bluuebunny/crossref_metadata_2025 huggingface dataset:
Externally Pressurized Bearings as Servomechanisms. I—The Simple Thrust Bearing
Authors: Wilcock Donald F.
Published: September 2011

The externally pressurized bearing may be considered and analyzed as an hydraulic closed-loop servomechanism. The use of restrictor feed devices introduces an inner loop that reduces the gain. The time-dependent flow due to the change in volume with film thickness creates a “lead” break frequency favorable to stability. Fluid compressibility, on the other hand, leads to a “lag” break frequency which, if it approaches or becomes less than the “lead” frequency, results in bearing instability. Analysis by transfer function furnishes fresh insight into EP bearing behavior.
The Influence of Lubricant Compressibility on the Performance of the 120 Degree Partial Journal Bearing
Authors: Gunter E. J.
Published: September 2011

This paper discusses the characteristics of the 120 deg bearing as the compressibility parameter Λ is increased from 0 to ∞. At low values of Λ and light loads, the gas bearing behaves as an incompressible lubricated bearing. Curves are developed to show under what conditions of bearing loading, film thickness, and speed the partial gas bearing may be treated by the incompressible theory. The compressibility parameter Λ has a considerable effect on the proper selection of the shoe pivot position and bearing clearance ratio for both maximum load capacity and minimum coefficient of friction. It is shown that the bearing clearance ratio and pivot location can vary considerably and still maintain close to optimum conditions at low compressibility numbers. At higher compressibility numbers, the choice of pivot location has a substantial effect on the bearing load capacity and coefficient of friction. Also discussed are the optimum design ranges of the compressibility number Λ.
A Computationally Efficient Methodology for Generating Training Data for a Transient Neural Network of a Tip-Jet Reaction Drive System
Authors: Kestner Brian K. , Tai Jimmy C.M. , Mavris Dimitri N.
Published: September 2011

This paper presents a computationally efficient methodology for generating training data for a transient neural network model of a tip-jet reaction drive system for potential use as an onboard model in a model based control application. This methodology significantly reduces the number of training points required to capture the transient performance of the system. The challenge in developing an onboard model for a tip-jet reaction drive system is that the model has to operate over the whole flight envelope, to account for the different dynamics present in the system, and to adjust to system degradation or potential faults. In addition, the onboard model must execute in less time than the update interval of the controller. To address these issues, a computationally efficient training methodology and neural network surrogate model have been developed that captures the transient performance of the tip-jet reaction system. As the number of inputs to a neural network becomes large, the computational time needed to generate the number of training points required to accurately represent the range of operating conditions of the system may become quite large also. A challenge for the tip-jet reaction drive system is to minimize the number of neural network training points, while maintaining the high accuracy. To address this issue, a novel training methodology is presented which first trains a steady-state neural network model and uses deviations from steady-state operating conditions to define the transient portion of the training data. The combined results from both the transient and the steady-state training data can then be used to create a single transient neural network of the system. The results in this paper demonstrate that a transient neural network using this new computationally efficient training methodology has the potential to be a feasible option for use as an onboard real-time model for model based control of a tip-jet reaction drive system.
Nanopatterning of PMMA on insulating surfaces with various anticharging schemes using 30 keV electron beam lithography
Authors: Muhammad Mustafa , Buswell Steven C. , Dew Steven K. , Stepanova Maria
Published: September 2011

As a low cost and high throughput method for nanoscale pattern replication, step and flash imprint lithography (SFIL) with UV transparent masters is gaining prominence for its potential in photonics and integrated-circuit fabrication. However, dielectric materials appropriate for fabricating nanostructured SFIL masters present a challenge when employing electron beam lithography (EBL) because insulator substrates covered by polymeric resists such as PMMA tend to accumulate charge during EBL exposures, thereby degrading the process. In this work we explore the performance of four different EBL anticharging schemes for nanofabrication of dense arrays of dots having diameters 16–30 nm in PMMA on UV transparent fused silica (FS) substrates. These include overlayers of aluminum or a water-soluble conducting polymer, as well as sandwiching of Al or Cr thin films between the substrate and PMMA. The quality of patterns transferred from PMMA into the underlying metallic layers was analyzed, and the grain size of the metal was found to be the limiting factor determining the edge roughness. The best resolution was attained employing the conducting polymer top-coating. This scheme also involves fewer processing steps. The authors have used this technique for lift-off of Cr and Au as well as Cr masked etch transfer of nanosized patterns into glass substrates for UV-transparent master mold fabrication.
Gα
s
-Biased β
2
-Adrenergic Receptor Signaling from Restoring Synchronous Contraction in the Failing Heart
Authors: Chakir Khalid , Depry Charlene , Dimaano Veronica L. , Zhu Wei-Zhong , Vanderheyden Marc , Bartunek Jozef , Abraham Theodore P. , Tomaselli Gordon F. , Liu Shu-bai , Xiang Yang K. , Zhang Manling , Takimoto Eiki , Dulin Nickolai , Xiao Rui Ping , Zhang Jin , Kass David A.
Published: September 2011

Synchronizing abnormal contraction in the failing hearts permanently alters β
2
-adrenergic signaling, pointing to a new therapeutic approach.
Biomedical Innovation in Academic Institutions: Mitigating Conflict of Interest
Authors: Nelsen Lita L. , Bierer Barbara E.
Published: September 2011

