bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical Measurement of Local and Global Transfer Functions for Equivalence Ratio Fluctuations in a Turbulent Swirl Flame
Authors: Bobusch Bernhard C. , Ćosić Bernhard , Moeck Jonas P. , Paschereit Christian Oliver
Published: November 2013

Equivalence ratio fluctuations are known to be one of the key factors controlling thermoacoustic stability in lean premixed gas turbine combustors. The mixing and thus the spatio-temporal evolution of these perturbations in the combustor flow is, however, difficult to account for in present low-order modeling approaches. To investigate this mechanism, experiments in an atmospheric combustion test rig are conducted. To assess the importance of equivalence ratio fluctuations in the present case, flame transfer functions for different injection positions are measured. By adding known perturbations in the fuel flow using a solenoid valve, the influence of equivalence ratio oscillations on the heat release rate is investigated. The spatially and temporally resolved equivalence ratio fluctuations in the reaction zone are measured using two optical chemiluminescence signals, captured with an intensified camera. A steady calibration measurement allows for the quantitative assessment of the equivalence ratio fluctuations in the flame. This information is used to obtain a mixing transfer function, which relates fluctuations in the fuel flow to corresponding fluctuations in the equivalence ratio of the flame. The current study focuses on the measurement of the global, spatially integrated, transfer function for equivalence ratio fluctuations and the corresponding modeling. In addition, the spatially resolved mixing transfer function is shown and discussed. The global mixing transfer function reveals that despite the good spatial mixing quality of the investigated generic burner, the ability to damp temporal fluctuations at low frequencies is rather poor. It is shown that the equivalence ratio fluctuations are the governing heat release rate oscillation response mechanism for this burner in the low-frequency regime. The global transfer function for equivalence ratio fluctuations derived from the measurements is characterized by a pronounced low-pass characteristic, which is in good agreement with the presented convection–diffusion mixing model.
LES Evaluation of Non-Linear Effects on the Dynamic Flame Response in a Real Gas Turbine Combustion Chamber
Authors: Hermeth Sebastian , Staffelbach Gabriel , Gicquel Laurent , Poinsot Thierry
Published: November 2013

Large Eddy Simulations (LES) of a lean swirl-stabilized gas turbine burner are used to analyze the non-linear response of the flame in a real gas turbine engine. For this study, two LES of the same geometry are performed: one where the inlet is acoustically modulated with a low perturbation amplitude in order to obtain a linear response, and one where a high amplitude forcing is applied. The high amplitude forced LES reveals that the averaged mean flame shape changes significantly compared to the linearly forced LES. During the oscillation cycle the flame undergoes strong variations in shape, with a typical mushroom shape roll-up. Based on these predictions, the measured global flame response shows that a high forcing amplitude does not only lead to a change in the amplitude response but also changes its delay quite significantly. Although different, the global gain remains quite similar between the linear and non-linear case. However, local variations of this index clearly point to the non compactness of these flames. This also means that high local gain values have opposite effects in regions where the local time delay changes rapidly. One mechanism by which the two configurations differ is revealed by studying PDF of equivalence ratio. In the non-linear case significantly stronger equivalence ratio perturbations act on the flame.
3-D Chemiluminescence Imaging of Unforced and Forced Swirl-Stabilized Flames in a Lean Premixed Multi-Nozzle Can Combustor
Authors: Samarasinghe Janith , Peluso Stephen , Szedlmayer Michael , De Rosa Alexander , Quay Bryan , Santavicca Domenic
Published: November 2013

