bluuebunny/crossref_metadata_2025 huggingface dataset:
Ground Water Model Calibration Using Pilot Points and Regularization
Authors: Doherty John
Published: December 2005

Use of nonlinear parameter estimation techniques is now commonplace in ground water model calibration. However, there is still ample room for further development of these techniques in order to enable them to extract more information from calibration datasets, to more thoroughly explore the uncertainty associated with model predictions, and to make them easier to implement in various modeling contexts.

This paper describes the use of “pilot points” as a methodology for spatial hydraulic property characterization. When used in conjunction with nonlinear parameter estimation software that incorporates advanced regularization functionality (such as PEST), use of pilot points can add a great deal of flexibility to the calibration process at the same time as it makes this process easier to implement. Pilot points can be used either as a substitute for zones of piecewise parameter uniformity, or in conjunction with such zones. In either case, they allow the disposition of areas of high and low hydraulic property value to be inferred through the calibration process, without the need for the modeler to guess the geometry of such areas prior to estimating the parameters that pertain to them.

Pilot points and regularization can also be used as an adjunct to geostatistically based stochastic parameterization methods. Using the techniques described herein, a series of hydraulic property fields can be generated, all of which recognize the stochastic characterization of an area at the same time that they satisfy the constraints imposed on hydraulic property values by the need to ensure that model outputs match field measurements. Model predictions can then be made using all of these fields as a mechanism for exploring predictive uncertainty.
Review of the Integrated Groundwater and Surface‐Water Model (IGSM)
Authors: LaBolle Eric M. , Ahmed Ayman A. , Fogg Graham E.
Published: December 2005

Development of the finite‐element‐based Integrated Groundwater and Surface‐Water Model (IGSM) began in the 1970s. Its popularity grew in the early 1990s with its application to California's Central Valley Groundwater Surface‐Water Model in support of the Central Valley Project Improvement Act. Since that time, IGSM has been applied by federal, state, and local agencies to model a number of major basins in California. Our review of the recently released version 5.0 of IGSM reveals a solution methodology that deviates from established solution techniques, potentially compromising its reliability under many circumstances. One difficulty occurs because of the semi‐explicit time discretization used. Combined with the fixed monthly time step of IGSM, this approach can prevent applications from accurately converging when using parameter values typically found in nature. Additionally, IGSM fails to properly couple and simultaneously solve ground water and surface water models with appropriate mass balance and head convergence under the reasonable conditions considered herein. As a result, IGSM‐predicted streamflow is error prone, and errors could exceed 100%. IGSM does not inform the user that there may be a convergence problem with the solution, but instead generally reports good mass balance. Although our review touches on only a few aspects of the code, which exceeds 17,000 lines, our experience is that similar problems arise in other parts of IGSM. Review and examples demonstrate the potential consequences of using the solution methods in IGSM for the prediction, planning, and management of water resources, and provide perspective on the roles of standards and code validation in ground water modeling.
Fast Transport Simulation with an Adaptive Grid Refinement
Authors: Haefner Frieder , Boy Siegrun
Published: December 2005

One of the main difficulties in transport modeling and calibration is the extraordinarily long computing times necessary for simulation runs. Improved execution time is a prerequisite for calibration in transport modeling. In this paper we investigate the problem of code acceleration using an adaptive grid refinement, neglecting subdomains, and devising a method by which the Courant condition can be ignored while maintaining accurate solutions. Grid refinement is based on dividing selected cells into regular subcells and including the balance equations of subcells in the equation system. The connection of coarse and refined cells satisfies the mass balance with an interpolation scheme that is implicitly included in the equation system. The refined subdomain can move with the average transport velocity of the subdomain. Very small time steps are required on a fine or a refined grid, because of the combined effect of the Courant and Peclet conditions. Therefore, we have developed a special upwind technique in small grid cells with high velocities (velocity suppression). We have neglected grid subdomains with very small concentration gradients (zero suppression). The resulting software, MODCALIF, is a three‐dimensional, modularly constructed FORTRAN code. For convenience, the package names used by the well‐known MODFLOW and MT3D computer programs are adopted, and the same input file structure and format is used, but the program presented here is separate and independent. Also, MODCALIF includes algorithms for variable density modeling and model calibration. The method is tested by comparison with an analytical solution, and illustrated by means of a two‐dimensional theoretical example and three‐dimensional simulations of the variable‐density Cape Cod and SALTPOOL experiments. Crossing from fine to coarse grid produces numerical dispersion when the whole subdomain of interest is refined; however, we show that accurate solutions can be obtained using a fraction of the execution time required by uniformly fine‐grid solutions.
Analytical Model for Computing Residence Times Near a Pumping Well
Authors: Simpson Matthew J. , Clement T. Prabhakar , Yeomans Francis E.
Published: December 2005

An analytical solution for calculating the residence time of fluid flowing toward a pumping well in an unconfined aquifer has been developed. The analytical solution was derived based on a radial, steady‐state, Dupuit‐Forchheimer flow model. The resulting integral expression involved computing the imaginary error function, for which a simple series expansion is proposed. The validity of the analytical expression is demonstrated by testing its results against numerical results for an example problem. The analytical solution compared favorably with the numerical approximation.
Estimating Ground Water Discharge by Hydrograph Separation
Authors: Hannula Steven R. , Esposito Kenneth J. , Chermak John A. , Runnells Donald D. , Keith David C. , Hall Larry E.
Published: December 2005

Iron Mountain is located in the West Shasta Mining District in California. An investigation of the generation of acid rock drainage and metals loading to Boulder Creek at Iron Mountain was conducted. As part of that investigation, a hydrograph separation technique was used to determine the contribution of ground water to total flow in Boulder Creek.