Conflicts of interest around academic innovation must be managed if universities and their medical centers are to maintain the public trust.
Diagnosis of Listeria monocytogenes Meningoencephalitis by Real-Time PCR for the
hly
Gene
Authors: Le Monnier Alban , Abachin Eric , Beretti Jean-Luc , Berche Patrick , Kayal Samer
Published: September 2011

Listeria monocytogenes
is a bacterial pathogen that can invade the central nervous system (CNS), causing meningoencephalitis and brain abscesses. The diagnosis of CNS listeriosis, based on the isolation of the bacteria in the cerebrospinal fluid (CSF), can be difficult because of previous antibiotic treatment and a low number of bacteria in the CSF. To improve the sensitivity of microbiological diagnosis, we have developed a real-time PCR assay for detecting and quantifying
L. monocytogenes
DNA in the CSF. The designed primers specifically amplify the
L. monocytogenes
hly
gene, which encodes listeriolysin O, a pore-forming cytolysin. The PCR assay for the
hly
gene (PCR-hly) provides reproducible quantitative results over a wide dynamic range of concentrations and was highly sensitive while detecting a single gene copy/ml. By assaying a large panel of bacterial species, including species secreting pore-forming cytolysin, we determined the specificity of the PCR-hly, which exclusively detects the
L. monocytogenes
DNA. We then analyzed 214 CSF samples from patients suspected of having CNS listeriosis. PCR-hly was positive in all cases in which
L. monocytogenes
was isolated by culture. Positive PCR-hly of the CSF was also obtained for five additional, clinically confirmed cases of CNS listeriosis for which bacterial cultures were negative presumably due to previous treatment with antibiotics. As a complement to classical bacteriological CSF culture, our designed real-time PCR-hly assay proved to be valuable by enhancing the rapidity and the accuracy of the diagnosis of CNS infection by
L. monocytogenes
. In addition, the quantitative results provided may, in some instances, be useful for the follow-up of patients under treatment.
Listeria monocytogenes: a Rare Complication of Ventriculoperitoneal Shunt in Children
Authors: Le Monnier Alban , Blanot Stéphane , Abachin Eric , Beretti Jean-Luc , Berche Patrick , Kayal Samer
Published: September 2011

We report a case of ventriculoperitoneal (VP) shunt infection in a 3-year-old boy caused by the food-borne pathogen
Listeria monocytogenes
, subsequent to acute peritonitis. This unusual presentation of central nervous system (CNS) listeriosis underlines the ability of the bacteria to form and survive within biofilms on indwelling medical devices. Bacterial persistence may lead to treatment failure and spreading. We highlight the helpfulness of specific quantitative real-time PCR for the
hly
gene (PCR-hly) for the diagnosis and follow-up of such infections in detecting bacterial persistence within medical devices despite effective antibiotic treatment. Only the surgical replacement of the VP shunt will resolve the infection.
Determination of Disk Diffusion and MIC Quality Control Ranges for GSK1322322, a Novel Peptide Deformylase Inhibitor
Authors: Ross James E. , Scangarella-Oman Nicole E. , Miller Linda A. , Sader Helio S. , Jones Ronald N.
Published: September 2011

GSK1322322 is a novel peptide deformylase inhibitor in the early phase of development for treatment of complicated bacterial skin and skin structure infection and hospitalized community-acquired pneumonia. This quality control (QC) study was performed to establish broth microdilution and disk diffusion QC ranges for strains
Staphylococcus aureus
ATCC 29213 (MIC range, 1 to 4 μg/ml),
Haemophilus influenzae
ATCC 49247 (MIC and disk diffusion zone diameter ranges, 0.5 to 4 μg/ml and 20 to 28 mm, respectively),
Streptococcus pneumoniae
ATCC 49619 (MIC and disk diffusion zone diameter ranges, 0.12 to 0.5 μg/ml and 23 to 30 mm, respectively), and
S. aureus
ATCC 25923 (disk diffusion zone diameter range, 18 to 26 mm). These ranges are crucial for evaluating GSK1322322 potency as it progresses through clinical trials.
Rapid Virological Diagnosis of Central Nervous System Infections by Use of a Multiplex Reverse Transcription-PCR DNA Microarray
Authors: Leveque Nicolas , Van Haecke Adrien , Renois Fanny , Boutolleau David , Talmud Deborah , Andreoletti Laurent
Published: September 2011

Viruses are the main etiological cause of central nervous system (CNS) infections. A rapid molecular diagnosis is recommended to improve the therapeutic management of patients. The aim of this study was to evaluate the performances of a DNA microarray, the Clart Entherpex kit (Genomica, Coslada, Spain), allowing the rapid and simultaneous detection of 9 DNA and RNA neurotropic viruses: herpes simplex virus 1 (HSV-1), HSV-2, varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), HHV-7, HHV-8, and the human enteroviruses (HEVs). This evaluation was performed with 28 samples from the European proficiency panels (Quality Control for Molecular Diagnostics [QCMD]; Glasgow, Scotland) and then with 78 cerebrospinal fluid (CSF) specimens. The majority of the QCMD results obtained by the DNA microarray were similar to those recorded by the overall QCMD participants. The main discrepant results were observed for low concentrations of HSV-2 and HEVs. From the clinical samples, the kit detected 27 of the 28 herpesvirus CNS infections and all of the 30 HEV-positive CSF samples. No false-positive result was observed among the 20 virus-negative CSF samples. The clinical sensitivity, specificity, and negative and positive predictive values of the assay were 98.3, 100, 95.2, and 100%, respectively, when the results were compared to those of commercially available PCR assays. Interestingly, HHV-7 was detected in 11 (37%) of the 30 HEV-positive CSF samples from children suffering from aseptic meningitis causing significantly longer lengths of stay at the hospital than infection with HEVs alone (2.4 versus 1.4 days;
P
= 0.038). In conclusion, this preliminary study showed that this DNA microarray could be a valuable molecular diagnostic tool for single and mixed DNA and RNA virus infections of the CNS.
Comparative Evaluation of Bruker Biotyper and BD Phoenix Systems for Identification of Bacterial Pathogens Associated with Urinary Tract Infections
Authors: Yan Yingjun , Meng Shufang , Bian Dongmo , Quinn Criziel , Li Haijing , Stratton Charles W. , Tang Yi-Wei
Published: September 2011

