bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible Role of Compressional Viscoelasticity in Concentrated Contact Lubrication
Authors: Fein R. S.
Published: September 2011

An equation relating liquid density and viscosity under transient pressure conditions is derived. The derivation combines approximate phenomenological descriptions of the viscoelastic compression of a liquid and the dependence of viscosity on pressure and density. Solutions of the equation for a “step”-pressure increase and a semielliptical pressure cycle show that density and viscosity of Newtonian lubricants may significantly lag pressure transients under concentrated-contact lubrication conditions. Qualitatively, the lag effects appear to account at least partially for anomalous experimental observations involving asperity interactions and elastohydrodynamic lubrication of rollers.
Exact Thermoelastic Solutions for Clearance Variation in a Short Cylindrical Bearing Configuration With Unsymmetrical Frictional Heating
Authors: Hsu Y. C. , Burton R. A.
Published: September 2011

Exact solutions are given for the variation of clearance in short, cylindrical, dry journal bearings with unsymmetrical frictional heating. It is assumed that the heating takes place uniformly over an arc of contact, 2β, between the inner cylinder and the outer cylinder, which are of identical materials. The steady-state thermoelastic reduction of clearance is computed for contact arcs such that 0 deg < 2β ⩽ 360 deg. The outer cylinder is cooled externally. Solutions are obtained in terms of seven parameters. They are offered in a form whereby they may be adapted to a variety of practical bearing problems.
Equilibrium Characteristics of Axial-Groove Gas-Lubricated Bearings
Authors: Castelli V. , Pirvics J.
Published: September 2011

This paper contains the description of a new general method for the solution of Reynold’s equation for compressible and incompressible lubrication. A great improvement in numerical stability and speed of convergence is derived for all fluid film geometries including converging-diverging ones. The method is used for the determination of load coefficients and attitude angles of three and four-pad axial-groove cylindrical bearings.
Gas Squeeze Film Stiffness and Damping Torques on a Circular Disk Oscillating About Its Diameter
Authors: Ausman J. S.
Published: September 2011

A solution of Reynolds’ equation, linearized for small squeeze film motions, is presented which gives the pressure between two disks, one of which is oscillating about its diameter. Integration of the pressure over the surface area of the oscillating disk yields the squeeze film torque acting on it. The stiffness and damping components of this torque are those portions which oppose angular offset and angular velocity, respectively.
A Study of Erosion Between Two Parallel Surfaces Oscillating at Close Proximity in Liquids
Authors: Endo K. , Okada T. , Nakashima M.
Published: September 2011

A disk was vibrated in close proximity to a plane surface while submerged in either water or one of several oils. The specimens suffered surface damage either by subsurface fatigue or cavitation erosion. The type and extent of damage depends upon the thickness of the fluid films and the viscosity of the liquid. Specimens with bearing alloy surface layers showed cracks due to surface shear followed by flaking off of the bearing alloy.
Measurement of Boundary Lubricant Viscosity at Metal-Deformation Pressures (3000 Atmospheres, 20 Tons/Sq In.)
Authors: Rowe G. W.
Published: September 2011

In many metalworking operations, such as rolling and wire drawing, the average pressure acting between the workpiece and the tool will be of the order of the yield stress of the metal, usually 20–50 tons/sq in. The lubricant temperature may also rise by 60 deg C or more. Any consideration of hydrodynamic lubrication in these operations should thus take account of the large viscosity changes which may occur under such pressures and temperatures. In addition, it is probable that the rate of shear will be important [1], but this will not be considered in this paper. Local pressures of the same order are developed in typical boundary-lubrication apparatus using a hemispherical slider on a flat surface under kilogram loads [2]. Information on the pressure and temperature coefficients of viscosity for lubricants is therefore important also in studies of boundary lubrication and elastohydrodynamic lubrication [3], especially in the presence of boundary additives [4]. This paper describes a simple apparatus for viscosity measurement at temperatures up to 70 deg C and pressures up to 20 tons/sq in. (3000 atmospheres) or with future modifications up to 45 tons/sq in., together with some results for fluids with and without boundary additives.
On the Stabilizing Methods of Externally Pressurized Thrust Gas Bearings
Authors: Mori Haruo , Mori Atsunobu
Published: September 2011

Two kinds of stabilizing methods for externally pressurized thrust gas bearings are presented and analyzed. Both stabilizers of them are composed of fluid restriction and capacitance. The first type of stabilizer, which has been investigated by Loch, has a pair of restriction and capacitance attached additionally to the bearing recess, and the second type has the pair inserted into the gas-supply line to the bearing recess. Since the theoretical base of Loch’s analysis had questionable points, the analysis by the authors is started from a new and different standpoint and applied to the second type as well as to the first type. Experimental results show good agreement with the analytical results and the design of the stabilizers has been established.
Non-Newtonian Flow in Infinite-Length Full Journal Bearing
Authors: Hsu Y. C.
Published: September 2011

