bluuebunny/crossref_metadata_2025 huggingface dataset:
Elastic Bounds of Bioinspired Nanocomposites
Authors: Lei H. J. , Zhang Z. Q. , Han F. , Liu B. , Zhang Y.-W. , Gao H. J.
Published: May 2013

Biological materials in nature serve as a valuable source of inspiration for developing novel synthetic materials with extraordinary properties or functions. Much effort to date has been directed toward fabricating and understanding bio-inspired nanocomposites with internal architectures mimicking those of nacre and collagen fibril. Here we establish simple and explicit analytical solutions for both upper and lower bounds of the elastic properties of biocomposites in terms of various physical and geometrical parameters including volume fraction and moduli of constituents, and aspect ratio and alignment pattern of stiff reinforcements. Numerical analyses based on the finite element method are performed to validate the derived elastic bounds.
A Unified Treatment of Axisymmetric Adhesive Contact on a Power-Law Graded Elastic Half-Space
Authors: Jin Fan , Guo Xu , Zhang Wei
Published: May 2013

In the present paper, axisymmetric frictionless adhesive contact between a rigid punch and a power-law graded elastic half-space is analytically investigated with use of Betti's reciprocity theorem and the generalized Abel transformation, a set of general closed-form solutions are derived to the Hertzian contact and Johnson–Kendall–Roberts (JKR)-type adhesive contact problems for an arbitrary punch profile within a circular contact region. These solutions provide analytical expressions of the surface stress, deformation fields, and equilibrium relations among the applied load, indentation depth, and contact radius. Based on these results, we then examine the combined effects of material inhomogeneities and punch surface morphologies on the adhesion behaviors of the considered contact system. The analytical results obtained in this paper include the corresponding solutions for homogeneous isotropic materials and the Gibson soil as special cases and, therefore, can also serve as the benchmarks for checking the validity of the numerical solution methods.
Global Output Feedback Stabilization of a Class of Nonlinear Systems With Multiple Output
Authors: Qian Chunjiang , Gong Qi
Published: May 2013

This paper considers global output feedback stabilization of a class of upper-triangular nonlinear systems with multiple outputs. By coupling a finite-time convergent observer and a saturated homogeneous stabilizer, the global output feedback stabilization can be achieved without the homogeneous growth condition. The proposed techniques are also extended to more general complex nonlinear systems. Various examples, including a ball-and-beam mechanical system and a planar vertical takeoff and landing aircraft, are presented to illustrate the design.
A Multiscale Approach to Modeling the Passive Mechanical Contribution of Cells in Tissues
Authors: Lai Victor K. , Hadi Mohammad F. , Tranquillo Robert T. , Barocas Victor H.
Published: May 2013

In addition to their obvious biological roles in tissue function, cells often play a significant mechanical role through a combination of passive and active behaviors. This study focused on the passive mechanical contribution of cells in tissues by improving our multiscale model via the addition of cells, which were treated as dilute spherical inclusions. The first set of simulations considered a rigid cell, with the surrounding ECM modeled as (1) linear elastic, (2) Neo-Hookean, and (3) a fiber network. Comparison with the classical composite theory for rigid inclusions showed close agreement at low cell volume fraction. The fiber network case exhibited nonlinear stress–strain behavior and Poisson's ratios larger than the elastic limit of 0.5, characteristics similar to those of biological tissues. The second set of simulations used a fiber network for both the cell (simulating cytoskeletal filaments) and matrix, and investigated the effect of varying relative stiffness between the cell and matrix, as well as the effect of a cytoplasmic pressure to enforce incompressibility of the cell. Results showed that the ECM network exerted negligible compression on the cell, even when the stiffness of fibers in the network was increased relative to the cell. Introduction of a cytoplasmic pressure significantly increased the stresses in the cell filament network, and altered how the cell changed its shape under tension. Findings from this study have implications on understanding how cells interact with their surrounding ECM, as well as in the context of mechanosensation.
An Adaptive Response to Uncertainty Generates Positive and Negative Contrast Effects
Authors: McNamara John M. , Fawcett Tim W. , Houston Alasdair I.
Published: May 2013

Choice in Changing Environments

Animals, including humans, generally tend to judge the world on relative, rather than absolute, terms. For example, the value of a particular object or reward is generally determined based on comparison to other rewards we have received in the past or to those that others have received. Such contrast effects can have negative or positive impacts on our behavior.

McNamara
et al.

(p.
1084
) used an optimality model to show that contrast effects could evolve as an adaptive response to environmental instability and unpredictability.
Accelerating Next-Generation Vaccine Development for Global Disease Prevention
Authors: Koff Wayne C. , Burton Dennis R. , Johnson Philip R. , Walker Bruce D. , King Charles R. , Nabel Gary J. , Ahmed Rafi , Bhan Maharaj K. , Plotkin Stanley A.
Published: May 2013

Building Better Vaccines

Vaccines are one of the most effective tools to protect against infectious diseases. Unfortunately, vaccines for diseases with the highest global health burdens, such as HIV, malaria, and tuberculosis, are not yet available.

Koff
et al.

(
1232910
) review the latest advances in vaccine development and why these particular diseases remain such a challenge. Respiratory syncytial virus (RSV) is a serious cause of morbidity and mortality in infants and young children worldwide. Although a prophylactic antibody is available for children at high risk, a vaccine is much needed. As a potential step toward this goal,

McLellan
et al.

