modifications of the RR tube test to permit rapid and inexpensive screening of large numbers of subjects for the diagnosis of syphilis. More than 2,000 sera were examined in parallel by the Venereal Disease Research Laboratory (VDRL) slide test, the rapid plasma reagin (RPR) card test and the RR plate and card tests. There was complete agreement between the RR plate and card tests and the VDRL slide and RPR card tests in 96.6% of sera. In a selected group of 1,530 sera examined, in addition, by the fluorescent treponemal antibody absorption (FTA-ABS) test, there was agreement between the RR plate and card tests and the FTA-ABS test in 74.3% of sera and between the VDRL and RPR tests and the FTA-ABS test in 73.7% of sera. The RR plate test was found to be sufficiently sensitive and specific for the diagnosis of syphilis, although the VDRL slide test is perhaps more sensitive in primary and late latent syphilis. Since the antigen used in the RR tests is colored and stable and the sera do not require inactivation before the test, the tests are easier to perform than the VDRL slide test: the RR plate and card tests could therefore replace the VDRL test as a screening test, with hardly any loss of accuracy.

A solid-phase assay for the detection of anti-sperm antibodies.

PubMed

Okada, H; Kamidono, S; Owens, G R; Nagamatsu, G R; Addonizio, J C

1993-05-01

ELISA is an ideal assay method for a large-scale screening of anti-sperm antibodies among a large number of infertile males. However, conventional ELISA with whole spermatozoa needs time-consuming steps of centrifugation. A solid-phase assay used for detecting anti-sperm antibodies was established. This assay is suitable not only for detecting circulating anti-sperm antibodies of IgG, IgM, and IgA subclass simultaneously but also for screening hybridomas secreting anti-sperm monoclonal antibodies (mAbs). The microtiter plates, on which solubilized sperm antigens are fixed, can be stored at -80 degrees C for up to six months without losing reactivity with anti-sperm antibodies. Using this assay, 53 sera (13 were proven positive and 40 were proven negative for sperm agglutination antibody) were tested. Although the false-negative rate was 0%, the false-positive rate was 32%. One thousand one hundred sixty-five supernatants from hybridomas constructed with splenocytes of mice who were hyperimmunized with human sperm and nonsecreting myeloma cells were tested by this solid-phase assay and two anti-sperm mAb secreting clones were selected and established. It is recommended that for research work this assay could be used for the first screening of the hybridoma secreting anti-sperm mAb, and for clinical use this assay might be suitable for the first screening of sera of infertile patients. However, conventional bioassays should follow to confirm the biological meaning of the positivity.

Blocking monocyte transmigration in in vitro system by an anti-CD99 human antibody in single chain fragment variable (scFv) format. Efficient large scale purification of biological active scFv from inclusion bodies in E. coli expression system

PubMed Central

Moricoli, Diego; Muller, William A.; Carbonella, Damiano Cosimo; Balducci, Maria Cristina; Dominici, Sabrina; Fiori, Valentina; Watson, Richard; Weber, Evan; Cianfriglia, Maurizio; Scotlandi, Katia; Magnani, Mauro

2015-01-01

Migration of leukocytes into a site of inflammation involves several steps mediated by various families of adhesion molecules. CD99 play a significant role in transendothelial migration (TEM) of leukocytes. Inhibition of TEM by specific monoclonal antibody (mAb) can provide a potent therapeutic approach to treating inflammatory conditions. However, the therapeutic utilization of whole IgG can lead to an inappropriate activation of Fc receptor-expressing cells inducing serious adverse side effects due to cytokine release. In this regard, specific recombinant antibody in single chain variable fragments (scFvs) originated by phage library may offer a solution by affecting TEM function in a safe clinical context. However, this consideration requires large scale production of functional scFv antibodies under GMP conditions and hence, the absence of toxic reagents utilized for the solubilization and refolding steps of inclusion bodies that may discourage industrial application of these antibody fragments. In order to apply the scFv anti-CD99 named C7A in a clinical setting we herein describe an efficient and large scale production of the antibody fragments expressed in E.coli as insoluble protein avoiding gel filtration chromatography approach, and laborious refolding step pre- and post-purification. Using differential salt elution which is a simple, reproducible and effective procedure we are able to separate scFv in monomer format from aggregates. The purified scFv antibody C7A exhibits inhibitory activity comparable to an antagonistic conventional mAb, thus providing an excellent agent for blocking CD99 signalling. Thanks to the original purification protocol that can be extended to other scFvs that are expressed as inclusion bodies in bacterial systems, the scFv anti-CD99 C7A herein described represents the first step towards the construction of new antibody therapeutic. PMID:24798881

Design of a large-scale femtoliter droplet array for single-cell analysis of drug-tolerant and drug-resistant bacteria.

PubMed

Iino, Ryota; Matsumoto, Yoshimi; Nishino, Kunihiko; Yamaguchi, Akihito; Noji, Hiroyuki

2013-01-01

Single-cell analysis is a powerful method to assess the heterogeneity among individual cells, enabling the identification of very rare cells with properties that differ from those of the majority. In this Methods Article, we describe the use of a large-scale femtoliter droplet array to enclose, isolate, and analyze individual bacterial cells. As a first example, we describe the single-cell detection of drug-tolerant persisters of Pseudomonas aeruginosa treated with the antibiotic carbenicillin. As a second example, this method was applied to the single-cell evaluation of drug efflux activity, which causes acquired antibiotic resistance of bacteria. The activity of the MexAB-OprM multidrug efflux pump system from Pseudomonas aeruginosa was expressed in Escherichia coli and the effect of an inhibitor D13-9001 were assessed at the single cell level.

Individual Differences in Temporal Selective Attention as Reflected in Pupil Dilation.

PubMed

Willems, Charlotte; Herdzin, Johannes; Martens, Sander

2015-01-01

Attention is restricted for the second of two targets when it is presented within 200-500 ms of the first target. This attentional blink (AB) phenomenon allows one to study the dynamics of temporal selective attention by varying the interval between the two targets (T1 and T2). Whereas the AB has long been considered as a robust and universal cognitive limitation, several studies have demonstrated that AB task performance greatly differs between individuals, with some individuals showing no AB whatsoever. Here, we studied these individual differences in AB task performance in relation to differences in attentional timing. Furthermore, we investigated whether AB magnitude is predictive for the amount of attention allocated to T1. For both these purposes pupil dilation was measured, and analyzed with our recently developed deconvolution method. We found that the dynamics of temporal attention in small versus large blinkers differ in a number of ways. Individuals with a relatively small AB magnitude seem better able to preserve temporal order information. In addition, they are quicker to allocate attention to both T1 and T2 than large blinkers. Although a popular explanation of the AB is that it is caused by an unnecessary overinvestment of attention allocated to T1, a more complex picture emerged from our data, suggesting that this may depend on whether one is a small or a large blinker. The use of pupil dilation deconvolution seems to be a powerful approach to study the temporal dynamics of attention, bringing us a step closer to understanding the elusive nature of the AB. We conclude that the timing of attention to targets may be more important than the amount of allocated attention in accounting for individual differences.

Designing Liquid Rocket Engine Injectors for Performance, Stability, and Cost

NASA Technical Reports Server (NTRS)

Westra, Douglas G.; West, Jeffrey S.

2014-01-01

NASA is developing the Space Launch System (SLS) for crewed exploration missions beyond low Earth orbit. Marshall Space Flight Center (MSFC) is designing rocket engines for the SLS Advanced Booster (AB) concepts being developed to replace the Shuttle-derived solid rocket boosters. One AB concept uses large, Rocket-Propellant (RP)-fueled engines that pose significant design challenges. The injectors for these engines require high performance and stable operation while still meeting aggressive cost reduction goals for access to space. Historically, combustion stability problems have been a critical issue for such injector designs. Traditional, empirical injector design tools and methodologies, however, lack the ability to reliably predict complex injector dynamics that often lead to combustion stability. Reliance on these tools alone would likely result in an unaffordable test-fail-fix cycle for injector development. Recently at MSFC, a massively parallel computational fluid dynamics (CFD) program was successfully applied in the SLS AB injector design process. High-fidelity reacting flow simulations were conducted for both single-element and seven-element representations of the full-scale injector. Data from the CFD simulations was then used to significantly augment and improve the empirical design tools, resulting in a high-performance, stable injector design.

Extracting DNA words based on the sequence features: non-uniform distribution and integrity.

PubMed

Li, Zhi; Cao, Hongyan; Cui, Yuehua; Zhang, Yanbo

2016-01-25

DNA sequence can be viewed as an unknown language with words as its functional units. Given that most sequence alignment algorithms such as the motif discovery algorithms depend on the quality of background information about sequences, it is necessary to develop an ab initio algorithm for extracting the "words" based only on the DNA sequences. We considered that non-uniform distribution and integrity were two important features of a word, based on which we developed an ab initio algorithm to extract "DNA words" that have potential functional meaning. A Kolmogorov-Smirnov test was used for consistency test of uniform distribution of DNA sequences, and the integrity was judged by the sequence and position alignment. Two random base sequences were adopted as negative control, and an English book was used as positive control to verify our algorithm. We applied our algorithm to the genomes of Saccharomyces cerevisiae and 10 strains of Escherichia coli to show the utility of the methods. The results provide strong evidences that the algorithm is a promising tool for ab initio building a DNA dictionary. Our method provides a fast way for large scale screening of important DNA elements and offers potential insights into the understanding of a genome.

Reducing the layer number of AB stacked multilayer graphene grown on nickel by annealing at low temperature.

PubMed

Velasco, J Marquez; Giamini, S A; Kelaidis, N; Tsipas, P; Tsoutsou, D; Kordas, G; Raptis, Y S; Boukos, N; Dimoulas, A

2015-10-09

Controlling the number of layers of graphene grown by chemical vapor deposition is crucial for large scale graphene application. We propose here an etching process of graphene which can be applied immediately after growth to control the number of layers. We use nickel (Ni) foil at high temperature (T = 900 °C) to produce multilayer-AB-stacked-graphene (MLG). The etching process is based on annealing the samples in a hydrogen/argon atmosphere at a relatively low temperature (T = 450 °C) inside the growth chamber. The extent of etching is mainly controlled by the annealing process duration. Using Raman spectroscopy we demonstrate that the number of layers was reduced, changing from MLG to few-layer-AB-stacked-graphene and in some cases to randomly oriented few layer graphene near the substrate. Furthermore, our method offers the significant advantage that it does not introduce defects in the samples, maintaining their original high quality. This fact and the low temperature our method uses make it a good candidate for controlling the layer number of already grown graphene in processes with a low thermal budget.

[Relationships of positive and negative affectivity to sleep quality in Japanese civil servants: 3-year follow-up study].

PubMed

Saeki, Urara; Nasermoaddeli, Ali; Sekine, Michikazu; Kagamimori, Sadanobu

2008-11-01

We conducted this longitudinal study to evaluate the relationships of positive and negative affectivity (Affect Balance Scale) to sleep quality among civil servants. For this study we evaluated 827 civil servants of T city in Toyama prefecture in the springs of 2001 (Baseline) and 2004 with complete information in both phases of the study. Based on the median score at each phase, we divided Affect Balance Scale (ABS) scores into high and low groups. We conducted logistic regression analysis to determine the odds ratios (OR) of 3-yr follow-up sleep quality by baseline and follow-up ABS scores. After adjusting for baseline sleep quality scores, age, sex, employment, job strain, and exercise habits, participants who had high ABS scores were more likely (OR: 3.13, 95% confidence interval (CI): 1.78-5.53) to have better sleep quality than those with low ABS scores at both phases. In addition, participants with low ABS scores at baseline and high ABS scores 3 yr later had better sleep quality (OR: 1.81, 95%CI: 1.02-3.20) than those with low ABS scores at both phases. These findings substantiate the relationships of positive and negative affectivity to sleep quality. Improving the affect balance condition as well as maintaining good affect balance condition may be important determinants of sleep quality in civil servants.

Sparse Regression Based Structure Learning of Stochastic Reaction Networks from Single Cell Snapshot Time Series.

PubMed

Klimovskaia, Anna; Ganscha, Stefan; Claassen, Manfred

2016-12-01

Stochastic chemical reaction networks constitute a model class to quantitatively describe dynamics and cell-to-cell variability in biological systems. The topology of these networks typically is only partially characterized due to experimental limitations. Current approaches for refining network topology are based on the explicit enumeration of alternative topologies and are therefore restricted to small problem instances with almost complete knowledge. We propose the reactionet lasso, a computational procedure that derives a stepwise sparse regression approach on the basis of the Chemical Master Equation, enabling large-scale structure learning for reaction networks by implicitly accounting for billions of topology variants. We have assessed the structure learning capabilities of the reactionet lasso on synthetic data for the complete TRAIL induced apoptosis signaling cascade comprising 70 reactions. We find that the reactionet lasso is able to efficiently recover the structure of these reaction systems, ab initio, with high sensitivity and specificity. With only < 1% false discoveries, the reactionet lasso is able to recover 45% of all true reactions ab initio among > 6000 possible reactions and over 102000 network topologies. In conjunction with information rich single cell technologies such as single cell RNA sequencing or mass cytometry, the reactionet lasso will enable large-scale structure learning, particularly in areas with partial network structure knowledge, such as cancer biology, and thereby enable the detection of pathological alterations of reaction networks. We provide software to allow for wide applicability of the reactionet lasso.

GPU implementation of the linear scaling three dimensional fragment method for large scale electronic structure calculations

NASA Astrophysics Data System (ADS)

Jia, Weile; Wang, Jue; Chi, Xuebin; Wang, Lin-Wang

2017-02-01

LS3DF, namely linear scaling three-dimensional fragment method, is an efficient linear scaling ab initio total energy electronic structure calculation code based on a divide-and-conquer strategy. In this paper, we present our GPU implementation of the LS3DF code. Our test results show that the GPU code can calculate systems with about ten thousand atoms fully self-consistently in the order of 10 min using thousands of computing nodes. This makes the electronic structure calculations of 10,000-atom nanosystems routine work. This speed is 4.5-6 times faster than the CPU calculations using the same number of nodes on the Titan machine in the Oak Ridge leadership computing facility (OLCF). Such speedup is achieved by (a) carefully re-designing of the computationally heavy kernels; (b) redesign of the communication pattern for heterogeneous supercomputers.

The Embedded Atom Model and large-scale MD simulation of tin under shock loading

NASA Astrophysics Data System (ADS)

Sapozhnikov, F. A.; Ionov, G. V.; Dremov, V. V.; Soulard, L.; Durand, O.

2014-05-01

The goal of the work was to develop an interatomic potential, that can be used in large-scale classical MD simulations to predict tin properties near the melting curve, the melting curve itself, and the kinetics of melting and solidification when shock and ramp loading. According to phase diagram, shocked tin melts from bcc phase, and since the main objective was to investigate melting, the EAM was parameterized for bcc phase. The EAM was optimized using isothermal compression data (experimental at T=300 K and ab-initio at T=0 K for bcc, fcc, bct structures), experimental and QMD data on the Hugoniot and on the melting at elevated pressures. The Hugoniostat calculations centred at β-tin at ambient conditions showed that the calculated Hugoniot is in good agreement with experimental and QMD data above p-bct transition pressure. Calculations of overcooled liquid in pressure range corresponding to bcc phase showed crystallization into bcc phase. Since the principal Hugoniot of tin originates from the β-tin that is not described by this EAM the special initial state of bcc samples was constructed to perform large-scale MD simulations of shock loading.

Hierarchical Cluster Formation in Concentrated Monoclonal Antibody Formulations

NASA Astrophysics Data System (ADS)

Godfrin, P. Douglas; Zarzar, Jonathan; Zarraga, Isidro Dan; Porcar, Lionel; Falus, Peter; Wagner, Norman; Liu, Yun

Reversible cluster formation has been identified as an underlying cause of large solution viscosities observed in some concentrated monoclonal antibody (mAb) formulations. As high solution viscosity prevents the use of subcutaneous injection as a delivery method for some mAbs, a fundamental understanding of the interactions responsible for high viscosities in concentrated mAb solutions is of significant relevance to mAb applications in human health care as well as of intellectual interest. Here, we present a detailed investigation of a well-studied IgG1 based mAb to relate the short time dynamics and microstructure to significant viscosity changes over a range of pharmaceutically relevant physiochemical conditions. Using a combination of experimental techniques, it is found that upon adding Na2SO4, these antibodies dimerize in solution. Proteins form strongly bounded reversible dimers at dilute concentrations that, when concentrated, interact with each other to form loosely bounded, large, transient clusters. The combined effect of forming strongly bounded dimers and a large transient network is a significant increase in the solution viscosity. Strongly bounded, reversible dimers may exist in many IgG1 based mAb systems such that these results contribute to a more comprehensive understanding of the physical mechanisms producing high viscosities in concentrated protein solutions.

Implementation of highly parallel and large scale GW calculations within the OpenAtom software

NASA Astrophysics Data System (ADS)

Ismail-Beigi, Sohrab

The need to describe electronic excitations with better accuracy than provided by band structures produced by Density Functional Theory (DFT) has been a long-term enterprise for the computational condensed matter and materials theory communities. In some cases, appropriate theoretical frameworks have existed for some time but have been difficult to apply widely due to computational cost. For example, the GW approximation incorporates a great deal of important non-local and dynamical electronic interaction effects but has been too computationally expensive for routine use in large materials simulations. OpenAtom is an open source massively parallel ab initiodensity functional software package based on plane waves and pseudopotentials (http://charm.cs.uiuc.edu/OpenAtom/) that takes advantage of the Charm + + parallel framework. At present, it is developed via a three-way collaboration, funded by an NSF SI2-SSI grant (ACI-1339804), between Yale (Ismail-Beigi), IBM T. J. Watson (Glenn Martyna) and the University of Illinois at Urbana Champaign (Laxmikant Kale). We will describe the project and our current approach towards implementing large scale GW calculations with OpenAtom. Potential applications of large scale parallel GW software for problems involving electronic excitations in semiconductor and/or metal oxide systems will be also be pointed out.

Gender and Ethnicity Differences on the Abridged Big Five Circumplex (AB5C) of Personality Traits: A Differential Item Functioning Analysis

ERIC Educational Resources Information Center

Mitchelson, Jacqueline K.; Wicher, Eliza W.; LeBreton, James M.; Craig, S. Bartholomew

2009-01-01

The current study evaluates the measurement precision of the Abridged Big Five Circumplex (AB5C) of personality traits by identifying those items that demonstrate differential item functioning by gender and ethnicity. Differential item functioning is found in 33 of 45 (73%) of the AB5C scales, across gender and ethnic groups (Caucasian vs. African…

Upper wing surface boundary layer measurements and static aerodynamic data obtained on a 0.015-scale model (42-0) or the SSV orbiter configuration 140A/B in the LTV HSWT at a Mach number of 4.6 (LA58)

NASA Technical Reports Server (NTRS)

Ball, J. W.; Lindahl, R. H.

1976-01-01

The purpose of the test was to investigate the nature of the Orbiter boundary layer characteristics at angles of attack from -4 to 32 degrees at a Mach number of 4.6. The effect of large grit, employed as transition strips, on both the nature of the boundary layer and the force and moment characteristics were investigated along with the effects of large negative elevon deflection on lee side separation. In addition, laminar and turbulent boundary layer separation phenomena which could cause asymmetric flow separation were investigated.

Large-scale exact diagonalizations reveal low-momentum scales of nuclei

NASA Astrophysics Data System (ADS)

Forssén, C.; Carlsson, B. D.; Johansson, H. T.; Sääf, D.; Bansal, A.; Hagen, G.; Papenbrock, T.

2018-03-01

Ab initio methods aim to solve the nuclear many-body problem with controlled approximations. Virtually exact numerical solutions for realistic interactions can only be obtained for certain special cases such as few-nucleon systems. Here we extend the reach of exact diagonalization methods to handle model spaces with dimension exceeding 1010 on a single compute node. This allows us to perform no-core shell model (NCSM) calculations for 6Li in model spaces up to Nmax=22 and to reveal the 4He+d halo structure of this nucleus. Still, the use of a finite harmonic-oscillator basis implies truncations in both infrared (IR) and ultraviolet (UV) length scales. These truncations impose finite-size corrections on observables computed in this basis. We perform IR extrapolations of energies and radii computed in the NCSM and with the coupled-cluster method at several fixed UV cutoffs. It is shown that this strategy enables information gain also from data that is not fully UV converged. IR extrapolations improve the accuracy of relevant bound-state observables for a range of UV cutoffs, thus making them profitable tools. We relate the momentum scale that governs the exponential IR convergence to the threshold energy for the first open decay channel. Using large-scale NCSM calculations we numerically verify this small-momentum scale of finite nuclei.

A reactive, scalable, and transferable model for molecular energies from a neural network approach based on local information

NASA Astrophysics Data System (ADS)

Unke, Oliver T.; Meuwly, Markus

2018-06-01

Despite the ever-increasing computer power, accurate ab initio calculations for large systems (thousands to millions of atoms) remain infeasible. Instead, approximate empirical energy functions are used. Most current approaches are either transferable between different chemical systems, but not particularly accurate, or they are fine-tuned to a specific application. In this work, a data-driven method to construct a potential energy surface based on neural networks is presented. Since the total energy is decomposed into local atomic contributions, the evaluation is easily parallelizable and scales linearly with system size. With prediction errors below 0.5 kcal mol-1 for both unknown molecules and configurations, the method is accurate across chemical and configurational space, which is demonstrated by applying it to datasets from nonreactive and reactive molecular dynamics simulations and a diverse database of equilibrium structures. The possibility to use small molecules as reference data to predict larger structures is also explored. Since the descriptor only uses local information, high-level ab initio methods, which are computationally too expensive for large molecules, become feasible for generating the necessary reference data used to train the neural network.

On the Signaling of Electrochemical Aptamer-Based Sensors: Collision- and Folding-Based Mechanisms

PubMed Central

Xiao, Yi; Uzawa, Takanori; White, Ryan J.; DeMartini, Daniel; Plaxco, Kevin W.

2010-01-01

Recent years have seen the emergence of a new class of electrochemical sensors predicated on target binding-induced folding of electrode-bound redox-modified aptamers and directed against targets ranging from small molecules to proteins. Previous studies of the relationship between gain and probe-density for these electrochemical, aptamer-based (E-AB) sensors suggest that signal transduction is linked to binding-induced changes in the efficiency with which the attached redox tag strikes the electrode. This, in turn, suggests that even well folded aptamers may support E-AB signaling if target binding sufficiently alters their flexibility. Here we investigate this using a thrombin-binding aptamer that undergoes binding-induced folding at low ionic strength but can be forced to adopt a folded conformation at higher ionic strength even in the absence of its protein target. We find that, under conditions in which the thrombin aptamer is fully folded prior to target binding, we still obtain a ca. 30% change in E-AB signal upon saturated target levels. In contrast, however, under conditions in which the aptamer is unfolded in the absence of target and thus undergoes binding-induced folding the observed signal change is twice as great. The ability of folded aptamers to support E-AB signaling, however, is not universal: a fully folded anti-IgE aptamer, for example, produces only an extremely small, ca. 2.5% signal change in the presence of target despite the larger steric bulk of this protein. Thus, while it appears that binding-induced changes in the dynamics in fully folded aptamers can support E-AB signaling, this signaling mechanism may not be general, and in order to ensure the design of high-gain sensors binding must be linked to a large-scale conformational change. PMID:20436787

Nonadiabatic effects in ultracold molecules via anomalous linear and quadratic Zeeman shifts.

PubMed

McGuyer, B H; Osborn, C B; McDonald, M; Reinaudi, G; Skomorowski, W; Moszynski, R; Zelevinsky, T

2013-12-13

Anomalously large linear and quadratic Zeeman shifts are measured for weakly bound ultracold 88Sr2 molecules near the intercombination-line asymptote. Nonadiabatic Coriolis coupling and the nature of long-range molecular potentials explain how this effect arises and scales roughly cubically with the size of the molecule. The linear shifts yield nonadiabatic mixing angles of the molecular states. The quadratic shifts are sensitive to nearby opposite f-parity states and exhibit fourth-order corrections, providing a stringent test of a state-of-the-art ab initio model.

Recent Theoretical Studies On Excitation and Recombination

NASA Technical Reports Server (NTRS)

Pradhan, Anil K.

2000-01-01

New advances in the theoretical treatment of atomic processes in plasmas are described. These enable not only an integrated, unified, and self-consistent treatment of important radiative and collisional processes, but also large-scale computation of atomic data with high accuracy. An extension of the R-matrix work, from excitation and photoionization to electron-ion recombination, includes a unified method that subsumes both the radiative and the di-electronic recombination processes in an ab initio manner. The extensive collisional calculations for iron and iron-peak elements under the Iron Project are also discussed.

A novel monoclonal antibody-based enzyme-linked immunosorbent assay to determine luteinizing hormone in bovine plasma.

PubMed

Borromeo, V; Berrini, A; De Grandi, F; Cremonesi, F; Fiandanese, N; Pocar, P; Secchi, C

2014-07-01

The development of a novel enzyme-linked immunosorbent assay (ELISA) for determining luteinizing hormone (LH) in bovine plasma is described. Anti-bovine LH (bLH) monoclonal antibodies (mAbs) were produced and characterized. One mAb recognizing the bLH β subunit was used for immunoaffinity purification of substantial amounts of biologically active bLH from pituitary glands. The purified bLH in combination with 2 anti-bLH β subunit mAbs was used to develop a sandwich ELISA, which satisfied all the criteria required to investigate LH secretory patterns in the bovine species. The ELISA standard curve was linear over the range 0.05 to 2.5 ng/mL, and the assay proved suitable for measuring bLH in plasma without any prior treatment of samples. Cross-reactivity and recovery tests confirmed the specificity of the method. The intra- and inter-assay coefficients of variation ranged between 3.41% and 9.40%, and 9.29% and 15.84%, respectively. The analytical specificity of the method was validated in vivo by provocative tests for LH in heifers, using the LH releasing peptide gonadotropin-releasing hormone. In conclusion, the adoption of mAbs for this ELISA for coating the wells and labeling, combined with the easy one-step production of reference bLH, ensures long-term continuity in large-scale measurements of LH in the bovine species. Copyright © 2014 Elsevier Inc. All rights reserved.

Results of investigations on an 0.004-scale 140A/B configuration space shuttle vehicle orbiter model (34-0) in the NASA/Langley Research Center hypersonic helium tunnel (OA88)

NASA Technical Reports Server (NTRS)

Hawthorne, P. J.

1974-01-01

Data obtained during a wind tunnel test of an 0.004-scale 140A/B configuration SSV Orbiter are reported. The test was conducted at a nominal Mach number of 20 and at Reynolds numbers of 0.7, 1.1, 2.0, and 4 x 10 to the 6th power per foot. The complete 140A/B model was tested with various elevon settings and additionally in wing off/bodyflap off configurations at angles of attack from 18 to 54 degrees at zero yaw. This test was performed to obtain high hypersonic longitudinal and lateral-directional stability and control characteristics of the SSV configuration.

The Atacama B-mode Search: Status and Prospect

NASA Astrophysics Data System (ADS)

Kusaka, Akito

2013-04-01

The Atacama B-mode Search (ABS) experiment is a 145 GHz polarimeter designed to measure the B-mode polarization of the Cosmic Microwave Background (CMB) at degre angular scales. In January 2012, ABS has deployed 240 polarimeters employing transition-edge sensor (TES) bolometers. ABS has unique advantages for the measurement of B modes. This includes a continuously rotating half-wave plate that provides fast and clean modulation, as well as systematically clean optics that consist of a cryogenic side-fed Dragone telescope and feedhorn coupled TES polarimeters. In this talk, we will present the status and prospect of ABS.

A strategy to accelerate protein production from a pool of clones in Chinese hamster ovary cells for toxicology studies.

PubMed

Hu, Zhilan; Hsu, Wendy; Pynn, Abby; Ng, Domingos; Quicho, Donna; Adem, Yilma; Kwong, Zephie; Mauger, Brad; Joly, John; Snedecor, Bradley; Laird, Michael W; Andersen, Dana C; Shen, Amy

2017-11-01

In the biopharmaceutical industry, a clonally derived cell line is typically used to generate material for investigational new drug (IND)-enabling toxicology studies. The same cell line is then used to generate material for clinical studies. If a pool of clones can be used to produce material for IND-enabling toxicology studies (Pool for Tox (PFT) strategy) during the time a lead clone is being selected for clinical material production, the toxicology studies can be accelerated significantly (approximately 4 months at Genentech), leading to a potential acceleration of 4 months for the IND submission. We explored the feasibility of the PFT strategy with three antibodies-mAb1, mAb2, and mAb3-at the 2 L scale. For each antibody, two lead cell lines were identified that generated material with similar product quality to the material generated from the associated pool. For two antibody molecules, mAb1 and mAb2, the material generated by the lead cell lines from 2 L bioreactors was tested in an accelerated stability study and was shown to have stability comparable to the material generated by the associated pool. Additionally, we used this approach for two antibody molecules, mAb4 and mAb5, at Tox and GMP production. The materials from the Tox batch at 400 L scale and three GMP batches at 2000 L scale have comparable product quality attributes for both molecules. Our results demonstrate the feasibility of using a pool of clonally derived cell lines to generate material of similar product quality and stability for use in IND-enabling toxicology studies as was derived from the final production clone, which enabled significant acceleration of timelines into clinical development. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1449-1455, 2017. © 2017 American Institute of Chemical Engineers.

Molecular identification of disk abalone (Haliotis discus discus) tetraspanin 33 and CD63: Insights into potent players in the disk abalone host defense system.

PubMed

Priyathilaka, Thanthrige Thiunuwan; Bathige, S D N K; Herath, H M L P B; Lee, Sukkyoung; Lee, Jehee

2017-10-01

Tetraspanins are a superfamily of transmembrane proteins involved in a diverse range of physiological processes including differentiation, adhesion, signal transduction, cell motility, and immune responses. In the present study, two tetraspanins, CD63 and tetraspanin 33 (TSPAN33) from disk abalone (AbCD63 and AbTSPAN33), were identified and characterized at the molecular level. The coding sequences for AbCD63 and AbTSPAN33 encoded polypeptides of 234 and 290 amino acids (aa) with predicted molecular mass of 25.3 and 32.5 kDa, respectively. The deduced AbCD63 and AbTSPAN33 protein sequences were also predicted to have a typical tetraspanin domain architecture, including four transmembrane domains (TM), short N- and C- terminal regions, a short intracellular loop, as well as a large and small extracellular loop. A characteristic CCG motif and cysteine residues, which are highly conserved across CD63 and TSPAN33 proteins of different species, were present in the large extracellular loop of both abalone tetraspanins. Phylogenetic analysis revealed that the AbCD63 and AbTSPAN33 clustered in the invertebrate subclade of tetraspanins, thus exhibiting a close relationship with tetraspanins of other mollusks. The AbCD63 and AbTSPAN33 mRNA transcripts were detected at early embryonic development stages of disk abalone with significantly higher amounts at the trochophore stage, suggesting the involvement of these proteins in embryonic development. Both AbCD63 and AbTSPAN33 were ubiquitously expressed in all the tissues of unchallenged abalones analyzed, with the highest expression levels found in hemocytes. Moreover, significant induction of AbCD63 and AbTSPAN33 mRNA expression was observed in immunologically important tissues, such as hemocytes and gills, upon stimulation with live bacteria (Vibrio parahaemolyticus and Listeria monocytogenes), virus (viral hemorrhagic septicemia virus), and two potent immune stimulators [polyinosinic:polycytidylic acid (poly I:C) and lipopolysaccharide (LPS)]. Collectively, these findings suggest that AbCD63 and AbTSPAN33 are involved in innate immune responses in disk abalone during pathogenic stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

Real‐time monitoring and control of the load phase of a protein A capture step

PubMed Central

Rüdt, Matthias; Brestrich, Nina; Rolinger, Laura

2016-01-01

ABSTRACT The load phase in preparative Protein A capture steps is commonly not controlled in real‐time. The load volume is generally based on an offline quantification of the monoclonal antibody (mAb) prior to loading and on a conservative column capacity determined by resin‐life time studies. While this results in a reduced productivity in batch mode, the bottleneck of suitable real‐time analytics has to be overcome in order to enable continuous mAb purification. In this study, Partial Least Squares Regression (PLS) modeling on UV/Vis absorption spectra was applied to quantify mAb in the effluent of a Protein A capture step during the load phase. A PLS model based on several breakthrough curves with variable mAb titers in the HCCF was successfully calibrated. The PLS model predicted the mAb concentrations in the effluent of a validation experiment with a root mean square error (RMSE) of 0.06 mg/mL. The information was applied to automatically terminate the load phase, when a product breakthrough of 1.5 mg/mL was reached. In a second part of the study, the sensitivity of the method was further increased by only considering small mAb concentrations in the calibration and by subtracting an impurity background signal. The resulting PLS model exhibited a RMSE of prediction of 0.01 mg/mL and was successfully applied to terminate the load phase, when a product breakthrough of 0.15 mg/mL was achieved. The proposed method has hence potential for the real‐time monitoring and control of capture steps at large scale production. This might enhance the resin capacity utilization, eliminate time‐consuming offline analytics, and contribute to the realization of continuous processing. Biotechnol. Bioeng. 2017;114: 368–373. © 2016 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals, Inc. PMID:27543789

Wavelet-Domain Nonlinear Energy and Enstrophy Transfers between Atmospheric Blocks and Local Eddies, Averaged over the NCEP Reanalysis

NASA Astrophysics Data System (ADS)

Fournier, A.

2001-05-01

There is reason to believe that weather is more predictable during atmospheric blocking (AB) events than during ``normal'' (N) meteorological states (Bengtsson 1981). Saltzman (1959) proposed that such quasi-permanent disturbances in general may be maintained by an up-scale nonlinear eddy kinetic energy (KE) cascade. This idea was later applied to or verified for AB observations or models by Green (1970,1977), Hansen & Chen (1982), Shutts (1983,1986), Haines & Marshall (1987), Butchart et al. (1989), Riyu & Ronghui (1996), Nakamura et al. (1997) and others. We present a study of the nonlinear-energetics contrast between Atlantic (A) and Pacific (P) AB and N, generalizing the Fourier-based approach originated by Saltzman (1957) and Hansen & Sutera (1984). The Wavelet Energetics (WE) recently introduced by the author is applied to the 53-y NCEP Reanalyis, extending his study of AB presented in AGU, 1995 and (Fournier 1998,1999,2000). Temporal mean and variance maps suggest that AB is associated with eddy activity concentrated on smaller scales on either side of the AB ridge. Correlating WE, AB relative to nonblocking, illumenates the AB similarities and differences between P and A, as the former's WE pattern is shifted over the latter's. The theoretical conservation of Wavelet Flux is numerically verified to well below observational tolerance. Statistical significance is estimated. Conclusions include the following. Wavelet KE and enstrophy stocks (localized at scale ≈21-jπ r⊕ cosǎrphi, zonal-wavenumber band ≈ ]2j-1,2j] and longitude ≈21-jkπ ) Kjk and Ejk increase upstream, decrease downstream of either block. Mean-flow transfer MKjk increases downstream, at j=2 (and j=4 for A, 5 for P). Eddy transfer TKjk has more complex changes, A!=qP except that TK1k decreases downstream. Eddy flux FKjk shows downscale (upscale) cascade downstream (upstream) of P (A blocks tend to migrate in λ more than do P, that would weaken this signal for A). MEjk and TEjk have less significant changes. Finally, FEjk shows some sign of downscale (upscale) cascade downstream (upstream) of both blocks.

Following the Cosmic Evolution of Pristine Gas. II. The Search for Pop III–bright Galaxies

NASA Astrophysics Data System (ADS)

Sarmento, Richard; Scannapieco, Evan; Cohen, Seth

2018-02-01

Direct observational searches for Population III (Pop III) stars at high redshift are faced with the question of how to select the most promising targets for spectroscopic follow-up. To help answer this, we use a large-scale cosmological simulation, augmented with a new subgrid model that tracks the fraction of pristine gas, to follow the evolution of high-redshift galaxies and the Pop III stars they contain. We generate rest-frame ultraviolet (UV) luminosity functions for our galaxies and find that they are consistent with current z≥slant 7 observations. Throughout the redshift range 7≤slant z≤slant 15, we identify “Pop III–bright” galaxies as those with at least 75% of their flux coming from Pop III stars. While less than 1% of galaxies brighter than {m}UV,{AB}}=31.4 mag are Pop III–bright in the range 7≤slant z≤slant 8, roughly 17% of such galaxies are Pop III–bright at z = 9, immediately before reionization occurs in our simulation. Moving to z = 10, {m}UV,{AB}}=31.4 mag corresponds to larger, more luminous galaxies, and the Pop III–bright fraction falls off to 5%. Finally, at the highest redshifts, a large fraction (29% at z = 14 and 41% at z = 15) of all galaxies are Pop III–bright regardless of magnitude. While {m}UV,{AB}}=31.4 mag galaxies are extremely rare during this epoch, we find that 13% of galaxies at z = 14 are Pop III–bright with {m}UV,{AB}}≤slant 33 mag, a intrinsic magnitude within reach of the James Webb Space Telescope using lensing. Thus, we predict that the best redshift to search for luminous Pop III–bright galaxies is just before reionization, while lensing surveys for fainter galaxies should push to the highest redshifts possible.

Checkpoint Antibodies but not T Cell-Recruiting Diabodies Effectively Synergize with TIL-Inducing γ-Irradiation.

PubMed

Hettich, Michael; Lahoti, Jayashree; Prasad, Shruthi; Niedermann, Gabriele

2016-08-15

T cell-recruiting bispecific antibodies (bsAb) show promise in hematologic malignancies and are also being evaluated in solid tumors. In this study, we investigated whether T cell-recruiting bsAbs synergize with hypofractionated tumor radiotherapy (hRT) and/or blockade of the programmed death-1 (PD-1) immune checkpoint, both of which can increase tumor-infiltrating lymphocyte (TIL) numbers. Unexpectedly, large melanomas treated with hRT plus bsAb (AC133×CD3) relapsed faster than those treated with hRT alone, accompanied by massive TIL apoptosis. This fast relapse was delayed by the further addition of anti-PD-1. Mechanistic investigations revealed restimulation-induced cell death mediated by BIM and FAS as an additional cause of bsAb-mediated TIL depletion. In contrast, the double combination of hRT and anti-PD-1 strongly increased TIL numbers, and even very large tumors were completely eradicated. Our study reveals the risk that CD3-engaging bsAbs can induce apoptotic TIL depletion followed by rapid tumor regrowth, reminiscent of tolerance induction by CD3 mAb-mediated T-cell depletion, warranting caution in their use for the treatment of solid tumors. Our findings also argue that combining radiotherapy and anti-PD-1 can be quite potent, including against very large tumors. Cancer Res; 76(16); 4673-83. ©2016 AACR. ©2016 American Association for Cancer Research.

Psychics, aliens, or experience? Using the Anomalistic Belief Scale to examine the relationship between type of belief and probabilistic reasoning.

PubMed

Prike, Toby; Arnold, Michelle M; Williamson, Paul

2017-08-01

A growing body of research has shown people who hold anomalistic (e.g., paranormal) beliefs may differ from nonbelievers in their propensity to make probabilistic reasoning errors. The current study explored the relationship between these beliefs and performance through the development of a new measure of anomalistic belief, called the Anomalistic Belief Scale (ABS). One key feature of the ABS is that it includes a balance of both experiential and theoretical belief items. Another aim of the study was to use the ABS to investigate the relationship between belief and probabilistic reasoning errors on conjunction fallacy tasks. As expected, results showed there was a relationship between anomalistic belief and propensity to commit the conjunction fallacy. Importantly, regression analyses on the factors that make up the ABS showed that the relationship between anomalistic belief and probabilistic reasoning occurred only for beliefs about having experienced anomalistic phenomena, and not for theoretical anomalistic beliefs. Copyright © 2017 Elsevier Inc. All rights reserved.

Ab Initio Studies of Shock-Induced Chemical Reactions of Inter-Metallics

NASA Astrophysics Data System (ADS)

Zaharieva, Roussislava; Hanagud, Sathya

2009-06-01

Shock-induced and shock assisted chemical reactions of intermetallic mixtures are studied by many researchers, using both experimental and theoretical techniques. The theoretical studies are primarily at continuum scales. The model frameworks include mixture theories and meso-scale models of grains of porous mixtures. The reaction models vary from equilibrium thermodynamic model to several non-equilibrium thermodynamic models. The shock-effects are primarily studied using appropriate conservation equations and numerical techniques to integrate the equations. All these models require material constants from experiments and estimates of transition states. Thus, the objective of this paper is to present studies based on ab initio techniques. The ab inito studies, to date, use ab inito molecular dynamics. This paper presents a study that uses shock pressures, and associated temperatures as starting variables. Then intermetallic mixtures are modeled as slabs. The required shock stresses are created by straining the lattice. Then, ab initio binding energy calculations are used to examine the stability of the reactions. Binding energies are obtained for different strain components super imposed on uniform compression and finite temperatures. Then, vibrational frequencies and nudge elastic band techniques are used to study reactivity and transition states. Examples include Ni and Al.

Dark Energy Domination In The Virgocentric Flow

NASA Astrophysics Data System (ADS)

Byrd, Gene; Chernin, A. D.; Karachentsev, I. D.; Teerikorpi, P.; Valtonen, M.; Dolgachev, V. P.; Domozhilova, L. M.

2011-04-01

Dark energy (DE) was first observationally detected at large Gpc distances. If it is a vacuum energy formulated as Einstein's cosmological constant, Λ, DE should also have dynamical effects at much smaller scales. Previously, we found its effects on much smaller Mpc scales in our Local Group (LG) as well as in other nearby groups. We used new HST observations of member 3D distances from the group centers and Doppler shifts. We find each group's gravity dominates a bound central system of galaxies but DE antigravity results in a radial recession increasing with distance from the group center of the outer members. Here we focus on the much larger (but still cosmologically local) Virgo Cluster and systems around it using new observations of velocities and distances. We propose an analytic model whose key parameter is the zero-gravity radius (ZGR) from the cluster center where gravity and DE antigravity balance. DE brings regularity to the Virgocentric flow. Beyond Virgo's 10 Mpc ZGR, the flow curves to approach a linear global Hubble law at larger distances. The Virgo cluster and its outer flow are similar to the Local Group and its local outflow with a scaling factor of about 10; the ZGR for Virgo is 10 times larger than that of the LG. The similarity of the two systems on the scales of 1 to 30 Mpc suggests that a quasi-stationary bound central component and an expanding outflow applies to a wide range of groups and clusters due to small scale action of DE as well as gravity. Chernin, et al 2009 Astronomy and Astrophysics 507, 1271 http://arxiv.org/abs/1006.0066 http://arxiv.org/abs/1006.0555

Increasing the efficiency and accuracy of time-resolved electronic spectra calculations with on-the-fly ab initio quantum dynamics methods

NASA Astrophysics Data System (ADS)

Vanicek, Jiri

2014-03-01

Rigorous quantum-mechanical calculations of coherent ultrafast electronic spectra remain difficult. I will present several approaches developed in our group that increase the efficiency and accuracy of such calculations: First, we justified the feasibility of evaluating time-resolved spectra of large systems by proving that the number of trajectories needed for convergence of the semiclassical dephasing representation/phase averaging is independent of dimensionality. Recently, we further accelerated this approximation with a cellular scheme employing inverse Weierstrass transform and optimal scaling of the cell size. The accuracy of potential energy surfaces was increased by combining the dephasing representation with accurate on-the-fly ab initio electronic structure calculations, including nonadiabatic and spin-orbit couplings. Finally, the inherent semiclassical approximation was removed in the exact quantum Gaussian dephasing representation, in which semiclassical trajectories are replaced by communicating frozen Gaussian basis functions evolving classically with an average Hamiltonian. Among other examples I will present an on-the-fly ab initio semiclassical dynamics calculation of the dispersed time-resolved stimulated emission spectrum of the 54-dimensional azulene. This research was supported by EPFL and by the Swiss National Science Foundation NCCR MUST (Molecular Ultrafast Science and Technology) and Grant No. 200021124936/1.

Emerging biologic therapies for hypercholesterolaemia.

PubMed

Pucci, Giacomo; Cicero, Arrigo F; Borghi, Claudio; Schillaci, Giuseppe

2017-09-01

LDL-cholesterol (LDL-C) is one of the most well-established risk factors for CV disease. Indeed, therapies that decrease LDL-C are proven to effectively reduce the risk of atherosclerotic CV disease. Monoclonal antibodies (mAbs) that target proprotein convertase subtilisin/kexin type 9 (PCSK9) have recently gained traction as a promising therapeutic strategy. Areas covered: In this review, the authors discuss the effectiveness of mAbs against PCSK9 in lowering low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipid fractions. The discontinuation in the development of bococizumab due to efficacy and safety concerns, and the initial promising data about inclisiran, a long-acting small inhibiting RNA molecule against PCSK9 synthesis, is also discussed. Expert opinion: Initial data about cardiovascular (CV) outcomes in large scale, long-term studies suggest a possible further therapeutic pathway for LDL-C reduction, and currently support the notion that further LDL-C reduction, obtained with PCSK9 inhibition on top of best available therapy, provides increased CV protection in subjects at very high CV risk. The development and marketing of mAbs against PCSK9 could help to redefine current therapeutic strategies aimed at reducing cardiovascular (CV) morbidity and risk, through the reduction of LDL-C concentrations. The cost-effectiveness of these emerging drugs is yet to be established.

Large scale ab initio modeling of structurally uncharacterized antimicrobial peptides reveals known and novel folds.

PubMed

Kozic, Mara; Fox, Stephen J; Thomas, Jens M; Verma, Chandra S; Rigden, Daniel J

2018-05-01

Antimicrobial resistance within a wide range of infectious agents is a severe and growing public health threat. Antimicrobial peptides (AMPs) are among the leading alternatives to current antibiotics, exhibiting broad spectrum activity. Their activity is determined by numerous properties such as cationic charge, amphipathicity, size, and amino acid composition. Currently, only around 10% of known AMP sequences have experimentally solved structures. To improve our understanding of the AMP structural universe we have carried out large scale ab initio 3D modeling of structurally uncharacterized AMPs that revealed similarities between predicted folds of the modeled sequences and structures of characterized AMPs. Two of the peptides whose models matched known folds are Lebocin Peptide 1A (LP1A) and Odorranain M, predicted to form β-hairpins but, interestingly, to lack the intramolecular disulfide bonds, cation-π or aromatic interactions that generally stabilize such AMP structures. Other examples include Ponericin Q42, Latarcin 4a, Kassinatuerin 1, Ceratotoxin D, and CPF-B1 peptide, which have α-helical folds, as well as mixed αβ folds of human Histatin 2 peptide and Garvicin A which are, to the best of our knowledge, the first linear αββ fold AMPs lacking intramolecular disulfide bonds. In addition to fold matches to experimentally derived structures, unique folds were also obtained, namely for Microcin M and Ipomicin. These results help in understanding the range of protein scaffolds that naturally bear antimicrobial activity and may facilitate protein design efforts towards better AMPs. © 2018 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

Efficient conformational space exploration in ab initio protein folding simulation.

PubMed

Ullah, Ahammed; Ahmed, Nasif; Pappu, Subrata Dey; Shatabda, Swakkhar; Ullah, A Z M Dayem; Rahman, M Sohel

2015-08-01

Ab initio protein folding simulation largely depends on knowledge-based energy functions that are derived from known protein structures using statistical methods. These knowledge-based energy functions provide us with a good approximation of real protein energetics. However, these energy functions are not very informative for search algorithms and fail to distinguish the types of amino acid interactions that contribute largely to the energy function from those that do not. As a result, search algorithms frequently get trapped into the local minima. On the other hand, the hydrophobic-polar (HP) model considers hydrophobic interactions only. The simplified nature of HP energy function makes it limited only to a low-resolution model. In this paper, we present a strategy to derive a non-uniform scaled version of the real 20×20 pairwise energy function. The non-uniform scaling helps tackle the difficulty faced by a real energy function, whereas the integration of 20×20 pairwise information overcomes the limitations faced by the HP energy function. Here, we have applied a derived energy function with a genetic algorithm on discrete lattices. On a standard set of benchmark protein sequences, our approach significantly outperforms the state-of-the-art methods for similar models. Our approach has been able to explore regions of the conformational space which all the previous methods have failed to explore. Effectiveness of the derived energy function is presented by showing qualitative differences and similarities of the sampled structures to the native structures. Number of objective function evaluation in a single run of the algorithm is used as a comparison metric to demonstrate efficiency.

Well-being as a moving target: measurement equivalence of the Bradburn Affect Balance Scale.

PubMed

Maitland, S B; Dixon, R A; Hultsch, D F; Hertzog, C

2001-03-01

Although the Bradburn Affect Balance scale (ABS) is a frequently used two-factor indicator of well-being in later life, its measurement and invariance properties are not well documented. We examined these issues using confirmatory factor analyses of cross-sectional (adults ages 54-87 years) and longitudinal data from the Victoria Longitudinal Study. Stability of the positive and negative affect factors was moderate across a 3-year period. Overall, factor loadings for positive affect items were invariant over time with the exception of the pleased item. Negative affect items were time invariant. However, age-group comparisons between young-old and old-old groups revealed age differences in loadings for the upset item at Time 1. Finally, gender groups differed in loadings for the top of the world and going your way items. Thus a pattern of partial measurement equivalence characterized item response to the ABS. Our results suggest that group comparisons and longitudinal change in ABS scale scores of positive and negative affect should be interpreted with caution.

Positive semidefinite tensor factorizations of the two-electron integral matrix for low-scaling ab initio electronic structure.

PubMed

Hoy, Erik P; Mazziotti, David A

2015-08-14

Tensor factorization of the 2-electron integral matrix is a well-known technique for reducing the computational scaling of ab initio electronic structure methods toward that of Hartree-Fock and density functional theories. The simplest factorization that maintains the positive semidefinite character of the 2-electron integral matrix is the Cholesky factorization. In this paper, we introduce a family of positive semidefinite factorizations that generalize the Cholesky factorization. Using an implementation of the factorization within the parametric 2-RDM method [D. A. Mazziotti, Phys. Rev. Lett. 101, 253002 (2008)], we study several inorganic molecules, alkane chains, and potential energy curves and find that this generalized factorization retains the accuracy and size extensivity of the Cholesky factorization, even in the presence of multi-reference correlation. The generalized family of positive semidefinite factorizations has potential applications to low-scaling ab initio electronic structure methods that treat electron correlation with a computational cost approaching that of the Hartree-Fock method or density functional theory.

Pathways of Leymus chinensis Individual Aboveground Biomass Decline in Natural Semiarid Grassland Induced by Overgrazing: A Study at the Plant Functional Trait Scale

PubMed Central

Wang, Zhen; Wu, Xinhong; Li, Xinle; Hu, Jing; Shi, Hongxiao; Guo, Fenghui; Zhang, Yong; Hou, Xiangyang

2015-01-01

Natural grassland productivity, which is based on an individual plant’s aboveground biomass (AB) and its interaction with herbivores, can obviously affect terrestrial ecosystem services and the grassland’s agricultural production. As plant traits have been linked to both AB and ecosystem success, they may provide a useful approach to understand the changes in individual plants and grassland productivity in response to grazing on a generic level. Unfortunately, the current lack of studies on how plant traits affect AB affected by herbivores leaves a major gap in our understanding of the mechanism of grassland productivity decline. This study, therefore, aims to analyze the paths of overgrazing-induced decline in the individual AB of Leymus chinensis (the dominant species of meadow-steppe grassland in northern China) on a plant functional trait scale. Using a paired-sampling approach, we compared the differences in the functional traits of L. chinensis in long-term grazing-excluded and experimental grazing grassland plots over a continuous period of approximately 20 years (located in meadow steppe lands in Hailar, Inner Mongolia, China). We found a highly significant decline in the individual height and biomass (leaf, stem, and the whole plant) of L. chinensis as a result of overgrazing. Biomass allocation and leaf mass per unit area were significantly affected by the variation in individual size. Grazing clearly enhanced the sensitivity of the leaf-to-stem biomass ratio in response to variation in individual size. Moreover, using a method of standardized major axis estimation, we found that the biomass in the leaves, stems, and the plant as a whole had highly significant allometric scaling with various functional traits. Also, the slopes of the allometric equations of these relationships were significantly altered by grazing. Therefore, a clear implication of this is that grazing promotes an asymmetrical response of different plant functional traits to variation in individual plant size, which influences biomass indirectly. Furthermore, we detected paths of individual AB decline in L. chinensis induced by grazing by fitting to a structural equation model. These results indicate that grazing causes AB decline primarily through a ‘bottom-up’ effect on plant height and stem traits. However, leaf traits, via the process of allometric scaling, affect plant AB indirectly. PMID:25942588

Pathways of Leymus chinensis Individual Aboveground Biomass Decline in Natural Semiarid Grassland Induced by Overgrazing: A Study at the Plant Functional Trait Scale.

PubMed

Li, Xiliang; Liu, Zhiying; Wang, Zhen; Wu, Xinhong; Li, Xinle; Hu, Jing; Shi, Hongxiao; Guo, Fenghui; Zhang, Yong; Hou, Xiangyang

2015-01-01

Natural grassland productivity, which is based on an individual plant's aboveground biomass (AB) and its interaction with herbivores, can obviously affect terrestrial ecosystem services and the grassland's agricultural production. As plant traits have been linked to both AB and ecosystem success, they may provide a useful approach to understand the changes in individual plants and grassland productivity in response to grazing on a generic level. Unfortunately, the current lack of studies on how plant traits affect AB affected by herbivores leaves a major gap in our understanding of the mechanism of grassland productivity decline. This study, therefore, aims to analyze the paths of overgrazing-induced decline in the individual AB of Leymus chinensis (the dominant species of meadow-steppe grassland in northern China) on a plant functional trait scale. Using a paired-sampling approach, we compared the differences in the functional traits of L. chinensis in long-term grazing-excluded and experimental grazing grassland plots over a continuous period of approximately 20 years (located in meadow steppe lands in Hailar, Inner Mongolia, China). We found a highly significant decline in the individual height and biomass (leaf, stem, and the whole plant) of L. chinensis as a result of overgrazing. Biomass allocation and leaf mass per unit area were significantly affected by the variation in individual size. Grazing clearly enhanced the sensitivity of the leaf-to-stem biomass ratio in response to variation in individual size. Moreover, using a method of standardized major axis estimation, we found that the biomass in the leaves, stems, and the plant as a whole had highly significant allometric scaling with various functional traits. Also, the slopes of the allometric equations of these relationships were significantly altered by grazing. Therefore, a clear implication of this is that grazing promotes an asymmetrical response of different plant functional traits to variation in individual plant size, which influences biomass indirectly. Furthermore, we detected paths of individual AB decline in L. chinensis induced by grazing by fitting to a structural equation model. These results indicate that grazing causes AB decline primarily through a 'bottom-up' effect on plant height and stem traits. However, leaf traits, via the process of allometric scaling, affect plant AB indirectly.

Self-consistent perturbation theory for two dimensional twisted bilayers

NASA Astrophysics Data System (ADS)

Shirodkar, Sharmila N.; Tritsaris, Georgios A.; Kaxiras, Efthimios

Theoretical modeling and ab-initio simulations of two dimensional heterostructures with arbitrary angles of rotation between layers involve unrealistically large and expensive calculations. To overcome this shortcoming, we develop a methodology for weakly interacting heterostructures that treats the effect of one layer on the other as perturbation, and restricts the calculations to their primitive cells. Thus, avoiding computationally expensive supercells. We start by approximating the interaction potential between the twisted bilayers to that of a hypothetical configuration (viz. ideally stacked untwisted layers), which produces band structures in reasonable agreement with full-scale ab-initio calculations for commensurate and twisted bilayers of graphene (Gr) and Gr/hexagonal boron nitride (h-BN) heterostructures. We then self-consistently calculate the charge density and hence, interaction potential of the heterostructures. In this work, we test our model for bilayers of various combinations of Gr, h-BN and transition metal dichalcogenides, and discuss the advantages and shortcomings of the self-consistently calculated interaction potential. Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA.

Igs expressed by chronic lymphocytic leukemia B cells show limited binding-site structure variability.

PubMed

Marcatili, Paolo; Ghiotto, Fabio; Tenca, Claudya; Chailyan, Anna; Mazzarello, Andrea N; Yan, Xiao-Jie; Colombo, Monica; Albesiano, Emilia; Bagnara, Davide; Cutrona, Giovanna; Morabito, Fortunato; Bruno, Silvia; Ferrarini, Manlio; Chiorazzi, Nicholas; Tramontano, Anna; Fais, Franco

2013-06-01

Ag selection has been suggested to play a role in chronic lymphocytic leukemia (CLL) pathogenesis, but no large-scale analysis has been performed so far on the structure of the Ag-binding sites (ABSs) of leukemic cell Igs. We sequenced both H and L chain V(D)J rearrangements from 366 CLL patients and modeled their three-dimensional structures. The resulting ABS structures were clustered into a small number of discrete sets, each containing ABSs with similar shapes and physicochemical properties. This structural classification correlates well with other known prognostic factors such as Ig mutation status and recurrent (stereotyped) receptors, but it shows a better prognostic value, at least in the case of one structural cluster for which clinical data were available. These findings suggest, for the first time, to our knowledge, on the basis of a structural analysis of the Ab-binding sites, that selection by a finite quota of antigenic structures operates on most CLL cases, whether mutated or unmutated.

An ab initio investigation of possible intermediates in the reaction of the hydroxyl and hydroperoxyl radicals

NASA Technical Reports Server (NTRS)

Jackels, C. F.

1985-01-01

Ab initio quantum chemical techniques are used to investigate covalently-bonded and hydrogen-bonded species that may be important intermediates in the reaction of hydroxyl and hydroperoxyl radicals. Stable structures of both types are identified. Basis sets of polarized double zeta quality and large scale configuration interaction wave functions are utilized. Based on electronic energies, the covalently bonded HOOOH species is 26.4 kcal/mol more stable than the OH and HO2 radicals. Similarly, the hydrogen bonded HO---HO2 species has an electronic energy 4.7 kcal/mol below that of the component radicals, after correction is made for the basis set superposition error. The hydrogen bonded form is planar, possesses one relatively normal hydrogen bond, and has the lowest energy 3A' and 1A' states that are essentially degenerate. The 1A" and 3A" excited states produced by rotation of the unpaired OH electron into the molecular plane are very slightly bound.

Global remote sensing of water-chlorophyll ratio in terrestrial plant leaves.

PubMed

Kushida, Keiji

2012-10-01

I evaluated the use of global remote sensing techniques for estimating plant leaf chlorophyll a + b (C(ab); μg cm(-2)) and water (C(w); mg cm(-2)) concentrations as well as the ratio of C(w)/C(ab) with the PROSAIL model under possible distributions for leaf and soil spectra, leaf area index (LAI), canopy geometric structure, and leaf size. First, I estimated LAI from the normalized difference vegetation index. I found that, at LAI values <2, C(ab), C(w), and C(w)/C(ab) could not be reliably estimated. At LAI values >2, C(ab) and C(w) could be estimated for only restricted ranges of the canopy structure; however, the ratio of C(w)/C(ab) could be reliably estimated for a variety of possible canopy structures with coefficients of determination (R(2)) ranging from 0.56 to 0.90. The remote estimation of the C(w)/C(ab) ratio from satellites offers information on plant condition at a global scale.

Dopamine and temporal attention: An attentional blink study in Parkinson's disease patients on and off medication.

PubMed

Slagter, H A; van Wouwe, N C; Kanoff, K; Grasman, R P P P; Claassen, D O; van den Wildenberg, W P M; Wylie, S A

2016-10-01

The current study aimed to shed more light on the role of dopamine in temporal attention. To this end, we pharmacologically manipulated dopamine levels in a large sample of Parkinson's disease patients (n=63) while they performed an attentional blink (AB) task in which they had to identify two targets (T1 and T2) presented in close temporal proximity among distractors. We specifically examined 1) differences in the magnitude of the AB between unmedicated Parkinson patients, who have depleted levels of striatal dopamine, and healthy controls, and 2) effects of two dopaminergic medications (l-DOPA and dopamine agonists) on the AB in the Parkinson patients at the group level and as a function of individual baseline performance. In line with the notion that relatively low levels of striatal dopamine may impair target detection in general, Parkinson patients OFF medications displayed overall poor target perception compared to healthy controls. Moreover, as predicted, effects of dopaminergic medication on AB performance critically depended on individual baseline AB size, although this effect was only observed for l-DOPA. l-DOPA generally decreased the size of the AB in patients with a large baseline AB (i.e., OFF medications), while l-DOPA generally increased the AB in patients with a small baseline AB. These findings may support a role for dopamine in the AB and temporal attention, more generally and corroborate the notion that there is an optimum dopamine level for cognitive function. They also emphasize the need for more studies that examine the separate effects of DA agonists and l-DOPA on cognitive functioning. Copyright © 2016 Elsevier Ltd. All rights reserved.

SIMULTANEOUS MULTIWAVELENGTH OBSERVATIONS OF MAGNETIC ACTIVITY IN ULTRACOOL DWARFS. IV. THE ACTIVE, YOUNG BINARY NLTT 33370 AB (= 2MASS J13142039+1320011)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, P. K. G.; Berger, E.; Irwin, J.

We present multi-epoch simultaneous radio, optical, Hα, UV, and X-ray observations of the active, young, low-mass binary NLTT 33370 AB (blended spectral type M7e). This system is remarkable for its extreme levels of magnetic activity: it is the most radio-luminous ultracool dwarf (UCD) known, and here we show that it is also one of the most X-ray luminous UCDs known. We detect the system in all bands and find a complex phenomenology of both flaring and periodic variability. Analysis of the optical light curve reveals the simultaneous presence of two periodicities, 3.7859 ± 0.0001 and 3.7130 ± 0.0002 hr. While these differmore » by only ∼2%, studies of differential rotation in the UCD regime suggest that it cannot be responsible for the two signals. The system's radio emission consists of at least three components: rapid 100% polarized flares, bright emission modulating periodically in phase with the optical emission, and an additional periodic component that appears only in the 2013 observational campaign. We interpret the last of these as a gyrosynchrotron feature associated with large-scale magnetic fields and a cool, equatorial plasma torus. However, the persistent rapid flares at all rotational phases imply that small-scale magnetic loops are also present and reconnect nearly continuously. We present a spectral energy distribution of the blended system spanning more than 9 orders of magnitude in wavelength. The significant magnetism present in NLTT 33370 AB will affect its fundamental parameters, with the components' radii and temperatures potentially altered by ∼+20% and ∼–10%, respectively. Finally, we suggest spatially resolved observations that could clarify many aspects of this system's nature.« less

Student Measurements of STFA 10AB (Theta Tauri)

NASA Astrophysics Data System (ADS)

Gillette, Sean; Estrada, Chris; Estrada, Reed; Aguilera, Sophia; Chavez, Valerie; Givens, Jalynn; Lindorfer, Sarah; Michels, Kaylie; Mobley, Makenzie; Reder, Gabriel; Renteria, Kayla; Shattles, Jenna; Wilkin, Aiden; Woodbury, Maisy; Rhoades, Breauna; Rhoades, Mark

2017-04-01

Eighth grade students at Vanguard Preparatory School measured the double star STFA 10AB using a 22-inch Newtonian Alt/Az telescope and a Celestron Micro Guide eyepiece. Bellatrix was used as the calibration star. The calculated means of multiple observations of STFA 10AB resulted in a separation of 45.18,” a scale constant of 7.88 arcseconds per division, and position angle of 257.9°. These measurements were compared to the most recent values in the Washington Double Star Catalog.

76 FR 50881 - Required Scale Tests

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-17

... RIN 0580-AB10 Required Scale Tests AGENCY: Grain Inspection, Packers and Stockyards Administration... required scale tests. Those documents defined ``limited seasonal basis'' incorrectly. This document... 20, 2011 (76 FR 3485) and on April 4, 2011 (76 FR 18348), concerning required scale tests. Those...

High Yield Chemical Vapor Deposition Growth of High Quality Large-Area AB Stacked Bilayer Graphene

PubMed Central

Liu, Lixin; Zhou, Hailong; Cheng, Rui; Yu, Woo Jong; Liu, Yuan; Chen, Yu; Shaw, Jonathan; Zhong, Xing; Huang, Yu; Duan, Xiangfeng

2012-01-01

Bernal stacked (AB stacked) bilayer graphene is of significant interest for functional electronic and photonic devices due to the feasibility to continuously tune its band gap with a vertical electrical field. Mechanical exfoliation can be used to produce AB stacked bilayer graphene flakes but typically with the sizes limited to a few micrometers. Chemical vapor deposition (CVD) has been recently explored for the synthesis of bilayer graphene but usually with limited coverage and a mixture of AB and randomly stacked structures. Herein we report a rational approach to produce large-area high quality AB stacked bilayer graphene. We show that the self-limiting effect of graphene growth on Cu foil can be broken by using a high H2/CH4 ratio in a low pressure CVD process to enable the continued growth of bilayer graphene. A high temperature and low pressure nucleation step is found to be critical for the formation of bilayer graphene nuclei with high AB stacking ratio. A rational design of a two-step CVD process is developed for the growth of bilayer graphene with high AB stacking ratio (up to 90 %) and high coverage (up to 99 %). The electrical transport studies demonstrated that devices made of the as-grown bilayer graphene exhibit typical characteristics of AB stacked bilayer graphene with the highest carrier mobility exceeding 4,000 cm2/V·s at room temperature, comparable to that of the exfoliated bilayer graphene. PMID:22906199

HtrA3 as an Early Marker for Preeclampsia: Specific Monoclonal Antibodies and Sensitive High-Throughput Assays for Serum Screening

PubMed Central

Dynon, Kemperly; Heng, Sophea; Puryer, Michelle; Li, Ying; Walton, Kelly; Endo, Yaeta; Nie, Guiying

2012-01-01

Mammalian HtrA3 (high temperature requirement A3) is a serine protease of the HtrA family. It has two isoforms [long (HtrA3-L) and short (HtrA3-S)] and is important for placental development and cancer progression. Recently, HtrA3 was identified as a potential diagnostic marker for early detection of preeclampsia, a life-threatening pregnancy-specific disorder. Currently there are no high-throughput assays available to detect HtrA3 in human serum. In this study we generated and fully tested a panel of five HtrA3 mouse monoclonal antibodies (mAbs). Three mAbs recognised both HtrA3-L and HtrA3-S and the other two detected HtrA3-L only. All five mAbs were highly specific to HtrA3 and applicable in western blotting and immunohistochemical analysis of endogenous HtrA3 proteins in the mouse and human tissues. Amplified luminescent proximity homogeneous assays-linked immunosorbent assays (AlphaLISAs), were developed to detect HtrA3 isoforms in picomolar levels in serum. The HtrA3 AlphaLISA detected significantly higher serum levels of HtrA3 in women at 13–14 weeks of gestation who subsequently developed preeclampsia compared to gestational-age matched controls. These HtrA3 mAbs are valuable for the development of immunoassays and characterisation of HtrA3 isoform-specific biology. The newly developed HtrA3 AlphaLISA assays are suitable for large scale screening of human serum. PMID:23049902

Predicting the breakdown strength and lifetime of nanocomposites using a multi-scale modeling approach

NASA Astrophysics Data System (ADS)

Huang, Yanhui; Zhao, He; Wang, Yixing; Ratcliff, Tyree; Breneman, Curt; Brinson, L. Catherine; Chen, Wei; Schadler, Linda S.

2017-08-01

It has been found that doping dielectric polymers with a small amount of nanofiller or molecular additive can stabilize the material under a high field and lead to increased breakdown strength and lifetime. Choosing appropriate fillers is critical to optimizing the material performance, but current research largely relies on experimental trial and error. The employment of computer simulations for nanodielectric design is rarely reported. In this work, we propose a multi-scale modeling approach that employs ab initio, Monte Carlo, and continuum scales to predict the breakdown strength and lifetime of polymer nanocomposites based on the charge trapping effect of the nanofillers. The charge transfer, charge energy relaxation, and space charge effects are modeled in respective hierarchical scales by distinctive simulation techniques, and these models are connected together for high fidelity and robustness. The preliminary results show good agreement with the experimental data, suggesting its promise for use in the computer aided material design of high performance dielectrics.