Analytic solutions are presented for the calculation of pressure distribution, flow rate, frictional force, load-carrying capacity, attitude angle, frictional coefficient, and Sommerfeld’s number for the steady, isothermal, and laminar flow of an incompressible, inelastic, non-Newtonian fluid in infinite-length full journal bearings. The Rabinowitsch equation, widely used empirical relation of non-Newtonian behavior, is used for introduction of the concept of shear dependent viscosity. Considering the continuity of flow and the journal stability condition, the corrected pressure boundry condition such that pˆ = 0 at θ = 0 and pˆ = dpˆ/dθ = 0 at θ = π + α is used. Solutions are applicable to both pseudoplastic and dilatant non-Newtonian fluids, and are valid over a large range of shear stresses. The chief advantage is in the simplicity of the use of the resulting equations. Examples are given for the analytic solutions, and these are shown to correspond well with the published numerical computer results.
Self-Acting Foil Bearings of Infinite Width
Authors: Barlow E. J.
Published: September 2011

In this report, the minimum gap between a rigid cylinder and a moving foil (or between a rotating cylinder and a stationary foil) is determined as a function of the wrap angle as well as of the foil speed and tension, the cylinder radius, and the viscosity of the lubricant.
A Theory for Turbulent Fluid Films and Its Application to Bearings
Authors: Elrod H. G. , Ng C. W.
Published: September 2011

In this paper a new turbulent lubrication analysis has been derived which takes into account certain well-established facts concerning turbulent shear flow. Consistent with lubrication-film theory, the nature of the local flow is taken to depend only on local film thickness, surface velocity, and pressure gradients. An eddy diffusivity treatment is used which incorporates the “law of wall” with the use of local (within the film) shear stress. Stress reversal phenomena are accommodated and isotropy of the turbulent exchange mechanism in the plane of the film is assured. Coefficients are developed for use in the generalized Reynolds (lubrication) equation, and computation procedures for the static and dynamic characteristics of turbulent, self-acting bearings have been prepared. The nonlinear effects due to the coupling of the shear induced flows and the flows due to the circumferential and axial pressure gradients are fully considered in this analysis. Thus, it is anticipated that it, unlike the previous linearized analysis, is directly applicable also to turbulent, externally pressurized, and hybrid bearings.
An Experimental Study of Annular Flows With Applications in Turbulent Film Lubrication
Authors: Burton R. A. , Carper H. J.
Published: September 2011

Experiments are reported on turbulent flows in air, in a large-scale bearing model of 6-ft dia, 2-ft length, 0.54-in. film thickness. Simulation of tilted pads, short journal bearings, and stepped pads is described. Pressure distributions are reported along with velocity and turbulence-intensity profiles. Wall shear stress is computed from the velocity profile measurements. The variations of these factors are compared with available data for plane Couette flow, wall law flow, and pressure flow in pipes, and the relationships among these are discussed. In addition, large pressure jumps at discontinuities are reported, and are shown to provide a major influence on the overall pressure distributions.
Friction and Adhesion of Copper in Vacuum
Authors: Brown R. D. , Burton R. A.
Published: September 2011

Friction and adhesion coefficients of copper on copper were measured in vacuum (5 × 10−10 to 4 × 10−7 torr) at temperatures ranging from −270 to 1000 F, and in controlled pressures of dry air ranging from 10−9 to 760 torr at 75 F. The effects of duration of exposure of surfaces to vacuum, and the effects of contact duration on adhesion were studied. Friction coefficients were very high (2.2 to over 16) and increased greatly with temperature; adhesion coefficients also increased with temperature, but at given temperatures, were about one-tenth the magnitudes of the friction coefficient.
The Determination of Stresses in Rolling-Contact Elements
Authors: Kannel J. W. , Walowit J. A. , Bell J. C. , Allen C. M.
Published: September 2011

Stress patterns in lubricated rolling-contact elements have been computed from surface pressures and temperatures between pairs of rolling disks, both cylindrical or both crowned, measured by means of evaporated surface transducers. The maximum mechanical shearing stresses computed for both cylindrical and crowned disks proved to be nearly equal to those that would have occurred under static contact, but the calculated depth of those stresses was reduced for cylindrical rollers in dynamic contact. The maximum shear reversals computed for rolling cylindrical disks were noticeably below the corresponding shear differences for the static cases. Local pressure anomalies, such as the pressure spike in the one particular case chosen for investigation, did not seem to alter significantly the shear-stress patterns. Thermal shearing stresses do not appear to be a significant portion of the maximum stress but do dominate over mechanical shearing stresses near the surface of the elements.
Wear and Compatibility Behavior of Liquid Metal Bearing Materials
Authors: Wallace M. J.
Published: September 2011

The wear and compatibility characteristics of selected bearing materials, including surface coatings and cemented refractory carbides were investigated in support of a pump development program for advanced Rankine cycle space power plants employing high temperature lithium and NaK. Compatibility of candidate materials with 1100-deg lithium in Cb-1 Zr alloy was studied in tilting capsule tests for durations to 7000 hr. The wear behavior of material combinations was evaluated with a rotating disk-static shoe assembly in lithium and NaK to 1000 deg. The best compatibility and wear characteristics were exhibited by high density molybdenum cemented carbides. Carburized Cb-1 Zr alloy wear resistance was inconsistent but, under the best conditions, was nearly equivalent to that of the cemented carbides. Plasma sprayed coatings of tungsten carbide and WC-Co gave encouraging results in NaK, but additional development of the coating process appeared necessary to assure reliable control of adhesion and performance.
Determination of Gas-Bearing Stability by Response to a Step-Jump
Authors: Elrod H. G. , McCabe J. T. , Chu T. Y.
Published: September 2011