The Bruker Biotyper and BD Phoenix systems were evaluated for identification of 1,024 bacterial urinary tract isolates. The Biotyper and Phoenix systems correctly identified 99.9% and 99.5% to the genus level and 99.1% and 98.5% to the species level, respectively. Both systems provide reliable results, and the Biotyper system offers a rapid tool for urine bacterial isolate identification.
Usefulness of Three-Channel Multiplex Real-Time PCR and Melting Curve Analysis for Simultaneous Detection and Identification of the Mycobacterium tuberculosis Complex and Nontuberculous Mycobacteria
Authors: Hong Yun Ji , Chung Young Hoon , Kim Taek Soo , Song Sang Hoon , Park Kyoung Un , Yim Jae Joon , Song Junghan , Lee Jae Ho , Kim Eui Chong
Published: September 2011

We attempted to determine the benefits of three-channel multiplex real-time PCR and melting curve analysis not only in detecting and distinguishing between nontuberculous mycobacteria (NTM) and the
Mycobacterium tuberculosis
complex but also in identifying NTM to the species level.
ADP Ribosylation Factor 1 Activity Is Required To Recruit AP-1 to the Major Histocompatibility Complex Class I (MHC-I) Cytoplasmic Tail and Disrupt MHC-I Trafficking in HIV-1-Infected Primary T Cells
Authors: Wonderlich Elizabeth R. , Leonard Jolie A. , Kulpa Deanna A. , Leopold Kay E. , Norman Jason M. , Collins Kathleen L.
Published: September 2011

HIV-1-infected cells are partially resistant to anti-HIV cytotoxic T lymphocytes (CTLs) due to the effects of the HIV Nef protein on antigen presentation by major histocompatibility complex class I (MHC-I), and evidence has been accumulating that this function of Nef is important
in vivo
. HIV Nef disrupts the normal expression of MHC-I by stabilizing a protein-protein interaction between the clathrin adaptor protein AP-1 and the MHC-I cytoplasmic tail. There is also evidence that Nef activates a phosphatidylinositol 3 kinase (PI3K)-dependent GTPase, ADP ribosylation factor 6 (ARF-6), to stimulate MHC-I internalization. However, the relative importance of these two pathways is unclear. Here we report that a GTPase required for AP-1 activity (ARF-1) was needed for Nef to disrupt MHC-I surface levels, whereas no significant requirement for ARF-6 was observed in Nef-expressing T cell lines and in HIV-infected primary T cells. An ARF-1 inhibitor blocked the ability of Nef to recruit AP-1 to the MHC-I cytoplasmic tail, and a dominant active ARF-1 mutant stabilized the Nef–MHC-I–AP-1 complex. These data support a model in which Nef and ARF-1 stabilize an interaction between MHC-I and AP-1 to disrupt the presentation of HIV-1 epitopes to CTLs.
Vesicular Stomatitis Virus-Based Vaccine Protects Hamsters against Lethal Challenge with Andes Virus
Authors: Brown Kyle S. , Safronetz David , Marzi Andrea , Ebihara Hideki , Feldmann Heinz
Published: September 2011

Andes virus (ANDV) is a highly pathogenic South American hantavirus that causes hantavirus pulmonary syndrome (HPS). A high case fatality rate, the potential for human-to-human transmission, the capacity to infect via aerosolization, and the absence of effective therapies make it imperative that a safe, fast-acting, and effective ANDV vaccine be developed. We generated and characterized a recombinant vesicular stomatitis virus (VSV) vector expressing the ANDV surface glycoprotein precursor (VSVΔG/ANDVGPC) as a possible vaccine candidate and tested its efficacy in the only lethal-disease animal model of HPS. Syrian hamsters immunized with a single injection of VSVΔG/ANDVGPC were fully protected against disease when challenged at 28, 14, 7, or 3 days postimmunization with a lethal dose of ANDV; however, the mechanism of protection seems to differ depending on when the immunization occurs. At 28 days postimmunization, a lack of detectable ANDV RNA in lung, liver, and blood tissue samples, as well as a lack of seroconversion to the ANDV nucleocapsidprotein in nearly all animals, suggested largely sterile immunity. The vaccine was able to generate high levels of neutralizing anti-ANDV G
N
/G
C
antibodies, which seem to play a role as a mechanism of vaccine protection. Administration of the vaccine at 7 or 3 days before challenge also resulted in full protection but with no specific neutralizing humoral immune response, suggesting a possible role of innate responses in protection against challenge virus replication. Administration of the vaccine 24 h postchallenge was successful in protecting 90% of hamsters and again suggested the induction of a potent antiviral state by the recombinant vector as a potential mechanism. Overall, our data suggest the potential for the use of the VSV platform as a fast-acting and effective prophylaxis/postexposure treatment against lethal hantavirus infections.
Feline Leukemia Virus Infection Requires a Post-Receptor Binding Envelope-Dependent Cellular Component
Authors: Hussain Naveen , Thickett Kelly R. , Na Hong , Leung Cherry , Tailor Chetankumar S.
Published: September 2011

