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  1. A Surface Exposed, Two-Domain Lipoprotein Cargo of a Type XI Secretion System Promotes Colonization of Host Intestinal Epithelia Expressing Glycans

    The only known required component of the newly described Type XI secretion system (TXISS) is an outer membrane protein (OMP) of the DUF560 family. TXISSOMPs are broadly distributed across proteobacteria, but properties of the cargo proteins they secrete are largely unexplored. We report biophysical, histochemical, and phenotypic evidence that Xenorhabdus nematophila NilC is surface exposed. Biophysical data and structure predictions indicate that NilC is a two-domain protein with a C-terminal, 8-stranded β-barrel. This structure has been noted as a common feature of TXISS effectors and may be important for interactions with the TXISSOMP. The NilC N-terminal domain is more enigmatic,more » but our results indicate it is ordered and forms a β-sheet structure, and bioinformatics suggest structural similarities to carbohydrate-binding proteins. X. nematophila NilC and its presumptive TXISSOMP partner NilB are required for colonizing the anterior intestine of Steinernema carpocapsae nematodes: the receptacle of free-living, infective juveniles and the anterior intestinal cecum (AIC) in juveniles and adults. We show that, in adult nematodes, the AIC expresses a Wheat Germ Agglutinin (WGA)-reactive material, indicating the presence of N-acetylglucosamine or N-acetylneuraminic acid sugars on the AIC surface. A role for this material in colonization is supported by the fact that exogenous addition of WGA can inhibit AIC colonization by X. nematophila. Conversely, the addition of exogenous purified NilC increases the frequency with which X. nematophila is observed at the AIC, demonstrating that abundant extracellular NilC can enhance colonization. NilC may facilitate X. nematophila adherence to the nematode intestinal surface by binding to host glycans, it might support X. nematophila nutrition by cleaving sugars from the host surface, or it might help protect X. nematophila from nematode host immunity. Proteomic and metabolomic analyses of wild type X. nematophila compared to those lacking nilB and nilC revealed differences in cell wall and secreted polysaccharide metabolic pathways. Additionally, purified NilC is capable of binding peptidoglycan, suggesting that periplasmic NilC may interact with the bacterial cell wall. Overall, these findings support a model that NilB-regulated surface exposure of NilC mediates interactions between X. nematophila and host surface glycans during colonization. This is a previously unknown function for a TXISS.« less
  2. ADIC : an extensible automatic differentiation tool for ANSI-C.

    In scientific computing, we often require the derivatives df/dx of a function f expressed as a program with respect to some input parameter(s) x, say. Automatic Differentiation (AD) techniques augment the program with derivative computation by applying the chain rule of calculus to elementary operations in an automated fashion. This article introduces ADIC (Automatic Differentiation of C), a new AD tool for ANSI-C programs. ADIC is currently the only tool for ANSI-C that employs a source-to-source program transformation approach; that is, it takes a C code and produces a new C code that computes the original results as well asmore » the derivatives. We first present ADIC by example to illustrate the functionality and ease of use of ADIC and then describe in detail the architecture of ADIC. ADIC incorporates a modular design that provides a foundation for both rapid prototyping of better AD algorithms and their sharing across AD tools for different languages. A component architecture called AIF (Automatic Differentiation Intermediate Form) separates core AD concepts from their language-specific implementation and allows the development of generic AD modules that can be reused directly in other AIF-based AD tools. The language-specific ADIC front-end and back-end canonicalize C programs to make them fit for semantic augmentation and manage, for example, the association of a program variable with its derivative object. We also report on applications of ADIC to a semiconductor device simulator, 3-D CFD grid generator, vehicle simulator, and neural network code.« less
  3. Evaluation of post-treatment filter, Part I: Experimental study of DMMP and DIMP filtration at high temperature and high dew point using activated carbon. Final report, November 1994-September 1995

    A series of experimental results are reported for breakthrough of the agent simulants DMMP and DIMP on coconut carbon. This adsorbent is used in filters for the Chemical Demiliterization program. The conditions were appropriate for a post treatment stack gas filter. Results indicate that high capacity and long filtration times are achievable under moderate humidity conditions up to 180 degrees F.
  4. The ADIFOR 2.0 system for the automatic differentiation of Fortran 77 programs

    Automatic Differentiation is a technique for augmenting computer programs with statements for the computation of derivatives based on the chain rule of differential calculus. The ADIFOR 2.0 system provides automatic differentiation of Fortran 77 programs for first-order derivatives. The ADIFOR 2.0 system consists of three main components: the ADIFOR 2.0 preprocessor, the ADIntrinsics Fortran 77 exception-handling system, and the SparsLinC library. The combination of these tools provides the ability to deal with arbitrary Fortran 77 syntax, to handle codes containing single- and double-precision real- or complex-valued data, to fully support and easily customize the translation of Fortran 77 intrinsics, andmore » to transparently exploit sparsity in derivative computations. ADIFOR 2.0 has been successfully applied to a 60,000-line code, which is believed to be a new record in automatic differentiation.« less
  5. Experiences with the application of the ADIC automatic differentiation tool for to the CSCMDO 3-D volume grid generation code