A tomographic image reconstruction technique has been developed to measure the 3-D distribution of CH* chemiluminescence of unforced and forced turbulent premixed flames. Measurements are obtained in a lean premixed, swirl-stabilized multi-nozzle can combustor. Line-of-sight images are acquired at equally spaced angle increments using a single ICCD camera. 3-D images of the flames are reconstructed by applying a filtered back projection algorithm to the acquired line-of-sight images. Methods of viewing 3-D images to characterize the structure, dynamics, interaction and spatial differences of multi-nozzle flames are presented. Accuracy of the reconstruction technique is demonstrated by comparing reconstructed line-of-sight images to measured line-of-sight downstream-view images of unforced flames. The effect of the number of acquired projection images on the quality of the reconstruction is assessed. The reconstructed 3-D images of the unforced multi-nozzle flames show the structure of individual flames as well as the interaction regions between flames. Forced flame images are obtained by phase-synchronizing the camera to the forcing cycle. The resulting 3-D reconstructions of forced flames reveal the spatial and temporal response of the multi-nozzle flame structure to imposed velocity fluctuations, information which is essential to identifying the underlying mechanisms responsible for this behavior.
Aerodynamic Interactions Between a High Pressure Turbine and the First Low Pressure Stator
Authors: Gougeon Pierre , Ngo Boum Ghislaine , Lebœuf Francis
Published: November 2013

This paper presents a numerical study on the interaction between a single-stage high-pressure turbine and the first vane row of a low-pressure turbine at aerodesign conditions. It focuses on the simulation of the flow within the inter-turbine duct and the loss generated in the downstream low-pressure vane.

Former experiments provided steady and unsteady measurements in the duct between the high and the low-pressure turbines and after the low-pressure nozzle. A 3D unsteady RANS approach with phase-lagged boundary conditions is used to characterize the unsteady periodic effects developing in the inter-turbine channel and downstream in the low-pressure vane.

For the numerical study, two different configurations were considered: a single stage high-pressure turbine configuration and a high-pressure rotor coupled with a low-pressure vane. For the second one, two inlet boundary conditions are considered upstream of the rotor: a circumferentially uniform boundary condition and a circumferentially non uniform rotating boundary condition. The resulting flow fields are compared within the intermediate duct.

A harmonic Fourier analysis is carried out to underline the effects of upstream and downstream stator and the interaction with the high-pressure rotor. An unsteady Adamczyk decomposition within a plane located in the duct showed the influence of the different components and the levels of unsteadiness. Comparisons with experimental data show a reasonable good agreement.
Effects of Non-Uniform Streamwise Spacing in Low Aspect Ratio Pin Fin Arrays
Authors: Ostanek Jason K. , Thole Karen A.
Published: November 2013

Pin fin arrays are commonly used to cool the trailing edge of gas turbine airfoils. While the majority of pin fin research focuses on uniformly-spaced arrays, the goal of the present work was to determine if non-uniform spacing in the streamwise direction could be utilized to maintain high heat transfer while simultaneously extending the array footprint. The uniqueness of the work lies in the basis for selecting the non-uniform spacing pattern. The non-uniform arrangement was chosen to exploit previously published row-by-row heat transfer development where the initial rows showed little variation with streamwise spacing. As such, a non-uniform array was considered where the initial rows had spacing of 3.46 diameters and the inner rows gradually decreased to a final spacing of 1.73 diameters. Three seven-row arrays were considered having constant streamwise spacing of 2.16, 2.60, and 3.03 pin fin diameters. All configurations had constant spanwise spacing of two diameters and constant pin height of one diameter. Three Reynolds numbers of 3.0e3, 1.0e4, and 2.0e4 were considered based on pin fin diameter and minimum area velocity. At high Reynolds numbers, heat transfer and pressure drop measurements were in agreement for the nonuniform array and for a closely spaced array having 2.16 diameter streamwise spacing. While array performance was similar, the non-uniform array covered 16.8% more streamwise distance than the closely spaced array. At low Reynolds numbers, however, the non-uniform array was outperformed by the closely spaced array.
A Skeletal Mechanism for the Reactive Flow Simulation of Methane Combustion
Authors: Karalus Megan F. , Fackler K. Boyd , Novosselov Igor V. , Kramlich John C. , Malte Philip C.
Published: November 2013

