bluuebunny/crossref_metadata_2025 huggingface dataset:
Demonstration of Model-Based, Off-Line Performance Analysis on a Gas Turbine Air Compressor
Authors: Wiese Ashley P. , Blom Matthew J. , Brear Michael J. , Manzie Chris , Kitchener Anthony
Published: January 2013

This paper presents a model-based, off-line method for analyzing the performance of individual components in an operating gas turbine. This integrated model combines submodels of the combustor efficiency, the combustor pressure loss, the hot-end heat transfer, the turbine inlet temperature, and the turbine performance. As part of this, new physics-based models are proposed for both the combustor efficiency and the turbine. These new models accommodate operating points that feature the flame extending beyond the combustor and combustion occurring in the turbine. Systematic model reduction is undertaken using experimental data from a prototype, microgas turbine rig built by the group. This so called gas turbine air compressor (GTAC) prototype utilizes a single compressor to provide cycle air and a supply of compressed air as its sole output. The most general model results in sensible estimates of all system parameters, including those obtained from the new models that describe variations in both the combustor and turbine performance. As with other microgas turbines, heat losses are also found to be significant.
Risk-Based Assessment of Unplanned Outage Events and Costs for Combined-Cycle Plants
Authors: Grace Dale , Christiansen Thomas
Published: January 2013

Unexpected outages and maintenance costs reduce plant availability and can consume significant resources to restore the unit to service. This paper describes a survey and analysis of unplanned outage events for 388 combined-cycle plants, based on 164 D/E-Class and 224 F-Class gas turbines. The 15-year timeframe included over 3000 unit-years of data. The causes and durations of forced outages and unscheduled maintenance were identified, and overall reliability and availability were established for each class of plant. Costs to restore the unit to service for each main outage cause were estimated, as were net revenues lost due to unplanned outages. A statistical approach to estimated costs and lost revenues provides a risk-based means to quantify the impact of unplanned events on plant cash flow as a function of class of gas turbine and plant subsystem. The risk-based assessment defines the range of probable costs of unplanned outage events.
Effect of Void Fraction on Pressure Drop in Upward Vertical Two-Phase Gas-Liquid Pipe Flow
Authors: Tang Clement C. , Tiwari Sanjib , Ghajar Afshin J.
Published: January 2013

Experimental data for the void fraction and two-phase frictional pressure drop from various sources has been compiled and analyzed. The experimental data revealed that at the lower range of superficial gas velocity and void fraction, the variations of the two-phase frictional pressure drop with superficial gas velocity and void fraction are relatively flat. However, as the superficial gas velocity and void fraction increase to higher values, the frictional pressure drop became significantly sensitive to the two parameters. In a situation when the two-phase pressure drop is sensitive to the variation of the void fraction, it is then that the proper and accurate characterization of the void fraction becomes significant. From the experimental data, regions where the pressure drop is sensitive to the variation of the void fraction are identified and evaluated.
Numerical Investigation of the Flow in a Hydrodynamic Thrust Bearing With Floating Disk
Authors: Fischer Magnus , Mueller Andreas , Rembold Benjamin , Ammann Bruno
Published: January 2013

In this paper we present a novel method for the numerical simulation of flow in a hydrodynamic thrust bearing with floating disk. Floating disks are commonly employed in turbochargers and are situated between the thrust collar, which is rotating at turbocharger speed, and the static casing. A floating disk reduces wear, improves the skew compensating capacity of the bearing, and is freely movable in the axial direction. The simulation model presented combines a commercial flow solver (ANSYS CFX) with a control unit. Based on physical principles and a predefined axial thrust, the control unit automatically sets the rotational speed of the floating disk, the mass flow of the oil supply, and the oil film thickness between the rotating disk and the casing wall and collar, respectively. The only additional inputs required are the temperature and the pressure of the oil at the oil feed and the turbocharger speed. The width of the computational grid of the thin lubricating oil film in the gaps is adjusted using a mesh-morphing approach. The temperature-dependent variation in viscosity is included in the model. The calculated solution of the flow field in the domain, the oil film thickness, and the resulting rotational velocity of the floating disk are validated against experimental data and demonstrate favorable agreement. The influence of uncertainties in the measurements and the behavior of the systems are thoroughly investigated in parametric studies that reveal the key influencing factors. These are the temperature-dependent viscosity of the oil, the axial thrust, and turbulence effects in the supply grooves and ducts of the floating disk. Using the model presented here, it is now possible to predict design variants for this type of bearing.
Life of Brian or Life of Jesus? Uses of Critical Biblical Scholarship and Non-orthodox Views of Jesus in Monty Python’s Life of Brian
Authors: Crossley James G.
Published: January 2013

It is often argued that Monty Python’s Life of Brian should not be regarded as blasphemous or offensive, largely because Brian and Jesus are two distinct characters in the film. Many religious opponents have claimed otherwise. This article argues that to some degree these pious opponents have a point: Brian does in someway represent Jesus. What Life of Brian does, through interaction with scholarly literature and ideas, is to attribute to Brian a whole host of mildly subversive and critical views about Jesus and effectively create a critical life of Jesus.
Rethinking Premodern Japanese Buddhist Texts: A Case Study of Prince Shōtoku’s "Sangyō-gisho"
Authors: Dennis Mark
Published: January 2013