During high‐flow storm events in the winter months, peak flow in Boulder Creek can exceed 22.7 m3/sec, and comprises surface runoff, interflow, and ground water discharge. A hydrograph separation technique was used to estimate ground water discharge into Boulder Creek during high‐flow conditions. Total ground water discharge to the creek approaches 0.31 m3/sec during the high‐flow season. The hydrograph separation technique combined with an extensive field data set provided reasonable estimates of ground water discharge. These estimates are useful for other investigations, such as determining a corresponding metals load from the metal‐rich ground water found at Iron Mountain and thus contributing to remedial alternatives.
Revisit of Well Function Approximation and An Easy Graphical Curve Matching Technique for Theis' Solution
Authors: Giao Pham Huy
Published: December 2005

Some approximations of Theis' solution are reviewed and compared with the numerical evaluation of the exponential integral by means of a short FORTRAN code. A graphical technique of Theis' curve matching is proposed to make this procedure as easy as plotting a graph.
The Journey from Safe Yield to Sustainability
Authors: Alley William M. , Leake Stanley A.
Published: December 2005

Safe‐yield concepts historically focused attention on the economic and legal aspects of ground water development. Sustainability concerns have brought environmental aspects more to the forefront and have resulted in a more integrated outlook. Water resources sustainability is not a purely scientific concept, but rather a perspective that can frame scientific analysis. The evolving concept of sustainability presents a challenge to hydrologists to translate complex, and sometimes vague, socioeconomic and political questions into technical questions that can be quantified systematically. Hydrologists can contribute to sustainable water resources management by presenting the longer‐term implications of ground water development as an integral part of their analyses.
Influence of Calibration Methodology on Ground Water Flow Predictions
Authors: Saiers James E. , Genereux David P. , Bolster Carl H.
Published: December 2005

We constructed a numerical model of transient ground water flow and solute transport for a portion of the Biscayne Aquifer in Florida, and calibrated the model with three different combinations of data from a 193‐day period: head (h) data alone, data on h and ground water discharge to a canal (q), and data on h, q, and ground water chloride concentration (C). We used each of the three calibrated models to predict h and q during a 182‐day test period separate from the calibration period. All three calibrated models predicted h equally well during the test period (r= 0.95, where r= 1 indicates perfect agreement between measured and simulated values), though the model calibrated on h alone had significantly different parameter values than the other two models. Predictions of q during the test period depended on calibration methodology; models calibrated with multiple targets simulated q more accurately than the model calibrated on h alone (r = 0.79 compared to r = 0.49). Based on the results of these simulations, we conclude: (1) Post‐calibration prediction is important in assessing the value of different data types in automated calibration; (2) inverse‐solution uniqueness is not a requirement for accurate h predictions; (3) relatively simple models can predict with reasonable accuracy transient ground water flow in a complex aquifer, and parameters governing this prediction can be estimated by nonlinear regression methods that incorporate both h and q data; (4) addition of C data to the calibration did not improve model predictive capacity because the information in the C data was similar to that in the q data, from the perspective of model calibration (the subsurface chemical signal in question was controlled mainly by seepage of high‐chloride canal water into the low‐chloride ground water system).
South China Karst Aquifer Storm‐Scale Hydrochemistry
Authors: Liu Zaihua , Groves Chris , Yuan Daoxian , Meiman Joe
Published: December 2005

The peak cluster and peak forest karst regions of Southeast Asia form one of the earth's most extensive karst regions. Although there exists a rich, descriptive tradition of geomorphic work performed there, little quantitative study has been made of carbonate hydrochemistry and related aquifer/landscape behavior and evolution. In this paper, high‐resolution measurements of ground water carbonate chemistry and flow were made and analyzed at two adjacent locations within the subtropical peak cluster karst of the Guilin Karst Experimental Site in Guangxi Province, China. While waters from a large, perennial spring represent the exit for the 2 km2 catchment's conduit flow, a nearby well (within 5 m) measures water in the conduit‐adjacent, fractured media. Results indicate that within peak cluster karst aquifer flow systems, spatially heterogeneous flow conditions can exist with respect to timing, magnitude, and, in some cases, direction of responses, as different controls can operate in the different flow system components. Storm‐scale chemical responses are controlled by dilution from rapid infiltration of rain water, CO2 gas sources and sinks, and water‐carbonate rock interactions. At this particular location, there is also an influence from high pH recharge, apparently buffered by atmospheric limestone dust. An example of the varying controls on storm‐scale responses within the flow system is that within the fractured medium, variations in the ground water calcite saturation index, a key parameter influencing rates of aquifer/landscape evolution, are small and controlled by CO2 gas, while in the conduit they are more significant and dominated instead by dilution with rain water.
Numerical Implementation of a Backward Probabilistic Model of Ground Water Contamination
Authors: Neupauer Roseanna M. , Wilson John L.
Published: December 2005