The stability of a gas bearing is treated by a new procedure in which the bearing film is characterised by its responses to step-jump displacements. Duhamel’s theorem is invoked to generalize these step responses in a system of dynamical equations. Stability is determined by calculation of a “growth factor” for each degree of freedom. Results are presented for the infinitely long self-acting sleeve bearing and for a finite length two-bearing system.
Evaluating Life-Cycle Environmental Impact of Data Centers
Authors: Shah Amip , Bash Cullen , Sharma Ratnesh , Christian Tom , Watson Brian J. , Patel Chandrakant
Published: September 2011

Numerous evaluation metrics and standards are being proposed across industry and government to measure and monitor the energy efficiency of data centers. However, the energy use of data centers is just one aspect of the environmental impact. In this paper, we explore the overall environmental footprint of data centers beyond just energy efficiency. Building upon established procedures from the environmental sciences, we create an end-to-end life-cycle model of the environmental footprint of data centers across a diverse range of impacts. We test this model in the case study of a hypothetical 2.2-MW data center. Our analysis suggests the need for evaluation metrics that go beyond just operational energy use in order to achieve sustainable data centers.
Optimization of Parallel, Horizontal, and Laminar Forced Air-Cooled Heat Generating Boards
Authors: Özdemir M. O. , Yüncü H.
Published: September 2011

The objective of this study is to predict numerically the optimal spacing between parallel heat generating boards. The isothermal boards are stacked in a fixed volume of electronic package enclosed by insulated lateral walls, and they are cooled by laminar forced convection of air with prescribed pressure drop. In the numerical procedure, governing equations for the solution of forced convection of constant property incompressible flow through one rectangular channel are solved. Resulting flow and temperature fields in each rectangular channel yield the optimal board-to-board spacing by which maximum heat dissipation rate from the package to the air is achieved. Next, generalized correlations for the determination of the maximum heat transfer rate from the package and optimal spacing between boards are derived in terms of prescribed pressure difference, board length, and density and kinematic viscosity of air. Finally, corresponding correlations are compared with the available two-dimensional studies in literature for infinite parallel plates.
Accelerated Life Testing in Epoxy Packaged High Luminosity Light Emitting Diodes
Authors: Nogueira Eduardo , Vázquez Manuel , Algora Carlos
Published: September 2011

In this work, we have evaluated the reliability of epoxy packaged light emitting diodes (LEDs) for outdoor applications by specific tests to enhance catastrophic failures that appear under high temperature and humidity operation conditions. The different failure mechanisms were analyzed observing two main types: one is open circuit catastrophic failures induced by moisture and the other one power luminosity degradation. The influence of temperature and humidity on catastrophic failures was modelled using the Arrhenius–Peck law obtaining an activation energy of 0.87 eV and a Peck parameter of 2.29. MTTF value of 1.582 × 106 h at low bias current, 10 mA, has been evaluated.
Engineering the Growth Factor Microenvironment with Fibronectin Domains to Promote Wound and Bone Tissue Healing
Authors: Martino Mikaël M. , Tortelli Federico , Mochizuki Mayumi , Traub Stephanie , Ben-David Dror , Kuhn Gisela A. , Müller Ralph , Livne Erella , Eming Sabine A. , Hubbell Jeffrey A.
Published: September 2011

A multifunctional fibronectin fragment enhances the regenerative effects of growth factors in vivo in animal models of chronic wounds and critical-size bone defects.
Identification and Immunological Characterization of Three Potential Vaccinogens against Cryptosporidium Species
Authors: Manque Patricio A. , Tenjo Fernando , Woehlbier Ute , Lara Ana M. , Serrano Myrna G. , Xu Ping , Alves João M. , Smeltz Ronald B. , Conrad Daniel H. , Buck Gregory A.
Published: September 2011

Cryptosporidiosis is a ubiquitous infectious disease, caused by the protozoan parasites
Cryptosporidium hominis
and
Cryptosporidium parvum
, leading to acute, persistent, and chronic diarrhea with life-threatening consequences in immunocompromised individuals. In developing countries, cryptosporidiosis in early childhood has been associated with subsequent significant impairment in growth, physical fitness, and intellectual abilities. Currently, vaccines are unavailable and chemotherapeutics are toxic and impractical, and agents for immunoprophylaxis or treatment of cryptosporidiosis are a high priority. Availability of the genome sequences for
C. hominis
and
C. parvum
provides new opportunities to procure and examine novel vaccine candidates. Using the novel approach of “reverse vaccinology,” we identified several new potential vaccine candidates. Three of these antigens—Cp15, profilin, and a
Cryptosporidium
apyrase—were delivered in heterologous prime-boost regimens as fusions with cytolysin A (ClyA) in a
Salmonella
live vaccine vector and as purified recombinant antigens, and they were found to induce specific and potent humoral and cellular immune responses, suggesting their potential as new vaccinogens against
Cryptosporidium
infection.
Analysis of Entamoeba histolytica Excretory-Secretory Antigen and Identification of a New Potential Diagnostic Marker
Authors: Wong Weng Kin , Tan Zi Ning , Othman Nurulhasanah , Lim Boon Huat , Mohamed Zeehaida , Olivos Garcia Alfonso , Noordin Rahmah
Published: September 2011