(p.
1113
, published online 25 April) solved the cocrystal structure of a neutralizing antibody (D25) bound to the prefusion F protein of RSV. Knowledge of the structure of the prefusion protein should help to guide vaccine design and the development of additional therapeutics.
Unwinding of a Skyrmion Lattice by Magnetic Monopoles
Authors: Milde P. , Köhler D. , Seidel J. , Eng L. M. , Bauer A. , Chacon A. , Kindervater J. , Mühlbauer S. , Pfleiderer C. , Buhrandt S. , Schütte C. , Rosch A.
Published: May 2013

Hedgehogs, Whirls, and Zippers

Topologically ordered materials at certain ranges of temperature and magnetic field can form a regular lattice of magnetic whirls called skyrmions.

Milde
et al.

(p.
1076
) studied the destruction of a skyrmion lattice with varying magnetic fields by imaging the surface magnetic structure. Magnetic force microscopy revealed a pairwise merging of skyrmions on the surface. Furthermore, in the bulk, a hedgehog-like spin structure with the properties of the elusive magnetic monopole was needed to "zip" together the corresponding skyrmion lines.
Structural MS Pulls Its Weight
Authors: Sharon Michal
Published: May 2013

Mass spectrometry provides insights into the structure and dynamics of ever-larger protein assemblies and associated biomolecules.
A New Twist on Cooperative Catalysis
Authors: Schindler Corinna S. , Jacobsen Eric N.
Published: May 2013

Two independent catalysts working synergistically allow the controlled synthesis of all four stereoisomers in a reaction that forms carbon-carbon bonds.

[Also see Research Article by

Krautwald
et al.

]
Pebbles on Mars
Authors: Jerolmack Douglas J.
Published: May 2013

The observation of conglomerates by the Mars rover Curiosity provides the most definitive proof yet of ancient river flow.

[Also see Research Article by

Williams
et al.

]
Visa Reform Advances in Senate as House Offers STEM Ideas
Authors: Malakoff David
Published: May 2013

A Senate panel approved a bipartisan plan to change U.S. immigration policy as House members struggled with competing visions of what reforms are needed.
Human Monocyte-Derived Dendritic Cells Exposed to Microorganisms Involved in Hypersensitivity Pneumonitis Induce a Th1-Polarized Immune Response
Authors: Bellanger Anne-Pauline , Pallandre Jean-René , Borg Christophe , Loeffert Sophie , Gbaguidi-Haore Houssein , Millon Laurence
Published: May 2013

Hypersensitivity pneumonitis (HP) is an immunoallergic disease characterized by a prominent interstitial infiltrate composed predominantly of lymphocytes secreting inflammatory cytokines. Dendritic cells (DCs) are known to play a pivotal role in the lymphocytic response. However, their cross talk with microorganisms that cause HP has yet to be elucidated. This study aimed to investigate the initial interactions between human monocyte-derived DCs (MoDCs) and four microorganisms that are different in nature (Saccharopolyspora rectivirgula[actinomycetes],Mycobacterium immunogenum[mycobacteria], andWallemia sebiandEurotium amstelodami[filamentous fungi]) and are involved in HP. Our objectives were to determine the cross talk between MoDCs and HP-causative agents and to determine whether the resulting immune response varied according to the microbial extract tested. The phenotypic activation of MoDCs was measured by the increased expression of costimulatory molecules and levels of cytokines in supernatants. The functional activation of MoDCs was measured by the ability of MoDCs to induce lymphocytic proliferation and differentiation in a mixed lymphocytic reaction (MLR).E. amstelodami-exposed (EA) MoDCs expressed higher percentages of costimulatory molecules than didW. sebi-exposed (WS),S. rectivirgula-exposed (SR), orM. immunogenum-exposed (MI) MoDCs (P< 0.05, Wilcoxon signed-rank test). EA-MoDCs, WS-MoDCs, SR-MoDCs, and MI-MoDCs induced CD4+T cell proliferation and a Th1-polarized immune response. The present study provides evidence that, although differences were initially observed between MoDCs exposed to filamentous fungi and MoDCs exposed to bacteria, a Th1 response was ultimately promoted by DCs regardless of the microbial extract tested.
Evaluation of the Immunogenicity of an Experimental Subunit Vaccine That Allows Differentiation between Infected and Vaccinated Animals against Bluetongue Virus Serotype 8 in Cattle
Authors: Anderson Jenna , Hägglund Sara , Bréard Emmanuel , Comtet Loic , Lövgren Bengtsson Karin , Pringle John , Zientara Stéphan , Valarcher Jean Francois
Published: May 2013