Backward location and travel time probabilities can be used to characterize known and unknown sources or prior positions of ground water contamination. Backward location probability describes the position of the observed contamination at some time in the past; backward travel time probability describes the amount of time prior to observation that the contamination was released from its source or was at a particular upgradient location. The governing equation for backward probabilities is the adjoint of the governing equation for contaminant transport, but with new load terms. Numerical codes that have been written to solve the forward equations of contaminant transport, e.g., the advection‐dispersion equation, can also be used to solve the adjoint equation for location and travel time probabilities; however, the interpretation of the results is different and some new approximations must be made for the load terms. We present the governing equations for backward location and travel time probabilities, and provide appropriate numerical approximations for these load terms using the cell‐centered finite difference method, one of the most popular numerical methods in ground water hydrology. We discuss some additional numerical considerations for the backward model including boundary conditions, reversal of the flow field, and interpretation of the results. We illustrate the implementation of the backward probability model using hypothetical examples in one‐ and two‐dimensional domains. We also present a three‐dimensional application of a pump‐and‐treat remediation capture zone delineation at the Massachusetts Military Reservation. The illustrations are performed using MODFLOW—96 for flow simulations and MT3DMS for transport simulations.
Effects of Rate‐Limited Mass Transfer on Water Sampling with Partially Penetrating Wells
Authors: Cosier Douglas J.
Published: December 2005

Nonequilibrium concentration type curves are numerically developed and sensitivity analyses are performed to examine the relationships between effluent concentrations in partially penetrating monitoring/extraction wells, the vertical plume shape, and the mass transfer characteristics of the aquifer. The governing two‐dimensional, axisym‐metric nonequilibrium solute transport equation is solved in three stages using an operator‐splitting approach. In the first two stages, the advection and dispersion terms are solved with the Eulerian‐Lagrangian method, based on the backward method of characteristics for advection and the standard implicit Galerkin finite element method for dispersion. In the third step, the first‐order, immobile‐mobile domain mass transfer term is computed analytically for both two‐site and lognormally distributed, multirate models. Effluent concentration variations with time and contour plots of the pore water concentration distribution in the aquifer are compared for a wide range of field‐ and laboratory ‐measured mass transfer rates, various plume shapes, and relevant physical/chemical parameter values, including pumping rate, vertical anisotropy ratio, retardation factor, and porosity. The simulation results show that rate‐limited mass transfer can have a significant impact on sample and aquifer pore water concentrations during three‐dimensional transport to a partially penetrating well. An alternative dimensionless form of the nonequilibrium solute transport equation is derived to illustrate the key parameter groupings that quantify rate‐limited sorption effects and show the relative importance of individual parameters. A hypothetical field application example demonstrates the fitting of dimensional type curves to discrete‐interval sampling data in order to evaluate the mass transfer characteristics of an aquifer and shows how type curve superposition can be used to model complex plume shapes.
Push‐Pull Tests for Assessing In Situ Aerobic Cometabolism
Authors: Kim Young , Istok Jonathan D. , Semprini Lewis
Published: December 2005

Three types of single‐well push‐pull tests were developed for use in assessing the feasibility of in situ aerobic cometabolism of chlorinated aliphatic hydrocarbons (CAHs). These included transport tests, biostimulation tests, and activity tests. Transport tests are conducted to evaluate the mobility of solutes used in subsequent tests. These included bromide or chloride (conservative tracers), propane (growth substrate), ethylene, propylene (CAH surrogates), dissolved oxygen (electron acceptor), and nitrate (a minor nutrient). Tests were conducted at an experimental wellfield of Oregon State University. At this site, extraction phase breakthrough curves for all solutes were similar, indicating apparent conservative transport of the dissolved gases and nitrate prior to biostimulation. Biostimulation tests were conducted to stimulate propane‐utilizing activity of indigenous microorganisms and consisted of sequential injections of site ground water containing dissolved propane and oxygen. Biostimulation was detected by the increase in rates of propane and oxygen utilization after each injection. Activity tests were conducted to quantify rates of substrate utilization and to confirm that CAH‐transforming activity had likely been stimulated. In particular, the transformation of injected CAH surrogates ethylene and propylene to the cometabolic byproducts ethylene oxide and propylene oxide provided evidence that activity of the monooxygenase enzyme system, responsible for aerobic cometabolic transformations of CAHs, had likely also been stimulated. Estimated zero‐order transformation rates decreased in the order propane > ethylene > propylene. The series of push‐pull tests developed and field tested in this study should prove useful for conducting rapid, low‐cost feasibility assessments for in situ aerobic cometabolism of CAHs.
Strontium Isotopic Identification of Water‐Rock Interaction and Ground Water Mixing
Authors: Frost Carol D. , Toner Rachel N.
Published: December 2005

87Sr/86Sr ratios of ground waters in the Bighorn and Laramie basins' carbonate and carbonate‐cemented aquifer systems, Wyoming, United States, reflect the distinctive strontium isotope signatures of the minerals in their respective aquifers. Well water samples from the Madison Aquifer (Bighorn Basin) have strontium isotopic ratios that match their carbonate host rocks. Casper Aquifer ground waters (Laramie Basin) have strontium isotopic ratios that differ from the bulk host rock; however, stepwise leaching of Casper Sandstone indicates that most of the strontium in Casper Aquifer ground waters is acquired from preferential dissolution of carbonate cement. Strontium isotope data from both Bighorn and Laramie basins, along with dye tracing experiments in the Bighorn Basin and tritium data from the Laramie Basin, suggest that waters in carbonate or carbonate‐cemented aquifers acquire their strontium isotope composition very quickly—on the order of decades.