Gammaretrovirus receptors have been suggested to contain the necessary determinants to mediate virus binding and entry. Here, we show that murine NIH 3T3 and baby hamster kidney (BHK) cells overexpressing receptors for subgroup A, B, and C feline leukemia viruses (FeLVs) are weakly susceptible (10
1
to 10
2
CFU/ml) to FeLV pseudotype viruses containing murine leukemia virus (MLV) core (Gag-Pol) proteins, whereas FeLV receptor-expressing murine
Mus dunni
tail fibroblast (MDTF) cells are highly susceptible (10
4
to 10
6
CFU/ml). However, NIH 3T3 cells expressing the FeLV subgroup B receptor PiT1 are highly susceptible to gibbon ape leukemia virus pseudotype virus, which differs from the FeLV pseudotype viruses only in the envelope protein. FeLV resistance is not caused by a defect in envelope binding, low receptor expression levels, or N-linked glycosylation. Resistance is not alleviated by substitution of the MLV core in the FeLV pseudotype virus with FeLV core proteins. Interestingly, FeLV resistance is alleviated by fusion of receptor-expressing NIH 3T3 and BHK cells with MDTF or human TE671 cells, suggesting the absence of an additional cellular component in NIH 3T3 and BHK cells that is required for FeLV infection. The putative FeLV-specific cellular component is not a secreted factor, as MDTF conditioned medium does not alleviate the block to FeLV infection. Together, our findings suggest that FeLV infection requires an additional envelope-dependent cellular component that is absent in NIH 3T3 and BHK cells but that is present in MDTF and TE671 cells.
Antibody-Mediated Enhancement of HIV-1 and HIV-2 Production from BST-2/Tetherin-Positive Cells
Authors: Miyagi Eri , Andrew Amy , Kao Sandra , Yoshida Takeshi , Strebel Klaus
Published: September 2011

BST-2/CD317/HM1.24/tetherin is a B-cell antigen overexpressed on the surface of myeloma cell lines and on neoplastic plasma cells of patients with multiple myeloma. Antibodies to BST-2 are in clinical trial for the treatment of multiple myeloma and are considered for the treatment of solid tumors with high BST-2 antigen levels. Functionally, BST-2 restricts the secretion of retroviruses, including human immunodeficiency virus type 1, as well as members of the herpesvirus, filovirus, and arenavirus families, presumably by tethering nascent virions to the cell surface. Here we report that BST-2 antibody treatment facilitates virus release from BST-2
+
cells by interfering with the tethering activity of BST-2. BST-2 antibodies were unable to release already tethered virions and were most effective when added early during virus production. BST-2 antibody treatment did not affect BST-2 dimerization and did not reduce the cell surface expression of BST-2. Interestingly, BST-2 antibody treatment reduced the nonspecific shedding of BST-2 and limited the encapsidation of BST-2 into virions. Finally, flotation analyses indicate that BST-2 antibodies affect the distribution of BST-2 within membrane rafts. Our data suggest that BST-2 antibody treatment may enhance virus release by inducing a redistribution of BST-2 at the cell surface, thus preventing it from accumulating at the sites of virus budding.
Characterization of the Human CD8+T Cell Response following Infection with 2009 Pandemic Influenza H1N1 Virus
Authors: Hillaire M. L. B. , van Trierum S. E. , Bodewes R. , van Baalen C. A. , van Binnendijk R. S. , Koopmans M. P. , Fouchier R. A. M. , Osterhaus A. D. M. E. , Rimmelzwaan G. F.
Published: September 2011

The 2009 H1N1 influenza pandemic provided an opportunity to study human virus-specific T cell responses after infection with a novel influenza virus against which limited humoral immunity existed in the population. Here we describe the magnitude, kinetics, and nature of the virus-specific T cell response using intracellular gamma interferon (IFN-γ) staining and fluorochrome-labeled major histocompatibility complex (MHC) class I-peptide complexes. We demonstrate that influenza virus-infected patients develop recall T cell responses that peak within 1 week postinfection and that contract rapidly. In particular, effector cell frequencies declined rapidly postinfection in favor of relatively larger proportions of central memory cells.
Gamma Interferon and Perforin Control the Strength, but Not the Hierarchy, of Immunodominance of an Antiviral CD8+T Cell Response
Authors: Remakus Sanda , Sigal Luis J.
Published: September 2011

The two major antiviral effector mechanisms of CD8+T cells are thought to be perforin (Prf)-mediated cell lysis and gamma interferon (IFN-γ)-mediated induction of an antiviral state. By affecting the expression of proteins involved in antigen presentation, IFN-γ is also thought to shape the magnitude and specificity of the CD8+T cell response. Here we studied the roles of Prf and IFN-γ in shaping the effector and memory CD8+T cell responses to vaccinia virus (VACV). IFN-γ deficiency resulted in increased numbers of anti-VACV effector and memory CD8+T cells, which were partly dependent on increased virus loads. On the other hand, Prf-deficient mice showed an increase in the number of VACV-specific CD8+T cells only in the memory phase. Treatment of the mice with the antiviral drug cidofovir reduced the numbers of effector and memory cells closer to wild-type levels in IFN-γ-deficient mice and reduced the numbers of memory CD8+T cells to wild-type levels in Prf-deficient mice. These data suggest that virus loads are the main reason for the increased strength of the CD8 response in IFN-γ- and Prf-deficient mice. Neither Prf deficiency nor IFN-γ deficiency had an effect on the immunodominance hierarchy of five Kb-restricted CD8+T cell determinants either during acute infection or after recovery. Thus, our work shows that CD8+T cell immunodominance during VACV infection is not affected by the effects of IFN-γ on the antigen presentation machinery.
Durable Mucosal Simian Immunodeficiency Virus-Specific Effector Memory T Lymphocyte Responses Elicited by Recombinant Adenovirus Vectors in Rhesus Monkeys
Authors: Li Hualin , Liu Jinyan , Carville Angela , Mansfield Keith G. , Lynch Diana , Barouch Dan H.
Published: September 2011