This article examines the Sangyō-gisho 三経義疏 (Commentaries on the Three Sūtras), three Buddhist texts written in classical Chinese that have been attributed to Japan's Prince Shōtoku (574-622 CE). I will focus on the different ways in which four figures from the Kamakura era (1185-1333 CE) understood, used, and valued these texts. Even among this small group of contemporary monks from the thirteenth century we will find distinct notions of what constitutes the "text," some of which differ in important ways from modern scholarly conceptions of the Sangyō-gisho. Through highlighting these different perspectives, I offer an alternative approach to a large body of modern scholarly studies, which has focused on a set of technical concerns looking back to the moment of the texts' composition.
A "Judeo-Christian" Myth of Disestablishment: The Legacy of McGowan v. Maryland
Authors: Rubens Heather Miller
Published: January 2013

While "Judeo-Christian" has been used to describe various aspects of American religion, there is scant discussion on how the term has affected the legal definition of religion in the United States. After briefly mapping the various ways the term has been used in Supreme Court opinions, I focus on the Court's very first use of the term in McGowan v. Maryland, unpacking the working definition of "Judeo-Christian" that is suggested, and tracing how "Judeo-Christian" has influenced the Court's understanding of religious establishment infringement. I argue that in the McGowan line of Court opinions, the term "Judeo-Christian," while intended to gesture towards religious inclusivity, works instead to support de facto Christian establishment.
Becoming 'Half a Doctor': Parent-Experts and the Normalisation of Childhood Asthma in Aotearoa/New Zealand
Authors: Trnka Susanna , McLaughlan Laura
Published: January 2013

In New Zealand, familial responses to childhood asthma largely pivot around the role of the parent-expert who takes primary responsibility for both the management and normalisation of their child’s condition. Based on a preliminary analysis of cultural texts and interviews with parents, healthcare professionals, representatives of asthma societies and environmental activists, this paper argues that childhood asthma is largely accepted as being a ‘normal’ part of life to the extent that parents and health professionals alike note that the dangerousness of this condition is frequently under-recognized. Strategies for both managing and normalising asthma are heavily reliant upon pharmaceutical therapies, though some attention is also paid to mitigating environmental triggers. Central to these endeavours is the role of the primary caregiver(s) who, with input from GPs, frequently adopts the position of the parent-expert in managing the idiosyncrasies of their child’s condition. Little emphasis is placed on collective therapeutics or social action, as the primary focus is on individually-tailored familial-based management of children’s symptoms.
Chemical reactions at CdS heterojunctions with CuInSe2
Authors: Aquino Angel , Rockett Angus
Published: January 2013

The stability of the CdS/CuInSe2 (CIS) heterojunction is critical to understanding the projected lifetime of CIS devices and the effect of processing conditions on the nanoscale chemistry of the heterojunction. This article reports the results of annealing heterojunctions between CdS deposited by chemical bath deposition and single crystal and polycrystalline CIS films between 200 and 500 °C for 10 to 150 min. No atomic movement was observed by secondary ion mass spectrometry at temperatures of 300 °C and below. At 400 °C even for the shortest time studied, Cu and In were found throughout the region initially consisting of CdS only and Cd was found to have moved into the CIS. In the polycrystal, annealing at 500 °C resulted in movement of Cd throughout the CIS layer. No time dependence was observed in the 400 and 500 °C anneals indicating that a reaction had occurred forming a compound that was in thermodynamic equilibrium with the remaining CIS. Diffusion turns on rapidly between 300 and 400 °C, indicating a high activation energy for atomic movement (∼2.4 eV). The onset of diffusion is consistent with the onset of Cu diffusion in CIS.
Glutamate-Dependent Neuroglial Calcium Signaling Differs Between Young and Adult Brain
Authors: Sun Wei , McConnell Evan , Pare Jean-Francois , Xu Qiwu , Chen Michael , Peng Weiguo , Lovatt Ditte , Han Xiaoning , Smith Yoland , Nedergaard Maiken
Published: January 2013

The Adult Astrocyte Is Different

The concept of the tripartite synapse, whereby astrocytes actively modulate the communication between the pre- and postsynaptic site, is widely accepted. The release of gliotransmitters has been linked to release of Ca
2÷
from intracellular stores via the activation of astrocytic metabotropic glutamate receptor 5 (mGluR5) by glutamate spillover from synapses. However, nearly all studies on the tripartite synapse have used brain tissue collected from young individuals. Many receptors undergo changes in expression level during development.

Sun
et al.

(p.
197
; see the Perspective by

Grosche and Reichenbach

) applied genomic analysis, electron microscopy, and calcium imaging in slices and in vivo to assess the presence and the functionality of mGluR5 and mGluR3 receptors during postnatal development in human and mouse astrocytes. Astrocytic expression of mGluR5 was lost by the third postnatal week in mice and was not present in human cortical astrocytes, which calls into question the viability of the tripartite synapse model for adult synapses.
Microglia: Scapegoat, Saboteur, or Something Else?
Authors: Aguzzi Adriano , Barres Ben A. , Bennett Mariko L.
Published: January 2013

Microglia are resident immune cells in the brain and spinal cord. These cells provide immune surveillance and are mobilized in response to disparate diseases and injuries. Although microglial activation is often considered neurotoxic, microglia are essential defenders against many neurodegenerative diseases. It also seems increasingly likely that microglial dysfunction can underlie certain neurological diseases without an obvious immune component.
Bio-Inspired Polymer Composite Actuator and Generator Driven by Water Gradients
Authors: Ma Mingming , Guo Liang , Anderson Daniel G. , Langer Robert
Published: January 2013

Mini Mighty Muscle

Actuators—or artificial muscles—take electrical or chemical energy and convert it into mechanical force. Typically, actuators made from polymers can show large deformations, but cannot generate a lot of force.