    Automatic differentiation (AD) is a methodology for developing reliable sensitivity-enhanced versions of arbitrary computer programs with little human effort. It can vastly accelerate the use of advanced simulation codes in multidisciplinary design optimization, since the time for generating and verifying derivative codes is greatly reduced. In this paper, we report on the application of the recently developed ADIC automatic differentiation tool for ANSI C programs to the CSCMDO multiblock three-dimensional volume grid generator. The ADIC-generated code can easily be interfaced with Fortran derivative codes generated with the ADIFOR AD tool FORTRAN 77 programs, thus providing efficient sensitivity-enhancement techniques for multilanguage,more » multidiscipline problems.« less
  6. Evaluating the environmental value of various coal switching/cleaning & blending options as an emission reduction technology using the Clean Air Technology (CAT) workstation

    Reducing SO{sub 2} and/or NO{sub X} emissions for fossil power plants, as mandated by the U.S. Environmental Protection Agency (EPA) under Title I and Title IV of the 1990 Clean Air Act Amendments (CAAA), may be accomplished by a number of selected technologies. However, the decision on how to most cost -effectively reach the new emission limits involves extensive analysis of the utility system. The Clean Air Technology (CAT) Workstation, co-funded by Sargent & Lundy and the Electric Power Research Institute (EPRI), was developed as a tool designed to aid utilities in the analysis of system-wide air emission reduction controlmore » strategies and cost optimization. The NO{sub X} enhancement to the Workstation and its capabilities were described in a previous paper, given at the April 25-27, 1994 American Power Conference. This paper will address use of CAT to evaluate a variety of fuel options and fuel blends as a means of meeting emission limits. The CAT Workstation enables the user to develop least-cost emission reduction strategies through user-supplied performance and cost data for each emission reduction technology or to quickly develop the input data using EPRI technology support programs.« less
  7. ADIFOR 2.0 user`s guide (Revision B)

    Automatic differentiation is a technique for computing the derivatives of functions described by computer programs. ADIFOR implements automatic differentiation by transforming a collection of FORTRAN 77 subroutines that compute a function {line_integral} into new FORTRAN 77 suborutines that compute the derivaties of the outputs of {line_integral} with respect to a specified set of inputs of {line_integral}. This guide describes step by step how to use version 2.0 of ADIFOR to generate derivative code. Familiarity with UNIX and FORTRAN 77 is assumed.
  8. Enzymological and mutational analysis of a complex primary hyperoxaluria type I phenotype involving alanine: Glyoxylate aminotransferase peroxisome-to-mitochondrion mistargeting and intraperoxisomal aggregation

    Primary hyperoxaluri type 1 (PH1) is a rare autosomal recessive disease caused by a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). Three unrelated PH1 patients, who possess a novel complex phenotype, are described. At the enzymological level, this phenotype is characterized by a complete, or nearly complete, absence of AGT catalytic activity and reduced AGT immunoreactivity. Unlike normal individuals in whom the AGT is confined to the peroxisomal matrix, the immunoreactive AGT in these three patients was distributed approximately equally between the peroxisomes and mitochondria. The peroxisomal AGT appeared to be aggregated into amorphous core-like structures in whichmore » no other peroxisomal enzymes could be identified. Mutational analysis of the AGT gene showed that two of the three patients were compound heterozygotes for two previously unrecognized point mutations which caused Gly41[yields]Arg and Phe152[yields]Iso amino acid substitutions. The third patient was shown to be a compound heterozygote for the Gly41[yields]Arg mutation and a previously recognized Gly170[yields]Arg mutation. All three patients were homozygous for the Pro11[yields]Leu polymorphism that had been found previously with a high allelic frequency in normal populations. It is suggested the the Phe152[yields]Iso and Gly170[yields]Arg substitutions, which are only eighteen residues apart and located in the same highly conserved internal region of 58 amino acids, might be involved in the inhibition of peroxisomal targeting and/or import of AGT and, in combination with the Pro11[yields]Leu polymorphism, be responsible for its aberrant mitochondrial compartmentalization. On the other hand, the Gly41[yields]Arg substitution, either in combination with the Pro11[yields]Leu polymorphism or by itself, is predicted to be responsible for the intraperoxisomal aggregation of the AGT protein. 50 refs., 8 figs., 4 tabs.« less
  9. Measurements of reduced corkscrew motion on the ETA-II linear induction accelerator

    The ETA-II linear induction accelerator is used to drive a microwave free electron laser (FEL). Corkscrew motion, which previously limited performance, has been reduced by: (1) an improved pulse distribution system which reduces energy sweep, (2) improved magnetic alignment achieved with a stretched wire alignment technique (SWAT) and (3) a unique magnetic tuning algorithm. Experiments have been carried out on a 20-cell version of ETA-II operating at 1500 A and 2.7 MeV. The measured transverse beam motion is less than 0.5 mm for 40 ns of the pulse, an improvement of a factor of 2 to 3 over previous results.more » Details of the computerized tuning procedure, estimates of the corkscrew phase, and relevance of these results to future FEL experiments are presented. 11 refs.« less
  10. Measurements of reduced corkscrew motion on the ETA-II linear induction accelerator

    The ETA-II linear induction accelerator is used to drive a microwave free electron laser (FEL). Corkscrew motion, which previously limited performance, has been reduced by: (1) an improved pulse distribution system which reduces energy sweep, (2) improved magnetic alignment achieved with a stretched wire alignment technique (SWAT) and (3) a unique magnetic tuning algorithm. Experiments have been carried out on a 20-cell version of ETA-II operating at 1500 A and 2.7 MeV. The measured transverse beam motion is less than 0.5 mm for 40 ns of the pulse, an improvement of a factor of 2 to 3 over previous results.more » Details of the computerized tuning procedure, estimates of the corkscrew phase, and relevance of these results to future FEL experiments are presented. 11 refs.« less
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