The induction of potent and durable cellular immune responses in both peripheral and mucosal tissues may be important for the development of effective vaccines against human immunodeficiency virus type 1 and other pathogens. In particular, effector responses at mucosal surfaces may be critical to respond rapidly to incoming mucosal pathogens. Here we report that intramuscular injection of nonreplicating recombinant adenovirus (rAd) vectors into rhesus monkeys induced remarkably durable simian immunodeficiency virus (SIV)-specific T lymphocyte responses that persisted for over 2 years in both peripheral blood and multiple mucosal tissues, including colorectal, duodenal, and vaginal biopsy specimens, as well as bronchoalveolar lavage fluid. In peripheral blood, SIV-specific T lymphocytes underwent the expected phenotypic evolution from effector memory T cells (TEM) to central memory T cells (TCM) following vaccination. In contrast, mucosal SIV-specific T lymphocytes exhibited a persistent and durable TEMphenotype that did not evolve over time. These data demonstrate that nonreplicating rAd vectors induce durable and widely distributed effector memory mucosal T lymphocyte responses that are phenotypically distinct from peripheral T lymphocyte responses. Vaccine-elicited TEMresponses at mucosal surfaces may prove critical for affording protection against invading pathogens at the mucosal portals of entry.
Human Cytomegalovirus Primase UL70 Specifically Interacts with Cellular Factor Snapin
Authors: Shen Ao , Lei Ji , Yang Edward , Pei Yonggang , Chen Yuan-Chuan , Gong Hao , Xiao Gengfu , Liu Fenyong
Published: September 2011

Genomic DNA synthesis is a universally conserved process for all herpesviruses, including human cytomegalovirus (HCMV). HCMV UL70 is believed to encode the primase of the DNA replication machinery, a function which requires localization in the nucleus, the site of viral DNA synthesis. No host factors that interact with UL70 have been reported. In this study, we provide the first direct evidence that UL70 specifically interacts with Snapin, a human protein that is predominantly localized in the cytoplasm and is associated with cellular vesicles. The interaction between UL70 and Snapin was identified in both the two-hybrid screen in yeast and coimmunoprecipitation in human cells. The nuclear import of UL70 was decreased in cells overexpressing Snapin and increased in cells in which the expression of Snapin was downregulated with anti-Snapin small interfering RNA (siRNA) molecules, respectively. Furthermore, viral DNA synthesis and progeny production were decreased in cells overexpressing Snapin and increased in the anti-Snapin siRNA-treated cells, respectively. In contrast, no significant difference in the nuclear level of UL70, viral DNA synthesis, and progeny production was found among the parental cells and cells that either expressed a control empty vector or were treated with control siRNA molecules that did not recognize any viral or cellular transcripts. Our results suggest that Snapin may play a key role in regulating the cellular localization of UL70 in HCMV, leading to modulation of viral DNA synthesis and progeny production.
Systems Virology Identifies a Mitochondrial Fatty Acid Oxidation Enzyme, Dodecenoyl Coenzyme A Delta Isomerase, Required for Hepatitis C Virus Replication and Likely Pathogenesis
Authors: Rasmussen Angela L. , Diamond Deborah L. , McDermott Jason E. , Gao Xiaoli , Metz Thomas O. , Matzke Melissa M. , Carter Victoria S. , Belisle Sarah E. , Korth Marcus J. , Waters Katrina M. , Smith Richard D. , Katze Michael G.
Published: September 2011

We previously employed systems biology approaches to identify the mitochondrial fatty acid oxidation enzyme dodecenoyl coenzyme A delta isomerase (DCI) as a bottleneck protein controlling host metabolic reprogramming during hepatitis C virus (HCV) infection. Here we present the results of studies confirming the importance of DCI to HCV pathogenesis. Computational models incorporating proteomic data from HCV patient liver biopsy specimens recapitulated our original predictions regarding DCI and link HCV-associated alterations in cellular metabolism and liver disease progression. HCV growth and RNA replication in hepatoma cell lines stably expressing DCI-targeting short hairpin RNA (shRNA) were abrogated, indicating that DCI is required for productive infection. Pharmacologic inhibition of fatty acid oxidation also blocked HCV replication. Production of infectious HCV was restored by overexpression of an shRNA-resistant DCI allele. These findings demonstrate the utility of systems biology approaches to gain novel insight into the biology of HCV infection and identify novel, translationally relevant therapeutic targets.
Persistent Infection Drives the Development of CD8
+
T Cells Specific for Late Lytic Infection Antigens in Lymphocryptovirus-Infected Macaques and Epstein-Barr Virus-Infected Humans
Authors: Orlova Nina , Wang Fred , Fogg Mark H.
Published: September 2011