Bluetongue virus (BTV), the causative agent of bluetongue in ruminants, is an emerging virus in northern Europe. The 2006 outbreak of BTV serotype 8 (BTV-8) in Europe was marked by an unusual teratogenic effect and a high frequency of clinical signs in cattle. Conventional control strategies targeting small ruminants were therefore extended to include cattle. Since cattle were not routinely vaccinated before 2006, the immune responses to BTV have not been studied extensively in this species. With the aims of developing a subunit vaccine against BTV-8 for differentiation between infected and vaccinated animals based on viral protein 7 (VP7) antibody detection and of improving the current understanding of the immunogenicity of BTV proteins in cattle, the immune responses induced by recombinant VP2 (BTV-8) and nonstructural protein 1 (NS1) and NS2 (BTV-2) were studied. Cows were immunized twice (with a 3-week interval) with the experimental vaccine, a commercial inactivated vaccine, or a placebo. The two vaccines induced similar neutralizing antibody responses to BTV-8. Furthermore, the antibody responses detected against VP2, NS1, and NS2 were strongest in the animals immunized with the experimental vaccine, and for the first time, a serotype cross-reactive antibody response to NS2 was shown in cattle vaccinated with the commercial vaccine. The two vaccines evoked measurable T cell responses against NS1, thereby supporting a bovine cross-reactive T cell response. Finally, VP7 seroconversion was observed after vaccination with the commercial vaccine, as in natural infections, but not after vaccination with the experimental vaccine, indicating that the experimental vaccine may allow the differentiation of vaccinated animals from infected animals regardless of BTV serotype. The experimental vaccine will be further evaluated during a virulent challenge in a high-containment facility.
Development of an Enzyme-Linked Immunosorbent Assay Using a Recombinant LigA Fragment Comprising Repeat Domains 4 to 7.5 as an Antigen for Diagnosis of Equine Leptospirosis
Authors: Yan Weiwei , Saleem Muhammad Hassan , McDonough Patrick , McDonough Sean P. , Divers Thomas J. , Chang Yung-Fu
Published: May 2013

Leptospiraimmunoglobulin (Ig)-like (Lig) proteins are a novel family of surface-associated proteins in which the N-terminal 630 amino acids are conserved. In this study, we truncated the LigA conserved region into 7 fragments comprising the 1st to 3rd (LigACon1-3), 4th to 7.5th (LigACon4-7.5), 4th (LigACon4), 4.5th to 5.5th (LigACon4.5–5.5), 5.5th to 6.5th (LigACon5.5–6.5), 4th to 5th (LigACon4-5), and 6th to 7.5th (LigACon6-7.5) repeat domains. All 7 recombinant Lig proteins were screened using a slot-shaped dot blot assay for the diagnosis of equine leptospirosis. Our results showed that LigACon4-7.5 is the best candidate diagnostic antigen in a slot-shaped dot blot assay. LigACon4-7.5 was further evaluated as an indirect enzyme-linked immunosorbent assay (ELISA) antigen for the detection ofLeptospiraantibodies in equine sera. This assay was evaluated with equine sera (n= 60) that were microscopic agglutination test (MAT) negative and sera (n= 220) that were MAT positive to the 5 serovars that most commonly cause equine leptospirosis. The indirect ELISA results showed that at a single serum dilution of 1:250, the sensitivity and specificity of ELISA were 80.0% and 87.2%, respectively, compared to those of MAT. In conclusion, an indirect ELISA was developed utilizing a recombinant LigA fragment comprising the 4th to 7.5th repeat domain (LigACon4-7.5) as a diagnostic antigen for equine leptospirosis. This ELISA was found to be sensitive and specific, and it yielded results that concurred with those of the standard MAT.
Multicentric Evaluation of a New Real-Time PCR Assay for Quantification of Cryptosporidium spp. and Identification of Cryptosporidium parvum and Cryptosporidium hominis
Authors: Mary C. , Chapey E. , Dutoit E. , Guyot K. , Hasseine L. , Jeddi F. , Menotti J. , Paraud C. , Pomares C. , Rabodonirina M. , Rieux A. , Derouin F. ,   for the ANOFEL Cryptosporidium National Network
Published: May 2013

Cryptosporidium
is a protozoan parasite responsible for gastroenteritis, especially in immunocompromised patients. Laboratory diagnosis of cryptosporidiosis relies on microscopy, antigen detection, and nucleic acid detection and analysis. Among the numerous molecular targets available, the 18S rRNA gene displays the best sensitivity and sequence variations between species and can be used for molecular typing assays. This paper presents a new real-time PCR assay for the detection and quantification of all
Cryptosporidium
species associated with the identification of
Cryptosporidium hominis
and
Cryptosporidium parvum
. The sensitivity and specificity of this new PCR assay were assessed on a multicentric basis, using well-characterized
Cryptosporidium
-positive and -negative human stool samples, and the efficiencies of nine extraction methods were comparatively assessed using
Cryptosporidium
-seeded stool samples and phosphate-buffered saline samples. A comparison of extraction yields showed that the most efficient extraction method was the Boom technique in association with mechanical grinding, and column extraction showed higher binding capacity than extraction methods based on magnetic silica. Our PCR assay was able to quantify at least 300 oocysts per gram of stool. Satisfactory reproducibility between laboratories was observed. The two main species causing human disease,
Cryptosporidium hominis
and
Cryptosporidium parvum
, were identified using a duplex real-time PCR assay with specific TaqMan minor-groove-binding ligand (MGB) probes for the same amplicon. To conclude, this one-step quantitative PCR is well suited to the routine diagnosis of cryptosporidiosis since practical conditions, including DNA extraction, quantification using well-defined standards, and identification of the two main species infecting humans, have been positively assessed.
Functional Characterization of the Alphavirus TF Protein
Authors: Snyder Jonathan E. , Kulcsar Kirsten A. , Schultz Kimberly L. W. , Riley Catherine P. , Neary Jacob T. , Marr Scott , Jose Joyce , Griffin Diane E. , Kuhn Richard J.
Published: May 2013