Electronic and molecular structure of carbon grains

NASA Technical Reports Server (NTRS)

Almloef, Jan; Luethi, Hans-Peter

1990-01-01

Clusters of carbon atoms have been studied with large-scale ab initio calculations. Planar, single-sheet graphite fragments with 6 to 54 atoms were investigated, as well as the spherical C(sub 60) Buckminsterfullerene molecule. Polycyclic aromatic hydrocarbons (PAHs) have also been considered. Thermodynamic differences between diamond- and graphite-like grains have been studied in particular. Saturation of the peripheral bonds with hydrogen is found to provide a smooth and uniform convergence of the properties with increasing cluster size. For the graphite-like clusters the convergence to bulk values is much slower than for the three-dimensional complexes.

Time Lapse of World’s Largest 3-D Printed Object

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2016-08-29

Researchers at the MDF have 3D-printed a large-scale trim tool for a Boeing 777X, the world’s largest twin-engine jet airliner. The additively manufactured tool was printed on the Big Area Additive Manufacturing, or BAAM machine over a 30-hour period. The team used a thermoplastic pellet comprised of 80% ABS plastic and 20% carbon fiber from local material supplier. The tool has proven to decrease time, labor, cost and errors associated with traditional manufacturing techniques and increased energy savings in preliminary testing and will undergo further, long term testing.

Infrared Time Lapse of World’s Largest 3D-Printed Object

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

Researchers at Oak Ridge National Laboratory have 3D-printed a large-scale trim tool for a Boeing 777X, the world’s largest twin-engine jet airliner. The additively manufactured tool was printed on the Big Area Additive Manufacturing, or BAAM machine over a 30-hour period. The team used a thermoplastic pellet comprised of 80% ABS plastic and 20% carbon fiber from local material supplier. The tool has proven to decrease time, labor, cost and errors associated with traditional manufacturing techniques and increased energy savings in preliminary testing and will undergo further, long term testing.

A-B Distinction in a Sample of Prominent Psychotherapists

ERIC Educational Resources Information Center

Geller, Jesse D.; Berzins, Juris I.

1976-01-01

A sample of prominent psychotherapists were asked to fill out the A-B therapist "type" scale and comment on their possible differential effectiveness in treating schizoid/schizophrenic versus neurotic patients. The data suggest that B therapists desire and seek more complex and exciting sensory-cognitive inputs during therapy hours than A…

Characterization and biodegradability of sludge from a high rate A-stage contact tank and B-stage membrane bioreactor of a pilot-scale AB system treating municipal wastewaters.

PubMed

Trzcinski, Antoine Prandota; Ganda, Lily; Kunacheva, Chinagarn; Zhang, Dong Qing; Lin, Li Leonard; Tao, Guihe; Lee, Yingjie; Ng, Wun Jern

2016-10-01

In light of global warming mitigation efforts, increasing sludge disposal costs, and need for reduction in the carbon footprint of wastewater treatment plants, innovation in treatment technology has been tailored towards energy self-sufficiency. The AB process is a promising technology for achieving maximal energy recovery from wastewaters with minimum energy expenditure and therefore inherently reducing excess sludge production. Characterization of this novel sludge and its comparison with the more conventional B-stage sludge are necessary for a deeper understanding of AB treatment process design. This paper presents a case study of a pilot-scale AB system treating municipal wastewaters as well as a bio- (biochemical methane potential and adenosine tri-phosphate analysis) and physico-chemical properties (chemical oxygen demand, sludge volume index, dewaterability, calorific value, zeta potential and particle size distribution) comparison of the organic-rich A-stage against the B-stage activated sludge. Compared to the B-sludge, the A-sludge yielded 1.4 to 4.9 times more methane throughout the 62-week operation.

Modeling the structure of the attitudes and belief scale 2 using CFA and bifactor approaches: Toward the development of an abbreviated version.

PubMed

Hyland, Philip; Shevlin, Mark; Adamson, Gary; Boduszek, Daniel

2014-01-01

The Attitudes and Belief Scale-2 (ABS-2: DiGiuseppe, Leaf, Exner, & Robin, 1988. The development of a measure of rational/irrational thinking. Paper presented at the World Congress of Behavior Therapy, Edinburg, Scotland.) is a 72-item self-report measure of evaluative rational and irrational beliefs widely used in Rational Emotive Behavior Therapy research contexts. However, little psychometric evidence exists regarding the measure's underlying factor structure. Furthermore, given the length of the ABS-2 there is a need for an abbreviated version that can be administered when there are time demands on the researcher, such as in clinical settings. This study sought to examine a series of theoretical models hypothesized to represent the latent structure of the ABS-2 within an alternative models framework using traditional confirmatory factor analysis as well as utilizing a bifactor modeling approach. Furthermore, this study also sought to develop a psychometrically sound abbreviated version of the ABS-2. Three hundred and thirteen (N = 313) active emergency service personnel completed the ABS-2. Results indicated that for each model, the application of bifactor modeling procedures improved model fit statistics, and a novel eight-factor intercorrelated solution was identified as the best fitting model of the ABS-2. However, the observed fit indices failed to satisfy commonly accepted standards. A 24-item abbreviated version was thus constructed and an intercorrelated eight-factor solution yielded satisfactory model fit statistics. Current results support the use of a bifactor modeling approach to determining the factor structure of the ABS-2. Furthermore, results provide empirical support for the psychometric properties of the newly developed abbreviated version.

Pain in patients with transverse myelitis and its relationship to aquaporin 4 antibody status.

PubMed

Kong, Yazhuo; Okoruwa, Helen; Revis, Jon; Tackley, George; Leite, Maria Isabel; Lee, Michael; Tracey, Irene; Palace, Jacqueline

2016-09-15

Pain in transverse myelitis has been poorly studied. The aim of the study was to investigate the relationship between transverse myelitis related pain and disability, quality of life, anxiety and depression, cognitive-affective states in neuromyelitis optica (NMO) patients and aquaporin4 antibody status (AQP4-Ab +ve as positive and AQP4-Ab -ve as negative). Transverse myelitis patients (44 in total; 29 AQP4-Ab +ve and 15 AQP4-Ab -ve) completed questionnaires including Pain Severity Index (PSI), Pain Catastrophising Scale (PCS), Hospital Anxiety and Depression Scale (HADS), Short Form-36 quality of life (SF-36 QOL). Clinical details such as disability, gender, age and spinal cord lesion type (short or long lesion) were noted. Correlation and multiple linear regression tests were performed using these clinical scores. Pain was found to be correlated strongly with quality of life in both groups but only correlated with disability in the AQP4-Ab +ve group. PCS, HADS and EDMUS were found to be highly correlated with pain severity using partial correlation, however, a stronger relationship between pain severity and PCS was found in the AQP4-Ab -ve group. Multiple regression analysis showed that pain severity was the most important factor for quality of life but not disability or anxiety and depression symptoms in the whole patient group. We confirm that pain is an important symptom of transverse myelitis and has more influence on quality of life than disability despite health services being predominantly focused on the latter. There may be different factors associated with pain between AQP4-Ab +ve and -ve patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Uncertainties in scaling factors for ab initio vibrational zero-point energies

NASA Astrophysics Data System (ADS)

Irikura, Karl K.; Johnson, Russell D.; Kacker, Raghu N.; Kessel, Rüdiger

2009-03-01

Vibrational zero-point energies (ZPEs) determined from ab initio calculations are often scaled by empirical factors. An empirical scaling factor partially compensates for the effects arising from vibrational anharmonicity and incomplete treatment of electron correlation. These effects are not random but are systematic. We report scaling factors for 32 combinations of theory and basis set, intended for predicting ZPEs from computed harmonic frequencies. An empirical scaling factor carries uncertainty. We quantify and report, for the first time, the uncertainties associated with scaling factors for ZPE. The uncertainties are larger than generally acknowledged; the scaling factors have only two significant digits. For example, the scaling factor for B3LYP/6-31G(d) is 0.9757±0.0224 (standard uncertainty). The uncertainties in the scaling factors lead to corresponding uncertainties in predicted ZPEs. The proposed method for quantifying the uncertainties associated with scaling factors is based upon the Guide to the Expression of Uncertainty in Measurement, published by the International Organization for Standardization. We also present a new reference set of 60 diatomic and 15 polyatomic "experimental" ZPEs that includes estimated uncertainties.

76 FR 3485 - Required Scale Tests

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-20

...-AB10 Required Scale Tests AGENCY: Grain Inspection, Packers and Stockyards Administration, USDA. ACTION... rule requires that regulated entities complete the first of the two scale tests between January 1 and June 30 of the calendar year. The remaining scale test must be completed between July 1 and December 31...

Light Absorption Enhancement of Black Carbon Aerosol Constrained by Particle Morphology.

PubMed

Wu, Yu; Cheng, Tianhai; Liu, Dantong; Allan, James D; Zheng, Lijuan; Chen, Hao

2018-06-19

The radiative forcing of black carbon aerosol (BC) is one of the largest sources of uncertainty in climate change assessments. Contrasting results of BC absorption enhancement ( E abs ) after aging are estimated by field measurements and modeling studies, causing ambiguous parametrizations of BC solar absorption in climate models. Here we quantify E abs using a theoretical model parametrized by the complex particle morphology of BC in different aging scales. We show that E abs continuously increases with aging and stabilizes with a maximum of ∼3.5, suggesting that previous seemingly contrast results of E abs can be explicitly described by BC aging with corresponding particle morphology. We also report that current climate models using Mie Core-Shell model may overestimate E abs at a certain aging stage with a rapid rise of E abs , which is commonly observed in the ambient. A correction coefficient for this overestimation is suggested to improve model predictions of BC climate impact.

Ultra-deep Large Binocular Camera U-band Imaging of the GOODS-North Field: Depth Versus Resolution

NASA Astrophysics Data System (ADS)

Ashcraft, Teresa A.; Windhorst, Rogier A.; Jansen, Rolf A.; Cohen, Seth H.; Grazian, Andrea; Paris, Diego; Fontana, Adriano; Giallongo, Emanuele; Speziali, Roberto; Testa, Vincenzo; Boutsia, Konstantina; O’Connell, Robert W.; Rutkowski, Michael J.; Ryan, Russell E.; Scarlata, Claudia; Weiner, Benjamin

2018-06-01

We present a study of the trade-off between depth and resolution using a large number of U-band imaging observations in the GOODS-North field from the Large Binocular Camera (LBC) on the Large Binocular Telescope (LBT). Having acquired over 30 hr of data (315 images with 5–6 minutes exposures), we generated multiple image mosaics, starting with the best atmospheric seeing images (FWHM ≲ 0.″8), which constitute ∼10% of the total data set. For subsequent mosaics, we added in data with larger seeing values until the final, deepest mosaic included all images with FWHM ≲ 1.″8 (∼94% of the total data set). From the mosaics, we made object catalogs to compare the optimal-resolution, yet shallower image to the lower-resolution but deeper image. We show that the number counts for both images are ∼90% complete to U AB ≲ 26 mag. Fainter than U AB ∼ 27 mag, the object counts from the optimal-resolution image start to drop-off dramatically (90% between U AB = 27 and 28 mag), while the deepest image with better surface-brightness sensitivity ({μ }U{AB} ≲ 32 mag arcsec‑2) show a more gradual drop (10% between U AB ≃ 27 and 28 mag). For the brightest galaxies within the GOODS-N field, structure and clumpy features within the galaxies are more prominent in the optimal-resolution image compared to the deeper mosaics. We conclude that for studies of brighter galaxies and features within them, the optimal-resolution image should be used. However, to fully explore and understand the faintest objects, the deeper imaging with lower resolution are also required. Finally, we find—for 220 brighter galaxies with U AB ≲ 23 mag—only marginal differences in total flux between the optimal-resolution and lower-resolution light-profiles to {μ }U{AB} ≲ 32 mag arcsec‑2. In only 10% of the cases are the total-flux differences larger than 0.5 mag. This helps constrain how much flux can be missed from galaxy outskirts, which is important for studies of the Extragalactic Background Light. Based on data acquired using the Large Binocular Telescope (LBT).

76 FR 18348 - Required Scale Tests

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-04

... RIN 0580-AB10 Required Scale Tests AGENCY: Grain Inspection, Packers and Stockyards Administration... published a document in the Federal Register on January 20, 2011 (76 FR 3485), defining required scale tests...-month period following each test. * * * * * Alan R. Christian, Acting Administrator, Grain Inspection...

A competitive ELISA for species-independent detection of Crimean-Congo hemorrhagic fever virus specific antibodies.

PubMed

Schuster, Isolde; Mertens, Marc; Köllner, Bernd; Korytář, Tomáš; Keller, Markus; Hammerschmidt, Bärbel; Müller, Thomas; Tordo, Noël; Marianneau, Philippe; Mroz, Claudia; Rissmann, Melanie; Stroh, Eileen; Dähnert, Lisa; Hammerschmidt, Felicitas; Ulrich, Rainer G; Groschup, Martin H

2016-10-01

Crimean-Congo hemorrhagic fever virus (CCHFV) circulates in many countries of Asia, Africa, and Europe. CCHFV can cause a severe hemorrhagic fever in humans with case-fatality rates of up to 80%. CCHF is considered to be one of the major emerging diseases spreading to and within Europe. Ticks of the genus Hyalomma function as vector as well as natural reservoir of CCHFV. Ticks feed on various domestic animals (e.g. cattle, sheep, goats) and on wildlife (e.g. hares, hedgehogs). Those animal species play an important role in the life cycle of the ticks as well as in amplification of CCHFV. Here we present a competitive ELISA (cELISA) for the species-independent detection of CCHFV-specific antibodies. For this purpose nucleocapsid (N) protein specific monoclonal antibodies (mAbs) were generated against an Escherichia coli (E. coli) expressed CCHFV N-protein. Thirty-three mAbs reacted with homologous and heterologous recombinant CCHFV antigens in ELISA and Western blot test and 20 of those 33 mAbs reacted additionally in an immunofluorescence assay with eukaryotic cells expressing the N-protein. Ten mAbs were further characterized in a prototype of the cELISA and nine of them competed with positive control sera of bovine origin. The cELISA was established by using the mAb with the strongest competition. For the validation, 833 sera from 12 animal species and from humans were used. The diagnostic sensitivity and specificity of the cELISA was determined to be 95% and 99%, respectively, and 2% of the sera gave inconclusive results. This cELISA offers the possibility for future large-scale screening approaches in various animal species to evaluate their susceptibility to CCHFV infection and to identify and monitor the occurrence of CCHFV. Copyright © 2016 Elsevier B.V. All rights reserved.

High-throughput screening of hybridoma supernatants using multiplexed fluorescent cell barcoding on live cells.

PubMed

Lu, Mei; Chan, Brian M; Schow, Peter W; Chang, Wesley S; King, Chadwick T

2017-12-01

With current available assay formats using either immobilized protein (ELISA, enzyme-linked immunosorbent assay) or immunostaining of fixed cells for primary monoclonal antibody (mAb) screening, researchers often fail to identify and characterize antibodies that recognize the native conformation of cell-surface antigens. Therefore, screening using live cells has become an integral and important step contributing to the successful identification of therapeutic antibody candidates. Thus the need for developing high-throughput screening (HTS) technologies using live cells has become a major priority for therapeutic mAb discovery and development. We have developed a novel technique called Multiplexed Fluorescent Cell Barcoding (MFCB), a flow cytometry-based method based upon the Fluorescent Cell Barcoding (FCB) technique and the Luminex fluorescent bead array system, but is applicable to high-through mAb screens on live cells. Using this technique in our system, we can simultaneously identify or characterize the antibody-antigen binding of up to nine unique fluorescent labeled cell populations in the time that it would normally take to process a single population. This has significantly reduced the amount of time needed for the identification of potential lead candidates. This new technology enables investigators to conduct large-scale primary hybridoma screens using flow cytometry. This in turn has allowed us to screen antibodies more efficiently than before and streamline identification and characterization of lead molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative performance of anodic oxidation and electrocoagulation as clean processes for electrocatalytic degradation of diazo dye Acid Brown 14 in aqueous medium.

PubMed

Bassyouni, D G; Hamad, H A; El-Ashtoukhy, E-S Z; Amin, N K; El-Latif, M M Abd

2017-08-05

In this study, a laboratory scale for the treatment of a recalcitrant and toxic synthetic wastewater containing diazo dye, acid brown 14 (AB-14) has been comparatively performed by two electro-catalytic treatment processes, namely anodic oxidation (AO) and electrocoagulation (EC) using a new batch electrochemical cell. Additionally, the influence of several operating parameters such as; current density (j), initial dye concentration (C o ), NaCl concentration (C N ), and pH on the color removal efficiency and chemical oxygen demand (COD) are evaluated. The powerful capability of the AO and EC of AB-14 which related to the mechanistic reaction pathway is shown. The poor degradation is ascribed to higher C o and pH, while the enhancement of j and C N is responsible for better degradation of AB-14 dye. The results indicate that the EC is more effective than AO under the same operational condition. A kinetic model is developed for evaluation of the pseudo-first-order-rate constant (k app ) as a function of various operational parameters. The results emphasize the high efficiency of AO and EC and the clean processes which are hopeful alternative for the treatment of the large volume wastewater of the textile industry. Copyright © 2017 Elsevier B.V. All rights reserved.

Collaborative Enhancement of Endothelial Targeting of Nanocarriers by Modulating Platelet-Endothelial Cell Adhesion Molecule-1/CD31 Epitope Engagement.

PubMed

Chacko, Ann-Marie; Han, Jingyan; Greineder, Colin F; Zern, Blaine J; Mikitsh, John L; Nayak, Madhura; Menon, Divya; Johnston, Ian H; Poncz, Mortimer; Eckmann, David M; Davies, Peter F; Muzykantov, Vladimir R

2015-07-28

Nanocarriers (NCs) coated with antibodies (Abs) to extracellular epitopes of the transmembrane glycoprotein PECAM (platelet endothelial cell adhesion molecule-1/CD31) enable targeted drug delivery to vascular endothelial cells. Recent studies revealed that paired Abs directed to adjacent, yet distinct epitopes of PECAM stimulate each other's binding to endothelial cells in vitro and in vivo ("collaborative enhancement"). This phenomenon improves targeting of therapeutic fusion proteins, yet its potential role in targeting multivalent NCs has not been addressed. Herein, we studied the effects of Ab-mediated collaborative enhancement on multivalent NC spheres coated with PECAM Abs (Ab/NC, ∼180 nm diameter). We found that PECAM Abs do mutually enhance endothelial cell binding of Ab/NC coated by paired, but not "self" Ab. In vitro, collaborative enhancement of endothelial binding of Ab/NC by paired Abs is modulated by Ab/NC avidity, epitope selection, and flow. Cell fixation, but not blocking of endocytosis, obliterated collaborative enhancement of Ab/NC binding, indicating that the effect is mediated by molecular reorganization of PECAM molecules in the endothelial plasmalemma. The collaborative enhancement of Ab/NC binding was affirmed in vivo. Intravascular injection of paired Abs enhanced targeting of Ab/NC to pulmonary vasculature in mice by an order of magnitude. This stimulatory effect greatly exceeded enhancement of Ab targeting by paired Abs, indicating that '"collaborative enhancement"' effect is even more pronounced for relatively large multivalent carriers versus free Abs, likely due to more profound consequences of positive alteration of epitope accessibility. This phenomenon provides a potential paradigm for optimizing the endothelial-targeted nanocarrier delivery of therapeutic agents.

Accurate ab initio dipole moment surfaces of ozone: First principle intensity predictions for rotationally resolved spectra in a large range of overtone and combination bands.

PubMed

Tyuterev, Vladimir G; Kochanov, Roman V; Tashkun, Sergey A

2017-02-14

Ab initio dipole moment surfaces (DMSs) of the ozone molecule are computed using the MRCI-SD method with AVQZ, AV5Z, and VQZ-F12 basis sets on a dense grid of about 1950 geometrical configurations. The analytical DMS representation used for the fit of ab initio points provides better behavior for large nuclear displacements than that of previous studies. Various DMS models were derived and tested. Vibration-rotation line intensities of 16 O 3 were calculated from these ab initio surfaces by the variational method using two different potential functions determined in our previous works. For the first time, a very good agreement of first principle calculations with the experiment was obtained for the line-by-line intensities in rotationally resolved ozone spectra in a large far- and mid-infrared range. This includes high overtone and combination bands up to ΔV = 6. A particular challenge was a correct description of the B-type bands (even ΔV 3 values) that represented major difficulties for the previous ab initio investigations and for the empirical spectroscopic models. The major patterns of various B-type bands were correctly described without empirically adjusted dipole moment parameters. For the 10 μm range, which is of key importance for the atmospheric ozone retrievals, our ab initio intensity results are within the experimental error margins. The theoretical values for the strongest lines of the ν 3 band lie in general between two successive versions of HITRAN (HIgh-resolution molecular TRANsmission) empirical database that corresponded to most extended available sets of observations. The overall qualitative agreement in a large wavenumber range for rotationally resolved cold and hot ozone bands up to about 6000 cm -1 is achieved here for the first time. These calculations reveal that several weak bands are yet missing from available spectroscopic databases.

Scattering on two Aharonov-Bohm vortices

NASA Astrophysics Data System (ADS)

Bogomolny, E.

2016-12-01

The problem of two Aharonov-Bohm (AB) vortices for the Helmholtz equation is examined in detail. It is demonstrated that the method proposed by Myers (1963 J. Math. Phys. 6 1839) for slit diffraction can be generalised to obtain an explicit solution for AB vortices. Due to the singular nature of AB interaction the Green function and scattering amplitude for two AB vortices obey a series of partial differential equations. Coefficients entering these equations, fulfil ordinary non-linear differential equations whose solutions can be obtained by solving the Painlevé III equation. The asymptotics of necessary functions for very large and very small vortex separations are calculated explicitly. Taken together, this means that the problem of two AB vortices is exactly solvable.

Nested high-resolution large-eddy simulations in WRF to support wind power

NASA Astrophysics Data System (ADS)

Mirocha, J.; Kirkil, G.; Kosovic, B.; Lundquist, J. K.

2009-12-01

The WRF model’s grid nesting capability provides a potentially powerful framework for simulating flow over a wide range of scales. One such application is computation of realistic inflow boundary conditions for large eddy simulations (LES) by nesting LES domains within mesoscale domains. While nesting has been widely and successfully applied at GCM to mesoscale resolutions, the WRF model’s nesting behavior at the high-resolution (Δx < 1000m) end of the spectrum is less well understood. Nesting LES within msoscale domains can significantly improve turbulent flow prediction at the scale of a wind park, providing a basis for superior site characterization, or for improved simulation of turbulent inflows encountered by turbines. We investigate WRF’s grid nesting capability at high mesh resolutions using nested mesoscale and large-eddy simulations. We examine the spatial scales required for flow structures to equilibrate to the finer mesh as flow enters a nest, and how the process depends on several parameters, including grid resolution, turbulence subfilter stress models, relaxation zones at nest interfaces, flow velocities, surface roughnesses, terrain complexity and atmospheric stability. Guidance on appropriate domain sizes and turbulence models for LES in light of these results is provided This work is performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344 LLNL-ABS-416482

PIV measurements of in-cylinder, large-scale structures in a water-analogue Diesel engine

NASA Astrophysics Data System (ADS)

Kalpakli Vester, A.; Nishio, Y.; Alfredsson, P. H.

2016-11-01

Swirl and tumble are large-scale structures that develop in an engine cylinder during the intake stroke. Their structure and strength depend on the design of the inlet ports and valves, but also on the valve lift history. Engine manufacturers make their design to obtain a specific flow structure that is assumed to give the best engine performance. Despite many efforts, there are still open questions, such as how swirl and tumble depend on the dynamics of the valves/piston as well as how cycle-to-cycle variations should be minimized. In collaboration with Swedish vehicle industry we perform PIV measurements of the flow dynamics during the intake stroke inside a cylinder of a water-analogue engine model having the same geometrical characteristics as a typical truck Diesel engine. Water can be used since during the intake stroke the flow is nearly incompressible. The flow from the valves moves radially outwards, hits the vertical walls of the cylinder, entrains surrounding fluid, moves along the cylinder walls and creates a central backflow, i.e. a tumble motion. Depending on the port and valve design and orientation none, low, or high swirl can be established. For the first time, the effect of the dynamic motion of the piston/valves on the large-scale structures is captured. Supported by the Swedish Energy Agency, Scania CV AB and Volvo GTT, through the FFI program.

Rapid Isolation of a Single-Chain Antibody against the Cyanobacterial Toxin Microcystin-LR by Phage Display and Its Use in the Immunoaffinity Concentration of Microcystins from Water

PubMed Central

McElhiney, Jacqui; Drever, Mathew; Lawton, Linda A.; Porter, Andy J.

2002-01-01

A naïve (unimmunized) human semisynthetic phage display library was employed to isolate recombinant antibody fragments against the cyanobacterial hepatotoxin microcystin-LR. Selected antibody scFv genes were cloned into a soluble expression vector and expressed in Escherichia coli for characterization against purified microcystin-LR by competition enzyme-linked immunosorbent assay (ELISA). The most sensitive single-chain antibody (scAb) isolated was capable of detecting microcystin-LR at levels below the World Health Organization limit in drinking water (1 μg liter−1) and cross-reacted with three other purified microcystin variants (microcystin-RR, -LW, and -LF) and the related cyanotoxin nodularin. Extracts of the cyanobacterium Microcystis aeruginosa were assayed by ELISA, and quantifications of microcystins in toxic samples showed good correlation with analysis by high-performance liquid chromatography. Immobilized scAb was also used to prepare immunoaffinity columns, which were assessed for the ability to concentrate microcystin-LR from water for subsequent analysis by high-performance liquid chromatography. Anti-microcystin-LR scAb was immobilized on columns via a hexahistidine tag, ensuring maximum exposure of antigen binding sites, and the performance of the columns was evaluated by directly applying 150 ml of distilled water spiked with 4 μg of purified microcystin-LR. The procedure was simple, and a recovery rate of 94% was achieved following elution in 1 ml of 100% methanol. Large-scale, low-cost production of anti-microcystin-LR scAb in E. coli is an exciting prospect for the development of biosensors and on-line monitoring systems for microcystins and will also facilitate a range of immunoaffinity applications for the cleanup and concentration of these toxins from environmental samples. PMID:12406716

Development and Application of Loop-Mediated Isothermal Amplification Assays for Rapid Visual Detection of cry2Ab and cry3A Genes in Genetically-Modified Crops

PubMed Central

Li, Feiwu; Yan, Wei; Long, Likun; Qi, Xing; Li, Congcong; Zhang, Shihong

2014-01-01

The cry2Ab and cry3A genes are two of the most important insect-resistant exogenous genes and had been widely used in genetically-modified crops. To develop more effective alternatives for the quick identification of genetically-modified organisms (GMOs) containing these genes, a rapid and visual loop-mediated isothermal amplification (LAMP) method to detect the cry2Ab and cry3A genes is described in this study. The LAMP assay can be finished within 60 min at an isothermal condition of 63 °C. The derived LAMP products can be obtained by a real-time turbidimeter via monitoring the white turbidity or directly observed by the naked eye through adding SYBR Green I dye. The specificity of the LAMP assay was determined by analyzing thirteen insect-resistant genetically-modified (GM) crop events with different Bt genes. Furthermore, the sensitivity of the LAMP assay was evaluated by diluting the template genomic DNA. Results showed that the limit of detection of the established LAMP assays was approximately five copies of haploid genomic DNA, about five-fold greater than that of conventional PCR assays. All of the results indicated that this established rapid and visual LAMP assay was quick, accurate and cost effective, with high specificity and sensitivity. In addition, this method does not need specific expensive instruments or facilities, which can provide a simpler and quicker approach to detecting the cry2Ab and cry3A genes in GM crops, especially for on-site, large-scale test purposes in the field. PMID:25167136

Development and application of loop-mediated isothermal amplification assays for rapid visual detection of cry2Ab and cry3A genes in genetically-modified crops.

PubMed

Li, Feiwu; Yan, Wei; Long, Likun; Qi, Xing; Li, Congcong; Zhang, Shihong

2014-08-27

The cry2Ab and cry3A genes are two of the most important insect-resistant exogenous genes and had been widely used in genetically-modified crops. To develop more effective alternatives for the quick identification of genetically-modified organisms (GMOs) containing these genes, a rapid and visual loop-mediated isothermal amplification (LAMP) method to detect the cry2Ab and cry3A genes is described in this study. The LAMP assay can be finished within 60 min at an isothermal condition of 63 °C. The derived LAMP products can be obtained by a real-time turbidimeter via monitoring the white turbidity or directly observed by the naked eye through adding SYBR Green I dye. The specificity of the LAMP assay was determined by analyzing thirteen insect-resistant genetically-modified (GM) crop events with different Bt genes. Furthermore, the sensitivity of the LAMP assay was evaluated by diluting the template genomic DNA. Results showed that the limit of detection of the established LAMP assays was approximately five copies of haploid genomic DNA, about five-fold greater than that of conventional PCR assays. All of the results indicated that this established rapid and visual LAMP assay was quick, accurate and cost effective, with high specificity and sensitivity. In addition, this method does not need specific expensive instruments or facilities, which can provide a simpler and quicker approach to detecting the cry2Ab and cry3A genes in GM crops, especially for on-site, large-scale test purposes in the field.

Anti-brain antibodies are associated with more severe cognitive and behavioral profiles in Italian children with Autism Spectrum Disorder

PubMed Central

Piras, I.S.; Haapanen, L.; Napolioni, V.; Sacco, R.; Van de Water, J.; Persico, A.M.

2014-01-01

Circulating 45 and 62 kDa antibodies targeting the cerebellum were previously associated with Autism Spectrum Disorder (ASD), lower adaptive/cognitive function and aberrant behaviors. Moreover, 37, 39 and 73 kDa maternal antibodies (mAb) targeting the fetal brain were previously correlated with broad autism spectrum, irritability, abnormal brain enlargement and impaired expressive language. The present study aims towards clinically characterizing individuals with brain-targeted IgG and/or exposed to maternal antibrain antibodies in a large sample of Italian autistic children (N = 355), their unaffected siblings (N = 142) and mothers (N = 333). The presence of patient- and mother-produced anti-brain antibodies does not confer increased risk of autism within the same sibship. However, the 45 and 62 kDa antibodies are correlated with autism severity: the 45 kDa Ab is associated with cognitive impairment and lower scores at the Vineland Adaptive Behavior Scales, the 62 kDa Ab with motor stereotypies, while both correlate with larger head circumference (all P < 0.05). On the other hand, maternal 37, 39 and 73 kDa antibrain antibodies, either alone or in combination, are correlated with impaired verbal and non-verbal language development, neurodevelopmental delay and sleep/wake cycle disturbances in their autistic children (P < 0.05). Presence of the 62 kDa autoAb in the child is significantly associated with presence of the 39 and/or 73 kDa antibodies in his/her mother. Our results confirm and extend previous observations in an ethnically distinct sample, providing further evidence of a pathomorphic role for antibrain antibodies in autism while demonstrating their familial clustering. PMID:24389156

Anti-brain antibodies are associated with more severe cognitive and behavioral profiles in Italian children with Autism Spectrum Disorder.

PubMed

Piras, I S; Haapanen, L; Napolioni, V; Sacco, R; Van de Water, J; Persico, A M

2014-05-01

Circulating 45 and 62kDa antibodies targeting the cerebellum were previously associated with Autism Spectrum Disorder (ASD), lower adaptive/cognitive function and aberrant behaviors. Moreover, 37, 39 and 73kDa maternal antibodies (mAb) targeting the fetal brain were previously correlated with broad autism spectrum, irritability, abnormal brain enlargement and impaired expressive language. The present study aims towards clinically characterizing individuals with brain-targeted IgG and/or exposed to maternal antibrain antibodies in a large sample of Italian autistic children (N=355), their unaffected siblings (N=142) and mothers (N=333). The presence of patient- and mother-produced anti-brain antibodies does not confer increased risk of autism within the same sibship. However, the 45 and 62kDa antibodies are correlated with autism severity: the 45kDa Ab is associated with cognitive impairment and lower scores at the Vineland Adaptive Behavior Scales, the 62kDa Ab with motor stereotypies, while both correlate with larger head circumference (all P<0.05). On the other hand, maternal 37, 39 and 73kDa antibrain antibodies, either alone or in combination, are correlated with impaired verbal and non-verbal language development, neurodevelopmental delay and sleep/wake cycle disturbances in their autistic children (P<0.05). Presence of the 62kDa autoAb in the child is significantly associated with presence of the 39 and/or 73kDa antibodies in his/her mother. Our results confirm and extend previous observations in an ethnically distinct sample, providing further evidence of a pathomorphic role for anti-brain antibodies in autism while demonstrating their familial clustering. Copyright © 2014 Elsevier Inc. All rights reserved.

Primordial environment of supermassive black holes. II. Deep Y- and J-band images around the z 6.3 quasar SDSS J1030+0524

NASA Astrophysics Data System (ADS)

Balmaverde, B.; Gilli, R.; Mignoli, M.; Bolzonella, M.; Brusa, M.; Cappelluti, N.; Comastri, A.; Sani, E.; Vanzella, E.; Vignali, C.; Vito, F.; Zamorani, G.

2017-10-01

Many cosmological studies predict that early supermassive black holes (SMBHs) can only form in the most massive dark matter halos embedded within large-scale structures marked by galaxy overdensities that may extend up to 10 physical Mpc. This scenario, however, has not been confirmed observationally, as the search for galaxy overdensities around high-z quasars has returned conflicting results. The field around the z = 6.31 quasar SDSSJ1030+0524 (J1030) is unique for multi-band coverage and represents an excellent data legacy for studying the environment around a primordial SMBH. In this paper we present wide-area ( 25' × 25') Y- and J-band imaging of the J1030 field obtained with the near infrared camera WIRCam at the Canada-France-Hawaii Telescope (CFHT). We built source catalogs in the Y- and J-band, and matched those with our photometric catalog in the r, z, and I bands presented in our previous paper and based on sources with zAB< 25.2 detected using z-band images from the the Large Binocular Cameras (LBC) at the Large Binocular Telescope (LBT) over the same field of view. We used these new infrared data together with H and K photometric measurements from the MUlti-wavelength Survey by Yale-Chile (MUSYC) and with the Spitzer Infrared Array Camera (IRAC) data to refine our selection of Lyman break galaxies (LBGs), extending our selection criteria to galaxies in the range 25.2 4σ. The overdensity value and its significance are higher than those found in our previous paper and we interpret this as evidence of an improved LBG selection.

Bright Localized Near-Infrared Emission at 1-4 AU in the AB Aurigae Disk Revealed by IOTA Closure Phases

NASA Astrophysics Data System (ADS)

Millan-Gabet, R.; Monnier, J. D.; Berger, J.-P.; Traub, W. A.; Schloerb, F. P.; Pedretti, E.; Benisty, M.; Carleton, N. P.; Haguenauer, P.; Kern, P.; Labeye, P.; Lacasse, M. G.; Malbet, F.; Perraut, K.; Pearlman, M.; Thureau, N.

2006-07-01

We report on the detection of localized off-center emission at 1-4 AU in the circumstellar environment of the young stellar object AB Aurigae. We used closure-phase measurements in the near-infrared that were made at the long-baseline interferometer IOTA, the first obtained on a young stellar object using this technique. When probing sub-AU scales, all closure phases are close to zero degrees, as expected given the previously determined size of the AB Aurigae inner-dust disk. However, a clear closure-phase signal of -3.5d +/- 0.5d is detected on one triangle containing relatively short baselines, requiring a high degree of non-point symmetry from emission at larger (AU-sized) scales in the disk. We have not identified any alternative explanation for these closure-phase results, and we demonstrate that a ``disk hot spot'' model can fit our data. We speculate that such detected asymmetric near-infrared emission might arise as a result of localized viscous heating due to a gravitational instability in the AB Aurigae disk, or to the presence of a close stellar companion or accreting substellar object.

Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort

PubMed Central

Landais, Elise; Huang, Xiayu; Havenar-Daughton, Colin; Murrell, Ben; Price, Matt A.; Wickramasinghe, Lalinda; Ramos, Alejandra; Bian, Charoan B.; Simek, Melissa; Allen, Susan; Karita, Etienne; Kilembe, William; Lakhi, Shabir; Inambao, Mubiana; Kamali, Anatoli; Sanders, Eduard J.; Anzala, Omu; Edward, Vinodh; Bekker, Linda-Gail; Tang, Jianming; Gilmour, Jill; Kosakovsky-Pond, Sergei L.; Phung, Pham; Wrin, Terri; Crotty, Shane; Godzik, Adam; Poignard, Pascal

2016-01-01

Broadly neutralizing antibodies (bnAbs) are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(-) genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design. PMID:26766578

Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort.

PubMed

Landais, Elise; Huang, Xiayu; Havenar-Daughton, Colin; Murrell, Ben; Price, Matt A; Wickramasinghe, Lalinda; Ramos, Alejandra; Bian, Charoan B; Simek, Melissa; Allen, Susan; Karita, Etienne; Kilembe, William; Lakhi, Shabir; Inambao, Mubiana; Kamali, Anatoli; Sanders, Eduard J; Anzala, Omu; Edward, Vinodh; Bekker, Linda-Gail; Tang, Jianming; Gilmour, Jill; Kosakovsky-Pond, Sergei L; Phung, Pham; Wrin, Terri; Crotty, Shane; Godzik, Adam; Poignard, Pascal

2016-01-01

Broadly neutralizing antibodies (bnAbs) are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(-) genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design.

Enhanced production of L-sorbose from D-sorbitol by improving the mRNA abundance of sorbitol dehydrogenase in Gluconobacter oxydans WSH-003.

PubMed

Xu, Sha; Wang, Xiaobei; Du, Guocheng; Zhou, Jingwen; Chen, Jian

2014-10-18

Production of L-sorbose from D-sorbitol by Gluconobacter oxydans is the first step to produce L-ascorbic acid on industrial scale. The sldhAB gene, which encodes the sorbitol dehydrogenase (SLDH), was overexpressed in an industrial strain G. oxydans WSH-003 with a strong promoter, P tufB . To enhance the mRNA abundance, a series of artificial poly(A/T) tails were added to the 3'-terminal of sldhAB gene. Besides, their role in sldhAB overexpression and their subsequent effects on L-sorbose production were investigated. The mRNA abundance of the sldhAB gene could be enhanced in G. oxydans by suitable poly(A/T) tails. By self-overexpressing the sldhAB gene in G. oxydans WSH-003 with an optimal poly(A/T) tail under the constitutive promoter P tufB , the titer and the productivity of L-sorbose were enhanced by 36.3% and 25.0%, respectively, in a 1-L fermenter. Immobilization of G. oxydans-sldhAB6 cells further improved the L-sorbose titer by 33.7% after 20 days of semi-continuous fed-batch fermentation. The artificial poly(A/T) tails could significantly enhance the mRNA abundance of the sldhAB. Immobilized G. oxydans-sldhAB6 cells could further enlarge the positive effect caused by enhanced mRNA abundance of the sldhAB.

Oriented conjugation of single-domain antibodies and quantum dots.

PubMed

Brazhnik, Kristina; Nabiev, Igor; Sukhanova, Alyona

2014-01-01

Nanoparticle-based biodetection routinely employs monoclonal antibodies (mAbs) for targeting. However, the large size of mAbs limits the number of ligands per nanoparticle and severely restricts the bioavailability and distribution of these probes in a sample. Furthermore, conventional conjugation techniques provide nanoprobes with irregular orientation of mAbs on the nanoparticle surface and often provoke mAb unfolding. Here, we describe a protocol for engineering a new generation of ultrasmall diagnostic nanoprobes through oriented conjugation of semiconductor quantum dots (QDs) with 13 kDa single-domain antibodies (sdAbs) derived from llama immunoglobulin G (IgG). The sdAbs are conjugated with QDs in a highly oriented manner via an additional cysteine residue specifically integrated into the sdAb C-terminus. The resultant nanoprobes are <12 nm in diameter, ten times smaller in volume compared to the known alternatives. They have been proved highly efficient in flow cytometry and immunuhistochemical diagnostics. This approach can be easily extended to other semiconductor and plasmonic nanoparticles.

VizieR Online Data Catalog: SNLS and SDSS SN surveys photometric calibration (Betoule+, 2013)

NASA Astrophysics Data System (ADS)

Betoule, M.; Marriner, J.; Regnault, N.; Cuillandre, J.-C.; Astier, P.; Guy, J.; Balland, C.; El, Hage P.; Hardin, D.; Kessler, R.; Le Guillou, L.; Mosher, J.; Pain, R.; Rocci, P.-F.; Sako, M.; Schahmaneche, K.

2012-11-01

We present a joined photometric calibration for the SNLS and the SDSS supernova surveys. Our main delivery are catalogs of natural AB magnitudes for a large set of selected tertiary standard stars covering the science field of both surveys. Those catalogs are calibrated to the AB flux scale through observations of 5 primary spectrophotometric standard stars, for which HST-STIS spectra are available in the CALSPEC database. The estimate of the uncertainties associated to this calibration are delivered as a single covariance matrix. We also provide a model of the transmission efficiency of the SNLS photometric instrument MegaCam. Those transmission functions are required for the interpretation of MegaCam natural magnitudes in term of physical fluxes. Similar curves for the SDSS photometric instrument have been published in Doi et al. (2010AJ....139.1628D). Last, we release the measured magnitudes of the five CALSPEC standard stars in the magnitude system of the tertiary catalogs. This makes it possible to update the calibration of the tertiary catalogs if CALSPEC spectra for the primary standards are revised. (11 data files).

Semiempirical Quantum Mechanical Methods for Noncovalent Interactions for Chemical and Biochemical Applications

PubMed Central

2016-01-01

Semiempirical (SE) methods can be derived from either Hartree–Fock or density functional theory by applying systematic approximations, leading to efficient computational schemes that are several orders of magnitude faster than ab initio calculations. Such numerical efficiency, in combination with modern computational facilities and linear scaling algorithms, allows application of SE methods to very large molecular systems with extensive conformational sampling. To reliably model the structure, dynamics, and reactivity of biological and other soft matter systems, however, good accuracy for the description of noncovalent interactions is required. In this review, we analyze popular SE approaches in terms of their ability to model noncovalent interactions, especially in the context of describing biomolecules, water solution, and organic materials. We discuss the most significant errors and proposed correction schemes, and we review their performance using standard test sets of molecular systems for quantum chemical methods and several recent applications. The general goal is to highlight both the value and limitations of SE methods and stimulate further developments that allow them to effectively complement ab initio methods in the analysis of complex molecular systems. PMID:27074247

CO2 capture in amine solutions: modelling and simulations with non-empirical methods

NASA Astrophysics Data System (ADS)

Andreoni, Wanda; Pietrucci, Fabio

2016-12-01

Absorption in aqueous amine solutions is the most advanced technology for the capture of CO2, although suffering from drawbacks that do not allow exploitation on large scale. The search for optimum solvents has been pursued with empirical methods and has also motivated a number of computational approaches over the last decade. However, a deeper level of understanding of the relevant chemical reactions in solution is required so as to contribute to this effort. We present here a brief critical overview of the most recent applications of computer simulations using ab initio methods. Comparison of their outcome shows a strong dependence on the structural models employed to represent the molecular systems in solution and on the strategy used to simulate the reactions. In particular, the results of very recent ab initio molecular dynamics augmented with metadynamics are summarized, showing the crucial role of water, which has been so far strongly underestimated both in the calculations and in the interpretation of experimental data. Indications are given for advances in computational approaches that are necessary if meant to contribute to the rational design of new solvents.

A new potential energy surface for vibration-vibration coupling in HF-HF collisions. Formulation and quantal scattering calculations

NASA Astrophysics Data System (ADS)

Schwenke, David W.; Truhlar, Donald G.

1988-04-01

We present new ab initio calculations of the HF-HF interaction potential for the case where both molecules are simultaneously displaced from their equilibrium internuclear distance. These and previous ab initio calculations are then fit to a new analytic representation which is designed to be efficient to evaluate and to provide an especially faithful account of the forces along the vibrational coordinates. We use the new potential for two sets of quantal scattering calculations for collisions in three dimensions with total angular momentum zero. First we test that the angular harmonic representation of the anisotropy is adequate by comparing quantal rigid rotator calculations to those carried out for potentials involving higher angular harmonics and for which the expansion in angular harmonics is systematically increased to convergence. Then we carry out large-scale quantal calculations of vibration-vibration energy transfer including the coupling of both sets of vibrational and rotational coordinates. These calculations indicate that significant rotational energy transfer accompanies the vibration-to-vibration energy transfer process.

Ab Initio Calculations of Ultrashort Carrier Dynamics in Two-Dimensional Materials: Valley Depolarization in Single-Layer WSe2

NASA Astrophysics Data System (ADS)

Molina-Sánchez, Alejandro; Sangalli, Davide; Wirtz, Ludger; Marini, Andrea

2017-08-01

In single-layer WSe$_2$, a paradigmatic semiconducting transition metal dichalcogenide, a circularly polarized laser field can selectively excite electronic transitions in one of the inequivalent $K^{\\pm}$ valleys. Such selective valley population corresponds to a pseudospin polarization. This can be used as a degree of freedom in a valleytronic device provided that the time scale for its depolarization is sufficiently large. Yet, the mechanism behind the valley depolarization still remains heavily debated. Recent time-dependent Kerr experiments have provided an accurate way to visualize the valley dynamics by measuring the rotation of a linearly polarized probe pulse applied after a circularly polarized pump pulse. We present here a clear, accurate and parameter-free description of the valley dynamics. By using an atomistic, ab initio, approach we fully disclose the elemental mechanisms that dictate the depolarization effects. Our results are in excellent agreement with recent time-dependent Kerr experiments. We explain the Kerr dynamics and its temperature dependence in terms of electron-phonon mediated processes that induce spin-flip inter-valley transitions.

On the isotropic Raman spectrum of Ar2 and how to benchmark ab initio calculations of small atomic clusters: Paradox lost.

PubMed

Chrysos, Michael; Dixneuf, Sophie; Rachet, Florent

2015-07-14

This is the long-overdue answer to the discrepancies observed between theory and experiment in Ar2 regarding both the isotropic Raman spectrum and the second refractivity virial coefficient, BR [Gaye et al., Phys. Rev. A 55, 3484 (1997)]. At the origin of this progress is the advent (posterior to 1997) of advanced computational methods for weakly interconnected neutral species at close separations. Here, we report agreement between the previously taken Raman measurements and quantum lineshapes now computed with the employ of large-scale CCSD or smartly constructed MP2 induced-polarizability data. By using these measurements as a benchmark tool, we assess the degree of performance of various other ab initio computed data for the mean polarizability α, and we show that an excellent agreement with the most recently measured value of BR is reached. We propose an even more refined model for α, which is solution of the inverse-scattering problem and whose lineshape matches exactly the measured spectrum over the entire frequency-shift range probed.

Design and scaleup of downstream processing of monoclonal antibodies for cancer therapy: from research to clinical proof of principle.

PubMed

Horenstein, Alberto L; Crivellin, Federico; Funaro, Ada; Said, Marcela; Malavasi, Fabio

2003-04-01

Murine monoclonal antibodies (mAb) from cell culture supernatants have been purified in order to acquire clinical grade for in vivo cancer treatment. The starting material was purified by high performance liquid chromatography (HPLC) systems ranging from the analytical scale process to a scaleup to 1 g per batch. Three columns (Protein A affinity chromatography with single-step elution, hydroxyapatite (HA) chromatography followed by linear gradient elution and endotoxin removing-gel chromatography), exploiting different properties of the mAb were applied. The final batches of antibody were subjected to a large panel of tests for the purpose of evaluating the efficacy of the downstream processing. The resulting data have allowed us to determine the maximum number of times the column can be used and to precisely and thoroughly characterize antibody integrity, specificity, and potency according to in-house reference standards. The optimized bioprocessing is rapid, efficient, and reproducible. Not less importantly, all the techniques applied are characterized by costs which are affordable to medium-sized laboratories. They represent the basis for implementing immunotherapeutic protocols transferable to clinical medicine.

Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection.

PubMed

Flyak, Andrew I; Shen, Xiaoli; Murin, Charles D; Turner, Hannah L; David, Joshua A; Fusco, Marnie L; Lampley, Rebecca; Kose, Nurgun; Ilinykh, Philipp A; Kuzmina, Natalia; Branchizio, Andre; King, Hannah; Brown, Leland; Bryan, Christopher; Davidson, Edgar; Doranz, Benjamin J; Slaughter, James C; Sapparapu, Gopal; Klages, Curtis; Ksiazek, Thomas G; Saphire, Erica Ollmann; Ward, Andrew B; Bukreyev, Alexander; Crowe, James E

2016-01-28

Recent studies have suggested that antibody-mediated protection against the Ebolaviruses may be achievable, but little is known about whether or not antibodies can confer cross-reactive protection against viruses belonging to diverse Ebolavirus species, such as Ebola virus (EBOV), Sudan virus (SUDV), and Bundibugyo virus (BDBV). We isolated a large panel of human monoclonal antibodies (mAbs) against BDBV glycoprotein (GP) using peripheral blood B cells from survivors of the 2007 BDBV outbreak in Uganda. We determined that a large proportion of mAbs with potent neutralizing activity against BDBV bind to the glycan cap and recognize diverse epitopes within this major antigenic site. We identified several glycan cap-specific mAbs that neutralized multiple ebolaviruses, including SUDV, and a cross-reactive mAb that completely protected guinea pigs from the lethal challenge with heterologous EBOV. Our results provide a roadmap to develop a single antibody-based treatment effective against multiple Ebolavirus infections. Copyright © 2016 Elsevier Inc. All rights reserved.

CROSS-REACTIVE AND POTENT NEUTRALIZING ANTIBODY RESPONSES IN HUMAN SURVIVORS OF NATURAL EBOLAVIRUS INFECTION

PubMed Central

Flyak, Andrew I.; Shen, Xiaoli; Murin, Charles D.; Turner, Hannah L.; David, Joshua A.; Fusco, Marnie L.; Lampley, Rebecca; Kose, Nurgun; Ilinykh, Philipp A.; Kuzmina, Natalia; Branchizio, Andre; King, Hannah; Brown, Leland; Bryan, Christopher; Davidson, Edgar; Doranz, Benjamin J.; Slaughter, James C.; Sapparapu, Gopal; Klages, Curtis; Ksiazek, Thomas G.; Saphire, Erica Ollmann; Ward, Andrew B.; Bukreyev, Alexander; Crowe, James E.

2015-01-01

Summary Recent studies have suggested that antibody-mediated protection against the Ebolaviruses may be achievable, but little is known about whether or not antibodies can confer cross-reactive protection against viruses belonging to diverse Ebolavirus species, such as Ebola virus (EBOV), Sudan virus (SUDV) and Bundibugyo virus (BDBV). We isolated a large panel of human monoclonal antibodies (mAbs) against BDBV glycoprotein (GP) using peripheral blood B cells from survivors of the 2007 BDBV outbreak in Uganda. We determined that a large proportion of mAbs with potent neutralizing activity against BDBV bind to the glycan cap and recognize diverse epitopes within this major antigenic site. We identified several glycan cap-specific mAbs that neutralized multiple ebolaviruses including SUDV, and a cross-reactive mAb that completely protected guinea pigs from the lethal challenge with heterologous EBOV. Our results provide a roadmap to develop a single antibody-based treatment effective against multiple Ebolavirus infections. PMID:26806128

Enhancing antibody patent protection using epitope mapping information

PubMed Central

Deng, Xiaoxiang; Storz, Ulrich; Doranz, Benjamin J.

2018-01-01

ABSTRACT As the $100B therapeutic monoclonal antibody (mAb) market continues to grow, developers of therapeutic mAbs increasingly face the need to strengthen patent protection of their products and enforce their patents in courts. In view of changes in the patent law landscape, patent applications are strategically using information on the precise binding sites of their mAbs, i.e., the epitopes, to support patent novelty, non-obviousness, subject matter, and a tightened written description requirement for broad genus antibody claims. Epitope data can also allow freedom-to-operate for second-generation mAbs by differentiation from patented first-generation mAbs. Numerous high profile court cases, including Amgen v. Sanofi over rival mAbs that block PCSK9 activity, have been centered on epitope mapping claims, highlighting the importance of epitopes in determining broad mAb patent rights. Based on these cases, epitope mapping claims must describe a sufficiently large number of mAbs that share an epitope, and each epitope must be described at amino acid resolution. Here, we review current best practices for the use of epitope information to overcome the increasing challenges of patenting mAbs, and how the quality, conformation, and resolution of epitope residue data can influence the breadth and strength of mAb patents. PMID:29120697

Numerical Investigation on Absorption Enhancement of Black Carbon Aerosols Partially Coated With Nonabsorbing Organics

NASA Astrophysics Data System (ADS)

Zhang, Xiaolin; Mao, Mao; Yin, Yan; Wang, Bin

2018-01-01

This study numerically evaluates the effects of aerosol microphysics, including coated volume fraction of black carbon (BC), shell/core ratio, and size distribution, on the absorption enhancement (Eab) of polydisperse BC aggregates partially coated by organics, which is calculated by the exact multiple-sphere T-matrix method. The coated volume fraction of BC plays a substantial role in determining the absorption enhancement of partially coated BC aggregates, which typically have an Eab in the range of 1.0-2.0 with a larger value for larger coated volume fraction of BC as the shell/core ratio, BC geometry, and size distribution are fixed. The shell/core ratio, BC geometry, and size distribution have little impact on the Eab of coated BC with small coated volume fraction of BC, while they become significant for large coated volume fraction of BC. The Eab of partially coated BC particles can be slightly less than 1.0 for the large BC in the accumulation mode exhibiting large shell/core ratio and small coated volume fraction of BC, indicating that the absorption shows even slight decrease relative to uncoated BC particles. For partially coated BC aggregates in the accumulation and coarse modes, the refractive index uncertainties of BC result in the Eab differences of less than 9% and 2%, respectively, while those of organics can induce larger variations with the maximum differences up to 22% and 18%, respectively. Our study indicates that accounting for particle coating microphysics, particularly the coated volume fraction of BC, can potentially help to understand the differences in observations of largely variable absorption enhancements over various regions.

A variety of human monoclonal antibodies against epidermal growth factor receptor isolated from a phage antibody library.

PubMed

Kurosawa, Gene; Kondo, Mariko; Kurosawa, Yoshikazu

2016-11-04

When the technology for constructing human antibody (Ab) libraries using a phage-display system was developed, many researchers in Ab-related fields anticipated that it would be widely applied to the development of pharmaceutical drugs against various diseases, including cancers. However, successful examples of such applications are very limited. Moreover, researchers who utilize phage-display technology now show divergent ways of thinking about phage Ab libraries. For example, there is debate about what should be the source of V H and V L genes for the construction of libraries to cover the whole repertoire of Abs present in the human body. In the immune system, the introduction of mutations into V genes followed by selection based on binding activity, termed Ab maturation, is required for the production of Abs exhibiting high affinity to the antigen (Ag). Therefore, introduction of mutations and selection are required for isolation of Abs with high affinity after isolation of clones from phage Ab libraries. We constructed a large human Ab library termed AIMS, developed a screening method termed ICOS, and succeeded in isolating many human monoclonal Abs (mAbs) that specifically and strongly bind to various tumor-associated Ags. Eight anti-EGFR mAbs were included, which we characterized. These mAbs showed various different activities against EGFR-expressing cancer cells. In this paper, we describe these data and discuss the possibility and necessity that the mAbs isolated from the AIMS library might be developed as therapeutic drugs against cancers without introduction of mutations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Torsional anharmonicity in the conformational thermodynamics of flexible molecules

NASA Astrophysics Data System (ADS)

Miller, Thomas F., III; Clary, David C.

We present an algorithm for calculating the conformational thermodynamics of large, flexible molecules that combines ab initio electronic structure theory calculations with a torsional path integral Monte Carlo (TPIMC) simulation. The new algorithm overcomes the previous limitations of the TPIMC method by including the thermodynamic contributions of non-torsional vibrational modes and by affordably incorporating the ab initio calculation of conformer electronic energies, and it improves the conventional ab initio treatment of conformational thermodynamics by accounting for the anharmonicity of the torsional modes. Using previously published ab initio results and new TPIMC calculations, we apply the algorithm to the conformers of the adrenaline molecule.

Effect of the Protein Corona on Antibody-Antigen Binding in Nanoparticle Sandwich Immunoassays.

PubMed

de Puig, Helena; Bosch, Irene; Carré-Camps, Marc; Hamad-Schifferli, Kimberly

2017-01-18

We investigated the effect of the protein corona on the function of nanoparticle (NP) antibody (Ab) conjugates in dipstick sandwich immunoassays. Ab specific for Zika virus nonstructural protein 1 (NS1) were conjugated to gold NPs, and another anti-NS1 Ab was immobilized onto the nitrocellulose membrane. Sandwich immunoassay formation was influenced by whether the strip was run in corona forming conditions, i.e., in human serum. Strips run in buffer or pure solutions of bovine serum albumin exhibited false positives, but those run in human serum did not. Serum pretreatment of the nitrocellulose also eliminated false positives. Corona formation around the NP-Ab in serum was faster than the immunoassay time scale. Langmuir binding analysis determined how the immobilized Ab affinity for the NP-Ab/NS1 was impacted by corona formation conditions, quantified as an effective dissociation constant, K D eff . Results show that corona formation mediates the specificity and sensitivity of the antibody-antigen interaction of Zika biomarkers in immunoassays, and plays a critical but beneficial role.

Comparison of the osteogenesis and fusion rates between activin A/BMP-2 chimera (AB204) and rhBMP-2 in a beagle's posterolateral lumbar spine model.

PubMed

Zheng, Guang Bin; Yoon, Byung-Hak; Lee, Jae Hyup

2017-10-01

Activin A/BMP-2 chimera (AB204) could promote bone healing more effectively than recombinant bone morphogenetic protein 2 (rhBMP-2) with much lower dose in a rodent model, but there is no report about the effectiveness of AB204 in a large animal model. The purpose of this study was to compare the osteogenesis and fusion rate between AB204 and rhBMP-2 using biphasic calcium phosphate (BCP) as a carrier in a beagle's posterolateral lumbar fusion model. This is a randomized control animal study. Seventeen male beagle dogs were included. Bilateral posterolateral fusion was performed at the L1-L2 and L4-L5 levels. Biphasic calcium phosphate (2 cc), rhBMP-2 (50 µg)+BCP (2 cc), or AB204 (50 µg)+BCP (2 cc) were implanted into the intertransverse space randomly. X-ray was performed at 4 and 8 weeks. After 8 weeks, the animals were sacrificed, and new bone formation and fusion rate were evaluated by manual palpation, computed tomography (CT), and undecalcified histology. The AB204 group showed significantly higher fusion rate (90%) than the rhBMP-2 group (15%) or the Osteon group (6.3%) by manual palpation. On x-ray and CT assessment, fusion rate and the volume of newly formed bone were also significantly higher in AB204 group than other groups. In contrast, more osteolysis was found in rhBMP-2 group (40%) than in AB204 group (10%) on CT study. In histologic results, new bone formation was sufficient between transverse processes in AB204 group, and obvious trabeculation and bone remodeling were observed. But in rhBMP-2 group, new bone formation was less than AB204 group and osteolysis was observed between the intertransverse spaces. A low dose of AB204 with BCP as a carrier significantly promotes the fusion rate in a large animal model when compared with the rhBMP-2. These findings demonstrate that AB204 could be an alternative to rhBMP-2 to improve fusion rate. Copyright © 2017 Elsevier Inc. All rights reserved.

Leukocyte adhesion: High-speed cells with ABS.

PubMed

van der Merwe, P A

1999-06-03

In order to decide where to exit blood vessels and enter tissues, leukocytes roll along endothelial surfaces. Recent studies suggest that an 'automatic braking system' (ABS), involving selectin cell-adhesion molecules, enables leukocytes to roll at a fairly constant velocity despite large variations in blood flow rate.

Evaluation of differences between dual salt-pH gradient elution and mono gradient elution using a thermodynamic model: Simultaneous separation of six monoclonal antibody charge and size variants on preparative-scale ion exchange chromatographic resin.

PubMed

Lee, Yi Feng; Jöhnck, Matthias; Frech, Christian

2018-02-21

The efficiencies of mono gradient elution and dual salt-pH gradient elution for separation of six mAb charge and size variants on a preparative-scale ion exchange chromatographic resin are compared in this study. Results showed that opposite dual salt-pH gradient elution with increasing pH gradient and simultaneously decreasing salt gradient is best suited for the separation of these mAb charge and size variants on Eshmuno ® CPX. Besides giving high binding capacity, this type of opposite dual salt-pH gradient also provides better resolved mAb variant peaks and lower conductivity in the elution pools compared to single pH or salt gradients. To have a mechanistic understanding of the differences in mAb variants retention behaviors of mono pH gradient, parallel dual salt-pH gradient, and opposite dual salt-pH gradient, a linear gradient elution model was used. After determining the model parameters using the linear gradient elution model, 2D plots were used to show the pH and salt dependencies of the reciprocals of distribution coefficient, equilibrium constant, and effective ionic capacity of the mAb variants in these gradient elution systems. Comparison of the 2D plots indicated that the advantage of opposite dual salt-pH gradient system with increasing pH gradient and simultaneously decreasing salt gradient is the noncontinuous increased acceleration of protein migration. Furthermore, the fitted model parameters can be used for the prediction and optimization of mAb variants separation in dual salt-pH gradient and step elution. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018. © 2018 American Institute of Chemical Engineers.

DARPA Ensemble-Based Modeling Large Graphs & Applications to Social Networks

DTIC Science & Technology

2015-07-29

Fortunato, and D. Krioukov. How random are complex networks. Nature Communications , submitted (2015). http://arxiv.org/abs/1505.07503 [p2] I. Miklos...enterprise communication networks, PLOS One, 10(3), e0119446 (2015). http://arxiv.org/abs/1404.3708v3 [p21] A. Nyberg, T. Gross, and K.E. Bassler...using a radiation model based on temporal ranges. Nature Communications , 5, 5347 (2014) | http://arxiv.org/abs/1410.4849 [p28] L.A. Székely, H. Wang

THE DEPENDENCE OF STELLAR MASS AND ANGULAR MOMENTUM LOSSES ON LATITUDE AND THE INTERACTION OF ACTIVE REGION AND DIPOLAR MAGNETIC FIELDS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garraffo, Cecilia; Drake, Jeremy J.; Cohen, Ofer

Rotation evolution of late-type stars is dominated by magnetic braking and the underlying factors that control this angular momentum loss are important for the study of stellar spin-down. In this work, we study angular momentum loss as a function of two different aspects of magnetic activity using a calibrated Alfvén wave-driven magnetohydrodynamic wind model: the strengths of magnetic spots and their distribution in latitude. By driving the model using solar and modified solar surface magnetograms, we show that the topology of the field arising from the net interaction of both small-scale and large-scale field is important for spin-down rates andmore » that angular momentum loss is not a simple function of large scale magnetic field strength. We find that changing the latitude of magnetic spots can modify mass and angular momentum loss rates by a factor of two. The general effect that causes these differences is the closing down of large-scale open field at mid- and high-latitudes by the addition of the small-scale field. These effects might give rise to modulation of mass and angular momentum loss through stellar cycles, and present a problem for ab initio attempts to predict stellar spin-down based on wind models. For all the magnetogram cases considered here, from dipoles to various spotted distributions, we find that angular momentum loss is dominated by the mass loss at mid-latitudes. The spin-down torque applied by magnetized winds therefore acts at specific latitudes and is not evenly distributed over the stellar surface, though this aspect is unlikely to be important for understanding spin-down and surface flows on stars.« less

Prospective iterative trial of proteasome inhibitor-based desensitization.

PubMed

Woodle, E S; Shields, A R; Ejaz, N S; Sadaka, B; Girnita, A; Walsh, R C; Alloway, R R; Brailey, P; Cardi, M A; Abu Jawdeh, B G; Roy-Chaudhury, P; Govil, A; Mogilishetty, G

2015-01-01

A prospective iterative trial of proteasome inhibitor (PI)-based therapy for reducing HLA antibody (Ab) levels was conducted in five phases differing in bortezomib dosing density and plasmapheresis timing. Phases included 1 or 2 bortezomib cycles (1.3 mg/m(2) × 6-8 doses), one rituximab dose and plasmapheresis. HLA Abs were measured by solid phase and flow cytometry (FCM) assays. Immunodominant Ab (iAb) was defined as highest HLA Ab level. Forty-four patients received 52 desensitization courses (7 patients enrolled in multiple phases): Phase 1 (n = 20), Phase 2 (n = 12), Phase 3 (n = 10), Phase 4 (n = 5), Phase 5 (n = 5). iAb reductions were observed in 38 of 44 (86%) patients and persisted up to 10 months. In Phase 1, a 51.5% iAb reduction was observed at 28 days with bortezomib alone. iAb reductions increased with higher bortezomib dosing densities and included class I, II, and public antigens (HLA DRβ3, HLA DRβ4 and HLA DRβ5). FCM median channel shifts decreased in 11/11 (100%) patients by a mean of 103 ± 54 mean channel shifts (log scale). Nineteen out of 44 patients (43.2%) were transplanted with low acute rejection rates (18.8%) and de novo DSA formation (12.5%). In conclusion, PI-based desensitization consistently and durably reduces HLA Ab levels providing an alternative to intravenous immune globulin-based desensitization. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Detailed statistical assessment of the characteristics of the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) threshold rules.

PubMed

Dafni, Urania; Karlis, Dimitris; Pedeli, Xanthi; Bogaerts, Jan; Pentheroudakis, George; Tabernero, Josep; Zielinski, Christoph C; Piccart, Martine J; de Vries, Elisabeth G E; Latino, Nicola Jane; Douillard, Jean-Yves; Cherny, Nathan I

2017-01-01

The European Society for Medical Oncology (ESMO) has developed the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS), a tool to assess the magnitude of clinical benefit from new cancer therapies. Grading is guided by a dual rule comparing the relative benefit (RB) and the absolute benefit (AB) achieved by the therapy to prespecified threshold values. The ESMO-MCBS v1.0 dual rule evaluates the RB of an experimental treatment based on the lower limit of the 95%CI (LL95%CI) for the hazard ratio (HR) along with an AB threshold. This dual rule addresses two goals: inclusiveness: not unfairly penalising experimental treatments from trials designed with adequate power targeting clinically meaningful relative benefit; and discernment: penalising trials designed to detect a small inconsequential benefit. Based on 50 000 simulations of plausible trial scenarios, the sensitivity and specificity of the LL95%CI rule and the ESMO-MCBS dual rule, the robustness of their characteristics for reasonable power and range of targeted and true HRs, are examined. The per cent acceptance of maximal preliminary grade is compared with other dual rules based on point estimate (PE) thresholds for RB. For particularly small or particularly large studies, the observed benefit needs to be relatively big for the ESMO-MCBS dual rule to be satisfied and the maximal grade awarded. Compared with approaches that evaluate RB using the PE thresholds, simulations demonstrate that the MCBS approach better exhibits the desired behaviour achieving the goals of both inclusiveness and discernment. RB assessment using the LL95%CI for HR rather than a PE threshold has two advantages: it diminishes the probability of excluding big benefit positive studies from achieving due credit and, when combined with the AB assessment, it increases the probability of downgrading a trial with a statistically significant but clinically insignificant observed benefit.