Strontium isotopes were also used successfully to verify previously identified mixed Redbeds‐Casper ground waters in the Laramie Basin. The strontium isotopic compositions of ground waters near Precambrian outcrops also suggest previously unrecognized mixing between Casper and Precambrian aquifers. These results demonstrate the utility of strontium isotopic ratio data in identifying ground water sources and aquifer interactions.
Identification of thesyr-sypBox in the Promoter Regions of Genes Dedicated to Syringomycin and Syringopeptin Production byPseudomonas syringaepv. syringae B301D
Authors: Wang Nian , Lu Shi-En , Yang Qingwu , Sze Sing-Hoi , Gross Dennis C.
Published: December 2005

The phytotoxins syringopeptin and syringomycin are synthesized by nonribosomal peptide synthetases which are encoded by the syringomycin (syr) and syringopeptin (syp) genomic island ofPseudomonas syringaepv. syringae. Previous studies demonstrated that expression of thesyr-sypgenes was controlled by thesalA-syrFregulatory pathway, which in turn was induced by plant signal molecules. In this study, the 132-kbsyr-sypgenomic island was found to be organized into five polycistronic operons along with eight individual genes based on reverse transcriptional PCR and bioinformatic analysis. The transcriptional start sites of thesalAgene and operons III and IV were located 63, 75, and 104 bp upstream of the start codons ofsalA,syrP, andsyrB1, respectively, using primer extension analysis. The predicted −10/−35 promoter region of operon IV was confirmed based on deletion and site-directed mutagenesis analyses of thesyrB1::uidAreporter with β-glucuronidase assays. A 20-bp conserved sequence (TGtCccgN6cggGaCA, termed thesyr-sypbox) with dyad symmetry around the −35 region was identified via computer analysis for thesyr-sypgenes/operons responsible for biosynthesis and secretion of syringomycin and syringopeptin. Expression of thesyrB1::uidAfusion was decreased 59% when 6 bp was deleted from the 5′ end of thesyr-sypbox in the promoter region of operon IV. These results demonstrate that the conserved promoter sequences of thesyr-sypgenes contribute to the coregulation of syringomycin and syringopeptin production.
Evidence for Clonal Evolution among Highly Polymorphic Genes in Methicillin-Resistant
Staphylococcus aureus
Authors: Kuhn G. , Francioli P. , Blanc D. S.
Published: December 2005

The evolution of
Staphylococcus aureus
has been described as predominantly clonal, based on evidence from seven housekeeping genes. We aimed to test if this was also true for more polymorphic genes. In a collection of 60 isolates including major European epidemic methicillin-resistant
S. aureus
(MRSA) and sporadic MRSA strains, we compared the partial gene sequences of seven housekeeping genes (
arcC
,
aroE
,
glpF
,
gmk
,
pta
,
tpi
, and
yqiL
), six core adhesion genes (present in all strains) (
clfA
,
clfB
,
fnbA
,
map
,
sdrC
, and
spa
), and four accessory adhesion genes (not present in all strains) (
ebpS
,
fnbB
,
sdrD
, and
sdrE
). Nucleotide diversity of adhesion genes was 2- to 10-fold higher than genes used for multilocus sequence typing. All genes showed evidence for purifying selection with a weakly reduced level among accessory adhesion genes. Among these highly variable genes, there was no evidence for a difference in molecular evolution between epidemic and sporadic strains. Gene trees constructed from concatenated sequences of housekeeping, core adhesion, and accessory adhesion genes were highly congruent, indicating clonality, despite some evidence for homologous exchange. Further evidence for clonality was found with an overall positive correlation of allelic and nucleotidic divergence for both seven housekeeping genes and six core adhesion genes. However, for small allelic differences that fit the demarcations of clonal complexes (CCs) there was no such correlation, suggesting that recombination occurred. Therefore, despite an overall clonal population structure, recombination between related isolates within CCs might have contributed to
S. aureus
evolution.
The
Pseudomonas aeruginosa
Lipid A Deacylase: Selection for Expression and Loss within the Cystic Fibrosis Airway
Authors: Ernst Robert K. , Adams Kristin N. , Moskowitz Samuel M. , Kraig Gretchen M. , Kawasaki Kiyoshi , Stead Christopher M. , Trent M. Stephen , Miller Samuel I.
Published: December 2005