Alphavirus dogma has long dictated the production of a discrete set of structural proteins during infection of a cell: capsid, pE2, 6K, and E1. However, bioinformatic analyses of alphavirus genomes (A. E. Firth, B. Y. Chung, M. N. Fleeton, and J. F. Atkins, Virol. J. 5:108, 2008) suggested that a ribosomal frameshifting event occurs during translation of the alphavirus structural polyprotein. Specifically, a frameshift event is suggested to occur during translation of the 6K gene, yielding production of a novel protein, termed transframe (TF), comprised of a C-terminal extension of the 6K protein in the −1 open reading frame (ORF). Here, we validate the findings of Firth and colleagues with respect to the production of the TF protein and begin to characterize the function of TF. Using a mass spectrometry-based approach, we identified TF in purified preparations of both Sindbis and Chikungunya virus particles. We next constructed a panel of Sindbis virus mutants with mutations which alter the production, size, or sequence of TF. We demonstrate that TF is not absolutely required in culture, although disrupting TF production leads to a decrease in virus particle release in both mammalian and insect cells. In a mouse neuropathogenesis model, mortality was <15% in animals infected with the TF mutants, whereas mortality was 95% in animals infected with the wild-type virus. Using a variety of additional assays, we demonstrate that TF retains ion-channel activity analogous to that of 6K and that lack of production of TF does not affect genome replication, particle infectivity, or envelope protein transit to the cell surface. The TF protein therefore represents a previously uncharacterized factor important for alphavirus assembly.
Mapping the Structural Determinants Responsible for Enhanced T Cell Activation to the Immunogenic Adeno-Associated Virus Capsid from Isolate Rhesus 32.33
Authors: Mays Lauren E. , Wang Lili , Tenney Rebeca , Bell Peter , Nam Hyun-Joo , Lin Jianping , Gurda Brittney , Van Vliet Kim , Mikals Kyle , Agbandje-McKenna Mavis , Wilson James M.
Published: May 2013

Avoiding activation of immunity to vector-encoded proteins is critical to the safe and effective use of adeno-associated viral (AAV) vectors for gene therapy. While commonly used serotypes, such as AAV serotypes 1, 2, 7, 8, and 9, are often associated with minimal and/or dysfunctional CD8
+
T cell responses in mice, the threshold for immune activation appears to be lower in higher-order species. We have modeled this discrepancy within the mouse by identifying two capsid variants with differential immune activation profiles: AAV serotype 8 (AAV8) and a hybrid between natural rhesus isolates AAVrh32 and AAVrh33 (AAVrh32.33). Here, we aimed to characterize the structural determinants of the AAVrh32.33 capsid that augment cellular immunity to vector-encoded proteins or those of AAV8 that may induce tolerance. We hypothesized that the structural domain responsible for differential immune activation could be mapped to surface-exposed regions of the capsid, such as hypervariable regions (HVRs) I to IX of VP3. To test this, a series of hybrid AAV capsids was constructed by swapping domains between AAV8 and AAVrh32.33. By comparing their ability to generate transgene-specific T cells
in vivo
versus the stability of transgene expression in the muscle, we confirmed that the functional domain lies within the VP3 portion of the capsid. Our studies were able to exclude the regions of VP3 which are not sufficient for augmenting the cellular immune response, notably, HVRs I, II, and V. We have also identified HVR IV as a region of interest in conferring the efficiency and stability of muscle transduction to AAVrh32.33.
Laser Capture Microdissection Assessment of Virus Compartmentalization in the Central Nervous Systems of Macaques Infected with Neurovirulent Simian Immunodeficiency Virus
Authors: Matsuda Kenta , Brown Charles R. , Foley Brian , Goeken Robert , Whitted Sonya , Dang Que , Wu Fan , Plishka Ronald , Buckler-White Alicia , Hirsch Vanessa M.
Published: May 2013

Nonhuman primate-simian immunodeficiency virus (SIV) models are powerful tools for studying the pathogenesis of human immunodeficiency virus type 1 (HIV-1) in the brain. Our laboratory recently isolated a neuropathogenic viral swarm, SIVsmH804E, a derivative of SIVsmE543-3, which was the result of sequential intravenous passages of viruses isolated from the brains of rhesus macaques with SIV encephalitis. Animals infected with SIVsmH804E or its precursor (SIVsmH783Br) developed SIV meningitis and/or encephalitis at high frequencies. Since we observed macaques with a combination of meningitis and encephalitis, as well as animals in which meningitis or encephalitis was the dominant component, we hypothesized that distinct mechanisms could be driving the two pathological states. Therefore, we assessed viral populations in the meninges and the brain parenchyma by laser capture microdissection. Viral RNAs were isolated from representative areas of the meninges, brain parenchyma, terminal plasma, and cerebrospinal fluid (CSF) and from the inoculum, and the SIV envelope fragment was amplified by PCR. Phylogenetic analysis of envelope sequences from the conventional progressors revealed compartmentalization of viral populations between the meninges and the parenchyma. In one of these animals, viral populations in meninges were closely related to those from CSF and shared signature truncations in the cytoplasmic domain of gp41, consistent with a common origin. Apart from magnetic resonance imaging (MRI) and positron-emission tomography (PET) imaging, CSF is the most accessible assess to the central nervous system for HIV-1-infected patients. However, our results suggest that the virus in the CSF may not always be representative of viral populations in the brain and that caution should be applied in extrapolating between the properties of viruses in these two compartments.
Emergence of gp120 V3 Variants Confers Neutralization Resistance in an R5 Simian-Human Immunodeficiency Virus-Infected Macaque Elite Neutralizer That Targets the N332 Glycan of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein
Authors: Sadjadpour Reza , Donau Olivia K. , Shingai Masashi , Buckler-White Alicia , Kao Sandra , Strebel Klaus , Nishimura Yoshiaki , Martin Malcolm A.
Published: May 2013