A skeletal mechanism for the prediction of NOx emissions from methane combustion at gas turbine conditions is developed in the present work. The goal is a mechanism that can be used in computational fluid dynamic modeling of lean premixed (LPM) combustors. A database of solutions from 0-D, adiabatic, homogeneous reactors (PSRs) is computed using CHEMKINPRO [1] over a parameter space chosen to include pressures from 1 to 30 atm, equivalence ratios from 0.4 to 1.0, and mean PSR residence times from slightly greater than blowout to 3ms. A resisidence time of 3 ms represents a useful maximum for the super-equilibrium flame zone where most of the NOx forms in LPM combustors. Fuel oxidation and NOx formation are treated separately in the reduction process. The method of Directed Relation Graph (DRG) is applied for methane oxidation and its extension, DRG-aided sensitivity analysis (DRGASA), is used to determine the skeletal NOx mechanism to append to the methane mechanism. Post-processing of the PSR solution database and implementation of the reduction algorithm are accomplished in SAGE [2], a Python based, open-source mathematics software package. The skeletal oxidation and NOx mechanisms are validated against full GRI 3.0 [3] in both PSR and laminar flame speed calculations. When compared with the detailed GRI 3.0 mechanism, NOx emissions are predicted within 7% near blowout and 3% at 3ms, and laminar flame speeds are predicted within 20% over the range of equivalence ratios and pressures. The skeletal mechanism is presented here and it should be noted that all reactions of the H2/CO submechanism are retained.

The skeletal mechanism consists of 22 species and 122 reactions for methane oxidation and an additional 8 species and 55 reactions to describe NOx formation (30 species, 177 reactions total). The final skeletal mechanism with NOx chemistry is available for download here [4]. To demonstrate the predictive capability of the validated mechanism in a reactive flow system, it is implemented in an ANSYS Fluent model of a single jet stirred reactor, the results of which are compared to experimental reactor data presented in [5] and [6]. Predicted and measured profiles of temperature and NOx emissions are shown. Temperature and NOx emissions compare well in the recirculation zone of the JSR, although both NOx emissions and temperature are under-predicted in the jet region. Finally, the contribution of each chemical pathway for NOx formation is evaluated.
Protected Areas and Effective Biodiversity Conservation
Authors: Le Saout Soizic , Hoffmann Michael , Shi Yichuan , Hughes Adrian , Bernard Cyril , Brooks Thomas M. , Bertzky Bastian , Butchart Stuart H. M. , Stuart Simon N. , Badman Tim , Rodrigues Ana S. L.
Published: November 2013

Increasing the collective contribution of protected areas toward preventing species extinctions requires the strategic allocation of management efforts.
High-Performance Silicon Photoanodes Passivated with Ultrathin Nickel Films for Water Oxidation
Authors: Kenney Michael J. , Gong Ming , Li Yanguang , Wu Justin Z. , Feng Ju , Lanza Mario , Dai Hongjie
Published: November 2013

Stabilizing Silicon

Solar-driven water splitting has potential as an energy storage mechanism to supplement the direct conversion of sunlight to electricity. A submersed integrated device has been proposed both to absorb the light and to catalyze the reaction, but stability has been a problem.

Kenney
et al.

(p.
836
; see the Perspective by

Turner

) found that a nickel coating, thin enough to let light through, could protect a silicon absorber in the alkaline environment of a lithium/potassium borate electrolyte. The nickel also functioned as the oxidation catalyst, and the lithium ions helped to establish a protective film structure in situ.
Changes in Cytoplasmic Volume Are Sufficient to Drive Spindle Scaling
Authors: Hazel James , Krutkramelis Kaspars , Mooney Paul , Tomschik Miroslav , Gerow Ken , Oakey John , Gatlin J. C.
Published: November 2013

Scaling Spindle Size

The difficulty of modulating cell size in vivo has made it hard to test hypotheses for organelle size scaling during development. To this end,

Hazel
et al.

(p.
853
) and

Good
et al.