Lipopolysaccharide (LPS) is the major surface component of gram-negative bacteria, and a component of LPS, lipid A, is recognized by the innate immune system through the Toll-like receptor 4/MD-2 complex.
Pseudomonas aeruginosa
, an environmental gram-negative bacterium that opportunistically infects the respiratory tracts of patients with cystic fibrosis (CF), can synthesize various structures of lipid A. Lipid A from
P. aeruginosa
strains isolated from infants with CF has a specific structure that includes the removal of the 3 position 3-OH C10 fatty acid. Here we demonstrate increased expression of the
P. aeruginosa
lipid A 3-
O
-deacylase (PagL) in isolates from CF infants compared to that in environmental isolates. PagL activity was increased in environmental isolates by growth in medium limited for magnesium and decreased by growth at low temperature in laboratory-adapted strains of
P. aeruginosa. P. aeruginosa
PagL was shown to be an outer membrane protein by isopycnic density gradient centrifugation. Heterologous expression of
P. aeruginosa pagL
in
Salmonella enterica
serovar Typhimurium and
Escherichia coli
resulted in removal of the 3-OH C14 fatty acid from lipid A, indicating that
P. aeruginosa
PagL recognizes either 3-OH C10 or 3-OH C14. Finally, deacylated lipid A species were not observed in some clinical
P. aeruginosa
isolates from patients with severe pulmonary disease, suggesting that loss of PagL function can occur during long-term adaptation to the CF airway.
Gene-Specific Random Mutagenesis of
Escherichia coli
In Vivo: Isolation of Temperature-Sensitive Mutations in the Acyl Carrier Protein of Fatty Acid Synthesis
Authors: De Lay Nicholas R. , Cronan John E.
Published: December 2005

Acyl carrier proteins (ACPs) are very small acidic proteins that play a key role in fatty acid and complex lipid synthesis. Moreover, recent data indicate that the acyl carrier protein of
Escherichia coli
has a large protein interaction network that extends beyond lipid synthesis. Despite extensive efforts over many years, no temperature-sensitive mutants with mutations in the structural gene (
acpP
) that encodes ACP have been isolated. We report the isolation of three such mutants by a new approach that utilizes error-prone PCR mutagenesis, overlap extension PCR, and phage λ Red-mediated homologous recombination and that should be generally applicable. These mutants plus other experiments demonstrate that ACP function is essential for the growth of
E. coli
. Each of the mutants was efficiently modified with the phosphopantetheinyl moiety essential for the function of ACP in lipid synthesis, and thus lack of function at the nonpermissive temperature cannot be attributed to a lack of prosthetic group attachment. All of the mutant proteins were largely stable at the nonpermissive temperature except the A68T/N73D mutant protein. Fatty acid synthesis in strains that carried the D38V or A68T/N73D mutations was inhibited upon a shift to the nonpermissive temperature and in the latter case declined to a small percentage of the rate of the wild-type strain.
Solution Structure of a Novel Tryptophan-Rich Peptide with Bidirectional Antimicrobial Activity
Authors: Wei Shu-Yi , Wu Jiun-Ming , Kuo Yen-Ya , Chen Heng-Li , Yip Bak-Sau , Tzeng Shiou-Ru , Cheng Jya-Wei
Published: December 2005

Trp-rich antimicrobial peptides play important roles in the host innate defense mechanisms of many plants, insects, and mammals. A new type of Trp-rich peptide, Ac-KWRRWVRWI-NH2, designated Pac-525, was found to possess improved activity against both gram-positive and -negative bacteria. We have determined that the solution structures of Pac-525 bound to membrane-mimetic sodium dodecyl sulfate (SDS) micelles. The SDS micelle-bound structure of Pac-525 adopts an α-helical segment at residues Trp2, Arg3, and Arg4. The positively charged residues are clustered together to form a hydrophilic patch. The three hydrophobic residues Trp2, Val6, and Ile9 form a hydrophobic core. The surface electrostatic potential map indicates the three tryptophan indole rings are packed against the peptide backbone and form an amphipathic structure. Moreover, the reverse sequence of Pac-525, Ac-IWRVWRRWK-NH2, designated Pac-525rev, also demonstrates similar antimicrobial activity and structure in membrane-mimetic micelles and vesicles. A variety of biophysical and biochemical methods, including circular dichroism, fluorescence spectroscopy, and microcalorimetry, were used to show that Pac-525 interacted strongly with negatively charged phospholipid vesicles and induced efficient dye release from these vesicles, suggesting that the antimicrobial activity of Pac-525 may be due to interactions with bacterial membranes.
RscA, a Member of the MDR1 Family of Transporters, Is Repressed by CovR and Required for Growth ofStreptococcus pyogenesunder Heat Stress
Authors: Dalton Tracy L. , Collins Julie T. , Barnett Timothy C. , Scott June R.
Published: December 2005

The ability ofStreptococcus pyogenes(group A streptococcus [GAS]) to respond to changes in environmental conditions is essential for this gram-positive organism to successfully cause disease in its human host. The two-component system CovRS controls expression of about 15% of the GAS genome either directly or indirectly. In most operons studied, CovR acts as a repressor. We previously linked CovRS to the GAS stress response by showing that the sensor kinase CovS is required to inactivate the response regulator CovR so that GAS can grow under conditions of heat, acid, and salt stress. Here, we sought to identify CovR-repressed genes that are required for growth under stress. To do this, global transcription profiles were analyzed by microarrays following exposure to increased temperature (40°C) and decreased pH (pH 6.0). The CovR regulon in an M type 6 strain of GAS was also examined by global transcriptional analysis. We identified a gene,rscA(regulated bystress andCov), whose transcription was confirmed to be repressed by CovR and activated by heat and acid. RscA is a member of the MDR1 family of ABC transporters, and we found that it is required for growth of GAS at 40°C but not at pH 6.0. Thus, for GAS to grow at 40°C, CovR repression must be alleviated so thatrscAcan be transcribed to allow the production of this potential exporter. Possible explanations for the thermoprotective role of RscA in this pathogen are discussed.
Host Deadenylation-Dependent mRNA Decapping Factors Are Required for a Key Step in Brome Mosaic Virus RNA Replication
Authors: Mas Antonio , Alves-Rodrigues Isabel , Noueiry Amine , Ahlquist Paul , Díez Juana
Published: December 2005