Ma
et al.

(p.
186
; see the Perspective by

Kim and Kwon

) describe a polymer composite based on a modified polypyrrole that expands in response to water absorption. The composite was able to generate large stresses and forces, and offered a high work density approaching those of the best conducting polymer electrochemical actuators. Magnetic nanoparticles incorporated into polymer films were used to control the locomotion of the actuator.
Leukocyte Behavior in Atherosclerosis, Myocardial Infarction, and Heart Failure
Authors: Swirski Filip K. , Nahrendorf Matthias
Published: January 2013

Cardiovascular diseases claim more lives worldwide than any other. Etiologically, the dominant trajectory involves atherosclerosis, a chronic inflammatory process of lipid-rich lesion growth in the vascular wall that can cause life-threatening myocardial infarction (MI). Those who survive MI can develop congestive heart failure, a chronic condition of inadequate pump activity that is frequently fatal. Leukocytes (white blood cells) are important participants at the various stages of cardiovascular disease progression and complication. This Review will discuss leukocyte function in atherosclerosis, MI, and heart failure.
Optimization of the Cutoff Value for a Commercial Anti-Dengue Virus IgG Immunoassay
Authors: Marrero-Santos Karla M. , Beltrán Manuela , Carrión-Lebrón Jessica , Sanchez-Vegas Carolina , Hamer Davidson H. , Barnett Elizabeth D. , Santiago Luis M. , Hunsperger Elizabeth A.
Published: January 2013

A commercial anti-dengue virus (anti-DENV) indirect IgG enzyme-linked immunosorbent assay (ELISA) for serological diagnosis was evaluated for its utility in determining previous DENV exposure in U.S. travelers. The Boston Area Travel Medicine Network clinics used Focus Diagnostics anti-DENV IgG ELISA to measure anti-DENV IgG antibodies in 591 pretravel specimens from U.S. residents who had traveled to countries where dengue is endemic. When using the manufacturer's index cutoff value for this ELISA, false-positive results were observed that overestimated the perceived past DENV exposure in U.S. travelers. Validation of 121 of these anti-DENV IgG results by plaque reduction neutralization test (PRNT) was used for receiver operating characteristic (ROC) curve optimization of the index cutoff value from 1 to 3.0, improving the specificity of the anti-DENV IgG ELISA from 24% to 95.7%. Additionally, previous vaccination with yellow fever virus contributed to 52.8% of the false-positive rate in the anti-DENV IgG ELISA results. Optimization of the cutoff value of the anti-DENV IgG ELISA provided better interpretation and confidence in the results and eliminated the need for confirmation by PRNT. The travel history of U.S. travelers was also useful for categorizing these travelers into groups for analysis of previous DENV exposure.
Molecular Epidemiological Surveillance of Multidrug-Resistant Pseudomonas aeruginosa Isolates in a Pediatric Population of Patients with Cystic Fibrosis and Determination of Risk Factors for Infection with the Houston-1 Strain
Authors: Luna Ruth Ann , Millecker Laura A. , Webb C. Renee , Mason Sally K. , Whaley Elaine M. , Starke Jeffrey R. , Hiatt Peter W. , Versalovic James
Published: January 2013

Multiyear molecular epidemiological surveillance of multidrug-resistant
Pseudomonas aeruginosa
(MRPA) in a pediatric cystic fibrosis care center identified an endemic MRPA strain (Houston-1). Recent hospitalization was found to be a statistically significant risk factor for acquisition of the endemic strain. Multiple infection control improvements led to the reduced incidence of the Houston-1 strain in the CF population.
Multilocus Sequence Typing of the Porcine and Human Gastric Pathogen Helicobacter suis
Authors: Liang Jungang , Ducatelle Richard , Pasmans Frank , Smet Annemieke , Haesebrouck Freddy , Flahou Bram
Published: January 2013

Helicobacter suis
is a Gram-negative bacterium colonizing the majority of pigs, in which it causes gastritis and decreased daily weight gain.
H. suis
is also the most prevalent gastric non-
Helicobacter pylori Helicobacter
species in humans, capable of causing gastric disorders. To gain insight into the genetic diversity of porcine and human
H. suis
strains, a multilocus sequence typing (MLST) method was developed. In a preliminary study, 7 housekeeping genes (
atpA
,
efp
,
mutY
,
ppa
,
trpC
,
ureI
, and
yphC
) of 10
H. suis
isolates cultured
in vitro
were investigated as MLST candidates. All genes, except the
ureI
gene, which was replaced by part of the
ureAB
gene cluster of
H. suis
, displayed several variable nucleotide sites. Subsequently, internal gene fragments, ranging from 379 to 732 bp and comprising several variable nucleotide sites, were selected. For validation of the developed MLST technique, gastric tissue from 17
H. suis
-positive pigs from 4 different herds and from 1
H. suis
-infected human patient was used for direct, culture-independent strain typing of
H. suis
. In addition to the 10 unique sequence types (STs) among the 10 isolates grown
in vitro
, 15 additional STs could be assigned. Individual animals were colonized by only 1
H. suis
strain, whereas multiple
H. suis
strains were present in all herds tested, revealing that
H. suis
is a genetically diverse bacterial species. The human
H. suis
strain showed a very close relationship to porcine strains. In conclusion, the developed MLST scheme may prove useful for direct, culture-independent typing of porcine and human
H. suis
strains.
Epidemiology, Antifungal Susceptibility, and Pathogenicity of Candida africana Isolates from the United Kingdom
Authors: Borman Andrew M. , Szekely Adrien , Linton Chistopher J. , Palmer Michael D. , Brown Phillipa , Johnson Elizabeth M.
Published: January 2013