(p.
856
) developed microfluidic systems in which cytoplasmic extracts are encapsulated in compartments with definable size. The size of mitotic spindles assembled within cell-free extracts scaled with the volume of the compartment within which the spindle assembled. The findings suggest that the diminished availability of cytoplasmic components, notably tubulin, concomitant with cell size reduction, prescribes a smaller spindle size.
Cytoplasmic Volume Modulates Spindle Size During Embryogenesis
Authors: Good Matthew C. , Vahey Michael D. , Skandarajah Arunan , Fletcher Daniel A. , Heald Rebecca
Published: November 2013

Scaling Spindle Size

The difficulty of modulating cell size in vivo has made it hard to test hypotheses for organelle size scaling during development. To this end,

Hazel
et al.

(p.
853
) and

Good
et al.

(p.
856
) developed microfluidic systems in which cytoplasmic extracts are encapsulated in compartments with definable size. The size of mitotic spindles assembled within cell-free extracts scaled with the volume of the compartment within which the spindle assembled. The findings suggest that the diminished availability of cytoplasmic components, notably tubulin, concomitant with cell size reduction, prescribes a smaller spindle size.
Complete Mitochondrial Genomes of Ancient Canids Suggest a European Origin of Domestic Dogs
Authors: Thalmann O. , Shapiro B. , Cui P. , Schuenemann V. J. , Sawyer S. K. , Greenfield D. L. , Germonpré M. B. , Sablin M. V. , López-Giráldez F. , Domingo-Roura X. , Napierala H. , Uerpmann H-P. , Loponte D. M. , Acosta A. A. , Giemsch L. , Schmitz R. W. , Worthington B. , Buikstra J. E. , Druzhkova A. , Graphodatsky A. S. , Ovodov N. D. , Wahlberg N. , Freedman A. H. , Schweizer R. M. , Koepfli K.-P. , Leonard J. A. , Meyer M. , Krause J. , Pääbo S. , Green R. E. , Wayne R. K.
Published: November 2013

Dog Domestication

The precise details of the domestication and origins of domestic dogs are unclear.

Thalmann
et al.

(p.
871
; see the cover) analyzed complete mitochondrial genomes from present-day dogs and wolves, as well as 18 fossil canids dating from 1000 to 36,000 years ago from the Old and New Worlds. The data suggest that an ancient, now extinct, central European population of wolves was directly ancestral to domestic dogs. Furthermore, several ancient dogs may represent failed domestication events.
High-Resolution Global Maps of 21st-Century Forest Cover Change
Authors: Hansen M. C. , Potapov P. V. , Moore R. , Hancher M. , Turubanova S. A. , Tyukavina A. , Thau D. , Stehman S. V. , Goetz S. J. , Loveland T. R. , Kommareddy A. , Egorov A. , Chini L. , Justice C. O. , Townshend J. R. G.
Published: November 2013

Forests in Flux

Forests worldwide are in a state of flux, with accelerating losses in some regions and gains in others.

Hansen
et al.

(p.
850
) examined global Landsat data at a 30-meter spatial resolution to characterize forest extent, loss, and gain from 2000 to 2012. Globally, 2.3 million square kilometers of forest were lost during the 12-year study period and 0.8 million square kilometers of new forest were gained. The tropics exhibited both the greatest losses and the greatest gains (through regrowth and plantation), with losses outstripping gains.
Understanding Lakes Near and Far
Authors: Hampton Stephanie E.
Published: November 2013

Satellite and in situ sensor data complement long-term studies of individual lakes to provide insights into the effects of climate change and pollution.
Enantioselective Lewis Acid Catalysis of Intramolecular Enone [2+2] Photocycloaddition Reactions
Authors: Brimioulle R. , Bach T.
Published: November 2013