Serodiagnosis of amoebiasis remains the preferred method for diagnosis of amoebic liver abscess (ALA). However, the commercially available kits are problematic in areas of endemicity due to the persistently high background antibody titers. Human serum samples (
n
= 38) from patients with ALA who live in areas of endemicity were collected from Hospital Universiti Sains Malaysia during the period of 2008 to 2010. Western blots using excretory-secretory antigen (ESA) collected from axenically grown
Entamoeba histolytica
were probed with the above serum samples. Seven antigenic proteins of ESA with various reactivities were identified, i.e., 152 kDa, 131 kDa, 123 kDa, 110 kDa, 100 kDa, 82 kDa, and 76 kDa. However, only the 152-kDa and 110-kDa proteins showed sensitivities above 80% in the Western blot analysis. All the antigenic proteins showed undetectable cross-reactivity when probed with healthy human serum samples (
n
= 30) and serum samples from other infections (
n
= 33). From the matrix-assisted laser desorption ionization–two-stage time of flight (MALDI-TOF/TOF) analysis, the proteins were identified as heavy subunits of
E. histolytica
lectin and
E. histolytica
pyruvate phosphate dikinase, respectively. Use of the
E. histolytica
lectin for diagnosis of ALA has been well reported by researchers and is being used in commercialized kits. However, this is the first report on the potential use of pyruvate phosphate dikinase for diagnosis of ALA; thus, this molecule merits further evaluation on its diagnostic value using a larger panel of serum samples.
Evaluation of Four Commercial Real-Time PCR Assays for Detection of Bordetella spp. in Nasopharyngeal Aspirates
Authors: Lanotte Philippe , Plouzeau Chloé , Burucoa Christophe , Grélaud Carole , Guillot Sophie , Guiso Nicole , Garnier Fabien
Published: September 2011

We evaluated the performances of 4 commercial real-time PCR kits for
Bordetella pertussis
IS
481
sequence detection in nasopharyngeal aspirates by comparison with an in-house real-time PCR assay. Among them, the Simplexa Bordetella pertussis/parapertussis assay (Focus Diagnostics), the SmartCycler
Bordetella pertussis
/
parapertussis
assay (Cepheid), and Bordetella R-gene (Argene) present sensitivities over 90%. One kit proved unsuitable for routine clinical use.
Aerococcus urinae and Trimethoprim-Sulfamethoxazole
Authors: Humphries Romney M. , Lee Courtney , Hindler Janet A.
Published: September 2011

Aerococcus urinae
has been described as resistant to trimethoprim-sulfamethoxazole (SXT), but the test medium may affect this observation. Twenty-seven clinical isolates of
A. urinae
tested susceptible to SXT in cation-adjusted Mueller-Hinton broth (CAMHB) plus lysed horse blood and resistant in CAMHB plus lysed sheep blood.
Decay-Accelerating Factor Binding Determines the Entry Route of Echovirus 11 in Polarized Epithelial Cells
Authors: Sobo Komla , Rubbia-Brandt Laura , Brown T. David K. , Stuart Amanda D. , McKee Thomas A.
Published: September 2011

The interaction between echovirus 11 strain 207 (EV11-207) and decay-accelerating factor (DAF or CD55) at the apical surface of polarized Caco-2 cells results in rapid transport of the virus to tight junctions and in its subsequent uptake. A virus mutant (EV11-207R) which differs at 6 amino acids and whose affinity for DAF is apparently significantly lower remains at the apical surface, from where its uptake occurs. Binding of EV11-207 to DAF and its transport to tight junctions result in a loss of function of the junctions. In contrast, the mutant virus EV11-207R is not transferred to tight junctions, nor does it impair the integrity of these junctions. Cholesterol depletion from the apical membrane leads to DAF aggregation and, presumably, internalization and inhibits infection by EV11-207. However, infection by EV11-207R is significantly less sensitive to cholesterol depletion than infection by EV11-207, confirming the DAF requirement for EV11-207, but not EV11-207R, to infect cells. These data strongly indicate that in the case of infection of polarized epithelial cells by echovirus 11, DAF binding appears be a key determinant in the choice of entry pathway, at least in cell culture.
Immunotherapy of Murine Retrovirus-Induced Acquired Immunodeficiency by CD4 T Regulatory Cell Depletion and PD-1 Blockade
Authors: Li Wen , Green William R.
Published: September 2011