Detailed statistical assessment of the characteristics of the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) threshold rules

PubMed Central

Dafni, Urania; Karlis, Dimitris; Pedeli, Xanthi; Bogaerts, Jan; Pentheroudakis, George; Tabernero, Josep; Zielinski, Christoph C; Piccart, Martine J; de Vries, Elisabeth G E; Latino, Nicola Jane; Douillard, Jean-Yves; Cherny, Nathan I

2017-01-01

Background The European Society for Medical Oncology (ESMO) has developed the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS), a tool to assess the magnitude of clinical benefit from new cancer therapies. Grading is guided by a dual rule comparing the relative benefit (RB) and the absolute benefit (AB) achieved by the therapy to prespecified threshold values. The ESMO-MCBS v1.0 dual rule evaluates the RB of an experimental treatment based on the lower limit of the 95%CI (LL95%CI) for the hazard ratio (HR) along with an AB threshold. This dual rule addresses two goals: inclusiveness: not unfairly penalising experimental treatments from trials designed with adequate power targeting clinically meaningful relative benefit; and discernment: penalising trials designed to detect a small inconsequential benefit. Methods Based on 50 000 simulations of plausible trial scenarios, the sensitivity and specificity of the LL95%CI rule and the ESMO-MCBS dual rule, the robustness of their characteristics for reasonable power and range of targeted and true HRs, are examined. The per cent acceptance of maximal preliminary grade is compared with other dual rules based on point estimate (PE) thresholds for RB. Results For particularly small or particularly large studies, the observed benefit needs to be relatively big for the ESMO-MCBS dual rule to be satisfied and the maximal grade awarded. Compared with approaches that evaluate RB using the PE thresholds, simulations demonstrate that the MCBS approach better exhibits the desired behaviour achieving the goals of both inclusiveness and discernment. Conclusions RB assessment using the LL95%CI for HR rather than a PE threshold has two advantages: it diminishes the probability of excluding big benefit positive studies from achieving due credit and, when combined with the AB assessment, it increases the probability of downgrading a trial with a statistically significant but clinically insignificant observed benefit. PMID:29067214

Occurrence, leaching, and degradation of Cry1Ab protein from transgenic maize detritus in agricultural streams

DOE PAGES

Griffiths, Natalie A.; Tank, Jennifer L.; Royer, Todd V.; ...

2017-03-15

The insecticidal Cry1Ab protein expressed by transgenic (Bt) maize can enter adjacent water bodies via multiple pathways, but its fate in stream ecosystems is not as well studied as in terrestrial systems. In this study, we used a combination of field sampling and laboratory experiments to examine the occurrence, leaching, and degradation of soluble Cry1Ab protein derived from Bt maize in agricultural streams. We surveyed 11 agricultural streams in northwestern Indiana, USA, on 6 dates that encompassed the growing season, crop harvest, and snowmelt/spring flooding, and detected Cry1Ab protein in the water column and in flowing subsurface tile drains atmore » concentrations of 3–60 ng/L. In a series of laboratory experiments, submerged Bt maize leaves leached Cry1Ab into stream water with 1% of the protein remaining in leaves after 70 d. Laboratory experiments suggested that dissolved Cry1Ab protein degraded rapidly in microcosms containing water-column microorganisms, and light did not enhance breakdown by stimulating assimilatory uptake of the protein by autotrophs. Here, the common detection of Cry1Ab protein in streams sampled across an agricultural landscape, combined with laboratory studies showing rapid leaching and degradation, suggests that Cry1Ab may be pseudo-persistent at the watershed scale due to the multiple input pathways from the surrounding terrestrial environment.« less

Occurrence, leaching, and degradation of Cry1Ab protein from transgenic maize detritus in agricultural streams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Griffiths, Natalie A.; Tank, Jennifer L.; Royer, Todd V.

The insecticidal Cry1Ab protein expressed by transgenic (Bt) maize can enter adjacent water bodies via multiple pathways, but its fate in stream ecosystems is not as well studied as in terrestrial systems. In this study, we used a combination of field sampling and laboratory experiments to examine the occurrence, leaching, and degradation of soluble Cry1Ab protein derived from Bt maize in agricultural streams. We surveyed 11 agricultural streams in northwestern Indiana, USA, on 6 dates that encompassed the growing season, crop harvest, and snowmelt/spring flooding, and detected Cry1Ab protein in the water column and in flowing subsurface tile drains atmore » concentrations of 3–60 ng/L. In a series of laboratory experiments, submerged Bt maize leaves leached Cry1Ab into stream water with 1% of the protein remaining in leaves after 70 d. Laboratory experiments suggested that dissolved Cry1Ab protein degraded rapidly in microcosms containing water-column microorganisms, and light did not enhance breakdown by stimulating assimilatory uptake of the protein by autotrophs. Here, the common detection of Cry1Ab protein in streams sampled across an agricultural landscape, combined with laboratory studies showing rapid leaching and degradation, suggests that Cry1Ab may be pseudo-persistent at the watershed scale due to the multiple input pathways from the surrounding terrestrial environment.« less

Atomic Spectral Methods for Ab Initio Molecular Electronic Energy Surfaces: Transitioning From Small-Molecule to Biomolecular-Suitable Approaches.

PubMed

Mills, Jeffrey D; Ben-Nun, Michal; Rollin, Kyle; Bromley, Michael W J; Li, Jiabo; Hinde, Robert J; Winstead, Carl L; Sheehy, Jeffrey A; Boatz, Jerry A; Langhoff, Peter W

2016-08-25

Continuing attention has addressed incorportation of the electronically dynamical attributes of biomolecules in the largely static first-generation molecular-mechanical force fields commonly employed in molecular-dynamics simulations. We describe here a universal quantum-mechanical approach to calculations of the electronic energy surfaces of both small molecules and large aggregates on a common basis which can include such electronic attributes, and which also seems well-suited to adaptation in ab initio molecular-dynamics applications. In contrast to the more familiar orbital-product-based methodologies employed in traditional small-molecule computational quantum chemistry, the present approach is based on an "ex-post-facto" method in which Hamiltonian matrices are evaluated prior to wave function antisymmetrization, implemented here in the support of a Hilbert space of orthonormal products of many-electron atomic spectral eigenstates familiar from the van der Waals theory of long-range interactions. The general theory in its various forms incorporates the early semiempirical atoms- and diatomics-in-molecules approaches of Moffitt, Ellison, Tully, Kuntz, and others in a comprehensive mathematical setting, and generalizes the developments of Eisenschitz, London, Claverie, and others addressing electron permutation symmetry adaptation issues, completing these early attempts to treat van der Waals and chemical forces on a common basis. Exact expressions are obtained for molecular Hamiltonian matrices and for associated energy eigenvalues as sums of separate atomic and interaction-energy terms, similar in this respect to the forms of classical force fields. The latter representation is seen to also provide a long-missing general definition of the energies of individual atoms and of their interactions within molecules and matter free from subjective additional constraints. A computer code suite is described for calculations of the many-electron atomic eigenspectra and the pairwise-atomic Hamiltonian matrices required for practical applications. These matrices can be retained as functions of scalar atomic-pair separations and employed in assembling aggregate Hamiltonian matrices, with Wigner rotation matrices providing analytical representations of their angular degrees of freedom. In this way, ab initio potential energy surfaces are obtained in the complete absence of repeated evaluations and transformations of the one- and two-electron integrals at different molecular geometries required in most ab inito molecular calculations, with large Hamiltonian matrix assembly simplified and explicit diagonalizations avoided employing partitioning and Brillouin-Wigner or Rayleigh-Schrödinger perturbation theory. Illustrative applications of the important components of the formalism, selected aspects of the scaling of the approach, and aspects of "on-the-fly" interfaces with Monte Carlo and molecular-dynamics methods are described in anticipation of subsequent applications to biomolecules and other large aggregates.

Alloy-assisted deposition of three-dimensional arrays of atomic gold catalyst for crystal growth studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang, Yin; Jiang, Yuanwen; Cherukara, Mathew J.

Large-scale assembly of individual atoms over smooth surfaces is difficult to achieve. A configuration of an atom reservoir, in which individual atoms can be readily extracted, may successfully address this challenge. In this work, we demonstrate that a liquid gold-silicon alloy established in classical vapor-liquid-solid growth can deposit ordered and three-dimensional rings of isolated gold atoms over silicon nanowire sidewalls. Here, we perform ab initio molecular dynamics simulation and unveil a surprising single atomic gold-catalyzed chemical etching of silicon. Experimental verification of this catalytic process in silicon nanowires yields dopant-dependent, massive and ordered 3D grooves with spacing down to similarmore » to 5 nm. Finally, we use these grooves as self-labeled and ex situ markers to resolve several complex silicon growths, including the formation of nodes, kinks, scale-like interfaces, and curved backbones.« less

Alloy-assisted deposition of three-dimensional arrays of atomic gold catalyst for crystal growth studies

DOE PAGES

Fang, Yin; Jiang, Yuanwen; Cherukara, Mathew J.; ...

2017-12-08

Large-scale assembly of individual atoms over smooth surfaces is difficult to achieve. A configuration of an atom reservoir, in which individual atoms can be readily extracted, may successfully address this challenge. In this work, we demonstrate that a liquid gold-silicon alloy established in classical vapor-liquid-solid growth can deposit ordered and three-dimensional rings of isolated gold atoms over silicon nanowire sidewalls. Here, we perform ab initio molecular dynamics simulation and unveil a surprising single atomic gold-catalyzed chemical etching of silicon. Experimental verification of this catalytic process in silicon nanowires yields dopant-dependent, massive and ordered 3D grooves with spacing down to similarmore » to 5 nm. Finally, we use these grooves as self-labeled and ex situ markers to resolve several complex silicon growths, including the formation of nodes, kinks, scale-like interfaces, and curved backbones.« less

Optimal immunization cocktails can promote induction of broadly neutralizing Abs against highly mutable pathogens.

PubMed

Shaffer, J Scott; Moore, Penny L; Kardar, Mehran; Chakraborty, Arup K

2016-10-24

Strategies to elicit Abs that can neutralize diverse strains of a highly mutable pathogen are likely to result in a potent vaccine. Broadly neutralizing Abs (bnAbs) against HIV have been isolated from patients, proving that the human immune system can evolve them. Using computer simulations and theory, we study immunization with diverse mixtures of variant antigens (Ags). Our results show that particular choices for the number of variant Ags and the mutational distances separating them maximize the probability of inducing bnAbs. The variant Ags represent potentially conflicting selection forces that can frustrate the Darwinian evolutionary process of affinity maturation. An intermediate level of frustration maximizes the chance of evolving bnAbs. A simple model makes vivid the origin of this principle of optimal frustration. Our results, combined with past studies, suggest that an appropriately chosen permutation of immunization with an optimally designed mixture (using the principles that we describe) and sequential immunization with variant Ags that are separated by relatively large mutational distances may best promote the evolution of bnAbs.

Optimal immunization cocktails can promote induction of broadly neutralizing Abs against highly mutable pathogens

PubMed Central

Shaffer, J. Scott; Moore, Penny L.; Kardar, Mehran; Chakraborty, Arup K.

2016-01-01

Strategies to elicit Abs that can neutralize diverse strains of a highly mutable pathogen are likely to result in a potent vaccine. Broadly neutralizing Abs (bnAbs) against HIV have been isolated from patients, proving that the human immune system can evolve them. Using computer simulations and theory, we study immunization with diverse mixtures of variant antigens (Ags). Our results show that particular choices for the number of variant Ags and the mutational distances separating them maximize the probability of inducing bnAbs. The variant Ags represent potentially conflicting selection forces that can frustrate the Darwinian evolutionary process of affinity maturation. An intermediate level of frustration maximizes the chance of evolving bnAbs. A simple model makes vivid the origin of this principle of optimal frustration. Our results, combined with past studies, suggest that an appropriately chosen permutation of immunization with an optimally designed mixture (using the principles that we describe) and sequential immunization with variant Ags that are separated by relatively large mutational distances may best promote the evolution of bnAbs. PMID:27791170

Immunoglobulin Gene Insertions and Deletions in the Affinity Maturation of HIV-1 Broadly Reactive Neutralizing Antibodies

PubMed Central

Kepler, Thomas B.; Liao, Hua-Xin; Alam, S. Munir; Bhaskarabhatla, Rekha; Zhang, Ruijun; Stewart, Shelley; Anasti, Kara; Kelsoe, Garnett; Parks, Robert; Lloyd, Krissey E.; Stolarchuk, Christina; Pritchett, Jamie; Solomon, Erika; Friberg, Emma; Morris, Lynn; Karim, Salim S. Abdool; Cohen, Myron S.; Walter, Emmanuel; Moody, M. Anthony; Wu, Xueling; Altae-Tran, Han R.; Georgiev, Ivelin S.; Kwong, Peter D.; Boyd, Scott D.; Fire, Andrew Z.; Mascola, John R.; Haynes, Barton F.

2014-01-01

Summary Induction of HIV-1 broad neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development but has remained challenging partially due to unusual traits of bnAbs, including high somatic hypermutation (SHM) frequencies and in-frame insertions and deletions (indels). Here we examined the propensity and functional requirement for indels within HIV-1 bnAbs. High-throughput sequencing of the immunoglobulin (Ig) VHDJH genes in HIV-1 infected and uninfected individuals revealed that the indel frequency was elevated among HIV-1-infected subjects, with no unique properties attributable to bnAb-producing individuals. This increased indel occurrence depended only on the frequency of SHM point-mutations. Indel-encoded regions were generally proximal to antigen binding sites. Additionally, reconstruction of a HIV-1 CD4-binding site bnAb clonal lineage revealed that a large compound VHDJH indel was required for bnAb activity. Thus, vaccine development should focus on designing regimens targeted at sustained activation of bnAb lineages to achieve the required SHM and indel events. PMID:25211073

Fluorescence dye-based detection of mAb aggregates in CHO culture supernatants.

PubMed

Paul, Albert Jesuran; Schwab, Karen; Prokoph, Nina; Haas, Elena; Handrick, René; Hesse, Friedemann

2015-06-01

Product yields, efficacy, and safety of monoclonal antibodies (mAbs) are reduced by the formation of higher molecular weight aggregates during upstream processing. In-process characterization of mAb aggregate formation is a challenge since there is a lack of a fast detection method to identify mAb aggregates in cell culture. In this work, we present a rapid method to characterize mAb aggregate-containing Chinese hamster ovary (CHO) cell culture supernatants. The fluorescence dyes thioflavin T (ThT) and 4-4-bis-1-phenylamino-8-naphthalene sulfonate (Bis-ANS) enabled the detection of soluble as well as large mAb aggregates. Partial least square (PLS) regression models were used to evaluate the linearity of the dye-based mAb aggregate detection in buffer down to a mAb aggregate concentration of 2.4 μg mL(-1). Furthermore, mAb aggregates were detected in bioprocess medium using Bis-ANS and ThT. Dye binding to aggregates was stable for 60 min, making the method robust and reliable. Finally, the developed method using 10 μmol L(-1) Bis-ANS enabled discrimination between CHO cell culture supernatants containing different levels of mAb aggregates. The method can be adapted for high-throughput screening, e.g., to screen for cell culture conditions influencing mAb product quality, and hence can contribute to the improvement of production processes of biopharmaceuticals in mammalian cell culture.

Large-Scale Sentinel-1 Processing for Solid Earth Science and Urgent Response using Cloud Computing and Machine Learning

NASA Astrophysics Data System (ADS)

Hua, H.; Owen, S. E.; Yun, S. H.; Agram, P. S.; Manipon, G.; Starch, M.; Sacco, G. F.; Bue, B. D.; Dang, L. B.; Linick, J. P.; Malarout, N.; Rosen, P. A.; Fielding, E. J.; Lundgren, P.; Moore, A. W.; Liu, Z.; Farr, T.; Webb, F.; Simons, M.; Gurrola, E. M.

2017-12-01

With the increased availability of open SAR data (e.g. Sentinel-1 A/B), new challenges are being faced with processing and analyzing the voluminous SAR datasets to make geodetic measurements. Upcoming SAR missions such as NISAR are expected to generate close to 100TB per day. The Advanced Rapid Imaging and Analysis (ARIA) project can now generate geocoded unwrapped phase and coherence products from Sentinel-1 TOPS mode data in an automated fashion, using the ISCE software. This capability is currently being exercised on various study sites across the United States and around the globe, including Hawaii, Central California, Iceland and South America. The automated and large-scale SAR data processing and analysis capabilities use cloud computing techniques to speed the computations and provide scalable processing power and storage. Aspects such as how to processing these voluminous SLCs and interferograms at global scales, keeping up with the large daily SAR data volumes, and how to handle the voluminous data rates are being explored. Scene-partitioning approaches in the processing pipeline help in handling global-scale processing up to unwrapped interferograms with stitching done at a late stage. We have built an advanced science data system with rapid search functions to enable access to the derived data products. Rapid image processing of Sentinel-1 data to interferograms and time series is already being applied to natural hazards including earthquakes, floods, volcanic eruptions, and land subsidence due to fluid withdrawal. We will present the status of the ARIA science data system for generating science-ready data products and challenges that arise from being able to process SAR datasets to derived time series data products at large scales. For example, how do we perform large-scale data quality screening on interferograms? What approaches can be used to minimize compute, storage, and data movement costs for time series analysis in the cloud? We will also present some of our findings from applying machine learning and data analytics on the processed SAR data streams. We will also present lessons learned on how to ease the SAR community onto interfacing with these cloud-based SAR science data systems.

Energetic Consistency and Coupling of the Mean and Covariance Dynamics

NASA Technical Reports Server (NTRS)

Cohn, Stephen E.

2008-01-01

The dynamical state of the ocean and atmosphere is taken to be a large dimensional random vector in a range of large-scale computational applications, including data assimilation, ensemble prediction, sensitivity analysis, and predictability studies. In each of these applications, numerical evolution of the covariance matrix of the random state plays a central role, because this matrix is used to quantify uncertainty in the state of the dynamical system. Since atmospheric and ocean dynamics are nonlinear, there is no closed evolution equation for the covariance matrix, nor for the mean state. Therefore approximate evolution equations must be used. This article studies theoretical properties of the evolution equations for the mean state and covariance matrix that arise in the second-moment closure approximation (third- and higher-order moment discard). This approximation was introduced by EPSTEIN [1969] in an early effort to introduce a stochastic element into deterministic weather forecasting, and was studied further by FLEMING [1971a,b], EPSTEIN and PITCHER [1972], and PITCHER [1977], also in the context of atmospheric predictability. It has since fallen into disuse, with a simpler one being used in current large-scale applications. The theoretical results of this article make a case that this approximation should be reconsidered for use in large-scale applications, however, because the second moment closure equations possess a property of energetic consistency that the approximate equations now in common use do not possess. A number of properties of solutions of the second-moment closure equations that result from this energetic consistency will be established.

Entry into and Release of Solvents by Escherichia coli in an Organic-Aqueous Two-Liquid-Phase System and Substrate Specificity of the AcrAB-TolC Solvent-Extruding Pump

PubMed Central

Tsukagoshi, Norihiko; Aono, Rikizo

2000-01-01

Growth of Escherichia coli is inhibited upon exposure to a large volume of a harmful solvent, and there is an inverse correlation between the degree of inhibition and the log POW of the solvent, where POW is the partition coefficient measured for the partition equilibrium established between the n-octanol and water phases. The AcrAB-TolC efflux pump system is involved in maintaining intrinsic solvent resistance. We inspected the solvent resistance of ΔacrAB and/or ΔtolC mutants in the presence of a large volume of solvent. Both mutants were hypersensitive to weakly harmful solvents, such as nonane (log POW = 5.5). The ΔtolC mutant was more sensitive to nonane than the ΔacrAB mutant. The solvent entered the E. coli cells rapidly. Entry of solvents with a log POW higher than 4.4 was retarded in the parent cells, and the intracellular levels of these solvents were maintained at low levels. The ΔtolC mutant accumulated n-nonane or decane (log POW = 6.0) more abundantly than the parent or the ΔacrAB mutant. The AcrAB-TolC complex likely extrudes solvents with a log POW in the range of 3.4 to 6.0 through a first-order reaction. The most favorable substrates for the efflux system were considered to be octane, heptane, and n-hexane. PMID:10940021

Nano and Mesoscale Ion and Water Transport in Perfluorosulfonic AcidMembranes

DTIC Science & Technology

2017-10-01

Nano- and Mesoscale Ion and Water Transport in Perfluorosulfonic-Acid Membranes A. R. Crothers a,b , C. J. Radke a,b , A. Z. Weber a a...Berkeley, CA 94720, USA Water and aqueous cations transport along multiple length scales in perfluorosulfonic-acid membranes. Molecular interactions...as a function of hydration. A resistor network upscales the nanoscale properties to predict effective membrane ion and water transport and their

The relationship between agitation and impairments of orientation and memory during the PTA period after traumatic brain injury.

PubMed

McKay, Adam; Love, Jasmine; Trevena-Peters, Jessica; Gracey, Jacinta; Ponsford, Jennie

2018-06-03

Agitation is common during the post-traumatic amnesia (PTA) period after traumatic brain injury (TBI), although our knowledge of what causes or predicts agitation is limited. The current study aimed to examine the association of agitation in PTA with the concurrent impairments in orientation and memory while controlling for covariates of agitation. Participants were 125 patients in PTA following moderate to extremely severe TBI recruited from an inpatient brain injury rehabilitation service who were assessed throughout PTA on the Agitated Behavior Scale (ABS) and the Westmead PTA Scale (WPTAS). Agitation was observed in 42.4% of participants (ABS score > 21), with disinhibited behaviours (e.g., distractibility and impulsivity) most common. Multilevel modelling found daily ABS scores to be associated with daily scores on the WPTAS but in a non-linear pattern. Analysis of covariates found that shorter time post-admission, younger age, presence of infection and higher antipsychotic doses were associated with higher ABS scores. These results support a relationship between agitation and the concurrent cognitive impairment during PTA. While a causal link cannot yet be inferred, management strategies that can potentially interfere with cognition (e.g., sedating medications, environmental changes) should be used cautiously in case they exacerbate agitation.

Accurate double many-body expansion potential energy surface of HS2A2A‧) by scaling the external correlation

NASA Astrophysics Data System (ADS)

Lu-Lu, Zhang; Yu-Zhi, Song; Shou-Bao, Gao; Yuan, Zhang; Qing-Tian, Meng

2016-05-01

A globally accurate single-sheeted double many-body expansion potential energy surface is reported for the first excited state of HS2 by fitting the accurate ab initio energies, which are calculated at the multireference configuration interaction level with the aug-cc-pVQZ basis set. By using the double many-body expansion-scaled external correlation method, such calculated ab initio energies are then slightly corrected by scaling their dynamical correlation. A grid of 2767 ab initio energies is used in the least-square fitting procedure with the total root-mean square deviation being 1.406 kcal·mol-1. The topographical features of the HS2(A2A‧) global potential energy surface are examined in detail. The attributes of the stationary points are presented and compared with the corresponding ab initio results as well as experimental and other theoretical data, showing good agreement. The resulting potential energy surface of HS2(A2A‧) can be used as a building block for constructing the global potential energy surfaces of larger S/H molecular systems and recommended for dynamic studies on the title molecular system. Project supported by the National Natural Science Foundation of China (Grant No. 11304185), the Taishan Scholar Project of Shandong Province, China, the Shandong Provincial Natural Science Foundation, China (Grant No. ZR2014AM022), the Shandong Province Higher Educational Science and Technology Program, China (Grant No. J15LJ03), the China Postdoctoral Science Foundation (Grant No. 2014M561957), and the Post-doctoral Innovation Project of Shandong Province, China (Grant No. 201402013).

Characterization and Peripheral Blood Biomarker Assessment of Jo-1 Antibody-Positive Interstitial Lung Disease

PubMed Central

Richards, Thomas J.; Eggebeen, Aaron; Gibson, Kevin; Yousem, Samuel; Fuhrman, Carl; Gochuico, Bernadette R.; Fertig, Noreen; Oddis, Chester V.; Kaminski, Naftali; Rosas, Ivan O.; Ascherman, Dana P.

2009-01-01

Objectives Combining clinical, radiographic, functional, and serum protein biomarker assessment, this study defines the prevalence and clinical characteristics of ILD in a large cohort of patients possessing anti-Jo-1 antibodies. Methods Clinical records, pulmonary function testing, and imaging studies determined the existence of ILD in anti-Jo-1 antibody positive (anti-Jo-1 Ab+) individuals accumulated in the University of Pittsburgh Myositis Database from 1982–2007. Multiplex ELISA of serum inflammatory markers, cytokines, chemokines, and matrix metalloproteinases in different patient subgroups then permitted assessment of serum proteins associated with anti-Jo-1 Ab+ ILD. Results Among 90 anti-Jo-1 Ab+ individuals with sufficient clinical, radiographic, and/or pulmonary function data, 77 (86%) met criteria for ILD. While computerized tomography scans revealed a variety of patterns suggestive of underlying UIP or NSIP, review of histopathologic abnormalities in a subset (n=22) of individuals undergoing open lung biopsy demonstrated a preponderance of UIP and DAD. Multiplex ELISA yielded statistically significant associations between Jo-1 Ab+ ILD and elevated serum levels of CRP, CXCL9, and CXCL10 that distinguished this subgroup from IPF and anti-SRP Ab+ myositis. Recursive partitioning further demonstrated that combinations of these and other serum protein biomarkers can distinguish these subgroups with high sensitivity and specificity. Conclusion In this large cohort of anti-Jo-1 Ab+ individuals, the incidence of ILD approaches 90%. Multiplex ELISA demonstrates disease-specific associations between Jo-1 Ab+ ILD and serum levels of CRP as well as the IFN-γ-inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD. PMID:19565490

A BioDesign Approach to Obtain High Yields of Biosimilars by Anti-apoptotic Cell Engineering: a Case Study to Increase the Production Yield of Anti-TNF Alpha Producing Recombinant CHO Cells.

PubMed

Gulce Iz, Sultan; Inevi, Muge Anil; Metiner, Pelin Saglam; Tamis, Duygu Ayyildiz; Kisbet, Nazli

2018-01-01

Recent developments in medical biotechnology have facilitated to enhance the production of monoclonal antibodies (mAbs) and recombinant proteins in mammalian cells. Human mAbs for clinical applications have focused on three areas, particularly cancer, immunological disorders, and infectious diseases. Tumor necrosis factor alpha (TNF-α), which has both proinflammatory and immunoregulatory functions, is an important target in biopharmaceutical industry. In this study, a humanized anti-TNF-α mAb producing stable CHO cell line which produces a biosimilar of Humira (adalimumab) was used. Adalimumab is a fully human anti-TNF mAb among the top-selling mAb products in recent years as a biosimilar. Products from mammalian cell bioprocesses are a derivative of cell viability and metabolism, which is mainly disrupted by cell death in bioreactors. Thus, different strategies are used to increase the product yield. Suppression of apoptosis, also called anti-apoptotic cell engineering, is the most remarkable strategy to enhance lifetime of cells for a longer production period. In fact, using anti-apoptotic cell engineering as a BioDesign approach was inspired by nature; nature gives prolonged life span to some cells like stem cells, tumor cells, and memory B and T cells, and researchers have been using this strategy for different purposes. In this study, as a biomimicry approach, anti-apoptotic cell engineering was used to increase the anti-TNF-α mAb production from the humanized anti-TNF-α mAb producing stable CHO cell line by Bcl-xL anti-apoptotic protein. It was shown that transient transfection of CHO cells by the Bcl-xL anti-apoptotic protein expressing plasmid prolonged the cell survival rate and protected cells from apoptosis. The transient expression of Bcl-xL using CHO cells enhanced the anti-TNF-α production. The production of anti-TNF-α in CHO cells was increased up to 215 mg/L with an increase of 160% after cells were transfected with Bcl-xL expressing plasmid with polyethylenimine (PEI) reagent at the ratio of 1:6 (DNA:PEI). In conclusion, the anti-apoptotic efficacy of the Bcl-xL expressing plasmid in humanized anti-TNF-α MAb producing stable CHO cells is compatible with curative effect for high efficiency recombinant protein production. Thus, this model can be used for large-scale production of biosimilars through transient Bcl-xL gene expression as a cost-effective method.

Magnetic and Electrical Transport Properties of Dirac Compound BaMnSb2*

NASA Astrophysics Data System (ADS)

Huang, Silu; Kim, Jisun; Shelton, William. A.; Plummer, Ward; Jin, Rongying

BaMnSb2 is a layered compound containing Sb square nets that is theoretically predicted to host Dirac fermions. We have carried out experimental investigations on electrical transport and magnetic properties of BaMnSb2 single crystals. Both in-plane (ρab) and c-axis (ρc) resistivities show metallic behavior with a small bump in ρc located near 40 K, while there is large anisotropy ρc / ρab ( 100 at 300 K) that increases with decreasing temperature to 1500 at 2 K. Interestingly, Shubnikov-de Hass (SdH) oscillations are observed for both ρab and ρc over a wide temperature and magnetic field range. Quantitative analysis indicates that large amplitude SdH oscillations result from nearly massless Dirac Fermions. Furthermore, our magnetic measurements indicate an A-type antiferromagnetic magnetic ordering below 286 K where ferromagnetic ordering is observed in the ab plane with antiferromagnetic coupling along the c direction. These results indicate that BaMnSb2 is a 2D magnetic Dirac material. This work is supported by NSF through Grant Number DMR-1504226.

Results of investigations (OA20C) on an 0.015-scale configuration 140A/B space shuttle vehicle orbiter model (49-0) in the NASA/Langley Research Center Unitary Plan Wind Tunnel

NASA Technical Reports Server (NTRS)

Nichols, M. E.

1974-01-01

Data obtained from the wind tunnel tests of a scale model of the space shuttle orbiter configuration 140 A/B are presented. The test was conducted at Mach numbers of 2.5, 3.9, and 4.6 with Reynolds numbers from 1.25 million per foot to 5.0 million per foot. Various control surface settings were used ranging from an angle of attack range from minus 4 to plus 42 degrees at zero angle of yaw. Longitudinal stability and control characteristics of the space shuttle configuration were analyzed.

Hugoniot equation of state of Si-doped glow discharge polymer and scaling to other plastic ablators

NASA Astrophysics Data System (ADS)

Huser, G.; Ozaki, N.; Colin-Lalu, P.; Recoules, V.; Sano, T.; Sakawa, Y.; Miyanishi, K.; Kodama, R.

2018-05-01

Pressure, density, and temperature were measured along the principal Hugoniot of the Si-doped Glow Discharge Polymer used in Inertial Confinement Fusion (ICF) capsules up to 5 Mbar, covering conditions beyond the first shock in a full-scale Inertial Confinement Fusion (ICF) capsule. The experiments were performed using the GEKKOXII laser at the Institute of Laser Engineering at Osaka University in Japan. Results are in good agreement with predictions obtained from ab initio Hugoniot calculations, but softer than the quotidian equation of state average atom model. Ab initio calculations show that dissociation of carbon bonds need to be taken into account in order to explain Hugoniot compressibility.

Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease.

PubMed

Jurynczyk, Maciej; Probert, Fay; Yeo, Tianrong; Tackley, George; Claridge, Tim D W; Cavey, Ana; Woodhall, Mark R; Arora, Siddharth; Winkler, Torsten; Schiffer, Eric; Vincent, Angela; DeLuca, Gabriele; Sibson, Nicola R; Isabel Leite, M; Waters, Patrick; Anthony, Daniel C; Palace, Jacqueline

2017-12-06

The overlapping clinical features of relapsing remitting multiple sclerosis (RRMS), aquaporin-4 (AQP4)-antibody (Ab) neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease mean that detection of disease specific serum antibodies is the gold standard in diagnostics. However, antibody levels are not prognostic and may become undetectable after treatment or during remission. Therefore, there is still a need to discover antibody-independent biomarkers. We sought to discover whether plasma metabolic profiling could provide biomarkers of these three diseases and explore if the metabolic differences are independent of antibody titre. Plasma samples from 108 patients (34 RRMS, 54 AQP4-Ab NMOSD, and 20 MOG-Ab disease) were analysed by nuclear magnetic resonance spectroscopy followed by lipoprotein profiling. Orthogonal partial-least squares discriminatory analysis (OPLS-DA) was used to identify significant differences in the plasma metabolite concentrations and produce models (mathematical algorithms) capable of identifying these diseases. In all instances, the models were highly discriminatory, with a distinct metabolite pattern identified for each disease. In addition, OPLS-DA identified AQP4-Ab NMOSD patient samples with low/undetectable antibody levels with an accuracy of 92%. The AQP4-Ab NMOSD metabolic profile was characterised by decreased levels of scyllo-inositol and small high density lipoprotein particles along with an increase in large low density lipoprotein particles relative to both RRMS and MOG-Ab disease. RRMS plasma exhibited increased histidine and glucose, along with decreased lactate, alanine, and large high density lipoproteins while MOG-Ab disease plasma was defined by increases in formate and leucine coupled with decreased myo-inositol. Despite overlap in clinical measures in these three diseases, the distinct plasma metabolic patterns support their distinct serological profiles and confirm that these conditions are indeed different at a molecular level. The metabolites identified provide a molecular signature of each condition which is independent of antibody titre and EDSS, with potential use for disease monitoring and diagnosis.

Characterization of ammonia borane for chemical propulsion applications

NASA Astrophysics Data System (ADS)

Weismiller, Michael

Ammonia borane (NH3BH3; AB), which has a hydrogen content of 19.6% by weight, has been studied recently as a potential means of hydrogen storage for use in fuel cell applications. Its gaseous decomposition products have a very low molecular weight, which makes AB attractive in a propulsion application, since specific impulse is inversely related to the molecular weight of the products. AB also contains boron, which is a fuel of interest for solid propellants because of its high energy density per unit volume. Although boron particles are difficult to ignite due to their passivation layer, the boron molecularly bound in AB may react more readily. The concept of fuel depots in low-earth orbit has been proposed for use in deep space exploration. These would require propellants that are easily storable for long periods of time. AB is a solid at standard temperature and pressure and would not suffer from mass loss due to boil-off like cryogenic hydrogen. The goal of this work is to evaluate AB as a viable fuel in chemical propulsion. Many studies have examined AB decomposition at slow heating rates, but in a propellant, AB will experience rapid heating. Since heating rate has been shown to affect the thermolysis pathways in energetic materials, AB thermolysis was studied at high heating rates using molecular dynamics simulations with a ReaxFF reactive force field and experimental studies with a confined rapid thermolysis set-up using time-of-flight mass spectrometry and FTIR absorption spectroscopy diagnostics. Experimental results showed the formation of NH3, H2NBH2, H2, and at later times, c-(N3B3H6) in the gas phase, while polymer formation was observed in the condensed phase. Molecular dynamics simulations provided an atomistic description of the reactions which likely form these compounds. Another subject which required investigation was the reaction of AB in oxidizing environments, as there were no previous studies in the literature. Oxygen bond descriptions were added to the ReaxFF force field and molecular dynamics simulations were performed to identify important species and reactions in the AB oxidation. Since the thermodynamic properties of many of these species were unknown, density functional theory (DFT) calculations were performed in the Jaguear 7.8 program using the B3LYP functional and 6-311G**++ basis set to calculate enthalpy and entropy of formation, as well as specific heat as a function of temperature. These results were used to create a gas-phase chemical kinetic mechanism for AB combustion. New elementary reactions (57) were combined with those found in the literature for ammonia and boron oxidation, to form a mechanism of 201 reversible reactions. Results from a simple homogenous, constant pressure and energy calculation are presented in this work. The results show that H2NBH2 can be dehydrogenated via radical attack when temperatures are too low to overcome the hydrogen elimination barrier and pressures are low enough to allow sufficient radicals to form. Molecular dynamics calculations require very high pressures to facilitate reactions over a short simulation time, and show the formation of heavy B/N/H/O molecules, such as HNBOH and H2NB(OH)2. On the other hand, the chemical kinetics calculations at 1 atm show that if the HNBO molecule is further oxidized, the products will likely fission with B-N bond cleavage. The final objective towards the research goal was to study how AB can be effectively integrated into a propulsion application. AB was added to a paraffin wax binder to form a heterogeneous solid fuel matrix. Opposed-flow burner experiments were performed where a flow of gaseous oxygen was impinged on the solid fuel surface and regression rates were measured. Regression rates were shown to increase with small additions of AB, but the condensed phase product build-up at higher AB concentrations limited the solid fuel regression. Solid fuel grains with various amounts of AB were manufactured and tested in a lab scale hybrid rocket engine, where performance parameters such as thrust, chamber pressure, specific impulse (Isp) and characteristic exhaust velocity (C*), were measured. AB addition was shown to increase I sp and C*, but large additions were shown to reduce the overall thrust due to the hindrance of the solid fuel regression.

The Waterfall Model in Large-Scale Development

NASA Astrophysics Data System (ADS)

Petersen, Kai; Wohlin, Claes; Baca, Dejan

Waterfall development is still a widely used way of working in software development companies. Many problems have been reported related to the model. Commonly accepted problems are for example to cope with change and that defects all too often are detected too late in the software development process. However, many of the problems mentioned in literature are based on beliefs and experiences, and not on empirical evidence. To address this research gap, we compare the problems in literature with the results of a case study at Ericsson AB in Sweden, investigating issues in the waterfall model. The case study aims at validating or contradicting the beliefs of what the problems are in waterfall development through empirical research.

Recruiting and retaining youth and young adults: challenges and opportunities in survey research for tobacco control.

PubMed

Cantrell, Jennifer; Hair, Elizabeth C; Smith, Alexandria; Bennett, Morgane; Rath, Jessica Miller; Thomas, Randall K; Fahimi, Mansour; Dennis, J Michael; Vallone, Donna

2018-03-01

Evaluation studies of population-based tobacco control interventions often rely on large-scale survey data from numerous respondents across many geographic areas to provide evidence of their effectiveness. Significant challenges for survey research have emerged with the evolving communications landscape, particularly for surveying hard-to-reach populations such as youth and young adults. This study combines the comprehensive coverage of an address-based sampling (ABS) frame with the timeliness of online data collection to develop a nationally representative longitudinal cohort of young people aged 15-21. We constructed an ABS frame, partially supplemented with auxiliary data, to recruit this hard-to-reach sample. Branded and tested mail-based recruitment materials were designed to bring respondents online for screening, consent and surveying. Once enrolled, respondents completed online surveys every 6 months via computer, tablet or smartphone. Numerous strategies were utilized to enhance retention and representativeness RESULTS: Results detail sample performance, representativeness and retention rates as well as device utilization trends for survey completion among youth and young adult respondents. Panel development efforts resulted in a large, nationally representative sample with high retention rates. This study is among the first to employ this hybrid ABS-to-online methodology to recruit and retain youth and young adults in a probability-based online cohort panel. The approach is particularly valuable for conducting research among younger populations as it capitalizes on their increasing access to and comfort with digital communication. We discuss challenges and opportunities of panel recruitment and retention methods in an effort to provide valuable information for tobacco control researchers seeking to obtain representative, population-based samples of youth and young adults in the U.S. as well as across the globe. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Selective sequential separation of ABS/HIPS and PVC from automobile and electronic waste shredder residue by hybrid nano-Fe/Ca/CaO assisted ozonisation process.

PubMed

Mallampati, Srinivasa Reddy; Lee, Byoung Ho; Mitoma, Yoshiharu; Simion, Cristian

2017-02-01

The separation of plastics containing brominated flame retardants (BFR) like (acrylonitrile-butadiene-styrene (ABS), high-impact polystyrene (HIPS), and polyvinyl chloride (PVC)) from automobile and electronic waste shredder residue (ASR/ESR) are a major concern for thermal recycling. In laboratory scale tests using a hybrid nano-Fe/Ca/CaO assisted ozonation treatment has been found to selectively hydrophilize the surface of ABS/HIPS and PVC plastics, enhancing ABS wettability and thereby promoting its separation from ASR/ESR by means of froth flotation. The water contact angles, of ABS/HIPS and PVC decreased, about 18.7°, 18.3°, and 17.9° in ASR and about 21.2°, 20.7°, and 20.0° in ESR respectively. SEM-EDS, FT-IR, and XPS analyses demonstrated a marked decrease in [Cl] and a significant increase in the number of hydrophilic groups, such as CO, CO, and (CO)O, on the PVC or ABS surface. Under froth flotation conditions at 50rpm, about 99.1% of combined fraction of ABS/HIPS in ASR samples and 99.6% of ABS/HIPS in ESR samples were separated as settled fraction. After separation, the purity of the recovered combined ABS/HIPS fraction was 96.5% and 97.6% in ASR and ESR samples respectively. Furthermore, at 150rpm a 100% PVC separation in the settled fraction, with 98% and 99% purity in ASR and ESR plastics, respectively. Total recovery of non-ABS/HIPS and PVC plastics reached nearly 100% in the floating fraction. Further, this process improved the quality of recycled ASR/ESR plastics by removing surface contaminants or impurities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Asbestos bodies in bronchoalveolar lavage in the 21st century: a time-trend analysis in a clinical population.

PubMed

Nuyts, Valerie; Vanhooren, Hadewijch; Begyn, Sarah; Nackaerts, Kristiaan; Nemery, Benoit

2017-01-01

Asbestos bodies (AB) in bronchoalveolar lavage (BAL) can be detected by light microscopy and their concentration is indicative of past cumulative asbestos exposure. We assessed clinical and exposure characteristics, as well as possible time trends, among patients in whom AB had been quantified in BAL. BAL samples obtained from 578 participants between January 1997 and December 2014 were available for analysis. The processing of samples and the microscopic analysis were performed by a single expert and 76% of samples came from a single tertiary care hospital, allowing clinical and exposure data to be extracted from patient files. The study population (95% males) had a mean age of 62.5 (±12.4) years. AB were detected in 55.2% of the samples, giving a median concentration of 0.5 AB/mL (95th centile: 23.6 AB/mL; highest value: 164.5 AB/mL). The AB concentration exceeded 1 AB/mL in 39.4% and 5 AB/mL in 17.8%. A significant decrease from a geometric mean of 0.93 AB/mL in 1997 to 0.2 AB/mL in 2014 was apparent. High AB concentrations generally corresponded with occupations with (presumed) high asbestos exposure. AB concentrations were higher among patients with asbestosis and pleural plaques, when compared with other disease groups. Nevertheless, a substantial proportion of participants with likely exposure to asbestos did not exhibit high AB counts. This retrospective study of a large clinical population supports the value of counting AB in BAL as a complementary approach to assess past exposure to asbestos. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Pressure effect in cuprates - manifestation of Le Chatelier's principle

NASA Astrophysics Data System (ADS)

Kallio, A.; Bräysy, V.; Hissa, J.

We show that the pressure dependence of Tc, the Hall coefficient scaling, resistivities etc. can be explained by the chemical equilibrium of bosons and their decay products the fermions applying essentially the classical theory. Above a temperature TBL the bosons form a lattice, which causes diffusion term in τab-1. Treatment of equilibrium in a magnetic field explains the dependence of quantities like the penetration depth λab uponm the field.

RVMAB: Using the Relevance Vector Machine Model Combined with Average Blocks to Predict the Interactions of Proteins from Protein Sequences.

PubMed

An, Ji-Yong; You, Zhu-Hong; Meng, Fan-Rong; Xu, Shu-Juan; Wang, Yin

2016-05-18

Protein-Protein Interactions (PPIs) play essential roles in most cellular processes. Knowledge of PPIs is becoming increasingly more important, which has prompted the development of technologies that are capable of discovering large-scale PPIs. Although many high-throughput biological technologies have been proposed to detect PPIs, there are unavoidable shortcomings, including cost, time intensity, and inherently high false positive and false negative rates. For the sake of these reasons, in silico methods are attracting much attention due to their good performances in predicting PPIs. In this paper, we propose a novel computational method known as RVM-AB that combines the Relevance Vector Machine (RVM) model and Average Blocks (AB) to predict PPIs from protein sequences. The main improvements are the results of representing protein sequences using the AB feature representation on a Position Specific Scoring Matrix (PSSM), reducing the influence of noise using a Principal Component Analysis (PCA), and using a Relevance Vector Machine (RVM) based classifier. We performed five-fold cross-validation experiments on yeast and Helicobacter pylori datasets, and achieved very high accuracies of 92.98% and 95.58% respectively, which is significantly better than previous works. In addition, we also obtained good prediction accuracies of 88.31%, 89.46%, 91.08%, 91.55%, and 94.81% on other five independent datasets C. elegans, M. musculus, H. sapiens, H. pylori, and E. coli for cross-species prediction. To further evaluate the proposed method, we compare it with the state-of-the-art support vector machine (SVM) classifier on the yeast dataset. The experimental results demonstrate that our RVM-AB method is obviously better than the SVM-based method. The promising experimental results show the efficiency and simplicity of the proposed method, which can be an automatic decision support tool. To facilitate extensive studies for future proteomics research, we developed a freely available web server called RVMAB-PPI in Hypertext Preprocessor (PHP) for predicting PPIs. The web server including source code and the datasets are available at http://219.219.62.123:8888/ppi_ab/.

Anti-Ebola therapies based on monoclonal antibodies: Current state and challenges ahead

PubMed Central

González-González, E; Alvarez, MM; Márquez-Ipiña, AR; Santiago, G Trujillo-de; Rodríguez-Martínez, LM; Annabi, N; Khademhosseini, A

2017-01-01

The 2014 Ebola outbreak, the largest recorded, took us largely unprepared, with no available vaccine or specific treatment. In this context, the World Health Organization (WHO) declared that the humanitarian use of experimental therapies against Ebola Virus (EBOV) is ethical. In particular, an experimental treatment consisting of a cocktail of three monoclonal antibodies (mAbs) produced in tobacco plants and specifically directed to the Ebola virus glycoprotein (GP) was tested in humans, apparently with good results. Several mAbs with high affinity to the GP have been described. This review discusses our current knowledge on this topic. Particular emphasis is devoted to those mAbs that have been assayed in animal models or humans as possible therapies against Ebola. Engineering aspects and challenges for the production of anti-Ebola mAbs are also briefly discussed; current platforms for the design and production of full-length mAbs are cumbersome and costly. PMID:26611830

Anti-Ebola therapies based on monoclonal antibodies: current state and challenges ahead.

PubMed

González-González, Everardo; Alvarez, Mario Moisés; Márquez-Ipiña, Alan Roberto; Trujillo-de Santiago, Grissel; Rodríguez-Martínez, Luis Mario; Annabi, Nasim; Khademhosseini, Ali

2017-02-01

The 2014 Ebola outbreak, the largest recorded, took us largely unprepared, with no available vaccine or specific treatment. In this context, the World Health Organization declared that the humanitarian use of experimental therapies against Ebola Virus (EBOV) is ethical. In particular, an experimental treatment consisting of a cocktail of three monoclonal antibodies (mAbs) produced in tobacco plants and specifically directed to the EBOV glycoprotein (GP) was tested in humans, apparently with good results. Several mAbs with high affinity to the GP have been described. This review discusses our current knowledge on this topic. Particular emphasis is devoted to those mAbs that have been assayed in animal models or humans as possible therapies against Ebola. Engineering aspects and challenges for the production of anti-Ebola mAbs are also briefly discussed; current platforms for the design and production of full-length mAbs are cumbersome and costly.

miRNAFold: a web server for fast miRNA precursor prediction in genomes.

PubMed

Tav, Christophe; Tempel, Sébastien; Poligny, Laurent; Tahi, Fariza

2016-07-08

Computational methods are required for prediction of non-coding RNAs (ncRNAs), which are involved in many biological processes, especially at post-transcriptional level. Among these ncRNAs, miRNAs have been largely studied and biologists need efficient and fast tools for their identification. In particular, ab initio methods are usually required when predicting novel miRNAs. Here we present a web server dedicated for miRNA precursors identification at a large scale in genomes. It is based on an algorithm called miRNAFold that allows predicting miRNA hairpin structures quickly with high sensitivity. miRNAFold is implemented as a web server with an intuitive and user-friendly interface, as well as a standalone version. The web server is freely available at: http://EvryRNA.ibisc.univ-evry.fr/miRNAFold. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Vibrational spectra and ab initio analysis of tert-butyl, trimethylsilyl, and trimethylgermyl derivatives of 3,3-dimethyl cyclopropene V. 3,3-Dimethyl-1-(trimethylgermyl)cyclopropene

NASA Astrophysics Data System (ADS)

De Maré, G. R.; Panchenko, Yu. N.; Abramenkov, A. V.; Baird, M. S.; Tverezovsky, V. V.; Nizovtsev, A. V.; Bolesov, I. G.

2004-02-01

3,3-Dimethyl-1-(trimethylgermyl)cyclopropene ( I) was synthesised using a standard procedure. The IR and Raman spectra of I in the liquid phase were measured. The molecular geometry of I was optimised completely at the HF/6-31G* level. The HF/6-31G*//HF/6-31G* force field was calculated and scaled using the set of scale factors transferred from those determined previously for scaling the theoretical force fields of 3,3-dimethylbutene-1 and 1-methyl-, 1,2-dimethyl-, and 3,3-dimethylcyclopropene. The assignments of the observed vibrational bands were performed using the theoretical frequencies calculated from the scaled HF/6-31G*//HF/6-31G* force field and the ab initio values of the IR intensities, Raman cross-sections and depolarisation ratios. The theoretical spectra are given. The completely optimised structural parameters of I and its vibrational frequencies are compared with corresponding data of related molecules.

Black Carbon Absorption at the Global Scale Is Affected by Particle-Scale Diversity in Composition

NASA Technical Reports Server (NTRS)

Fierce, Laura; Bond, Tami C.; Bauer, Susanne E.; Mena, Francisco; Riemer, Nicole

2016-01-01

Atmospheric black carbon (BC) exerts a strong, but uncertain, warming effect on the climate. BC that is coated with non-absorbing material absorbs more strongly than the same amount of BC in an uncoated particle, but the magnitude of this absorption enhancement (E(sub abs)) is not well constrained. Modelling studies and laboratory measurements have found stronger absorption enhancement than has been observed in the atmosphere. Here, using a particle-resolved aerosol model to simulate diverse BC populations, we show that absorption is overestimated by as much as a factor of two if diversity is neglected and population-averaged composition is assumed across all BC-containing particles. If, instead, composition diversity is resolved, we find E(sub abs) = 1 - 1.5 at low relative humidity, consistent with ambient observations. This study offers not only an explanation for the discrepancy between modelled and observed absorption enhancement, but also demonstrates how particle-scale simulations can be used to develop relationships for global-scale models.

In Situ Time Constant and Optical Efficiency Measurements of TRUCE Pixels in the Atacama B-Mode Search

NASA Astrophysics Data System (ADS)

Simon, S. M.; Appel, J. W.; Cho, H. M.; Essinger-Hileman, T.; Irwin, K. D.; Kusaka, A.; Niemack, M. D.; Nolta, M. R.; Page, L. A.; Parker, L. P.; Raghunathan, S.; Sievers, J. L.; Staggs, S. T.; Visnjic, K.

2014-09-01

The Atacama B-mode Search (ABS) instrument, which began observation in February of 2012, is a crossed-Dragone telescope located at an elevation of 5,100 m in the Atacama Desert in Chile. The primary scientific goal of ABS is to measure the B-mode polarization spectrum of the Cosmic Microwave Background from multipole moments of about 50 to 500 (angular scales from to ), a range that includes the primordial B-mode peak from inflationary gravitational waves. The ABS focal plane array consists of 240 pixels designed for observation at 145 GHz by the TRUCE collaboration. Each pixel has its own individual, single-moded feedhorn and contains two transition-edge sensor bolometers coupled to orthogonal polarizations that are read out using time domain multiplexing. We will report on the current status of ABS and discuss the time constants and optical efficiencies of the TRUCE detectors in the field.

J-type Carbon Stars: A Dominant Source of 14 N-rich Presolar SiC Grains of Type AB

DOE PAGES

Liu, Nan; Stephan, Thomas; Boehnke, Patrick; ...

2017-07-21

Here, we report Mo isotopic data of 27 new presolar SiC grains, including 12 14N-rich AB ( 14N/ 15N > 440, AB2) and 15 mainstream (MS) grains, and their correlated Sr and Ba isotope ratios when available. Direct comparison of the data for the MS grains, which came from low-mass asymptotic giant branch (AGB) stars with large s-process isotope enhancements, with the AB2 grain data demonstrates that AB2 grains show near-solar isotopic compositions and lack s-process enhancements. The near-normal Sr, Mo, and Ba isotopic compositions of AB2 grains clearly exclude born-again AGB stars, where the intermediate neutron-capture process (i-process) takesmore » place, as their stellar source. On the other hand, low-mass CO novae and early R- and J-type carbon stars show 13C and 14N excesses but no s-process enhancements and are thus potential stellar sources of AB2 grains. And because both early R-type carbon stars and CO novae are rare objects, the abundant J-type carbon stars (10%–15% of all carbon stars) are thus likely to be a dominant source of AB2 grains.« less

J-type Carbon Stars: A Dominant Source of {sup 14}N-rich Presolar SiC Grains of Type AB

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Nan; Nittler, Larry R.; Alexander, Conel M. O’D.

We report Mo isotopic data of 27 new presolar SiC grains, including 12 {sup 14}N-rich AB ({sup 14}N/{sup 15}N > 440, AB2) and 15 mainstream (MS) grains, and their correlated Sr and Ba isotope ratios when available. Direct comparison of the data for the MS grains, which came from low-mass asymptotic giant branch (AGB) stars with large s -process isotope enhancements, with the AB2 grain data demonstrates that AB2 grains show near-solar isotopic compositions and lack s -process enhancements. The near-normal Sr, Mo, and Ba isotopic compositions of AB2 grains clearly exclude born-again AGB stars, where the intermediate neutron-capture processmore » ( i -process) takes place, as their stellar source. On the other hand, low-mass CO novae and early R- and J-type carbon stars show {sup 13}C and {sup 14}N excesses but no s -process enhancements and are thus potential stellar sources of AB2 grains. Because both early R-type carbon stars and CO novae are rare objects, the abundant J-type carbon stars (10%–15% of all carbon stars) are thus likely to be a dominant source of AB2 grains.« less

J-type Carbon Stars: A Dominant Source of 14 N-rich Presolar SiC Grains of Type AB

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Nan; Stephan, Thomas; Boehnke, Patrick

Here, we report Mo isotopic data of 27 new presolar SiC grains, including 12 14N-rich AB ( 14N/ 15N > 440, AB2) and 15 mainstream (MS) grains, and their correlated Sr and Ba isotope ratios when available. Direct comparison of the data for the MS grains, which came from low-mass asymptotic giant branch (AGB) stars with large s-process isotope enhancements, with the AB2 grain data demonstrates that AB2 grains show near-solar isotopic compositions and lack s-process enhancements. The near-normal Sr, Mo, and Ba isotopic compositions of AB2 grains clearly exclude born-again AGB stars, where the intermediate neutron-capture process (i-process) takesmore » place, as their stellar source. On the other hand, low-mass CO novae and early R- and J-type carbon stars show 13C and 14N excesses but no s-process enhancements and are thus potential stellar sources of AB2 grains. And because both early R-type carbon stars and CO novae are rare objects, the abundant J-type carbon stars (10%–15% of all carbon stars) are thus likely to be a dominant source of AB2 grains.« less

J-type Carbon Stars: A Dominant Source of 14 N-rich Presolar SiC Grains of Type AB

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Nan; Stephan, Thomas; Boehnke, Patrick

We report Mo isotopic data of 27 new presolar SiC grains, including 12 N-14-rich AB (N-14/N-15 > 440, AB2) and 15 mainstream (MS) grains, and their correlated Sr and Ba isotope ratios when available. Direct comparison of the data for the MS grains, which came from low-mass asymptotic giant branch (AGB) stars with large s-process isotope enhancements, with the AB2 grain data demonstrates that AB2 grains show near-solar isotopic compositions and lack s-process enhancements. The near-normal Sr, Mo, and Ba isotopic compositions of AB2 grains clearly exclude born-again AGB stars, where the intermediate neutron-capture process (i-process) takes place, as theirmore » stellar source. On the other hand, low-mass CO novae and early R-and J-type carbon stars show C-13 and N-14 excesses but no s-process enhancements and are thus potential stellar sources of AB2 grains. Because both early R-type carbon stars and CO novae are rare objects, the abundant J-type carbon stars (10%-15% of all carbon stars) are thus likely to be a dominant source of AB2 grains.« less

AB INITIO Molecular Dynamics Simulations of Water Under Static and Shock Compressed Conditions

NASA Astrophysics Data System (ADS)

Goldman, Nir; Fried, Laurence E.; Mundy, Christopher J.; Kuo, I.-F. William; Curioni, Alessandro; Reed, Evan J.

2007-12-01

We report herein a series of ab initio simulations of water under both static and shocked conditions. We have calculated the coherent x-ray scattering intensity of several phases of water under high pressure, using ab initio Density Functional Theory (DFT). We provide new atomic scattering form factors for water at extreme conditions, which take into account frequently neglected changes in ionic charge and electron delocalization. We have also simulated liquid water undergoing shock loading of velocities from 5-11 km/s using the Multi-Scale Shock Technique (MSST). We show that Density Functional Theory (DFT) molecular dynamics results compare extremely well to experiments on the water shock Hugoniot.

Spectroscopic evidence supporting the gravitational lens hypothesis for 1635+267 A,B

NASA Technical Reports Server (NTRS)

Turner, Edwin L.; Hillenbrand, Lynne A.; Schneider, Donald P.; Hewitt, Jacqueline N.; Burke, Bernard F.

1988-01-01

The gravitational lens hypothesis is tested for 1613+267 A,B by comparing the detailed line widths and shapes of the 2799-A Mg II and semiforbidden 1909-A C-III lines in each component. Following subtraction of an interpolating polynomial fit to the continua and the determination of a single optimum scaling factor (an amplification ratio of 2.83), reasonable agreement between the profiles of both lines in the two composites is obtained. Comparison of these lines to those in an unrelated quasar with a similar redshift and apparent magnitude does not produce a good match. It is suggested that the observed match in the 1635+267 A,B spectra arises from gravitational lensing.

Convergence acceleration of molecular dynamics methods for shocked materials using velocity scaling

NASA Astrophysics Data System (ADS)

Taylor, DeCarlos E.

2017-03-01

In this work, a convergence acceleration method applicable to extended system molecular dynamics techniques for shock simulations of materials is presented. The method uses velocity scaling to reduce the instantaneous value of the Rankine-Hugoniot conservation of energy constraint used in extended system molecular dynamics methods to more rapidly drive the system towards a converged Hugoniot state. When used in conjunction with the constant stress Hugoniostat method, the velocity scaled trajectories show faster convergence to the final Hugoniot state with little difference observed in the converged Hugoniot energy, pressure, volume and temperature. A derivation of the scale factor is presented and the performance of the technique is demonstrated using the boron carbide armour ceramic as a test material. It is shown that simulation of boron carbide Hugoniot states, from 5 to 20 GPa, using both a classical Tersoff potential and an ab initio density functional, are more rapidly convergent when the velocity scaling algorithm is applied. The accelerated convergence afforded by the current algorithm enables more rapid determination of Hugoniot states thus reducing the computational demand of such studies when using expensive ab initio or classical potentials.

Development of an audio-based virtual gaming environment to assist with navigation skills in the blind.

PubMed

Connors, Erin C; Yazzolino, Lindsay A; Sánchez, Jaime; Merabet, Lotfi B

2013-03-27

Audio-based Environment Simulator (AbES) is virtual environment software designed to improve real world navigation skills in the blind. Using only audio based cues and set within the context of a video game metaphor, users gather relevant spatial information regarding a building's layout. This allows the user to develop an accurate spatial cognitive map of a large-scale three-dimensional space that can be manipulated for the purposes of a real indoor navigation task. After game play, participants are then assessed on their ability to navigate within the target physical building represented in the game. Preliminary results suggest that early blind users were able to acquire relevant information regarding the spatial layout of a previously unfamiliar building as indexed by their performance on a series of navigation tasks. These tasks included path finding through the virtual and physical building, as well as a series of drop off tasks. We find that the immersive and highly interactive nature of the AbES software appears to greatly engage the blind user to actively explore the virtual environment. Applications of this approach may extend to larger populations of visually impaired individuals.

Accuracy and Transferability of Ab Initio Electronic Band Structure Calculations for Doped BiFeO3

NASA Astrophysics Data System (ADS)

Gebhardt, Julian; Rappe, Andrew M.

2017-11-01

BiFeO3 is a multiferroic material and, therefore, highly interesting with respect to future oxide electronics. In order to realize such devices, pn junctions need to be fabricated, which are currently impeded by the lack of successful p-type doping in this material. In order to guide the numerous research efforts in this field, we recently finished a comprehensive computational study, investigating the influence of many dopants onto the electronic structure of BiFeO3. In order to allow for this large scale ab initio study, the computational setup had to be accurate and efficient. Here we discuss the details of this assessment, showing that standard density-functional theory (DFT) yields good structural properties. The obtained electronic structure, however, suffers from well-known shortcomings. By comparing the conventional DFT results for alkali and alkaline-earth metal doping with more accurate hybrid-DFT calculations, we show that, in this case, the problems of standard DFT go beyond a simple systematic error. Conventional DFT shows bad transferability and the more reliable hybrid-DFT has to be chosen for a qualitatively correct prediction of doping induced changes in the electronic structure of BiFeO3.

A GENERALIZED TWO-COMPONENT MODEL OF SOLAR WIND TURBULENCE AND AB INITIO DIFFUSION MEAN-FREE PATHS AND DRIFT LENGTHSCALES OF COSMIC RAYS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiengarten, T.; Fichtner, H.; Kleimann, J.

2016-12-10

We extend a two-component model for the evolution of fluctuations in the solar wind plasma so that it is fully three-dimensional (3D) and also coupled self-consistently to the large-scale magnetohydrodynamic equations describing the background solar wind. The two classes of fluctuations considered are a high-frequency parallel-propagating wave-like piece and a low-frequency quasi-two-dimensional component. For both components, the nonlinear dynamics is dominanted by quasi-perpendicular spectral cascades of energy. Driving of the fluctuations by, for example, velocity shear and pickup ions is included. Numerical solutions to the new model are obtained using the Cronos framework, and validated against previous simpler models. Comparing results frommore » the new model with spacecraft measurements, we find improved agreement relative to earlier models that employ prescribed background solar wind fields. Finally, the new results for the wave-like and quasi-two-dimensional fluctuations are used to calculate ab initio diffusion mean-free paths and drift lengthscales for the transport of cosmic rays in the turbulent solar wind.« less

A Simplified Ab Initio Cosmic-ray Modulation Model with Simulated Time Dependence and Predictive Capability

NASA Astrophysics Data System (ADS)

Moloto, K. D.; Engelbrecht, N. E.; Burger, R. A.

2018-06-01

A simplified ab initio approach is followed to model cosmic-ray proton modulation, using a steady-state three-dimensional stochastic solver of the Parker transport equation that simulates some effects of time dependence. Standard diffusion coefficients based on Quasilinear Theory and Nonlinear Guiding Center Theory are employed. The spatial and temporal dependences of the various turbulence quantities required as inputs for the diffusion, as well as the turbulence-reduced drift coefficients, follow from parametric fits to results from a turbulence transport model as well as from spacecraft observations of these turbulence quantities. Effective values are used for the solar wind speed, magnetic field magnitude, and tilt angle in the modulation model to simulate temporal effects due to changes in the large-scale heliospheric plasma. The unusually high cosmic-ray intensities observed during the 2009 solar minimum follow naturally from the current model for most of the energies considered. This demonstrates that changes in turbulence contribute significantly to the high intensities during that solar minimum. We also discuss and illustrate how this model can be used to predict future cosmic-ray intensities, and comment on the reliability of such predictions.

Evaluation of a fully automated treponemal test and comparison with conventional VDRL and FTA-ABS tests.

PubMed

Park, Yongjung; Park, Younhee; Joo, Shin Young; Park, Myoung Hee; Kim, Hyon-Suk

2011-11-01

We evaluated analytic performances of an automated treponemal test and compared this test with the Venereal Disease Research Laboratory test (VDRL) and fluorescent treponemal antibody absorption test (FTA-ABS). Precision performance of the Architect Syphilis TP assay (TP; Abbott Japan, Tokyo, Japan) was assessed, and 150 serum samples were assayed with the TP before and after heat inactivation to estimate the effect of heat inactivation. A total of 616 specimens were tested with the FTA-ABS and TP, and 400 were examined with the VDRL. The TP showed good precision performance with total imprecision of less than a 10% coefficient of variation. An excellent linear relationship between results before and after heat inactivation was observed (R(2) = 0.9961). The FTA-ABS and TP agreed well with a κ coefficient of 0.981. The concordance rate between the FTA-ABS and TP was the highest (99.0%), followed by the rates between FTA-ABS and VDRL (85.0%) and between TP and VDRL (83.8%). The automated TP assay may be adequate for screening for syphilis in a large volume of samples and can be an alternative to FTA-ABS.

The FhaB/FhaC two-partner secretion system is involved in adhesion of Acinetobacter baumannii AbH12O-A2 strain

PubMed Central

Pérez, A.; Merino, M.; Rumbo-Feal, S.; Álvarez-Fraga, L.; Vallejo, J. A.; Beceiro, A.; Ohneck, E. J.; Mateos, J.; Fernández-Puente, P.; Actis, L. A.; Poza, M.; Bou, G.

2017-01-01

ABSTRACT Acinetobacter baumannii is a hospital-acquired pathogen that shows an extraordinary capacity to stay in the hospital environment. Adherence of the bacteria to eukaryotic cells or to abiotic surfaces is the first step for establishing an infection. The A. baumannii strain AbH12O-A2 showed an exceptional ability to adhere to A549 epithelial cells. The AbFhaB/FhaC 2-partner secretion (TPS) system involved in adhesion was discovered after the screening of the recently determined A. baumannii AbH12O-A2 strain genome (CP009534.1). The AbFhaB is a large exoprotein which transport to the bacterial surface is mediated by the AbFhaC protein. In the present study, the role of this TPS system in the AbH12O-A2 adherence phenotype was investigated. The functional inactivation of this 2-partner secretion system was addressed by analyzing the outer membrane vesicles (OMV) proteomic profile from the wild-type strain and its derivative mutant AbH12O-A2ΔfhaC demonstrating that AbFhaB is no longer detected in the absence of AbFhaC. Scanning electron microscopy (SEM) and adhesion experiments demonstrated that inactivation of the AbFhaB/FhaC system significantly decreases bacterial attachment to A549 alveolar epithelial cells. Moreover, it has been demonstrated that this 2-partner secretion system is involved in fibronectin-mediated adherence of the A. baumannii AbH12O-A2 isolate. Finally, we report that the AbFhaB/FhaC system is involved in virulence when tested using invertebrate and vertebrate hosts. These data suggest the potential role that this AbFhaB/FhaC secretion system could play in the pathobiology of A. baumannii. PMID:27858524

The FhaB/FhaC two-partner secretion system is involved in adhesion of Acinetobacter baumannii AbH12O-A2 strain.

PubMed

Pérez, A; Merino, M; Rumbo-Feal, S; Álvarez-Fraga, L; Vallejo, J A; Beceiro, A; Ohneck, E J; Mateos, J; Fernández-Puente, P; Actis, L A; Poza, M; Bou, G

2017-08-18

Acinetobacter baumannii is a hospital-acquired pathogen that shows an extraordinary capacity to stay in the hospital environment. Adherence of the bacteria to eukaryotic cells or to abiotic surfaces is the first step for establishing an infection. The A. baumannii strain AbH12O-A2 showed an exceptional ability to adhere to A549 epithelial cells. The AbFhaB/FhaC 2-partner secretion (TPS) system involved in adhesion was discovered after the screening of the recently determined A. baumannii AbH12O-A2 strain genome (CP009534.1). The AbFhaB is a large exoprotein which transport to the bacterial surface is mediated by the AbFhaC protein. In the present study, the role of this TPS system in the AbH12O-A2 adherence phenotype was investigated. The functional inactivation of this 2-partner secretion system was addressed by analyzing the outer membrane vesicles (OMV) proteomic profile from the wild-type strain and its derivative mutant AbH12O-A2ΔfhaC demonstrating that AbFhaB is no longer detected in the absence of AbFhaC. Scanning electron microscopy (SEM) and adhesion experiments demonstrated that inactivation of the AbFhaB/FhaC system significantly decreases bacterial attachment to A549 alveolar epithelial cells. Moreover, it has been demonstrated that this 2-partner secretion system is involved in fibronectin-mediated adherence of the A. baumannii AbH12O-A2 isolate. Finally, we report that the AbFhaB/FhaC system is involved in virulence when tested using invertebrate and vertebrate hosts. These data suggest the potential role that this AbFhaB/FhaC secretion system could play in the pathobiology of A. baumannii.