The genomes of positive-strand RNA [(+)RNA] viruses perform two mutually exclusive functions: they act as mRNAs for the translation of viral proteins and as templates for viral replication. A universal key step in the replication of (+)RNA viruses is the coordinated transition of the RNA genome from the cellular translation machinery to the viral replication complex. While host factors are involved in this step, their nature is largely unknown. By using the ability of the higher eukaryotic (+)RNA virus brome mosaic virus (BMV) to replicate in yeast, we previously showed that the host Lsm1p protein is required for efficient recruitment of BMV RNA from translation to replication. Here we show that in addition to Lsm1p, all tested components of the Lsm1p-7p/Pat1p/Dhh1p decapping activator complex, which functions in deadenylation-dependent decapping of cellular mRNAs, are required for BMV RNA recruitment for RNA replication. In contrast, other proteins of the decapping machinery, such as Edc1p and Edc2p from the deadenylation-dependent decapping pathway and Upf1p, Upf2p, and Upf3p from the deadenylation-independent decapping pathway, had no significant effects. The dependence of BMV RNA recruitment on the Lsm1p-7p/Pat1p/Dhh1p complex was linked exclusively to the 3′ noncoding region of the BMV RNA. Collectively, our results suggest that the Lsm1p-7p/Pat1p/Dhh1p complex that transfers cellular mRNAs from translation to degradation might act as a key regulator in the switch from BMV RNA translation to replication.
In Vivo and In Vitro Analysis of Factor Binding Sites in Jaagsiekte Sheep Retrovirus Long Terminal Repeat Enhancer Sequences: Roles of HNF-3, NF-I, and C/EBP for Activity in Lung Epithelial Cells
Authors: McGee-Estrada Kathleen , Fan Hung
Published: December 2005

Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma, a contagious lung cancer of sheep that arises from type II pneumocytes and Clara cells of the lung epithelium. Studies of the tropism of this virus have been hindered by the lack of an efficient system for viral replication in tissue culture. To map regulatory regions important for transcriptional activation, an in vivo footprinting method that couples dimethyl sulfate treatment and ligation-mediated PCR was performed in murine type II pneumocyte-derived MLE-15 cells infected with a chimeric Moloney murine leukemia virus driven by the JSRV enhancers (ΔMo+JS Mo-MuLV). In vivo footprints were found in the JSRV enhancers in two regions previously shown to be important for JSRV long terminal repeat (LTR) activity: a binding site for the lung-specific transcription factor HNF-3β and an E-box element in the distal enhancer adjacent to an NF-κB-like binding site. In addition, in vivo footprints were detected in two downstream motifs likely to bind C/EBP and NF-I. Mutational analysis of a JSRV LTR reporter construct (pJS
21
luc) revealed that the C/EBP binding site is critical for LTR activity, while the putative NF-I binding element is less important; elimination of these sites resulted in 70% and 40% drops in LTR activity, respectively. Electrophoretic mobility shift assays using nuclear extracts from MLE-15 murine Clara cell-derived mtCC1-2 cells with probes corresponding to the NF-I or C/EBP sites revealed several complexes. Antiserum directed against NF-IA, C/EBPα, or C/EBPβ supershifted the corresponding protein-DNA complexes, indicating that these isoforms, which are also important for the expression of several cellular lung-specific genes, may be important for JSRV expression in lung epithelial cells.
Resistance of Neonatal Mice to Scrapie Is Associated with Inefficient Infection of the Immature Spleen
Authors: Ierna Michelle , Farquhar Christine F. , Outram George W. , Bruce Moira E.
Published: December 2005

Previous studies demonstrated that neonatal mice up to about a week old are less susceptible than adult mice to infection by intraperitoneal inoculation with mouse-passaged scrapie. In peripherally inoculated adult mice, scrapie replicates in lymphoid tissues such as the spleen before invading the central nervous system. Here, we investigated scrapie susceptibility in neonatal mice in more detail, concentrating on spleen involvement. First, we demonstrated that neonatal mice are about 10 times less susceptible than adults to intraperitoneal scrapie inoculation. Then we injected mice intraperitoneally with a scrapie dose that produced disease in all mice inoculated at 10 days or older but in only about a third of neonatally inoculated mice. In this experiment, spleens collected 70 days after scrapie injection of mice 10 days old or older almost all contained pathological prion protein, PrPSc, and those that were bioassayed all contained high infectivity levels. In contrast, at this early stage, only two of six spleens from neonatally inoculated mice had detectable, low infectivity levels; no PrPScwas detected, even in the two spleens. Therefore, neonatal mice have an impaired ability to replicate scrapie in their spleens, suggesting that replication sites are absent or sparse at birth but mature within 10 days. The increase in susceptibility with age correlated with the first immunocytochemical detection of the normal cellular form of prion protein, PrPc, on maturing follicular dendritic cell networks. As lymphoid tissues are more mature at birth in sheep, cattle, and humans than in mice, our results suggest that in utero infection with scrapie-like agents is theoretically possible in these species.
Frequency and Dynamics of Recombination within Different Species of Human Enteroviruses
Authors: Simmonds Peter , Welch Jon
Published: December 2005