Neutralization-resistant simian-human immunodeficiency virus AD8 (SHIV
AD8
) variants that emerged in an infected macaque elite neutralizer targeting the human immunodeficiency virus type 1 (HIV-1) gp120 N332 glycan acquired substitutions of critical amino acids in the V3 region rather than losing the N332 glycosylation site. One of these resistant variants, carrying the full complement of gp120 V3 changes, was also resistant to the potent anti-HIV-1 monoclonal neutralizing antibodies PGT121 and 10-1074, both of which are also dependent on the presence of the gp120 N332 glycan.
Cell-Cell Contact-Mediated Hepatitis C Virus (HCV) Transfer, Productive Infection, and Replication and Their Requirement for HCV Receptors
Authors: Liu Ziqing , He Johnny J.
Published: May 2013

Hepatitis C virus (HCV) infection is believed to begin with interactions between cell-free HCV and cell receptors that include CD81, scavenger receptor B1 (SR-B1), claudin-1 (CLDN1), and occludin (OCLN). In this study, we have demonstrated that HCV spreading from infected hepatocytes to uninfected hepatocytes leads to the transfer of HCV and the formation of infection foci and is cell density dependent. This cell-cell contact-mediated (CCCM) HCV transfer occurs readily and requires all these known HCV receptors and an intact actin cytoskeleton. With a fluorescently labeled replication-competent HCV system, the CCCM transfer process was further dissected by live-cell imaging into four steps: donor cell-target cell contact, formation of viral puncta-target cell conjugation, transfer of viral puncta, and posttransfer. Importantly, the CCCM HCV transfer leads to productive infection of target cells. Taken together, these results show that CCCM HCV transfer constitutes an important and effective route for HCV infection and dissemination. These findings will aid in the development of new and novel strategies for preventing and treating HCV infection.
Absence of CXCL10 Aggravates Herpes Stromal Keratitis with Reduced Primary Neutrophil Influx in Mice
Authors: Shen Fang-Hsiu , Wang Shainn-Wei , Yeh Trai-Ming , Tung Yuk-Ying , Hsu Sheng-Min , Chen Shun-Hua
Published: May 2013

Herpes simplex virus 1 (HSV-1) replication initiates inflammation and angiogenesis responses in the cornea to result in herpetic stromal keratitis (HSK), which is a leading cause of infection-induced vision impairment. Chemokines are secreted to modulate HSK by recruiting leukocytes, which affect virus growth, and by influencing angiogenesis. The present study used a murine infection model to investigate the significance of the chemokine CXC chemokine ligand 10 (CXCL10; gamma interferon-inducible protein 10 [IP-10]) in HSK. Here, we show that HSV-1 infection of the cornea induced CXCL10 protein expression in epithelial cells. The corneas of mice with a targeted disruption of the gene encoding CXCL10 displayed decreases in levels of neutrophil-attracting cytokine (interleukin-6), primary neutrophil influx, and viral clearance 2 or 3 days postinfection. Subsequently, absence of CXCL10 aggravated HSK with elevated levels of interleukin-6, chemokines for CD4+T cells and/or neutrophils (macrophage inflammatory protein-1α and macrophage inflammatory protein-2), angiogenic factor (vascular endothelial growth factor A), and secondary neutrophil influx, as well as infiltration of CD4+T cells to exacerbate opacity and angiogenesis in the cornea at 14 and up to 28 days postinfection. Our results collectively show that endogenous CXCL10 contributes to recruit the primary neutrophil influx and to affect the expression of cytokines, chemokines, and angiogenic factors as well as to reduce the viral titer and HSK severity.
Selection of Drug-Resistant Feline Immunodeficiency Virus (FIV) Encoding FIV/HIV Chimeric Protease in the Presence of HIV-Specific Protease Inhibitors
Authors: Lin Ying-Chuan , Happer Meaghan , Elder John H.
Published: May 2013