Probing Inflationary Cosmology: The Atacama B-Mode Search (ABS)

NASA Astrophysics Data System (ADS)

Essinger-Hileman, Thomas

Observations of the Cosmic Microwave Background (CMB) have provided compelling evidence for the Standard Model of Cosmology and have led to the most precise estimates of cosmological parameters to date. Through its sensitivity to gravitational waves, the CMB provides a glimpse into the state of the universe just 10-35 seconds after the Big Bang and of physics on grand-unification-theory (GUT) energy scales around 1016 GeV, some 13 orders of magnitude above the energies achievable by current terrestrial particle accelerators. A gravitational-wave background (GWB) in the early universe would leave a unique, odd-parity pattern of polarization in the CMB called B modes, the magnitude of which is characterized by the tensor-to-scalar ratio, r. A GWB is generically predicted to exist by inflationary theories, and the current generation of CMB polarization experiments will probe the interesting parameter space of r < 0.05 corresponding to single-field inflationary models at GUT scales. I detail the design and construction of the Atacama B-Mode Search (ABS), which aims to measure the polarization of the CMB at degree angular scales where the primordial B-mode signal is expected to peak. ABS is a 145-GHz polarimeter that will operate from a high-altitude site in the Atacama Desert of Chile, consisting of a 60-cm crossed-Dragone telescope with cryogenic primary and secondary reflectors; an array of 240 feedhorn-coupled, transition-edge-sensor, bolometric polarimeters; and, a continuously-rotating, warm, sapphire half-wave plate (HWP) that will provide modulation of the incoming polarization of light. In this thesis, I describe the optical, mechanical, and cryogenic design of the receiver, including the reflector design, focal-plane layout, HWP design, and free-space lowpass filters. I describe physical-optics modeling of the reflector and feedhorn to validate the optical design. A matrix model that allows the calculation of the Mueller matrix of the anti-reflection-coated HWP for arbitrary frequency and angle of incidence is outlined. This will provide a framework for characterizing the ABS HWP in the field. Finally, the development of metal-mesh free space filters for ABS is described. ABS is anticipated to measure or place an upper limit on the tensor-to-scalar ratio at a level of r ˜ 0.03.

A dilute Cu(Ni) alloy for synthesis of large-area Bernal stacked bilayer graphene using atmospheric pressure chemical vapour deposition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Madito, M. J.; Bello, A.; Dangbegnon, J. K.

2016-01-07

A bilayer graphene film obtained on copper (Cu) foil is known to have a significant fraction of non-Bernal (AB) stacking and on copper/nickel (Cu/Ni) thin films is known to grow over a large-area with AB stacking. In this study, annealed Cu foils for graphene growth were doped with small concentrations of Ni to obtain dilute Cu(Ni) alloys in which the hydrocarbon decomposition rate of Cu will be enhanced by Ni during synthesis of large-area AB-stacked bilayer graphene using atmospheric pressure chemical vapour deposition. The Ni doped concentration and the Ni homogeneous distribution in Cu foil were confirmed with inductively coupledmore » plasma optical emission spectrometry and proton-induced X-ray emission. An electron backscatter diffraction map showed that Cu foils have a single (001) surface orientation which leads to a uniform growth rate on Cu surface in early stages of graphene growth and also leads to a uniform Ni surface concentration distribution through segregation kinetics. The increase in Ni surface concentration in foils was investigated with time-of-flight secondary ion mass spectrometry. The quality of graphene, the number of graphene layers, and the layers stacking order in synthesized bilayer graphene films were confirmed by Raman and electron diffraction measurements. A four point probe station was used to measure the sheet resistance of graphene films. As compared to Cu foil, the prepared dilute Cu(Ni) alloy demonstrated the good capability of growing large-area AB-stacked bilayer graphene film by increasing Ni content in Cu surface layer.« less

A dilute Cu(Ni) alloy for synthesis of large-area Bernal stacked bilayer graphene using atmospheric pressure chemical vapour deposition

NASA Astrophysics Data System (ADS)

Madito, M. J.; Bello, A.; Dangbegnon, J. K.; Oliphant, C. J.; Jordaan, W. A.; Momodu, D. Y.; Masikhwa, T. M.; Barzegar, F.; Fabiane, M.; Manyala, N.

2016-01-01

A bilayer graphene film obtained on copper (Cu) foil is known to have a significant fraction of non-Bernal (AB) stacking and on copper/nickel (Cu/Ni) thin films is known to grow over a large-area with AB stacking. In this study, annealed Cu foils for graphene growth were doped with small concentrations of Ni to obtain dilute Cu(Ni) alloys in which the hydrocarbon decomposition rate of Cu will be enhanced by Ni during synthesis of large-area AB-stacked bilayer graphene using atmospheric pressure chemical vapour deposition. The Ni doped concentration and the Ni homogeneous distribution in Cu foil were confirmed with inductively coupled plasma optical emission spectrometry and proton-induced X-ray emission. An electron backscatter diffraction map showed that Cu foils have a single (001) surface orientation which leads to a uniform growth rate on Cu surface in early stages of graphene growth and also leads to a uniform Ni surface concentration distribution through segregation kinetics. The increase in Ni surface concentration in foils was investigated with time-of-flight secondary ion mass spectrometry. The quality of graphene, the number of graphene layers, and the layers stacking order in synthesized bilayer graphene films were confirmed by Raman and electron diffraction measurements. A four point probe station was used to measure the sheet resistance of graphene films. As compared to Cu foil, the prepared dilute Cu(Ni) alloy demonstrated the good capability of growing large-area AB-stacked bilayer graphene film by increasing Ni content in Cu surface layer.

[Relationship between the thyroid autoimmunity and the risk of preterm birth in pregnant women: a meta-analysis].

PubMed

Li, M; Wang, S W; Huang, S; Mao, Y

2016-05-25

To evaluate the relationship between thyroid autoimmunity and the risk of preterm birth. Literature search was done among PubMed, Embase, Wanfang Medical Database, China Academic Journal Network Publishing Database and China Biology Medicine disc from Jan. 1(st) 1980 to July 31(st), 2015. (1) Literature were extracted according to inclusion and exclusion standards, and the quality of the extracted literature were evaluated by Newcastle-Ottawa Scale (NOS). (2) Meta-analysis was performed by RevMan 5 software formulated by using the Cochrane library databases. Various heterogeneity of the research was inspected firstly. According to the results of the inspection a certain effect model was selected (including fixed effects model, the random effects model) to be utilized in merger analysis. In this study pregnant women with both thyroid peroxidase antibodies (TPO-Ab) and thyroglobulin (TG-Ab) positive were defined as thyroid antibody positive pregnant women. Pregnant women with only TPO-Ab positive were defined as TPO-Ab positive pregnant women. Then the relationship of antibody positive and the risk of a preterm birth was analyzed respectively. (1) Ten cohort studies were enrolled, of which NOS scale score were 7 or higher. All the studies are of medium quality and above. A total of 1 322 cases of preterm birth occurred among 19 910 pregnant women. (2) Positive thyroid autoantibodies did not increase the risk of preterm birth in euthyroid pregnant women (OR=1.41, 95%CI: 0.83-2.40, P=0.200) or in pregnant women with hypothyroidism (OR=0.68, 95% CI: 0.32-1.44, P=0.310) . Positive TPO-Ab in euthyroid pregnant women increase the risk of preterm birth significantly (OR=2.08, 95%CI: 1.09-3.97, P=0.030), but positive TPO-Ab in pregnant women with hypothyroidism did not increase the risk of preterm birth significantly (OR=1.21, 95%CI: 0.65-2.24, P=0.550). Positive TPO-Ab is an independent risk factor of preterm birth in euthyroid pregnant women.

Production of human monoclonal antibody in eggs of chimeric chickens.

PubMed

Zhu, Lei; van de Lavoir, Marie-Cecile; Albanese, Jenny; Beenhouwer, David O; Cardarelli, Pina M; Cuison, Severino; Deng, David F; Deshpande, Shrikant; Diamond, Jennifer H; Green, Lynae; Halk, Edward L; Heyer, Babette S; Kay, Robert M; Kerchner, Allyn; Leighton, Philip A; Mather, Christine M; Morrison, Sherie L; Nikolov, Zivko L; Passmore, David B; Pradas-Monne, Alicia; Preston, Benjamin T; Rangan, Vangipuram S; Shi, Mingxia; Srinivasan, Mohan; White, Steven G; Winters-Digiacinto, Peggy; Wong, Susan; Zhou, Wen; Etches, Robert J

2005-09-01

The tubular gland of the chicken oviduct is an attractive system for protein expression as large quantities of proteins are deposited in the egg, the production of eggs is easily scalable and good manufacturing practices for therapeutics from eggs have been established. Here we examined the ability of upstream and downstream DNA sequences of ovalbumin, a protein produced exclusively in very high quantities in chicken egg white, to drive tissue-specific expression of human mAb in chicken eggs. To accommodate these large regulatory regions, we established and transfected lines of chicken embryonic stem (cES) cells and formed chimeras that express mAb from cES cell-derived tubular gland cells. Eggs from high-grade chimeras contained up to 3 mg of mAb that possesses enhanced antibody-dependent cellular cytotoxicity (ADCC), nonantigenic glycosylation, acceptable half-life, excellent antigen recognition and good rates of internalization.

Teaching the blind to find their way by playing video games.

PubMed

Merabet, Lotfi B; Connors, Erin C; Halko, Mark A; Sánchez, Jaime

2012-01-01

Computer based video games are receiving great interest as a means to learn and acquire new skills. As a novel approach to teaching navigation skills in the blind, we have developed Audio-based Environment Simulator (AbES); a virtual reality environment set within the context of a video game metaphor. Despite the fact that participants were naïve to the overall purpose of the software, we found that early blind users were able to acquire relevant information regarding the spatial layout of a previously unfamiliar building using audio based cues alone. This was confirmed by a series of behavioral performance tests designed to assess the transfer of acquired spatial information to a large-scale, real-world indoor navigation task. Furthermore, learning the spatial layout through a goal directed gaming strategy allowed for the mental manipulation of spatial information as evidenced by enhanced navigation performance when compared to an explicit route learning strategy. We conclude that the immersive and highly interactive nature of the software greatly engages the blind user to actively explore the virtual environment. This in turn generates an accurate sense of a large-scale three-dimensional space and facilitates the learning and transfer of navigation skills to the physical world.

Thermal Conductivities in Solids from First Principles: Accurate Computations and Rapid Estimates

NASA Astrophysics Data System (ADS)

Carbogno, Christian; Scheffler, Matthias

In spite of significant research efforts, a first-principles determination of the thermal conductivity κ at high temperatures has remained elusive. Boltzmann transport techniques that account for anharmonicity perturbatively become inaccurate under such conditions. Ab initio molecular dynamics (MD) techniques using the Green-Kubo (GK) formalism capture the full anharmonicity, but can become prohibitively costly to converge in time and size. We developed a formalism that accelerates such GK simulations by several orders of magnitude and that thus enables its application within the limited time and length scales accessible in ab initio MD. For this purpose, we determine the effective harmonic potential occurring during the MD, the associated temperature-dependent phonon properties and lifetimes. Interpolation in reciprocal and frequency space then allows to extrapolate to the macroscopic scale. For both force-field and ab initio MD, we validate this approach by computing κ for Si and ZrO2, two materials known for their particularly harmonic and anharmonic character. Eventually, we demonstrate how these techniques facilitate reasonable estimates of κ from existing MD calculations at virtually no additional computational cost.

Results of investigations (OA77 and OA78) on an 0.015-scale 140A/B configuration space shuttle vehicle orbiter model 49-0 in the AEDC VKF B and C wind tunnels, revision A

NASA Technical Reports Server (NTRS)

Gillins, R. L.

1975-01-01

Aerodynamic data obtained from wind tunnel tests of an 0.015-scale 140A/B configuration SSV Orbiter model in the AEDC VKF B and C wind tunnels are presented. Tests were conducted at Mach numbers of 6 and 8 in the B tunnel and at a Mach number of 10 to in the C tunnel to verify hypersonic stability and control characteristics, determine control surface effectiveness, and investigate Reynolds number effects of the 140A/B configuration. Force data were obtained for various control surface settings and Reynolds numbers in the angle-of-attack range of 15 deg to 45 deg and at angles of sideslip of -5 deg to +10 deg. Data were obtained for a few configurations at angles of attack from -27 deg to 45 deg. Control surface variables included elevon, rudder, speedbrake and bodyflap deflections. The effects of an alternate wing leading edge shape were investigated to determine its hypersonic stability and control characteristics.

Materials Engineering and Scale Up of Fluid Phase Chemical Hydrogen Storage for Automotive Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Westman, Matthew P.; Chun, Jaehun; Choi, Young Joon

Among candidates for chemical hydrogen storage in PEM fuel cell automotive applications, ammonia borane (AB, NH3BH3) is considered to be one of the most promising materials due to its high hydrogen content of 14-16 wt% below 200°C and high volumetric density. In our previous paper, we selected AB in silicone oil as a role model for a slurry hydrogen storage system. Materials engineering properties were optimized by increasing solid loading by using an ultra-sonic process. In this paper, we proceeded to scale up to liter size batches with solid loadings up to 50 wt% (8 wt% H2) with dynamic viscositiesmore » less than 1000cP at 25°C. The use of a non-ionic surfactant, Triton X-15, shows significant promise in controlling the level of foaming produced during the thermal dehydrogenation of the AB. Through the development of new and efficient processing techniques and the ability to adequately control the foaming, stable homogenous slurries of high solid loading have been demonstrated as a viable hydrogen delivery source.« less

Development of an optical microscopy system for automated bubble cloud analysis.

PubMed

Wesley, Daniel J; Brittle, Stuart A; Toolan, Daniel T W

2016-08-01

Recently, the number of uses of bubbles has begun to increase dramatically, with medicine, biofuel production, and wastewater treatment just some of the industries taking advantage of bubble properties, such as high mass transfer. As a result, more and more focus is being placed on the understanding and control of bubble formation processes and there are currently numerous techniques utilized to facilitate this understanding. Acoustic bubble sizing (ABS) and laser scattering techniques are able to provide information regarding bubble size and size distribution with minimal data processing, a major advantage over current optical-based direct imaging approaches. This paper demonstrates how direct bubble-imaging methods can be improved upon to yield high levels of automation and thus data comparable to ABS and laser scattering. We also discuss the added benefits of the direct imaging approaches and how it is possible to obtain considerable additional information above and beyond that which ABS and laser scattering can supply. This work could easily be exploited by both industrial-scale operations and small-scale laboratory studies, as this straightforward and cost-effective approach is highly transferrable and intuitive to use.

Theoretical Modeling of Molecular Mechanisms, Time Scales, and Strains in Prion Diseases

DTIC Science & Technology

2006-07-01

head region. The conformations shown are for Ab40, but Ab42 has similar conformations with two additional residues ( isoleucine and alanine) at the C...hydrophobicity of the C-terminus (see sequence in Fig. 4), as both are nonpolar and isoleucine is strongly hydrophobic. One might well ask, however, why...small change between isoleucine and valine. Unsurprisingly, the A2S mutant makes no change to insertion behavior (residue 2 is firmly in the upper

A Force Balanced Fragmentation Method for ab Initio Molecular Dynamic Simulation of Protein.

PubMed

Xu, Mingyuan; Zhu, Tong; Zhang, John Z H

2018-01-01

A force balanced generalized molecular fractionation with conjugate caps (FB-GMFCC) method is proposed for ab initio molecular dynamic simulation of proteins. In this approach, the energy of the protein is computed by a linear combination of the QM energies of individual residues and molecular fragments that account for the two-body interaction of hydrogen bond between backbone peptides. The atomic forces on the caped H atoms were corrected to conserve the total force of the protein. Using this approach, ab initio molecular dynamic simulation of an Ace-(ALA) 9 -NME linear peptide showed the conservation of the total energy of the system throughout the simulation. Further a more robust 110 ps ab initio molecular dynamic simulation was performed for a protein with 56 residues and 862 atoms in explicit water. Compared with the classical force field, the ab initio molecular dynamic simulations gave better description of the geometry of peptide bonds. Although further development is still needed, the current approach is highly efficient, trivially parallel, and can be applied to ab initio molecular dynamic simulation study of large proteins.

The DEAD-box RNA helicase Ddx39ab is essential for myocyte and lens development in zebrafish.

PubMed

Zhang, Linlin; Yang, Yuxi; Li, Beibei; Scott, Ian C; Lou, Xin

2018-04-23

RNA helicases from the DEAD-box family are found in almost all organisms and have important roles in RNA metabolism, including RNA synthesis, processing and degradation. The function and mechanism of action of most of these helicases in animal development and human disease remain largely unexplored. In a zebrafish mutagenesis screen to identify genes essential for heart development we identified a mutant that disrupts the gene encoding the RNA helicase DEAD-box 39ab ( ddx39ab ). Homozygous ddx39ab mutant embryos exhibit profound cardiac and trunk muscle dystrophy, along with lens abnormalities, caused by abrupt terminal differentiation of cardiomyocyte, myoblast and lens fiber cells. Loss of ddx39ab hindered splicing of mRNAs encoding epigenetic regulatory factors, including members of the KMT2 gene family, leading to misregulation of structural gene expression in cardiomyocyte, myoblast and lens fiber cells. Taken together, these results show that Ddx39ab plays an essential role in establishment of the proper epigenetic status during differentiation of multiple cell lineages. © 2018. Published by The Company of Biologists Ltd.

Generation of monoclonal pan-hemagglutinin antibodies for the quantification of multiple strains of influenza

PubMed Central

Zou, Wei; Marcil, Anne; Paquet, Eric; Gadoury, Christine; Jaentschke, Bozena; Li, Xuguang; Petiot, Emma; Durocher, Yves; Baardsnes, Jason; Rosa-Calatrava, Manuel; Ansorge, Sven; Kamen, Amine A.

2017-01-01

Vaccination is the most effective course of action to prevent influenza. About 150 million doses of influenza vaccines were distributed for the 2015–2016 season in the USA alone according to the Centers for Disease Control and Prevention. Vaccine dosage is calculated based on the concentration of hemagglutinin (HA), the main surface glycoprotein expressed by influenza which varies from strain to strain. Therefore yearly-updated strain-specific antibodies and calibrating antigens are required. Preparing these quantification reagents can take up to three months and significantly slows down the release of new vaccine lots. Therefore, to circumvent the need for strain-specific sera, two anti-HA monoclonal antibodies (mAbs) against a highly conserved sequence have been produced by immunizing mice with a novel peptide-conjugate. Immunoblots demonstrate that 40 strains of influenza encompassing HA subtypes H1 to H13, as well as B strains from the Yamagata and Victoria lineage were detected when the two mAbs are combined to from a pan-HA mAb cocktail. Quantification using this pan-HA mAbs cocktail was achieved in a dot blot assay and results correlated with concentrations measured in a hemagglutination assay with a coefficient of correlation of 0.80. A competitive ELISA was also optimised with purified viral-like particles. Regardless of the quantification method used, pan-HA antibodies can be employed to accelerate process development when strain-specific antibodies are not available, and represent a valuable tool in case of pandemics. These antibodies were also expressed in CHO cells to facilitate large-scale production using bioreactor technologies which might be required to meet industrial needs for quantification reagents. Finally, a simulation model was created to predict the binding affinity of the two anti-HA antibodies to the amino acids composing the highly conserved epitope; different probabilities of interaction between a given amino acid and the antibodies might explain the affinity of each antibody against different influenza strains. PMID:28662134

Anti-neuropeptide Y plasma immunoglobulins in relation to mood and appetite in depressive disorder.

PubMed

Garcia, Frederico D; Coquerel, Quentin; do Rego, Jean-Claude; Cravezic, Aurore; Bole-Feysot, Christine; Kiive, Evelyn; Déchelotte, Pierre; Harro, Jaanus; Fetissov, Sergueï O

2012-09-01

Depression and eating disorders are frequently associated, but the molecular pathways responsible for co-occurrence of altered mood, appetite and body weight are not yet fully understood. Neuropeptide Y (NPY) has potent antidepressant and orexigenic properties and low central NPY levels have been reported in major depression. In the present study, we hypothesized that in patients with major depression alteration of mood, appetite and body weight may be related to NPY-reactive autoantibodies (autoAbs). To test this hypothesis, we compared plasma levels and affinities of NPY-reactive autoAbs between patients with major depression and healthy controls. Then, to evaluate if changes of NPY autoAb properties can be causally related to altered mood and appetite, we developed central and peripheral passive transfer models of human autoAbs in mice and studied depressive-like behavior in forced-swim test and food intake. We found that plasma levels of NPY IgG autoAbs were lower in patients with moderate but not with mild depression correlating negatively with the Montgomery-Åsberg Depression Rating Scale scores and with immobility time of the forced-swim test in mice after peripheral injection of autoAbs. No significant differences in NPY IgG autoAb affinities between patients with depression and controls were found, but higher affinity of IgG autoAbs for NPY was associated with lower body mass index and prevented NPY-induced orexigenic response in mice after their central injection. These data suggest that changes of plasma levels of anti-NPY autoAbs are relevant to altered mood, while changes of their affinity may participate in altered appetite and body weight in patients with depressive disorder. Copyright © 2012 Elsevier Ltd. All rights reserved.

Scale-up of a physiologically-based pharmacokinetic model to predict the disposition of monoclonal antibodies in monkeys.

PubMed

Glassman, Patrick M; Chen, Yang; Balthasar, Joseph P

2015-10-01

Preclinical assessment of monoclonal antibody (mAb) disposition during drug development often includes investigations in non-human primate models. In many cases, mAb exhibit non-linear disposition that relates to mAb-target binding [i.e., target-mediated disposition (TMD)]. The goal of this work was to develop a physiologically-based pharmacokinetic (PBPK) model to predict non-linear mAb disposition in plasma and in tissues in monkeys. Physiological parameters for monkeys were collected from several sources, and plasma data for several mAbs associated with linear pharmacokinetics were digitized from prior literature reports. The digitized data displayed great variability; therefore, parameters describing inter-antibody variability in the rates of pinocytosis and convection were estimated. For prediction of the disposition of individual antibodies, we incorporated tissue concentrations of target proteins, where concentrations were estimated based on categorical immunohistochemistry scores, and with assumed localization of target within the interstitial space of each organ. Kinetics of target-mAb binding and target turnover, in the presence or absence of mAb, were implemented. The model was then employed to predict concentration versus time data, via Monte Carlo simulation, for two mAb that have been shown to exhibit TMD (2F8 and tocilizumab). Model predictions, performed a priori with no parameter fitting, were found to provide good prediction of dose-dependencies in plasma clearance, the areas under plasma concentration versu time curves, and the time-course of plasma concentration data. This PBPK model may find utility in predicting plasma and tissue concentration versus time data and, potentially, the time-course of receptor occupancy (i.e., mAb-target binding) to support the design and interpretation of preclinical pharmacokinetic-pharmacodynamic investigations in non-human primates.

Dissection of epitope-specific mechanisms of neutralization of influenza virus by intact IgG and Fab fragments.

PubMed

Williams, James A; Gui, Long; Hom, Nancy; Mileant, Alexander; Lee, Kelly K

2017-12-20

The neutralizing antibody (nAb) response against the influenza virus's hemagglutinin (HA) fusion glycoprotein is important for preventing viral infection, but we lack a comprehensive understanding of the mechanisms by which these antibodies act. Here we investigated the effect of nAb binding and the role of IgG bivalency on inhibition of HA function for nAbs targeting distinct HA epitopes. HC19 targets the receptor-binding pocket at HA's distal end, while FI6v3 binds primarily to the HA2 fusion subunit towards the base of the stalk. Surprisingly, HC19 inhibited HA's ability to induce lipid mixing by preventing structural rearrangement of HA under fusion activating conditions. These results suggest that nAbs such as HC19 not only act by blocking receptor binding, but also inhibit key late-stage HA conformational changes required for fusion. Intact HC19 IgG was also shown to crosslink separate virus particles, burying large proportions of HA within aggregates where they are blocked from interacting with target membranes; Fabs yielded no such aggregation and displayed weaker neutralization than IgG, emphasizing the impact of bivalency on the ability to neutralize virus. In contrast, the stem-targeting nAb FI6v3 did not aggregate particles. The Fab was significantly less effective than IgG in preventing both membrane disruption and fusion. We infer that inter-spike crosslinking within a given particle by FI6v3 IgG may be critical to its potent neutralization, as no significant neutralization occurred with Fabs. These results demonstrate that IgG bivalency enhances HA inhibition through functionally important modes not evident in pared down Fab-soluble HA structures. IMPORTANCE The influenza virus's hemagglutinin (HA) fusion glycoprotein mediates entry into target cells and is the primary antigenic target of neutralizing antibodies (nAbs). Our current structural understanding of mechanisms of Ab-mediated neutralization largely relies on high resolution characterization of antigen binding fragments (Fab) in complex with soluble, isolated antigen constructs by cryo-EM single particle reconstruction or X-ray crystallography. Interactions between full-length IgG and whole virions have not been well-characterized, and a gap remains in our understanding of how intact Abs neutralize virus and prevent infection. Using structural and biophysical approaches, we observed that Ab-mediated inhibition of HA function and neutralization of virus infectivity occurs by multiple coexisting mechanisms and is largely dependent on the specific epitope that is targeted and is highly dependent on the bivalent nature of IgG molecules. Copyright © 2017 American Society for Microbiology.

Pharmacokinetics and pharmacokinetic-pharmacodynamic relationships of monoclonal antibodies in children.

PubMed

Edlund, Helena; Melin, Johanna; Parra-Guillen, Zinnia P; Kloft, Charlotte

2015-01-01

Monoclonal antibodies (mAbs) constitute a therapeutically and economically important drug class with increasing use in both adult and paediatric patients. The rather complex pharmacokinetic and pharmacodynamic properties of mAbs have been extensively reviewed in adults. In children, however, limited information is currently available. This paper aims to comprehensively review published pharmacokinetic and pharmacokinetic-pharmacodynamic studies of mAbs in children. The current status of mAbs in the USA and in Europe is outlined, including a critical discussion of the dosing strategies of approved mAbs. The pharmacokinetic properties of mAbs in children are exhaustively summarised along with comparisons to reports in adults: for each pharmacokinetic process, we discuss the general principles and mechanisms of the pharmacokinetic/pharmacodynamic characteristics of mAbs, as well as key growth and maturational processes in children that might impact these characteristics. Throughout this review, considerable knowledge gaps are identified, especially regarding children-specific properties that influence pharmacokinetics, pharmacodynamics and immunogenicity. Furthermore, the large heterogeneity in the presentation of pharmacokinetic/pharmacodynamic data limited clinical inferences in many aspects of paediatric mAb therapy. Overall, further studies are needed to fully understand the impact of body size and maturational changes on drug exposure and response. To maximise future knowledge gain, we propose a 'Guideline for Best Practice' on how to report pharmacokinetic and pharmacokinetic-pharmacodynamic results from mAb studies in children which also facilitates comparisons. Finally, we advocate the use of more sophisticated modelling strategies (population analysis, physiology-based approaches) to appropriately characterise pharmacokinetic-pharmacodynamic relationships of mAbs and, thus, allow for a more rational use of mAb in the paediatric population.

The effect of arginine glutamate on the stability of monoclonal antibodies in solution.

PubMed

Kheddo, Priscilla; Tracka, Malgorzata; Armer, Jonathan; Dearman, Rebecca J; Uddin, Shahid; van der Walle, Christopher F; Golovanov, Alexander P

2014-10-01

Finding excipients which mitigate protein self-association and aggregation is an important task during formulation. Here, the effect of an equimolar mixture of l-Arg and l-Glu (Arg·Glu) on colloidal and conformational stability of four monoclonal antibodies (mAb1-mAb4) at different pH is explored, with the temperatures of the on-set of aggregation (Tagg) and unfolding (Tm1) measured by static light scattering and intrinsic fluorescence, respectively. Arg·Glu increased the Tagg of all four mAbs in concentration-dependent manner, especially as pH increased to neutral. Arg·Glu also increased Tm1 of the least thermally stable mAb3, but without similar direct effect on the Tm1 of other mAbs. Raising pH itself from 5 to 7 increased Tm1 for all four mAbs. Selected mAb formulations were assessed under accelerated stability conditions for the monomer fraction remaining in solution after storage. The aggregation of mAb3 was suppressed to a greater extent by Arg·Glu than by Arg·HCl. Furthermore, Arg·Glu suppressed the aggregation of mAb1 at neutral pH such that the fraction monomer was near to that at the more typical formulation pH of 5.5. We conclude that Arg·Glu can suppress mAb aggregation with increasing temperature/pH and, importantly, under accelerated stability conditions at weakly acidic to neutral pH. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor.

PubMed

Adams, André A; Okagbare, Paul I; Feng, Juan; Hupert, Matuesz L; Patterson, Don; Göttert, Jost; McCarley, Robin L; Nikitopoulos, Dimitris; Murphy, Michael C; Soper, Steven A

2008-07-09

A novel microfluidic device that can selectively and specifically isolate exceedingly small numbers of circulating tumor cells (CTCs) through a monoclonal antibody (mAB) mediated process by sampling large input volumes (>/=1 mL) of whole blood directly in short time periods (<37 min) was demonstrated. The CTCs were concentrated into small volumes (190 nL), and the number of cells captured was read without labeling using an integrated conductivity sensor following release from the capture surface. The microfluidic device contained a series (51) of high-aspect ratio microchannels (35 mum width x 150 mum depth) that were replicated in poly(methyl methacrylate), PMMA, from a metal mold master. The microchannel walls were covalently decorated with mABs directed against breast cancer cells overexpressing the epithelial cell adhesion molecule (EpCAM). This microfluidic device could accept inputs of whole blood, and its CTC capture efficiency was made highly quantitative (>97%) by designing capture channels with the appropriate widths and heights. The isolated CTCs were readily released from the mAB capturing surface using trypsin. The released CTCs were then enumerated on-device using a novel, label-free solution conductivity route capable of detecting single tumor cells traveling through the detection electrodes. The conductivity readout provided near 100% detection efficiency and exquisite specificity for CTCs due to scaling factors and the nonoptimal electrical properties of potential interferences (erythrocytes or leukocytes). The simplicity in manufacturing the device and its ease of operation make it attractive for clinical applications requiring one-time use operation.

Monoclonal antibody-based serological assays and immunocapture-RT-PCR for detecting Rice dwarf virus in field rice plants and leafhopper vectors.

PubMed

Wu, Jianxiang; Ni, Yuequn; Liu, Huan; Ding, Ming; Zhou, Xueping

2014-01-01

Rice dwarf virus (RDV) causes Rice dwarf disease, which leads to considerable losses in rice production in Asia. Purified RDV virions were used as the immunogen to prepare monoclonal antibodies (mAbs). Three murine mAbs against RDV were prepared. Plate-trapped antigen enzyme-linked immunosorbent assay (PTA-ELISA), dot enzyme-linked immunosorbent assay (dot-ELISA) and immunocapture-RT-PCR (IC-RT-PCR) were then developed for sensitive, specific, and rapid detection of RDV in rice and leafhopper samples obtained in the field using the mAbs. The PTA-ELISA, dot-ELISA and IC-RT-PCR detected the virus in infected tissue crude extracts diluted at 1:81,920, 1:10,240 and 1:655,360 (w/v, g mL(-1)), in individual viruliferous rice green leafhopper crude extracts diluted at 1:25,600, 1:6400 and 1:3,276,800 (individual leafhopper/μL), respectively. 878 rice field samples and 531 leafhopper field samples from ten provinces of China were screened for the presence of RDV using the two serological assays and the IC-RT-PCR and the results indicated that 37 of the 878 rice samples and 22 of the 531 leafhopper samples were infected by RDV. All positive samples were from Yunnan Province, indicating that RDV is prevalent in this province, but not in the other nine provinces. The dot-ELISA is suitable for routine detection of large-scale rice and leafhopper samples in field surveys. Copyright © 2013 Elsevier B.V. All rights reserved.

Highly Efficient Circulating Tumor Cell Isolation from Whole Blood and Label-Free Enumeration Using Polymer-Based Microfluidics with an Integrated Conductivity Sensor

PubMed Central

Adams, André A.; Okagbare, Paul I.; Feng, Juan; Hupert, Matuesz L.; Patterson, Don; Göttert, Jost; McCarley, Robin L.; Nikitopoulos, Dimitris; Murphy, Michael C.; Soper, Steven A.

2008-01-01

A novel microfluidic device that can selectively and specifically isolate exceedingly small numbers of circulating tumor cells (CTCs) through a monoclonal antibody (mAB) mediated process by sampling large input volumes (≥1 mL) of whole blood directly in short time periods (<37 min) was demonstrated. The CTCs were concentrated into small volumes (190 nL), and the number of cells captured was read without labeling using an integrated conductivity sensor following release from the capture surface. The microfluidic device contained a series (51) of high-aspect ratio microchannels (35 μm width × 150 μm depth) that were replicated in poly(methyl methacrylate), PMMA, from a metal mold master. The microchannel walls were covalently decorated with mABs directed against breast cancer cells overexpressing the epithelial cell adhesion molecule (EpCAM). This microfluidic device could accept inputs of whole blood, and its CTC capture efficiency was made highly quantitative (>97%) by designing capture channels with the appropriate widths and heights. The isolated CTCs were readily released from the mAB capturing surface using trypsin. The released CTCs were then enumerated on-device using a novel, label-free solution conductivity route capable of detecting single tumor cells traveling through the detection electrodes. The conductivity readout provided near 100% detection efficiency and exquisite specificity for CTCs due to scaling factors and the nonoptimal electrical properties of potential interferences (erythrocytes or leukocytes). The simplicity in manufacturing the device and its ease of operation make it attractive for clinical applications requiring one-time use operation. PMID:18557614

Isolation and characterization of a new enterovirus F in yak feces in the Qinghai-Tibetan Plateau.

PubMed

He, Huan; Tang, Cheng; Chen, Xinnuo; Yue, Hua; Ren, Yupeng; Liu, Yan; Zhang, Bin

2017-02-01

An enterovirus (EV) strain, designated as SWUN-AB001, was isolated in the Qinghai-Tibetan Plateau from a yak with severe diarrheal disease. The complete genome of strain SWUN-AB001 was 7,382 bp in length and shared 35.1-68.5% nt identities with bovine EVs belonging to a candidate new type EV-F7. Using the sequence difference values in the VP1 gene as a criterion for demarcating a new serotype/genotype in the Enterovirus genus, strain SWUN-AB001 had only a 71.1% nt and a 79.2% aa identity, in the VP1 region, with the most closely matched EV, further indicating that a new type of EV had been identified. Phylogenetic analysis of the nt sequence of the viral polyprotein and of VP1 genes demonstrated that the virus fell within the EV-F cluster, but was located in a unique lineage. Furthermore, a large-scale surveillance study indicated that the prevalence of this EV in yaks was 31.05% (95% CI = 25.5-37.6%) in 235 animals with diarrhea and 24.13% (95% CI = 17.4-32.4%) in 116 healthy yaks. However, there was no significant difference in virus prevalence between diarrheal and healthy samples. Interestingly, in the Tibet region, diarrheal feces had a higher incidence of EVs than feces of healthy yaks (odd ratios = 6.03, 95% CI = 1.93-18.86), indicating that the incidence of EV was potentially correlated with the clinical symptom of diarrhea in yaks.

Investigations of immunogenic, allergenic and adjuvant properties of Cry1Ab protein after intragastric exposure in a food allergy model in mice.

PubMed

Andreassen, Monica; Bøhn, Thomas; Wikmark, Odd-Gunnar; Bodin, Johanna; Traavik, Terje; Løvik, Martinus; Nygaard, Unni Cecilie

2016-05-04

In genetically modified (GM) crops there is a risk that the inserted genes may introduce new allergens and/or adjuvants into the food and feed chain. The MON810 maize, expressing the insecticidal Cry1Ab toxin, is grown in many countries worldwide. In animal models, intranasal and intraperitoneal immunisations with the purified Cry1Ab proteins have induced immune responses, and feeding trials with Cry1Ab-containing feed have revealed some altered immune responses. Previous investigations have primarily measured antibody responses to the protein, while investigations of clinical food allergy symptoms, or allergy promotion (adjuvant effect) associated with the Cry1Ab protein are largely missing. We aimed to investigate immunogenic, allergenic and adjuvant properties of purified Cry1Ab toxin (trypCry1Ab, i.e., trypsin activated Cry1Ab) in a mouse model of food allergy. Female C3H/HeJ mice were immunized by intragastric gavage of 10 μg purified, trypsin activated Cry1Ab toxin (trypCry1Ab) alone or together with the food allergen lupin. Cholera toxin was added as a positive control for adjuvant effect to break oral tolerance. Clinical symptoms (anaphylaxis) as well as humoral and cellular responses were assessed. In contrast to results from previous airway investigations, we observed no indication of immunogenic properties of trypCry1Ab protein after repeated intragastric exposures to one dose, with or without CT as adjuvant. Moreover, the results indicated that trypCry1Ab given by the intragastric route was not able to promote allergic responses or anaphylactic reactions against the co-administered allergen lupin at the given dose. The study suggests no immunogenic, allergenic or adjuvant capacity of the given dose of trypCry1Ab protein after intragastric exposure of prime aged mice.

Serotonergic correlation with anger and aggressive behavior in acute stroke patients: an intensity dependence of auditory evoked potentials (IDAP) study.

PubMed

Toscano, Massimiliano; Viganò, Alessandro; Puledda, Francesca; Verzina, Angela; Rocco, Andrea; Lenzi, Gian Luigi; Di Piero, Vittorio

2014-01-01

Anger and aggressive behavior (AB) are two of the main post-stroke behavioral manifestations, which could imply both an anger trait (TA) or a state condition of anger (SA). Serotonergic system is thought to play an inhibitory control on aggressive impulse. Nevertheless, whether 5HT has the same role in TA and in SA, is still debated. Intensity dependence of auditory evoked potentials (IDAP) is thought to be inversely related to the central 5HT tone. The aim of this study was to evaluate, in acute stroke patients, the 5HT system involvement in AB by IDAP. Consecutive stroke patients were evaluated and compared with healthy controls. The Spielberger Trait Anger Scale (STAS) was used to assess AB, SA and TA. Patients with AB and TA showed a significantly increased IDAP value, whereas patients with SA had a significantly lower IDAP; this indicates an increased 5HT tone. In acute stroke patients with AB, there is a decreased central 5HT tone. Surprisingly, we found an opposite 5HT feature between patients with TA and those showing SA, suggesting that the hypothesis of aggression based on 5HT deficiency requires further investigations. This might open new strategies in the treatment of post-stroke AB. © 2014 S. Karger AG, Basel.

Edge reconstruction in armchair phosphorene nanoribbons revealed by discontinuous Galerkin density functional theory.

PubMed

Hu, Wei; Lin, Lin; Yang, Chao

2015-12-21

With the help of our recently developed massively parallel DGDFT (Discontinuous Galerkin Density Functional Theory) methodology, we perform large-scale Kohn-Sham density functional theory calculations on phosphorene nanoribbons with armchair edges (ACPNRs) containing a few thousands to ten thousand atoms. The use of DGDFT allows us to systematically achieve a conventional plane wave basis set type of accuracy, but with a much smaller number (about 15) of adaptive local basis (ALB) functions per atom for this system. The relatively small number of degrees of freedom required to represent the Kohn-Sham Hamiltonian, together with the use of the pole expansion the selected inversion (PEXSI) technique that circumvents the need to diagonalize the Hamiltonian, results in a highly efficient and scalable computational scheme for analyzing the electronic structures of ACPNRs as well as their dynamics. The total wall clock time for calculating the electronic structures of large-scale ACPNRs containing 1080-10,800 atoms is only 10-25 s per self-consistent field (SCF) iteration, with accuracy fully comparable to that obtained from conventional planewave DFT calculations. For the ACPNR system, we observe that the DGDFT methodology can scale to 5000-50,000 processors. We use DGDFT based ab initio molecular dynamics (AIMD) calculations to study the thermodynamic stability of ACPNRs. Our calculations reveal that a 2 × 1 edge reconstruction appears in ACPNRs at room temperature.

Hexon and fiber of adenovirus type 14 and 55 are major targets of neutralizing antibody but only fiber-specific antibody contributes to cross-neutralizing activity.

PubMed

Feng, Ying; Sun, Xikui; Ye, Xianmiao; Feng, Yupeng; Wang, Jinlin; Zheng, Xuehua; Liu, Xinglong; Yi, Changhua; Hao, Mingli; Wang, Qian; Li, Feng; Xu, Wei; Li, Liang; Li, Chufang; Zhou, Rong; Chen, Ling; Feng, Liqiang

2018-05-01

Re-emerging human adenoviruses type 14 (HAdV14) and 55 (HAdV55) represent two highly virulent adenoviruses. The neutralizing antibody (nAb) responses elicited by infection or immunization remain largely unknown. Herein, we generated hexon-chimeric HAdV14 viruses harboring each single or entire hexon hyper-variable-regions (HVR) from HAdV55, and determined the neutralizing epitopes of human and mouse nAbs. In human sera, hexon-targeting nAbs are type-specific and mainly recognize HVR2, 5, and 7. Fiber-targeting nAbs are only detectable in sera cross-neutralizing HAdV14 and HAdV55 and contribute substantially to cross-neutralization. Penton-binding antibodies, however, show no significant neutralizing activities. In mice immunized with HAdV14 or HAdV55, a single immunization mainly elicited hexon-specific nAbs, which recognized HAdV14 HVR1, 2, and 7 and HAdV55 HVR1 and 2, respectively. After a booster immunization, cross-neutralizing fiber-specific nAbs became detectable. These results indicated that hexon elicits type-specific nAbs whereas fiber induces cross-neutralizing nAbs to HAdV14 and HAdV55, which are of significance in vaccine development. Copyright © 2018 Elsevier Inc. All rights reserved.

A novel impedance-based cellular assay for the detection of anti-calcium channel autoantibodies in type 1 diabetes.

PubMed

Jackson, Michael W; Gordon, Tom P

2010-09-30

We have recently postulated that functional autoantibodies (Abs) against L-type voltage-gated calcium channels (VGCCs) contribute to autonomic dysfunction in type 1 diabetes (T1D). Previous studies based on whole-organ assays have proven valuable in establishing the mechanism of anti-VGCC Ab activity, but are complex and unsuitable for screening large patient cohorts. In the current study, we used real-time dynamic monitoring of cell impedance to demonstrate that anti-VGCC Abs from patients with T1D inhibit the adherence of Rin A12 cells. The functional effect of the anti-VGCC Abs was mimicked by the dihydropyridine agonist, Bay K8644, and reversed by the antagonist, nicardipine, providing a pharmacological link to the whole-organ studies. IVIg neutralized the effect on cell adhesion of the anti-VGCC Abs, consistent with the presence of anti-idiotypic Abs in IVIg that may prevent the emergence of pathogenic Abs in healthy individuals. The cell impedance assay can be performed in a 96 well plate format, and represents a simple method for detecting the presence of anti-VGCC activity in patient immunoglobulin (IgG). The new cell assay should prove useful for further studies to determine the prevalence of the Ab and its association with symptoms of autonomic dysfunction in patients with T1D. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

Antibodies causing thrombocytopenia in patients treated with RGD-mimetic platelet inhibitors recognize ligand-specific conformers of αIIb/β3 integrin

PubMed Central

Rasmussen, Mark; Zhu, Jieqing; Aster, Richard H.

2012-01-01

Arginine-glycine-aspartic acid (RGD)–mimetic platelet inhibitors act by occupying the RGD recognition site of αIIb/β3 integrin (GPIIb/IIIa), thereby preventing the activated integrin from reacting with fibrinogen. Thrombocytopenia is a well-known side effect of treatment with this class of drugs and is caused by Abs, often naturally occurring, that recognize αIIb/β3 in a complex with the drug being administered. RGD peptide and RGD-mimetic drugs are known to induce epitopes (ligand-induced binding sites [LIBS]) in αIIb/β3 that are recognized by certain mAbs. It has been speculated, but not shown experimentally, that Abs from patients who develop thrombocytopenia when treated with an RGD-mimetic inhibitor similarly recognize LIBS determinants. We addressed this question by comparing the reactions of patient Abs and LIBS-specific mAbs against αIIb/β3 in a complex with RGD and RGD-mimetic drugs, and by examining the ability of selected non-LIBS mAbs to block binding of patient Abs to the liganded integrin. Findings made provide evidence that the patient Abs recognize subtle, drug-induced structural changes in the integrin head region that are clustered about the RGD recognition site. The target epitopes differ from classic LIBS determinants, however, both in their location and by virtue of being largely drug-specific. PMID:22490676

Structural and electron diffraction scaling of twisted graphene bilayers

NASA Astrophysics Data System (ADS)

Zhang, Kuan; Tadmor, Ellad B.

2018-03-01

Multiscale simulations are used to study the structural relaxation in twisted graphene bilayers and the associated electron diffraction patterns. The initial twist forms an incommensurate moiré pattern that relaxes to a commensurate microstructure comprised of a repeating pattern of alternating low-energy AB and BA domains surrounding a high-energy AA domain. The simulations show that the relaxation mechanism involves a localized rotation and shrinking of the AA domains that scales in two regimes with the imposed twist. For small twisting angles, the localized rotation tends to a constant; for large twist, the rotation scales linearly with it. This behavior is tied to the inverse scaling of the moiré pattern size with twist angle and is explained theoretically using a linear elasticity model. The results are validated experimentally through a simulated electron diffraction analysis of the relaxed structures. A complex electron diffraction pattern involving the appearance of weak satellite peaks is predicted for the small twist regime. This new diffraction pattern is explained using an analytical model in which the relaxation kinematics are described as an exponentially-decaying (Gaussian) rotation field centered on the AA domains. Both the angle-dependent scaling and diffraction patterns are in quantitative agreement with experimental observations. A Matlab program for extracting the Gaussian model parameters accompanies this paper.

Molecular Basis of 9G4 B Cell Autoreactivity in Human Systemic Lupus Erythematosus

PubMed Central

Richardson, Christopher; Chida, Asiya Seema; Adlowitz, Diana; Silver, Lin; Fox, Erin; Jenks, Scott A.; Palmer, Elise; Wang, Youliang; Heimburg-Molinaro, Jamie; Li, Quan-Zhen; Mohan, Chandra; Cummings, Richard; Tipton, Christopher

2013-01-01

9G4+ IgG Abs expand in systemic lupus erythematosus (SLE) in a disease-specific fashion and react with different lupus Ags including B cell Ags and apoptotic cells. Their shared use of VH4-34 represents a unique system to understand the molecular basis of lupus autoreactivity. In this study, a large panel of recombinant 9G4+ mAbs from single naive and memory cells was generated and tested against B cells, apoptotic cells, and other Ags. Mutagenesis eliminated the framework-1 hydrophobic patch (HP) responsible for the 9G4 idiotype. The expression of the HP in unselected VH4-34 cells was assessed by deep sequencing. We found that 9G4 Abs recognize several Ags following two distinct structural patterns. B cell binding is dependent on the HP, whereas anti-nuclear Abs, apoptotic cells, and dsDNA binding are HP independent and correlate with positively charged H chain third CDR. The majority of mutated VH4-34 memory cells retain the HP, thereby suggesting selection by Ags that require this germline structure. Our findings show that the germline-encoded HP is compulsory for the anti–B cell reactivity largely associated with 9G4 Abs in SLE but is not required for reactivity against apoptotic cells, dsDNA, chromatin, anti-nuclear Abs, or cardiolipin. Given that the lupus memory compartment contains a majority of HP+ VH4-34 cells but decreased B cell reactivity, additional HP-dependent Ags must participate in the selection of this compartment. This study represents the first analysis, to our knowledge, of VH-restricted autoreactive B cells specifically expanded in SLE and provides the foundation to understand the antigenic forces at play in this disease. PMID:24108696

The production of O(1D) from dissociative recombination of O2(+)

NASA Technical Reports Server (NTRS)

Guberman, Steven L.

1988-01-01

The results of large scale ab initio calculations of the rates for production of O(1D) by dissociative combination of O2(+) are presented for electron temperatures in the range 100 to 3000 K. A 1-delta-u state is the dominant dissociative route from v = 0 and a 3-sigma-u(-) state is the most important route from v = 1 and v = 2. The calculated total rate for O(1D) production from v = 0 is 2.21(+0.21, -0.24) x 10(-7) x (T sub e/300) exp -.46 near room temperature. The v = 1 and v = 2 rates are about 17 percent and 47 percent smaller respectively, than the v = 0 rate at 300 K.

The production of O(1D) from dissociative recombination of O2(+)

NASA Technical Reports Server (NTRS)

Guberman, Steven L.

1987-01-01

The results of large scale ab initio calculations of the rates for production of O(1D) by dissociative combination of O2(+) are presented for electron temperatures in the range 100 to 3000 K. A 1-delta-u state is the dominant dissociative route from v = 0 and a 3-sigma-u(-) state is the most important route from v = 1 and v = 2. The calculated total rate for O(1D) production from v = 0 is 2.21(+0.21,-0.24) x 10(-7) x (T sub e/300) exp -.46 near room temperature. The v = 1 and v = 2 rates are about 17% and 47% smaller respectively, than the v = 0 rate at 300 K.

High-throughput density-functional perturbation theory phonons for inorganic materials

NASA Astrophysics Data System (ADS)

Petretto, Guido; Dwaraknath, Shyam; P. C. Miranda, Henrique; Winston, Donald; Giantomassi, Matteo; van Setten, Michiel J.; Gonze, Xavier; Persson, Kristin A.; Hautier, Geoffroy; Rignanese, Gian-Marco

2018-05-01

The knowledge of the vibrational properties of a material is of key importance to understand physical phenomena such as thermal conductivity, superconductivity, and ferroelectricity among others. However, detailed experimental phonon spectra are available only for a limited number of materials, which hinders the large-scale analysis of vibrational properties and their derived quantities. In this work, we perform ab initio calculations of the full phonon dispersion and vibrational density of states for 1521 semiconductor compounds in the harmonic approximation based on density functional perturbation theory. The data is collected along with derived dielectric and thermodynamic properties. We present the procedure used to obtain the results, the details of the provided database and a validation based on the comparison with experimental data.

A refined quartic potential energy surface and large scale vibrational calculations for S0 thiophosgene.

PubMed

Rashev, Svetoslav; Moule, David C

2015-04-05

In this work we present a full 6D quartic potential energy surface (PES) for S0 thiophosgene in curvilinear symmetrized bond-angle coordinates. The PES was refined starting from an ab initio field derived from acc-pVTZ basis set with CCSD(T) corrections for electron correlation. In the present calculations we used our variational method that was recently tested on formaldehyde and some of its isotopomers, along with additional improvements. The lower experimentally known vibrational levels for 35Cl2CS were reproduced quite well in the calculations, which can be regarded as a test for the feasibility of the obtained quartic PES. Copyright © 2015 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rajbhandari, Samyam; NIkam, Akshay; Lai, Pai-Wei

Tensor contractions represent the most compute-intensive core kernels in ab initio computational quantum chemistry and nuclear physics. Symmetries in these tensor contractions makes them difficult to load balance and scale to large distributed systems. In this paper, we develop an efficient and scalable algorithm to contract symmetric tensors. We introduce a novel approach that avoids data redistribution in contracting symmetric tensors while also avoiding redundant storage and maintaining load balance. We present experimental results on two parallel supercomputers for several symmetric contractions that appear in the CCSD quantum chemistry method. We also present a novel approach to tensor redistribution thatmore » can take advantage of parallel hyperplanes when the initial distribution has replicated dimensions, and use collective broadcast when the final distribution has replicated dimensions, making the algorithm very efficient.« less

Mining Naïve Rabbit Antibody Repertoires by Phage Display for Monoclonal Antibodies of Therapeutic Utility.

PubMed

Peng, Haiyong; Nerreter, Thomas; Chang, Jing; Qi, Junpeng; Li, Xiuling; Karunadharma, Pabalu; Martinez, Gustavo J; Fallahi, Mohammad; Soden, Jo; Freeth, Jim; Beerli, Roger R; Grawunder, Ulf; Hudecek, Michael; Rader, Christoph

2017-09-15

Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but, in some cases, also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity. Moreover, ROR1- and ROR2-targeting rabbit mAbs demonstrated therapeutic utility as components of chimeric antigen receptor-engineered T cells, further corroborating the value of the naïve rabbit antibody library as a rich and virtually unlimited source of rabbit mAbs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Asbestos bodies in bronchoalveolar lavage fluid. A study of 20 asbestos-exposed individuals and comparison to patients with other chronic interstitial lung diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roggli, V.L.; Piantadosi, C.A.; Bell, D.Y.

1986-09-01

We studied the asbestos body (AB) content of bronchoalveolar lavage fluid from 20 patients with a history of occupational asbestos exposure, 31 patients with sarcoidosis and 5 patients with idiopathic pulmonary fibrosis. The cellular lavage pellet was digested in sodium hypochlorite and filtered onto Nuclepore filters for AB quantification by light microscopy. ABs were found in 15 of 20 asbestos-exposed individuals, 9 of 31 sarcoidosis cases and 2 of 5 patients with idiopathic pulmonary fibrosis. There was a statistically significant difference in the number of ABs per million cells recovered or per milliliter of recovered lavage fluid in the asbestos-exposedmore » group as compared to the other categories of chronic interstitial lung disease. The highest levels occurred in patients with asbestosis. Large numbers of asbestos bodies in the lavage fluid (greater than 1 AB/10(6) cells) were indicative of considerable occupational asbestos exposure, whereas occasional bodies were a nonspecific finding.« less

A large microRNA cluster on chromosome 19 is a transcriptional hallmark of WHO type A and AB thymomas.

PubMed

Radovich, Milan; Solzak, Jeffrey P; Hancock, Bradley A; Conces, Madison L; Atale, Rutuja; Porter, Ryan F; Zhu, Jin; Glasscock, Jarret; Kesler, Kenneth A; Badve, Sunil S; Schneider, Bryan P; Loehrer, Patrick J

2016-02-16

Thymomas are one of the most rarely diagnosed malignancies. To better understand its biology and to identify therapeutic targets, we performed next-generation RNA sequencing. The RNA was sequenced from 13 thymic malignancies and 3 normal thymus glands. Validation of microRNA expression was performed on a separate set of 35 thymic malignancies. For cell-based studies, a thymoma cell line was used. Hierarchical clustering revealed 100% concordance between gene expression clusters and WHO subtype. A substantial differentiator was a large microRNA cluster on chr19q13.42 that was significantly overexpressed in all A and AB tumours and whose expression was virtually absent in the other thymomas and normal tissues. Overexpression of this microRNA cluster activates the PI3K/AKT/mTOR pathway. Treatment of a thymoma AB cell line with a panel of PI3K/AKT/mTOR inhibitors resulted in marked reduction of cell viability. A large microRNA cluster on chr19q13.42 is a transcriptional hallmark of type A and AB thymomas. Furthermore, this cluster activates the PI3K pathway, suggesting the possible exploration of PI3K inhibitors in patients with these subtypes of tumour. This work has led to the initiation of a phase II clinical trial of PI3K inhibition in relapsed or refractory thymomas (http://clinicaltrials.gov/ct2/show/NCT02220855).

A large microRNA cluster on chromosome 19 is a transcriptional hallmark of WHO type A and AB thymomas

PubMed Central

Radovich, Milan; Solzak, Jeffrey P; Hancock, Bradley A; Conces, Madison L; Atale, Rutuja; Porter, Ryan F; Zhu, Jin; Glasscock, Jarret; Kesler, Kenneth A; Badve, Sunil S; Schneider, Bryan P; Loehrer, Patrick J

2016-01-01

Background: Thymomas are one of the most rarely diagnosed malignancies. To better understand its biology and to identify therapeutic targets, we performed next-generation RNA sequencing. Methods: The RNA was sequenced from 13 thymic malignancies and 3 normal thymus glands. Validation of microRNA expression was performed on a separate set of 35 thymic malignancies. For cell-based studies, a thymoma cell line was used. Results: Hierarchical clustering revealed 100% concordance between gene expression clusters and WHO subtype. A substantial differentiator was a large microRNA cluster on chr19q13.42 that was significantly overexpressed in all A and AB tumours and whose expression was virtually absent in the other thymomas and normal tissues. Overexpression of this microRNA cluster activates the PI3K/AKT/mTOR pathway. Treatment of a thymoma AB cell line with a panel of PI3K/AKT/mTOR inhibitors resulted in marked reduction of cell viability. Conclusions: A large microRNA cluster on chr19q13.42 is a transcriptional hallmark of type A and AB thymomas. Furthermore, this cluster activates the PI3K pathway, suggesting the possible exploration of PI3K inhibitors in patients with these subtypes of tumour. This work has led to the initiation of a phase II clinical trial of PI3K inhibition in relapsed or refractory thymomas (http://clinicaltrials.gov/ct2/show/NCT02220855). PMID:26766736

Small-scale screening method for low-viscosity antibody solutions using small-angle X-ray scattering.

PubMed

Fukuda, Masakazu; Watanabe, Atsushi; Hayasaka, Akira; Muraoka, Masaru; Hori, Yuji; Yamazaki, Tadao; Imaeda, Yoshimi; Koga, Akiko

2017-03-01

In this study, we investigated the concentration range in which self-association starts to form in humanized IgG monoclonal antibody (mAb) solutions. Furthermore, on the basis of the results, we developed a practical method of screening for low-viscosity antibody solutions by using small-angle X-ray scattering (SAXS) measurements utilizing small quantities of samples. With lower-viscosity mAb3, self-association was not detected in the range of 1-80mg/mL. With higher-viscosity mAb1, on the other hand, self-association was detected in the range of 10-20mg/mL and was clearly enhanced by a decrease in temperature. The viscosities of mAb solutions at 160, 180, and 200mg/mL at 25°C quantitatively correlated very well with the particle size parameters obtained by SAXS measurements of mAb solutions at 15mg/mL at 5°C. The quantity of mAb sample required for the SAXS measurements was only 0.15mg, which is about one-hundredth of that required for actual viscosity measurements at a high concentration, and such quantities could be available even at an early stage of development. In conclusion, the SAXS analysis method proposed in this study is a valuable tool for the development of concentrated mAb therapeutics with high manufacturability and high usability for subcutaneous injection. Copyright © 2016 Elsevier B.V. All rights reserved.

The relationship between clinical characteristics, radiographic osteoarthritis and 3D bone area: data from the osteoarthritis initiative.

PubMed

Barr, A J; Dube, B; Hensor, E M A; Kingsbury, S R; Peat, G; Bowes, M A; Conaghan, P G

2014-10-01

Radiographic measures of osteoarthritis (OA) are based upon two dimensional projection images. Active appearance modelling (AAM) of knee magnetic resonance imaging (MRI) enables accurate, 3D quantification of joint structures in large cohorts. This cross-sectional study explored the relationship between clinical characteristics, radiographic measures of OA and 3D bone area (tAB). Clinical data and baseline paired radiographic and MRI data, from the medial compartment of one knee of 2588 participants were obtained from the NIH Osteoarthritis Initiative (OAI). The medial femur (MF) and tibia (MT) tAB were calculated using AAM. 'OA-attributable' tAB (OA-tAB) was calculated using data from regression models of tAB of knees without OA. Associations between OA-tAB and radiographic measures of OA were investigated using linear regression. In univariable analyses, height, weight, and age in female knees without OA explained 43.1%, 32.1% and 0.1% of the MF tAB variance individually and 54.4% when included simultaneously in a multivariable model. Joint space width (JSW), osteophytes and sclerosis explained just 5.3%, 14.9% and 10.1% of the variance of MF OA-tAB individually and 17.4% when combined. Kellgren Lawrence (KL) grade explained approximately 20% of MF OA-tAB individually. Similar results were seen for MT OA-tAB. Height explained the majority of variance in tAB, confirming an allometric relationship between body and joint size. Radiographic measures of OA, derived from a single radiographic projection, accounted for only a small amount of variation in 3D knee OA-tAB. The additional structural information provided by 3D bone area may explain the lack of a substantive relationship with these radiographic OA measures. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

15. Photocopy of scaled drawing (from the Engineering Office of ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

15. Photocopy of scaled drawing (from the Engineering Office of the Veterans Administration) drawn by A.B. Metcalf, issued February 5, 1935). Tree planting plan of R-VAH site, showing Building #6 in relation to its surroundings. - Roanoke Veterans Administration Hospital, Building No. 6, 1970 Roanoke Boulevard, Salem, Salem, VA

Toxicokinetic and toxicodynamic analyses of Androctonus australis hector venom in rats: Optimization of antivenom therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hammoudi-Triki, D.; Laboratoire de Biologie Cellulaire et Moleculaire, Faculte des Sciences Biologiques, Universite des Sciences et de la Technologie 'Houari Boumedienne' Bab Ezzouar, Alger, Algerie; Laboratoire de Recherche et de Developpement sur les Venins, Institut Pasteur d'Algerie, Algerie

2007-02-01

This paper reports the simultaneous determination of toxicokinetic and toxicodynamic properties of Androctonus australis hector venom, in the absence and presence of antivenom (F(ab'){sub 2} and Fab), in envenomed rats. After subcutaneous injection of the venom, toxins showed a complete absorption phase from the site of injection associated with a distribution into a large extravascular compartment. The injection of Fab and F(ab'){sub 2} induced the neutralization of venom antigens in the blood compartment, as well as the redistribution of venom components from the extravascular compartment to the blood compartment. Interestingly, F(ab'){sub 2} and Fab showed distinct efficiencies depending on theirmore » route of injection. F(ab'){sub 2} induced a faster venom neutralization and redistribution than Fab when injected intravenously. Fab was more effective than F(ab'){sub 2} by the intramuscular route. The hemodynamic effects of Aah venom were further investigated. Changes in mean arterial pressure and heart rate were observed in parallel with an upper airway obstruction. Fab was more effective than F(ab'){sub 2} for preventing early symptoms of envenomation, whatever their route of administration. Intraperitoneal injection of F(ab'){sub 2} and Fab was similar for the prevention of the delayed symptoms, even after a late administration. Fab was more effective than F(ab'){sub 2} in the inhibition of airway resistance, independent of the route and time of administration. These results show that the treatment for scorpion stings might be improved by the intravascular injection of a mixture of Fab and F(ab'){sub 2}. If antivenom cannot be administered intravenously, Fab might be an alternative as they are more effective than F(ab'){sub 2} when injected intramuscularly.« less

Compactness Aromaticity of Atoms in Molecules

PubMed Central

Putz, Mihai V.

2010-01-01

A new aromaticity definition is advanced as the compactness formulation through the ratio between atoms-in-molecule and orbital molecular facets of the same chemical reactivity property around the pre- and post-bonding stabilization limit, respectively. Geometrical reactivity index of polarizability was assumed as providing the benchmark aromaticity scale, since due to its observable character; with this occasion new Hydrogenic polarizability quantum formula that recovers the exact value of 4.5 a03 for Hydrogen is provided, where a0 is the Bohr radius; a polarizability based–aromaticity scale enables the introduction of five referential aromatic rules (Aroma 1 to 5 Rules). With the help of these aromatic rules, the aromaticity scales based on energetic reactivity indices of electronegativity and chemical hardness were computed and analyzed within the major semi-empirical and ab initio quantum chemical methods. Results show that chemical hardness based-aromaticity is in better agreement with polarizability based-aromaticity than the electronegativity-based aromaticity scale, while the most favorable computational environment appears to be the quantum semi-empirical for the first and quantum ab initio for the last of them, respectively. PMID:20480020

Investigations on an 0.030-scale space shuttle vehicle configuration 140A/B orbiter model in the Ames Research Center unitary plan 8 by 7-foot supersonic wind tunnel (0A53C)

NASA Technical Reports Server (NTRS)

Nichols, M. E.

1974-01-01

A wind tunnel test was conducted of an 0.030 scale model of the space shuttle orbiter in a supersonic wind tunnel. Tests were conducted at Mach numbers of 2.5, 3.0, and 3.5. Reynolds numbers ranged from 0.75 million per foot to 4.00 million per foot. The objective of the test was to establish and verify longitudinal and lateral-directional aerodynamic performance, stability, and control characteristics for the configuration 140 A/B SSV Orbiter. Six-component force and moment data, base and cavity pressures, body-flap, elevon, speedbrake, and rudder hinge moments, and vertical tail forces and moments were measured.

Processing Impact on Monoclonal Antibody Drug Products: Protein Subvisible Particulate Formation Induced by Grinding Stress.

PubMed

Gikanga, Benson; Eisner, Devon Roshan; Ovadia, Robert; Day, Eric S; Stauch, Oliver B; Maa, Yuh-Fun

2017-01-01

Subvisible particle formation in monoclonal antibody drug product resulting from mixing and filling operations represents a significant processing risk that can lead to filter fouling and thereby lead to process delays or failures. Several previous studies from our lab and others demonstrated the formation of subvisible particulates in mAb formulations resulting from mixing operations using some bottom-mounted mixers or stirrer bars. It was hypothesized that the stress (e.g., shear/cavitation) derived from tight clearance and/or close contact between the impeller and shaft was responsible for protein subvisible particulate generation. These studies, however, could not distinguish between the two surfaces without contact (tight clearance) or between two contacting surfaces (close contact). In the present study we expand on those findings and utilize small-scale mixing models that are able to, for the first time, distinguish between tight clearances and tight contact. In this study we evaluated different mixer types including a top-mounted mixer, several impeller-based bottom-mounted mixers, and a rotary piston pump. The impact of tight clearance/close contact on subvisible particle formation in at-scale mixing platforms was demonstrated in the gap between the impeller and drive unit as well as between the piston and the housing of the pump. Furthermore, small-scale mixing models based on different designs of magnetic stir bars that mimic the tight clearance/close contact of the manufacturing-scale mixers also induced subvisible particles in mAb formulations. Additional small-scale models that feature tight clearance but no close contact (grinding) suggested that it is the repeated grinding/contacting of the moving parts and not the presence of tight clearance in the processing equipment that is the root cause of protein subvisible particulate formation. When multiple mAbs, Fabs (fragment antigen binding), or non-antibody related proteins were mixed in the small-scale mixing model, for molecules investigated, it was observed that mAbs and Fabs appear to be more susceptible to particle formation than non-antibody-related proteins. In the grinding zone, mAb/Fab molecules aggregated into insoluble particles with neither detectable soluble aggregates nor fragmented species. This investigation represents a step closer to the understanding of the underlying stress mechanism leading to mAb subvisible particulate formation as the result of drug product processing. LAY ABSTRACT: Mixing and fill finish are important unit operations in drug product manufacturing for compounding (dilution, pooling, homogenization, etc.) and filling into primary packaging containers (vials, pre-filled syringes, etc.), respectively. The current trend in adopting bottom-mounted mixers as well as low fill-volume filling systems has raised concerns about their impact on drug product quality and process performance. However, investigations into the effects of their use for biopharmaceutical products, particularly monoclonal antibody formulations, are rarely published. The purpose of this study is three-fold: (1) to revisit the impact of bottom-mounted mixer design on monoclonal antibody subvisible particle formation; (2) to identify the root cause for subvisible particle formation; and (3) to fully utilize available particle analysis tools to demonstrate the correlation between particle count in the solution and filter fouling during sterile filtration. The outcomes of this study will benefit scientists and engineers who develop biologic product manufacturing processes by providing a better understanding of drug product process challenges. © PDA, Inc. 2017.

Future sensitivity to new physics in Bd, Bs, and K mixings

NASA Astrophysics Data System (ADS)

Charles, Jérôme; Descotes-Genon, Sébastien; Ligeti, Zoltan; Monteil, Stéphane; Papucci, Michele; Trabelsi, Karim

2014-02-01

We estimate, in a large class of scenarios, the sensitivity to new physics in Bd and Bs mixings achievable with 50 ab-1 of Belle II and 50 fb-1 of LHCb data. We find that current limits on new physics contributions in both Bd ,s systems can be improved by a factor of ˜5 for all values of the CP-violating phases, corresponding to over a factor of 2 increase in the scale of new physics probed. Assuming the same suppressions by Cabbibo-Kobayashi-Maskawa matrix elements as those of the standard model box diagrams, the scale probed will be about 20 TeV for tree-level new physics contributions, and about 2 TeV for new physics arising at one loop. We also explore the future sensitivity to new physics in K mixing. Implications for generic new physics and for various specific scenarios, such as minimal flavor violation, light third-generation dominated flavor violation, or U(2) flavor models are studied.