We examined the CD8
+
T cell repertoire against lytic infection antigens in rhesus macaques persistently infected with the Epstein-Barr virus (EBV)-related lymphocryptovirus (rhLCV). CD8
+
T cells specific for late (L) antigens were detected at rates comparable to those for early antigens and were associated with increasing duration of infection. L antigen-specific CD8
+
T cells were also readily detected in adult, EBV-positive humans. Thus, viral major histocompatibility complex class I (MHCI) immune evasion genes expressed during lytic LCV infection do not prevent L-specific CD8
+
T cell development over time during persistent infection.
Baculovirus Infection Induces a DNA Damage Response That Is Required for Efficient Viral Replication
Authors: Huang Ning , Wu Wenbi , Yang Kai , Passarelli A. Lorena , Rohrmann George F. , Clem Rollie J.
Published: September 2011

Several mammalian viruses have been shown to induce a cellular DNA damage response during replication, and in some cases, this response is required for optimal virus replication. However, nothing is known about whether a DNA damage response is stimulated by DNA viruses in invertebrates. Cell cycle arrest and apoptosis are two of the downstream effects of the DNA damage response, and both are stimulated by baculovirus infection, suggesting a possible relationship between baculoviruses and the DNA damage response. In the study described in this report, we found that replication of the baculovirusAutographa californicaM nucleopolyhedrovirus (AcMNPV) in the cell line Sf9, derived from the lepidopteran insectSpodoptera frugiperda, stimulated a DNA damage response, as indicated by an increased abundance of theS. frugiperdaP53 protein (SfP53) and phosphorylation of the histone variant protein H2AX. Stimulation of the DNA damage response was dependent on viral DNA replication. Inhibition of the DNA damage response prevented both the increase in SfP53 accumulation and H2AX phosphorylation and also caused a 10- to 100-fold reduction in virus production, along with decreased viral DNA replication and late gene expression. However, silencing ofSfp53expression by RNA interference did not significantly affect AcMNPV replication or induction of apoptosis by a mutant of AcMNPV lacking the antiapoptotic genep35, indicating that these processes are not dependent on SfP53 in Sf9 cells.
010 Quality, performance and performance indicators: use of a standardised template to develop and promote quality and performance in Australasian Emergency Departments: Abstract 010 Figure 1
Authors: Richardson P G
Published: September 2011

Objectives and Backgrounds

What counts as quality or performance in the modern emergency department has changed since the inception of the Australasian College for Emergency Medicine (ACEM). Most if not all modern Emergency Physicians already know, that in addition to service provision, they are active and performing a number of other important domains: education and teaching research administration tasks crossing safety, risk management and continuity domains Professional development These other activities have previously not been formally recognised as valid performance measures.

Methods

Emergency physicians at the Royal Brisbane and Women's Hospital in Australia embarked on a process to develop a national template to facilitate individual emergency department quality and performance and have this adopted by the ACEM RBWH is the largest adult emergency department in Australasia with 75 000 attendances and staffed by 18 FTE FACEMs. In 2009 a modified Delphi was undertaken following a review of the current literature to identify what could be considered important quality and performance indicators of a highly functioning emergency department. This led to the development of a unifying template the identified all the core areas where emergency physicians are active and are required to show performance in for continuing professional development compliance. These domains can no longer be considered incidental to service provision.

Results

A template was developed with five core domains for emergency departments to show activity in: Quality and Performance Template (Figure 1) .

Abstract 010 Figure 1

Conclusions

The template was adopted by the ACEM Quality Sub Committee in September 2010 for further development as a standardised tool and template for promoting quality and performance in Australasian ED's. It will further be developed and enhanced by further research nationally and internationally as to its effectiveness and utility.
019 Nerve blocks: the next hip thing?
Authors: Buxton L
Published: September 2011

Objectives and Backgrounds

Fractured neck of femur (NOF) is a common presentation to UK emergency departments (ED) with approximately 75 000 patients admitted annually. Pain control and time to admission are important in this vulnerable group, and yet this is where we repeatedly underperform. Fascia iliac compartment block (FICB) is a well-established and efficacious method of analgesia for fractured hips with fewer side effects than systemic opiates and a longer duration of action. They do, however, mandate 60 min post-block observation in ED to check for signs of local anaesthetic toxicity. Objectives of this study were to evaluate whether delivery of a nerve block prolonged the time patients spent in the department (primary outcome) and whether need for additional analgesia were reduced in those patients receiving nerve blocks (secondary outcomes).

Methods

Ultrasound-guided FICBs were introduced into practice in Barnsley Hospital ED in July 2010. Training to enable ED nursing staff to deliver landmark-technique blocks commenced in February 2010 as well as a revision of the fractured NOF pathway to incorporate this new practice. An ST5 emergency medicine (EM) trainee and consultant delivered this training with input from the acute pain team. A retrospective review of case notes of all patients with fractured NOF from July 2010 to January 2011 was undertaken to evaluate outcome measures as above. Following introduction of the nurse training, a prospective service evaluation commenced on 01 February 2011 to evaluate outcome measures in patients receiving US guided or landmark technique FICB and standard analgesia. (This data collection is ongoing until 30 June 2011 and results given below are, therefore, preliminary findings).

Results

Patients identified with fractured NOF n=121; of these, 101 received “standard analgesia” (SA) and 21 received a nerve block (NB). Mean “time to admission” for SA=167 min (SD 63.3) and NB= 169 min (SD 48.5) p=0.736* (95% CI −31.2 to 22.1). Mean time to x-ray for SA= 72.54 min (SD 46.4) and NB=49.95 min (SD 24.5) p=0.003* (95% CI 8.15 to 37.03). 71.4% NBs were performed between 08:00 and 18:00 h and 28.6% between 18:00 and 24:00 h. Percentage of patients requiring additional analgesia: SA=20.5%, NB=19%. *Independent t test calculated using SPSS software.