[2+2] Asymmetrically

Catalysts in thermal reactions operate by lowering energy barriers of bound substrates, and thereby increasing the proportion of reagents that can proceed to products at a given temperature. In photochemical reactions, light provides the energy to surmount the barrier. It is therefore challenging to alter selectivity through catalysis, because the catalyst may not be bound when a given reagent absorbs the light.
Brimioulle and Bach
(p.
840
) surmounted this problem in the light-induced intramolecular [2+2] cycloaddition of enones by using a catalyst that shifted the absorption wavelength of the bound substrate. The light was thus predominantly absorbed by substrate-catalyst complexes, enabling asymmetric induction by the catalyst to provide enantiomerically enriched products.
Coming to Grips with Learning with Others
Social Learning
An Introduction to Mechanisms, Methods, and Models

by William Hoppitt and Kevin N. Laland

Princeton University Press, Princeton, NJ, 2013. 319 pp. $75, £52. ISBN 9780691150703. Paper, $49.50, £34.95. ISBN 9780691150710.
Authors: Fragaszy Dorothy M. , Eshchar Yonat
Published: November 2013

Hoppitt and Laland offer a comprehensive introduction to the theory, practice, and results of investigations of social learning.
Out of the African Humid Period
Authors: Bard Edouard
Published: November 2013

Data from an East African marine core help to explain the transition from the more humid conditions in the early Holocene to today's arid climate.

[Also see Report by
Tierney and deMenocal
]
Time to Deal with Antibiotics
Authors: Kennedy Donald
Published: November 2013

Antibiotic drugs—penicillin, tetracycline, and their more modern successors—have been critical elements in the world's efforts to sustain health and deal with human diseases. Unfortunately, the vital role of these drugs has been critically compromised by the prevalence of dangerous infections that antibiotics can no longer control, because bacteria are resistant to them. Even nations with strong health care systems, respected medical centers, and fine hospitals are experiencing a growing epidemic of infections that they now simply cannot cure. Here in the United States, such infections kill nearly 23,000 people each year, according to the Centers for Disease Control and Prevention's (CDC's) report
Antibiotic Resistance Threats in the United States, 2013.
Farming practices are largely to blame for the rise of antibiotic-resistant strains, and at last there is hope for reform.
Old Dogs Teach a New Lesson About Canine Origins
Authors: Pennisi Elizabeth
Published: November 2013

By comparing the mitochondrial genomes of 18 ancient canids with modern dogs, wolves, and coyotes, researchers conclude that dogs were domesticated first in Europe from a lineage of gray wolves that no longer exists.
Increased Proportions of Bifidobacterium and the Lactobacillus Group and Loss of Butyrate-Producing Bacteria in Inflammatory Bowel Disease
Authors: Wang Wei , Chen Liping , Zhou Rui , Wang Xiaobing , Song Lu , Huang Sha , Wang Ge , Xia Bing
Published: November 2013

Dysbiosis in the intestinal microbiota of persons with inflammatory bowel disease (IBD) has been described, but there are still varied reports on changes in the abundance of
Bifidobacterium
and
Lactobacillus
organisms in patients with IBD. The aim of this investigation was to compare the compositions of mucosa-associated and fecal bacteria in patients with IBD and in healthy controls (HCs). Fecal and biopsy samples from 21 HCs, 21 and 15 Crohn's disease (CD) patients, and 34 and 29 ulcerative colitis (UC) patients, respectively, were analyzed by quantitative real-time PCR targeting the 16S rRNA gene. The bacterial numbers were transformed into relative percentages for statistical analysis. The proportions of bacteria were uniformly distributed along the colon regardless of the disease state.
Bifidobacterium
was significantly increased in the biopsy specimens of active UC patients compared to those in the HCs (4.6% versus 2.1%,
P
= 0.001), and the proportion of
Bifidobacterium
was significantly higher in the biopsy specimens than in the fecal samples in active CD patients (2.7% versus 2.0%,
P
= 0.012). The
Lactobacillus
group was significantly increased in the biopsy specimens of active CD patients compared to those in the HCs (3.4% versus 2.3%,
P
= 0.036). Compared to the HCs,
Faecalibacterium prausnitzii
was sharply decreased in both the fecal and biopsy specimens of the active CD patients (0.3% versus 14.0%,
P
< 0.0001 for fecal samples; 0.8% versus 11.4%,
P
< 0.0001 for biopsy specimens) and the active UC patients (4.3% versus 14.0%,
P
= 0.001 for fecal samples; 2.8% versus 11.4%,
P
< 0.0001 for biopsy specimens). In conclusion,
Bifidobacterium
and the
Lactobacillus
group were increased in active IBD patients and should be used more cautiously as probiotics during the active phase of IBD. Butyrate-producing bacteria might be important to gut homeostasis.
Pretreatment of Urine Samples with SDS Improves Direct Identification of Urinary Tract Pathogens with Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry
Authors: Sánchez-Juanes F. , Siller Ruiz M. , Moreno Obregón F. , Criado González M. , Hernández Egido S. , de Frutos Serna M. , González-Buitrago J. M. , Muñoz-Bellido J. L.
Published: November 2013