LP-BM5 retrovirus induces a complex disease featuring an acquired immunodeficiency syndrome termed murine AIDS (MAIDS) in susceptible strains of mice, such as C57BL/6 (B6). CD4 T helper effector cells are required for MAIDS induction and progression of viral pathogenesis. CD8 T cells are not needed for viral pathogenesis, but rather, are essential for protection from disease in resistant strains, such as BALB/c. We have discovered an immunodominant cytolytic T lymphocyte (CTL) epitope encoded in a previously unrecognized LP-BM5 retroviral alternative (+1 nucleotide [nt])gagtranslational open reading frame. CTLs specific for this crypticgagepitope are the basis of protection from LP-BM5-induced immunodeficiency in BALB/c mice, and the inability of B6 mice to mount an anti-gagCTL response appears critical to the initiation and progression of LP-BM5-induced MAIDS. However, uninfected B6 mice primed by LP-BM5-induced tumors can generate CTL responses to an LP-BM5 retrovirus infection-associated epitope(s) that is especially prevalent on such MAIDS tumor cells, indicating the potential to mount a protective CD8 T-cell response. Here, we utilized this LP-BM5 retrovirus-induced disease system to test whether modulation of normal immune down-regulatory mechanisms can alter retroviral pathogenesis. Thus, followingin vivodepletion of CD4 T regulatory (Treg) cells and/or selective interruption of PD-1 negative signaling in the CD8 T-cell compartment, retroviral pathogenesis was significantly decreased, with the combined treatment of CD4 Tregcell depletion and PD-1 blockade working in a synergistic fashion to substantially reduce the induction of MAIDS.
Proteinase K-Resistant Material in ARR/VRQ Sheep Brain Affected with Classical Scrapie Is Composed Mainly of VRQ Prion Protein
Authors: Jacobs J. G. , Bossers A. , Rezaei H. , van Keulen L. J. M. , McCutcheon S. , Sklaviadis T. , Lantier I. , Berthon P. , Lantier F. , van Zijderveld F. G. , Langeveld J. P. M.
Published: September 2011

Classical scrapie is a prion disease in sheep and goats. In sheep, susceptibility to disease is genetically influenced by single amino acid substitutions. Genetic breeding programs aimed at enrichment of arginine-171 (171R) prion protein (PrP), the so-called ARR allele, in the sheep population have been demonstrated to be effective in reducing the occurrence of classical scrapie in the field. Understanding the molecular basis for this reduced prevalence would serve the assessment of ARR adaptation. The prion formation mechanism and conversion of PrP from the normal form (PrP
C
) to the scrapie-associated form (PrP
Sc
) could play a key role in this process. Therefore, we investigated whether the ARR allele substantially contributes to scrapie prion formation in naturally infected heterozygous 171Q/R animals. Two methods were applied to brain tissue of 171Q/R heterozygous sheep with natural scrapie to determine the relative amount of the 171R PrP fraction in PrP
res
, the proteinase K-resistant PrP
Sc
core. An antibody test differentiating between 171Q and 171R PrP fragments showed that PrP
res
was mostly composed of the 171Q allelotype. Furthermore, using a novel tool for prion research, endoproteinase Lys-C-digested PrP
res
yielded substantial amounts of a nonglycosylated and a monoglycosylated PrP fragment comprising codons 114 to 188. Following two-dimensional gel electrophoresis, only marginal amounts (<9%) of 171R PrP
res
were detected. Enhanced 171R
res
proteolytic susceptibility could be excluded. Thus, these data support a nearly zero contribution of 171R PrP in PrP
res
of 171R/Q field scrapie-infected animals. This is suggestive of a poor adaptation of classical scrapie to this resistance allele under these natural conditions.
Cross-Species Analysis of the Replication Complex of Old World Arenaviruses Reveals Two Nucleoprotein Sites Involved in L Protein Function
Authors: Kerber Romy , Rieger Toni , Busch Carola , Flatz Lukas , Pinschewer Daniel D. , Kümmerer Beate M. , Günther Stephan
Published: September 2011

Lassa virus (LASV) causing hemorrhagic Lassa fever in West Africa, Mopeia virus (MOPV) from East Africa, and lymphocytic choriomeningitis virus (LCMV) are the main representatives of the Old World arenaviruses. Little is known about how the components of the arenavirus replication machinery, i.e., the genome, nucleoprotein (NP), and L protein, interact. In addition, it is unknown whether these components can function across species boundaries. We established minireplicon systems for MOPV and LCMV in analogy to the existing LASV system and exchanged the components among the three systems. The functional and physical integrity of the resulting complexes was tested by reporter gene assay, Northern blotting, and coimmunoprecipitation studies. The minigenomes, NPs, and L proteins of LASV and MOPV could be exchanged without loss of function. LASV and MOPV L protein was also active in conjunction with LCMV NP, while the LCMV L protein required homologous NP for activity. Analysis of LASV/LCMV NP chimeras identified a single LCMV-specific NP residue (Ile-53) and the C terminus of NP (residues 340 to 558) as being essential for LCMV L protein function. The defect of LASV and MOPV NP in supporting transcriptional activity of LCMV L protein was not caused by a defect in physical NP-L protein interaction. In conclusion, components of the replication complex of Old World arenaviruses have the potential to functionally and physically interact across species boundaries. Residue 53 and the C-terminal domain of NP are important for function of L protein during genome replication and transcription.
Gag Cytotoxic T Lymphocyte Escape Mutations Can Increase Sensitivity of HIV-1 to Human TRIM5α, Linking Intrinsic and Acquired Immunity
Authors: Battivelli Emilie , Migraine Julie , Lecossier Denise , Yeni Patrick , Clavel François , Hance Allan J.
Published: September 2011