Conclusions

Results suggest that patients receiving nerve blocks do not wait longer for admission than those receiving standard analgesia. In a time-target driven world, time to undertake a new intervention is of paramount importance when considering adopting new practice. Nerve blocks were carried out predominantly during the day when senior cover in the department was at a maximum. The mean length of time waiting for an x-ray is lower in the nerve block group suggesting that blocks are done when the department is less busy. As more staff become trained and experienced at nerve block delivery, it is expected that this trend will improve to a “round the clock” service and that block “success” will improve accordingly with reduced additional analgesia requirements.
020 Proformas: how to ensure compliance and is there any point? The Birmingham experience
Authors: Wimalasena Y , Ahee P , Borowska A
Published: September 2011

Objectives and Backgrounds

In most Emergency Departments (EDs) around the country proformas are in use for the management of patients with specific complaints. Proformas improve documentation, handover and are seen to reduce clinical risk by giving visible guidance to physicians. SWBH encompasses two large EDs seeing over 190 000 patients per year. Head injury, alcohol intoxication and headache proformas were introduced in November 2009, following an analysis of serious untoward incidents (SUIs), to decrease these incidents and improve patient safety. This retrospective analysis was done to evaluate if weekly auditing of proforma use and feedback to clinicians would improve compliance of proforma use and to analyse if use of proformas decreased serious untoward incidents.

Methods

Each week (from 31 January 2011 to 09 May 2011) the ED records identified as belonging to patients with head injury, alcohol intoxication or headache were identified by manually combing the triage notes. The use of the proformas for these three conditions was audited. Results were emailed weekly to all clinicians and some were contacted individually. Incidents involving these three conditions were retrospectively looked at for the past 3 years (April 2008 to March 2011).

Results

During the study period 780 patients with head injuries, 303 with headache and 127 intoxicated patients were seen. Proforma compliance increased from week 1 to week 15 for head injury (36% to 79%), headache (8% to 64%) and intoxication (38% to 62%). The total number of red and amber incidents involving head injury, headache and intoxication rose from 30 in 2008/2009 to 38 in 2009/2010 and decreased to 23 in 2010/2011.

Conclusions

Proformas for head injury, alcohol intoxication or headache, were effective at reducing risk and improving patient safety. No patient involved in a serious clinical incident had a proforma used! Our retrospective feedback audit has shown that regular auditing with feedback can improve compliance in proforma use.

Abstract 020 Table 1

Week vs compliance (%)

Head injury proformaAlcohol intoxicationHeadache proformaWeek 136428Week 242743Week 3706342Week 4814429Week 5776458Week 6735761Week 7725050Week 8708567Week 9825025Week 10738071Week 11796264Week 12746658Abstract 020 Figure 1
024 Matrix marking system: a future for debrief and assessment
Authors: Hanson J , Pimblett M , Dickinson M , Jones G , Davis M
Published: September 2011

Objectives and Backgrounds

Medical error accounts for 40 000 deaths per year in the UK, of which 50% are regarded as preventable. There is currently a greater emphasis on patient safety in medical practice; the practice of medicine is dependent on human cognition and although medical error is inevitable, training in both technical and non-technical skills can minimise this. Simulation enables practice in a safe environment and debrief is vital in these skills. The aim of this session is to describe a debrief system which enhances real-time marking through instant video feedback of performance in both technical and non-technical skills.

Methods

Initially analogue video systems were used for feedback. Identifying elements for debriefing was time-consuming and unreliable. Using digital recording systems integrated with Studiocode software, we are able to capture elements of a scenario directly onto a hard drive. I Coda software, initially developed to analyse sports performance, is used to code performance against templates developed for specific clinical scenarios. Both technical and non-technical performance can be observed, analysed and coded using an iPad or PDA. This has been developed as a portable system to facilitate observations in theatres, hospital transfers or other clinical environments.

Results

The Matrix Marking System provides opportunities for instantaneous debriefing after the simulation event in both technical and non-technical skills, based on performance evidence. The facilitator has access to a summary of ratings of performance and an opportunity to replay these for exploration and further analysis.

Conclusions

This brings a new dimension to the debriefing of individual or team performance. The learning conversation (debrief), which develops can be highlighted with instant video feedback to reinforce points for discussion. This system is undergoing validation for debriefing and assessments. We will be looking to report on progress in future meetings.
005 An external validation of the PECARN clinical decision rule for minor head injury
Authors: Fuller G , Lecky F , Batchelor J , Dunning J
Published: September 2011

Objectives and Backgrounds

500 000 children present to UK hospitals annually following minor head injury (MHI). Mortality is low (6–10 per 100 000), and most patients can be safely discharged from emergency departments. However, a small proportion of children with significant intracranial pathology are at risk for deterioration. CT is the gold-standard for investigation of MHI, but resource limitations, and risks from ionising radiation and pharmacological sedation, preclude its universal use. Clinical decision rules (CDR) were recently developed in a North American population by the PECARN research group, to guide CT use in childhood MHI. Our aim was to externally validate the rule for children over 5 years in a UK setting.