We pretreated with SDS 71 urine samples with bacterial counts of >10
5
CFU/ml and matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) identification scores of <2, in order to minimize failure rates. Identification improved in 46.5% of samples, remained unchanged in 49.3%, and worsened in 4.2%. The improvement was more evident for Gram-negative (54.3%) than for Gram-positive (32%) bacteria.
Copy Numbers of Telomeric Repeat Sequences of Human Herpesvirus 6B in Clinical Isolates: Possibility of Mixed Infections
Authors: Kato Yuri , Ihira Masaru , Umeda Mami , Higashimoto Yuki , Kawamura Yoshiki , Ohashi Masahiro , Ishi Junichi , Yoshikawa Tetsushi
Published: November 2013

In order to determine whether mixed infections of human herpesvirus 6B (HHV-6B) occur in immunocompetent and immunocompromised individuals, we examined the copy numbers of telomeric repeat sequences (TRS) of clinical isolates. In clinical isolates obtained from patients with exanthem subitum caused by primary HHV-6B infection, PCR products with HHV-6B TRS ranging between 400 and 800 bp were amplified. PCR products of various sizes were amplified in four clinical isolates from drug-induced hypersensitivity syndrome (DIHS) patients and 15 isolates from hematopoietic stem cell transplant (HSCT) recipients with HHV-6B reactivation. Based on the sequence analysis of the PCR products, the copy numbers of TRS in DIHS and HSCT patients were between 42 and 82 and 22 and >90, respectively. For two of the HSCT recipients, HHV-6B TRS PCR products of different sizes were detected in several isolates from each patient, which suggests mixed HHV-6B infections. In two of the posttransplant HHV-6B encephalitis patients, the sizes of the TRS nested PCR products amplified from the reactivated virus detected in the central nervous system differed from those of the virus detected in initial isolates from peripheral blood mononuclear cells. Taken together, these results suggest that PCR analysis of TRS copy number is a reliable tool for the discrimination of HHV-6B clinical isolates. Additionally, mixed HHV-6B infections occurred in HSCT recipients, and in some cases, compartmentalization of the HHV-6B strains to the central nervous system versus the blood compartment occurred in posttransplant HHV-6B encephalitis patients.
Incorporation of a Proteotyping Approach Using Mass Spectrometry for Surveillance of Influenza Virus in Cell-Cultured Strains
Authors: Fernandes Neil D. , Downard Kevin M.
Published: November 2013