An infectious chimeric feline immunodeficiency virus (FIV)/HIV strain carrying six HIV-like protease (PR) mutations (I37V/N55M/V59I/I98S/Q99V/P100N) was subjected to selection in culture against the PR inhibitor lopinavir (LPV), darunavir (DRV), or TL-3. LPV selection resulted in the sequential emergence of V99A (strain S-1X), I59V (strain S-2X), and I108V (strain S-3X) mutations, followed by V37I (strain S-4X). Mutant PRs were analyzed
in vitro
, and an isogenic virus producing each mutant PR was analyzed in culture for LPV sensitivity, yielding results consistent with the original selection. The 50% inhibitory concentrations (IC
50
s) for S-1X, S-2X, S-3X, and S-4X were 95, 643, 627, and 1,543 nM, respectively. The primary resistance mutations, V99
82
A, I59
50
V, and V37
32
I, are consistent with the resistance pattern developed by HIV-1 under similar selection conditions. While resistance to LPV emerged readily, similar PR mutations causing resistance to either DRV or TL-3 failed to emerge after passage for more than a year. However, a G37D mutation in the nucleocapsid (NC) was observed in both selections and an isogenic G37D mutant replicated in the presence of 100 nM DRV or TL-3, whereas parental chimeric FIV could not. An additional mutation, L92V, near the PR active site in the folded structure recently emerged during TL-3 selection. The L92V mutant PR exhibited an IC
50
of 50 nM, compared to 35 nM for 6s-98S PR, and processed the NC-p2 junction more efficiently, consistent with increased viral fitness. These findings emphasize the role of mutations outside the active site of PR in increasing viral resistance to active-site inhibitors and suggest additional targets for inhibitor development.
Shear strength and slope stability in a shallow clayey soil regolith
Authors: Anderson Scott A. , Sitar Nicholas
Published: May 2013

The results of three types of laboratory strength tests on undisturbed samples of a saturated clayey soil regolith are analyzed. Drained-direct shear tests, aniso-tropically consolidated-undrained triaxial compression tests with pore pressure measurement, and constant-shear-drained unloading test results indicate different modes of failure and different strength parameters. Based on the grain-size distribution and plasticity test results, it appears that the behavior and strength of the regolith would be dominated by the clay content; however, the results of the strength tests illustrate the soil has a structure formed by cemented bonds. This structure has a larger influence on the behavior and strength than the clay content does, at least at the depth of failure. At the in-situ stress level of the shallow regolith, the consequence of failure is found to be a function of the stress path. As a result, some slope failures may move slowly for short distances, and others many mobilize into rapid flow failures because of differences in the stress path leading to failure.
Slope stability considerations in differentially weathered mudrocks
Authors: Shakoor Abdul
Published: May 2013

Mudrock sequences usually occur as harder, more competent strata (siltstones, sandstones, limestones) alternating with softer, less competent strata (claystones, mudstones, shales). This type of stratigraphy is highly susceptible to differential weathering that results in undercutting of the competent layers by the incompetent layers. Undercutting promotes a variety of slope movements such as rock falls, plane failures, and wedge failures that may not occur otherwise. Examples of such failures from selected sites in Ohio, Pennsylvania, and West Virginia are presented. Because of their high speed, suddenness of occurrence, and occasionally large volume of rock involved, undercutting-induced failures can be quite hazardous.

A variety of remedial measures are employed to reduce the potential for undercutting-induced failures. For a timely implementation of these remedial measures, it is essential to estimate the anticipated rate of undercutting for a given site. In order to develop a method that could be used to predict the rate of undercutting, the amount of undercutting was measured for 14 road-cut sites in Ohio, Pennsylvania, and West Virginia. Information regarding the excavation dates of these cuts was obtained from the highway department records. The maximum amount of undercutting at each site was divided by the time since excavation to obtain the rate of undercutting. The rate of undercutting was then correlated with the slake durability index values of the undercutting units to develop prediction equations for estimating the maximum expected rate of undercutting for different types of mudrock. The paper also reviews various methods of treating slopes subject to differential weathering.
Military geology in war and peace
Authors: Guth Peter L.
Published: May 2013

In warfare military geologists pursue five main categories of work: tactical and strategic terrain analysis, fortifications and tunneling, resource acquisition, defense installations, and field construction and logistics. In peace they train for wartime operations and may be involved in peace-keeping and nation-building exercises. Although many geologists view military geology as a branch of engineering geology, the U.S. military does not include geologists in its force structure and gets geological assistance on an ad hoc basis. The army does, however, include organic terrain teams at division and higher levels to provide routine information for mission planning and execution. The classic dilemma for military geology has been whether support can best be provided by civilian technical-matter experts or by uniformed soldiers who routinely work with the combat units.
Swords into plowshares
Authors: Neal James T.
Published: May 2013

Military geology and national security projects are comparable, achieving their raison d'etre in support of national goals, military operations, and the systems that support them—all for vital national interests. The application of geoscience to these ends, especially engineering geology, has occurred from pole to pole and included every conceivable environment and natural condition. In the conduct of such projects, the geosciences have advanced, and vice versa.

Desert trafficability, most notably regarding playa surfaces, is temporary and variable and not a persistent condition as some early authors believed. Playas in Australia, Iran, and the United States show that saline efflorescence is removed following surface water dissolution and subsequent deflation, resulting in very hard crusts. Magadiite, a hydrous sodium silicate and possible precursor of bedded chert, was first discovered in North America at Alkali Lake, Oregon, during a military project. Pleistocene Lake Trinity, a small and mostly buried evaporite basin in the northern Jornada del Muerto, New Mexico, was discovered during exploratory drilling in support of a military test program.