Enteroviruses are members of the family
Picornaviridae
that cause widespread infections in human and other mammalian populations. Enteroviruses are genetically and antigenically highly variable, and recombination within and between serotypes contributes to their genetic diversity. To investigate the dynamics of the recombination process, sequence phylogenies between three regions of the genome (VP4, VP1, and 3Dpol) were compared among species A and B enterovirus variants detected in a human population-based survey in Scotland between 2000 and 2001, along with contemporary virus isolates collected in the same geographical region. This analysis used novel bioinformatic methods to quantify phylogenetic compatibility and correlations with serotype assignments of evolutionary trees constructed for different regions of the enterovirus genome. Species B enteroviruses showed much more frequent, time-correlated recombination events than those found for species A, despite the equivalence in population sampling, concordant with a linkage analysis of previously characterized enterovirus sequences obtained over longer collection periods. An analysis of recombination among complete genome sequences by computation of a phylogenetic compatibility matrix (PCM) demonstrated sharply defined boundaries between the VP2/VP3/VP1 block and sequences to either side in phylogenetic compatibility. The PCM also revealed equivalent or frequently greater degrees of incompatibility between different parts within the nonstructural region (2A-3D), indicating the occurrence of extensive recombination events in the past evolution of this part of the genome. Together, these findings provide new insights into the dynamics of species A and B enterovirus recombination and evolution and into the contribution of structured sampling to documenting reservoirs, emergence, and spread of novel recombinant forms in human populations.
Crimean-Congo Hemorrhagic Fever Virus Glycoprotein Precursor Is Cleaved by Furin-Like and SKI-1 Proteases To Generate a Novel 38-Kilodalton Glycoprotein
Authors: Sanchez Angela J. , Vincent Martin J. , Erickson Bobbie R. , Nichol Stuart T.
Published: December 2005

Crimean-Congo hemorrhagic fever virus (genusNairovirus, familyBunyaviridae) genome M segment encodes an unusually large (in comparison to members of other genera) polyprotein (1,684 amino acids in length) containing the two major structural glycoproteins, Gn and Gc, that are posttranslationally processed from precursors PreGn and PreGc by SKI-1 and SKI-1-like proteases, respectively. The characteristics of the N-terminal 519 amino acids located upstream of the mature Gn are unknown. A highly conserved furin/proprotein convertase (PC) cleavage site motif (RSKR247) is located between the variable N-terminal region that is predicted to have mucin-like properties and the rest of PreGn. Mutational analysis of the RSKR247motif and use of a specific furin/PC inhibitor and brefeldin A demonstrate that furin/PC cleavage occurs at the RSKR247motif of PreGn as the protein transits thetransGolgi network and generates a novel glycoprotein designated GP38. Immunoprecipitation analysis identified two additional proteins, GP85 and GP160, which contain both mucin and GP38 domain regions, and whose generation does not involve furin/PC cleavage. Consistent with glycosylation predictions, heavy O-linked glycosylation and moderate levels of N-glycans were detected in the GP85 and GP160 proteins, both of which contain the mucin domain. GP38, GP85, and GP160 are likely soluble proteins based on the lack of predicted transmembrane domains, their detection in virus-infected cell supernatants, and the apparent absence from virions. Analogy with soluble glycoproteins and mucin-like proteins encoded by other hemorrhagic fever-associated RNA viruses suggests these proteins could play an important role in viral pathogenesis.
Functional Domains of Murine Cytomegalovirus Nuclear Egress Protein M53/p38
Authors: Lötzerich Mark , Ruzsics Zsolt , Koszinowski Ulrich H.
Published: December 2005

Two conserved herpes simplex virus 1 proteins, UL31 and UL34, form a complex at the inner nuclear membrane which governs primary envelopment and nuclear egress of the herpesvirus nucleocapsids. In mouse
cytomegalovirus, a member of the betaherpesvirus subfamily, the homologous proteins M53/p38 and M50/p35 form the nuclear egress complex (NEC). Since the interaction of these proteins is essential for
functionality, the definition of the mutual binding sites is a prerequisite for further analysis. Using a comprehensive random mutagenesis procedure, we have mapped the M53/p38 binding site of M50/p35 (A. Bubeck, M. Wagner, Z. Ruzsics, M. Lötzerich, M. Iglesias, I. R. Singh, and U. H. Koszinowski, J. Virol.
78:
8026-8035). Here we describe a corresponding analysis for the UL31 homolog M53/p38. A total of 72 individual mutants were reinserted into the genome to test the complementation of the lethal M53 null phenotype. The mutants were also studied for colocalization and for coprecipitation with M50/p35. The analysis revealed that the nonconserved N-terminal one-third of M53/p38 provides the nuclear localization signal as an essential function. The collective results for many mutants localized the binding site for
M50/p35 to amino acids (aa) 112 to 137. No single aa exchange for alanine could destroy NEC formation, but virus attenuation revealed a major role for aa K128, Y129, and L130. The lethal phenotype of several
insertion and stop mutants indicated the functional importance of the C terminus of the
protein.
Diabetes in African Americans
Authors: Marshall M C
Published: December 2005