OWL: A scalable Monte Carlo simulation suite for finite-temperature study of materials

NASA Astrophysics Data System (ADS)

Li, Ying Wai; Yuk, Simuck F.; Cooper, Valentino R.; Eisenbach, Markus; Odbadrakh, Khorgolkhuu

The OWL suite is a simulation package for performing large-scale Monte Carlo simulations. Its object-oriented, modular design enables it to interface with various external packages for energy evaluations. It is therefore applicable to study the finite-temperature properties for a wide range of systems: from simple classical spin models to materials where the energy is evaluated by ab initio methods. This scheme not only allows for the study of thermodynamic properties based on first-principles statistical mechanics, it also provides a means for massive, multi-level parallelism to fully exploit the capacity of modern heterogeneous computer architectures. We will demonstrate how improved strong and weak scaling is achieved by employing novel, parallel and scalable Monte Carlo algorithms, as well as the applications of OWL to a few selected frontier materials research problems. This research was supported by the Office of Science of the Department of Energy under contract DE-AC05-00OR22725.

Global analysis of double-strand break processing reveals in vivo properties of the helicase-nuclease complex AddAB

PubMed Central

Badrinarayanan, Anjana; Cisse, Ibrahim I.

2017-01-01

In bacteria, double-strand break (DSB) repair via homologous recombination is thought to be initiated through the bi-directional degradation and resection of DNA ends by a helicase-nuclease complex such as AddAB. The activity of AddAB has been well-studied in vitro, with translocation speeds between 400–2000 bp/s on linear DNA suggesting that a large section of DNA around a break site is processed for repair. However, the translocation rate and activity of AddAB in vivo is not known, and how AddAB is regulated to prevent excessive DNA degradation around a break site is unclear. To examine the functions and mechanistic regulation of AddAB inside bacterial cells, we developed a next-generation sequencing-based approach to assay DNA processing after a site-specific DSB was introduced on the chromosome of Caulobacter crescentus. Using this assay we determined the in vivo rates of DSB processing by AddAB and found that putative chi sites attenuate processing in a RecA-dependent manner. This RecA-mediated regulation of AddAB prevents the excessive loss of DNA around a break site, limiting the effects of DSB processing on transcription. In sum, our results, taken together with prior studies, support a mechanism for regulating AddAB that couples two key events of DSB repair–the attenuation of DNA-end processing and the initiation of homology search by RecA–thereby helping to ensure that genomic integrity is maintained during DSB repair. PMID:28489851

Large magnetic penetration depth and thermal fluctuations in a superconducting Ca10(Pt3As8)[(Fe1 xPtx)2As2]5 (x = 0.097) single crystal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim J.; Nazaretski E.; Ronning, F.

2012-05-18

We have measured the temperature dependence of the absolute value of the magnetic penetration depth {lambda}(T) in a Ca{sub 10}(Pt{sub 3}As{sub 8})[(Fe{sub 1-x}Pt{sub x}){sub 2}As{sub 2}]{sub 5} (x = 0.097) single crystal using a low-temperature magnetic force microscope (MFM). We obtain {lambda}{sub ab}(0) {approx} 1000 nm via extrapolating the data to T = 0. This large {lambda} and pronounced anisotropy in this system are responsible for large thermal fluctuations and the presence of a liquid vortex phase in this low-temperature superconductor with a critical temperature of 11 K, consistent with the interpretation of the electrical transport data. The superconducting parametersmore » obtained from {lambda} and coherence length {zeta} place this compound in the extreme type II regime. Meissner responses (via MFM) at different locations across the sample are similar to each other, indicating good homogeneity of the superconducting state on a submicron scale.« less

Characterization of anti-CD20 monoclonal antibody produced by transgenic silkworms (Bombyx mori).

PubMed

Tada, Minoru; Tatematsu, Ken-ichiro; Ishii-Watabe, Akiko; Harazono, Akira; Takakura, Daisuke; Hashii, Noritaka; Sezutsu, Hideki; Kawasaki, Nana

2015-01-01

In response to the successful use of monoclonal antibodies (mAbs) in the treatment of various diseases, systems for expressing recombinant mAbs using transgenic animals or plants have been widely developed. The silkworm (Bombyx mori) is a highly domesticated insect that has recently been used for the production of recombinant proteins. Because of their cost-effective breeding and relatively easy production scale-up, transgenic silkworms show great promise as a novel production system for mAbs. In this study, we established a transgenic silkworm stably expressing a human-mouse chimeric anti-CD20 mAb having the same amino acid sequence as rituximab, and compared its characteristics with rituximab produced by Chinese hamster ovary (CHO) cells (MabThera®). The anti-CD20 mAb produced in the transgenic silkworm showed a similar antigen-binding property, but stronger antibody-dependent cell-mediated cytotoxicity (ADCC) and weaker complement-dependent cytotoxicity (CDC) compared to MabThera. Post-translational modification analysis was performed by peptide mapping using liquid chromatography/mass spectrometry. There was a significant difference in the N-glycosylation profile between the CHO- and the silkworm-derived mAbs, but not in other post-translational modifications including oxidation and deamidation. The mass spectra of the N-glycosylated peptide revealed that the observed biological properties were attributable to the characteristic N-glycan structures of the anti-CD20 mAbs produced in the transgenic silkworms, i.e., the lack of the core-fucose and galactose at the non-reducing terminal. These results suggest that the transgenic silkworm may be a promising expression system for the tumor-targeting mAbs with higher ADCC activity.

Composition design for Laves phase-related body-centered cubic-V solid solution alloys with large hydrogen storage capacities.

PubMed

Wang, H B; Wang, Q; Dong, C; Yuan, L; Xu, F; Sun, L X

2008-03-19

This paper analyzes the characteristics of alloy compositions with large hydrogen storage capacities in Laves phase-related body-centered cubic (bcc) solid solution alloy systems using the cluster line approach. Since a dense-packed icosahedral cluster A(6)B(7) characterizes the local structure of AB(2) Laves phases, in an A-B-C ternary system, such as Ti-Cr (Mn, Fe)-V, where A-B forms AB(2) Laves phases while A-C and B-C tend to form solid solutions, a cluster line A(6)B(7)-C is constructed by linking A(6)B(7) to C. The alloy compositions with large hydrogen storage capacities are generally located near this line and are approximately expressed with the cluster-plus-glue-atom model. The cluster line alloys (Ti(6)Cr(7))(100-x)V(x) (x = 2.5-70 at.%) exhibit different structures and hence different hydrogen storage capacities with increasing V content. The alloys (Ti(6)Cr(7))(95)V(5) and Ti(30)Cr(40)V(30) with bcc solid solution structure satisfy the cluster-plus-glue-atom model.

Two Novel Tau Antibodies Targeting the 396/404 Region Are Primarily Taken Up by Neurons and Reduce Tau Protein Pathology*

PubMed Central

Gu, Jiaping; Congdon, Erin E.; Sigurdsson, Einar M.

2013-01-01

Aggregated Tau proteins are hallmarks of Alzheimer disease and other tauopathies. Recent studies from our group and others have demonstrated that both active and passive immunizations reduce Tau pathology and prevent cognitive decline in transgenic mice. To determine the efficacy and safety of targeting the prominent 396/404 region, we developed two novel monoclonal antibodies (mAbs) with distinct binding profiles for phospho and non-phospho epitopes. The two mAbs significantly reduced hyperphosphorylated soluble Tau in long term brain slice cultures without apparent toxicity, suggesting the therapeutic importance of targeting the 396/404 region. In mechanistic studies, we found that neurons were the primary cell type that internalized the mAbs, whereas a small amount of mAbs was taken up by microglia cells. Within neurons, the two mAbs were highly colocalized with distinct pathological Tau markers, indicating their affinity toward different stages or forms of pathological Tau. Moreover, the mAbs were largely co-localized with endosomal/lysosomal markers, and partially co-localized with autophagy pathway markers. Additionally, the Fab fragments of the mAbs were able to enter neurons, but unlike the whole antibodies, the fragments were not specifically localized in pathological neurons. In summary, our Tau mAbs were safe and efficient to clear pathological Tau in a brain slice model. Fc-receptor-mediated endocytosis and the endosome/autophagosome/lysosome system are likely to have a critical role in antibody-mediated clearance of Tau pathology. PMID:24089520

The Pariser-Parr-Pople model for trans-polyenes. I. Ab initio and semiempirical study of the bond alternation in trans-butadiene

NASA Astrophysics Data System (ADS)

Förner, Wolfgang

1992-03-01

Ab initio investigations of the bond alternation in butadiene are presented. The atomic basis sets applied range from minimal to split valence plus polarization quality. With the latter one the Hartree-Fock limit for the bond alternation is reached. Correlation is considered on Møller-Plesset many-body perturbation theory of second order (MP2), linear coupled cluster doubles (L-CCD) and coupled cluster doubles (CCD) level. For the smaller basis sets it is shown that for the bond alternation π-π correlations are essential while the effects of σ-σ and σ-π correlations are, though large, nearly independent of bond alternation. On MP2 level the variation of σ-π correlation with bond alternation is surprisingly large. This is discussed as an artefact of MP2. Comparative Su-Schrieffer-Heeger (SSH) and Pariser-Parr-Pople (PPP) calculations show that these models in their usual parametrizations cannot reproduce the ab initio results.

Ab initio density functional theory investigation of crystalline bundles of polygonized single-walled silicon carbide nanotubes

NASA Astrophysics Data System (ADS)

Moradian, Rostam; Behzad, Somayeh; Chegel, Raad

2008-11-01

By using ab initio density functional theory, the structural characterizations and electronic properties of two large-diameter (13, 13) and (14, 14) armchair silicon carbide nanotube (SiCNT) bundles are investigated. Full structural optimizations show that the cross sections of these large-diameter SiCNTs in the bundles have a nearly hexagonal shape. The effects of inter-tube coupling on the electronic dispersions of large-diameter SiCNT bundles are demonstrated. By comparing the band structures of the triangular lattices of (14, 14) SiCNTs with nearly hexagonal and circular cross sections we found that the polygonization of the tubes in the bundle leads to a further dispersion of the occupied bands and an increase in the bandgap by 0.18 eV.

Ab initio density functional theory investigation of crystalline bundles of polygonized single-walled silicon carbide nanotubes.

PubMed

Moradian, Rostam; Behzad, Somayeh; Chegel, Raad

2008-11-19

By using ab initio density functional theory, the structural characterizations and electronic properties of two large-diameter (13, 13) and (14, 14) armchair silicon carbide nanotube (SiCNT) bundles are investigated. Full structural optimizations show that the cross sections of these large-diameter SiCNTs in the bundles have a nearly hexagonal shape. The effects of inter-tube coupling on the electronic dispersions of large-diameter SiCNT bundles are demonstrated. By comparing the band structures of the triangular lattices of (14, 14) SiCNTs with nearly hexagonal and circular cross sections we found that the polygonization of the tubes in the bundle leads to a further dispersion of the occupied bands and an increase in the bandgap by 0.18 eV.

Dust around Mira variables: An analysis of IRAS LRS spectra

NASA Technical Reports Server (NTRS)

Slijkhuis, S.

1989-01-01

The spatial extent and spectral appearance of the thin dust shell around Mira variables is determined largely by the dust absorptivity, Q(sub abs)(lambda), and the dust condensation temperature T(sub cond). Both Q(sub abs)(lambda) and T(sub cond) are extracted from IRAS low-resolution spectra (LRS) spectra. In order to do this, the assumption that the ratio of total power in the 10 micron feature to that in the 20 micron feature should be equal to that measured in other amorphous silicates (e.g., synthesized amorphous Mg2SiO4). It was found that T(sub cond) decreases with decreasing strength of the 10 micron feature, from T(sub cond) = 1000 K to 500 K (estimated error 20 percent). A value for the near-infrared dust absorptivity could not be determined. Although this parameter strongly affects the condensation radius, it hardly affects the shape of the LRS spectrum (as long as the optically thin approximation is valid), because it scales the spatial distribution of the dust. Information on the magnitude of the near-infrared dust absorptivity may be deduced from the unique carbon star BM Gem. This star has a LRS spectrum with silicate features indication an inner dust shell temperature of at least 1000 K. However, on the basis of observations in the 1920s-30s one may infer an inner dust shell radius of at least 6x10(exp 12)m. To have this high temperature at such a large distance, the near-infrared absorptivity of the dust must be high.

How Germinal Centers Evolve Broadly Neutralizing Antibodies: the Breadth of the Follicular Helper T Cell Response

DOE PAGES

De Boer, Rob J.; Perelson, Alan S.

2017-09-06

Many HIV-1-infected patients evolve broadly neutralizing antibodies (bnAbs). This evolutionary process typically takes several years and is poorly understood as selection taking place in germinal centers occurs on the basis of antibody affinity. B cells with the highest-affinity receptors tend to acquire the most antigen from the follicular dendritic cell (FDC) network and present the highest density of cognate peptides to follicular helper T (Tfh) cells, which provide survival signals to the B cell. bnAbs are therefore expected to evolve only when the B cell lineage evolving breadth is consistently capturing and presenting more peptides to Tfh cells than othermore » lineages of more specific B cells. Here we develop mathematical models of Tfh cells in germinal centers to explicitly define the mechanisms of selection in this complex evolutionary process. Our results suggest that broadly reactive B cells presenting a high density of peptides bound to major histocompatibility complex class II molecules (pMHC) are readily outcompeted by B cells responding to lineages of HIV-1 that transiently dominate the within host viral population. Conversely, if broadly reactive B cells acquire a large variety of several HIV-1 proteins from the FDC network and present a high diversity of several pMHC, they can be rescued by a large fraction of the Tfh cell repertoire in the germinal center. Under such circumstances the evolution of bnAbs is much more consistent. Increasing either the magnitude of the Tfh cell response or the breadth of the Tfh cell repertoire markedly facilitates the evolution of bnAbs. Because both the magnitude and breadth can be increased by vaccination with several HIV-1 proteins, this calls for experimental testing. Many HIV-infected patients slowly evolve antibodies that can neutralize a large variety of viruses. Such broadly neutralizing antibodies (bnAbs) could in the future become therapeutic agents. bnAbs appear very late, and patients are typically not protected by them. At the moment, we fail to understand why this takes so long and how the immune system selects for broadly neutralizing capacity. Typically, antibodies are selected based on affinity and not on breadth. We developed mathematical models to study two different mechanisms by which the immune system can select for broadly neutralizing capacity. One of these is based upon the repertoire of different follicular helper T (Tfh) cells in germinal centers. In conclusion, we suggest that broadly reactive B cells may interact with a larger fraction of this repertoire and demonstrate that this would select for bnAbs. Intriguingly, this suggests that broadening the Tfh cell repertoire by vaccination may speed up the evolution of bnAbs.« less

How Germinal Centers Evolve Broadly Neutralizing Antibodies: the Breadth of the Follicular Helper T Cell Response

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Boer, Rob J.; Perelson, Alan S.

Many HIV-1-infected patients evolve broadly neutralizing antibodies (bnAbs). This evolutionary process typically takes several years and is poorly understood as selection taking place in germinal centers occurs on the basis of antibody affinity. B cells with the highest-affinity receptors tend to acquire the most antigen from the follicular dendritic cell (FDC) network and present the highest density of cognate peptides to follicular helper T (Tfh) cells, which provide survival signals to the B cell. bnAbs are therefore expected to evolve only when the B cell lineage evolving breadth is consistently capturing and presenting more peptides to Tfh cells than othermore » lineages of more specific B cells. Here we develop mathematical models of Tfh cells in germinal centers to explicitly define the mechanisms of selection in this complex evolutionary process. Our results suggest that broadly reactive B cells presenting a high density of peptides bound to major histocompatibility complex class II molecules (pMHC) are readily outcompeted by B cells responding to lineages of HIV-1 that transiently dominate the within host viral population. Conversely, if broadly reactive B cells acquire a large variety of several HIV-1 proteins from the FDC network and present a high diversity of several pMHC, they can be rescued by a large fraction of the Tfh cell repertoire in the germinal center. Under such circumstances the evolution of bnAbs is much more consistent. Increasing either the magnitude of the Tfh cell response or the breadth of the Tfh cell repertoire markedly facilitates the evolution of bnAbs. Because both the magnitude and breadth can be increased by vaccination with several HIV-1 proteins, this calls for experimental testing. Many HIV-infected patients slowly evolve antibodies that can neutralize a large variety of viruses. Such broadly neutralizing antibodies (bnAbs) could in the future become therapeutic agents. bnAbs appear very late, and patients are typically not protected by them. At the moment, we fail to understand why this takes so long and how the immune system selects for broadly neutralizing capacity. Typically, antibodies are selected based on affinity and not on breadth. We developed mathematical models to study two different mechanisms by which the immune system can select for broadly neutralizing capacity. One of these is based upon the repertoire of different follicular helper T (Tfh) cells in germinal centers. In conclusion, we suggest that broadly reactive B cells may interact with a larger fraction of this repertoire and demonstrate that this would select for bnAbs. Intriguingly, this suggests that broadening the Tfh cell repertoire by vaccination may speed up the evolution of bnAbs.« less

Effectiveness of motorcycle antilock braking systems (ABS) in reducing crashes, the first cross-national study.

PubMed

Rizzi, Matteo; Strandroth, Johan; Kullgren, Anders; Tingvall, Claes; Fildes, Brian

2015-01-01

This study set out to evaluate the effectiveness of motorcycle antilock braking systems (ABS) in reducing real-life crashes. Since the European Parliament has voted on legislation making ABS mandatory on all new motorcycles over 125 cc from 2016, the fitment rate in Europe is likely to increase in the coming years. Though previous research has focused on mostly large displacement motorcycles, this study used police reports from Spain (2006-2009), Italy (2009), and Sweden (2003-2012) in order to analyze a wide range of motorcycles, including scooters, and compare countries with different motorcycling habits. The statistical analysis used odds ratio calculations with an induced exposure approach. Previous research found that head-on crashes were the least ABS-affected crash type and was therefore used as the nonsensitive crash type for ABS in these calculations. The same motorcycle models, with and without ABS, were compared and the calculations were carried out for each country separately. Crashes involving only scooters were further analyzed. The effectiveness of motorcycle ABS in reducing injury crashes ranged from 24% (95% confidence interval [CI], 12-36) in Italy to 29% (95% CI, 20-38) in Spain, and 34% (95% CI, 16-52) in Sweden. The reductions in severe and fatal crashes were even greater, at 34% (95% CI, 24-44) in Spain and 42% (95% CI, 23-61) in Sweden. The overall reductions of crashes involving ABS-equipped scooters (at least 250 cc) were 27% (95% CI, 12-42) in Italy and 22% (95% CI, 2-42) in Spain. ABS on scooters with at least a 250 cc engine reduced severe and fatal crashes by 31% (95% CI, 12-50), based on Spanish data alone. At this stage, there is more than sufficient scientific-based evidence to support the implementation of ABS on all motorcycles, even light ones. Further research should aim at understanding the injury mitigating effects of motorcycle ABS, possibly in combination with combined braking systems.

Prediction of probable mutations in influenza virus hemagglutinin protein based on large-scale ab initio fragment molecular orbital calculations.

PubMed

Yoshioka, Akio; Fukuzawa, Kaori; Mochizuki, Yuji; Yamashita, Katsumi; Nakano, Tatsuya; Okiyama, Yoshio; Nobusawa, Eri; Nakajima, Katsuhisa; Tanaka, Shigenori

2011-09-01

Ab initio electronic-state calculations for influenza virus hemagglutinin (HA) trimer complexed with Fab antibody were performed on the basis of the fragment molecular orbital (FMO) method at the second and third-order Møller-Plesset (MP2 and MP3) perturbation levels. For the protein complex containing 2351 residues and 36,160 atoms, the inter-fragment interaction energies (IFIEs) were evaluated to illustrate the effective interactions between all the pairs of amino acid residues. By analyzing the calculated data on the IFIEs, we first discussed the interactions and their fluctuations between multiple domains contained in the trimer complex. Next, by combining the IFIE data between the Fab antibody and each residue in the HA antigen with experimental data on the hemadsorption activity of HA mutants, we proposed a protocol to predict probable mutations in HA. The proposed protocol based on the FMO-MP2.5 calculation can explain the historical facts concerning the actual mutations after the emergence of A/Hong Kong/1/68 influenza virus with subtype H3N2, and thus provides a useful methodology to enumerate those residue sites likely to mutate in the future. Copyright © 2011 Elsevier Inc. All rights reserved.

Giant increase of critical current density and vortex pinning in Mn doped K{sub x}Fe{sub 2−y}Se{sub 2} single crystals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Mingtao; Zhang, Jincang, E-mail: jczhang@staff.shu.edu.cn; Materials Genome Institute, Shanghai University, Shanghai 200444

2014-11-10

We report a comparative study of the critical current density (J{sub c}) and vortex pinning among pure and Mn doped K{sub x}Fe{sub 2−y}Se{sub 2} single crystals. It is found that the J{sub c} values can be greatly improved by Mn doping and post-quenching treatment when comparing to pristine pure sample. In contrast to pure samples, an anomalous second magnetization peak (SMP) effect is observed in both 1% and 2% Mn doped samples at T = 3 K for H∥ab but not for H∥c. Referring to Dew-Hughes and Kramer's model, we performed scaling analyses of the vortex pinning force density vs magnetic field inmore » 1% Mn doped and quenched pristine crystals. The results show that the normal point defects are the dominant pinning sources, which probably originate from the variations of intercalated K atoms. We propose that the large nonsuperconducting K-Mn-Se inclusions may contribute to the partial normal surface pinning and give rise to the anomalous SMP effect for H∥ab in Mn doped crystals. These results may facilitate further understanding of the superconductivity and vortex pinning in intercalated iron-selenides superconductors.« less

Production and characterization of murine monoclonal antibody against synthetic peptide of CD34.

PubMed

Maleki, Leili Aghebati; Majidi, Jafar; Baradaran, Behzad; Abdolalizadeh, Jalal; Akbari, Aliakbar Movassaghpour

2013-01-01

The treatment of hematologic malignancies and immunodeficiency diseases are offered by hematopoietic stem cells (HSCs) as a unique self-renewal and differentiation source which most commonly is selected by CD34 surface marker for HSC. The purpose of this study was to develop and characterize monoclonal antibody against CD34 antigen for detection of hematopoietic stem cells. Balb/c mice were immunized with two synthetic peptides of CD34 and Spleen cells were fused with SP2/0.Fused cells were grown in hypoxanthine, aminopterine and thymidine (HAT) selective medium and cloned by limiting dilution. Large scale of monoclonal antibodies was produced by mouse ascites production of mAb (in vivo) method. Monoclonal antibody was purified by chromatography. Then reactivity of these antibodies was evaluated in different immunological assays including ELISA, immunofluorescence (IF), western blot (WB) and flowcytometry. In this study, between five positive clone wells, two clones were chosen for limiting dilution. Limiting dilution product was one monoclone (3-D5 monoclone) with absorbance about 2. Isotype of this mAb was identified as IgG1 class with Kappa (κ) light chain. This antibody is highly specific and functional in biomedical applications such as ELISA, flowcytometry, immunofluorescence, and western blot assays.

Recombinant antibodies encoded by IGHV1-69 react with pUL32, a phosphoprotein of cytomegalovirus and B-cell superantigen

PubMed Central

Steininger, Christoph; Widhopf, George F.; Ghia, Emanuela M.; Morello, Christopher S.; Vanura, Katrina; Sanders, Rebecca; Spector, Deborah; Guiney, Don; Jäger, Ulrich

2012-01-01

Leukemia cells from patients with chronic lymphocytic leukemia (CLL) express a highly restricted immunoglobulin heavy variable chain (IGHV) repertoire, suggesting that a limited set of antigens reacts with leukemic cells. Here, we evaluated the reactivity of a panel of different CLL recombinant antibodies (rAbs) encoded by the most commonly expressed IGHV genes with a panel of selected viral and bacterial pathogens. Six different CLL rAbs encoded by IGHV1-69 or IGHV3-21, but not a CLL rAb encoded by IGHV4-39 genes, reacted with a single protein of human cytomegalovirus (CMV). The CMV protein was identified as the large structural phosphoprotein pUL32. In contrast, none of the CLL rAbs bound to any other structure of CMV, adenovirus serotype 2, Salmonella enterica serovar Typhimurium, or of cells used for propagation of these microorganisms. Monoclonal antibodies or humanized rAbs of irrelevant specificity to pUL32 did not react with any of the proteins present in the different lysates. Still, rAbs encoded by a germ line IGHV1-69 51p1 allele from CMV-seropositive and -negative adults also reacted with pUL32. The observed reactivity of multiple different CLL rAbs and natural antibodies from CMV-seronegative adults with pUL32 is consistent with the properties of a superantigen. PMID:22234695

Autoantibody Signaling in Pemphigus Vulgaris: Development of an Integrated Model

PubMed Central

Sajda, Thomas; Sinha, Animesh A.

2018-01-01

Pemphigus vulgaris (PV) is an autoimmune skin blistering disease effecting both cutaneous and mucosal epithelia. Blister formation in PV is known to result from the binding of autoantibodies (autoAbs) to keratinocyte antigens. The primary antigenic targets of pathogenic autoAbs are known to be desmoglein 3, and to a lesser extent, desmoglein 1, cadherin family proteins that partially comprise the desmosome, a protein structure responsible for maintaining cell adhesion, although additional autoAbs, whose role in blister formation is still unclear, are also known to be present in PV patients. Nevertheless, there remain large gaps in knowledge concerning the precise mechanisms through which autoAb binding induces blister formation. Consequently, the primary therapeutic interventions for PV focus on systemic immunosuppression, whose side effects represent a significant health risk to patients. In an effort to identify novel, disease-specific therapeutic targets, a multitude of studies attempting to elucidate the pathogenic mechanisms downstream of autoAb binding, have led to significant advancements in the understanding of autoAb-mediated blister formation. Despite this enhanced characterization of disease processes, a satisfactory explanation of autoAb-induced acantholysis still does not exist. Here, we carefully review the literature investigating the pathogenic disease mechanisms in PV and, taking into account the full scope of results from these studies, provide a novel, comprehensive theory of blister formation in PV. PMID:29755451

FeP(Im)–AB Bonding Energies Evaluated with A Large Number of Density Functionals (P = porphine, Im = imidazole, AB = CO, NO, and O2)

PubMed Central

Liao, Meng-Sheng; Huang, Ming-Ju; Watts, John D.

2011-01-01

Sixty-four (64) density functionals, ranging from GGA, meta-GGA, hybrid GGA to hybrid meta-GGA, were tested to evaluate the FeP(Im)-AB bonding energies (Ebond) in the heme model complexes FeP(Im)(AB) (P = porphine, Im = imidazole, AB = CO, NO, and O2). The results indicate that an accurate prediction of Ebond for the various ligands to heme is difficult with the DFT methods; usually a functional successful for one system does not perform equally well for the other system(s). Relatively satisfactory results for the various FeP(Im)-AB bonding energies are obtained with the meta-GGA funtionals BLAP3 and Bmτ1; they yield Ebond values of ca.1.1, 1.2, and 0.4 eV for AB = CO, NO, and O2, respectively, which are in reasonable agreement with experimental data (0.78 – 0.85 eV for CO, 0.99 eV for NO, and 0.44 – 0.53 eV for O2). The other functionals show more or less deficiency for one or two of the systems. The performances of the various functionals in describing the spin-state energetics of the five-coordinate FeP(Im) complex were also examined. PMID:22228914

Platelet-rich plasma versus autologous blood versus steroid injection in lateral epicondylitis: systematic review and network meta-analysis.

PubMed

Arirachakaran, Alisara; Sukthuayat, Amnat; Sisayanarane, Thaworn; Laoratanavoraphong, Sorawut; Kanchanatawan, Wichan; Kongtharvonskul, Jatupon

2016-06-01

Clinical outcomes between the use of platelet-rich plasma (PRP), autologous blood (AB) and corticosteroid (CS) injection in lateral epicondylitis are still controversial. A systematic review and network meta-analysis of randomized controlled trials was conducted with the aim of comparing relevant clinical outcomes between the use of PRP, AB and CS injection. Medline and Scopus databases were searched from inception to January 2015. A network meta-analysis was performed by applying weight regression for continuous outcomes and a mixed-effect Poisson regression for dichotomous outcomes. Ten of 374 identified studies were eligible. When compared to CS, AB injection showed significantly improved effects with unstandardized mean differences (UMD) in pain visual analog scale (VAS), Disabilities of Arm Shoulder and Hand (DASH), Patient-Related Tennis Elbow Evaluation (PRTEE) score and pressure pain threshold (PPT) of -2.5 (95 % confidence interval, -3.5, -1.5), -25.5 (-33.8, -17.2), -5.3 (-9.1, -1.6) and 9.9 (5.6, 14.2), respectively. PRP injections also showed significantly improved VAS and DASH scores when compared with CS. PRP showed significantly better VAS with UMD when compared to AB injection. AB injection has a higher risk of adverse effects, with a relative risk of 1.78 (1.00, 3.17), when compared to CS. The network meta-analysis suggested no statistically significant difference in multiple active treatment comparisons of VAS, DASH and PRTEE when comparing PRP and AB injections. However, AB injection had improved DASH score and PPT when compared with PRP injection. In terms of adverse effects, AB injection had a higher risk than PRP injection. This network meta-analysis provided additional information that PRP injection can improve pain and lower the risk of complications, whereas AB injection can improve pain, disabilities scores and pressure pain threshold but has a higher risk of complications. Level I evidence.

Spatiotemporal heterogeneity of antibiotic pollution and ecological risk assessment in Taihu Lake Basin, China.

PubMed

Xu, Zhaoan; Li, Tao; Bi, Jun; Wang, Ce

2018-06-20

Natural lakes play a vital role as receiving system of a cocktail of antibiotics (ABs) which have triggered a major health concern. The comparisons of ABs concentrations have been substantially implemented throughout the worldwide range. However, from lake management, the questions are not yet adequately solved: "when and where does the overall pollution level of ABs present more serious, and what AB species dominate". In this study, we detected 22 ABs in water column and sediment bottom in Taihu Lake Basin in January, April, July and October in 2017. Non-metric multi-dimensional scaling (NMDS) was applied to characterize spatiotemporal dissimilarity of ABs concentrations. Combined with a method of summed standardized concentrations, analysis of variance was applied to evaluate the overall pollution level of ABs at different sites and time periods, instead of, traditionally, a comparison of concentration. The results showed that 90% CI of Macrolides, Sulfonamides, Tetracyclines and Quinolones were 0.020-5.646, 0.040-7.887, 0.100-13.308 and 0.130-9.631 ng/L in water column, respectively; and 0.005-1.532, 0.002-0.120, 0.010-0.902 and 0.006-3.972 μg/kg in sediment, respectively. ABs concentrations approximately presented spatial homogeneity in the whole basin which included all main inflow rivers, outflow rivers and the lake body itself. Species composition was seasonally distinct and the overall pollution level was significantly lower in autumn. A critical body residue analysis showed that ABs concentrations presented a neglectable cumulative risk for fish species. This research added to the body of knowledge to develop pollution management strategies on point and non-point source loads for Taihu Lake Basin, and also the methodology provided reference for spatiotemporal characterization of dissolved pollutant in other water bodies. Copyright © 2018 Elsevier B.V. All rights reserved.

Thyroid peroxidase antibodies during early gestation and the subsequent risk of first-onset postpartum depression: A prospective cohort study.

PubMed

Wesseloo, Richard; Kamperman, Astrid M; Bergink, Veerle; Pop, Victor J M

2018-01-01

During the postpartum period, women are at risk for the new onset of both auto-immune thyroid disorders and depression. The presence of thyroid peroxidase antibodies (TPO-ab) during early gestation is predictive for postpartum auto-immune thyroid dysfunction. The aim of this study was to investigate the association between TPO-ab status during early gestation and first-onset postpartum depression. Prospective cohort study (n = 1075) with follow-up during pregnancy up to one year postpartum. Thyroid function and TPO-ab status were measured during early gestation. Depressive symptomatology was assessed during each trimester and at four time points postpartum with the Edinburgh Depression Scale (EDS). Women with antenatal depression were not eligible for inclusion. Self-reported postpartum depression was defined with an EDS cut-off of ≥ 13. The cumulative incidence of self-reported first-onset depression in the first postpartum year was 6.3%. A positive TPO-ab status was associated with an increased risk for self-reported first-onset depression at four months postpartum (adjusted OR 3.8; 95% CI 1.3-11.6), but not at other postpartum time points. Prevalence rates of self-reported postpartum depression declined after four months postpartum in the TPO-ab positive group, but remained constant in the TPO-ab negative group. Depression was defined with a self-rating questionnaire (EDS). Women with an increased TPO-ab titer during early gestation are at increased risk for self-reported first-onset depression. The longitudinal pattern of self-reported postpartum depression in the TPO-ab positive group was similar to the typical course of postpartum TPO-ab titers changes. This suggests overlap in the etiology of first-onset postpartum depression and auto-immune thyroid dysfunction. Thyroid function should be evaluated in women with first-onset postpartum depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigations for Thermal and Electrical Conductivity of ABS-Graphene Blended Prototypes

PubMed Central

Singh, Rupinder; Sandhu, Gurleen S.; Penna, Rosa; Farina, Ilenia

2017-01-01

The thermoplastic materials such as acrylonitrile-butadiene-styrene (ABS) and Nylon have large applications in three-dimensional printing of functional/non-functional prototypes. Usually these polymer-based prototypes are lacking in thermal and electrical conductivity. Graphene (Gr) has attracted impressive enthusiasm in the recent past due to its natural mechanical, thermal, and electrical properties. This paper presents the step by step procedure (as a case study) for development of an in-house ABS-Gr blended composite feedstock filament for fused deposition modelling (FDM) applications. The feedstock filament has been prepared by two different methods (mechanical and chemical mixing). For mechanical mixing, a twin screw extrusion (TSE) process has been used, and for chemical mixing, the composite of Gr in an ABS matrix has been set by chemical dissolution, followed by mechanical blending through TSE. Finally, the electrical and thermal conductivity of functional prototypes prepared from composite feedstock filaments have been optimized. PMID:28773244

Modeling the hydration of mono-atomic anions from the gas phase to the bulk phase: the case of the halide ions F-, Cl-, and Br-.

PubMed

Trumm, Michael; Martínez, Yansel Omar Guerrero; Réal, Florent; Masella, Michel; Vallet, Valérie; Schimmelpfennig, Bernd

2012-01-28

In this work, we investigate the hydration of the halide ions fluoride, chloride, and bromide using classical molecular dynamics simulations at the 10 ns scale and based on a polarizable force-field approach, which treats explicitly the cooperative bond character of strong hydrogen bond networks. We have carried out a thorough analysis of the ab initio data at the MP2 or CCSD(T) level concerning anion/water clusters in gas phase to adjust the force-field parameters. In particular, we consider the anion static polarizabilities computed in gas phase using large atomic basis sets including additional diffuse functions. The information extracted from trajectories in solution shows well structured first hydration shells formed of 6.7, 7.0, and 7.6 water molecules at about 2.78 Å, 3.15 Å, and 3.36 Å for fluoride, chloride, and bromide, respectively. These results are in excellent agreement with the latest neutron- and x-ray diffraction studies. In addition, our model reproduces several other properties of halide ions in solution, such as diffusion coefficients, description of hydration processes, and exchange reactions. Moreover, it is also able to reproduce the electrostatic properties of the anions in solution (in terms of anion dipole moment) as reported by recent ab initio quantum simulations. All the results show the ability of the proposed model in predicting data, as well as the need of accounting explicitly for the cooperative character of strong hydrogen bonds to reproduce ab initio potential energy surfaces in a mean square sense and to build up a reliable force field. © 2012 American Institute of Physics

The molecular composition of dense interstellar clouds

NASA Technical Reports Server (NTRS)

Allen, M.; Robinson, G. W.

1977-01-01

Presented in this paper is an ab initio chemical model for dense interstellar clouds that incorporates 598 grain surface reactions, with small grains providing the reaction area. Gas-phase molecules are depleted through collisions with grains. The abundances of 372 chemical species are calculated as a function of time and are found to be of sufficient magnitude to explain most observations. Peak abundances are achieved on time scales of the order of 100,000 to 1 million years, depending on cloud density and kinetic temperature. The reaction rates for ion-molecule chemistry are approximately the same, indicating that surface and gas-phase chemistry may be coupled in certain regions. The composition of grain mantles is shown to be a function of grain radius. In certain grain-size ranges, large molecules containing two or more heavy atoms are more predominant than lighter 'ices' - H2O, NH3, and CH4. It is possible that absorption due to these large molecules in the mantle may contribute to the observed 3-micron band in astronomical spectra.

Adaptive optics imaging of healthy and abnormal regions of retinal nerve fiber bundles of patients with glaucoma.

PubMed

Chen, Monica F; Chui, Toco Y P; Alhadeff, Paula; Rosen, Richard B; Ritch, Robert; Dubra, Alfredo; Hood, Donald C

2015-01-08

To better understand the nature of glaucomatous damage of the macula, especially the structural changes seen between relatively healthy and clearly abnormal (AB) retinal regions, using an adaptive optics scanning light ophthalmoscope (AO-SLO). Adaptive optics SLO images and optical coherence tomography (OCT) vertical line scans were obtained on one eye of seven glaucoma patients, with relatively deep local arcuate defects on the 10-2 visual field test in one (six eyes) or both hemifields (one eye). Based on the OCT images, the retinal nerve fiber (RNF) layer was divided into two regions: (1) within normal limits (WNL), relative RNF layer thickness within mean control values ±2 SD; and (2) AB, relative thickness less than -2 SD value. As seen on AO-SLO, the pattern of AB RNF bundles near the border of the WNL and AB regions differed across eyes. There were normal-appearing bundles in the WNL region of all eyes and AB-appearing bundles near the border with the AB region. This region with AB bundles ranged in extent from a few bundles to the entire AB region in the case of one eye. All other eyes had a large AB region without bundles. However, in two of these eyes, a few bundles were seen within this region of otherwise missing bundles. The AO-SLO images revealed details of glaucomatous damage that are difficult, if not impossible, to see with current OCT technology. Adaptive optics SLO may prove useful in following progression in clinical trials, or in disease management, if AO-SLO becomes widely available and easy to use. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Thermoelectric properties of Bi 2Sr 2Co 2O y thin films and single crystals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diao, Zhenyu; Lee, Ho Nyung; Chisholm, Matthew F.

Bi 2Sr 2Co 2O 9 exhibits a misfit-layered structure with good thermoelectric properties. We have investigated the thermoelectric properties of Bi 2Sr 2Co 2O y in both thin-film and single-crystal forms. Among thin films grown at different temperatures, we find that both the in-plane thermoelectric power (Sab) and electrical resistivity (ρab) vary in an opposite trend, i.e., Sab is high when ρab is small. This results in large power factor (S ab 2/ρab~5.5 μW/K 2 cm for the film grown at 700 °C), comparable to that for whiskers. For single crystals, the electrical resistivity shows metallic behavior in a largemore » temperature range, but has higher magnitude than that of films grown at 675 °C and 700 °C. The annealing of single crystals under Ar atmosphere leads to even higher resistivity while S ab is improved. Lastly, we discuss the thermoelectric performance of this material considering both oxygen concentration and phase purity.« less

Thermoelectric properties of Bi 2Sr 2Co 2O y thin films and single crystals

DOE PAGES

Diao, Zhenyu; Lee, Ho Nyung; Chisholm, Matthew F.; ...

2017-02-02

Bi 2Sr 2Co 2O 9 exhibits a misfit-layered structure with good thermoelectric properties. We have investigated the thermoelectric properties of Bi 2Sr 2Co 2O y in both thin-film and single-crystal forms. Among thin films grown at different temperatures, we find that both the in-plane thermoelectric power (Sab) and electrical resistivity (ρab) vary in an opposite trend, i.e., Sab is high when ρab is small. This results in large power factor (S ab 2/ρab~5.5 μW/K 2 cm for the film grown at 700 °C), comparable to that for whiskers. For single crystals, the electrical resistivity shows metallic behavior in a largemore » temperature range, but has higher magnitude than that of films grown at 675 °C and 700 °C. The annealing of single crystals under Ar atmosphere leads to even higher resistivity while S ab is improved. Lastly, we discuss the thermoelectric performance of this material considering both oxygen concentration and phase purity.« less

Role of Fc in Antibody-Mediated Protection from Ricin Toxin

PubMed Central

Pincus, Seth. H.; Das, Anushka; Song, Kejing; Maresh, Grace A.; Corti, Miriam; Berry, Jody

2014-01-01

We have studied the role of the antibody (Ab) Fc region in mediating protection from ricin toxicity. We compared the in vitro and in vivo effects of intact Ig and of Fab fragments derived from two different neutralizing Ab preparations, one monoclonal, the other polyclonal. Consistent results were obtained from each, showing little difference between Ig and Fab in terms of antigen binding and in vitro neutralization, but with relatively large differences in protection of animals. We also studied whether importing Ab into the cell by Fc receptors enhanced the intracellular neutralization of ricin toxin. We found that the imported Ab was found in the ER and Golgi, a compartment traversed by ricin, as it traffics through the cell, but intracellular Ab did not contribute to the neutralization of ricin. These results indicate that the Fc region of antibody is important for in vivo protection, although the mechanism of enhanced protection by intact Ig does not appear to operate at the single cell level. When using xenogeneic antibodies, the diminished immunogenicity of Fab/F(ab’)2 preparations should be balanced against possible loss of protective efficacy. PMID:24811206

Expression and purification of a novel therapeutic single-chain variable fragment antibody against BNP from inclusion bodies of Escherichia coli.

PubMed

Bu, Dawei; Zhou, Yuwei; Tang, Jian; Jing, Fang; Zhang, Wei

2013-12-01

Abnormal brain natriuretic peptide (BNP) secretion is regarded as the dominating mechanism of cerebral salt wasting syndrome (CSW), which results from a renal loss of sodium and water during intracranial disease leading to hyponatremia. Scale preparation of therapeutic single-chain variable fragment (scFv) that can neutralize elevated circulating BNP may have potential value for clinical use. In this report, we used a recently isolated humanized anti-BNP scFv fragment (3C1) as model antibody (Ab) to evaluate the potential of scale production of this therapeutic protein. The truncated gene encoding for scFv fragment cloned in pET22b (+) was mainly overexpressed as inclusion bodies in Escherichia coli (E. coli) Rosetta (DE3) pLysS cells. The insoluble fragment was solubilized and purified by Ni-NTA agarose resin under denaturation conditions, and recovered via an effective refolding buffer containing 50 mM Tris-HCl, pH 8.0, 0.15 M NaCl, 1 mM EDTA, 0.5 M arginine, 2 mM GSH, 1 mM GSSG, and 5% glycerol. The refolded scFv fragment was concentrated by PEG20000, and dialyzed in PBS (containing 5% glycerol, pH 7.4). The final yield was approximately 10.2 mg active scFv fragment per liter of culture (3.4 g wet weight cells). The scFv fragment was more than 95% pure assessed by SDS-PAGE assay. Recombinant scFv fragment with His tag displayed its immunoreactivity with anti-His tag Ab by western blotting. ELISA showed the scFv fragment specifically bound to BNP, and it displayed similar activity as the traditional anti-BNP monoclonal Ab (mAb). Thus, the current strategy allows convenient small-scale production of this therapeutic protein. Copyright © 2013 Elsevier Inc. All rights reserved.

Teaching the Blind to Find Their Way by Playing Video Games

PubMed Central

Merabet, Lotfi B.; Connors, Erin C.; Halko, Mark A.; Sánchez, Jaime

2012-01-01

Computer based video games are receiving great interest as a means to learn and acquire new skills. As a novel approach to teaching navigation skills in the blind, we have developed Audio-based Environment Simulator (AbES); a virtual reality environment set within the context of a video game metaphor. Despite the fact that participants were naïve to the overall purpose of the software, we found that early blind users were able to acquire relevant information regarding the spatial layout of a previously unfamiliar building using audio based cues alone. This was confirmed by a series of behavioral performance tests designed to assess the transfer of acquired spatial information to a large-scale, real-world indoor navigation task. Furthermore, learning the spatial layout through a goal directed gaming strategy allowed for the mental manipulation of spatial information as evidenced by enhanced navigation performance when compared to an explicit route learning strategy. We conclude that the immersive and highly interactive nature of the software greatly engages the blind user to actively explore the virtual environment. This in turn generates an accurate sense of a large-scale three-dimensional space and facilitates the learning and transfer of navigation skills to the physical world. PMID:23028703

Ab initio calculation of the shear viscosity of neon in the liquid and hypercritical state over a wide pressure and temperature range

NASA Astrophysics Data System (ADS)

Eggenberger, Rolf; Gerber, Stefan; Huber, Hanspeter; Searles, Debra; Welker, Marc

1992-08-01

The shear viscosity is calculated ab initio for the liquid and hypercritical state, i.e. a previously published potential for Ne 2, obtained from ab initio calculations including electron correlation, is used in classical equilibrium molecular dynamics simulations to obtain the shear viscosity from a Green-Kubo integral. The quality of the results is quite uniform over a large pressure range up to 1000 MPa and a wide temperature range from 26 to 600 K. In most cases the calculated shear viscosity deviates by less than 10% from the experimental value, in general the error being only a few percent.

Cell Culture Systems To Study Human Herpesvirus 6A/B Chromosomal Integration.

PubMed

Gravel, Annie; Dubuc, Isabelle; Wallaschek, Nina; Gilbert-Girard, Shella; Collin, Vanessa; Hall-Sedlak, Ruth; Jerome, Keith R; Mori, Yasuko; Carbonneau, Julie; Boivin, Guy; Kaufer, Benedikt B; Flamand, Louis

2017-07-15

Human herpesviruses 6A/B (HHV-6A/B) can integrate their viral genomes in the telomeres of human chromosomes. The viral and cellular factors contributing to HHV-6A/B integration remain largely unknown, mostly due to the lack of efficient and reproducible cell culture models to study HHV-6A/B integration. In this study, we characterized the HHV-6A/B integration efficiencies in several human cell lines using two different approaches. First, after a short-term infection (5 h), cells were processed for single-cell cloning and analyzed for chromosomally integrated HHV-6A/B (ciHHV-6A/B). Second, cells were infected with HHV-6A/B and allowed to grow in bulk for 4 weeks or longer and then analyzed for the presence of ciHHV-6. Using quantitative PCR (qPCR), droplet digital PCR, and fluorescent in situ hybridization, we could demonstrate that HHV-6A/B integrated in most human cell lines tested, including telomerase-positive (HeLa, MCF-7, HCT-116, and HEK293T) and telomerase-negative cell lines (U2OS and GM847). Our results also indicate that inhibition of DNA replication, using phosphonoacetic acid, did not affect HHV-6A/B integration. Certain clones harboring ciHHV-6A/B spontaneously express viral genes and proteins. Treatment of cells with phorbol ester or histone deacetylase inhibitors triggered the expression of many viral genes, including U39 , U90 , and U100 , without the production of infectious virus, suggesting that the tested stimuli were not sufficient to trigger full reactivation. In summary, both integration models yielded comparable results and should enable the identification of viral and cellular factors contributing to HHV-6A/B integration and the screening of drugs influencing viral gene expression, as well as the release of infectious HHV-6A/B from the integrated state. IMPORTANCE The analysis and understanding of HHV-6A/B genome integration into host DNA is currently limited due to the lack of reproducible and efficient viral integration systems. In the present study, we describe two quantitative cell culture viral integration systems. These systems can be used to define cellular and viral factors that play a role in HHV-6A/B integration. Furthermore, these systems will allow us to decipher the conditions resulting in virus gene expression and excision of the integrated viral genome resulting in reactivation. Copyright © 2017 American Society for Microbiology.

How Many-Body Correlations and α Clustering Shape He 6

DOE Office of Scientific and Technical Information (OSTI.GOV)

Romero-Redondo, Carolina; Quaglioni, Sofia; Navrátil, Petr

The Borromean 6He nucleus is an exotic system characterized by two halo neutrons orbiting around a compact 4He (or α) core, in which the binary subsystems are unbound. The simultaneous reproduction of its small binding energy and extended matter and point-proton radii has been a challenge for ab initio theoretical calculations based on traditional bound-state methods. Using soft nucleon-nucleon interactions based on chiral effective field theory potentials, we show that supplementing the model space with 4He + n + n cluster degrees of freedom largely solves this issue. Lastly, we analyze the role played by α clustering and many-body correlations,more » and study the dependence of the energy spectrum on the resolution scale of the interaction.« less

Precision Mass Measurements of Cr-6358 : Nuclear Collectivity Towards the N =40 Island of Inversion

NASA Astrophysics Data System (ADS)

Mougeot, M.; Atanasov, D.; Blaum, K.; Chrysalidis, K.; Goodacre, T. Day; Fedorov, D.; Fedosseev, V.; George, S.; Herfurth, F.; Holt, J. D.; Lunney, D.; Manea, V.; Marsh, B.; Neidherr, D.; Rosenbusch, M.; Rothe, S.; Schweikhard, L.; Schwenk, A.; Seiffert, C.; Simonis, J.; Stroberg, S. R.; Welker, A.; Wienholtz, F.; Wolf, R. N.; Zuber, K.

2018-06-01

The neutron-rich isotopes Cr 58 - 63 were produced for the first time at the ISOLDE facility and their masses were measured with the ISOLTRAP spectrometer. The new values are up to 300 times more precise than those in the literature and indicate significantly different nuclear structure from the new mass-surface trend. A gradual onset of deformation is found in this proton and neutron midshell region, which is a gateway to the second island of inversion around N =40 . In addition to comparisons with density-functional theory and large-scale shell-model calculations, we present predictions from the valence-space formulation of the ab initio in-medium similarity renormalization group, the first such results for open-shell chromium isotopes.

Electron-phonon interaction within classical molecular dynamics

DOE PAGES

Tamm, A.; Samolyuk, G.; Correa, A. A.; ...

2016-07-14

Here, we present a model for nonadiabatic classical molecular dynamics simulations that captures with high accuracy the wave-vector q dependence of the phonon lifetimes, in agreement with quantum mechanics calculations. It is based on a local view of the e-ph interaction where individual atom dynamics couples to electrons via a damping term that is obtained as the low-velocity limit of the stopping power of a moving ion in a host. The model is parameter free, as its components are derived from ab initio-type calculations, is readily extended to the case of alloys, and is adequate for large-scale molecular dynamics computermore » simulations. We also show how this model removes some oversimplifications of the traditional ionic damped dynamics commonly used to describe situations beyond the Born-Oppenheimer approximation.« less

How Many-Body Correlations and α Clustering Shape He 6

DOE PAGES

Romero-Redondo, Carolina; Quaglioni, Sofia; Navrátil, Petr; ...

2016-11-23

The Borromean 6He nucleus is an exotic system characterized by two halo neutrons orbiting around a compact 4He (or α) core, in which the binary subsystems are unbound. The simultaneous reproduction of its small binding energy and extended matter and point-proton radii has been a challenge for ab initio theoretical calculations based on traditional bound-state methods. Using soft nucleon-nucleon interactions based on chiral effective field theory potentials, we show that supplementing the model space with 4He + n + n cluster degrees of freedom largely solves this issue. Lastly, we analyze the role played by α clustering and many-body correlations,more » and study the dependence of the energy spectrum on the resolution scale of the interaction.« less

Ultracold Atoms in a Square Lattice with Spin-Orbit Coupling: Charge Order, Superfluidity, and Topological Signatures

NASA Astrophysics Data System (ADS)

Rosenberg, Peter; Shi, Hao; Zhang, Shiwei

2017-12-01

We present an ab initio, numerically exact study of attractive fermions in square lattices with Rashba spin-orbit coupling. The ground state of this system is a supersolid, with coexisting charge and superfluid order. The superfluid is composed of both singlet and triplet pairs induced by spin-orbit coupling. We perform large-scale calculations using the auxiliary-field quantum Monte Carlo method to provide the first full, quantitative description of the charge, spin, and pairing properties of the system. In addition to characterizing the exotic physics, our results will serve as essential high-accuracy benchmarks for the intense theoretical and especially experimental efforts in ultracold atoms to realize and understand an expanding variety of quantum Hall and topological superconductor systems.

Scaled effective on-site Coulomb interaction in the DFT+U method for correlated materials

NASA Astrophysics Data System (ADS)

Nawa, Kenji; Akiyama, Toru; Ito, Tomonori; Nakamura, Kohji; Oguchi, Tamio; Weinert, M.

2018-01-01

The first-principles calculation of correlated materials within density functional theory remains challenging, but the inclusion of a Hubbard-type effective on-site Coulomb term (Ueff) often provides a computationally tractable and physically reasonable approach. However, the reported values of Ueff vary widely, even for the same ionic state and the same material. Since the final physical results can depend critically on the choice of parameter and the computational details, there is a need to have a consistent procedure to choose an appropriate one. We revisit this issue from constraint density functional theory, using the full-potential linearized augmented plane wave method. The calculated Ueff parameters for the prototypical transition-metal monoxides—MnO, FeO, CoO, and NiO—are found to depend significantly on the muffin-tin radius RMT, with variations of more than 2-3 eV as RMT changes from 2.0 to 2.7 aB. Despite this large variation in Ueff, the calculated valence bands differ only slightly. Moreover, we find an approximately linear relationship between Ueff(RMT) and the number of occupied localized electrons within the sphere, and give a simple scaling argument for Ueff; these results provide a rationalization for the large variation in reported values. Although our results imply that Ueff values are not directly transferable among different calculation methods (or even the same one with different input parameters such as RMT), use of this scaling relationship should help simplify the choice of Ueff.

Multi-scale theoretical investigation of hydrogen storage in covalent organic frameworks.

PubMed

Tylianakis, Emmanuel; Klontzas, Emmanouel; Froudakis, George E

2011-03-01

The quest for efficient hydrogen storage materials has been the limiting step towards the commercialization of hydrogen as an energy carrier and has attracted a lot of attention from the scientific community. Sophisticated multi-scale theoretical techniques have been considered as a valuable tool for the prediction of materials storage properties. Such techniques have also been used for the investigation of hydrogen storage in a novel category of porous materials known as Covalent Organic Frameworks (COFs). These framework materials are consisted of light elements and are characterized by exceptional physicochemical properties such as large surface areas and pore volumes. Combinations of ab initio, Molecular Dynamics (MD) and Grand Canonical Monte-Carlo (GCMC) calculations have been performed to investigate the hydrogen adsorption in these ultra-light materials. The purpose of the present review is to summarize the theoretical hydrogen storage studies that have been published after the discovery of COFs. Experimental and theoretical studies have proven that COFs have comparable or better hydrogen storage abilities than other competitive materials such as MOF. The key factors that can lead to the improvement of the hydrogen storage properties of COFs are highlighted, accompanied with some recently presented theoretical multi-scale studies concerning these factors.

Ga(+) Basicity and Affinity Scales Based on High-Level Ab Initio Calculations.

PubMed

Brea, Oriana; Mó, Otilia; Yáñez, Manuel

2015-10-26

The structure, relative stability and bonding of complexes formed by the interaction between Ga(+) and a large set of compounds, including hydrocarbons, aromatic systems, and oxygen-, nitrogen-, fluorine and sulfur-containing Lewis bases have been investigated through the use of the high-level composite ab initio Gaussian-4 theory. This allowed us to establish rather accurate Ga(+) cation affinity (GaCA) and Ga(+) cation basicity (GaCB) scales. The bonding analysis of the complexes under scrutiny shows that, even though one of the main ingredients of the Ga(+) -base interaction is electrostatic, it exhibits a non-negligible covalent character triggered by the presence of the low-lying empty 4p orbital of Ga(+) , which favors a charge donation from occupied orbitals of the base to the metal ion. This partial covalent character, also observed in AlCA scales, is behind the dissimilarities observed when GaCA are compared with Li(+) cation affinities, where these covalent contributions are practically nonexistent. Quite unexpectedly, there are some dissimilarities between several Ga(+) -complexes and the corresponding Al(+) -analogues, mainly affecting the relative stability of π-complexes involving aromatic compounds. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Collagen-Based Fillers as Alternatives to Cyanoacrylate Glue for the Sealing of Large Corneal Perforations.

PubMed

Samarawickrama, Chameen; Samanta, Ayan; Liszka, Aneta; Fagerholm, Per; Buznyk, Oleksiy; Griffith, May; Allan, Bruce

2018-05-01

To describe the use of collagen-based alternatives to cyanoacrylate glue for the sealing of acute corneal perforations. A collagen analog comprising a collagen-like peptide conjugated to polyethylene glycol (CLP-PEG) and its chemical crosslinker were tested for biocompatibility. These CLP-PEG hydrogels, which are designed to act as a framework for corneal tissue regeneration, were then tested as potential fillers in ex vivo human corneas with surgically created full-thickness perforations. Bursting pressures were measured in each of 3 methods (n = 10 for each condition) of applying a seal: 1) cyanoacrylate glue with a polyethylene patch applied ab externo (gold standard); 2) a 100-μm thick collagen hydrogel patch applied ab interno, and 3) the same collagen hydrogel patch applied ab interno supplemented with CLP-PEG hydrogel molded in situ to fill the remaining corneal stromal defect. Cyanoacrylate gluing achieved a mean bursting pressure of 325.9 mm Hg, significantly higher than the ab interno patch alone (46.3 mm Hg) and the ab interno patch with the CLP-PEG filler (86.6 mm Hg). All experimental perforations were sealed effectively using 100 μm hydrogel sheets as an ab interno patch, whereas conventional ab externo patching with cyanoacrylate glue failed to provide a seal in 30% (3/10) cases. An ab interno patch system using CLP-PEG hydrogels designed to promote corneal tissue regeneration may be a viable alternative to conventional cyanoacrylate glue patching for the treatment of corneal perforation. Further experimentation and material refinement is required in advance of clinical trials.

The impact of viral RNA on the association free energies of capsid protein assembly: bacteriophage MS2 as a case study.

PubMed

ElSawy, Karim M

2017-02-01

A large number of single-stranded RNA viruses assemble their capsid and their genomic material simultaneously. The RNA viral genome plays multiple roles in this process that are currently only partly understood. In this work, we investigated the thermodynamic basis of the role of viral RNA on the assembly of capsid proteins. The viral capsid of bacteriophage MS2 was considered as a case study. The MS2 virus capsid is composed of 60 AB and 30 CC protein dimers. We investigated the effect of RNA stem loop (the translational repressor TR) binding to the capsid dimers on the dimer-dimer relative association free energies. We found that TR binding results in destabilization of AB self-association compared with AB and CC association. This indicates that the association of the AB and CC dimers is the most likely assembly pathway for the MS2 virus, which explains the experimental observation of alternating patterns of AB and CC dimers in dominant assembly intermediates of the MS2 virus. The presence of viral RNA, therefore, dramatically channels virus assembly to a limited number of pathways, thereby enhancing the efficiency of virus self-assembly process. Interestingly, Thr59Ser and Thr45Ala mutations of the dimers, in the absence of RNA stem loops, lead to stabilization of AB self-association compared with the AB and CC associations, thereby channelling virus assembly towards a fivefold (AB) 5 pentamer intermediate, providing a testable hypothesis of our thermodynamic arguments.

Atacama B-mode Search: Scientific Motivations and Design Overview

NASA Astrophysics Data System (ADS)

Yoon, Ki Won

2009-05-01

The Atacama B-mode Search (ABS) is a new experiment designed to characterize the polarization of the cosmic microwave background (CMB) to unprecedented levels at degree angular scales, where the signature of primordial gravitational waves from an inflationary epoch in the early universe is expected to peak. ABS employs a novel optical design using a cryogenically-cooled crossed-Dragone reflective telescope coupled to an array of ˜200 direct-machined feedhorns, each of which in turn couples the incoming radiation onto a ``polarimeter-on-a-chip'' consisting of a planar ortho-mode transducer, microstrip band-defining filters, and a pair of transition-edge sensors (TES) that measure both polarizations simultaneously. The array will be initially designed for operation at 145 GHz. ABS is currently scheduled to begin observation in the Atacama Desert of Chile in late 2009.

Chronic lymphocytic leukemia antibodies with a common stereotypic rearrangement recognize nonmuscle myosin heavy chain IIA

PubMed Central

Catera, Rosa; Hatzi, Katerina; Yan, Xiao-Jie; Zhang, Lu; Wang, Xiao Bo; Fales, Henry M.; Allen, Steven L.; Kolitz, Jonathan E.; Rai, Kanti R.; Chiorazzi, Nicholas

2008-01-01

Leukemic B lymphocytes of a large group of unrelated chronic lymphocytic leukemia (CLL) patients express an unmutated heavy chain immunoglobulin variable (V) region encoded by IGHV1-69, IGHD3-16, and IGHJ3 with nearly identical heavy and light chain complementarity-determining region 3 sequences. The likelihood that these patients developed CLL clones with identical antibody V regions randomly is highly improbable and suggests selection by a common antigen. Monoclonal antibodies (mAbs) from this stereotypic subset strongly bind cytoplasmic structures in HEp-2 cells. Therefore, HEp-2 cell extracts were immunoprecipitated with recombinant stereotypic subset-specific CLL mAbs, revealing a major protein band at approximately 225 kDa that was identified by mass spectrometry as nonmuscle myosin heavy chain IIA (MYHIIA). Reactivity of the stereotypic mAbs with MYHIIA was confirmed by Western blot and immunofluorescence colocalization with anti-MYHIIA antibody. Treatments that alter MYHIIA amounts and cytoplasmic localization resulted in a corresponding change in binding to these mAbs. The appearance of MYHIIA on the surface of cells undergoing stress or apoptosis suggests that CLL mAb may generally bind molecules exposed as a consequence of these events. Binding of CLL mAb to MYHIIA could promote the development, survival, and expansion of these leukemic cells. PMID:18812466

A targeted boost-and-sort immunization strategy using Escherichia coli BamA identifies rare growth inhibitory antibodies.

PubMed

Vij, Rajesh; Lin, Zhonghua; Chiang, Nancy; Vernes, Jean-Michel; Storek, Kelly M; Park, Summer; Chan, Joyce; Meng, Y Gloria; Comps-Agrar, Laetitia; Luan, Peng; Lee, Sophia; Schneider, Kellen; Bevers, Jack; Zilberleyb, Inna; Tam, Christine; Koth, Christopher M; Xu, Min; Gill, Avinash; Auerbach, Marcy R; Smith, Peter A; Rutherford, Steven T; Nakamura, Gerald; Seshasayee, Dhaya; Payandeh, Jian; Koerber, James T

2018-05-08

Outer membrane proteins (OMPs) in Gram-negative bacteria are essential for a number of cellular functions including nutrient transport and drug efflux. Escherichia coli BamA is an essential component of the OMP β-barrel assembly machinery and a potential novel antibacterial target that has been proposed to undergo large (~15 Å) conformational changes. Here, we explored methods to isolate anti-BamA monoclonal antibodies (mAbs) that might alter the function of this OMP and ultimately lead to bacterial growth inhibition. We first optimized traditional immunization approaches but failed to identify mAbs that altered cell growth after screening >3000 hybridomas. We then developed a "targeted boost-and-sort" strategy that combines bacterial cell immunizations, purified BamA protein boosts, and single hybridoma cell sorting using amphipol-reconstituted BamA antigen. This unique workflow improves the discovery efficiency of FACS + mAbs by >600-fold and enabled the identification of rare anti-BamA mAbs with bacterial growth inhibitory activity in the presence of a truncated lipopolysaccharide layer. These mAbs represent novel tools for dissecting the BamA-mediated mechanism of β-barrel folding and our workflow establishes a new template for the efficient discovery of novel mAbs against other highly dynamic membrane proteins.

Establishment and comparison of four constitutive relationships of PC/ABS from low to high uniaxial strain rates

NASA Astrophysics Data System (ADS)

Wang, Haitao; Zhang, Yun; Huang, Zhigao; Tang, Zhongbin; Wang, Yanpei; Zhou, Huamin

2017-10-01

The objective of this paper is to accurately predict the rate/temperature-dependent deformation of a polycarbonate (PC) and acrylonitrile-butadiene-styrene (ABS) blend at low, moderate, and high strain rates for various temperatures. Four constitutive models have been employed to predict stress-strain responses of PC/ABS under these conditions, including the DSGZ model, the original Mulliken-Boyce (M-B) model, the modified M-B model, and an adiabatic model named the Wang model. To more accurately capture the large deformation of PC/ABS under the high strain rate loading, the original M-B model is modified by allowing for the evolution of the internal shear strength. All of the four constitutive models above have been implemented in the finite element software ABAQUS/Explicit. A comparison of prediction accuracies of the four constitutive models over a wide range of strain rates and temperatures has been presented. The modified M-B model is observed to be more accurate in predicting the deformation of PC/ABS at high strain rates for various temperatures than the original M-B model, and the Wang model is demonstrated to be the most accurate in simulating the deformation of PC/ABS at low, moderate, and high strain rates for various temperatures.

Ab initio study of the diatomic fluorides FeF, CoF, NiF, and CuF.

PubMed

Koukounas, Constantine; Mavridis, Aristides

2008-11-06

The late-3d transition-metal diatomic fluorides MF = FeF, CoF, NiF, and CuF have been studied using variational multireference (MRCI) and coupled-cluster [RCCSD(T)] methods, combined with large to very large basis sets. We examined a total of 35 (2S+1)|Lambda| states, constructing as well 29 full potential energy curves through the MRCI method. All examined states are ionic, diabatically correlating to M(+)+F(-)((1)S). Notwithstanding the "eccentric" character of the 3d transition metals and the difficulties to accurately be described with all-electron ab initio methods, our results are, in general, in very good agreement with available experimental numbers.

Morphology Formation in PC/ABS Blends during Thermal Processing and the Effect of the Viscosity Ratio of Blend Partners

PubMed Central

Bärwinkel, Stefanie; Seidel, Andreas; Hobeika, Sven; Hufen, Ralf; Mörl, Michaela; Altstädt, Volker

2016-01-01

Morphology formation during compounding, as well as injection molding of blends containing 60 wt % polycarbonate (PC) and 40 wt % polybutadiene rubber-modified styrene-acrylonitrile copolymers (ABS), has been investigated by transmission electron microscopy (TEM). Profiles of the blend morphology have been recorded in injection-molded specimens and significant morphology gradients observed between their skin and core. A <10 µm thick surface layer with strongly dispersed and elongated nano-scale (streak-like) styrene acrylonitrile (SAN) phases and well-dispersed, isolated SAN-grafted polybutadiene rubber particles is followed by a 50–150 µm thick skin layer in which polymer morphology is characterized by lamellar SAN/ABS phases. Thickness of these lamellae increases with the distance from the specimen’s surface. In the core of the specimens the SAN-grafted polybutadiene rubber particles are exclusively present within the SAN phases, which exhibit a much coarser and less oriented, dispersed morphology compared to the skin. The effects of the viscosity of the SAN in the PC/ABS blends on phase morphologies and correlations with fracture mechanics in tensile and impact tests were investigated, including scanning electron microscopy (SEM) assessment of the fracture surfaces. A model explaining the mechanisms of morphology formation during injection molding of PC/ABS blends is discussed. PMID:28773780

Preclinical characterization of therapeutic antibodies targeted at the carboxy-terminus of Sonic hedgehog

PubMed Central

Tolani, Bhairavi; Hoang, Ngoc T.; Acevedo, Luis A.; Leprieur, Etienne Giroux; Li, Hui; He, Biao; Jablons, David M.