The Strategic Petroleum Reserve (SPR), operated by the U.S. Department of Energy, has underground cavern storage of ~600 million barrels of crude oil in five Gulf Coast salt domes. The geologic characterization of the SPR sites is a major component of these comprehensive engineered works—unparalleled in modern times and on a comparable scale with the Panama Canal. Numerous studies of salt-stock heterogeneity, salt-karst features, and structural and physical attributes of salt deposits are broadening the database for use in the commercial storage industry. Geologists serving in military and national security endeavors are fully functioning members of the project technical teams and have made significant advances to the geosciences.
Geoenvironmental factors in the regeneration of military airfields in Great Britain
Authors: Blake Ronald N.E.
Published: May 2013

Britain is littered with active and disused military airfields, arguably the most distinctive feature of its twentieth-century defenses. More than 850 airfields were active during World War II, covering about 162000 hectares or 0.7% of the national land area. Today, fewer than 50 remain active, the majority having been transferred to ground defense roles, civil flying, agriculture, and other land uses.

There is a strong spatial association between the leading air bases and well-drained Middle Jurassic limestone, Upper Cretaceous chalk, and Quaternary fluvioglacial sands and gravels. Peacetime consolidation at a dwindling number of key bases has intensified impacts on these permeable lithologies, which are vulnerable to groundwater contamination, soil degradation, and erosion of landscapes rich in ecological and archaeological heritage.

Demolition for agriculture has been uncoordinated and incomplete. Alternative uses include laboratories, prisons, and motor racing, many introduced without environmental controls. Asset stripping of valuable infrastructure has become a public issue since the ending of the Cold War.

Disused airfields are now the foci of comprehensive regeneration schemes. Options include mineral extraction, afforestation, new towns, and runway conversion to airports. Decision making involves careful assessment of geological resources, geologic hazards, and available remediation technologies within the framework of a systematic environmental audit.

Britain’s “airfield problem” is the unique product of a densely settled countryside, a rich aeronautical history, and an imperfect planning system. Experience gained trying to solve this problem has many international applications.
An overview of nuclear power plant siting and licensing
Authors: McClure Cole R. , Hatheway Allen W.
Published: May 2013

Studies on nuclear power plant siting and licensing are expensive and complex undertakings requiring critical geologic input for the planning, design, and construction phases. Commercial production of nuclear power in the United States began in 1959, in an era when geologic hazards were seemingly not as critical as they are today to designers, constructors, and regulatory agencies. By the early 1970s, however, siting work required a more sophisticated appreciation of geologic hazards such as earthquake effects, subsidence, slope stability, and foundation integrity. These concerns were formalized by the U.S. Atomic Energy Commission (AEC) in 1971 in its "Seismic and Geologic Siting Criteria for Nuclear Power Plants" and in 1972 in the Standard Format.

The required Federal license to construct and operate nuclear power plants is awarded through a careful and demanding process. Construction permits are not granted until high levels of assurance are attained as to suitability of the site; the construction process must be observed and monitored. Electric utility applicants for construction permits and operating licenses organize large teams of scientific and technical personnel to compile the Preliminary Safety Analysis Report (PSAR) required for each nuclear power plant. Geologists constitute a key part of these teams, producing site-specific and regional assessments that are accurate enough to withstand scrutiny and timely enough to avoid costly delays in the programmed design-and-construct sequence.

Management techniques must be applied to coordinate data-collection efforts and timely release of findings. As soon as a complete set of findings is compiled to the specifications of the Standard Format, the PSAR is accepted for review by the Nuclear Regulatory Commission (NRC). These reports become complex documents and include the responses to subsequent review questions which are included as amendments. The Final Safety Analysis Report (FSAR) includes supplementary reports dealing with geologic findings revealed during construction.

Many of the key geologic issues identified in siting and licensing are often analogous to those problems that confront researchers in the geological sciences today, such as evaluation of remote imagery, proof of subsurface stratigraphic continuity, evaluation of potential fault activity, a thorough assessment of ground-water conditions at each site, and subsidence potential including evaluation of dissolution of foundation material.

The overriding goal of each applicant utility is the construction of a safe power plant; however, the future of the industry in the United States is dependent on its ability to maintain construction schedules while staying within allotted budgets. Lessons learned from previous sitings have pointed out that effective management and judgment, efficient communication, and coordination contribute to timely and cost-efficient license studies.
Measurement of in situ dynamic properties in relation to geologic conditions
Authors: Dobecki T.L.
Published: May 2013

Evaluation of nuclear power plant sites from a material stability standpoint requires measurement of in situ dynamic properties. These are derived from measurement of shear-wave propagation velocity in subsurface materials by utilizing either the seismic downhole or seismic cross-hole techniques, or both. The downhole technique is rapid and less expensive than the cross-hole survey but is limited in maximum survey depth and resolution of thin, higher velocity beds. The cross-hole test, although less subject to depth and resolution limitations, requires more boreholes and is therefore more expensive. This test is also more exacting because of borehole drift considerations and timing corrections that may or may not be required for the particular energy source used.

Actual field cross-hole examples for several sites of varied subsurface geology illustrate the variation of shear velocity versus material make-up and condition. High shear-wave velocities are characteristic of massive crystalline rock, whereas fractured rock and unconsolidated sediments show progressively reduced values.