Methods

The CHALICE database consists of all children (<16 years) presenting to the emergency departments of 10 northwest England hospitals with head injury between February 2000 and August 2002. A dataset of demographic, clinical, radiological and outcome variables were recorded prospectively, and clinically significant head injuries identified. CHALICE patients >5 years were categorised according to PECARN CDR predictors and outcomes (clinically important head injury [ciHI]: death from HI, neurosurgery, intubation >24 h, hospital admission >2 nights with positive CT head). We then calculated the sensitivity, specificity, and negative predictive value for identifying ciHI in the CHALICE population using the PECARN CDR.

Results

The CHLAICE database consists of 22 772 children, with 65% males, and a mean age of 5.7 years. Following application of PECARN exclusion criteria a study population of 10 415 children aged >5 years were available for study. 2778 children met PECARN CT scanning criteria, and 246 had ciHI. Information for assessing severity of injury mechanism was incomplete (patient ejection and vehicle rollover variables absent). Data were present for all other PECARN predictors and outcomes. The PECARN rule demonstrated a sensitivity of 95% (95% CI 91 to 97), specificity of 75% (95% CI 74 to 76), and negative predictive value of 99.8% (95% CI 99.7 to 99.9) for the prediction of ciHI.

Conclusions

The PECARN clinical prediction rule for children >5 years performed well in a large UK cohort of children. Further work will examine refinements to the PECARN rule, and validate the CDR for children <2 years.
008 Risk assessment of patients presenting to the ED with chest pain and equivocal cardiac troponin T (cTnT) levels: the lost tribe?
Authors: Cook C , Krom A , Sood T
Published: September 2011

Objectives and Backgrounds

New high-sensitivity cTnT assays are being used to determine myocardial necrosis. These tests include an equivocal range for myocardial necrosis (0.014–0.030 μg/l), data on both clinical risk and outcomes for this group are limited. There is no explicit national guidance on the management of patients presenting with chest pain and equivocal cTnT values.

Objectives

(1) Individually risk asses patients presenting to the ED with chest pain and equivocal cTnT values [0.014 to <0.03 μg/l] for future adverse cardiovascular events using the Global Registry of Acute Cardiac Events [GRACE] risk scoring system. (2) Record the referral/discharge pathways of these patients.

Methods

Patients presenting to the ED with cTnTs in the equivocal range over a 1-month period were identified. Future risk of adverse cardiovascular events was retrospectively calculated using the GRACE risk scoring system.

Results

40 patients with cardiac type chest pain, adequate documentation and equivocal cTnT levels were identified. 49% of these patients were assessed as “high risk”, 36% “medium risk” and 15% “low risk” when retrospectively GRACE scored. Of the “high risk” patients, 58% were discharged home without any documentation of specialist involvement, in-patient [IP] investigation or follow-up. 72% of these patients may have been suitable for IP angiogram ± intervention within 96 h of admission, but just 15% of these patients received this.

Conclusions

Patients with cTnT concentrations in the equivocal range present a diagnostic dilemma for the ED clinician. They appear at increased risk of ACS when applying clinical risk stratification using a GRACE score. This increase in risk appears poorly appreciated, leading to opportunities for intervention being missed.
SPIN-ORBIT ENHANCED POLARON IN A SINGLE QUANTUM WELL
Authors: PANDA S. , PANDA B. K.
Published: September 2011

The polaronic corrections to the electron energy and effective mass are calculated taking the Rashba spin-orbit coupling in the compositionally asymmetric single quantum well based on heterostructures of narrow gap semiconductors InGaAs and InAs . The electron interaction with the confined longitudinal optic phonon is considered in the Fröhlich form for calculating the polaron properties. In the weak coupling limit, the polaron properties are enhanced by the Rashba spin-orbit coupling in the asymmetric quantum well.
k⋅p WURTZITE HAMILTONIAN AND OPTICAL MATRIX WITH BULK INVERSION ASYMMETRY
Authors: CHEN CHUN-NAN , SU WEI-LONG , WANG WAN-TSANG , JEN JEN-YI , LI YIMING
Published: September 2011

A k⋅p wurtzite Hamiltonian including the bulk (or intracell) inversion asymmetry is developed. Meanwhile, a k⋅p wurtzite optical matrix including this intracell asymmetry is also established.
THE INFLUENCES OF CARDIOVASCULAR PROPERTIES ON SUPRASYSTOLIC BRACHIAL CUFF WAVE STUDIED BY A SIMPLE ARTERIAL-TREE MODEL
Authors: LIANG FUYOU , TAKAGI SHU , LIU HAO
Published: September 2011

It has been found that a pronounced secondary systolic peak appears on the oscillometric wave recorded by a brachial oscillometric cuff as cuff pressure is raised to a suprasystolic level. This finding has accordingly motivated some studies aimed to explore the potential value carried by the cuff wave for assessing arterial stiffness. However, so far, there remain considerable controversies in the literature regarding the cardiovascular properties that dominate the characteristics of the cuff wave. In this context, we developed a simple arterial-tree model and applied it to investigate the respective influence on the cuff wave of various cardiovascular properties and the associated wave interaction phenomena. It was found that (1) neither aortic stiffness nor brachial arterial stiffness can uniquely determine the time lag (Δt) between the first and secondary peaks of the cuff wave, although both of them significantly influence Δt; and (2) the BAIx (an index that characterize the height of the secondary peak relative to the first) is sensitive to most of the investigated cardiovascular properties and physiological conditions, such as arterial stiffness, intensity of wave reflection in the lower body and heart rate, etc. These findings suggest that the reliability of assessing aortic stiffness based solely on the timings and heights of the two peaks is limited. Moreover, we argued that the controversial findings presented in previous model-based studies are likely to be caused by limitations related to the research objectives or computation conditions of the studies.