Candida africana
was previously proposed as a new species within the
Candida albicans
species complex, together with
C. albicans
and
C. dubliniensis
, although further phylogenetic analyses better support its status as an unusual variant within
C. albicans
. Here we show that
C. africana
can be distinguished from
C. albicans
and
C. dubliniensis
by pyrosequencing of a short region of ITS2, and we have evaluated its occurrence in clinical samples by pyrosequencing all presumptive isolates of
C. albicans
submitted to the Mycology Reference Laboratory over a 9-month period. The
C. albicans
complex constituted 826/1,839 (44.9%) of yeast isolates received over the study period and included 783 isolates of
C. albicans
, 28 isolates of
C. dubliniensis
, and 15 isolates of
C. africana
. In agreement with previous reports,
C. africana
was isolated exclusively from genital specimens, in women in the 18-to-35-year age group. Indeed,
C. africana
constituted 15/251 (6%) of “
C. albicans
” isolates from female genital specimens during the study period.
C. africana
isolates were germ tube positive, grew significantly more slowly than
C. albicans
and
C. dubliniensis
on conventional mycological media, could be distinguished from the other members of the
C. albicans
complex by appearance on chromogenic agar, and were incapable of forming chlamydospores. Here we present the detailed evaluation of epidemiological, phenotypic, and clinical features and antifungal susceptibility profiles of United Kingdom isolates of
C. africana
. Furthermore, we demonstrate that
C. africana
is significantly less pathogenic than
C. albicans
and
C. dubliniensis
in the
Galleria mellonella
insect systemic infection model.
Differences and Similarities between Culture-Confirmed Human Granulocytic Anaplasmosis and Early Lyme Disease
Authors: Wormser Gary P. , Aguero-Rosenfeld Maria E. , Cox Mary E. , Nowakowski John , Nadelman Robert B. , Holmgren Diane , McKenna Donna , Bittker Susan , Zentmaier Lois , Cooper Denise , Liveris Dionysios , Schwartz Ira , Horowitz Harold W.
Published: January 2013

Lyme disease is transmitted by the bite of certain
Ixodes
ticks, which can also transmit
Anaplasma phagocytophilum
, the cause of human granulocytic anaplasmosis (HGA). Although culture can be used to identify patients infected with
A. phagocytophilum
and is the microbiologic gold standard, few studies have evaluated culture-confirmed patients with HGA. We conducted a prospective study in which blood culture was used to detect HGA infection in patients with a compatible clinical illness. Early Lyme disease was defined by the presence of erythema migrans. The epidemiologic, clinical, and laboratory features of 44 patients with culture-confirmed HGA were compared with those of a convenience sample of 62 patients with early Lyme disease. Coinfected patients were excluded. Patients with HGA had more symptoms (
P
= 0.003) and had a higher body temperature on presentation (
P
< 0.001) than patients with early Lyme disease. HGA patients were also more likely to have a headache, dizziness, myalgias, abdominal pain, anorexia, leukopenia, lymphopenia, thrombocytopenia, or elevated liver enzymes. A direct correlation between the number of symptoms and the duration of illness at time of presentation (rho = 0.389,
P
= 0.009) was observed for HGA patients but not for patients with Lyme disease. In conclusion, although there are overlapping features, culture-confirmed HGA is a more severe illness than early Lyme disease.
A Real-Time PCR Assay for Rapid Detection and Quantification of Exserohilum rostratum, a Causative Pathogen of Fungal Meningitis Associated with Injection of Contaminated Methylprednisolone
Authors: Zhao Yanan , Petraitiene Ruta , Walsh Thomas J. , Perlin David S.
Published: January 2013

A species-specific molecular beacon real-time PCR assay was developed for rapid diagnosis of
Exserohilum rostratum
infection. As low as 100 fg of
E. rostratum
DNA can be reliably detected in the presence of 50 ng of human DNA, with a dynamic linear quantification range from 20 ng to 200 fg.
A Mutation in the Ebola Virus Envelope Glycoprotein Restricts Viral Entry in a Host Species- and Cell-Type-Specific Manner
Authors: Martinez Osvaldo , Ndungo Esther , Tantral Lee , Miller Emily Happy , Leung Lawrence W. , Chandran Kartik , Basler Christopher F.
Published: January 2013

Zaire Ebola virus (EBOV) is a zoonotic pathogen that causes severe hemorrhagic fever in humans. A single viral glycoprotein (GP) mediates viral attachment and entry. Here, virus-like particle (VLP)-based entry assays demonstrate that a GP mutant, GP-F88A, which is defective for entry into a variety of human cell types, including antigen-presenting cells (APCs), such as macrophages and dendritic cells, can mediate viral entry into mouse CD11b
+
APCs. Like that of wild-type GP (GP-wt), GP-F88A-mediated entry occurs via a macropinocytosis-related pathway and requires endosomal cysteine proteases and an intact fusion peptide. Several additional hydrophobic residues lie in close proximity to GP-F88, including L111, I113, L122, and F225. GP mutants in which these residues are mutated to alanine displayed preferential and often impaired entry into several cell types, although not in a species-specific manner. Niemann-Pick C1 (NPC1) protein is an essential filovirus receptor that binds directly to GP. Overexpression of NPC1 was recently demonstrated to rescue GP-F88A-mediated entry. A quantitative enzyme-linked immunosorbent assay (ELISA) demonstrated that while the F88A mutation impairs GP binding to human NPC1 by 10-fold, it has little impact on GP binding to mouse NPC1. Interestingly, not all mouse macrophage cell lines permit GP-F88A entry. The IC-21 cell line was permissive, whereas RAW 264.7 cells were not. Quantitative reverse transcription (RT)-PCR assays demonstrate higher NPC1 levels in GP-F88A permissive IC-21 cells and mouse peritoneal macrophages than in RAW 264.7 cells. Cumulatively, these studies suggest an important role for NPC1 in the differential entry of GP-F88A into mouse versus human APCs.
Role of Interactions between Autographa californica Multiple Nucleopolyhedrovirus Procathepsin and Chitinase Chitin-Binding or Active-Site Domains in Viral Cathepsin Processing
Authors: Hodgson Jeffrey J. , Arif Basil M. , Krell Peter J.
Published: January 2013