The combination of the dynamic model with a proposed design earthquake event produces the basic data upon which site evaluation from an engineering standpoint may be made. An example from a deep sand sediment site shows the increased potential for liquefaction as the strength of the design earthquake is increased.
Ground-water studies for nuclear power plant siting
Authors: Farrel Clifford R. , Harshbarger John W.
Published: May 2013

Ground-water studies for nuclear power plant sites call for extraordinary and extensive effort in comparison to site investigations for more conventional, large engineering structures, primarily to assure the stability and safe operation of the plant. Providing that assurance may require unusually complex design solutions to foundation problems. Basic data collection must be extensive and thorough in response to the requirements of the Safety Analysis Report (SAR) for a detailed and well-documented description on the occurrence and movement of ground water in the site vicinity. The ground-water studies presented in the SAR must demonstrate that normal operation of the plant will not have a serious impact on the ground water and that water levels will not rise to a height that might affect the stability of plant foundations. Further, the studies must be thorough enough to assure that any accidental spill of radioactive fluid will either be dispersed harmlessly or will be intercepted by a monitoring system before the spill could percolate to a usable off-site aquifer.
Subsidence over oil and gas fields
Authors: Martin J. C. , Serdengecti S.
Published: May 2013

Most oil and gas reservoirs experience only small amounts of compaction and surface subsidence. Significant subsidence due to production of hydrocarbons has been observed over some oil and gas fields. This paper presents a review of the fundamentals of reservoir compaction and surface subsidence over oil and gas fields and explains why large-scale subsidence is rare. A new method of estimating maximum potential subsidence is presented and used to analyze the subsidence over oil and gas fields in Louisiana. Large-scale compaction and subsidence are evidently associated with inelastic behavior of the reservoir rock and in some cases of the surrounding rock. No reliable methods have been established for predicting either the transition from elastic to inelastic reservoir rock behavior or large-scale reservoir compaction and subsidence.

The preconsolidation effect evident in some field data introduces an additional difficulty in understanding and predicting subsidence. Various possible causes for the effect include uplift and erosion, temporary pressure drop or an increase in horizontal stresses prior to hydrocarbon production, effects of loading rate on reservoir rock, and changes from elastic to inelastic behavior of the reservoir rock or surrounding formations.
Probabilistic seismic-hazard analysis using expert opinion; An example from the Pacific Northwest
Authors: Coppersmith Kevin J. , Youngs Robert R.
Published: May 2013

To illustrate methods for incorporating uncertainty into seismic-hazard analyses, we describe the characterization of earthquake sources used in a seismic-hazard analysis for a site in western Washington. A simple and effective tool for incorporating uncertainty into seismic-hazard analysis is called a logic tree; one was used in this study to include the range of possible characteristics of the Cascadia subduction zone seismic sources. At present, considerable uncertainty exists regarding the earthquake potential of the Cascadia zone, particularly due to the completely aseismic nature of the interface between the Juan de Fuca and North America plates. A key issue is whether this aseismic behavior is merely a function of our short period of historical observation (i.e., interseismic quiescence) or representative of longer-term behavior (i.e., aseismic subduction). To develop a complete seismic-source characterization spanning the range of interpretations regarding the earthquake potential of Cascadia, a group of 14 experts was selected based on their experience with the Cascadia subduction zone. These experts assessed source characteristics, including subduction-zone geometry, potential seismic sources, probability that each potential source is active, expected locations and dimensions of rupture, maximum earthquake magnitude, earthquake recurrence models, geologic recurrence intervals, plate convergence rate, and seismic coupling.

In general, all of the experts identified two distinct subduction-zone earthquake sources: an “intra-slab” source representing earthquakes within the subducting Juan de Fuca plate, and the plate interface between the Juan de Fuca and North American plates. An analysis of uncertainties given by individual experts, as well as their differences of opinion, shows that some characteristics of subduction-zone sources are relatively agreed upon, while other characteristics are highly uncertain. For example, it was generally believed that the intra-slab source is seismogenic and that the future locations of earthquakes within the slab will follow the spatial pattern represented by historical seismicity. In contrast, a wide range of assessments was given for the probability that the plate interface is seismogenic and for the amount of seismic coupling between the plates. In making these assessments, the experts relied on a wide range of data sets, including analogies to other subduction zones, thermal-mechanical models of subduction, and geophysical imaging of the Cascadia subduction zone.

The study demonstrates the viability of using expert opinion to assess seismic hazards and illustrates one approach to obtaining a realistic estimate of the uncertainty in the seismic hazard.
Landslide mitigation using horizontal drains, Pacific Palisades area, Los Angeles, California
Authors: Krohn James P.
Published: May 2013

Horizontal drains have been successfully used for a number of years in many areas for improving slope stability within landslide and/or landslide-prone areas. One such application of their use is discussed relative to a more than 66-m-high (220+ ft) 2:1 (26°) southwest-facing cut slope located in the Pacific Palisades area of the city of Los Angeles, California.

The slope is somewhat unusual in that the geologic structure of the bedrock (i.e., siltstone) appears to be neutral and/or favorable relative to the orientation of the slope surface. However, the slope underwent minor downslope movement (i.e., sagging, creep) following the heavy rains of 1978. Manifested mostly by cracks within paved terrace drains and/or downdrains, the movement appears to be related to local perched ground water and a northwest-southeast-trending fault zone that cuts across the southern part of the slope.

Horizontal drains are currently being used to improve slope stability by reducing the amount of ground water, especially within the vicinity of the fault zone. Ground water was encountered in 11 of the 16 horizontal drains; initial flow rates were up to 5.71 (1.5 gal) per minute. Calculations suggest that the dewatering of the slope could increase slope stability to a factor of safety of more than 1.5.