The reemergence of deadly pandemic influenza virus strains has necessitated the development of improved methods for rapid detection and subtyping of influenza viruses that will enable more strains to be characterized at the molecular level. Representative circulating strains of human influenza viruses from primary clinical specimens were grown in cell culture, purified through polyethylene glycol precipitation, proteolytically digested with an endoproteinase, and analyzed and identified by high-resolution mass spectrometry using unique signature peptides that are characteristic of type A H1N1 and H3N2 and type B influenza viruses. This proteotyping approach enabled circulating strains of type A influenza virus to be typed and subtyped, cocirculating seasonal and pandemic H1N1 viruses to be differentiated, and the lineage of type B viruses to be determined through single-ion detection by high-resolution mass spectrometry. Results were obtained using virus titers comparable to those used in reverse transcription (RT)-PCR assays with clinical specimens grown in cell cultures. The methodology represents a more rapid and direct approach than RT-PCR and can be integrated into existing procedures currently used for the surveillance of emerging pandemic and seasonal influenza viruses.
Risk Assessment of H2N2 Influenza Viruses from the Avian Reservoir
Authors: Jones Jeremy C. , Baranovich Tatiana , Marathe Bindumadhav M. , Danner Angela F. , Seiler Jon P. , Franks John , Govorkova Elena A. , Krauss Scott , Webster Robert G.
Published: November 2013

H2N2 influenza A viruses were the cause of the 1957-1958 pandemic. Historical evidence demonstrates they arose from avian virus ancestors, and while the H2N2 subtype has disappeared from humans, it persists in wild and domestic birds. Reemergence of H2N2 in humans is a significant threat due to the absence of humoral immunity in individuals under the age of 50. Thus, examination of these viruses, particularly those from the avian reservoir, must be addressed through surveillance, characterization, and antiviral testing. The data presented here are a risk assessment of 22 avian H2N2 viruses isolated from wild and domestic birds over 6 decades. Our data show that they have a low rate of genetic and antigenic evolution and remained similar to isolates circulating near the time of the pandemic. Most isolates replicated in mice and human bronchial epithelial cells, but replication in swine tissues was low or absent. Multiple isolates replicated in ferrets, and 3 viruses were transmitted to direct-contact cage mates. Markers of mammalian adaptation in hemagglutinin (HA) and PB2 proteins were absent from all isolates, and they retained a preference for avian-like α2,3-linked sialic acid receptors. Most isolates remained antigenically similar to pandemic A/Singapore/1/57 (H2N2) virus, suggesting they could be controlled by the pandemic vaccine candidate. All viruses were susceptible to neuraminidase inhibitors and adamantanes. Nonetheless, the sustained pathogenicity of avian H2N2 viruses in multiple mammalian models elevates their risk potential for human infections and stresses the need for continual surveillance as a component of prepandemic planning.
Immunoprevalence and Immunodominance of HLA-Cw∗0801-Restricted T Cell Response Targeting the Hepatitis B Virus Envelope Transmembrane Region
Authors: Tan Anthony T. , Sodsai Pimpayao , Chia Adeline , Moreau Eglantine , Chng Melissa H. Y. , Tham Christine Y. L. , Ho Zi Zong , Banu Nasirah , Hirankarn Nattiya , Bertoletti Antonio
Published: November 2013

HLA-C-restricted T cells have been shown to play an important role in HIV control, but their impact on protection or pathogenesis in other viral infections remains elusive. Here, we characterized the hierarchy of HLA class I-restricted hepatitis B virus (HBV) epitopes targeted by CD8 T cells in HBV-infected subjects. The frequency of CD8 T cells specific for a panel of 18 HBV epitopes (restricted by HLA-A∗0201/03/07 [hereinafter HLA-A0201/03/07], -A1101, -A2402/07, -B5801, -B4001, -B1301, and -Cw0801) was quantified in a total of 59 subjects who resolved HBV infection. We found that the HLA-Cw0801-restricted epitope comprised of Env residues 171 to 180 (Env
171–180
) is immunoprevalent in the Southeast Asian subjects (10/17 HLA-Cw0801-positive subjects) and immunodominant in the majority of HLA-Cw0801-positive subjects able to control HBV infection. HLA-Cw0801-restricted Env
171–180
-specific CD8 T cells recognized endogenously produced HBV surface antigen (HBsAg) and tolerated amino acid variations within the epitope detected in HBV genotypes B and C. In conclusion, we demonstrate that the HLA-Cw0801-restricted Env
171–180
T cell response is an important component of the HBV-specific adaptive T cell immunity in Asians infected with HBV. Thus, HLA-C restricted T cells might play an important role in various viral infections.
Human Cytomegalovirus Major Immediate Early 1 Protein Targets Host Chromosomes by Docking to the Acidic Pocket on the Nucleosome Surface
Authors: Mücke Katrin , Paulus Christina , Bernhardt Katharina , Gerrer Katrin , Schön Kathrin , Fink Alina , Sauer Eva-Maria , Asbach-Nitzsche Alexandra , Harwardt Thomas , Kieninger Bärbel , Kremer Werner , Kalbitzer Hans Robert , Nevels Michael
Published: November 2013