The binding of
Autographa californica
multiple nucleopolyhedrovirus chitinase (CHIA) to viral cathepsin protease progenitor (proV-CATH) governs cellular/endoplasmic reticulum (ER) coretention of CHIA and proV-CATH, thus coordinating simultaneous cellular release of both host tissue-degrading enzymes upon host cell death. CHIA is a proposed proV-CATH folding chaperone because insertional inactivation of
chiA
causes production of proV-CATH aggregates that are incompetent for proteolytic maturation into active V-CATH enzyme. We wanted to determine whether the N-terminal chitin-binding domain (CBD, 149 residues) and C-terminal CHIA active-site domain (ASD, 402 residues) of CHIA bind to proV-CATH independently of one another and whether either domain is dispensable for CHIA's putative proV-CATH folding chaperone activity. We demonstrate that N-terminally green fluorescent protein (GFP)-fused CHIA, ASD, and CBD each colocalize with proV-CATH-RFP in ER-like patterns and that both ASD and CBD independently associate with proV-CATH
in vivo
using bimolecular fluorescence complementation (BiFC) and
in vitro
using reciprocal nickel-histidine pulldown assays. Altogether, the data from colocalization, BiFC, and reciprocal copurification analyses suggest specific and independent interactions between proV-CATH and both domains of CHIA. These data also demonstrate that either CHIA domain is dispensable for normal proV-CATH processing. Furthermore, in contrast to prior evidence suggesting that a lack of
chiA
expression causes proV-CATH to become aggregated, insoluble, and unable to mature into V-CATH, a
chiA
deletion bacmid virus we engineered to express just
v-cath
produced soluble proV-CATH that was prematurely secreted from cells and proteolytically matured into active V-CATH enzyme.
Efavirenz Enhances HIV-1 Gag Processing at the Plasma Membrane through Gag-Pol Dimerization
Authors: Sudo Sho , Haraguchi Hiyori , Hirai Yoko , Gatanaga Hiroyuki , Sakuragi Jun-ichi , Momose Fumitaka , Morikawa Yuko
Published: January 2013

Efavirenz (EFV), a nonnucleoside reverse transcriptase (RT) inhibitor, also inhibits HIV-1 particle release through enhanced Gag/Gag-Pol processing by protease (PR). To better understand the mechanisms of the EFV-mediated enhancement of Gag processing, we examined the intracellular localization of Gag/Gag-Pol processing products and their precursors. Confocal microscopy revealed that in the presence of EFV, the N-terminal p17 matrix (p17MA) fragment was uniformly distributed at the plasma membrane (PM) but the central p24 capsid (p24CA) and the Pol-encoded RT antigens were diffusely distributed in the cytoplasm, and all of the above were observed in puncta at the PM in the absence of EFV. EFV did not impair PM targeting of Gag/Gag-Pol precursors. Membrane flotation analysis confirmed these findings. Such uniform distribution of p17MA at the PM was not seen by overexpression of Gag-Pol and was suppressed when EFV-resistant HIV-1 was used. Forster's fluorescence resonance energy transfer assay revealed that Gag-Pol precursor dimerization occurred mainly at the PM and that EFV induced a significant increase of the Gag-Pol dimerization at the PM. Gag-Pol dimerization was not enhanced when HIV-1 contained the EFV resistance mutation in RT. Bacterial two-hybrid assay showed that EFV enhanced the dimerization of PR-RT fragments and restored the dimerization impaired by the dimerization-defective mutation in the RT tryptophan repeat motif but not that impaired by the mutation at the PR dimer interface. Collectively, our data indicate that EFV enhances Gag-Pol precursor dimerization, likely after PM targeting but before complete particle assembly, resulting in uniform distribution of p17MA to and dissociation of p24CA and RT from the PM.
CD22 Is Required for Protection against West Nile Virus Infection
Authors: Ma Daphne Y. , Suthar Mehul S. , Kasahara Shinji , Gale Michael , Clark Edward A.
Published: January 2013