2018-01-01

The Sonic Hedgehog (Shh) signaling pathway has been implicated in the development and tumor progression of a number of human cancers. Using synthetic peptide mimics to mount an immune response, we generated a mouse mAb to the carboxy (C)-terminus of the Shh protein and characterized its preclinical antitumor effects. In vitro screening guided selection of the best candidate for mAb scale-up production and therapeutic development. C-term anti-Shh, Ab 1C11-2G4 was selected based on ELISA screens, Western blotting, and flow cytometric analyses. Purified Ab 1C11-2G4 was shown to recognize and bind both Shh peptide mimics and cell surface Shh. Administration of Ab 1C11-2G4 not only reduced cell viability in 7 cancer cell lines but also significantly inhibitted tumor growth in a xenograft model of A549 lung cancer cells. Ex vivo analyses of xenograft tumors revealed a reduction in Shh signal transduction and apoptosis in 2G4-treated mice. Collectively, our results provide early demonstration of the antitumor utility of antibodies specific for the C-terminal region of Shh, and support continued development to evaluate their potential efficacy in cancers in which Shh activity is elevated. PMID:29581846

Ab initio molecular simulations with numeric atom-centered orbitals

NASA Astrophysics Data System (ADS)

Blum, Volker; Gehrke, Ralf; Hanke, Felix; Havu, Paula; Havu, Ville; Ren, Xinguo; Reuter, Karsten; Scheffler, Matthias

2009-11-01

We describe a complete set of algorithms for ab initio molecular simulations based on numerically tabulated atom-centered orbitals (NAOs) to capture a wide range of molecular and materials properties from quantum-mechanical first principles. The full algorithmic framework described here is embodied in the Fritz Haber Institute "ab initio molecular simulations" (FHI-aims) computer program package. Its comprehensive description should be relevant to any other first-principles implementation based on NAOs. The focus here is on density-functional theory (DFT) in the local and semilocal (generalized gradient) approximations, but an extension to hybrid functionals, Hartree-Fock theory, and MP2/GW electron self-energies for total energies and excited states is possible within the same underlying algorithms. An all-electron/full-potential treatment that is both computationally efficient and accurate is achieved for periodic and cluster geometries on equal footing, including relaxation and ab initio molecular dynamics. We demonstrate the construction of transferable, hierarchical basis sets, allowing the calculation to range from qualitative tight-binding like accuracy to meV-level total energy convergence with the basis set. Since all basis functions are strictly localized, the otherwise computationally dominant grid-based operations scale as O(N) with system size N. Together with a scalar-relativistic treatment, the basis sets provide access to all elements from light to heavy. Both low-communication parallelization of all real-space grid based algorithms and a ScaLapack-based, customized handling of the linear algebra for all matrix operations are possible, guaranteeing efficient scaling (CPU time and memory) up to massively parallel computer systems with thousands of CPUs.

Efficient Ab initio Modeling of Random Multicomponent Alloys

DOE PAGES

Jiang, Chao; Uberuaga, Blas P.

2016-03-08

Here, we present in this Letter a novel small set of ordered structures (SSOS) method that allows extremely efficient ab initio modeling of random multi-component alloys. Using inverse II-III spinel oxides and equiatomic quinary bcc (so-called high entropy) alloys as examples, we also demonstrate that a SSOS can achieve the same accuracy as a large supercell or a well-converged cluster expansion, but with significantly reduced computational cost. In particular, because of this efficiency, a large number of quinary alloy compositions can be quickly screened, leading to the identification of several new possible high entropy alloy chemistries. Furthermore, the SSOS methodmore » developed here can be broadly useful for the rapid computational design of multi-component materials, especially those with a large number of alloying elements, a challenging problem for other approaches.« less

Ab initio Potential Energy Surface for H-H2

NASA Technical Reports Server (NTRS)

Partridge, Harry; Bauschlicher, Charles W., Jr.; Stallcop, James R.; Levin, Eugene

1993-01-01

Ab initio calculations employing large basis sets are performed to determine an accurate potential energy surface for H-H2 interactions for a broad range of separation distances. At large distances, the spherically averaged potential determined from the calculated energies agrees well with the corresponding results determined from dispersion coefficients; the van der Waals well depth is predicted to be 75 +/- (mu)E(sub h). Large basis sets have also been applied to reexamine the accuracy of theoretical repulsive potential energy surfaces. Multipolar expansions of the computed H-H2 potential energy surface are reported for four internuclear separation distances (1.2, 1.401, 1.449, and 1.7a(sub 0) of the hydrogen molecule. The differential elastic scattering cross section calculated from the present results is compared with the measurements from a crossed beam experiment.

Expression of rabies glycoprotein and ricin toxin B chain (RGP-RTB) fusion protein in tomato hairy roots: a step towards oral vaccination for rabies.

PubMed

Singh, Ankit; Srivastava, Subhi; Chouksey, Ankita; Panwar, Bhupendra Singh; Verma, Praveen C; Roy, Sribash; Singh, Pradhyumna K; Saxena, Gauri; Tuli, Rakesh

2015-04-01

Transgenic hairy roots of Solanum lycopersicum were engineered to express a recombinant protein containing a fusion of rabies glycoprotein and ricin toxin B chain (rgp-rtxB) antigen under the control of constitutive CaMV35S promoter. Asialofetuin-mediated direct ELISA of transgenic hairy root extracts was performed using polyclonal anti-rabies antibodies (Ab1) and epitope-specific peptidal anti-RGP (Ab2) antibodies which confirmed the expression of functionally viable RGP-RTB fusion protein. Direct ELISA based on asialofetuin-binding activity was used to screen crude protein extracts from five transgenic hairy root lines. Expressions of RGP-RTB fusion protein in different tomato hairy root lines varied between 1.4 and 8 µg in per gram of tissue. Immunoblotting assay of RGP-RTB fusion protein from these lines showed a protein band on monomeric size of ~84 kDa after denaturation. Tomato hairy root line H03 showed highest level of RGP-RTB protein expression (1.14 %) and was used further in bench-top bioreactor for the optimization of scale-up process to produce large quantity of recombinant protein. Partially purified RGP-RTB fusion protein was able to induce the immune response in BALB/c mice after intra-mucosal immunization. In the present investigation, we have not only successfully scaled up the hairy root culture but also established the utility of this system to produce vaccine antigen which subsequently will reduce the total production cost for implementing rabies vaccination programs in developing nations. This study in a way aims to provide consolidated base for low-cost preparation of improved oral vaccine against rabies.

Biomass assessment of microbial surface communities by means of hyperspectral remote sensing data.

PubMed

Rodríguez-Caballero, Emilio; Paul, Max; Tamm, Alexandra; Caesar, Jennifer; Büdel, Burkhard; Escribano, Paula; Hill, Joachim; Weber, Bettina

2017-05-15

Dryland vegetation developed morphological and physiological strategies to cope with drought. However, as aridity increases, vascular plant coverage gets sparse and microbially-dominated surface communities (MSC), comprising cyanobacteria, algae, lichens and bryophytes together with heterotropic bacteria, archaea and fungi, gain relevance. Nevertheless, the relevance of MSC net primary productivity has only rarely been considered in ecosystem scale studies, and detailed information on their contribution to the total photosynthetic biomass reservoir is largely missing. In this study, we mapped the spatial distribution of two different MSC (biological soil crusts and quartz fields hosting hypolithic crusts) at two different sites within the South African Succulent Karoo (Soebatsfontein and Knersvlakte). Then we characterized both types of MSC in terms of chlorophyll content, and combining these data with the biocrust and quartz field maps, we estimated total biomass values of MSCs and their spatial patterns within the two different ecosystems. Our results revealed that MSC are important vegetation components of the South African Karoo biome, revealing clear differences between the two sites. At Soebatsfontein, MSC occurred as biological soil crusts (biocrusts), which covered about one third of the landscape reaching an overall biomass value of ~480gha -1 of chlorophyll a+b at the landscape scale. In the Knersvlakte, which is characterized by harsher environmental conditions (i.e. higher solar radiation and potential evapotranspiration), MSC occurred as biocrusts, but also formed hypolithic crusts growing on the lower soil-immersed parts of translucent quartz pebbles. Whereas chlorophyll concentrations of biocrusts and hypolithic crusts where insignificantly lower in the Knersvlakte, the overall MSC biomass reservoir was by far larger with ~780gha -1 of chlorophyll a+b. Thus, the complementary microbially-dominated surface communities promoted biomass formation within the environmentally harsh Knersvlakte ecosystem. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of Transcranial Direct Current Stimulation over Left Dorsolateral pFC on the Attentional Blink Depend on Individual Baseline Performance.

PubMed

London, Raquel E; Slagter, Heleen A

2015-12-01

Selection mechanisms that dynamically gate only relevant perceptual information for further processing and sustained representation in working memory are critical for goal-directed behavior. We examined whether this gating process can be modulated by anodal transcranial direct current stimulation (tDCS) over left dorsolateral pFC (DLPFC)--a region known to play a key role in working memory and conscious access. Specifically, we examined the effects of tDCS on the magnitude of the so-called "attentional blink" (AB), a deficit in identifying the second of two targets presented in rapid succession. Thirty-four participants performed a standard AB task before (baseline), during, and after 20 min of 1-mA anodal and cathodal tDCS in two separate sessions. On the basis of previous reports linking individual differences in AB magnitude to individual differences in DLPFC activity and on suggestions that effects of tDCS depend on baseline brain activity levels, we hypothesized that anodal tDCS over left DLPFC would modulate the magnitude of the AB as a function of individual baseline AB magnitude. Indeed, individual differences analyses revealed that anodal tDCS decreased the AB in participants with a large baseline AB but increased the AB in participants with a small baseline AB. This effect was only observed during (but not after) stimulation, was not found for cathodal tDCS, and could not be explained by regression to the mean. Notably, the effects of tDCS were not apparent at the group level, highlighting the importance of taking individual variability in performance into account when evaluating the effectiveness of tDCS. These findings support the idea that left DLPFC plays a critical role in the AB and in conscious access more generally. They are also in line with the notion that there is an optimal level of prefrontal activity for cognitive function, with both too little and too much activity hurting performance.

Presence, location, type and size of denuded areas of subchondral bone in the knee as a function of radiographic stage of OA - data from the OA initiative.

PubMed

Frobell, R B; Wirth, W; Nevitt, M; Wyman, B T; Benichou, O; Dreher, D; Davies, R Y; Lee, J H; Baribaud, F; Gimona, A; Hudelmaier, M; Cotofana, S; Eckstein, F

2010-05-01

To assess the presence, location, type and size of denuded areas of subchondral bone (dAB) in the femorotibial joint, measured quantitatively with 3T MRI, in a large subset of OAI participants. One knee of 633 subjects (250 men, 383 women, aged 61.7+/-9.6 y) were studied, spanning all radiographic osteoarthritis (OA) stages. dABs were determined quantitatively using segmentations of coronal FLASHwe images, representing areas where the subchondral bone was not covered by cartilage. Post hoc visual examination of segmented images determined whether dABs represented full thickness cartilage loss or internal osteophyte. 7% Of the knees were Kellgren & Lawrence (KL) grade 0, 6% grade 1, 41% grade 2, 41% grade 3, and 5% grade 4. 39% Of the participants (48% of the men and 33% of the women) displayed dABs; 61% of the dABs represented internal osteophytes. 1/47 Participants with KL grade 0 displayed 'any' dAB whereas 29/32 of the KL grade 4 knees were affected. Even as early as KL grade 1, 29% of the participants showed dABs. There were significant relationships of dAB with increasing KL grades (P<0.001) and with ipsi-compartimental JSN (P< or =0.001). Internal osteophytes were more frequent laterally (mainly posterior tibia and internal femur) whereas full thickness cartilage loss was more frequent medially (mainly external tibia and femur). dABs occur already at earliest stages of radiographic OA (KL grades 1 and 2) and become more common (and larger) with increasing disease severity. Almost all KL grade 4 knees exhibited dABs, with cartilage loss being more frequent than internal osteophytes. Copyright 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Self-transcendence and emotional well-being in women with advanced breast cancer.

PubMed

Coward, D D

1991-07-01

Self-transcendence has been associated, in previous studies, with stressful life events and emotional well-being. This study examined the relationships among self-transcendence, emotional well-being, and illness-related distress in women with advanced breast cancer. The study employed a cross-sectional correlational design in a convenience sample (n = 107) of women with Stage IIIb and Stage IV breast cancer. Subjects completed a questionnaire that included Reed's Self-Transcendence Scale; Bradburn's Affect Balance Scale (ABS); a Cognitive Well-Being (CWB) Scale based on work by Campbell, Converse, and Rogers; McCorkle and Young's Symptom Distress Scale (SDS); and the Karnofsky Performance Scale (KPS). Data were analyzed using factor analytic structural equations modeling. Self-transcendence decreased illness distress (assessed by the SDS and the KPS) through the mediating effect of emotional well-being (assessed by the ABS and the CWB Scale). Self-transcendence directly affected emotional well-being (beta = 0.69), and emotional well-being had a strong negative effect on illness distress (beta = -0.84). A direct path from self-transcendence to illness distress (beta = -0.31) became nonsignificant (beta = -0.08) when controlling for emotional well-being. Further research using longitudinal data will seek to validate these relationships and to explain how nurses can promote self-transcendence in women with advanced breast cancer, as well as in others with life-threatening illnesses.

Results of a space shuttle vehicle ferry configuration afterbody fairing optimization study using a 140A/B 0.0405-scale model orbiter (43-0) in the Rockwell International 7.75 by 11.0 ft low speed wind tunnel (OA124)

NASA Technical Reports Server (NTRS)

Houlihan, S. R.

1975-01-01

Experimental aerodynamic investigations were conducted on a dual-strut mounted 0.0405-scale representation of the 140A/B outer mold line space shuttle orbiter vehicle. The tests, conducted from 11 Oct., 1974 through 22 Oct., 1974, were primarily to investigate aerodynamic stability and control characteristics of the space shuttle orbiter ferry configuration. Four afterbody fairing configurations and various additions to them in the form of horizontal and ventral fins strakes and other aerodynamic protuberances were tested. Base line data on the basic orbiter with MPS nozzles and bodyflap were recorded. The drag of the optimum ferry configuration was increased to the level of the basic orbiter for possible flight test configurations by the addition of two sizes of perforated speed brakes on the tail cone surface.

Results of an investigation to determine local flow characteristics at the air data probe locations using an 0.030-scale model (45-0) of the space shuttle vehicle orbiter configuration 140A/B (modified) in the NASA Ames Research Center unitary plan wind tunnel (OA161, A, B, C), volume 1

NASA Technical Reports Server (NTRS)

Nichols, M. E.

1976-01-01

Results are presented of wind tunnel test 0A161 of a 0.030-scale model 45-0 of the configuration 140A/B (modified) space shuttle vehicle orbiter in the NASA Ames Research Center Unitary Plan Wind Tunnel facilities. The purpose of this test was to determine local total and static pressure environments for the air data probe locations and relative effectiveness of alternate flight-test probe configurations. Testing was done in the Mach number range from 0.30 to 3.5. Angle of attack was varied from -8 to 25 degrees while sideslip varied between -8 and 8 degrees.

Therapeutischer Einsatz monoklonaler Antikörper

NASA Astrophysics Data System (ADS)

Baron, D.

Three monoclonal antibodies (mAbs) have been approved for the treatment of transplant rejection, sepsis, and colorectal carcinoma. The breakthrough, however, has not yet been achieved, in contrast to diagnostic mabs. The general applicability for a large number of patients and long-term therapeutic success have not yet been proven. A complete cure by mAbs alone has been observed in only a few cases. In many cases conventional medications have to be administered in parallel. There are a number of inherent problems which reside in both the biochemistry of the antibodies and the biology of the patients. There is no doubt, however, that in 5-7 years mAbs will be used routinely to treat cases of rejection of transplanted organs, autoimmune diseases, infections and cancer.

Einstein coefficients and oscillator strengths for low lying state of CO molecules

NASA Astrophysics Data System (ADS)

Swer, S.; Syiemiong, A.; Ram, M.; Jha, A. K.; Saxena, A.

2018-04-01

Einstein Coefficients and Oscillator Strengths for different state of CO molecule have been calculated using LEROY'S LEVEL program and MOLCAS ab initio code. Using the wave function derived from Morse potential and transition dipole moment obtained from ab initio calculation, The potential energy functions were computed for these states using the spectroscopic constants. The Morse potential of these states and electronic transition dipole moment of the transition calculated in a recent ab initio study have been used in LEVEL program to produce transition dipole matrix element for a large number of bands. Einstein Coefficients have also been used to compute the radiative lifetimes of several vibrational levels and the calculated values are compared with other theoretical results and experimental values.

Space Shuttle Orbiter trimmed center-of-gravity extension study. Volume 7: Effects of configuration modifications on the subsonic aerodynamic characteristics of the 1140 A/B orbbiter at high Reynolds numbers. [Langley low turbulence pressure tunnel

NASA Technical Reports Server (NTRS)

Phillips, W. P.

1981-01-01

Subsonic longitudinal andd laternal directional characteristics were obtained for several modified configurations of the 140 A/B orbiter (0.010 scale). These modifications, designed to extend longitudinal trim capability forward of the 65 percent fuselage length station, consisted of modified wing planform fillet and a canard. Tests were performed in the Langley Low Turbulence Pressure Tunnel at Reynolds numbers from about 4.2 million to 14.3 million based on the fuselage reference length.

The hydrogen diffusion in liquid aluminum alloys from ab initio molecular dynamics

NASA Astrophysics Data System (ADS)

Jakse, N.; Pasturel, A.

2014-09-01

We study the hydrogen diffusion in liquid aluminum alloys through extensive ab initio molecular dynamics simulations. At the microscopic scale, we show that the hydrogen motion is characterized by a broad distribution of spatial jumps that does not correspond to a Brownian motion. To determine the self-diffusion coefficient of hydrogen in liquid aluminum alloys, we use a generalized continuous time random walk model recently developed to describe the hydrogen diffusion in pure aluminum. In particular, we show that the model successfully accounts the effects of alloying elements on the hydrogen diffusion in agreement with experimental features.

Autogenous bone versus deproteinised bovine bone matrix in 1-stage lateral sinus floor elevation in the severely atrophied maxilla: a randomised controlled trial.

PubMed

Merli, Mauro; Moscatelli, Marco; Mariotti, Giorgia; Rotundo, Roberto; Nieri, Michele

2013-01-01

To compare 100% deproteinised bovine bone matrix (DBBM) grafts (test group) with 100% autogenous bone (AB) grafts (control group) for lateral maxillary sinus floor elevation in a parallel group, superiority, randomised controlled trial. Patients with 1 to 3 mm of residual bone height below the maxillary sinus were randomised for sinus floor elevation with DBBM and AB grafts and simultaneous implant placement. Randomisation was computer generated with allocation concealment by sealed envelopes and the radiographic examiner was blinded to group assignment. The abutment connection was performed 8 months after surgery and insertion of the provisional prostheses was performed 9 months after surgery. Outcome variables were implant failures, prosthetic failures, complications, chair time, postoperative pain and radiographic bone level 6 months after loading. Forty patients were randomised: 20 (32 implants) to the DBBM group and 20 (27 implants) to the AB group. One patient from the AB group dropped out. Two implant failures occurred in the DBBM group and no implant failure occurred in the AB group (P = 0.4872). All of the planned prostheses could be delivered. One complication occurred in the DBBM group and 2 in the AB group (P = 0.6050). Chair time was shorter for the DBBM group, with a difference of 27.3 minutes (P = 0.0428). Pain difference measured with a visual analogue scale for 6 days post-surgery was 0.2 in favour of the DBBM group (P = 0.6838). The difference in vertical bone height was 0.0 mm (95% CI -1.1, 1.1; P = 0.9703) and the difference in marginal bone level was 0.3 in favour of AB (95% CI -0.3, 0.9; P = 0.3220). No differences apart from chair time were observed when comparing DBBM and AB grafts with simultaneous implant placement in sinus elevation.

Reduction of ammonia and volatile organic compounds from food waste-composting facilities using a novel anti-clogging biofilter system.

PubMed

Ryu, Hee Wook; Cho, Kyung-Suk; Lee, Tae-Ho

2011-04-01

The performance of a pilot-scale anti-clogging biofilter system (ABS) was evaluated over a period of 125days for treating ammonia and volatile organic compounds emitted from a full-scale food waste-composting facility. The pilot-scale ABS was designed to intermittently and automatically remove excess biomass using an agitator. When the pressure drop in the polyurethane filter bed was increased to a set point (50 mm H(2)O m(-1)), due to excess biomass acclimation, the agitator automatically worked by the differential pressure switch, without biofilter shutdown. A high removal efficiency (97-99%) was stably maintained for the 125 days after an acclimation period of 1 week, even thought the inlet gas concentrations fluctuated from 0.16 to 0.55 g m(-3). Due the intermittent automatic agitation of the filter bed, the biomass concentration and pressure drop in the biofilter were maintained within the ranges of 1.1-2.0 g-DCW g PU(-1) and below 50 mm H(2)O m(-1), respectively. Copyright © 2011 Elsevier Ltd. All rights reserved.

Aerodynamic results of a separation test (CA20) conducted at the Boeing transonic wind tunnel using 0.030-scale models of the configuration 140A/B (modified) SSV orbiter (model no. 45-0) and the Boeing 747 carrier (model no. AX 1319 I-1), volume 1. [wind tunnel tests

NASA Technical Reports Server (NTRS)

Dziubala, T.; Esparza, V.; Gillins, R. L.; Petrozzi, M.

1975-01-01

A Rockwell built 0.030-scale 45-0 modified Space Shuttle Orbiter Configuration 14?A/B model and a Boeing built 0.030-scale 747 carrier model were tested to provide six component force and moment data for each vehicle in proximity to the other at a matrix of relative positions, attitudes and test conditions (angles of attack and sideslip were varied). Orbiter model support system tare effects were determined for corrections to obtain support-free aerodynamics. In addition to the balance force data, pressures were measured. Pressure orifices were located at the base of the Orbiter, on either side of the vertical blade strut, and at the mid-root chord on either side of the vertical tail. Strain gages were installed on the Boeing 747 vertical tail to indicate buffet onset. Photographs of aerodynamic configurations tested are shown.

Comparative Proteomics and Pulmonary Toxicity of Instilled Single-Walled Carbon Nanotubes, Crocidolite Asbestos, and Ultrafine Carbon Black in Mice

PubMed Central

Teeguarden, Justin G.; Webb-Robertson, Bobbie-Jo; Waters, Katrina M.; Murray, Ashley R.; Kisin, Elena R.; Varnum, Susan M.; Jacobs, Jon M.; Pounds, Joel G.; Zanger, Richard C.; Shvedova, Anna A.

2011-01-01

Reflecting their exceptional potential to advance a range of biomedical, aeronautic, and other industrial products, carbon nanotube (CNT) production and the potential for human exposure to aerosolized CNTs are increasing. CNTs have toxicologically significant structural and chemical similarities to asbestos (AB) and have repeatedly been shown to cause pulmonary inflammation, granuloma formation, and fibrosis after inhalation/instillation/aspiration exposure in rodents, a pattern of effects similar to those observed following exposure to AB. To determine the degree to which responses to single-walled CNTs (SWCNT) and AB are similar or different, the pulmonary response of C57BL/6 mice to repeated exposures to SWCNTs, crocidolite AB, and ultrafine carbon black (UFCB) were compared using high-throughput global high performance liquid chromatography fourier transform ion cyclotron resonance mass spectrometry (HPLC-FTICR-MS) proteomics, histopathology, and bronchoalveolar lavage cytokine analyses. Mice were exposed to material suspensions (40 micrograms per mouse) twice a week for 3 weeks by pharyngeal aspiration. Histologically, the incidence and severity of inflammatory and fibrotic responses were greatest in mice treated with SWCNTs. SWCNT treatment affected the greatest changes in abundance of identified lung tissue proteins. The trend in number of proteins affected (SWCNT [376] > AB [231] > UFCB [184]) followed the potency of these materials in three biochemical assays of inflammation (cytokines). SWCNT treatment uniquely affected the abundance of 109 proteins, but these proteins largely represent cellular processes affected by AB treatment as well, further evidence of broad similarity in the tissue-level response to AB and SWCNTs. Two high-sensitivity markers of inflammation, one (S100a9) observed in humans exposed to AB, were found and may be promising biomarkers of human response to SWCNT exposure. PMID:21135415

Automation bias and verification complexity: a systematic review.

PubMed

Lyell, David; Coiera, Enrico

2017-03-01

While potentially reducing decision errors, decision support systems can introduce new types of errors. Automation bias (AB) happens when users become overreliant on decision support, which reduces vigilance in information seeking and processing. Most research originates from the human factors literature, where the prevailing view is that AB occurs only in multitasking environments. This review seeks to compare the human factors and health care literature, focusing on the apparent association of AB with multitasking and task complexity. EMBASE, Medline, Compendex, Inspec, IEEE Xplore, Scopus, Web of Science, PsycINFO, and Business Source Premiere from 1983 to 2015. Evaluation studies where task execution was assisted by automation and resulted in errors were included. Participants needed to be able to verify automation correctness and perform the task manually. Tasks were identified and grouped. Task and automation type and presence of multitasking were noted. Each task was rated for its verification complexity. Of 890 papers identified, 40 met the inclusion criteria; 6 were in health care. Contrary to the prevailing human factors view, AB was found in single tasks, typically involving diagnosis rather than monitoring, and with high verification complexity. The literature is fragmented, with large discrepancies in how AB is reported. Few studies reported the statistical significance of AB compared to a control condition. AB appears to be associated with the degree of cognitive load experienced in decision tasks, and appears to not be uniquely associated with multitasking. Strategies to minimize AB might focus on cognitive load reduction. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Multiscale Quantum Mechanics/Molecular Mechanics Simulations with Neural Networks.

PubMed

Shen, Lin; Wu, Jingheng; Yang, Weitao

2016-10-11

Molecular dynamics simulation with multiscale quantum mechanics/molecular mechanics (QM/MM) methods is a very powerful tool for understanding the mechanism of chemical and biological processes in solution or enzymes. However, its computational cost can be too high for many biochemical systems because of the large number of ab initio QM calculations. Semiempirical QM/MM simulations have much higher efficiency. Its accuracy can be improved with a correction to reach the ab initio QM/MM level. The computational cost on the ab initio calculation for the correction determines the efficiency. In this paper we developed a neural network method for QM/MM calculation as an extension of the neural-network representation reported by Behler and Parrinello. With this approach, the potential energy of any configuration along the reaction path for a given QM/MM system can be predicted at the ab initio QM/MM level based on the semiempirical QM/MM simulations. We further applied this method to three reactions in water to calculate the free energy changes. The free-energy profile obtained from the semiempirical QM/MM simulation is corrected to the ab initio QM/MM level with the potential energies predicted with the constructed neural network. The results are in excellent accordance with the reference data that are obtained from the ab initio QM/MM molecular dynamics simulation or corrected with direct ab initio QM/MM potential energies. Compared with the correction using direct ab initio QM/MM potential energies, our method shows a speed-up of 1 or 2 orders of magnitude. It demonstrates that the neural network method combined with the semiempirical QM/MM calculation can be an efficient and reliable strategy for chemical reaction simulations.

General Rule of Negative Effective Ueff System & Materials Design of High-Tc Superconductors by ab initio Calculations

NASA Astrophysics Data System (ADS)

Katayama-Yoshida, Hiroshi; Nakanishi, Akitaka; Uede, Hiroki; Takawashi, Yuki; Fukushima, Tetsuya; Sato, Kazunori

2014-03-01

Based upon ab initio electronic structure calculation, I will discuss the general rule of negative effective U system by (1) exchange-correlation-induced negative effective U caused by the stability of the exchange-correlation energy in Hund's rule with high-spin ground states of d5 configuration, and (2) charge-excitation-induced negative effective U caused by the stability of chemical bond in the closed-shell of s2, p6, and d10 configurations. I will show the calculated results of negative effective U systems such as hole-doped CuAlO2 and CuFeS2. Based on the total energy calculations of antiferromagnetic and ferromagnetic states, I will discuss the magnetic phase diagram and superconductivity upon hole doping. I also discuss the computational materials design method of high-Tc superconductors by ab initio calculation to go beyond LDA and multi-scale simulations.

A Bacteriophage-Related Chimeric Marine Virus Infecting Abalone

PubMed Central

Zhuang, Jun; Cai, Guiqin; Lin, Qiying; Wu, Zujian; Xie, Lianhui

2010-01-01

Marine viruses shape microbial communities with the most genetic diversity in the sea by multiple genetic exchanges and infect multiple marine organisms. Here we provide proof from experimental infection that abalone shriveling syndrome-associated virus (AbSV) can cause abalone shriveling syndrome. This malady produces histological necrosis and abnormally modified macromolecules (hemocyanin and ferritin). The AbSV genome is a 34.952-kilobase circular double-stranded DNA, containing putative genes with similarity to bacteriophages, eukaryotic viruses, bacteria and endosymbionts. Of the 28 predicted open reading frames (ORFs), eight ORF-encoded proteins have identifiable functional homologues. The 4 ORF products correspond to a predicted terminase large subunit and an endonuclease in bacteriophage, and both an integrase and an exonuclease from bacteria. The other four proteins are homologous to an endosymbiont-derived helicase, primase, single-stranded binding (SSB) protein, and thymidylate kinase, individually. Additionally, AbSV exhibits a common gene arrangement similar to the majority of bacteriophages. Unique to AbSV, the viral genome also contains genes associated with bacterial outer membrane proteins and may lack the structural protein-encoding ORFs. Genomic characterization of AbSV indicates that it may represent a transitional form of microbial evolution from viruses to bacteria. PMID:21079776

Rapid assessment of oxidation via middle-down LCMS correlates with methionine side-chain solvent-accessible surface area for 121 clinical stage monoclonal antibodies.

PubMed

Yang, Rong; Jain, Tushar; Lynaugh, Heather; Nobrega, R Paul; Lu, Xiaojun; Boland, Todd; Burnina, Irina; Sun, Tingwan; Caffry, Isabelle; Brown, Michael; Zhi, Xiaoyong; Lilov, Asparouh; Xu, Yingda

Susceptibility of methionine to oxidation is an important concern for chemical stability during the development of a monoclonal antibody (mAb) therapeutic. To minimize downstream risks, leading candidates are usually screened under forced oxidation conditions to identify oxidation-labile molecules. Here we report results of forced oxidation on a large set of in-house expressed and purified mAbs with variable region sequences corresponding to 121 clinical stage mAbs. These mAb samples were treated with 0.1% H 2 O 2 for 24 hours before enzymatic cleavage below the hinge, followed by reduction of inter-chain disulfide bonds for the detection of the light chain, Fab portion of heavy chain (Fd) and Fc by liquid chromatography-mass spectrometry. This high-throughput, middle-down approach allows detection of oxidation site(s) at the resolution of 3 distinct segments. The experimental oxidation data correlates well with theoretical predictions based on the solvent-accessible surface area of the methionine side-chains within these segments. These results validate the use of upstream computational modeling to predict mAb oxidation susceptibility at the sequence level.

Parallel Quantum Circuit in a Tunnel Junction

NASA Astrophysics Data System (ADS)

Faizy Namarvar, Omid; Dridi, Ghassen; Joachim, Christian

2016-07-01

Spectral analysis of 1 and 2-states per line quantum bus are normally sufficient to determine the effective Vab(N) electronic coupling between the emitter and receiver states through the bus as a function of the number N of parallel lines. When Vab(N) is difficult to determine, an Heisenberg-Rabi time dependent quantum exchange process must be triggered through the bus to capture the secular oscillation frequency Ωab(N) between those states. Two different linear and regimes are demonstrated for Ωab(N) as a function of N. When the initial preparation is replaced by coupling of the quantum bus to semi-infinite electrodes, the resulting quantum transduction process is not faithfully following the Ωab(N) variations. Because of the electronic transparency normalisation to unity and of the low pass filter character of this transduction, large Ωab(N) cannot be captured by the tunnel junction. The broadly used concept of electrical contact between a metallic nanopad and a molecular device must be better described as a quantum transduction process. At small coupling and when N is small enough not to compensate for this small coupling, an N2 power law is preserved for Ωab(N) and for Vab(N).

Parallel Quantum Circuit in a Tunnel Junction

PubMed Central

Faizy Namarvar, Omid; Dridi, Ghassen; Joachim, Christian

2016-01-01

Spectral analysis of 1 and 2-states per line quantum bus are normally sufficient to determine the effective Vab(N) electronic coupling between the emitter and receiver states through the bus as a function of the number N of parallel lines. When Vab(N) is difficult to determine, an Heisenberg-Rabi time dependent quantum exchange process must be triggered through the bus to capture the secular oscillation frequency Ωab(N) between those states. Two different linear and regimes are demonstrated for Ωab(N) as a function of N. When the initial preparation is replaced by coupling of the quantum bus to semi-infinite electrodes, the resulting quantum transduction process is not faithfully following the Ωab(N) variations. Because of the electronic transparency normalisation to unity and of the low pass filter character of this transduction, large Ωab(N) cannot be captured by the tunnel junction. The broadly used concept of electrical contact between a metallic nanopad and a molecular device must be better described as a quantum transduction process. At small coupling and when N is small enough not to compensate for this small coupling, an N2 power law is preserved for Ωab(N) and for Vab(N). PMID:27453262

Parallel Quantum Circuit in a Tunnel Junction.

PubMed

Faizy Namarvar, Omid; Dridi, Ghassen; Joachim, Christian

2016-07-25

Spectral analysis of 1 and 2-states per line quantum bus are normally sufficient to determine the effective Vab(N) electronic coupling between the emitter and receiver states through the bus as a function of the number N of parallel lines. When Vab(N) is difficult to determine, an Heisenberg-Rabi time dependent quantum exchange process must be triggered through the bus to capture the secular oscillation frequency Ωab(N) between those states. Two different linear and regimes are demonstrated for Ωab(N) as a function of N. When the initial preparation is replaced by coupling of the quantum bus to semi-infinite electrodes, the resulting quantum transduction process is not faithfully following the Ωab(N) variations. Because of the electronic transparency normalisation to unity and of the low pass filter character of this transduction, large Ωab(N) cannot be captured by the tunnel junction. The broadly used concept of electrical contact between a metallic nanopad and a molecular device must be better described as a quantum transduction process. At small coupling and when N is small enough not to compensate for this small coupling, an N(2) power law is preserved for Ωab(N) and for Vab(N).

Structure-guided Design and Immunological Characterization of Immunogens Presenting the HIV-1 gp120 V3 Loop on a CTB Scaffold

DOE Office of Scientific and Technical Information (OSTI.GOV)

M Totrov; X Jiang; X Kong

2011-12-31

V3 loop is a major neutralizing determinant of the HIV-1 gp120. Using 3D structures of cholera toxin B subunit (CTB), complete V3 in the gp120 context, and V3 bound to a monoclonal antibody (mAb), we designed two V3-scaffold immunogen constructs (V3-CTB). The full-length V3-CTB presenting the complete V3 in a structural context mimicking gp120 was recognized by the large majority of our panel of 24 mAbs. The short V3-CTB presenting a V3 fragment in the conformation observed in the complex with the 447-52D Fab, exhibited high-affinity binding to this mAb. The immunogens were evaluated in rabbits using DNA-prime/protein-boost protocol. Boostingmore » with the full-length V3-CTB induced high anti-V3 titers in sera that potently neutralize multiple HIV virus strains. The short V3-CTB was ineffective. The results suggest that very narrow antigenic profile of an immunogen is associated with poor Ab response. An immunogen with broader antigenic activity elicits robust Ab response.« less

Model Order Reduction Algorithm for Estimating the Absorption Spectrum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Beeumen, Roel; Williams-Young, David B.; Kasper, Joseph M.

The ab initio description of the spectral interior of the absorption spectrum poses both a theoretical and computational challenge for modern electronic structure theory. Due to the often spectrally dense character of this domain in the quantum propagator’s eigenspectrum for medium-to-large sized systems, traditional approaches based on the partial diagonalization of the propagator often encounter oscillatory and stagnating convergence. Electronic structure methods which solve the molecular response problem through the solution of spectrally shifted linear systems, such as the complex polarization propagator, offer an alternative approach which is agnostic to the underlying spectral density or domain location. This generality comesmore » at a seemingly high computational cost associated with solving a large linear system for each spectral shift in some discretization of the spectral domain of interest. In this work, we present a novel, adaptive solution to this high computational overhead based on model order reduction techniques via interpolation. Model order reduction reduces the computational complexity of mathematical models and is ubiquitous in the simulation of dynamical systems and control theory. The efficiency and effectiveness of the proposed algorithm in the ab initio prediction of X-ray absorption spectra is demonstrated using a test set of challenging water clusters which are spectrally dense in the neighborhood of the oxygen K-edge. On the basis of a single, user defined tolerance we automatically determine the order of the reduced models and approximate the absorption spectrum up to the given tolerance. We also illustrate that, for the systems studied, the automatically determined model order increases logarithmically with the problem dimension, compared to a linear increase of the number of eigenvalues within the energy window. Furthermore, we observed that the computational cost of the proposed algorithm only scales quadratically with respect to the problem dimension.« less

Characterizing monoclonal antibody formulations in arginine glutamate solutions using 1H NMR spectroscopy

PubMed Central

Kheddo, Priscilla; Cliff, Matthew J.; Uddin, Shahid; van der Walle, Christopher F.; Golovanov, Alexander P.

2016-01-01

ABSTRACT Assessing how excipients affect the self-association of monoclonal antibodies (mAbs) requires informative and direct in situ measurements for highly concentrated solutions, without sample dilution or perturbation. This study explores the application of solution nuclear magnetic resonance (NMR) spectroscopy for characterization of typical mAb behavior in formulations containing arginine glutamate. The data show that the analysis of signal intensities in 1D 1H NMR spectra, when compensated for changes in buffer viscosity, is invaluable for identifying conditions where protein-protein interactions are minimized. NMR-derived molecular translational diffusion rates for concentrated solutions are less useful than transverse relaxation rates as parameters defining optimal formulation. Furthermore, NMR reports on the solution viscosity and mAb aggregation during accelerated stability study assessment, generating data consistent with that acquired by size-exclusion chromatography. The methodology developed here offers NMR spectroscopy as a new tool providing complementary information useful to formulation development of mAbs and other large therapeutic proteins. PMID:27589351

Industrialization of mAb production technology The bioprocessing industry at a crossroads

PubMed Central

2009-01-01

Manufacturing processes for therapeutic monoclonal antibodies (mAbs) have evolved tremendously since the first licensed mAb product in 1986. The rapid growth in product demand for mAbs triggered parallel efforts to increase production capacity through construction of large bulk manufacturing plants as well as improvements in cell culture processes to raise product titers. This combination has led to an excess of manufacturing capacity, and together with improvements in conventional purification technologies, promises nearly unlimited production capacity in the foreseeable future. The increase in titers has also led to a marked reduction in production costs, which could then become a relatively small fraction of sales price for future products which are sold at prices at or near current levels. The reduction of capacity and cost pressures for current state-of-the-art bulk production processes may shift the focus of process development efforts and have important implications for both plant design and product development strategies for both biopharmaceutical and contract manufacturing companies. PMID:20065641

Characterizing monoclonal antibody formulations in arginine glutamate solutions using 1H NMR spectroscopy.

PubMed

Kheddo, Priscilla; Cliff, Matthew J; Uddin, Shahid; van der Walle, Christopher F; Golovanov, Alexander P

2016-10-01

Assessing how excipients affect the self-association of monoclonal antibodies (mAbs) requires informative and direct in situ measurements for highly concentrated solutions, without sample dilution or perturbation. This study explores the application of solution nuclear magnetic resonance (NMR) spectroscopy for characterization of typical mAb behavior in formulations containing arginine glutamate. The data show that the analysis of signal intensities in 1D 1 H NMR spectra, when compensated for changes in buffer viscosity, is invaluable for identifying conditions where protein-protein interactions are minimized. NMR-derived molecular translational diffusion rates for concentrated solutions are less useful than transverse relaxation rates as parameters defining optimal formulation. Furthermore, NMR reports on the solution viscosity and mAb aggregation during accelerated stability study assessment, generating data consistent with that acquired by size-exclusion chromatography. The methodology developed here offers NMR spectroscopy as a new tool providing complementary information useful to formulation development of mAbs and other large therapeutic proteins.

Well-characterized sequence features of eukaryote genomes and implications for ab initio gene prediction.

PubMed

Huang, Ying; Chen, Shi-Yi; Deng, Feilong

2016-01-01

In silico analysis of DNA sequences is an important area of computational biology in the post-genomic era. Over the past two decades, computational approaches for ab initio prediction of gene structure from genome sequence alone have largely facilitated our understanding on a variety of biological questions. Although the computational prediction of protein-coding genes has already been well-established, we are also facing challenges to robustly find the non-coding RNA genes, such as miRNA and lncRNA. Two main aspects of ab initio gene prediction include the computed values for describing sequence features and used algorithm for training the discriminant function, and by which different combinations are employed into various bioinformatic tools. Herein, we briefly review these well-characterized sequence features in eukaryote genomes and applications to ab initio gene prediction. The main purpose of this article is to provide an overview to beginners who aim to develop the related bioinformatic tools.

Anti-osteopontin monoclonal antibody prevents ovariectomy-induced osteoporosis in mice by promotion of osteoclast apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Bo; PLA General Hospital Cancer Center and PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing; Dai, Jianxin

Highlight: • We first report that anti-osteopontin mAb could protect osteoporosis in mice. • Anti-osteopontin mAb could promote the osteoclast apoptosis. • Targeting osteopontin might have therapeutic potentials for osteoporosis. - Abstract: Osteopontin (OPN) is abundant in mineralized tissues and has long been implicated in bone remodeling. However, the therapeutic effect of targeting OPN in bone loss diseases and the underlying molecular mechanism remain largely unknown. Here, we reported that anti-OPN mAb (23C3) could protect against ovariectomy-induced osteoporosis in mice, demonstrated by microcomputed tomography analysis and histopathology evaluation. In vitro assay showed that 23C3 mAb reduced osteoclasts (OCs)-mediated bone resorptionmore » through promotion of mature OC apoptosis. Thus, the study has important implications for understanding the role of OPN in OC bone resorption and survival, and OPN antagonists may have therapeutic potential for osteoporosis and other osteopenic diseases.« less

Curved-line search algorithm for ab initio atomic structure relaxation

NASA Astrophysics Data System (ADS)

Chen, Zhanghui; Li, Jingbo; Li, Shushen; Wang, Lin-Wang

2017-09-01

Ab initio atomic relaxations often take large numbers of steps and long times to converge, especially when the initial atomic configurations are far from the local minimum or there are curved and narrow valleys in the multidimensional potentials. An atomic relaxation method based on on-the-flight force learning and a corresponding curved-line search algorithm is presented to accelerate this process. Results demonstrate the superior performance of this method for metal and magnetic clusters when compared with the conventional conjugate-gradient method.

Antigenic modulation limits the efficacy of anti-CD20 antibodies: implications for antibody selection.

PubMed

Beers, Stephen A; French, Ruth R; Chan, H T Claude; Lim, Sean H; Jarrett, Timothy C; Vidal, Regina Mora; Wijayaweera, Sahan S; Dixon, Sandra V; Kim, Hyungjin; Cox, Kerry L; Kerr, Jonathan P; Johnston, David A; Johnson, Peter W M; Verbeek, J Sjef; Glennie, Martin J; Cragg, Mark S

2010-06-24

Rituximab, a monoclonal antibody that targets CD20 on B cells, is now central to the treatment of a variety of malignant and autoimmune disorders. Despite this success, a substantial proportion of B-cell lymphomas are unresponsive or develop resistance, hence more potent anti-CD20 monoclonal antibodies (mAbs) are continuously being sought. Here we demonstrate that type II (tositumomab-like) anti-CD20 mAbs are 5 times more potent than type I (rituximab-like) reagents in depleting human CD20 Tg B cells, despite both operating exclusively via activatory Fcgamma receptor-expressing macrophages. Much of this disparity in performance is attributable to type I mAb-mediated internalization of CD20 by B cells, leading to reduced macrophage recruitment and the degradation of CD20/mAb complexes, shortening mAb half-life. Importantly, human B cells from healthy donors and most cases of chronic lymphatic leukemia and mantle cell lymphoma, showed rapid CD20 internalization that paralleled that seen in the Tg mouse B cells, whereas most follicular lymphoma and diffuse large B-cell lymphoma cells were far more resistant to CD20 loss. We postulate that differences in CD20 modulation may play a central role in determining the relative efficacy of rituximab in treating these diseases and strengthen the case for focusing on type II anti-CD20 mAb in the clinic.

Heat shock factor 1 induces crystallin-αB to protect against cisplatin nephrotoxicity

PubMed Central

Lou, Qiang; Hu, Yanzhong; Ma, Yuanfang

2016-01-01

Cisplatin, a wildly used chemotherapy drug, induces nephrotoxicity that is characterized by renal tubular cell apoptosis. In response to toxicity, tubular cells can activate cytoprotective mechanisms, such as the heat shock response. However, the role and regulation of the heat shock response in cisplatin-induced nephrotoxicity remain largely unclear. In the present study, we demonstrated the induction of heat shock factor (Hsf)1 and the small heat shock protein crystallin-αB (CryAB) during cisplatin nephrotoxicity in mice. Consistently, cisplatin induced Hsf1 and CryAB in a cultured renal proximal tubular cells (RPTCs). RPTCs underwent apoptosis during cisplatin treatment, which was increased when Hsf1 was knocked down. Transfection or restoration of Hsf1 into Hsf1 knockdown cells suppressed cisplatin-induced apoptosis, further supporting a cytoprotective role of Hsf1 and its associated heat shock response. Moreover, Hsf1 knockdown increased Bax translocation to mitochondria and cytochrome c release into the cytosol. In RPTCs, Hsf1 knockdown led to a specific downregulation of CryAB. Transfection of CryAB into Hsf1 knockdown cells diminished their sensitivity to cisplatin-induced apoptosis, suggesting that CryAB may be a key mediator of the cytoprotective effect of Hsf1. Taken together, these results demonstrate a heat shock response in cisplatin nephrotoxicity that is mediated by Hsf1 and CryAB to protect tubular cells against apoptosis. PMID:27194715

Weak Interactions Govern the Viscosity of Concentrated Antibody Solutions: High-Throughput Analysis Using the Diffusion Interaction Parameter

PubMed Central

Connolly, Brian D.; Petry, Chris; Yadav, Sandeep; Demeule, Barthélemy; Ciaccio, Natalie; Moore, Jamie M.R.; Shire, Steven J.; Gokarn, Yatin R.

2012-01-01

Weak protein-protein interactions are thought to modulate the viscoelastic properties of concentrated antibody solutions. Predicting the viscoelastic behavior of concentrated antibodies from their dilute solution behavior is of significant interest and remains a challenge. Here, we show that the diffusion interaction parameter (kD), a component of the osmotic second virial coefficient (B2) that is amenable to high-throughput measurement in dilute solutions, correlates well with the viscosity of concentrated monoclonal antibody (mAb) solutions. We measured the kD of 29 different mAbs (IgG1 and IgG4) in four different solvent conditions (low and high ion normality) and found a linear dependence between kD and the exponential coefficient that describes the viscosity concentration profiles (|R| ≥ 0.9). Through experimentally measured effective charge measurements, under low ion normality where the electroviscous effect can dominate, we show that the mAb solution viscosity is poorly correlated with the mAb net charge (|R| ≤ 0.6). With this large data set, our results provide compelling evidence in support of weak intermolecular interactions, in contrast to the notion that the electroviscous effect is important in governing the viscoelastic behavior of concentrated mAb solutions. Our approach is particularly applicable as a screening tool for selecting mAbs with desirable viscosity properties early during lead candidate selection. PMID:22828333

Atomic-scale study of stacking faults in Zr hydrides and implications on hydride formation.

PubMed

Besson, Remy; Thuinet, L; Louchez, Marc-Antoine

2018-06-25

We performed atomic-scale ab initio calculations to investigate the stacking fault (SF) properties of the metastable zeta-Zr2H zirconium hydride. The effect of H near the SF was found to entail the existence of negative SF energies, showing that the zeta compound is probably unstable with respect to shearing in the basal plane. The effect of temperature on SFs was investigated by means of free energy calculations in the quasiharmonic approximation. This evidenced unexpectedly large temperature effects, confirming the main conclusions drawn at 0 K, in particular the zeta mechanical instability. The complex behaviour of H atoms during the shear process suggested zeta-hcp --> Zr2H[111]-fcc as a plausible shear path leading to an fcc compound with same composition as zeta. Finally, as shown by an analysis based on microelasticity, this Zr2H[111]-fcc intermediate compound may be relevant for better interpreting the currently intricate issue of hydride habit planes in zirconium. © 2018 IOP Publishing Ltd.

Comparison of AGE and Spectral Methods for the Simulation of Far-Wakes

NASA Technical Reports Server (NTRS)

Bisset, D. K.; Rogers, M. M.; Kega, Dennis (Technical Monitor)

1999-01-01

Turbulent flow simulation methods based on finite differences are attractive for their simplicity, flexibility and efficiency, but not always for accuracy or stability. This report demonstrates that a good compromise is possible with the Advected Grid Explicit (AGE) method. AGE has proven to be both efficient and accurate for simulating turbulent free-shear flows, including planar mixing layers and planar jets. Its efficiency results from its localized fully explicit finite difference formulation (Bisset 1998a,b) that is very straightforward to compute, outweighing the need for a fairly small timestep. Also, most of the successful simulations were slightly under-resolved, and therefore they were, in effect, large-eddy simulations (LES) without a sub-grid-scale (SGS) model, rather than direct numerical simulations (DNS). The principle is that the role of the smallest scales of turbulent motion (when the Reynolds number is not too low) is to dissipate turbulent energy, and therefore they do not have to be simulated when the numerical method is inherently dissipative at its resolution limits. Such simulations are termed 'auto-LES' (LES with automatic SGS modeling) in this report.

Intracellular Crosslinking of Filoviral Nucleoproteins with Xintrabodies Restricts Viral Packaging

PubMed Central

Darling, Tamarand Lee; Sherwood, Laura Jo; Hayhurst, Andrew

2017-01-01

Viruses assemble large macromolecular repeat structures that become part of the infectious particles or virions. Ribonucleocapsids (RNCs) of negative strand RNA viruses are a prime example where repetition of nucleoprotein (NP) along the genome creates a core polymeric helical scaffold that accommodates other nucleocapsid proteins including viral polymerase. The RNCs are transported through the cytosol for packaging into virions through association with viral matrix proteins at cell membranes. We hypothesized that RNC would be ideal targets for crosslinkers engineered to promote aberrant protein–protein interactions, thereby blocking their orderly transport and packaging. Previously, we had generated single-domain antibodies (sdAbs) against Filoviruses that have all targeted highly conserved C-terminal regions of NP known to be repetitively exposed along the length of the RNCs of Marburgvirus (MARV) and Ebolavirus (EBOV). Our crosslinker design consisted of dimeric sdAb expressed intracellularly, which we call Xintrabodies (X- for crosslinking). Electron microscopy of purified NP polymers incubated with purified sdAb constructs showed NP aggregation occurred in a genus-specific manner with dimeric and not monomeric sdAb. A virus-like particle (VLP) assay was used for initial evaluation where we found that dimeric sdAb inhibited NP incorporation into VP40-based VLPs whereas monomeric sdAb did not. Inhibition of NP packaging was genus specific. Confocal microscopy revealed dimeric sdAb was diffuse when expressed alone but focused on pools of NP when the two were coexpressed, while monomeric sdAb showed ambivalent partition. Infection of stable Vero cell lines expressing dimeric sdAb specific for either MARV or EBOV NP resulted in smaller plaques and reduced progeny of cognate virus relative to wild-type Vero cells. Though the impact was marginal at later time-points, the collective data suggest that viral replication can be reduced by crosslinking intracellular NP using relatively small amounts of dimeric sdAb to restrict NP packaging. The stoichiometry and ease of application of the approach would likely benefit from transitioning away from intracellular expression of crosslinking sdAb to exogenous delivery of antibody. By retuning sdAb specificity, the approach of crosslinking highly conserved regions of assembly critical proteins may well be applicable to inhibiting replication processes of a broad spectrum of viruses. PMID:29021793

Clinical aggressiveness and long-term outcome in patients with papillary thyroid cancer and circulating anti-thyroglobulin autoantibodies.

PubMed

Durante, Cosimo; Tognini, Sara; Montesano, Teresa; Orlandi, Fabio; Torlontano, Massimo; Puxeddu, Efisio; Attard, Marco; Costante, Giuseppe; Tumino, Salvatore; Meringolo, Domenico; Bruno, Rocco; Trulli, Fabiana; Toteda, Maria; Redler, Adriano; Ronga, Giuseppe; Filetti, Sebastiano; Monzani, Fabio

2014-07-01

The association between papillary thyroid cancer (PTC) and Hashimoto's thyroiditis is widely recognized, but less is known about the possible link between circulating anti-thyroglobulin antibody (TgAb) titers and PTC aggressiveness. To shed light on this issue, we retrospectively examined a large series of PTC patients with and without positive TgAb. Data on 220 TgAb-positive PTC patients (study cohort) were retrospectively collected in 10 hospital-based referral centers. All the patients had undergone near-total thyroidectomy with or without radioiodine remnant ablation. Tumor characteristics and long-term outcomes (follow-up range: 2.5-24.8 years) were compared with those recently reported in 1020 TgAb-negative PTC patients with similar demographic characteristics. We also assessed the impact on clinical outcome of early titer disappearance in the TgAb-positive group. At baseline, the study cohort (mean age 45.9 years, range 12.5-84.1 years; 85% female) had a significantly higher prevalence of high-risk patients (6.9% vs. 3.2%, p<0.05) and extrathyroidal tumor extension (28.2% vs. 24%; p<0.0001) than TgAb-negative controls. Study cohort patients were also more likely than controls to have persistent disease at the 1-year visit (13.6% vs. 7.0%, p=0.001) or recurrence during subsequent follow-up (5.8% vs. 1.4%, p=0.0001). At the final follow-up visit, the percentage of patients with either persistent or recurrent disease in the two cohorts was significantly different (6.4% of TgAb-positive patients vs. 1.7% in the TgAb-negative group, p<0.0001). At the 1-year visit, titer normalization was observed in 85 of the 220 TgAb-positive individuals. These patients had a significantly lower rate of persistent disease than those who were still TgAb positive (8.2% vs. 17.3%. p=0.05), and no relapses were observed among patients with no evidence of disease during subsequent follow-up. PTC patients with positive serum TgAb titer during the first year after primary treatment were more likely to have persistent/recurrent disease than those who were consistently TgAb-negative. Negative titers at 1 year may be associated with more favorable outcomes.

High-efficiency wavefunction updates for large scale Quantum Monte Carlo

NASA Astrophysics Data System (ADS)

Kent, Paul; McDaniel, Tyler; Li, Ying Wai; D'Azevedo, Ed

Within ab intio Quantum Monte Carlo (QMC) simulations, the leading numerical cost for large systems is the computation of the values of the Slater determinants in the trial wavefunctions. The evaluation of each Monte Carlo move requires finding the determinant of a dense matrix, which is traditionally iteratively evaluated using a rank-1 Sherman-Morrison updating scheme to avoid repeated explicit calculation of the inverse. For calculations with thousands of electrons, this operation dominates the execution profile. We propose a novel rank- k delayed update scheme. This strategy enables probability evaluation for multiple successive Monte Carlo moves, with application of accepted moves to the matrices delayed until after a predetermined number of moves, k. Accepted events grouped in this manner are then applied to the matrices en bloc with enhanced arithmetic intensity and computational efficiency. This procedure does not change the underlying Monte Carlo sampling or the sampling efficiency. For large systems and algorithms such as diffusion Monte Carlo where the acceptance ratio is high, order of magnitude speedups can be obtained on both multi-core CPU and on GPUs, making this algorithm highly advantageous for current petascale and future exascale computations.

Genomic characterization and expression profiles upon bacterial infection of a novel cystatin B homologue from disk abalone (Haliotis discus discus).

PubMed

Premachandra, H K A; Wan, Qiang; Elvitigala, Don Anushka Sandaruwan; De Zoysa, Mahanama; Choi, Cheol Young; Whang, Ilson; Lee, Jehee

2012-12-01

Cystatins are a large family of cysteine proteinase inhibitors which are involved in diverse biological and pathological processes. In the present study, we identified a gene related to cystatin superfamily, AbCyt B, from disk abalone Haliotis discus discus by expressed sequence tag (EST) analysis and BAC library screening. The complete cDNA sequence of AbCyt B is comprised of 1967 nucleotides with a 306 bp open reading frame (ORF) encoding for 101 amino acids. The amino acid sequence consists of a single cystatin-like domain, which has a cysteine proteinase inhibitor signature, a conserved Gly in N-terminal region, QVVAG motif and a variant of PW motif. No signal peptide, disulfide bonds or carbohydrate side chains were identified. Analysis of deduced amino acid sequence revealed that AbCyt B shares up to 44.7% identity and 65.7% similarity with the cystatin B genes from other organisms. The genomic sequence of AbCyt B is approximately 8.4 Kb, consisting of three exons and two introns. Phylogenetic tree analysis showed that AbCyt B was closely related to the cystatin B from pacific oyster (Crassostrea gigas) under the family 1.Functional analysis of recombinant AbCyt B protein exhibited inhibitory activity against the papain, with almost 84% inhibition at a concentration of 3.5 μmol/L. In tissue expression analysis, AbCyt B transcripts were expressed abundantly in the hemocyte, gill, mantle, and digestive tract, while weakly in muscle, testis, and hepatopancreas. After the immune challenge with Vibrio parahemolyticus, the AbCyt B showed significant (P<0.05) up-regulation of relative mRNA expression in gill and hemocytes at 24 and 6 h of post infection, respectively. These results collectively suggest that AbCyst B is a potent inhibitor of cysteine proteinases and is also potentially involved in immune responses against invading bacterial pathogens in abalone. Copyright © 2012 Elsevier Ltd. All rights reserved.

Rapid polyclonal desensitization with antibodies to IgE and FcεRIα.

PubMed

Khodoun, Marat V; Kucuk, Zeynep Yesim; Strait, Richard T; Krishnamurthy, Durga; Janek, Kevin; Lewkowich, Ian; Morris, Suzanne C; Finkelman, Fred D

2013-06-01

Rapid desensitization, a procedure in which persons allergic to an antigen are treated at short intervals with increasing doses of that antigen until they tolerate a large dose, is an effective, but risky, way to induce temporary tolerance. We wanted to determine whether this approach can be adapted to suppress all IgE-mediated allergies in mice by injecting serially increasing doses of monoclonal antibodies (mAbs) to IgE or FcεRIα. Active and passive models of antigen- and anti-IgE mAb-induced IgE-mediated anaphylaxis were used. Mice were desensitized with serially increasing doses of anti-IgE mAb, anti-FcεRIα mAb, or antigen. Development of shock (hypothermia), histamine and mast cell protease release, cytokine secretion, calcium flux, and changes in cell number and FcεRI and IgE expression were evaluated. Rapid desensitization with anti-IgE mAb suppressed IgE-mediated immediate hypersensitivity; however, some mice developed mild anaphylaxis during desensitization. Rapid desensitization with anti-FcεRIα mAb that only binds FcεRI that is not occupied by IgE suppressed both active and passive IgE-mediated anaphylaxis without inducing disease. It quickly, but temporarily, suppressed IgE-mediated anaphylaxis by decreasing mast cell signaling through FcεRI, then slowly induced longer lasting mast cell unresponsiveness by removing membrane FcεRI. Rapid desensitization with anti-FcεRIα mAb was safer and longer lasting than rapid desensitization with antigen. A rapid desensitization approach with anti-FcεRIα mAb safely desensitizes mice to IgE-mediated anaphylaxis by inducing mast cell anergy and later removing all mast cell IgE. Rapid desensitization with an anti-human FcεRIα mAb may be able to prevent human IgE-mediated anaphylaxis. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Rapid polyclonal desensitization with antibodies to IgE and FcεRIα

PubMed Central

Khodoun, Marat V.; Kucuk, Zeynep Yesim; Strait, Richard T.; Krishnamurthy, Durga; Janek, Kevin; Lewkowich, Ian; Morris, Suzanne C.; Finkelman, Fred D.

2013-01-01

Background Rapid desensitization,a procedure in which individuals allergic to an antigen are treated at short intervals with increasing doses of that antigen until they tolerate a large dose, is an effective, but risky way to induce temporary tolerance. Objective To determine whether this approach can be adapted to suppress all IgE-mediated in mice by injecting serially increasing doses of monoclonal antibodies (mAbs) to IgE or FcεRIα. Methods Active and passive models of antigen- and anti-IgE mAb-induced IgE-mediated anaphylaxis were used. Mice were desensitized with serially increasing doses of anti-IgE mAb, anti-FcεRIα mAb or antigen. Development of shock (hypothermia), histamine and mast cell protease release, cytokine secretion, calcium flux and changes in cell number and FcεRI and IgE expression were evaluated. Results Rapid desensitization with anti-IgE mAb suppressed IgE-mediated immediate hypersensitivity; however, some mice developed mild anaphylaxis during desensitization. Rapid desensitization with anti-FcεRIα mAb that only binds FcεRI that is not occupied by IgE suppressed both active and passive IgE-mediated anaphylaxis without inducing disease. It quickly, but temporarily, suppressed IgE-mediated anaphylaxis by decreasing mast cell signaling through FcεRI, then slowly slowlyinduced longer lasting mast cell unresponsiveness by removing membrane FcεRI. Rapid desensitization with anti-FcεRIα mAb was safer and longer-lasting than rapid desensitization with antigen. Conclusion A rapid desensitization approach with anti-FcεRIα mAb safely desensitizes mice to IgE-mediated anaphylaxis by inducing mast cell anergy and later, removing all mast cell IgE. Rapid desensitization with an anti-human FcεRIα mAb may be able to prevent human IgE-mediated anaphylaxis. PMID:23632296

Nanostructures based on quantum dots for application in promising methods of single- and multiphoton imaging and diagnostics

NASA Astrophysics Data System (ADS)

Nabiev, I. R.

2017-01-01

Molecules recognizing biomarkers of diseases (monoclonal antibodies (monoABs)) are often too large for biomedical applications, and the conditions that are used to bind them with nanolabels lead to disordered orientation of monoABs with respect to the nanoparticle surface. Extremely small nanoprobes, designed via oriented conjugation of quantum dots (QDs) with single-domain antibodies (sdABs) derived from the immunoglobulin of llama and produced in the E. coli culture, have a hydrodynamic diameter less than 12 nm and contain equally oriented sdAB molecules on the surface of each QD. These nanoprobes exhibit excellent specificity and sensitivity in quantitative determination of a small number of cells expressing biomarkers. In addition, the higher diffusion coefficient of sdABs makes it possible to perform immunohistochemical analysis in bulk tissue, inaccessible for conventional monoABs. The necessary conditions for implementing high-quality immunofluorescence diagnostics are a high specificity of labeling and clear differences between the fluorescence of nanoprobes and the autofluorescence of tissues. Multiphoton micros-copy with excitation in the near-IR spectral range, which is remote from the range of tissue autofluorescence excitation, makes it possible to solve this problem and image deep layers in biological tissues. The two-photon absorption cross sections of CdSe/ZnS QDs conjugated with sdABs exceed the corresponding values for organic fluorophores by several orders of magnitude. These nanoprobes provide clear discrimination between the regions of tumor and normal tissues with a ratio of the sdAB fluorescence to the tissue autofluorescence upon two-photon excitation exceeding that in the case of single-photon excitation by a factor of more than 40. The data obtained indicate that the sdAB-QD conjugates used as labels provide the same, or even better, quality as the "gold standard" of immunohistochemical diagnostics. The developed nanoprobes are expected to find wide application in high-efficiency imaging of tumor and multiparameter diagnostics.

Clinical Benefits of Rivastigmine in the Real World Dementia Clinics of the Okayama Rivastigmine Study (ORS).

PubMed

Matsuzono, Kosuke; Sato, Kota; Kono, Syoichiro; Hishikawa, Nozomi; Ohta, Yasuyuki; Yamashita, Toru; Deguchi, Kentaro; Nakano, Yumiko; Abe, Koji

2015-01-01

Alzheimer's disease (AD) is one of the most important diseases in an aging society, but the clinical effects of rivastigmine have not been fully examined in real world domestic clinics. We performed the "Okayama Rivastigmine Study (ORS)" to retrospectively analyze the clinical effects of rivastigmine (n = 75) or donepezil (n = 71) on AD patients with seven dementia assessment batteries at the baseline, 3, 6, and 12 months. In addition, we divided the rivastigmine group into two subgroups at the baseline: the mild behavioral and psychological symptoms of dementia (BPSD) group (Abe's BPSD score (ABS) <6) and the severe BPSD group (6≤ABS). In these two subgroups, baseline scores and changes were also retrospectively analyzed until 12 months. Rivastigmine significantly improved the Mini-Mental State Examination score at 3 months (*p <  0.05 versus baseline) and at 6 months (*p <  0.05), the Frontal Assessment Battery (FAB) at 6 months (*p <  0.05), and ABS at 3 months (**p <  0.01) while donepezil only stabilized the three cognitive scores. On the other hand, the Geriatric Depression Scale and the Apathy Scale were stable until 12 months in both groups. Baseline BPSD severity-dependent analysis showed a small improvement of FAB at 6 months in the mild BPSD subgroup (*p <  0.05) and a great improvement of ABS at 3 months in the severe BPSD subgroup (**p <  0.01) in the rivastigmine group. Our present study showed that rivastigmine improved both cognitive and affective functions at 3 and 6 months, and suggested an advantage at 3 and 6 months compared to donepezil in real world dementia clinics.

Fine-Scale Community Structure Analysis of ANME in Nyegga Sediments with High and Low Methane Flux

PubMed Central

Roalkvam, Irene; Dahle, Håkon; Chen, Yifeng; Jørgensen, Steffen Leth; Haflidason, Haflidi; Steen, Ida Helene

2012-01-01

To obtain knowledge on how regional variations in methane seepage rates influence the stratification, abundance, and diversity of anaerobic methanotrophs (ANME), we analyzed the vertical microbial stratification in a gravity core from a methane micro-seeping area at Nyegga by using 454-pyrosequencing of 16S rRNA gene tagged amplicons and quantitative PCR. These data were compared with previously obtained data from the more active G11 pockmark, characterized by higher methane flux. A down core stratification and high relative abundance of ANME were observed in both cores, with transition from an ANME-2a/b dominated community in low-sulfide and low methane horizons to ANME-1 dominance in horizons near the sulfate-methane transition zone. The stratification was over a wider spatial region and at greater depth in the core with lower methane flux, and the total 16S rRNA copy numbers were two orders of magnitude lower than in the sediments at G11 pockmark. A fine-scale view into the ANME communities at each location was achieved through operational taxonomical units (OTU) clustering of ANME-affiliated sequences. The majority of ANME-1 sequences from both sampling sites clustered within one OTU, while ANME-2a/b sequences were represented in unique OTUs. We suggest that free-living ANME-1 is the most abundant taxon in Nyegga cold seeps, and also the main consumer of methane. The observation of specific ANME-2a/b OTUs at each location could reflect that organisms within this clade are adapted to different geochemical settings, perhaps due to differences in methane affinity. Given that the ANME-2a/b population could be sustained in less active seepage areas, this subgroup could be potential seed populations in newly developed methane-enriched environments. PMID:22715336

Understanding the bacterial polysaccharide antigenicity of Streptococcus agalactiae versus Streptococcus pneumoniae.

PubMed

Kadirvelraj, Renuka; Gonzalez-Outeiriño, Jorge; Foley, B Lachele; Beckham, Meredith L; Jennings, Harold J; Foote, Simon; Ford, Michael G; Woods, Robert J

2006-05-23

Bacterial surface capsular polysaccharides (CPS) that are similar in carbohydrate sequence may differ markedly in immunogenicity and antigenicity. The structural origin of these phenomena is poorly understood. Such a case is presented by the Gram-positive bacteria Streptococcus agalactiae (Group B Streptococcus; GBS) type III (GBSIII) and Streptococcus pneumoniae (Pn) type 14 (Pn14), which share closely related CPS sequences. Nevertheless, antibodies (Abs) against GBSIII rarely cross-react with the CPS from Pn14. To establish the origin for the variation in CPS antigenicity, models for the immune complexes of CPS fragments from GBSIII and Pn14, with the variable fragment (Fv) of a GBS-specific mAb (mAb 1B1), are presented. The complexes are generated through a combination of comparative Ab modeling and automated ligand docking, followed by explicitly solvated 10-ns molecular dynamics simulations. The relationship between carbohydrate sequence and antigenicity is further quantified through the computation of interaction energies using the Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) method, augmented by conformational entropy estimates. Despite the electrostatic differences between Pn14 and GBSIII CPS, analysis indicates that entropic penalties are primarily responsible for the loss of affinity of the highly flexible Pn14 CPS for mAb 1B1. The similarity of the solution conformation of the relatively rigid GBSIII CPS with that in the immune complex characterizes the previously undescribed 3D structure of the conformational epitope. The analysis provides a comprehensive interpretation for a large body of biochemical and immunological data related to Ab recognition of bacterial polysaccharides and should be applicable to other Ab-carbohydrate interactions.

Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xinsheng, E-mail: xzhang@iavi.org; Molecular and Cellular Biology Program, State University of New York, Brooklyn, NY; Wallace, Olivia L.

Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions,more » which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies. - Highlights: • Screened 146 serum samples for measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb). • MV nAb is prevalent in the sera. • CDV neutralizing activity is generally low or absent and when detected it is present in sera with high MV nAb titers. • A neutralization-resistant CDV mutant was isolated using human serum selection. • A mutation was identified in the receptor-binding region of CDV hemagglutinin protein that confers the neutralization resistance.« less

The Introduction into Bacillus sphaericus of the Bacillus thuringiensis subsp. medellin cyt1Ab1 Gene Results in Higher Susceptibility of Resistant Mosquito Larva Populations to B. sphaericus

PubMed Central

Thiéry, I.; Hamon, S.; Delécluse, A.; Orduz, S.

1998-01-01

The fragment containing the gene encoding the cytolytic Cyt1Ab1 protein from Bacillus thuringiensis subsp. medellin and its flanking sequences (I. Thiery, A. Delécluse, M. C. Tamayo, and S. Orduz, Appl. Environ. Microbiol. 63:468–473, 1997) was introduced into Bacillus sphaericus toxic strains 2362, 2297, and Iab872 by electroporation with the shuttle vector pMK3. Only small amounts of the protein were produced in recombinant strains 2362 and Iab872. The protein was detected in these strains only by Western blotting and immunodetection with antibody raised against Cyt1Ab1 protein. Large amounts of Cyt1Ab1 protein were produced in B. sphaericus recombinant strain 2297, and there was an additional crystal, other than that of the binary toxin, within the exosporium. The production of the Cyt1Ab1 protein in addition to the binary toxin did not increase the larvicidal activity of the B. sphaericus recombinant strain against susceptible mosquito populations of Culex pipiens or Aedes aegypti. However, it partially restored (10 to 20 times) susceptibility of the resistant mosquito populations of C. pipiens (SPHAE) and Culex quinquefasciatus (GeoR) to the binary toxin. The Cyt1Ab1 protein produced in recombinant B. thuringiensis SPL407(pcyt1Ab1) was synthesized in two types of crystal—one round and with various dense areas, surrounded by an envelope, and the other a regular cuboid crystal, very similar to that found in the B. sphaericus recombinant strain. PMID:9758818

The successful merger of theoretical thermochemistry with fragment-based methods in quantum chemistry.

PubMed

Ramabhadran, Raghunath O; Raghavachari, Krishnan

2014-12-16

CONSPECTUS: Quantum chemistry and electronic structure theory have proven to be essential tools to the experimental chemist, in terms of both a priori predictions that pave the way for designing new experiments and rationalizing experimental observations a posteriori. Translating the well-established success of electronic structure theory in obtaining the structures and energies of small chemical systems to increasingly larger molecules is an exciting and ongoing central theme of research in quantum chemistry. However, the prohibitive computational scaling of highly accurate ab initio electronic structure methods poses a fundamental challenge to this research endeavor. This scenario necessitates an indirect fragment-based approach wherein a large molecule is divided into small fragments and is subsequently reassembled to compute its energy accurately. In our quest to further reduce the computational expense associated with the fragment-based methods and overall enhance the applicability of electronic structure methods to large molecules, we realized that the broad ideas involved in a different area, theoretical thermochemistry, are transferable to the area of fragment-based methods. This Account focuses on the effective merger of these two disparate frontiers in quantum chemistry and how new concepts inspired by theoretical thermochemistry significantly reduce the total number of electronic structure calculations needed to be performed as part of a fragment-based method without any appreciable loss of accuracy. Throughout, the generalized connectivity based hierarchy (CBH), which we developed to solve a long-standing problem in theoretical thermochemistry, serves as the linchpin in this merger. The accuracy of our method is based on two strong foundations: (a) the apt utilization of systematic and sophisticated error-canceling schemes via CBH that result in an optimal cutting scheme at any given level of fragmentation and (b) the use of a less expensive second layer of electronic structure method to recover all the missing long-range interactions in the parent large molecule. Overall, the work featured here dramatically decreases the computational expense and empowers the execution of very accurate ab initio calculations (gold-standard CCSD(T)) on large molecules and thereby facilitates sophisticated electronic structure applications to a wide range of important chemical problems.

Copy Number Heterogeneity, Large Origin Tandem Repeats, and Interspecies Recombination in Human Herpesvirus 6A (HHV-6A) and HHV-6B Reference Strains

PubMed Central

Roychoudhury, Pavitra; Makhsous, Negar; Hanson, Derek; Chase, Jill; Krueger, Gerhard; Xie, Hong; Huang, Meei-Li; Saunders, Lindsay; Ablashi, Dharam; Koelle, David M.; Cook, Linda; Jerome, Keith R.

2018-01-01

ABSTRACT Quantitative PCR is a diagnostic pillar for clinical virology testing, and reference materials are necessary for accurate, comparable quantitation between clinical laboratories. Accurate quantitation of human herpesvirus 6A/B (HHV-6A/B) is important for detection of viral reactivation and inherited chromosomally integrated HHV-6A/B in immunocompromised patients. Reference materials in clinical virology commonly consist of laboratory-adapted viral strains that may be affected by the culture process. We performed next-generation sequencing to make relative copy number measurements at single nucleotide resolution of eight candidate HHV-6A and seven HHV-6B reference strains and DNA materials from the HHV-6 Foundation and Advanced Biotechnologies Inc. Eleven of 17 (65%) HHV-6A/B candidate reference materials showed multiple copies of the origin of replication upstream of the U41 gene by next-generation sequencing. These large tandem repeats arose independently in culture-adapted HHV-6A and HHV-6B strains, measuring 1,254 bp and 983 bp, respectively. The average copy number measured was between 5 and 10 times the number of copies of the rest of the genome. We also report the first interspecies recombinant HHV-6A/B strain with a HHV-6A backbone and a >5.5-kb region from HHV-6B, from U41 to U43, that covered the origin tandem repeat. Specific HHV-6A reference strains demonstrated duplication of regions at U1/U2, U87, and U89, as well as deletion in the U12-to-U24 region and the U94/U95 genes. HHV-6A/B strains derived from cord blood mononuclear cells from different laboratories on different continents with fewer passages revealed no copy number differences throughout the viral genome. These data indicate that large origin tandem duplications are an adaptation of both HHV-6A and HHV-6B in culture and show interspecies recombination is possible within the Betaherpesvirinae. IMPORTANCE Anything in science that needs to be quantitated requires a standard unit of measurement. This includes viruses, for which quantitation increasingly determines definitions of pathology and guidelines for treatment. However, the act of making standard or reference material in virology can alter its very accuracy through genomic duplications, insertions, and rearrangements. We used deep sequencing to examine candidate reference strains for HHV-6, a ubiquitous human virus that can reactivate in the immunocompromised population and is integrated into the human genome in every cell of the body for 1% of people worldwide. We found large tandem repeats in the origin of replication for both HHV-6A and HHV-6B that are selected for in culture. We also found the first interspecies recombinant between HHV-6A and HHV-6B, a phenomenon that is well known in alphaherpesviruses but to date has not been seen in betaherpesviruses. These data critically inform HHV-6A/B biology and the standard selection process. PMID:29491155

A two-stage algorithm for Clostridium difficile including PCR: can we replace the toxin EIA?

PubMed

Orendi, J M; Monnery, D J; Manzoor, S; Hawkey, P M

2012-01-01

A two step, three-test algorithm for Clostridium difficile infection (CDI) was reviewed. Stool samples were tested by enzyme immunoassays for C. difficile common antigen glutamate dehydrogenase (G) and toxin A/B (T). Samples with discordant results were tested by polymerase chain reaction detecting the toxin B gene (P). The algorithm quickly identified patients with detectable toxin A/B, whereas a large group of patients excreting toxigenic C. difficile but with toxin A/B production below detection level (G(+)T(-)P(+)) was identified separately. The average white blood cell count in patients with a G(+)T(+) result was higher than in those with a G(+)T(-)P(+) result. Copyright © 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Recent advances in jointed quantum mechanics and molecular mechanics calculations of biological macromolecules: schemes and applications coupled to ab initio calculations.

PubMed

Hagiwara, Yohsuke; Tateno, Masaru

2010-10-20

We review the recent research on the functional mechanisms of biological macromolecules using theoretical methodologies coupled to ab initio quantum mechanical (QM) treatments of reaction centers in proteins and nucleic acids. Since in most cases such biological molecules are large, the computational costs of performing ab initio calculations for the entire structures are prohibitive. Instead, simulations that are jointed with molecular mechanics (MM) calculations are crucial to evaluate the long-range electrostatic interactions, which significantly affect the electronic structures of biological macromolecules. Thus, we focus our attention on the methodologies/schemes and applications of jointed QM/MM calculations, and discuss the critical issues to be elucidated in biological macromolecular systems. © 2010 IOP Publishing Ltd

Assessing the accuracy of improved force-matched water models derived from Ab initio molecular dynamics simulations.

PubMed

Köster, Andreas; Spura, Thomas; Rutkai, Gábor; Kessler, Jan; Wiebeler, Hendrik; Vrabec, Jadran; Kühne, Thomas D

2016-07-15

The accuracy of water models derived from ab initio molecular dynamics simulations by means on an improved force-matching scheme is assessed for various thermodynamic, transport, and structural properties. It is found that although the resulting force-matched water models are typically less accurate than fully empirical force fields in predicting thermodynamic properties, they are nevertheless much more accurate than generally appreciated in reproducing the structure of liquid water and in fact superseding most of the commonly used empirical water models. This development demonstrates the feasibility to routinely parametrize computationally efficient yet predictive potential energy functions based on accurate ab initio molecular dynamics simulations for a large variety of different systems. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

An ab initio molecular orbital study of the mechanism for the gas-phase water-mediated decomposition and the formation of hydrates of peroxyacetyl nitrate (PAN).

PubMed

Li, Yumin; Francisco, Joseph S

2005-08-31

There is uncertainty in the mechanism for the hydrolysis of peroxyacetyl nitrate (PAN), and experimental attempts to detect products of the direct reaction have been unsuccessful. Ab initio calculations are used to examine the energetics of water-mediated decomposition of gas-phase PAN into acetic acid and peroxynitric acid. On the basis of ab initio calculations, an alternative reaction mechanism for the decomposition of PAN is proposed. The calculations indicate that the barrier for one water addition to PAN is large. However, including additional water molecules reveals a substantially lower energy route. The calculations suggest that the formation of PAN hydrate complexes are energetically favorable and stable. Additional waters are increasingly efficient at stabilizing hydrated PAN.

Theoretical studies of the local structures and spin Hamiltonian parameters for Cu2+ in alkaline earth alumino borate glasses

NASA Astrophysics Data System (ADS)

Guo, Jia-Xing; Wu, Shao-Yi; Kuang, Min-Quan; Peng, Li; Wu, Li-Na

2018-01-01

The local structures and spin Hamiltonian parameters are theoretically studied for Cu2+ in alkaline earth alumino borate (XAB, X = Mg, Ca and Sr) glasses by using the perturbation calculations for tetragonally elongated octahedral 3d9 groups. The [CuO6]10- groups are subject to the large relative tetragonal elongation ratios of 15.4%, 13.4% and 13.0% for MgAB, CaAB and SrAB glasses, respectively, arising from the Jahn-Teller effect. The decreasing cubic field parameter Dq, orbital reduction factor k and relative elongation ratio with the increase of the radius of alkaline earth ion X from Mg to Ca or Sr are analyzed for the studied systems in a uniform way.

The Hα line forming region of AB Aurigae spatially resolved at sub-AU with the VEGA/CHARA spectro-interferometer

NASA Astrophysics Data System (ADS)

Rousselet-Perraut, K.; Benisty, M.; Mourard, D.; Rajabi, S.; Bacciotti, F.; Bério, Ph.; Bonneau, D.; Chesneau, O.; Clausse, J. M.; Delaa, O.; Marcotto, A.; Roussel, A.; Spang, A.; Stee, Ph.; Tallon-Bosc, I.; McAlister, H.; ten Brummelaar, T.; Sturmann, J.; Sturmann, L.; Turner, N.; Farrington, C.; Goldfinger, P. J.

2010-06-01

Context. A crucial issue in star formation is to understand the physical mechanism by which mass is accreted onto and ejected by a young star. To derive key constraints on the launching point of the jets and on the geometry of the winds, the visible spectro-polarimeter VEGA installed on the CHARA optical array can be an efficient means of probing the structure and the kinematics of the hot circumstellar gas at sub-AU. Aims: For the first time, we observed the Herbig Ae star AB Aur in the Hα emission line, using the VEGA low spectral resolution (R = 1700) on two baselines of the array. Methods: We computed and calibrated the spectral visibilities of AB Aur between 610 nm and 700 nm in spectral bands of 20.4 nm. To simultaneously reproduce the line profile and the inferred visibility around Hα, we used a 1D radiative transfer code (RAMIDUS/PROFILER) that calculates level populations for hydrogen atoms in a spherical geometry and that produces synthetic spectro-interferometric observables. Results: We clearly resolved AB Aur in the Hα line and in a part of the continuum, even at the smallest baseline of 34 m. The small P-Cygni absorption feature is indicative of an outflow but could not be explained by a spherical stellar wind model. Instead, it favors a magneto-centrifugal X-disk or disk-wind geometry. The fit of the spectral visibilities from 610 to 700 nm could not be accounted for by a wind alone, so another component inducing a visibility modulation around Hα needed to be considered. We thus considered a brightness asymmetry possibly caused by large-scale nebulosity or by the known spiral structures. Conclusions: Thanks to the unique capabilities of VEGA, we managed to simultaneously record for the first time a spectrum at a resolution of 1700 and spectral visibilities in the visible range on a target as faint as mV = 7.1. It was possible to rule out a spherical geometry for the wind of AB Aur and provide realistic solutions to account for the Hα emission compatible with magneto-centrifugal acceleration. It was difficult, however, to determine the exact morphology of the wind because of the surrounding asymmetric nebulosity. The study illustrates the advantages of optical interferometry and motivates observations of other bright young stars in the same way to shed light on the accretion/ejection processes.

Large-scale displacement following the 2016 Kaikōura earthquake

NASA Astrophysics Data System (ADS)

Wang, T.; Peng, D.; Barbot, S.; Wei, S.; Shi, X.

2017-12-01

The 2016 Mw 7.9 Kaikōura earthquake occurred near the southern termination of the Hikurangi subduction system, where a transition from subduction to strike-slip motion dominates the pre-seismic strain accumulation. Dense spatial coverage of the GPS measurements and large amount of Interferometric Synthetic Aperture Radar (InSAR) images provide valuable constraints, from the near field to the far field, to study how the slip is distributed among the subduction interface and the overlying fault system before, during and after the earthquake. We extract time-series deformation from the New Zealand continuous GPS network, and SAR images acquired from Japanese ALOS-2 and European Sentinel-1A/B satellites to image the surface deformation related to the 2016 Kaikōura earthquake. Both GPS and InSAR data, which cover the entire New Zealand region, show that the co-seismic and post-seismic deformations are distributed in an extraordinary large area, as far as to the north tip of the North Island. Based on a coseismic slip model derived from seismic and geodetic observations, we calculate the stress perturbation incurred by the earthquake. We explore a range of possibilities of friction laws and rheology via a linear combination of strain rate in finite volumes and slip velocity on ruptured faults. We obtain the slip distribution that can best explain our geodetic measurements using outlier-insensitive hierarchical Bayesian model, to better understand different mechanisms behind the localized shallow after slip and distributed deformation. Our results indicate that complex interactions between the subduction interface and the overlying fault system play an important role in causing such large-scale deformation during and after the earthquake event.

Genetic basis of Bartter syndrome in Korea.

PubMed

Lee, Beom Hee; Cho, Hee Yeon; Lee, HyunKyung; Han, Kyoung Hee; Kang, Hee Gyung; Ha, Il Soo; Lee, Joo Hoon; Park, Young Seo; Shin, Jae Il; Lee, Dae-Yeol; Kim, Su-Yung; Choi, Yong; Cheong, Hae Il

2012-04-01

Bartter syndrome (BS) is clinically classified into antenatal or neonatal BS (aBS) and classic BS (cBS) as well as five subtypes based on the underlying mutant gene; SLC12A1 (BS I), KCNJ1 (BS II), CLCNKB (BS III), BSND (BS IV) and CASR (BS V). Clinico-genetic features of a nationwide cohort of 26 Korean children with BS were investigated. The clinical diagnosis was aBS in 8 (30.8%), cBS in 15 (57.7%) and mixed Bartter-Gitelman phenotype in 3 cases (11.5%). Five of eight patients with aBS and all 18 patients with either cBS or mixed Bartter-Gitelman phenotype had CLCNKB mutations. Among the 23 patients (46 alleles) with CLCNKB mutations, p.W610X and large deletions were detected in 25 (54.3%) and 10 (21.7%) alleles, respectively. There was no genotype-phenotype correlation in patients with CLCNKB mutations. Twenty-three (88.5%) of the 26 BS patients involved in this study had CLCNKB mutations. The p.W610X mutation and large deletion were two common types of mutations in CLCNKB. The clinical manifestations of BS III were heterogeneous without a genotype-phenotype correlation, typically manifesting cBS phenotype but also aBS or mixed Bartter-Gitelman phenotypes. The molecular diagnostic steps for patients with BS in our population should be designed taking these peculiar genotype distributions into consideration, and a new more clinically relevant classification including BS and Gitelman syndrome is required.

Performance optimization of Qbox and WEST on Intel Knights Landing

NASA Astrophysics Data System (ADS)

Zheng, Huihuo; Knight, Christopher; Galli, Giulia; Govoni, Marco; Gygi, Francois

We present the optimization of electronic structure codes Qbox and WEST targeting the Intel®Xeon Phi™processor, codenamed Knights Landing (KNL). Qbox is an ab-initio molecular dynamics code based on plane wave density functional theory (DFT) and WEST is a post-DFT code for excited state calculations within many-body perturbation theory. Both Qbox and WEST employ highly scalable algorithms which enable accurate large-scale electronic structure calculations on leadership class supercomputer platforms beyond 100,000 cores, such as Mira and Theta at the Argonne Leadership Computing Facility. In this work, features of the KNL architecture (e.g. hierarchical memory) are explored to achieve higher performance in key algorithms of the Qbox and WEST codes and to develop a road-map for further development targeting next-generation computing architectures. In particular, the optimizations of the Qbox and WEST codes on the KNL platform will target efficient large-scale electronic structure calculations of nanostructured materials exhibiting complex structures and prediction of their electronic and thermal properties for use in solar and thermal energy conversion device. This work was supported by MICCoM, as part of Comp. Mats. Sci. Program funded by the U.S. DOE, Office of Sci., BES, MSE Division. This research used resources of the ALCF, which is a DOE Office of Sci. User Facility under Contract DE-AC02-06CH11357.

MD modeling of screw dislocation influence upon initiation and mechanism of BCC-HCP polymorphous transition in iron

NASA Astrophysics Data System (ADS)

Dremov, V. V.; Ionov, G. V.; Sapozhnikov, F. A.; Smirnov, N. A.; Karavaev, A. V.; Vorobyova, M. A.; Ryzhkov, M. V.

2015-09-01

The present work is devoted to classical molecular dynamics investigation into microscopic mechanisms of the bcc-hcp transition in iron. The interatomic potential of EAM type used in the calculations was tested for the capability to reproduce ab initio data on energy evolution along the bcc-hcp transformation path (Burgers deformation + shuffe) and then used in the large-scale MD simulations. The large-scale simulations included constant volume deformation along the Burgers path to study the origin and nature of the plasticity, hydrostatic volume compression of defect free samples above the bcc to hcp transition threshold to observe the formation of new phase embryos, and the volume compression of samples containing screw dislocations to study the effect of the dislocations on the probability of the new phase critical embryo formation. The volume compression demonstrated high level of metastability. The transition starts at pressure much higher than the equilibrium one. Dislocations strongly affect the probability of the critical embryo formation and significantly reduce the onset pressure of transition. The dislocations affect also the resulting structure of the samples upon the transition. The formation of layered structure is typical for the samples containing the dislocations. The results of the simulations were compared with the in-situ experimental data on the mechanism of the bcc-hcp transition in iron.

Robust production of virus-like particles and monoclonal antibodies with geminiviral replicon vectors in lettuce

PubMed Central

Lai, Huafang; He, Junyun; Engle, Michael; Diamond, Michael S.; Chen, Qiang

2011-01-01

Summary Pharmaceutical protein production in plants has been greatly promoted by the development of viral-based vectors and transient expression systems. Tobacco and related Nicotiana species are currently the most common host plants for generation of plant-made pharmaceutical proteins (PMPs). Downstream processing of target PMPs from these plants, however, is hindered by potential technical and regulatory difficulties due to the presence of high levels of phenolics and toxic alkaloids. Here, we explored the use of lettuce, which grows quickly yet produces low levels of secondary metabolites, and viral vector-based transient expression systems to develop a robust PMP production platform. Our results showed that a geminiviral replicon system based on the bean yellow dwarf virus permits high-level expression in lettuce of virus-like particles (VLP) derived from the Norwalk virus capsid protein and therapeutic monoclonal antibodies (mAbs) against Ebola and West Nile viruses. These vaccine and therapeutic candidates can be readily purified from lettuce leaves with scalable processing methods while fully retaining functional activity. Furthermore, this study also demonstrated the feasibility of using commercially produced lettuce for high-level PMP production. This allows our production system to have access to unlimited quantities of inexpensive plant material for large-scale production. These results establish a new production platform for biological pharmaceutical agents that is effective, safe, low-cost, and amenable to large-scale manufacturing. PMID:21883868

Influence of illuminants on the color distribution of shade guides.

PubMed

Park, Ji-Hoon; Lee, Yong-Keun; Lim, Bum-Soon

2006-12-01

Although a shade tab in a shade guide is matched to a natural tooth in the order of value, hue, and chroma, there are limited data on the color distribution of currently available shade guides sorted by these 3 parameters. Furthermore, spectrophotometric color measurements of shade tabs differ depending on the standard illuminant employed. The purpose of this study was to determine the color distributions of 2 shade guides in value (CIE L( *)), chroma (C( *)(ab)) and hue angle (h(o)) scale relative to the standard illuminants D(65), A, and F2. Color of shade tabs (n=36) from 2 shade guides (Vita Lumin and Chromascop) were measured, and the distributions for CIE L( *), C( *)(ab) and h(o) values were compared. Color differences of shade tabs depending on the illuminant were calculated. The distributions of the ratios of CIE L( *) and C( *)(ab) values of each shade tab compared with the lowest value tab or the lowest chroma tab were determined. The data for the value, chroma, and hue angle within each shade guide were analyzed with a 2-way ANOVA with the factors of shade designation and type of illuminant (alpha=.05). Color difference caused by change of illuminant was analyzed with a 2-way ANOVA with the factors of shade designation and pair of illuminants compared (alpha=.05). The Scheffe multiple comparison test was performed as a post hoc test. CIE L( *), C( *)(ab) and h(o) values were influenced by shade designation and type of illuminant in both shade guides. Color difference caused by change of the illuminant was influenced by the shade designation and pair of illuminants compared. The order of mean color differences of 16 Vita Lumin shade tabs by pairs of illuminants compared was as follows: DeltaE( *)(ab) (D(65)/F2) = 1.63 3.7). Color distribution of 2 shade guides by the value and chroma was not logical.

Correction for faking in self-report personality tests.

PubMed

Sjöberg, Lennart

2015-10-01

Faking is a common problem in testing with self-report personality tests, especially in high-stakes situations. A possible way to correct for it is statistical control on the basis of social desirability scales. Two such scales were developed and applied in the present paper. It was stressed that the statistical models of faking need to be adapted to different properties of the personality scales, since such scales correlate with faking to different extents. In four empirical studies of self-report personality tests, correction for faking was investigated. One of the studies was experimental, and asked participants to fake or to be honest. In the other studies, job or school applicants were investigated. It was found that the approach to correct for effects of faking in self-report personality tests advocated in the paper removed a large share of the effects, about 90%. It was found in one study that faking varied as a function of degree of how important the consequences of test results could be expected to be, more high-stakes situations being associated with more faking. The latter finding is incompatible with the claim that social desirability scales measure a general personality trait. It is concluded that faking can be measured and that correction for faking, based on such measures, can be expected to remove about 90% of its effects. © 2015 Psykologisk Metod AB. Scandinavian Journal of Psychology published by Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Oxidation Protection Systems for Carbon-Carbon Composites Formed by Chemical Vapor Deposition and Plasma Assisted Chemical Vapor Deposition Techniques

DTIC Science & Technology

1992-04-22

Illinois University at Carbondale, 1991, in printing. I 42. E. Tatarzycki, ABS Report-4538216:#3, 10, 1990. 43. C. Ju, et. al., Proc. of 6th Materials...transducer, ie. a more positive scaleI I 34 thickness of fairly continuous conversion layer carbon 10 , •O.0000 resina 0 0 Fiber O0c00.a 0 Bundlea • 06...at 13000C, 0.1 atm. 1 93 IZ- ... an rI pia irgaho tea-ccv~ ab .. au .re ;--24- Oo. C:caI micrograpt~h ofcin th e csr ossivc sczrbc2 ccirzza Fck

Scaling the Shear-flow Stabilized Z-pinch to Reactor Conditions

NASA Astrophysics Data System (ADS)

McLean, H. S.; Schmidt, A.; Shumlak, U.; Nelson, B. A.; Golingo, R. P.; Cleveau, E.

2015-11-01

We present a conceptual design along with scaling calculations for a pulsed fusion reactor based on the shear-flow-stabilized Z-pinch device. Experiments performed on the ZaP device, at the University of Washington, have demonstrated stable operation for durations of 20 usec at ~100kA discharge current for pinches that are ~1 cm in diameter and 100 cm long. The inverse of the pinch diameter and plasma energy density scale strongly with pinch current and calculations show that maintaining stabilization durations of ~7 usec for increased discharge current (~15x) in a shortened pinch (10 cm) results in a pinch diameter of ~200 um and plasma conditions that approach those needed to support significant fusion burn and energy gain (Ti ~ 30keV, density ~ 3e26/m3, ntau ~1.4e20 sec/m3). Compelling features of the concept include operation at modest discharge current (1.5 MA) and voltage (40kV) along with direct adoption of liquid metals for at least one electrode--technological capabilities that have been proven in existing, commercial, pulse power devices such as large ignitrons. LLNL-ABS-674920. This work performed under the auspices of the U.S. Department of Energy ARPAe ALPHA Program by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Biennial Hazardous Waste Report

EPA Pesticide Factsheets

Federal regulations require large quantity generators to submit a report (EPA form 8700-13A/B) every two years regarding the nature, quantities and disposition of hazardous waste generated at their facility.

Analyzing Real-World Light Duty Vehicle Efficiency Benefits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gonder, Jeffrey; Wood, Eric; Chaney, Larry

Off-cycle technologies represent an important pathway to achieve real-world fuel savings, through which OEMs can potentially receive credit toward CAFE compliance. DOE national labs such as NREL are well positioned to provide objective input on these technologies using large, national data sets in conjunction with OEM- and technology-specific testing. This project demonstrates an approach that combines vehicle testing (dynamometer and on-road) with powertrain modeling and simulation over large, representative datasets to quantify real-world fuel economy. The approach can be applied to specific off-cycle technologies (engine encapsulation, start/stop, connected vehicle, etc.) in A/B comparisons to support calculation of realistic real-world impacts.more » Future work will focus on testing-based A/B technology comparisons that demonstrate the significance of this approach.« less

Density functional simulations as a tool to probe molecular interactions in wet supercritical CO2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glezakou, Vassiliki Alexandra; McGrail, B. Peter

2013-06-03

Recent advances in mixed Gaussian and plane wave algorithms have made possible the effective use of density functional theory (DFT) in ab initio molecular dynamics (AIMD) simulations for large and chemically complex models of condensed phase materials. In this chapter, we are reviewing recent progress on the modeling and characterization of co-sequestration processes and reactivity in wet supercritical CO2 (sc-CO2). We examine the molecular transformations of mineral and metal components of a sequestration system in contact with water-bearing scCO2 media and aim to establish a reliable correspondence between experimental observations and theory models with predictive ability and transferability of resultsmore » in large scale geomechanical simulators. This work is funded by the Department of Energy, Office of Fossil Energy. A portion of the research was performed using EMSL, a national scientific user facility sponsored by the Department of Energy’s Office of Biological and Environmental Research located at Pacific Northwest National Laboratory. The Pacific Norhtwest National Laboratory (PNNL) is operated by Battelle for DOE under contract DE-AC06-76RL01830.« less

Impeding 99Tc(IV) mobility in novel waste forms

DOE PAGES

Lee, Mal-Soon; Um, Wooyong; Wang, Guohui; ...

2016-06-30

Technetium ( 99Tc) is a long-lived radioactive fission product whose mobility in the subsurface is largely governed by its oxidation state1. Immobilization of Tc in mineral substrates is crucial for radioactive waste management and environmental remediation. Tc(IV) incorporation in spinels2, 3 has been proposed as a novel method to increase Tc retention in glass waste forms. However, experiments with Tc-magnetite under high temperature and oxic conditions showed re-oxidation of Tc(IV) to volatile pertechnetate Tc(VII)O4-.4, 5 Here we address this problem with large-scale ab initio molecular dynamics simulations and propose that elevated temperatures, 1st row transition metal dopants can significantly enhancemore » Tc retention in the order Co > Zn > Ni. Experiments with doped spinels at T=700 ºC provided quantitative confirmation of increased Tc retention in the same order predicted by theory. This work highlights the power of modern state-of-the-art simulations to provide essential insights and generate bottom-up design criteria of complex oxide materials at elevated temperatures.« less

Improved energy output levels from small-scale Microbial Fuel Cells.

PubMed

Ieropoulos, I; Greenman, J; Melhuish, C

2010-04-01

This study reports on the findings from the investigation into small-scale (6.25 mL) MFCs, connected together as a network of multiple units. The MFCs contained unmodified (no catalyst) carbon fibre electrodes and for initial and later experiments, a standard ion-exchange membrane for the proton transfer from the anode to the cathode. The anode microbial culture was of the type commonly found in domestic wastewater fed with 5 mM acetate as the carbon-energy (C/E) source. The cultures were mature and acclimatised in the MFC environment for approximately 2 months before being re-inoculated in the experimental MFC units. The cathode was of the O(2) diffusion open-to-air type, but for the purposes of the polarization experiments, the cathodic electrodes were moistened with ferricyanide. The main aim of this study was to investigate the effects of connecting multiples of MFC units together as a method of scale up by using stacks and comparison of the effects of different PEM and MFC structural materials on the performance. Impedance matching (maximum-power-transfer) was achieved through calculation of total internal impedance. Three different PEM materials were compared in otherwise identical MFCs in sets of three. For individual isolated MFCs, Hyflon E87-03 was shown to produce twice, whilst E87-10 produced approximately 1.5 times the power output of the control (standard) PEM. However, when MFCs containing the E87-03 and E87-10 membranes were connected in a stack, the system suffered from severe instability and cell reversal. To study the effects of the various polymeric MFC structural materials, four small-scale units were manufactured from three different types of RP material; acrylo-butadiene-styrene coated (ABS), ABS coated (ABS-MEK) and polycarbonate (polyC). The stack of four (4) units prototyped out of polyC produced the highest power density values in polarisation experiments (80 mW/m(2)). 2009 Elsevier B.V. All rights reserved.

Thermal Conductivity of Liquid Water from Reverse Nonequilibrium Ab Initio Molecular Dynamics

NASA Astrophysics Data System (ADS)

Tsuchida, Eiji

2018-02-01

We report on a theoretical framework for calculating the thermal conductivity of liquid water from first principles with the aid of the linear scaling method. We also discuss the possibility of obtaining equilibrium properties from a nonequilibrium trajectory.

Universal scaling of potential energy functions describing intermolecular interactions. II. The halide-water and alkali metal-water interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Werhahn, Jasper C.; Akase, Dai; Xantheas, Sotiris S.

2014-08-14

The scaled versions of the newly introduced [S. S. Xantheas and J. C. Werhahn, J. Chem. Phys.141, 064117 (2014)] generalized forms of some popular potential energy functions (PEFs) describing intermolecular interactions – Mie, Lennard-Jones, Morse, and Buckingham exponential-6 – have been used to fit the ab initio relaxed approach paths and fixed approach paths for the halide-water, X -(H 2O), X = F, Cl, Br, I, and alkali metal-water, M +(H 2O), M = Li, Na, K, Rb, Cs, interactions. The generalized forms of those PEFs have an additional parameter with respect to the original forms and produce fits tomore » the ab initio data that are between one and two orders of magnitude better in the χ 2 than the original PEFs. They were found to describe both the long-range, minimum and repulsive wall of the respective potential energy surfaces quite accurately. Overall the 4-parameter extended Morse (eM) and generalized Buckingham exponential-6 (gBe-6) potentials were found to best fit the ab initio data for these two classes of ion-water interactions. Finally, the fitted values of the parameter of the (eM) and (gBe-6) PEFs that control the repulsive wall of the potential correlate remarkably well with the ionic radii of the halide and alkali metal ions.« less

Assessment of ability of murine and human anti-lipid A monoclonal antibodies to bind and neutralize lipopolysaccharide

PubMed Central

1993-01-01

The use of monoclonal antibodies (mAbs) directed to lipid A for the therapy of gram-negative sepsis is controversial. In an attempt to understand their biologic basis of action, we used a fluid-phase radioimmunoassay to measure binding between bacterial lipopolysaccharide (LPS) and two IgM mAbs directed to lipid A that are being evaluated for the treatment of gram-negative bacterial sepsis. Both antibodies bound 3H-LPS prepared from multiple strains of gram- negative bacteria when large excesses of antibody were used, although binding was modest and only slightly greater than control preparations. We also studied the ability of each anti-lipid A antibody to neutralize some of the biological effects of LPS in vitro. Despite large molar excesses, neither antibody neutralized LPS as assessed by the limulus lysate test, by a mitogenic assay for murine splenocytes, or by the production of cytokines interleukin (IL)-1, IL-6, or tumor necrosis factor from human monocytes in culture medium or in whole blood. Our experiments do not support the hypothesis that either of these anti- lipid A mAbs function by neutralizing the toxic effects of LPS. PMID:8418211

Methods for Melting Temperature Calculation

NASA Astrophysics Data System (ADS)

Hong, Qi-Jun

Melting temperature calculation has important applications in the theoretical study of phase diagrams and computational materials screenings. In this thesis, we present two new methods, i.e., the improved Widom's particle insertion method and the small-cell coexistence method, which we developed in order to capture melting temperatures both accurately and quickly. We propose a scheme that drastically improves the efficiency of Widom's particle insertion method by efficiently sampling cavities while calculating the integrals providing the chemical potentials of a physical system. This idea enables us to calculate chemical potentials of liquids directly from first-principles without the help of any reference system, which is necessary in the commonly used thermodynamic integration method. As an example, we apply our scheme, combined with the density functional formalism, to the calculation of the chemical potential of liquid copper. The calculated chemical potential is further used to locate the melting temperature. The calculated results closely agree with experiments. We propose the small-cell coexistence method based on the statistical analysis of small-size coexistence MD simulations. It eliminates the risk of a metastable superheated solid in the fast-heating method, while also significantly reducing the computer cost relative to the traditional large-scale coexistence method. Using empirical potentials, we validate the method and systematically study the finite-size effect on the calculated melting points. The method converges to the exact result in the limit of a large system size. An accuracy within 100 K in melting temperature is usually achieved when the simulation contains more than 100 atoms. DFT examples of Tantalum, high-pressure Sodium, and ionic material NaCl are shown to demonstrate the accuracy and flexibility of the method in its practical applications. The method serves as a promising approach for large-scale automated material screening in which the melting temperature is a design criterion. We present in detail two examples of refractory materials. First, we demonstrate how key material properties that provide guidance in the design of refractory materials can be accurately determined via ab initio thermodynamic calculations in conjunction with experimental techniques based on synchrotron X-ray diffraction and thermal analysis under laser-heated aerodynamic levitation. The properties considered include melting point, heat of fusion, heat capacity, thermal expansion coefficients, thermal stability, and sublattice disordering, as illustrated in a motivating example of lanthanum zirconate (La2Zr2O7). The close agreement with experiment in the known but structurally complex compound La2Zr 2O7 provides good indication that the computation methods described can be used within a computational screening framework to identify novel refractory materials. Second, we report an extensive investigation into the melting temperatures of the Hf-C and Hf-Ta-C systems using ab initio calculations. With melting points above 4000 K, hafnium carbide (HfC) and tantalum carbide (TaC) are among the most refractory binary compounds known to date. Their mixture, with a general formula TaxHf 1-xCy, is known to have a melting point of 4215 K at the composition Ta4HfC 5, which has long been considered as the highest melting temperature for any solid. Very few measurements of melting point in tantalum and hafnium carbides have been documented, because of the obvious experimental difficulties at extreme temperatures. The investigation lets us identify three major chemical factors that contribute to the high melting temperatures. Based on these three factors, we propose and explore a new class of materials, which, according to our ab initio calculations, may possess even higher melting temperatures than Ta-Hf-C. This example also demonstrates the feasibility of materials screening and discovery via ab initio calculations for the optimization of "higher-level" properties whose determination requires extensive sampling of atomic configuration space.

The flared inner disk of the Herbig Ae star AB Aurigae revealed by VLTI/MIDI in the N-band

NASA Astrophysics Data System (ADS)

di Folco, E.; Dutrey, A.; Chesneau, O.; Wolf, S.; Schegerer, A.; Leinert, Ch.; Lopez, B.

2009-06-01

Aims: We aim at using the long baselines of the VLT Interferometer and the mid-IR combiner MIDI (8-13 μm) to derive the morphology of the protoplanetary disk surrounding the Herbig Ae star AB Aurigae Methods: We present the first N-band analysis of AB Aur performed with a maximum angular resolution of 17 mas (2.5 AU at the Taurus-Auriga distance). We used the radiative transfer code MC3D and a silicate-dominated dust grain mixture to fit the spectral energy distribution (SED), together with the N-band dispersed visibilities (λ / δλ ~ 30) and to constrain the inner-disk spatial structure. Results: The silicate band is prominent in the ~ 300 mas FOV of the MIDI instrument, the emission reaches 70 to 90% of the total flux measured by ISO. The circumstellar emission (CSE) is resolved even at the shortest baselines. The spectrally dispersed visibilities show a steep drop between 8 and 9.5 μm, followed by a plateau between 10 and 13 μm. Our modelling shows that the observed SED and visibilities can be reproduced with a simple passive disk model. For such a weakly inclined disk (i ~ 30 deg), the mid-IR visibilities can directly determine the flaring index, while the scale height can be subsequently and unambiguously derived from the combination of the spectral and interferometric constraints. The modelling yields typical values for the scale height of about 8 AU at a radial distance of 100 AU and a flaring index in the range 1.25-1.30 for the explored range of model input parameters. Conclusions: The radial structure of the circumstellar inner disk around AB Aur is directly determined by MIDI. The radiative transfer modelling demonstrates the powerful synergy of interferometry and spectro-photometry to alleviate the degeneracy, which may hamper determining the disk morphology. Our analysis supports the classification of AB Aur among the flared disks of the first group in the Meeus classification. Based on observations collected at ESO (Paranal Observatory) with the VLT Interferometer - Prog ID: 074.C-552 & 076.C-252.

Atom-dimer scattering in a heteronuclear mixture with a finite intraspecies scattering length

NASA Astrophysics Data System (ADS)

Gao, Chao; Zhang, Peng

2018-04-01

We study the three-body problem of two ultracold identical bosonic atoms (denoted by B ) and one extra atom (denoted by X ), where the scattering length aB X between each bosonic atom and atom X is resonantly large and positive. We calculate the scattering length aad between one bosonic atom and the shallow dimer formed by the other bosonic atom and atom X , and investigate the effect induced by the interaction between the two bosonic atoms. We find that even if this interaction is weak (i.e., the corresponding scattering length aB B is of the same order of the van der Waals length rvdW or even smaller), it can still induce a significant effect for the atom-dimer scattering length aad. Explicitly, an atom-dimer scattering resonance can always occur when the value of aB B varies in the region with | aB B|≲ rvdW . As a result, both the sign and the absolute value of aad, as well as the behavior of the aad-aB X function, depends sensitively on the exact value of aB B. Our results show that, for a good quantitative theory, the intraspecies interaction is required to be taken into account for this heteronuclear system, even if this interaction is weak.

Antibodies to watch in 2010

PubMed Central

2010-01-01

Monoclonal antibodies (mAbs) are a burgeoning class of therapeutics, with more than 25 approved in countries worldwide. Novel molecules are entering clinical study at a rate of nearly 40 per year, and the commercial pipeline includes approximately 240 mAb therapeutics in clinical studies that have not yet progressed to regulatory approval or been approved. Of particular interest are the 26 mAbs that are currently at Phase 3, when safety and efficacy data critical to approval is established. Phase 3 study lengths are typically two to four years, so results for some studies might be announced in 2010, but data from others might not be presented until 2014. This overview of the 26 candidates provides a brief description of the background and the on-going Phase 3 studies of each mAb. Additional mAbs that have progressed to regulatory review or been approved may also be in Phase 3 studies, but these, as well as Fc fusion proteins, have been excluded. Due to the large body of primary literature about the 26 candidates, only selected references are given, with a focus on recent publications and articles that were relevant to Phase 3 studies. Current as of October 2009, the results presented here will serve as a baseline against which future progress can be measured. PMID:20065640

Quantum wavepacket ab initio molecular dynamics: an approach for computing dynamically averaged vibrational spectra including critical nuclear quantum effects.

PubMed

Sumner, Isaiah; Iyengar, Srinivasan S

2007-10-18

We have introduced a computational methodology to study vibrational spectroscopy in clusters inclusive of critical nuclear quantum effects. This approach is based on the recently developed quantum wavepacket ab initio molecular dynamics method that combines quantum wavepacket dynamics with ab initio molecular dynamics. The computational efficiency of the dynamical procedure is drastically improved (by several orders of magnitude) through the utilization of wavelet-based techniques combined with the previously introduced time-dependent deterministic sampling procedure measure to achieve stable, picosecond length, quantum-classical dynamics of electrons and nuclei in clusters. The dynamical information is employed to construct a novel cumulative flux/velocity correlation function, where the wavepacket flux from the quantized particle is combined with classical nuclear velocities to obtain the vibrational density of states. The approach is demonstrated by computing the vibrational density of states of [Cl-H-Cl]-, inclusive of critical quantum nuclear effects, and our results are in good agreement with experiment. A general hierarchical procedure is also provided, based on electronic structure harmonic frequencies, classical ab initio molecular dynamics, computation of nuclear quantum-mechanical eigenstates, and employing quantum wavepacket ab initio dynamics to understand vibrational spectroscopy in hydrogen-bonded clusters that display large degrees of anharmonicities.

An enzyme-linked immunosorbent assay for detection of botulinum toxin-antibodies.

PubMed

Dressler, Dirk; Gessler, Frank; Tacik, Pawel; Bigalke, Hans

2014-09-01

Antibodies against botulinum neurotoxin (BNT-AB) can be detected by the mouse protection assay (MPA), the hemidiaphragm assay (HDA), and by enzyme-linked immunosorbent assays (ELISA). Both MPA and HDA require sacrifice of experimental animals, and they are technically delicate and labor intensive. We introduce a specially developed ELISA for detection of BNT-A-AB and evaluate it against the HDA. Thirty serum samples were tested by HDA and by the new ELISA. Results were compared, and receiver operating characteristic analyses were used to optimize ELISA parameter constellation to obtain either maximal overall accuracy, maximal test sensitivity, or maximal test specificity. When the ELISA is optimized for sensitivity, a sensitivity of 100% and a specificity of 55% can be reached. When it is optimized for specificity, a specificity of 100% and a sensitivity of 90% can be obtained. We present an ELISA for BNT-AB detection that can be-for the first time-customized for special purposes. Adjusted for optimal sensitivity, it reaches the best sensitivity of all BNT-AB tests available. Using the new ELISA together with the HDA as a confirmation test allows testing for BNT-AB in large numbers of patients receiving BT drugs in an economical, fast, and more animal-friendly way. © 2014 International Parkinson and Movement Disorder Society.

Protein Adsorption and Layer Formation at the Stainless Steel-Solution Interface Mediates Shear-Induced Particle Formation for an IgG1 Monoclonal Antibody.

PubMed

Kalonia, Cavan K; Heinrich, Frank; Curtis, Joseph E; Raman, Sid; Miller, Maria A; Hudson, Steven D

2018-03-05

Passage of specific protein solutions through certain pumps, tubing, and/or filling nozzles can result in the production of unwanted subvisible protein particles (SVPs). In this work, surface-mediated SVP formation was investigated. Specifically, the effects of different solid interface materials, interfacial shear rates, and protein concentrations on SVP formation were measured for the National Institute of Standards and Technology monoclonal antibody (NISTmAb), a reference IgG1 monoclonal antibody (mAb). A stainless steel rotary piston pump was used to identify formulation and process parameters that affect aggregation, and a flow cell (alumina or stainless steel interface) was used to further investigate the effect of different interface materials and/or interfacial shear rates. SVP particles produced were monitored using flow microscopy or flow cytometry. Neutron reflectometry and a quartz crystal microbalance with dissipation monitoring were used to characterize adsorption and properties of NISTmAb at the stainless steel interface. Pump/shear cell experiments showed that the NISTmAb concentration and interface material had a significant effect on SVP formation, while the effects of interfacial shear rate and passage number were less important. At the higher NISTmAb concentrations, the adsorbed protein became structurally altered at the stainless steel interface. The primary adsorbed layer remained largely undisturbed during flow, suggesting that SVP formation at high NISTmAb concentration was caused by the disruption of patches and/or secondary interactions.

Associations of perceived social support and positive psychological resources with fatigue symptom in patients with rheumatoid arthritis

PubMed Central

Xu, NeiLi; Zhao, Shuai; Xue, HongXia; Fu, WenYi; Liu, Li; Zhang, TianQi; Huang, Rui; Zhang, Ning

2017-01-01

Objective This study aimed to assess the association between perceived social support (PSS) and fatigue and the roles of hope, optimism, general self-efficacy and resilience as mediators or moderators on PSS-fatigue association among Rheumatoid Arthritis (RA) patients in China. Methods A multi-center, cross-sectional study was conducted withinpatients diagnosed with RA in northeast China, in which 305 eligible inpatients were enrolled. The Multidimensional Fatigue Inventory, Multidimensional Scale of Perceived Social Support, Herth Hope Index, Life Orientation Test Revised, General Self-Efficacy Scale and Ego-Resiliency Scale were completed. The associations of PSS, hope, optimism, general self-efficacy and resilience with fatigue and the moderating roles of these positive psychological constructs were tested by hierarchical linear regression. Asymptotic and resampling strategies were utilized to assess the mediating roles of hope, optimism, general self-efficacy and resilience. Results The mean score of the MFI was 57.88 (SD = 9.50). PSS, hope, optimism and resilience were negatively associated with RA-related fatigue, whereas DAS28-CRP was positively associated. Only resilience positively moderated the PSS-fatigue association (B = 0.03, β = 0.13, P<0.01). Hope, optimism and resilience may act as partial mediators in the association between PSS and fatigue symptoms (hope: a*b = -0.16, BCa 95%CI: -0.27, -0.03; optimism: a*b = -0.20, BCa 95%CI: -0.30, -0.10; resilience: a*b = -0.12, BCa 95%CI: -0.21–0.04). Conclusions Fatigue is a severe symptom among RA patients. Resilience may positively moderate the PSS-fatigue association. Hope, optimism and resilience may act as partial mediators in the association. PSS, hope, optimism and resilience may contribute as effective recourses to alleviate fatigue, upon which PSS probably has the greatest effect. PMID:28291837

Associations of perceived social support and positive psychological resources with fatigue symptom in patients with rheumatoid arthritis.

PubMed

Xu, NeiLi; Zhao, Shuai; Xue, HongXia; Fu, WenYi; Liu, Li; Zhang, TianQi; Huang, Rui; Zhang, Ning

2017-01-01

This study aimed to assess the association between perceived social support (PSS) and fatigue and the roles of hope, optimism, general self-efficacy and resilience as mediators or moderators on PSS-fatigue association among Rheumatoid Arthritis (RA) patients in China. A multi-center, cross-sectional study was conducted withinpatients diagnosed with RA in northeast China, in which 305 eligible inpatients were enrolled. The Multidimensional Fatigue Inventory, Multidimensional Scale of Perceived Social Support, Herth Hope Index, Life Orientation Test Revised, General Self-Efficacy Scale and Ego-Resiliency Scale were completed. The associations of PSS, hope, optimism, general self-efficacy and resilience with fatigue and the moderating roles of these positive psychological constructs were tested by hierarchical linear regression. Asymptotic and resampling strategies were utilized to assess the mediating roles of hope, optimism, general self-efficacy and resilience. The mean score of the MFI was 57.88 (SD = 9.50). PSS, hope, optimism and resilience were negatively associated with RA-related fatigue, whereas DAS28-CRP was positively associated. Only resilience positively moderated the PSS-fatigue association (B = 0.03, β = 0.13, P<0.01). Hope, optimism and resilience may act as partial mediators in the association between PSS and fatigue symptoms (hope: a*b = -0.16, BCa 95%CI: -0.27, -0.03; optimism: a*b = -0.20, BCa 95%CI: -0.30, -0.10; resilience: a*b = -0.12, BCa 95%CI: -0.21-0.04). Fatigue is a severe symptom among RA patients. Resilience may positively moderate the PSS-fatigue association. Hope, optimism and resilience may act as partial mediators in the association. PSS, hope, optimism and resilience may contribute as effective recourses to alleviate fatigue, upon which PSS probably has the greatest effect.

Strategic, Tactical and Doctrinal Military Concepts. The Deterrence Concept: A Synthesis Based on a Survey of the Literature.

DTIC Science & Technology

1980-04-01

influence appears strongest, that the work is most ab - stract, and that the results have seemed to cause the most prob- lems when applied to the real...deterrence to the world at large, for Churchill’s clear exposi - tion of the basic concept, and as probably the first major statement on deterrence...works cited are in general ab - stract and theoretical, or minor and irrelevant. Also, since most of the bibliography cited is from the 1950’s (a single

The relationship between agricultural biodiversity, dietary diversity, household food security, and stunting of children in rural Kenya.

PubMed

M'Kaibi, Florence K; Steyn, Nelia P; Ochola, Sophie A; Du Plessis, Lissane

2017-03-01

The study was to determine the role of Dietary diversity (DD), household food security (HFS), and agricultural biodiversity (AB) on stunted growth in children. Two cross-sectional studies were undertaken 6 months apart. Interviews were done with mothers/caregivers and anthropometric measurements of children 24-59 months old. HFS was assessed by household food insecurity access scale (HFIAS). A repeated 24-h recall was used to calculate a dietary diversity score (DDS). Agricultural biodiversity (AB) was calculated by counting the number of edible plants and animals. The study was undertaken in resource-poor households in two rural areas in Kenya. Mothers/Care givers and household with children of 24-59 months of age were the main subjects. The prevalence of underweight [WAZ <-2SD] ranged between 16.7% and 21.6% and stunting [HAZ <-2SD] from 26.3% to 34.7%. Mean DDS ranged from 2.9 to 3.7 and HFIAS ranged from 9.3 to 16.2. AB was between 6.6 and 7.2 items. Households with and without children with stunted growth were significantly different in DDS ( P  = 0.047) after the rainy season and HFIAS ( P  = 0.009) in the dry season, but not with AB score ( P  = 0.486). The mean AB for households with children with stunted growth were lower at 6.8, compared to 7.0 for those with normal growth, however, the difference was insignificant. Data indicate that households with children with stunted growth and those without are significantly different in DDS and HFIAS but not with AB. This suggests some potential in using DDS and HFIAS as proxy measures for stunting.

Effect of the human leukocyte antigen HLA-DRB1 and anti-cyclic citrullinated peptide on the outcome of rheumatoid arthritis patients.

PubMed

Farouk, H M; Mansour, H E; Rahman, S A; Mostafa, A A; Shamy, H A; Zarouk, W A

2009-09-01

Our objective was to determine whether the presence of the human leukocyte antigen HLA-DRB1 locus is associated with production of anti-cyclic citrullinated peptide antibodies (anti-CCP Abs) and to what extent they are associated with increased susceptibility to and severity of rheumatoid arthritis (RA) in Egyptian patients. Twenty-nine RA patients gave informed consent to participate in a case-control study that was approved by the Ain Shams University Medical Ethics Committee. RA disease activity and severity were determined using the simplified disease activity index and Larsen scores, respectively. We used a wide scale national study on the pattern of HLA typing in normal Egyptians as a control study. Anti-CCP Abs and HLA-DRB1 typing were determined for all subjects. The alleles most strongly associated with RA were HLA-DRB1 [*01 , *04 and *06] (41.4%). RA patients with serum anti-CCP Ab titers above 60 U/mL had a significantly higher frequency of HLA-DRB1*01 (58.3%) and HLA-DRB1*04 alleles (83.3%). Significant positive correlations were found between serum and synovial anti-CCP Ab titer, RA disease activity, and severity (r = 0.87, 0.66 and 0.63, respectively; P < 0.05). HLA-DRB1 SE+ alleles [*01 and *04] were highly expressed among Egyptian RA patients. The presence of these alleles was associated with higher anti-CCP Ab titer, active and severe RA disease. Early determination of HLA-DRB1 SE+ alleles and serum anti-CCP Ab could facilitate the prediction of the clinical course and prognosis of RA when first evaluated leading to better disease control.

Stress-coping skills and neuroticism in apical ballooning syndrome (Takotsubo/stress cardiomyopathy).

PubMed

Scantlebury, Dawn C; Rohe, Daniel E; Best, Patricia J M; Lennon, Ryan J; Lerman, Amir; Prasad, Abhiram

2016-01-01

Apical ballooning syndrome (ABS) is typically associated with an antecedent stressful situation. Affected patients have been reported to have higher frequencies of premorbid affective disorders. We hypothesised that patients with ABS would have elevated levels of neuroticism (tendency to experience negative affect) and greater vulnerability to stress. In this cross-sectional study, all active participants in the Mayo Clinic ABS prospective follow-up registry were invited to complete the third edition of the NEO Personality Inventory (NEO-PI-3). The NEO-PI-3 is the universally accepted measure of the 'Five-Factor Model' of personality. Inventory responses were scored using the NEO-PI-3 computer program and the data were compared with US normative sample used in standardisation of the inventory. Significance was set at 0.0014 to account for multiple comparisons. Of 106 registry participants approached, 53 completed the inventory. There was no difference in age, gender, time from ABS diagnosis, type of antecedent stressor (emotional, physical or none) or severity of initial illness between the responders and non-responders. Responders had mean Neuroticism T-scores of 48.0±10.6 (95% CI 45.1 to 50.9); p=0.18, when compared with the normal mean of 50. There was also no significant difference in the facet scale of Vulnerability: 46.9±8.4 (44.6 to 49.2), p=0.038, at α=0.0014. Contrary to our hypothesis, patients with ABS do not manifest higher levels of neuroticism and do not have greater vulnerability to stress than the general population. These findings have implications for the clinicians' perception of, and approach to, patients with ABS.

Recombinase-mediated cassette exchange (RMCE) for monoclonal antibody expression in the commercially relevant CHOK1SV cell line.

PubMed

Zhang, Lin; Inniss, Mara C; Han, Shu; Moffat, Mark; Jones, Heather; Zhang, Baohong; Cox, Wendy L; Rance, James R; Young, Robert J

2015-01-01

To meet product quality and cost parameters for therapeutic monoclonal antibody (mAb) production, cell lines are required to have excellent growth, stability, and productivity characteristics. In particular, cell line generation stability is critical to the success of a program, especially where high cell line generation numbers are required for large in-market supply. However, a typical process for developing such cell lines is laborious, lengthy, and costly. In this study, we applied a FLP/FRT recombinase-mediated cassette exchange (RMCE) system to build a site-specific integration (SSI) system for mAb expression in the commercially relevant CHOK1SV cell line. Using a vector with a FRT-flanked mAb expression cassette, we generated a clonal cell line with good productivity, long-term production stability, and low mAb gene-copy number indicating the vector was located in a 'hot-spot.' A SSI host cell line was made by removing the mAb genes from the 'hot-spot' by RMCE, creating a 'landing pad' containing two recombination cassettes that allow targeting of one or two copies of recombinant genes. Cell lines made from this host exhibited excellent growth and productivity profiles, and stability for at least 100 generations in the absence of selection agents. Importantly, while clones containing two copies had higher productivity than single copy clones, both were stable over many generations. Taken together, this study suggests the use of FLP-based RMCE to develop SSI host cells for mAb production in CHOK1SV offers significant savings in both resources and overall cell line development time, leading to a shortened 'time-to-clinic' for therapeutic mAbs. © 2015 American Institute of Chemical Engineers.

Development of autoantibodies in the TrialNet Natural History Study.

PubMed

Vehik, Kendra; Beam, Craig A; Mahon, Jeffrey L; Schatz, Desmond A; Haller, Michael J; Sosenko, Jay M; Skyler, Jay S; Krischer, Jeffrey P

2011-09-01

Understanding the relationship between age and islet autoantibody (Ab) seroconversion can establish the optimal screening interval(s) to assess risk for type 1 diabetes, identify subjects who can participate in prevention trials, and determine associated costs. This study assessed the rates of seroconversion to glutamic acid decarboxylase positive (GAD65(+)), insulin positive (mIAA(+)), and insulinoma-associated protein 2 positive (ICA512(+)) in a large cohort of relatives of type 1 diabetes probands undergoing Ab rescreening in the TrialNet Natural History Study. Of 32,845 children aged <18 years screened for Abs, 1,287 (3.9%) were GAD65(+), 778 (2.4%) were mIAA(+), 677 (2.1%) were ICA512(+), and 31,038 were Ab-negative. Ab-negative children were offered annual rescreening up to 18 years of age. Cox regression was used to estimate the risk for GAD65, mIAA, and ICA512 seroconversion. RESULTS There were 205 children who seroconverted to GAD65(+), 155 who seroconverted to mIAA(+), and 53 who seroconverted to ICA512(+) over 5.8 years of follow-up. The risk of mIAA (hazard ratio 0.89 [95% CI 0.85-0.92]) and GAD65 (0.96 [0.93-0.99]) seroconversion significantly decreased with increasing age (i.e., for each 1-year increase in age, the risk of seroconversion decreased by 11% [P < 0.0001] for mIAA and 4% [P = 0.04] for GAD65) across all ages. The cumulative Ab seroconversion was 2% for those <10 years of age versus 0.7% for those ≥10 years of age. The risk of development of islet Abs declines with increasing age in type 1 diabetes relatives. These data support annual screening for children <10 years of age and one additional screening in adolescence.

Charge-mediated Fab-Fc interactions in an IgG1 antibody induce reversible self-association, cluster formation, and elevated viscosity.

PubMed

Arora, Jayant; Hu, Yue; Esfandiary, Reza; Sathish, Hasige A; Bishop, Steven M; Joshi, Sangeeta B; Middaugh, C Russell; Volkin, David B; Weis, David D

Concentration-dependent reversible self-association (RSA) of monoclonal antibodies (mAbs) poses a challenge to their pharmaceutical development as viable candidates for subcutaneous delivery. While the role of the antigen-binding fragment (Fab) in initiating RSA is well-established, little evidence supports the involvement of the crystallizable fragment (Fc). In this report, a variety of biophysical tools, including hydrogen exchange mass spectrometry, are used to elucidate the protein interface of such non-covalent protein-protein interactions. Using dynamic and static light scattering combined with viscosity measurements, we find that an IgG1 mAb (mAb-J) undergoes RSA primarily through electrostatic interactions and forms a monomer-dimer-tetramer equilibrium. We provide the first direct experimental mapping of the interface formed between the Fab and Fc domains of an antibody at high protein concentrations. Charge distribution heterogeneity between the positively charged interface spanning complementarity-determining regions CDR3H and CDR2L in the Fab and a negatively charged region in C H 3/Fc domain mediates the RSA of mAb-J. When arginine and NaCl are added, they disrupt RSA of mAb-J and decrease the solution viscosity. Fab-Fc domain interactions between mAb monomers may promote the formation of large transient antibody complexes that ultimately cause increases in solution viscosity. Our findings illustrate how limited specific arrangements of amino-acid residues can cause mAbs to undergo RSA at high protein concentrations and how conserved regions in the Fc portion of the antibody can also play an important role in initiating weak and transient protein-protein interactions.

Analysis of the binding loops configuration and surface adaptation of different crystallized single-domain antibodies in response to various antigens.

PubMed

Al Qaraghuli, Mohammed M; Ferro, Valerie A

2017-04-01

Monoclonal antibodies have revolutionized the biomedical field through their ubiquitous utilization in different diagnostics and therapeutic applications. Despite this widespread use, their large size and structural complexity have limited their versatility in specific applications. The antibody variable region that is responsible for binding antigen is embodied within domains that can be rescued individually as single-domain antibody (sdAb) fragments. Because of the unique characteristics of sdAbs, such as low molecular weight, high physicochemical stability, and the ability to bind antigens inaccessible to conventional antibodies, they represent a viable alternative to full-length antibodies. Consequently, 149 crystal structures of sdAbs, originating from human (VH), camelids (VHH), or sharks (VNAR), were retrieved from the Protein Data Bank, and their structures were compared. The 3 types of sdAbs displayed complementarity determining regions (CDRs) with different lengths and configurations. CDR3 of the VHH and VNAR domains were dominated by pleated and extended orientations, respectively. Although VNAR showed the smallest average molecular weight and molecular surface area compared with VHH and VH antibodies. However, the solvent accessible surface area measurements of the 3 tested sdAbs types were very similar. All the antihapten VHH antibodies showed pleated CDR3, which were sufficient to create a binding pocket to accommodate haptens (methotrexate and azo dyes) in terms of shape and electrostatic potential. The sdAbs that recognized lysozyme showed more diversity in their CDR3 orientation to enable them to recognize various topographies of lysozyme. Subsequently, the three sdAb classes were different in size and surface area and have shown distinguishable ability to optimize their CDR length and orientation to recognize different antigen classes. Copyright © 2016 John Wiley & Sons, Ltd.

Can The Periods of Some Extra-Solar Planetary Systems be Quantized?

NASA Astrophysics Data System (ADS)

El Fady Morcos, Abd

A simple formula was derived before by Morcos (2013 ), to relate the quantum numbers of planetary systems and their periods. This formula is applicable perfectly for the solar system planets, and some extra-solar planets , of stars of approximately the same masses like the Sun. This formula has been used to estimate the periods of some extra-solar planet of known quantum numbers. The used quantum numbers were calculated previously by other authors. A comparison between the observed and estimated periods, from the given formula has been done. The differences between the observed and calculated periods for the extra-solar systems have been calculated and tabulated. It is found that there is an error of the range of 10% The same formula has been also used to find the quantum numbers, of some known periods, exo-planet. Keywords: Quantization; Periods; Extra-Planetary; Extra-Solar Planet REFERENCES [1] Agnese, A. G. and Festa, R. “Discretization on the Cosmic Scale Inspirred from the Old Quantum Mechanics,” 1998. http://arxiv.org/abs/astro-ph/9807186 [2] Agnese, A. G. and Festa, R. “Discretizing ups-Andro- medae Planetary System,” 1999. http://arxiv.org/abs/astro-ph/9910534. [3] Barnothy, J. M. “The Stability of the Solar Systemand of Small Stellar Systems,” Proceedings of the IAU Sympo-sium 62, Warsaw, 5-8 September 1973, pp. 23-31. [4] Morcos, A.B. , “Confrontation between Quantized Periods of Some Extra-Solar Planetary Systems and Observations”, International Journal of Astronomy and Astrophysics, 2013, 3, 28-32. [5] Nottale, L. “Fractal Space-Time and Microphysics, To-wards a Theory of Scale Relativity,” World Scientific, London, 1994. [6] Nottale , L., “Scale-Relativity and Quantization of Extra- Solar Planetary Systems,” Astronomy & Astrophysics, Vol. 315, 1996, pp. L9-L12 [7] Nottale, L., Schumacher, G. and Gay, J. “Scale-Relativity and Quantization of the Solar Systems,” Astronomy & Astrophysics letters, Vol. 322, 1997, pp. 1018-10 [8]Nottale, L. “Scale-Relativity and Quantization of Exo- planet Orbital Semi-Major Axes,” Astronomy & Astro- physics, Vol. 361, 2000, pp. 379-387.

Ultra-Wideband Radar Transient Detection using Time-Frequency and Wavelet Transforms.

DTIC Science & Technology

1992-12-01

if p==2, mesh(flipud(abs(spdatamatrix).A2)) end 2. Wigner - Ville Distribution function P = wvd (data,winlenstep,begintheendp) % Filename: wvd.m % Title...short time Fourier transform (STFT), the Instantaneous Power Spectrum and the Wigner - Ville distribution , and time-scale methods, such as the a trous...such as the short time Fourier transform (STFT), the Instantaneous Power Spectrum and the Wigner - Ville distribution [1], and time-scale methods, such

Throttleable GOX/ABS launch assist hybrid rocket motor for small scale air launch platform

NASA Astrophysics Data System (ADS)

Spurrier, Zachary S.

Aircraft-based space-launch platforms allow operational flexibility and offer the potential for significant propellant savings for small-to-medium orbital payloads. The NASA Armstrong Flight Research Center's Towed Glider Air-Launch System (TGALS) is a small-scale flight research project investigating the feasibility for a remotely-piloted, towed, glider system to act as a versatile air launch platform for nano-scale satellites. Removing the crew from the launch vehicle means that the system does not have to be human rated, and offers a potential for considerable cost savings. Utah State University is developing a small throttled launch-assist system for the TGALS platform. This "stage zero" design allows the TGALS platform to achieve the required flight path angle for the launch point, a condition that the TGALS cannot achieve without external propulsion. Throttling is required in order to achieve and sustain the proper launch attitude without structurally overloading the airframe. The hybrid rocket system employs gaseous-oxygen and acrylonitrile butadiene styrene (ABS) as propellants. This thesis summarizes the development and testing campaign, and presents results from the clean-sheet design through ground-based static fire testing. Development of the closed-loop throttle control system is presented.

Characterization of corrosion products of AB{sub 5}-type hydrogen storage alloys for nickel-metal hydride batteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maurel, F.; Knosp, B.; Backhaus-Ricoult, M.

2000-01-01

To better understand the decrease in storage capacity of AB{sub 5}-type alloys in rechargeable Ni/MH batteries undergoing repeated charge/discharge cycles, the corrosion of a MnNi{sub 3.55}Co{sub 0.75}Mn{sub 0.4}Al{sub 0.3} alloy in aqueous KOH electrolyte was studied. The crystal structure, chemical composition, and distribution of corrosion products were characterized by X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. Hollow and filed needles of a mixed rare earth hydroxide Mn(OH){sub 3} were found to cover a continuous nanocrystalline corrosion scale composed of metal (Ni, Co) solid solution, oxide (Ni,Co)O solid solution and rare earth hydroxide, and a Mn-depleted alloy subscale. Corrosionmore » kinetics were measured for three different temperatures. Growth kinetics of the continuous corrosion scale and of the Mm(OH){sub 3} needles obeyed linear and parabolic rate laws, respectively. Models for the corrosion mechanism were developed on the basis of diffusional transport of Mn and OH through the hydroxide needles and subsequent diffusion along grain boundaries through the nanocrystalline scale.« less

Tick bites and red meat allergy

PubMed Central

Commins, Scott P.; Platts-Mills, Thomas A.E.