African Americans have a high risk for type 2 diabetes. Genetic traits, the prevalence of obesity, and insulin resistance all contribute to the risk of diabetes in the African American community. African Americans have a high rate of diabetic complications, because of poor glycaemic control and racial disparities in health care in the USA. African Americans with diabetes may have an atypical presentation that simulates type 1 diabetes, but then their subsequent clinical course is typical of type 2 diabetes. Culturally sensitive strategies, structured disease management protocols, and the assistance of nurses, diabetic educators, and other health care professionals are effective in improving the outcome of diabetes in the African American community.
Unexpected development of artistic talents
Authors: Gordon N
Published: December 2005

The development of exceptional and unexpected artistic skills at any age must be a matter of curiosity. This can occur among young children with severe learning difficulties, especially if they are autistic. Some examples of these so called idiot-savants are given, and the way in which their brains may function. It is also true that elderly people who suffer from frontotemporal dementia can find that they are able to express themselves in remarkable art forms. This can occur in other types of dementia, but then more often it is the changes that result in the paintings of established artists, for example in the paintings of de Kooning. Possible links between these two phenomenon are discussed, and it is suggested that in both instances it may be that if the brain is relieved of a number of functions it can concentrate on the remaining ones. Ways in which this may operate in both groups are reviewed.
EOQ MODEL FOR TIME-DEPENDENT DETERIORATION RATE WITH A TEMPORARY PRICE DISCOUNT
Authors: SHAH BHAVIN J. , SHAH NITA H. , SHAH Y. K.
Published: December 2005

Deterioration is defined as decay, damage, spoilage, evaporation, obsolescence, pilferage, and loss of utility or loss of marginal value of a commodity that reduces usefulness from original ones. Blood, fish, fruits and vegetables, alcohol, gasoline, radioactive chemicals, medicines, etc., lose their utility with respect to time. In this case, a discount price policy is implemented by the suppliers of these products to promote sales. In this study, a mathematical model is developed for an inventory system that considers a temporary price discount when commodities in an inventory system are subject to deterioration with respect to time. Our goal in this article is to maximize the difference between two costs (gain) — taking advantage of price discount by ordering a large quantity, which in turn increases inventory holding cost as well deterioration cost and by not ordering a large quantity at a discounted price. An attempt is made to find bounds on the beneficial discount rate. The model is supported with a numerical example.
DETERMINATION OF EOQ OF MULTI-ITEM INVENTORY PROBLEMS THROUGH NONLINEAR GOAL PROGRAMMING WITH PENALTY FUNCTION
Authors: PANDA S. , BANERJEE K. , BASU M.
Published: December 2005

This paper proposes a nonlinear goal programming technique for obtaining economic order quantity of multi-item inventory problems. In the decision-making context, penalty functions are incorporated in the goal programming formulation. The proposed technique has been demonstrated via a case study.
WAVELET DEFORMATION ANALYSIS FOR SPHERICAL BODIES
Authors: FREEDEN W. , MICHEL V.
Published: December 2005

In this paper, we introduce a multiscale technique for the analysis of deformation phenomena of the Earth. Classically, the basis functions under use are globally defined and show polynomial character. In consequence, only a global analysis of deformations is possible such that, for example, the water load of an artificial reservoir is hardly to model in that way. Up till now, the alternative to realize a local analysis can only be established by assuming the investigated region to be flat.

In what follows, we propose a local analysis based on tools (Navier scaling functions and wavelets) taking the (spherical) surface of the Earth into account. Our approach, in particular, enables us to perform a zooming-in procedure. In fact, the concept of Navier wavelets is formulated in such a way that subregions with larger or smaller data density can accordingly be modelled with a higher or lower resolution of the model, respectively.
UTILISATION OF SUSTAINABILITY INDICATORS AND IMPACT THROUGH POLICY LEARNING IN THE MALAYSIAN POLICY PROCESSES
Authors: HEZRI ADNAN A.
Published: December 2005

It is axiomatic that indicator systems are indispensable in informing the societal transition toward sustainability. However, our understanding of how sustainability indicators systems are linked to policy systems and processes is still limited. Using a 'policy orientation' as an analytical strategy, we investigate the processes surrounding the creation, diffusion, dissemination, and utilisation of sustainability indicators at the national scale of policy-making. Utilising an empirical case study of Malaysia, this paper seeks to answer two questions: How are indicators currently used in policy systems; and, have sustainability indicators had policy impacts in the past? The latter is addressed using policy learning as a frame of analysis.
Diffusion Coefficient of As and P in HfO2
Authors: Suzuki Kunihiro , Tashiro Hiroko , Morisaki Yusuke , Sugita Yoshihiro
Published: December 2005

We implanted As and P ions in a 110-nm-thick HfO2 layer, subjected the substrates to various thermal processes, and evaluated their diffusion coefficients by comparing experimental and numerical data. We found that the diffusion coefficients of As and P in HfO2 are almost the same as that of B and are much higher, by two orders, than that of B in SiO2. The impurity penetration through the HfO2 gate insulator is much more severe than that of SiO2 even though a thicker HfO2 layer is available.