West Nile virus (WNV) is a RNA virus of the familyFlaviviridaeand the leading cause of mosquito-borne encephalitis in the United States. Humoral immunity is essential for protection against WNV infection; however, the requirements for initiating effective antibody responses against WNV infection are still unclear. CD22 (Siglec-2) is expressed on B cells and regulates B cell receptor signaling, cell survival, proliferation, and antibody production. In this study, we investigated how CD22 contributes to protection against WNV infection and found that CD22 knockout (Cd22−/−) mice were highly susceptible to WNV infection and had increased viral loads in the serum and central nervous system (CNS) compared to wild-type (WT) mice. This was not due to a defect in humoral immunity, asCd22−/−mice had normal WNV-specific antibody responses. However,Cd22−/−mice had decreased WNV-specific CD8+T cell responses compared to those of WT mice. These defects were not simply due to reduced cytotoxic activity or increased cell death but, rather, were associated with decreased lymphocyte migration into the draining lymph nodes (dLNs) of infectedCd22−/−mice.Cd22−/−mice had reduced production of the chemokine CCL3 in the dLNs after infection, suggesting that CD22 affects chemotaxis via controlling chemokine production. CD22 was not restricted to B cells but was also expressed on a subset of splenic DCIR2+dendritic cells that rapidly expand early after WNV infection. Thus, CD22 plays an essential role in controlling WNV infection by governing cell migration and CD8+T cell responses.
Viral Inhibition of BAK Promotes Murine Cytomegalovirus Dissemination to Salivary Glands
Authors: Handke Wiebke , Luig Christina , Popović Branka , Krmpotić Astrid , Jonjić Stipan , Brune Wolfram
Published: January 2013

Apoptosis induction is an important host defense mechanism to control viral infection, which is antagonized by viral proteins. Murine cytomegalovirus m41.1 encodes a viral inhibitor of BAK oligomerization (vIBO) that blocks the mitochondrial apoptosis mediator BAK. However, its importance for viral fitness
in vivo
has not been investigated. Here, we show that an m41.1-deficient virus attains reduced titers in salivary glands of wild-type but not
Bak1
−/−
mice, indicating a requirement of BAK inhibition for optimal dissemination
in vivo
.
Estimating Cytomegalovirus Growth Rates by Using Only a Single Point
Authors: Cromer Deborah , Tey Siok-Keen , Khanna Rajiv , Davenport Miles P.
Published: January 2013

Calculation of pathogen growth rates is important in understanding the natural history of infection and effects of therapy. However, it is often difficult to estimate pathogen growth because patients are treated immediately upon the detection of infection, leaving only one nonzero untreated reading. Previous approaches have relied on the flawed assumption that pathogen loads just prior to detection are at the assay detection threshold. We have developed a novel method for estimating the pathogen growth rate from a single reading and investigated the initial growth of cytomegalovirus (CMV) in allogeneic hematopoietic stem cell transplant (HSCT) patients. We applied this approach to CMV viral loads measured at least weekly in 122 patients in the 3 months posttransplant. Viral growth rates were estimated by using a modeling approach that accounts for the viral load and the time since the last negative reading. Viral growth rates decreased rapidly within the first week, from 0.72/day (doubling time, 0.96 day) at the point of reactivation to 0.22/day (doubling time, 3.1 days) at 1 week. Results from this method correlated closely with a two-point regression analysis of a subset of 58 patients with detectable subthreshold viral loads immediately prior to overt reactivation. Patients with lymphocyte counts of ≥0.5 × 10
9
/liter had significantly slower viral growth than patients with low lymphocyte counts (0.612/day versus 0.325/day,
P
< 0.0001). Thus, our novel method of estimating pathogen growth rates reveals a rapid slowing of CMV growth during reactivation in HSCT patients and a significant impact of the lymphocyte count on CMV growth.
The Amino Terminus of Herpes Simplex Virus 1 Glycoprotein K Is Required for Virion Entry via the Paired Immunoglobulin-Like Type-2 Receptor Alpha
Authors: Chowdhury Sona , Chouljenko Vladimir N. , Naderi Misagh , Kousoulas Konstantin G.
Published: January 2013

The herpes simplex virus 1 (HSV-1) glycoprotein K (gK)/UL20 protein complex is incorporated into virion envelopes and cellular membranes and functions during virus entry and cell-to-cell spread. To investigate the role of gK/UL20 in the context of a highly neurovirulent virus strain, the HSV-1(McKrae) genome was cloned into a bacterial artificial chromosome plasmid (McKbac) and utilized to construct the mutant virus McK(gKΔ31-68), carrying a 37-amino-acid deletion within the gK amino terminus. The McKbac virus entered efficiently into Chinese hamster ovary (CHO) cells constitutively expressing HSV-1 human receptors, nectin-1, herpesvirus entry mediator (HVEM), or paired immunoglobulin-like type-2 receptor alpha (PILRα). In contrast, the McK(gKΔ31-68) virus failed to enter into CHO-PILRα cells, while it entered CHO cells expressing HVEM and nectin-1 more efficiently than the McKbac virus. Both McKbac and McK(gKΔ31-68) viruses entered all CHO cells expressing HSV-1 receptors via a pH-independent pathway. The HSV-1(F) gBΔ28syn mutant virus, encoding a carboxyl-terminal truncated gB, causes extensive cell fusion. Previously, we showed that the gKΔ31-68 amino acid deletion abrogated gBΔ28syn virus-induced cell fusion, indicating that the amino terminus of gK is required for gB-mediated virus-induced cell fusion (V. N. Chouljenko, A. V. Iyer, S. Chowdhury, D. V. Chouljenko, and K. G. J. Kousoulas, Virology
83:
12301–12313, 2009). Surprisingly, the gKΔ31-68/gBΔ28syn virus caused extensive fusion of CHO-nectin-1 cells but limited cell fusion of CHO-PILRα cells. Coimmunoprecipitation experiments revealed that both gK and PILRα bound gB in infected cells. Collectively, these results indicate that the amino terminus of gK is functionally and physically associated with the gB-PILRα protein complex and regulates membrane fusion of the viral envelope with cellular membranes during virus entry as well as virus-induced cell-to-cell fusion.
The Virion Host Shutoff RNase Plays a Key Role in Blocking the Activation of Protein Kinase R in Cells Infected with Herpes Simplex Virus 1
Authors: Sciortino Maria Teresa , Parisi Tiziana , Siracusano Gabriel , Mastino Antonio , Taddeo Brunella , Roizman Bernard
Published: January 2013