Although laboratory-adapted HIV-1 strains are largely resistant to the human restriction factor TRIM5α (hTRIM5α), we have recently shown that some viruses carrying capsid (CA) sequences from clinical isolates can be more sensitive to this restriction factor. In this study we evaluated the contribution to this phenotype of CA mutations known to be associated with escape from cytotoxic T lymphocyte (CTL) responses. Recombinant viruses carrying HIV-1 CA sequences from NL4-3 and three different clinical isolates were prepared, along with variants in which mutations associated with CTL resistance were modified by site-directed mutagenesis, and the infectivities of these viruses in target cells expressing hTRIM5α and cells in which TRIM5α activity had been inhibited by overexpression of TRIM5γ were compared. For both hTRIM5α-sensitive viruses studied, CTL-associated mutations were found to be responsible for this phenotype. Both CTL resistance mutations occurring within HLA-restricted CA epitopes and compensatory mutations occurring outside CTL epitopes influenced hTRIM5α sensitivity, and mutations associated with CTL resistance selected in prior hosts can contribute to this effect. The impact of CTL resistance mutations on hTRIM5α sensitivity was context dependent, because mutations shown to be responsible for the TRIM5α-sensitive phenotype in viruses from one patient could have little or no impact on this parameter when introduced into another virus. No fixed relationship between changes in hTRIM5α sensitivity and infectivity was discernible in our studies. Taken together, these findings suggest that CTL mutations may influence HIV-1 replication by modifying both viral infectivity and sensitivity to TRIM5α.
Increased Pathogenicity of a Reassortant 2009 Pandemic H1N1 Influenza Virus Containing an H5N1 Hemagglutinin
Authors: Cline Troy D. , Karlsson Erik A. , Freiden Pamela , Seufzer Bradley J. , Rehg Jerold E. , Webby Richard J. , Schultz-Cherry Stacey
Published: September 2011

A novel H1N1 influenza virus emerged in 2009 (pH1N1) to become the first influenza pandemic of the 21st century. This virus is now cocirculating with highly pathogenic H5N1 avian influenza viruses in many parts of the world, raising concerns that a reassortment event may lead to highly pathogenic influenza strains with the capacity to infect humans more readily and cause severe disease. To investigate the virulence of pH1N1-H5N1 reassortant viruses, we created pH1N1 (A/California/04/2009) viruses expressing individual genes from an avian H5N1 influenza strain (A/Hong Kong/483/1997). Using several
in vitro
models of virus replication, we observed increased replication for a reassortant CA/09 virus expressing the hemagglutinin (HA) gene of HK/483 (CA/09-483HA) relative to that of either parental CA/09 virus or reassortant CA/09 expressing other HK/483 genes. This increased replication correlated with enhanced pathogenicity in infected mice similar to that of the parental HK/483 strain. The serial passage of the CA/09 parental virus and the CA/09-483HA virus through primary human lung epithelial cells resulted in increased pathogenicity, suggesting that these viruses easily adapt to humans and become more virulent. In contrast, serial passage attenuated the parental HK/483 virus
in vitro
and resulted in slightly reduced morbidity
in vivo
, suggesting that sustained replication in humans attenuates H5N1 avian influenza viruses. Taken together, these data suggest that reassortment between cocirculating human pH1N1 and avian H5N1 influenza strains will result in a virus with the potential for increased pathogenicity in mammals.
Major Histocompatibility Complex Class II Expression and Hemagglutinin Subtype Influence the Infectivity of Type A Influenza Virus for Respiratory Dendritic Cells
Authors: Hargadon Kristian M. , Zhou Haixia , Albrecht Randy A. , Dodd Haley A. , García-Sastre Adolfo , Braciale Thomas J.
Published: September 2011

Dendritic cells (DC) play a key role in antiviral immunity, functioning both as innate effector cells in early phases of the immune response and subsequently as antigen-presenting cells that activate the adaptive immune response. In the murine respiratory tract, there are several respiratory dendritic cell (RDC) subsets, including CD103+DC, CD11bhiDC, monocyte/macrophage DC, and plasmacytoid DC. However, little is known about the interaction between these tissue-resident RDC and viruses that are encountered during natural infection in the respiratory tract. Here, we show bothin vitroandin vivothat the susceptibility of murine RDC to infection with type A influenza virus varies with the level of MHC class II expression by RDC and with the virus strain. Both CD103+and CD11bhiRDC, which express the highest basal level of major histocompatibility complex (MHC) class II, are highly susceptible to infection by type A influenza virus. However, efficient infection is restricted to type A influenza virus strains of the H2N2 subtype. Furthermore, enhanced infectivity by viruses of the H2N2 subtype is linked to expression of the I-E MHC class II locus product. These results suggest a potential novel role for MHC class II molecules in influenza virus infection and pathogenesis in the respiratory tract.
011 Pilot project evaluating HIV testing in St George's Emergency Department
Authors: Hempling M C , Pakianathan M , Majewska W , Shields K , Davey S , Karim J
Published: September 2011

Objectives and Backgrounds

With the availability of highly active antiretroviral therapy, HIV is now very treatable. However, a third of those with HIV remain undiagnosed and the majority of deaths occurring in those with HIV are due to late diagnosis.

Aims

To improve the detection rate of HIV early to offer people the opportunity to tackle the disease more effectively. To assess acceptability of the test to patients and staff within the ED.