2014-01-01

Purpose of review A novel form of anaphylaxis has been described that is due to IgE antibody (Ab) directed against a mammalian oligosaccharide epitope, galactose-alpha-1, 3-galactose (alpha-gal). Ongoing work regarding the cause and distribution of this IgE response is reviewed. Recent findings Our recent work has identified a novel IgE Ab response that has been associated with two distinct forms of anaphylaxis: immediate-onset anaphylaxis during first exposure to intravenous cetuximab and delayed-onset anaphylaxis 3–6 h after ingestion of mammalian food products (e.g. beef and pork). Further studies strongly suggested that tick bites were a cause, if not the only significant cause, of IgE Ab responses to alpha-gal in the United States and internationally. Summary Large numbers of patients with IgE Ab to alpha-gal continue to be identified in the USA and globally. Clinicians should be aware of this IgE response as the reactions often appear to be idiopathic because of the significant delay between eating mammalian meat and the appearance of symptoms. PMID:23743512

An antibody raised against a pathogenic serpin variant induces mutant-like behaviour in the wild-type protein

PubMed Central

Irving, James A.; Miranda, Elena; Haq, Imran; Perez, Juan; Kotov, Vadim R.; Faull, Sarah V.; Motamedi-Shad, Neda; Lomas, David A.

2015-01-01

A monoclonal antibody (mAb) that binds to a transient intermediate may act as a catalyst for the corresponding reaction; here we show this principle can extend on a macro molecular scale to the induction of mutant-like oligomerization in a wild-type protein. Using the common pathogenic E342K (Z) variant of α1-antitrypsin as antigen–whose native state is susceptible to the formation of a proto-oligomeric intermediate–we have produced a mAb (5E3) that increases the rate of oligomerization of the wild-type (M) variant. Employing ELISA, gel shift, thermal stability and FRET time-course experiments, we show that mAb5E3 does not bind to the native state of α1-antitrypsin, but recognizes a cryptic epitope in the vicinity of the post-helix A loop and strand 4C that is revealed upon transition to the polymerization intermediate, and which persists in the ensuing oligomer. This epitope is not shared by loop-inserted monomeric conformations. We show the increased amenity to polymerization by either the pathogenic E342K mutation or the binding of mAb5E3 occurs without affecting the energetic barrier to polymerization. As mAb5E3 also does not alter the relative stability of the monomer to intermediate, it acts in a manner similar to the E342K mutant, by facilitating the conformational interchange between these two states. PMID:25738741

The use of native cation-exchange chromatography to study aggregation and phase separation of monoclonal antibodies

PubMed Central

Chen, Shuang; Lau, Hollis; Brodsky, Yan; Kleemann, Gerd R; Latypov, Ramil F

2010-01-01

This study introduces a novel analytical approach for studying aggregation and phase separation of monoclonal antibodies (mAbs). The approach is based on using analytical scale cation-exchange chromatography (CEX) for measuring the loss of soluble monomer in the case of individual and mixed protein solutions. Native CEX outperforms traditional size-exclusion chromatography in separating complex protein mixtures, offering an easy way to assess mAb aggregation propensity. Different IgG1 and IgG2 molecules were tested individually and in mixtures consisting of up to four protein molecules. Antibody aggregation was induced by four different stress factors: high temperature, low pH, addition of fatty acids, and rigorous agitation. The extent of aggregation was determined from the amount of monomeric protein remaining in solution after stress. Consequently, it was possible to address the role of specific mAb regions in antibody aggregation by co-incubating Fab and Fc fragments with their respective full-length molecules. Our results revealed that the relative contribution of Fab and Fc regions in mAb aggregation is strongly dependent on pH and the stress factor applied. In addition, the CEX-based approach was used to study reversible protein precipitation due to phase separation, which demonstrated its use for a broader range of protein–protein association phenomena. In all cases, the role of Fab and Fc was clearly dissected, providing important information for engineering more stable mAb-based therapeutics. PMID:20512972

Personality differences in high risk sports amateurs and instructors.

PubMed

Watson, Alison E; Pulford, Briony D

2004-08-01

This study investigated the personality differences of 21 amateurs and 20 instructors who participated in the high risk sports of skydiving, hang-gliding, paragliding, scuba diving, microlighting, and rock climbing, versus those who did not. 38 men and 28 women (M age=32.6 yr., SD= 10.0) were assessed using the Eysenck Personality Questionnaire-Revised, the General Health Questionnaire, the Generalised Self-efficacy Scale, and a Type A/B personality measure. Instructors and Amateurs scored significantly higher on Extroversion and lower on Neuroticism than Nonparticipants; however, they differed from each other on the General Health Questionnaire and Type A/B personality scores. Amateurs scored significantly higher on Psychoticism and Self-efficacy than Instructors and Nonparticipants. In conclusion, these test scores suggest that people who are attracted to high risk sports tend to be at the extroverted and emotionally stable end of the scale, with a tendency to exhibit Type A characteristics; however, Instructors' scores on Psychoticism and Self-efficacy are more akin to those of Nonparticipants.

A Historical Overview of Aeroelasticity Branch and Transonic Dynamics Tunnel Contributions to Rotorcraft Technology and Development

NASA Technical Reports Server (NTRS)

Yeager, William T., Jr.; Kvaternik, Raymond G.

2001-01-01

A historical account of the contributions of the Aeroelasticity Branch (AB) and the Langley Transonic Dynamics Tunnel (TDT) to rotorcraft technology and development since the tunnel's inception in 1960 is presented. The paper begins with a summary of the major characteristics of the TDT and a description of the unique capability offered by the TDT for testing aeroelastic models by virtue of its heavy gas test medium. This is followed by some remarks on the role played by scale models in the design and development of rotorcraft vehicles and a review of the basic scaling relationships important for designing and building dynamic aeroelastic models of rotorcraft vehicles for testing in the TDT. Chronological accounts of helicopter and tiltrotor research conducted in AB/TDT are then described in separate sections. Both experimental and analytical studies are reported and include a description of the various physical and mathematical models employed, the specific objectives of the investigations, and illustrative experimental and analytical results.

Results of tests OA63 and IA29 on an 0.015 scale model of the space shuttle configuration 140 A/B in the NASA/ARC 6- by 6-foot transonic wind tunnel, volume 1

NASA Technical Reports Server (NTRS)

Spangler, R. H.; Thornton, D. E.

1974-01-01

Tests were conducted in the NASA/ARC 6- by 6-foot transonic wind tunnel from September 12 to September 28, 1973 on an 0.015-scale model of the space shuttle configuration 140 A/B. Surface pressure data were obtained for the orbiter for both launch and entry configuration at Mach numbers from 0.6 to 2.0. The surface pressures were obtained in the vicinity of the cargo bay door hinge and parting lines, the side of the fuselage at the crew compartment and below the OMS pods at the aft compartment. Data were obtained at angles of attack and sideslip consistent with the expected divergencies along the nominal trajectory. These tests were first in a series of tests supporting the orbiter venting analysis. The series will include tests in three facilities covering a total Mach number range from 0.6 to 10.4.

Molecular Analysis of the Human Autoantibody Response to α-Fodrin in Sjögren’s Syndrome Reveals Novel Apoptosis-Induced Specificity

PubMed Central

Maruyama, Toshiaki; Saito, Ichiro; Hayashi, Yoshio; Kompfner, Elizabeth; Fox, Robert I.; Burton, Dennis R.; Ditzel, Henrik J.

2004-01-01

Lymphocyte infiltration of salivary and lacrimal glands leading to diminished secretion and gland destruction as a result of apoptosis is thought to be pivotal in the pathogenesis of Sjögren’s syndrome (SS). The cytoskeletal protein α-fodrin is cleaved during this apoptotic process, and a strong antibody (Ab) response is elicited to a 120-kd fragment of cleaved α-fodrin in the majority of SS patients, but generally not in other diseases in which apoptosis also occurs. Little is known about the anti-α-fodrin autoantibody response on a molecular level. To address this issue, IgG phage display libraries were generated from the bone marrow of two SS donors and a panel of anti-α-fodrin IgGs was isolated by selection on α-fodrin immunoblots. All of the human monoclonal Abs (hmAbs) reacted with a 150-kd fragment and not with the 120-kd fragment or intact α-fodrin, indicating that the epitope recognized became exposed after α-fodrin cleavage. Analysis of a large panel of SS patients (defined by the strict San Diego diagnostic criteria) showed that 25% of SS sera exhibited this 150-kd α-fodrin specificity. The hmAbs stained human cultured salivary acinar cells and the staining was redistributed to surface blebs during apoptosis. They also stained inflamed acinar/ductal epithelial cells in SS salivary tissue biopsies, and only partially co-localized with monoclonal Abs recognizing the full-length α-fodrin. Our study shows that in SS patients, neoepitopes on the 150-kd cleaved product of α-fodrin become exposed to the immune system, frequently eliciting anti-150-kd α-fodrin Abs in addition to the previously reported anti-120-kd Abs. The anti-150-kd α-fodrin hmAbs may serve as valuable reagents for the study of SS pathogenesis and diagnostic analyses of SS salivary gland tissue. PMID:15215161

Structural similarities between hematoidin crystals and asteroid bodies: evidence of lipid composition.

PubMed

Brenner, D S; Drachenberg, C B; Papadimitriou, J C

2001-02-01

Hematoidin crystals (HC) are found in tissues where extravasated erythrocytes undergo degradation. Previous studies have determined that hematoidin is composed, in part, of a bilirubin-like pigment. In a previous study (Papadimitriou and Drachenberg, Ultrastruct. Pathol. 16, 413-421, 1992), we demonstrated that giant cell asteroid bodies (AB) are formed by membrane lipid bilayers. We evaluated three cases in which HC developed within splenic infarcts. The crystals were analyzed by light microscopy (LM), electron microscopy (EM), and X-ray microanalysis. A case of sarcoidosis with multiple epithelioid granulomas containing AB was studied for comparison. By LM the HC demonstrated intense, golden-color, fine threads, both intracellularly and extracellularly, in small and large clusters, and in radiating, star-shape patterns ranging in size from 2 to 200 microm. By EM the HC were composed of a core of empty clefts, consistent with dissolved lipids, suggestive of cholesterol crystals, and were surrounded by myelinoid membrane aggregates. The AB showed by LM significant morphological similarities with the intracellular HC. By EM, the AB were composed of a core of dense phospholipid bilayer tubes surrounded by a halo of myelinoid membranes. No accumulation of specific elements was found in either HC or AB by X-ray microanalysis. HC and AB show a similar star-shape morphology by both LM and EM. We postulate that this shape is due to the physicochemical properties of the accumulated lipids which originate from superfluous cell membranes created during cell fusion in the case of AB and after cellular (predominantly red cell) breakdown in the case of HC. The golden color of the HC likely results from adsorption of hydrophobic bilirubin-like pigments left over from erythrocyte breakdown into the accumulated lipids. Thus, this study shows two different (patho)physiological processes that lead to a markedly similar morphological end-product and provides further support to our proposed mechanism for AB formation.

Characterizing the Promiscuity of LigAB, a Lignin Catabolite Degrading Extradiol Dioxygenase from Sphingomonas paucimobilis SYK-6

PubMed Central

Barry, Kevin P.; Taylor, Erika A.

2014-01-01

LigAB from Sphingomonas paucimobilis SYK-6 is the only structurally characterized dioxygenase of the largely uncharacterized superfamily of Type II extradiol dioxygenases (EDO). This enzyme catalyzes the oxidative ring-opening of protocatechuate (3,4-dihydroxybenzoic acid or PCA) in a pathway allowing the degradation of lignin derived aromatic compounds (LDACs). LigAB has also been shown to utilize two other LDACs from the same metabolic pathway as substrates, gallate, and 3-O-methyl gallate; however, kcat/KM had not been reported for any of these compounds. In order to assess the catalytic efficiency and get insights into the observed promiscuity of this enzyme, steady-state kinetic analyses were performed for LigAB with these and a library of related compounds. The dioxygenation of PCA by LigAB was highly efficient, with a kcat of 51 s−1 and a kcat/KM of 4.26 × 106 M−1s−1. LigAB demonstrated the ability to use a variety of catecholic molecules as substrates beyond the previously identified gallate and 3-O-methyl gallate, including 3,4-dihydroxybenzamide, homoprotocatechuate, catechol, and 3,4-dihydroxybenzonitrile. Interestingly, 3,4-dihydroxybenzamide (DHBAm) behaves in a manner similar to that of the preferred benzoic acid substrates, with a kcat/Km value only ~4-fold lower than that for gallate and ~10-fold higher than that for 3-O-methyl gallate. All of these most active substrates demonstrate mechanistic inactivation of LigAB. Additionally, DHBAm exhibits potent product inhibition that leads to an inactive enzyme, being more highly deactivating at lower substrate concentration, a phenomena that, to our knowledge, has not been reported for another dioxygenase substrate/product pair. These results provide valuable catalytic insight into the reactions catalyzed by LigAB and make it the first Type II EDO that is fully characterized both structurally and kinetically. PMID:23977959

Temporal Characteristics of Brown Carbon over the Central Indo-Gangetic Plain.

PubMed

Satish, Rangu; Shamjad, Puthukkadan; Thamban, Navaneeth; Tripathi, Sachchida; Rastogi, Neeraj

2017-06-20

Recent global models estimate that light absorption by brown carbon (BrC) in several regions of the world is ∼30-70% of that due to black carbon (BC). It is, therefore, important to understand its sources and characteristics on temporal and spatial scales. In this study, we conducted semicontinuous measurements of water-soluble organic carbon (WSOC) and BrC using particle-into-liquid sampler coupled with a liquid waveguide capillary cell and total organic carbon analyzer (PILS-LWCC-TOC) over Kanpur (26.5°N, 80.3°E, 142 m amsl) during a winter season (December 2015 to February 2016). In addition, mass concentrations of organic and inorganic aerosol and BC were also measured. Diurnal variability in the absorption coefficient of BrC at 365 nm (b abs_365 ) showed higher values (35 ± 21 Mm -1 ) during late evening to early morning hours and was attributed to primary emissions from biomass burning (BB) and fossil fuel burning (FFB). The b abs_365 reduced by more than 80% as the day progressed, which was ascribed to photo bleaching/volatilization of BrC and/or due to rising boundary layer height. Further, diurnal variability in the ratios of b abs_405 /b abs_365 and b abs_420 /b abs_365 suggests that the BrC composition was not uniform throughout a day. WSOC exhibited a strong correlation with b abs_365 (slope = 1.22 ± 0.007, r 2 = 0.70, n = 13 265, intercept = -0.69 ± 0.17), suggesting the presence of a significant but variable fraction of chromophores. Mass absorption efficiency (MAE) values of WSOC ranged from 0.003 to 5.26 m 2 g -1 (1.16 ± 0.60) during the study period. Moderate correlation (r 2 = 0.50, slope = 1.58 ± 0.019, n = 6471) of b abs_365 was observed with the semivolatile oxygenated organic aerosols (SV-OOA) fraction of BB resolved from positive matrix factorization (PMF) analysis of organic mass spectral data obtained from a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS). The low-volatility OOA (LV-OOA) fraction of BB had a similar correlation to b abs_365 (r 2 = 0.54, slope = 0.38 ± 0.004, n = 6471) but appears to have a smaller contribution to the absorption.

Towards an ab-initio treatment of nonlocal electronic correlations with dynamical vertex approximation

NASA Astrophysics Data System (ADS)

Galler, Anna; Gunacker, Patrik; Tomczak, Jan; Thunström, Patrik; Held, Karsten

Recently, approaches such as the dynamical vertex approximation (D ΓA) or the dual-fermion method have been developed. These diagrammatic approaches are going beyond dynamical mean field theory (DMFT) by including nonlocal electronic correlations on all length scales as well as the local DMFT correlations. Here we present our efforts to extend the D ΓA methodology to ab-initio materials calculations (ab-initio D ΓA). Our approach is a unifying framework which includes both GW and DMFT-type of diagrams, but also important nonlocal correlations beyond, e.g. nonlocal spin fluctuations. In our multi-band implementation we are using a worm sampling technique within continuous-time quantum Monte Carlo in the hybridization expansion to obtain the DMFT vertex, from which we construct the reducible vertex function using the two particle-hole ladders. As a first application we show results for transition metal oxides. Support by the ERC project AbinitioDGA (306447) is acknowledged.

Aharanov-Bohm quantum interference in a reconfigurable electron system

NASA Astrophysics Data System (ADS)

Irvin, P.; Lu, S.; Annadi, A.; Cheng, G.; Tomczyk, M.; Huang, M.; Levy, J.; Lee, J.-W.; Lee, H.; Eom, C.-B.

Aharanov-Bohm (AB) interference can arise in transport experiments when magnetic flux threads through two or more transport channels. The existence of this behavior requires long-range ballistic transport and is typically observed only in exceptionally clean materials. We observe AB interference in wide (w 100 nm) channels created at the LaAlO3/SrTiO3 interface using conductive AFM lithography. Interference occurs above a critical field B 4 T and increases in magnitude with increasing magnetic field. The period of oscillation implies a ballistic length that greatly exceeds the micron-scale length of the channel, consistent with Fabry-Perot interference in 1D channels. The conditions under which AB oscillations are observed will be discussed in the context of the electron pairing mechanism in LaAlO3/SrTiO3. We gratefully acknowledge financial support from AFOSR FA9550-12-1-0342 (CBE), NSF DMR-1234096 (CBE), and ONR N00014-15-1-2847 (JL).

Verification of Anderson Superexchange in MnO via Magnetic Pair Distribution Function Analysis and ab initio Theory

NASA Astrophysics Data System (ADS)

Frandsen, Benjamin A.; Brunelli, Michela; Page, Katharine; Uemura, Yasutomo J.; Staunton, Julie B.; Billinge, Simon J. L.

2016-05-01

We present a temperature-dependent atomic and magnetic pair distribution function (PDF) analysis of neutron total scattering measurements of antiferromagnetic MnO, an archetypal strongly correlated transition-metal oxide. The known antiferromagnetic ground-state structure fits the low-temperature data closely with refined parameters that agree with conventional techniques, confirming the reliability of the newly developed magnetic PDF method. The measurements performed in the paramagnetic phase reveal significant short-range magnetic correlations on a ˜1 nm length scale that differ substantially from the low-temperature long-range spin arrangement. Ab initio calculations using a self-interaction-corrected local spin density approximation of density functional theory predict magnetic interactions dominated by Anderson superexchange and reproduce the measured short-range magnetic correlations to a high degree of accuracy. Further calculations simulating an additional contribution from a direct exchange interaction show much worse agreement with the data. The Anderson superexchange model for MnO is thus verified by experimentation and confirmed by ab initio theory.

Expression of a recombinant human sperm-agglutinating mini-antibody in tobacco (Nicotiana tabacum L.).

PubMed

Xu, Bingfang; Copolla, Michael; Herr, John C; Timko, Michael P

2007-01-01

The murine monoclonal antibody (mAB) S19 recognizes an N-linked carbohydrate antigen designated sperm agglutination antigen-1 (SAGA1) located on the membrane protein CD52. This antigen is added to the sperm surface during epididymal maturation. Binding of the S19 mAB to SAGA-1 causes the rapid agglutination of sperm and blocks pre-fertilization events. Previous studies indicated that the S19 mAB may be a potential specific spermicidal agent (termed a spermistatic) capable of replacing current spermicidal products that contain harsh detergents with harmful side effects. The nucleotide sequences encoding the heavy (H) and light (L) chains of the S19 antibody were cloned. A chimeric gene was constructed using the nucleotide sequences encoding the variable regions of both the H and L chains, and this gene (scFv1 9) was expressed in transgenic tobacco (Nicotiana tabacum L.) to produce a recombinant anti-sperm antibody (RASA). Highest levels of RASA expression were observed in BY-2 plant cell suspension cultures and regenerated N. tabacum cv. Xanthi plants transformant in which the RASA coding sequences were expressed under the control of the Cauliflower Mosaic Virus 35S promoter containing a double-enhancer sequence (2X CaMV 35S). Subsequent modifications of the transgene including the addition of a 5'-untranslated sequence from the tobacco etch virus (TEV leader sequence), N-terminal fusion of the coding region with an endoplasmic reticulum targeting signal of patatin (pat) and C-terminal fusion with the endoplasmic reticulum retention signal peptide KDEL showed further enhancement of RASA expression. The plant-expressed RASA formed intrachain disulfide bonds and was primarily soluble in the cytoplasmic fraction of the cells. Introduction of a poly-histidine (6xHIS) tag in the recombinant RASA protein allowed for rapid purification of the recombinant protein using Ni-NTA chromatography. Optimization of scale-up production and purification of this plant-derived recombinant protein should provide large quantities of an inexpensive spermistatic plantibody.

THE DURABILITY OF LARGE-SCALE ADDITIVE MANUFACTURING COMPOSITE MOLDS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Post, Brian K; Love, Lonnie J; Duty, Chad

2016-01-01

Oak Ridge National Laboratory s Big Area Additive Manufacturing (BAAM) technology permits the rapid production of thermoplastic composite molds using a carbon fiber filled Acrylonitrile-Butadiene-Styrene (ABS) thermoplastic. Demonstration tools (i.e. 0.965 m X 0.559 m X 0.152 m) for composite part fabrication have been printed, coated, and finished with a traditional tooling gel. We present validation results demonstrating the stability of thermoplastic printed molds for room temperature Vacuum Assisted Resin Transfer Molding (VARTM) processes. Arkema s Elium thermoplastic resin was investigated with a variety of reinforcement materials. Experimental results include dimensional characterization of the tool surface using laser scanning techniquemore » following demolding of 10 parts. Thermoplastic composite molds offer rapid production compared to traditionally built thermoset molds in that near-net deposition allows direct digital production of the net geometry at production rate of 45 kg/hr.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graslund, C.; Hellstrand, E.

Sweden benefits in many ways from the reactor safety research performed in other countries. Its own activity complements this effort, but a certain fraction is oriented toward safety issues that are intimately related to the special design of the ASEA-ATOM boiling-water reactor. Through the availability of the decommissioned Marviken reactor plant, Sweden has been able to play a leading role in integral containment experiments with international participation. Joint efforts with other countries are now devoted to defining new large-scale experiments to be performed in the unique Marviken facility. The largest portion of the safety research program in Sweden is performedmore » by Studsvik Energiteknik AB, but various universities, consultant firms, and research institutes are also involved. In addition, a substantial amount of work is done by the reactor vendor ASEA-ATOM. The overall annual budget is at present between $7 and $8 million, with three governmental authorities as the main financing bodies.« less

A Large Inversion Involving GNAS Exon A/B and All Exons Encoding Gsα Is Associated With Autosomal Dominant Pseudohypoparathyroidism Type Ib (PHP1B).

PubMed

Grigelioniene, Giedre; Nevalainen, Pasi I; Reyes, Monica; Thiele, Susanne; Tafaj, Olta; Molinaro, Angelo; Takatani, Rieko; Ala-Houhala, Marja; Nilsson, Daniel; Eisfeldt, Jesper; Lindstrand, Anna; Kottler, Marie-Laure; Mäkitie, Outi; Jüppner, Harald

2017-04-01

Pseudohypoparathyroidism type Ib (PHP1B) is characterized primarily by resistance to parathyroid hormone (PTH) and thus hypocalcemia and hyperphosphatemia, in most cases without evidence for Albright hereditary osteodystrophy (AHO). PHP1B is associated with epigenetic changes at one or several differentially-methylated regions (DMRs) within GNAS, which encodes the α-subunit of the stimulatory G protein (Gsα) and splice variants thereof. Heterozygous, maternally inherited STX16 or GNAS deletions leading to isolated loss-of-methylation (LOM) at exon A/B alone or at all maternal DMRs are the cause of autosomal dominant PHP1B (AD-PHP1B). In this study, we analyzed three affected individuals, the female proband and her two sons. All three revealed isolated LOM at GNAS exon A/B, whereas the proband's healthy maternal grandmother and uncle showed normal methylation at this locus. Haplotype analysis was consistent with linkage to the STX16/GNAS region, yet no deletion could be identified. Whole-genome sequencing of one of the patients revealed a large heterozygous inversion (1,882,433 bp). The centromeric breakpoint of the inversion is located 7,225 bp downstream of GNAS exon XL, but its DMR showed no methylation abnormality, raising the possibility that the inversion disrupts a regulatory element required only for establishing or maintaining exon A/B methylation. Because our three patients presented phenotypes consistent with PHP1B, and not with PHP1A, the Gsα promoter is probably unaffected by the inversion. Our findings expand the spectrum of genetic mutations that lead to LOM at exon A/B alone and thus biallelic expression of the transcript derived from this alternative first GNAS exon. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Development of a highly-sensitive multi-plex assay using monoclonal antibodies for the simultaneous measurement of kappa and lambda immunoglobulin free light chains in serum and urine.

PubMed

Campbell, John P; Cobbold, Mark; Wang, Yanyun; Goodall, Margaret; Bonney, Sarah L; Chamba, Anita; Birtwistle, Jane; Plant, Timothy; Afzal, Zaheer; Jefferis, Roy; Drayson, Mark T

2013-05-31

Monoclonal κ and λ immunoglobulin free light chain (FLC) paraproteins in serum and urine are important markers in the diagnosis and monitoring of B cell dyscrasias. Current nephelometric and turbidimetric methods that use sheep polyclonal antisera to quantify serum FLC have a number of well-observed limitations. In this report, we describe an improved method using specific mouse anti-human FLC monoclonal antibodies (mAbs). Anti-κ and anti-λ FLC mAbs were, separately, covalently coupled to polystyrene Xmap® beads and assayed, simultaneously, in a multi-plex format by Luminex® (mAb assay). The mAbs displayed no cross-reactivity to bound LC, the alternate LC type, or other human proteins and had improved sensitivity and specificity over immunofixation electrophoresis (IFE) and Freelite™. The assay gives good linearity and sensitivity (<1 mg/L), and the competitive inhibition format gave a broad calibration curve up to 437.5 mg/L and prevented anomalous results for samples in antigen excess i.e. high FLC levels. The mAbs displayed good concordance with Freelite™ for the quantitation of normal polyclonal FLC in plasma from healthy donors (n=249). The mAb assay identified all monoclonal FLC in serum from consecutive patient samples (n=1000; 50.1% with monoclonal paraprotein by serum IFE), and all FLC in a large cohort of urine samples tested for Bence Jones proteins (n=13090; 22.8% with monoclonal κ, 9.0% with monoclonal λ, and 0.8% with poly LC detected by urine IFE). Importantly this shows that the mAbs are at least close to the ideal of detecting FLC from all patients and neoplastic plasma cell clones. Given the overall effectiveness of the anti-FLC mAbs, further clinical validation is now warranted on serial samples from a range of patients with B cell disorders. Use of these mAbs on other assay platforms should also be investigated. Copyright © 2013 Elsevier B.V. All rights reserved.

Mega-solubility of quartz resulting from highly alkaline fluids produced by dissolved albite in H2O at deep crustal conditions

NASA Astrophysics Data System (ADS)

Makhluf, A. R.; Manning, C. E.

2017-12-01

Models of H2O-rich fluids equilibrated with rocks at high P and T fail to predict the high solubilities observed experimentally, chiefly because thermodynamic data for the most abundant solutes is lacking. We investigated the effects of dissolved albite (Ab) on the solubility of quartz (Qz) at 1.0 GPa and 675-900 °C using a piston-cylinder apparatus to quantify possible mineral buffering or enhancement effects. We found a very large enhancement effect on the solubility of Qz when dissolved in dilute aqueous Ab solutions. SiO2 concentrations are similar to Qz solubility in strongly alkaline KOH solutions. At the highest temperature of 900 °C, we found that the solubility of Qz in 1.0 molal Ab solution increases by of factor of 4.5 over that in pure H2O, which corresponds to 10.7 molal SiO2. The nearly identical solubility of Qz in KOH(aq) and Ab solutions of the same concentration, P, and T, strongly suggest that NaOH(aq) liberated from NaAlSi3O8 in H2O fluids effects SiO2 solubility in a similar manner to that of KOH(aq). The deprotonated silica dimer was found to be a key species responsible for the high solubility of Qz in KOH(aq) and is likely responsible for the high solubility of Qz in Ab solutions. While the binaries Qz-H2O, Ab-H2O, and Qz-Ab are well known at 1.0 GPa, little data exists on the ternary system. The new results help quantify the ternary relations in the Ab-Qz-H2O system, which can be used as a simple model for liquid-vapor immiscibility granitic magmas. In addition, these highly alkaline solute-rich aqueous fluids suggest a mechanism for Ab-Qz metasomatism in subduction zones, such as in the Catalina schist (Bebout and Barton 1993), which provides an alternative to high P-T magmas. Our results show that subduction zone and metasomatic fluids may be much more alkaline and have significantly higher dissolving power than previously thought.

Multiscale, Intermittent, Turbulent Fluctuations in Space Plasmas and Their Influence on the Interscale Behavior of the Space Environment

DTIC Science & Technology

2012-06-26

s and the PDFs vary with δ as power laws: δB2/δa = I and P/δb = J , where (a,b) are the exponents and (I , J ) are constants – i.e. invariants with...following scaling form for the PDFs: P ( δB2,δ ) δs =Ps ( δB2/δs ) (1) where s = a = −b is the lone scaling exponent , and Ps is a scaling function of the...intermittency in space plasmas 547 The scaling exponent s may be interpreted as the fractal (monofractal) measure for (1). If the PDFs are self-similar

A microstructural model of motion of macro-twin interfaces in Ni-Mn-Ga 10 M martensite

NASA Astrophysics Data System (ADS)

Seiner, Hanuš; Straka, Ladislav; Heczko, Oleg

2014-03-01

We present a continuum-based model of microstructures forming at the macro-twin interfaces in thermoelastic martensites and apply this model to highly mobile interfaces in 10 M modulated Ni-Mn-Ga martensite. The model is applied at three distinct spatial scales observed in the experiment: meso-scale (modulation twinning), micro-scale (compound a-b lamination), and nano-scale (nanotwining in the concept of adaptive martensite). We show that two mobile interfaces (Type I and Type II macro-twins) have different micromorphologies at all considered spatial scales, which can directly explain their different twinning stress observed in experiments. The results of the model are discussed with respect to various experimental observations at all three considered spatial scales.

Lattice contraction with boron doping in fully strained SiGe epitaxial layers

NASA Astrophysics Data System (ADS)

Shin, Keun Wook; Song, Sukchan; Kim, Hyun-Woo; Lee, Gun-Do; Yoon, Euijoon

2018-06-01

Changes in lattice constants of epitaxial SiGe layers by boron (B) doping were studied by using high resolution X-ray diffraction (HRXRD) by using SiGe:B with Ge and B concentrations in the range of 11–23% and (1.5–4.2) × 1019 cm‑3, respectively. The lattice contraction coefficient (β) of B in SiGe was measured to be (9.6 ± 0.6) × 10‑24 cm3, which was approximately twice as large as that of B in Si. The ab initio calculation of β, 9.35 × 10‑24 cm3, was in excellent agreement with the experiment. From the ab initio calculation, it is found that the large lattice contraction is due to the favorability of Si–B bond than Si–Ge bond.

Synthesis of Large-grain, Single-crystalline Monolayer and AB-stacking Bilayer Graphene

NASA Astrophysics Data System (ADS)

Zhang, Luyao; Lin, Yung-Chen; Zhang, Yi; Chang, Han-Wen; Yeh, Wen-Cheng; Zhou, Chongwu; USC Nanotechnology Research Laboratory Team

2013-03-01

We report the growth of large-grain, single-crystalline monolayer and AB-stacking bilayer graphene by the combination of ambient pressure chemical vapor deposition and low pressure chemical vapor deposition. The shape of the monolayer graphene was modified to be either hexagons or flowers under different growth conditions. The size of the bilayer graphene region was enlarged under ambient pressure growth conditions with low methane concentration. Raman spectra and selected area electron diffraction of individual graphene grain indicated that the each graphene grain is single-crystalline. With electron beam lithography patterned PMMA seeds, graphene nucleation can be controlled and graphene monolayer and bilayer arrays were synthesized on copper foil. Electron backscatter diffraction study revealed that the graphene morphology had little correlation with the crystalline orientation of underlying copper substrate. Mork Family Department of Chemical Engineering and Materials Science

Ab initio quantum chemical calculation of electron transfer matrix elements for large molecules

NASA Astrophysics Data System (ADS)

Zhang, Linda Yu; Friesner, Richard A.; Murphy, Robert B.

1997-07-01

Using a diabatic state formalism and pseudospectral numerical methods, we have developed an efficient ab initio quantum chemical approach to the calculation of electron transfer matrix elements for large molecules. The theory is developed at the Hartree-Fock level and validated by comparison with results in the literature for small systems. As an example of the power of the method, we calculate the electronic coupling between two bacteriochlorophyll molecules in various intermolecular geometries. Only a single self-consistent field (SCF) calculation on each of the monomers is needed to generate coupling matrix elements for all of the molecular pairs. The largest calculations performed, utilizing 1778 basis functions, required ˜14 h on an IBM 390 workstation. This is considerably less cpu time than would be necessitated with a supermolecule adiabatic state calculation and a conventional electronic structure code.

Ab initio simulation of elastic and mechanical properties of Zn- and Mg-doped hydroxyapatite (HAP).

PubMed

Aryal, Sitaram; Matsunaga, Katsuyuki; Ching, Wai-Yim

2015-07-01

Hydroxyapatite (HAP) is an important bioceramic which constitutes the mineral components of bones and hard tissues in mammals. It is bioactive and used as bioceramic coatings for metallic implants and bone fillers. HAP readily absorbs a large amount of impurities. Knowledge on the elastic and mechanical properties of impurity-doped HAP is a subject of great importance to its potential for biomedical applications. Zn and Mg are the most common divalent cations HAP absorbs. Using density function theory based ab initio methods, we have carried out a large number of ab initio calculations to obtain the bulk elastic and mechanical properties of HAP with Zn or Mg doped in different concentration at the Ca1 and Ca2 sites using large 352-atom supercells. Detailed information on their dependece on the concetraion of the substitued impurity is obtained. Our results show that Mg enhances overall elastic and bulk mechanical properties whereas Zn tends to degrade except at low concentrations. At a higher concentration, the mechanical properties of Zn and Mg doped HAP also depend significantly on impurity distribution between the Ca1 and Ca2 sites. There is a strong evidence that Zn prefers Ca2 site for substituion whereas Mg has no such preference. These results imply that proper control of dopant concentration and their site preference must carefully considered in using doped HAP for specific biomedical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ab Initio Study of Interfacial Structure Transformation of Amorphous Carbon Catalyzed by Ti, Cr, and W Transition Layers.

PubMed

Li, Xiaowei; Li, Lei; Zhang, Dong; Wang, Aiying

2017-11-29

Amorphous carbon (a-C) films composited with transition layers exhibit the desirable improvement of adhesion strength between films and substrate, but the further understanding on the interfacial structure transformation of a-C structure induced by transition layers is still lacked. In this paper, using ab initio calculations, we comparatively studied the interfacial structure between Ti, Cr, or W transition layers and a-C film from the atomic scale, and demonstrated that the addition of Ti, Cr, or W catalyzed the graphitic transformation of a-C structure at different levels, which provided the theoretical guidance for designing a multilayer nanocomposite film for renewed application.

Stress is not associated with thyroid peroxidase autoantibodies in euthyroid women.

PubMed

Strieder, Thea G A; Prummel, Mark F; Tijssen, Jan G P; Brosschot, Jos F; Wiersinga, Wilmar M

2005-05-01

Multiple genes and environmental factors play a role in the etiology of autoimmune thyroid disease (AITD). In Graves' hyperthyroidism, stress is such an environmental factor, but whether it plays a role in Hashimoto's hypothyroidism is unknown. We used validated questionnaires to evaluate an association between TPO antibodies, an early marker for AITD, and self-reported stress. Recently Experienced Stressful Life Events, Daily Hassles, and mood (tendency to report positive and negative affects) were assessed in 759 euthyroid subjects. TPO antibodies were found in 183/759 (24%) of subjects. The TPO-Ab positive subjects were older (39.7+/-12 vs. 34.2+/-12 years; p<.001) than the TPO-Ab negative subjects, but the number of daily hassles (24+/-14 vs. 25+/-14; p=.24), the number of stressful life events (10+/-6 vs. 11+/-6; p=.09), and the scores on the affect scales (22.1+/-7.4 vs. 22.2+/-7.3; p=.89 for negative affect and 38.2+/-5.1 vs. 38.3+/-5.3; p=.91 for positive affect) were similar in TPO-Ab positive and TPO- Ab negative subjects. We found no association between recently experienced stressful life events, daily hassles or mood and the presence of TPO antibodies in these euthyroid women.

A near-infrared variability campaign of TMR-1: New light on the nature of the candidate protoplanet TMR-1C

NASA Astrophysics Data System (ADS)

Riaz, B.; Martín, E. L.; Petr-Gotzens, M. G.; Monin, J.-L.

2013-11-01

We present a near-infrared (NIR) photometric variability study of the TMR-1 system, a Class I protobinary located in the Taurus molecular cloud. Our aim is to confirm NIR variability for the candidate protoplanet, TMR-1C, located at a separation of about 10″ (~1000 AU) from the protobinary. We conducted a photometric monitoring campaign between October 2011 and January 2012 using the CFHT/WIRCam imager. We were able to obtain 44 epochs of observations in each of the H and Ks filters, resulting in high-quality photometry with uncertainties of less than one-tenth of a magnitude. The shortest time difference between two epochs is ~14 min, and the longest is ~4 months. Based on the final accuracy of our observations, we do not find any strong evidence of short-term NIR variability at amplitudes of ≥0.15-0.2 mag for TMR-1C or TMR-1AB. Our present observations, however, have reconfirmed the large-amplitude long-term variations in the NIR emission for TMR-1C, which were observed between 1998 and 2002, and have also shown that no particular correlation exists between the brightness and the color changes. The object TMR-1C became brighter in the H band by ~1.8 mag between 1998 and 2002, and then fainter again by ~0.7 mag between 2002 and 2011. In contrast, TMR-1C became continually brighter in the Ks band in the period between 1998 and 2011. The (H - Ks) color for TMR-1C shows large variations, from a red value of 1.3 ± 0.07 and 1.6 ± 0.05 mag in 1998 and 2000, to a much bluer color of -0.1 ± 0.5 mag in 2002, and then again a red color of 1.1 ± 0.08 mag in 2011. The difference in the variability trends observed in the H and Ks bands suggests the presence of more than one origin for the observed variations. The observed variability from 1998 to 2011 suggests that TMR-1C becomes fainter when it gets redder, as expected from variable extinction, while the brightening observed in the Ks band could be due to physical variations in the inner disk structure of TMR-1C. We have argued in favor of TMR-1C being a young stellar object (YSO), rather than a faint background star passing behind some foreground material. There may exist short-term NIR variations at an amplitude level lower than our detection limit (~0.2 mag), which would be consistent with the YSO hypothesis. If the observed long-term variability is due to foreground extinction, then we would expect simultaneous brightening/dimming in the H and Ks bands, which we do not find to be the case. Variable foreground extinction is also expected to occur over a large spatial scale; we monitored several other objects within 4'× 4' of the TMR-1 system, and found only two objects which show long-term variations, indicating that this is not a large-scale effect. The NIR colors for TMR-1C obtained using the high-precision photometry from 1998, 2000, and 2011 observations are similar to the protostars in Taurus, suggesting that it could be a faint dusty Class I source. This object is thus a strong candidate YSO, but final confirmation as a protoplanet remains elusive and requires further investigation. Our study has also revealed two new variable sources in the vicinity of TMR-1AB that show long-term variations of ~1-2 mag in the NIR colors between 2002 and 2011. The proper motions measured for TMR-1AB and TMR-1C are -40,+58 mas/yr and -22,+5 mas/yr, respectively, with an uncertainty of ~31 mas/yr. A larger baseline of 20 years or more is required to confidently confirm the physical association of TMR-1AB and C. Tables 1-4 are available in electronic form at http://www.aanda.org

Isolation of dengue virus-specific memory B cells with live virus antigen from human subjects following natural infection reveals the presence of diverse novel functional groups of antibody clones.

PubMed

Smith, Scott A; de Alwis, A Ruklanthi; Kose, Nurgun; Jadi, Ramesh S; de Silva, Aravinda M; Crowe, James E

2014-11-01

Natural dengue virus (DENV) infection in humans induces antibodies (Abs) that neutralize the serotype of infection in a potent and type-specific manner; however, most Abs generated in response to infection are serotype cross-reactive and poorly neutralizing. Such cross-reactive Abs may enhance disease during subsequent infection with a virus of a different DENV serotype. Previous screening assays for DENV-specific human B cells and antibodies, using viral and recombinant antigens, mainly led to the isolation of dominant nonneutralizing B cell clones. To improve upon our ability to recover and study rare but durable and potently neutralizing DENV-specific Abs, we isolated human DENV-specific B cells by using a primary screen of binding to live virus, followed by a secondary screen with a high-throughput, flow cytometry-based neutralization assay to identify DENV-specific B cell lines prior to generation of hybridomas. Using this strategy, we identified several new classes of serotype-specific and serotype-cross-neutralizing anti-DENV monoclonal Abs (MAbs), including ultrapotent inhibitory antibodies with neutralizing activity concentrations of <10 ng/ml. We isolated serotype-specific neutralizing Abs that target diverse regions of the E protein, including epitopes present only on the intact, fully assembled viral particle. We also isolated a number of serotype-cross-neutralizing MAbs, most of which recognized a region in E protein domain I/II containing the fusion loop. These data provide insights into targets of the protective Ab-mediated immune response to natural DENV infection, which will prove valuable in the design and testing of new experimental DENV vaccines. Dengue virus infection is one of the most common mosquito-borne diseases and occurs in most countries of the world. Infection of humans with dengue virus induces a small number of antibodies that inhibit the infecting strain but also induces a large number of antibodies that can bind but do not inhibit dengue virus strains of other serotypes. We used a focused screening strategy to discover a large number of rare potently inhibiting antibodies, and we mapped the regions on the virus that were recognized by such antibodies. Our studies revealed that humans have the potential to generate very potent antibodies directed to diverse regions of the dengue virus surface protein. These studies provide important new information about protection from dengue virus infection that will be useful in the design and testing of new experimental dengue vaccines for humans. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Isolation of Dengue Virus-Specific Memory B Cells with Live Virus Antigen from Human Subjects following Natural Infection Reveals the Presence of Diverse Novel Functional Groups of Antibody Clones

PubMed Central

Smith, Scott A.; de Alwis, A. Ruklanthi; Kose, Nurgun; Jadi, Ramesh S.; de Silva, Aravinda M.

2014-01-01

ABSTRACT Natural dengue virus (DENV) infection in humans induces antibodies (Abs) that neutralize the serotype of infection in a potent and type-specific manner; however, most Abs generated in response to infection are serotype cross-reactive and poorly neutralizing. Such cross-reactive Abs may enhance disease during subsequent infection with a virus of a different DENV serotype. Previous screening assays for DENV-specific human B cells and antibodies, using viral and recombinant antigens, mainly led to the isolation of dominant nonneutralizing B cell clones. To improve upon our ability to recover and study rare but durable and potently neutralizing DENV-specific Abs, we isolated human DENV-specific B cells by using a primary screen of binding to live virus, followed by a secondary screen with a high-throughput, flow cytometry-based neutralization assay to identify DENV-specific B cell lines prior to generation of hybridomas. Using this strategy, we identified several new classes of serotype-specific and serotype-cross-neutralizing anti-DENV monoclonal Abs (MAbs), including ultrapotent inhibitory antibodies with neutralizing activity concentrations of <10 ng/ml. We isolated serotype-specific neutralizing Abs that target diverse regions of the E protein, including epitopes present only on the intact, fully assembled viral particle. We also isolated a number of serotype-cross-neutralizing MAbs, most of which recognized a region in E protein domain I/II containing the fusion loop. These data provide insights into targets of the protective Ab-mediated immune response to natural DENV infection, which will prove valuable in the design and testing of new experimental DENV vaccines. IMPORTANCE Dengue virus infection is one of the most common mosquito-borne diseases and occurs in most countries of the world. Infection of humans with dengue virus induces a small number of antibodies that inhibit the infecting strain but also induces a large number of antibodies that can bind but do not inhibit dengue virus strains of other serotypes. We used a focused screening strategy to discover a large number of rare potently inhibiting antibodies, and we mapped the regions on the virus that were recognized by such antibodies. Our studies revealed that humans have the potential to generate very potent antibodies directed to diverse regions of the dengue virus surface protein. These studies provide important new information about protection from dengue virus infection that will be useful in the design and testing of new experimental dengue vaccines for humans. PMID:25100837

Comparing the economic and health benefits of different approaches to diagnosing Clostridium difficile infection.

PubMed

Bartsch, Sarah M; Umscheid, Craig A; Nachamkin, Irving; Hamilton, Keith; Lee, Bruce Y

2015-01-01

Accurate diagnosis of Clostridium difficile infection (CDI) is essential to effectively managing patients and preventing transmission. Despite the availability of several diagnostic tests, the optimal strategy is debatable and their economic values are unknown. We modified our previously existing C. difficile simulation model to determine the economic value of different CDI diagnostic approaches from the hospital perspective. We evaluated four diagnostic methods for a patient suspected of having CDI: 1) toxin A/B enzyme immunoassay, 2) glutamate dehydrogenase (GDH) antigen/toxin AB combined in one test, 3) nucleic acid amplification test (NAAT), and 4) GDH antigen/toxin AB combination test with NAAT confirmation of indeterminate results. Sensitivity analysis varied the proportion of those tested with clinically significant diarrhoea, the probability of CDI, NAAT cost and CDI treatment delay resulting from a false-negative test, length of stay and diagnostic sensitivity and specificity. The GDH/toxin AB plus NAAT approach leads to the timeliest treatment with the fewest unnecessary treatments given, resulted in the best bed management and generated the lowest cost. The NAAT-alone approach also leads to timely treatment. The GDH/toxin AB diagnostic (without NAAT confirmation) approach resulted in a large number of delayed treatments, but results in the fewest secondary colonisations. Results were robust to the sensitivity analysis. Choosing the right diagnostic approach is a matter of cost and test accuracy. GDH/toxin AB plus NAAT diagnosis led to the timeliest treatment and was the least costly. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Large hydrogen-bonded pre-nucleation (HSO4-)(H2SO4)m(H2O)k and (HSO4-)(NH3)(H2SO4)m(H2O)k clusters in the earth's atmosphere.

PubMed

Herb, Jason; Xu, Yisheng; Yu, Fangqun; Nadykto, A B

2013-01-10

The importance of pre-nucleation cluster stability as the key parameter controlling nucleation of atmospheric airborne ions is well-established. In this Article, large ternary ionic (HSO(4)(-))(H(2)SO(4))(m)(NH(3))(H(2)O)(n) clusters have been studied using Density Functional Theory (DFT) and composite ab initio methods. Twenty classes of clusters have been investigated, and thermochemical properties of common atmospheric (HSO(4)(-))(H(2)SO(4))(m)(NH(3))(0)(H(2)O)(k) and (HSO(4)(-))(H(2)SO(4))(m)(NH(3))(1)(H(2)O)(n) clusters (with m, k, and n up to 3) have been obtained. A large amount of new themochemical and structural data ready-to-use for constraining kinetic nucleation models has been reported. We have performed a comprehensive thermochemical analysis of the obtained data and have investigated the impacts of ammonia and negatively charged bisulfate ion on stability of binary clusters in some detail. The comparison of theoretical predictions and experiments shows that the PW91PW91/6-311++G(3df,3pd) results are in very good agreement with both experimental data and high level ab initio CCSD(T)/CBS values and suggest that the PW91PW91/6-311++G(3df,3pd) method is a viable alternative to higher level ab initio methods in studying large pre-nucleation clusters, for which the higher level computations are prohibitively expensive. The uncertainties in both theory and experiments have been investigated, and possible ways of their reduction have been proposed.

Fast parametric relationships for the large-scale reservoir simulation of mixed CH 4-CO 2 gas hydrate systems

DOE PAGES

Reagan, Matthew T.; Moridis, George J.; Seim, Katie S.

2017-03-27

A recent Department of Energy field test on the Alaska North Slope has increased interest in the ability to simulate systems of mixed CO 2-CH 4 hydrates. However, the physically realistic simulation of mixed-hydrate simulation is not yet a fully solved problem. Limited quantitative laboratory data leads to the use of various ab initio, statistical mechanical, or other mathematic representations of mixed-hydrate phase behavior. Few of these methods are suitable for inclusion in reservoir simulations, particularly for systems with large number of grid elements, 3D systems, or systems with complex geometric configurations. In this paper, we present a set ofmore » fast parametric relationships describing the thermodynamic properties and phase behavior of a mixed methane-carbon dioxide hydrate system. We use well-known, off-the-shelf hydrate physical properties packages to generate a sufficiently large dataset, select the most convenient and efficient mathematical forms, and fit the data to those forms to create a physical properties package suitable for inclusion in the TOUGH+ family of codes. Finally, the mapping of the phase and thermodynamic space reveals the complexity of the mixed-hydrate system and allows understanding of the thermodynamics at a level beyond what much of the existing laboratory data and literature currently offer.« less

Fast parametric relationships for the large-scale reservoir simulation of mixed CH4-CO2 gas hydrate systems

NASA Astrophysics Data System (ADS)

Reagan, Matthew T.; Moridis, George J.; Seim, Katie S.

2017-06-01

A recent Department of Energy field test on the Alaska North Slope has increased interest in the ability to simulate systems of mixed CO2-CH4 hydrates. However, the physically realistic simulation of mixed-hydrate simulation is not yet a fully solved problem. Limited quantitative laboratory data leads to the use of various ab initio, statistical mechanical, or other mathematic representations of mixed-hydrate phase behavior. Few of these methods are suitable for inclusion in reservoir simulations, particularly for systems with large number of grid elements, 3D systems, or systems with complex geometric configurations. In this work, we present a set of fast parametric relationships describing the thermodynamic properties and phase behavior of a mixed methane-carbon dioxide hydrate system. We use well-known, off-the-shelf hydrate physical properties packages to generate a sufficiently large dataset, select the most convenient and efficient mathematical forms, and fit the data to those forms to create a physical properties package suitable for inclusion in the TOUGH+ family of codes. The mapping of the phase and thermodynamic space reveals the complexity of the mixed-hydrate system and allows understanding of the thermodynamics at a level beyond what much of the existing laboratory data and literature currently offer.

Fast parametric relationships for the large-scale reservoir simulation of mixed CH 4-CO 2 gas hydrate systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reagan, Matthew T.; Moridis, George J.; Seim, Katie S.

A recent Department of Energy field test on the Alaska North Slope has increased interest in the ability to simulate systems of mixed CO 2-CH 4 hydrates. However, the physically realistic simulation of mixed-hydrate simulation is not yet a fully solved problem. Limited quantitative laboratory data leads to the use of various ab initio, statistical mechanical, or other mathematic representations of mixed-hydrate phase behavior. Few of these methods are suitable for inclusion in reservoir simulations, particularly for systems with large number of grid elements, 3D systems, or systems with complex geometric configurations. In this paper, we present a set ofmore » fast parametric relationships describing the thermodynamic properties and phase behavior of a mixed methane-carbon dioxide hydrate system. We use well-known, off-the-shelf hydrate physical properties packages to generate a sufficiently large dataset, select the most convenient and efficient mathematical forms, and fit the data to those forms to create a physical properties package suitable for inclusion in the TOUGH+ family of codes. Finally, the mapping of the phase and thermodynamic space reveals the complexity of the mixed-hydrate system and allows understanding of the thermodynamics at a level beyond what much of the existing laboratory data and literature currently offer.« less

Atomic defects in monolayer WSe2 tunneling FETs studied by systematic ab initio calculations

NASA Astrophysics Data System (ADS)

Wu, Jixuan; Fan, Zhiqiang; Chen, Jiezhi; Jiang, Xiangwei

2018-05-01

Atomic defects in monolayer WSe2 tunneling FETs (TFETs) are studied through systematic ab initio calculations aiming at performance predictions and enhancements. The effects of various defect positions and different passivation atoms are characterized in WSe2 TFETs by rigorous ab initio quantum transport simulations. It is suggested that the Se vacancy (VSe) defect located in the gate-controlled channel region tends to increase the OFF current (I off), whereas it can be well suppressed by oxygen passivation. It is demonstrated that chlorine (Cl) passivation at the source-side tunneling region can largely suppress I off, leading to an impressively improved on–off ratio (I on/I off) compared with that without any defect. However, it is also observed that randomly positioned atomic defects tend to induce significant fluctuation of the TFET output. Further discussions are made with focus on the performance-variability trade-off for robust circuit design.

Ab initio results for intermediate-mass, open-shell nuclei

NASA Astrophysics Data System (ADS)

Baker, Robert B.; Dytrych, Tomas; Launey, Kristina D.; Draayer, Jerry P.

2017-01-01

A theoretical understanding of nuclei in the intermediate-mass region is vital to astrophysical models, especially for nucleosynthesis. Here, we employ the ab initio symmetry-adapted no-core shell model (SA-NCSM) in an effort to push first-principle calculations across the sd-shell region. The ab initio SA-NCSM's advantages come from its ability to control the growth of model spaces by including only physically relevant subspaces, which allows us to explore ultra-large model spaces beyond the reach of other methods. We report on calculations for 19Ne and 20Ne up through 13 harmonic oscillator shells using realistic interactions and discuss the underlying structure as well as implications for various astrophysical reactions. This work was supported by the U.S. NSF (OCI-0904874 and ACI -1516338) and the U.S. DOE (DE-SC0005248), and also benefitted from the Blue Waters sustained-petascale computing project and high performance computing resources provided by LSU.

Optimized expression and purification of NavAb provide the structural insight into the voltage dependence.

PubMed

Irie, Katsumasa; Haga, Yukari; Shimomura, Takushi; Fujiyoshi, Yoshinori

2018-01-01

Voltage-gated sodium channels are crucial for electro-signalling in living systems. Analysis of the molecular mechanism requires both fine electrophysiological evaluation and high-resolution channel structures. Here, we optimized a dual expression system of NavAb, which is a well-established standard of prokaryotic voltage-gated sodium channels, for E. coli and insect cells using a single plasmid vector to analyse high-resolution protein structures and measure large ionic currents. Using this expression system, we evaluated the voltage dependence and determined the crystal structures of NavAb wild-type and two mutants, E32Q and N49K, whose voltage dependence were positively shifted and essential interactions were lost in voltage sensor domain. The structural and functional comparison elucidated the molecular mechanisms of the voltage dependence of prokaryotic voltage-gated sodium channels. © 2017 Federation of European Biochemical Societies.

Synthesis, anisotropy, and superconducting properties of LiFeAs single crystal

NASA Astrophysics Data System (ADS)

Song, Yoo Jang; Ghim, Jin Soo; Min, Byeong Hun; Kwon, Yong Seung; Jung, Myung Hwa; Rhyee, Jong-Soo

2010-05-01

A LiFeAs single crystal with Tconset˜19.7 K was grown in a sealed tungsten crucible using the Bridgeman method. The electrical resistivity experiments revealed a ratio of room temperature to residual resistivity of approximately 46 and 18 for the in-plane and out-of plane directions, respectively. The estimated anisotropic resistivity, γρ=ρc/ρab, was approximately 3.3 at Tconset. The upper critical fields had large Hc2∥ab and Hc2∥c values of 83.4 T and 72.5 T, respectively, and an anisotropy ratio is γH=Hc2∥ab/Hc2∥c˜1.15. The high upper critical field value and small anisotropy highlight the potential use of LiFeAs in a variety of applications. The calculated critical current density (Jc) from the M-H loop is approximately 103 A/cm2

A global ab initio potential for HCN/HNC, exact vibrational energies, and comparison to experiment

NASA Technical Reports Server (NTRS)

Bentley, Joseph A.; Bowman, Joel M.; Gazdy, Bela; Lee, Timothy J.; Dateo, Christopher E.

1992-01-01

An ab initio (i.e., from first principles) calculation of vibrational energies of HCN and HNC is reported. The vibrational calculations were done with a new potential derived from a fit to 1124 ab initio electronic energies which were calculated using the highly accurate CCSD(T) coupled-cluster method in conjunction with a large atomic natural orbital basis set. The properties of this potential are presented, and the vibrational calculations are compared to experiment for 54 vibrational transitions, 39 of which are for zero total angular momentum, J = 0, and 15 of which are for J = 1. The level of agreement with experiment is unprecedented for a triatomic with two nonhydrogen atoms, and demonstrates the capability of the latest computational methods to give reliable predictions on a strongly bound triatomic molecule at very high levels of vibrational excitation.

Ab initio study of MF2 (M=Mn, Fe, Co, Ni) rutile-type compounds using the periodic unrestricted Hartree-Fock approach

NASA Astrophysics Data System (ADS)

de P. R. Moreira, Ibério; Dovesi, Roberto; Roetti, Carla; Saunders, Victor R.; Orlando, Roberto

2000-09-01

The ab initio periodic unrestricted Hartree-Fock method has been applied in the investigation of the ground-state structural, electronic, and magnetic properties of the rutile-type compounds MF2 (M=Mn, Fe, Co, and Ni). All electron Gaussian basis sets have been used. The systems turn out to be large band-gap antiferromagnetic insulators; the optimized geometrical parameters are in good agreement with experiment. The calculated most stable electronic state shows an antiferromagnetic order in agreement with that resulting from neutron scattering experiments. The magnetic coupling constants between nearest-neighbor magnetic ions along the [001], [111], and [100] (or [010]) directions have been calculated using several supercells. The resulting ab initio magnetic coupling constants are reasonably satisfactory when compared with available experimental data. The importance of the Jahn-Teller effect in FeF2 and CoF2 is also discussed.

Nuclear shielding constants by density functional theory with gauge including atomic orbitals

NASA Astrophysics Data System (ADS)

Helgaker, Trygve; Wilson, Philip J.; Amos, Roger D.; Handy, Nicholas C.

2000-08-01

Recently, we introduced a new density-functional theory (DFT) approach for the calculation of NMR shielding constants. First, a hybrid DFT calculation (using 5% exact exchange) is performed on the molecule to determine Kohn-Sham orbitals and their energies; second, the constants are determined as in nonhybrid DFT theory, that is, the paramagnetic contribution to the constants is calculated from a noniterative, uncoupled sum-over-states expression. The initial results suggested that this semiempirical DFT approach gives shielding constants in good agreement with the best ab initio and experimental data; in this paper, we further validate this procedure, using London orbitals in the theory, having implemented DFT into the ab initio code DALTON. Calculations on a number of small and medium-sized molecules confirm that our approach produces shieldings in excellent agreement with experiment and the best ab initio results available, demonstrating its potential for the study of shielding constants of large systems.

Accelerated path-integral simulations using ring-polymer interpolation

NASA Astrophysics Data System (ADS)

Buxton, Samuel J.; Habershon, Scott

2017-12-01

Imaginary-time path-integral (PI) molecular simulations can be used to calculate exact quantum statistical mechanical properties for complex systems containing many interacting atoms and molecules. The limiting computational factor in a PI simulation is typically the evaluation of the potential energy surface (PES) and forces at each ring-polymer "bead"; for an n-bead ring-polymer, a PI simulation is typically n times greater than the corresponding classical simulation. To address the increased computational effort of PI simulations, several approaches have been developed recently, most notably based on the idea of ring-polymer contraction which exploits either the separation of the PES into short-range and long-range contributions or the availability of a computationally inexpensive PES which can be incorporated to effectively smooth the ring-polymer PES; neither approach is satisfactory in applications to systems modeled by PESs given by on-the-fly ab initio calculations. In this article, we describe a new method, ring-polymer interpolation (RPI), which can be used to accelerate PI simulations without any prior assumptions about the PES. In simulations of liquid water modeled by an empirical PES (or force field) under ambient conditions, where quantum effects are known to play a subtle role in influencing experimental observables such as radial distribution functions, we find that RPI can accurately reproduce the results of fully-converged PI simulations, albeit with far fewer PES evaluations. This approach therefore opens the possibility of large-scale PI simulations using ab initio PESs evaluated on-the-fly without the drawbacks of current methods.

Novel Cross-Slip Mechanism of Pyramidal Screw Dislocations in Magnesium.

PubMed

Itakura, Mitsuhiro; Kaburaki, Hideo; Yamaguchi, Masatake; Tsuru, Tomohito

2016-06-03

Compared to cubic metals, whose primary slip mode includes twelve equivalent systems, the lower crystalline symmetry of hexagonal close-packed metals results in a reduced number of equivalent primary slips and anisotropy in plasticity, leading to brittleness at the ambient temperature. At higher temperatures, the ductility of hexagonal close-packed metals improves owing to the activation of secondary ⟨c+a⟩ pyramidal slip systems. Thus, understanding the fundamental properties of corresponding dislocations is essential for the improvement of ductility at the ambient temperature. Here, we present the results of large-scale ab initio calculations for ⟨c+a⟩ pyramidal screw dislocations in magnesium and show that their slip behavior is a stark counterexample to the conventional wisdom that a slip plane is determined by the stacking fault plane of dislocations. A stacking fault between dissociated partial dislocations can assume a nonplanar shape with a negligible energy cost and can migrate normal to its plane by a local shuffling of atoms. Partial dislocations dissociated on a {21[over ¯]1[over ¯]2} plane "slither" in the {011[over ¯]1} plane, dragging the stacking fault with them in response to an applied shear stress. This finding resolves the apparent discrepancy that both {21[over ¯]1[over ¯]2} and {011[over ¯]1} slip traces are observed in experiments while ab initio calculations indicate that dislocations preferably dissociate in the {21[over ¯]1[over ¯]2} planes.

A method for the isolation and characterization of functional murine monoclonal antibodies by single B cell cloning.

PubMed

Carbonetti, Sara; Oliver, Brian G; Vigdorovich, Vladimir; Dambrauskas, Nicholas; Sack, Brandon; Bergl, Emilee; Kappe, Stefan H I; Sather, D Noah

2017-09-01

Monoclonal antibody technologies have enabled dramatic advances in immunology, the study of infectious disease, and modern medicine over the past 40years. However, many monoclonal antibody discovery procedures are labor- and time-intensive, low efficiency, and expensive. Here we describe an optimized mAb discovery platform for the rapid and efficient isolation, cloning and characterization of monoclonal antibodies in murine systems. In this platform, antigen-binding splenic B cells from immunized mice are isolated by FACS and cocultured with CD40L positive cells to induce proliferation and mAb production. After 12days of coculture, cell culture supernatants are screened for antigen, and IgG positivity and RNA is isolated for reverse-transcription. Positive-well cDNA is then amplified by PCR and the resulting amplicons can be cloned into ligation-independent expression vectors, which are then used directly to transfect HEK293 cells for recombinant antibody production. After 4days of growth, conditioned medium can be screened using biolayer interferometry for antigen binding and affinity measurements. Using this method, we were able to isolate six unique, functional monoclonal antibodies against an antigen of the human malaria parasite Plasmodium falciparum. Importantly, this method incorporates several important advances that circumvent the need for single-cell PCR, restriction cloning, and large scale protein production, and can be applied to a wide array of protein antigens. Copyright © 2017 Elsevier B.V. All rights reserved.

Debris flow runup on vertical barriers and adverse slopes

USGS Publications Warehouse

Iverson, Richard M.; George, David L.; Logan, Matthew

2016-01-01

Runup of debris flows against obstacles in their paths is a complex process that involves profound flow deceleration and redirection. We investigate the dynamics and predictability of runup by comparing results from large-scale laboratory experiments, four simple analytical models, and a depth-integrated numerical model (D-Claw). The experiments and numerical simulations reveal the important influence of unsteady, multidimensional flow on runup, and the analytical models highlight key aspects of the underlying physics. Runup against a vertical barrier normal to the flow path is dominated by rapid development of a shock, or jump in flow height, associated with abrupt deceleration of the flow front. By contrast, runup on sloping obstacles is initially dominated by a smooth flux of mass and momentum from the flow body to the flow front, which precedes shock development and commonly increases the runup height. D-Claw simulations that account for the emergence of shocks show that predicted runup heights vary systematically with the adverse slope angle and also with the Froude number and degree of liquefaction (or effective basal friction) of incoming flows. They additionally clarify the strengths and limitations of simplified analytical models. Numerical simulations based on a priori knowledge of the evolving dynamics of incoming flows yield quite accurate runup predictions. Less predictive accuracy is attained in ab initio simulations that compute runup based solely on knowledge of static debris properties in a distant debris flow source area. Nevertheless, the paucity of inputs required in ab initio simulations enhances their prospective value in runup forecasting.

Development of an enzyme-linked immunosorbent assay and a beta-1 adrenergic receptor-based assay for monitoring the drug atenolol.

PubMed

Sapir, A; Shalev, A Hariton; Skalka, N; Bronshtein, A; Altstein, M

2013-03-01

Two approaches for monitoring atenolol (ATL) were applied: an immunochemical assay and a competitive-binding assay, based on the interaction between ATL and its target receptor, β1 adrenergic receptor (β1AR). Polyclonal antibodies (Abs) for ATL were generated, and a highly specific microplate immunochemical assay, that is, an enzyme-linked immunosorbent assay (ELISA), for its detection was developed. The ATL ELISA exhibited I50 and limit of detection (I20) values of 0.15 ± 0.048 and 0.032 ± 0.016 ng/ml, respectively, and the Abs did not cross-react with any of the tested beta-blocker drugs. Furthermore, a human β1AR (h-β1AR) was stably expressed in Spodoptera frugiperda cells (Sf9). The receptor was employed to develop a competitive-binding assay that monitored binding of ATL in the presence of isoproteranol by quantification of secondary messenger, cyclic adenosine monophosphate (cAMP), levels in the transfected cells. The assay showed that the recombinant h-β1AR was functional, could bind the agonistic ligand isoproterenol as well as the antagonist ATL, as indicated by a dose-dependent elevation of cAMP in the presence of isoproteranol, and decrease after ATL addition. The highly efficient and sensitive ELISA and the receptor assay represent two methods suitable for efficient and cost-effective large-scale, high-throughput monitoring of ATL in environmental, agricultural, and biological samples. Copyright © 2012 SETAC.

The Global and Small-scale Magnetic Fields of Fully Convective, Rapidly Spinning M Dwarf Pair GJ65 A and B

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kochukhov, Oleg; Lavail, Alexis

2017-01-20

The nearby M dwarf binary GJ65 AB, also known as BL Cet and UV Cet, is a unique benchmark for investigation of dynamo-driven activity of low-mass stars. Magnetic activity of GJ65 was repeatedly assessed by indirect means, such as studies of flares, photometric variability, X-ray, and radio emission. Here, we present a direct analysis of large-scale and local surface magnetic fields in both components. Interpreting high-resolution circular polarization spectra (sensitive to a large-scale field geometry) we uncovered a remarkable difference of the global stellar field topologies. Despite nearly identical masses and rotation rates, the secondary exhibits an axisymmetric, dipolar-like globalmore » field with an average strength of 1.3 kG while the primary has a much weaker, more complex, and non-axisymmetric 0.3 kG field. On the other hand, an analysis of the differential Zeeman intensification (sensitive to the total magnetic flux) shows the two stars having similar magnetic fluxes of 5.2 and 6.7 kG for GJ65 A and B, respectively, although there is evidence that the field strength distribution in GJ65 B is shifted toward a higher field strength compared to GJ65 A. Based on these complementary magnetic field diagnostic results, we suggest that the dissimilar radio and X-ray variability of GJ65 A and B is linked to their different global magnetic field topologies. However, this difference appears to be restricted to the upper atmospheric layers but does not encompass the bulk of the stars and has no influence on the fundamental stellar properties.« less

Characterization of Centrifugally-Loaded Flame Migration for Ultra-Compact Combustors

DTIC Science & Technology

2011-10-01

11 T04 combustor exit temperature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Q b combustor heat addition...11 Q ab afterburner heat addition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11...the mass flow rates, with heat addition, lead to reaching a specific g-load. In addition to varying g-load, a larger scale UCC will require a