Earlier studies have shown that active MEK blocks the activation of protein kinase R (PKR), a component of antiviral innate immune responses. In this report we show that the herpes simplex virus 1 virion host shutoff (VHS) RNase protein and MEK (mitogen-activated protein kinase kinase) act cooperatively in blocking the activation of PKR. This conclusion is based on the following. (i) In contrast to viral gene expression in the parental cell line or a cell line expressing a constitutively active MEK, the replication of a VHS mutant is particularly impaired in cells expressing dominant negative MEK. In this cell line PKR is activated by phosphorylation, and the accumulation of several viral proteins is delayed. (ii) In transfected cells, wild-type VHS blocked the activation of PKR, whereas PKR was activated in cells transfected with a mutant VHS or with plasmids encoding the VHS RNase and VP16 and VP22, the two viral proteins that neutralize the RNase activity of VHS. The results suggest that early in infection the VHS RNase degrades RNAs that activate PKR. Coupled with published data, the results suggest that inhibition of activation of PKR or its effect on viral replication is staged early in infection by VHS, postsynthesis of VP16 and VP22 by the γ
1
34.5 protein, and very late in infection by the U
S
11 protein.
Tumour-to-tumour metastases: prostate carcinoma metastasising to a renal oncocytoma
Authors: Petts Gemma , Rashid Tina , Hrouda David , Ngo Nye-Thane
Published: January 2013

This is a case report of prostate carcinoma metastasising to a renal oncocytoma. The report demonstrates the unusual presentation of metastases from a common cancer to a common benign tumour, and reviews the rare phenomenon of tumour-to-tumour metastases.
Hunter syndrome follow-up after 1 year of enzyme-replacement therapy
Authors: Puiu Maria , Chiriţă-Emandi Adela , Dumitriu Simona , Arghirescu Smaranda
Published: January 2013

Mucopolysaccharidosis II (Hunter syndrome) is a rare x-linked disorder caused by a deficiency in the lysosomal enzyme iduronate-2-sulphatase, leading to an accumulation of the glycosaminoglycans (GAGs) dermatansulphate and heparan sulphate. The consequence of GAGs accumulation is progressive, multiorgan disease. Enzyme-replacement therapy is hypothesised to result in disease stabilisation and improved prognosis. We present a severe case of Hunter syndrome diagnosed at age 2 years and 4 months, who started enzyme-replacement therapy at the age of 3 years and 3 months. We report his evolution after 1 year of treatment. The treatment response was good and there was significant improvement in the quality of life. Owing to the rarity of Hunter syndrome, the multisystem nature and the heterogeneity of disease progression, patient care implies interdisciplinary consultations with a wide range of specialists. The best management can be provided in reference centres for metabolic diseases.
Non-compaction of the left ventricular myocardium with Cor-triatriatum and associated anomalies
Authors: Singh Neha , Aga Pallavi , Singh Ragini , Tiwari Bhuwan
Published: January 2013

Non-compaction of ventricular myocardium (NVM) is a rare clinical entity. It has been reported more frequently in recent years because of continuous improvements in imaging techniques and resolution. Although apical region of the left ventricle is the most commonly involved site, biventricular involvement has also been reported in the published literature. This abnormality is often associated with other congenital cardiac and extracardiac anomalies. We describe such a case, incidentally detected and documented by the combination of echocardiography and multidetector CT coronary angiography. In our case, NVM was associated with Cor-triatriutum, ventricular septal defect, persistent left superior vena cava and an anomalous extracardiac vessel. Synchronous association of all these anomalies in a child has never been reported in the literature.
Influence of the Manchester triage system on waiting time, treatment time, length of stay and patient satisfaction; a before and after study
Authors: Storm-Versloot Marja N , Vermeulen Hester , van Lammeren Nienke , Luitse Jan SK , Goslings J Carel
Published: January 2013

Objectives

To compare waiting time, treatment time, length of stay (LOS), patient satisfaction and distribution of waiting times over levels of urgency before and after the implementation of the Manchester Triage system (MTS) at an emergency department (ED).

Methods

Before and after study, by means of timeline measurements and questionnaires on satisfaction in two consecutive patient series (n=1808). Questionnaires covered aspects of provision of information, opportunity given to explain problems, waiting time and sorting out the problem. After implementation of MTS, patients were triaged between 12:00 and 22:00. Subanalysis was performed on triaging and non-triaging; and between urgency levels.

Results

Waiting time did not decrease after implementation of the MTS, however, treatment time and LOS were significantly longer. Total LOS did not differ. After implementation, waiting time was better distributed over urgency levels.

Furthermore, after implementation, patient satisfaction scored significantly lower on the provision of information and opportunity to explain their problems, however, waiting time and the feeling that their problem had been sorted out scored better. No significant differences were found between triaged and non-triaged patients. Although not significant, patients in the lower urgency levels seemed more satisfied than patients in the higher urgency levels.