Methods

Eligible patients were adults between 18 and 65 who attend the ED from 1 to 31 March 2011 having blood tests and able to consent. A trained member of staff obtained verbal consent. Patients were given an information leaflet and opportunity to ask questions. Testing was undertaken by laboratory staff and a telephone results line set up. Positive results were followed up by GUM staff. A survey was sent to the ED staff for further feedback.

Results

Results 2726 eligible patients had blood tests taken during the pilot period. 584 HIV tests were taken. Three new positives were diagnosed. In addition at least two patients with known HIV also attended during giving a prevalence of 0.85%. Over 50% of patients declined testing. The commonest reason was that they did not perceive that they were at risk. A minority were offended by being offered the test. The majority of staff responding to the survey were comfortable offering HIV testing (86%) and felt it appropriate to offer the test in the ED (81%).

Conclusions

Most staff who answered the survey were happy to offer HIV testing. However, in many cases, the test was not offered or patients declined. Further training of the ED staff would be beneficial as we could have missed opportunities to pick up many more positives. Although three new diagnoses is a small number, this gives a prevalence that far exceeds the 2 in 1000 suggested by national HIV guidelines to make offering routine testing worthwhile. However, further cost analysis and assessment of overall impact on the ED would need to be done before we could continue to offer routine testing.
012 Retrospective analysis of cervical spine radiography in a tertiary head injury centre
Authors: Shafei R , Baneke A , Fink D , Costello J
Published: September 2011

Objectives and Backgrounds

The EAST (Eastern Association for the Surgery of Trauma) guidelines define adequate radiography of the cervical spine. Previous studies looking at emergency department cervical spine radiographs have found a significant proportion to be inadequate. This study will ascertain the adequacy of cervical spine imaging on trauma patients in a major London tertiary referral centre. Local reporting of cervical spine radiographs are compared to the gold standard EAST guidelines.

Methods

Data were examined from 100 consecutive patients. We applied the EAST criteria retrospectively to all cervical spine radiology undertaken in this cohort of patients to define adequate or inadequate films. We assessed the performance of local radiology reporting.

Results

99% of patients undergoing a full trauma series had at least one inadequate initial image. Of these, 85% had at least one inadequate lateral or peg view. 74% with inadequate initial lateral or peg views had repeats performed. Only 23% of all inadequate initial and repeat lateral or peg views were explicitly reported as inadequate on the radiology report. In total 36% of all trauma patients left the emergency department with inadequate cervical spine imaging (no full trauma series or no repeat after an inadequate film).

Conclusions

Inadequate radiography of the cervical spine is common in trauma. Over one-third of trauma patients may not receive adequate imaging of their cervical spine; these findings suggest that there is significant process variability, which is compounded by the heterogamous population. We offer solutions.
014 Routine HIV testing in the Emergency Department: a tale of two trials: Abstract 014 Table 1
Authors: Finlay S , Rayment M , Rae C , Roberts P , Sullivan A
Published: September 2011

Objectives and Backgrounds

The problem of undiagnosed HIV in the UK, resulting in preventable transmission rates, morbidity, mortality and cost, needs to be addressed. The HINTS (“HIV testing in Non-Traditional Settings”) trial showed that HIV testing in the ED is acceptable to patients and successful in identifying previously undiagnosed individuals. We aim to establish a model for sustainable HIV screening in the ED. HEDsUP (“HIV Testing in Emergency Departments: A Universal Offer Programme”) investigates ED-led delivery of testing within a network of four North West London EDs.

Methods

We implemented 24/7 doctor-delivered testing of all 16–65-year-old ED patients able to consent, as a part of routine care. Patient information leaflets were given and promotional material displayed. Salivary tests collected in the ED were processed in the local virology laboratory. Patients received results by text message (negative result) or telephone call if test reactive to arrange confirmatory serology. Local sexual health services organised all follow-up. ED and Sexual Health staff met weekly to review key outcome measures (number of eligible patients, numbers of tests offered and accepted). Sustainability methodology (real time run charts, statistical control methods, plan-do-study-act cycles) was used to modify processes in an iterative fashion.

Results

See Abstract 014 table below. Marked weekly variation was noted in all key outcome measures. Plan-do-study-act cycles with notable positive impact included introduction of local champions, in-house teaching, and increased prominence of promotional material.

Abstract 014 Table 1

Results

HINTSHEDsUP (wks 1–20)Eligible40707262Offered3469715Accepted2123 (61.2%)468 (65.5%)Sero-positivity4 (0.19%)1 (0.21%)

Conclusions

HIV testing in EDs is feasible and remains acceptable (arguably more so) when doctor-delivered. Main challenges identified were expanding and maintaining provision across all shifts and all staff. An IT solution to prompt further testing is planned. Further work is underway to identify barriers to testing through focus groups and 1:1 interviews.
021 Non-standard practice of phlebotomy techniques: a significant cause of wasted samples and potential misleading results in Emergency Medicine
Authors: Berg J E , Berg J D , Ahee P
Published: September 2011

Objectives and Backgrounds

Phlebotomy is a potential cause of pre-analytical errors in the setting of a busy Emergency Department. We have studied current phlebotomy techniques in the Majors area comparing these to standard protocols that should be followed. We have looked at the incidence of haemolysed samples and compared this with that seen in the wider hospital.

Methods

Phlebotomy episodes (n=50) were observed and compared to standard procedures. A computer based search of the number of haemolysed samples from Emergency Medicine and all hospital in-patients was reviewed.

Results

A total of 13 different types of Emergency Department staff were observed undertaking 50 phlebotomy episodes in the Majors area of the Emergency Department. Four different ways of taking blood were observed; cannulation and a syringe (38%), cannula with evacuated tube and adaptor (42%), syringe and needle into vein (14%), evacuated tube system used conventionally (6%). Where a syringe was used, two methods of transfer into the sample tube were observed; needle kept on with cap piercing (77%) and needle and evacuated cap both removed (23%). On 20 out of 50 phlebotomy episodes (40%), the potassium EDTA tube was filled prior to the biochemistry tube. A study of ward based phlebotomy found 30 of 1034 samples were haemolysed (2.9%). In the 50 phlebotomy episodes in the Majors area of the Emergency Department 24% produced a haemolysed sample (p<0.0001). Study of the samples taken from all areas of Emergency Medicine over a 7-day period showed 52 of 485 were haemolysed (10.7%; p<0.0001).

Conclusions

Our results show that phlebotomy techniques in the Emergency Department vary considerably to those set out in standard protocols and manufacturers' guidelines. The evacuated tube system was used incorrectly over 50% of the time. In particular our results suggest that the use of small lumen cannula in the Majors area is a significant cause of haemolysed samples. Most staff were clearly unaware of the importance of the order of sample draw, which can lead to incorrect results for important analytes such as potassium, calcium and magnesium. There is also likely to be an increased incidence of needle stick injuries with samples being stabbed into collection tubes. Addressing these issues will help improve performance in hard times.
023 Multiprofessional morning handover in the Emergency Department: is it effective?
Authors: Lajko K , Dev S , Adshead N
Published: September 2011

Objectives and Backgrounds

Emergency Department (ED) handovers are arguably more complex than that which takes place in ward environments. This is because of an unpredictable patient load, compressed time-frames to meet operational and performance targets and undifferentiated and undiagnosed nature of the clinical problems. In order to ensure safe, relevant and accurate handovers in our department, we have implemented a novel multiprofessional model incorporating appropriate information exchange, learning opportunities and social interaction. In this study we investigated the effectiveness and usefulness of this new morning handover structure.

Methods

A questionnaire containing 10 questions were given to staff over a 1-week period (14 to 20 March 2011). The questions included the following: (a) usefulness of multiprofessional handover (MPH) as a source of information about departmental and trust updates; (b) patient care and operational issues; (c) interprofessional education forum; and (d) comparison with previous handover experience.

Results

We obtained data from 75 staff members comprising a mixture of the multiprofessional team (clinical lead, matron, all grades of medical staff, all grades of nursing staff, medical and nursing students, emergency pharmacist, domestic violence team, general manager, practice development team and alcohol liaison nurse). The results demonstrated that staff mostly supported the new morning handover structure. It was thought to be a very useful source of information in regards to departmental and trust updates in a multiprofessional forum (75 staff members). Staff members felt it was a forum for interprofessional education (65 staff members). Also, majority agreed that it improved patient care and operational issues within the department and trust wide (67 staff members).

Conclusions

Our unique morning handover structure ensures patient safety as well as appropriate transfer of information and responsibility to all involved with the care of patients in the Emergency Department. It offers the opportunity for multiprofessional learning, encourages team work and improves the operational processes within the Emergency Department.
025 Management and outcomes of febrile infants
Authors: Hare M , Burke D , Rimmer C
Published: September 2011

Objectives and Background

One of the new Emergency Department (ED) clinical quality indicators (CQIs) defines febrile infants as “high risk” patients requiring consultant “sign-off” prior to discharge. A service evaluation of the management and outcomes of febrile infants attending our ED in 2010 was undertaken in order to determine how our department would have complied with this CQI.

Methods

The sample population was identified and data collected retrospectively using the department's electronic database. Of those, 100 patients discharged but not initially seen by a consultant were randomly selected and had their case notes reviewed.

Results

1137 febrile infants attended the ED and 8% were re-attendances (Abstract 025 figure 1). 75% attended outside of normal working hours, of which 22% attended at night, when a consultant is not routinely on site (Abstract 025 figure 2). 78% of the infants were discharged, 22% were admitted, and only an estimated 6% of those discharged were “signed-off” by a consultant. The majority of febrile infants were seen by an SHO (Abstract 025 figure 3). 2.5% were well, 93% had a minor illness, 3.6% had a serious illness and in 0.9% the diagnosis was unknown. None of the patients died.

Abstract 025 Figure 1

SCMED activity in 2010.

Abstract 025 Figure 2

Time of attendance.

Abstract 025 Figure 3

Grade of ED officer doing initial assessment.

Conclusion

Febrile infants represent a significant proportion of our ED attendances (2.5%). A high proportion of febrile infants re-attend, and few are signed off by a consultant prior to discharge. The majority of febrile infants have minor illnesses. This service evaluation would suggest that the threshold for defining high-risk should be reviewed, possibly to include other clinical signs/symptoms in the definition, or to reduce the defined age to <6 months. Otherwise significant changes to ED consultant working patterns are likely to be required in order to increase the number of patients in this high-risk group achieving consultant “sign-off”.