Conclusions

Implementing MTS on its own is not sufficient to improve efficiency and quality of EDs. More complex interventions including process redesigning that targets various groups of ED patients should be evaluated in the future by using rigorous research designs for quality improvement of EDs.
Direct relationship between aging and overcrowding in the ED, and a calculation formula for demand projection: a cross-sectional study
Authors: Kawano Takahisa , Nishiyama Kei , Anan Hideaki , Tujimura Yuka
Published: January 2013

Objective

Although it has been suggested that the increase in older population contributes to overcrowding in emergency departments (EDs), there are limited data defining this relationship. This study examines whether patients’ mean age per day affects length of ED stay.

Methods

This cross-sectional analysis evaluated how patient age affects length of ED stay. The study was conducted at an ED attached to Fujisawa City Hospital, Japan, between 1 November 2009 and 31 October 2010. Patients scheduled to visit for childbirth and patients under age 15 were excluded. The primary outcome measure was the relationship between length of ED stay and patient age. The secondary outcome was the relationship between patient age and patient dispositions indicated by column chart and 100% staked column chart.

Results

Over the study period, there were 17 744 patient visits to the ED. The study included 15 840 (89.3%) patients. The mean (SD) age of these patients was 56.9 (21.5) years. In single and multiple linear regression analyses, mean patient age per day was an important factor in length of ED stay for the total number of patients visiting the ED (single linear regression analysis: regression coefficient=1.59 min/year, r2=0.005, p<0.001; multiple linear regression analysis: regression coefficient=0.72 min/year, r2=0.24, p<0.001). The ratio of admitted and transferred patients increased with patient age.

Conclusion

The increase in older patients visiting the ED has a direct significant negative effect on overcrowding in the ED.
In-hospital falls and fall-related injuries: a protocol for a cost of fall study
Authors: Morello Renata Teresa , Barker Anna Luica , Haines Terry , Zavarsek Silva , Watts Jennifer J , Hill Keith , Brand Caroline , Sherrington Catherine , Wolfe Rory , Bohensky Megan , Stoelwinder Johannes
Published: January 2013

Background

In-hospital falls are common and pose significant economic burden on the healthcare system. To date, few studies have quantified the additional cost of hospitalisation associated with an in-hospital fall or fall-related injury. The aim of this study is to determine the additional length of stay and hospitalisation costs associated with in-hospital falls and fall-related injuries, from the acute hospital perspective.

Methods and design

A multisite prospective study will be conducted as part of a larger falls-prevention clinical trial—the 6-PACK project. This study will involve 12 acute medical and surgical wards from six hospitals across Australia. Patient and admission characteristics, outcome and hospitalisation cost data will be prospectively collected on approximately 15 000 patients during the 15-month study period. A review of all in-hospital fall events will be conducted using a multimodal method (medical record review and daily verbal report from the nurse unit manager, triangulated with falls recorded in the hospital incident reporting and administrative database), to ensure complete case ascertainment. Hospital clinical costing data will be used to calculate patient-level hospitalisation costs incurred by a patient during their inpatient stay. Additional hospital and hospital resource utilisation costs attributable to in-hospital falls and fall-related injuries will be calculated using linear regression modelling, adjusting for a priori-defined potential confounding factors.

Discussion

This protocol provides the detailed statement of the planned analysis. The results from this study will be used to support healthcare planning, policy making and allocation of funding relating to falls prevention within acute hospitals.
Roughness effects of commercial steel pipe in turbulent flow: universal scaling
Authors: Afzal Noor
Published: January 2013

The mean turbulent flow over a transitional rough commercial steel pipe is considered in terms of alternate inner roughness variables. The matching of inner layer and outer layer in the overlap region leads to the universal log laws for velocity profile and friction factor, explicitly independent of surface roughness of all kinds. The roughness function, for commercial steel pipe differs from inflectional (sand grain) roughness. The traditional wall law and friction factor depends on type of surface roughness.
Scolosaurus cutleri (Ornithischia: Ankylosauria) from the Upper Cretaceous Dinosaur Park Formation of Alberta, Canada
Authors: Penkalski Paul , Blows William T.
Published: January 2013

The synonymy of the ankylosaurid dinosaur Scolosaurus with Euoplocephalus has been widely accepted since the 1970s. However, Scolosaurus cutleri exhibits differences which separate it from Euoplocephalus tutus and Dyoplosaurus acutosquameus. Although the holotype of Euoplocephalus is fragmentary, several other specimens can be reliably referred to this taxon and thus used for comparison. Scolosaurus differs from Euoplocephalus in cervical half-ring, osteoderm, and forelimb morphology. Scolosaurus differs from Dyoplosaurus primarily in pelvic morphology and osteoderm shape. Recognition of Scolosaurus as a valid taxon adds to the growing concept that the Upper Cretaceous ankylosaurid fauna of North America was more diverse than previously thought.
Preliminary heat-flow density data from Tunisia and the Pelagian Sea
Authors: Lucazeau Francis , Dhia Hammed Ben
Published: January 2013

Heat-flow density values at 78 sites in Tunisia and the Pelagian Sea are derived from oil exploration wells. Bottom-hole temperatures (BHT) are systematically corrected for mud circulation cooling effects either by a Horner technique when several temperature records are available at a given depth or by a statistical method based on the comparison of all BHT with test temperatures (DST) that are representative of the actual formation temperatures. Thermal conductivities are estimated from detailed studies of stratigraphic and geophysical logs. An inverse technique is used to estimate heat-flow density for each borehole, as well as interpolated temperatures at constant depths. Results are discussed with maps that include heat-flow density data in neighbouring areas (Algeria and the Strait of Sicily). The general trend corresponds remarkably to the recent structural evolution of the Tunisian margin with high values in the Pelagian Sea and decreasing values toward the stable platform.