The 72-kDa immediate early 1 (IE1) protein encoded by human cytomegalovirus (hCMV) is a nuclearly localized promiscuous regulator of viral and cellular transcription. IE1 has long been known to associate with host mitotic chromatin, yet the mechanisms underlying this interaction have not been specified. In this study, we identify the cellular chromosome receptor for IE1. We demonstrate that the viral protein targets human nucleosomes by directly binding to core histones in a nucleic acid-independent manner. IE1 exhibits two separable histone-interacting regions with differential binding specificities for H2A-H2B and H3-H4. The H2A-H2B binding region was mapped to an evolutionarily conserved 10-amino-acid motif within the chromatin-tethering domain (CTD) of IE1. Results from experimental approaches combined with molecular modeling indicate that the IE1 CTD adopts a β-hairpin structure, docking with the acidic pocket formed by H2A-H2B on the nucleosome surface. IE1 binds to the acidic pocket in a way similar to that of the latency-associated nuclear antigen (LANA) of the Kaposi's sarcoma-associated herpesvirus. Consequently, the IE1 and LANA CTDs compete for binding to nucleosome cores and chromatin. Our work elucidates in detail how a key viral regulator is anchored to human chromosomes and identifies the nucleosomal acidic pocket as a joint target of proteins from distantly related viruses. Based on the striking similarities between the IE1 and LANA CTDs and the fact that nucleosome targeting by IE1 is dispensable for productive replication even in “clinical” strains of hCMV, we speculate that the two viral proteins may serve analogous functions during latency of their respective viruses.
Expression Profile of MicroRNAs in Epstein-Barr Virus-Infected AGS Gastric Carcinoma Cells
Authors: Marquitz Aron R. , Mathur Anuja , Chugh Pauline E. , Dittmer Dirk P. , Raab-Traub Nancy
Published: November 2013

Latent infection with Epstein-Barr virus (EBV) is responsible for multiple types of malignancies, including 10% of all gastric carcinomas. The microRNA (miRNA) expression in several EBV-infected AGS gastric carcinoma cell lines was determined. Infected cells expressed the viral BamHI A rightward transcript (BART) miRNAs at high levels and had consistently decreased expression of a small fraction of cellular miRNAs with specific downregulation of tumor suppressor miRNAs. These changes likely reflect expression of the viral noncoding RNAs and not latent protein expression.
Mechanism of HIV-1 Neutralization by Antibodies Targeting a Membrane-Proximal Region of gp41
Authors: Chen Jia , Frey Gary , Peng Hanqin , Rits-Volloch Sophia , Garrity Jetta , Seaman Michael S. , Chen Bing
Published: November 2013

Induction of broadly neutralizing antibodies (bNAbs) is an important goal for HIV-1 vaccine development. Two autoreactive bNAbs, 2F5 and 4E10, recognize a conserved region on the HIV-1 envelope glycoprotein gp41 adjacent to the viral membrane known as the membrane-proximal external region (MPER). They block viral infection by targeting a fusion-intermediate conformation of gp41, assisted by an additional interaction with the viral membrane. Another MPER-specific antibody, 10E8, has recently been reported to neutralize HIV-1 with potency and breadth much greater than those of 2F5 or 4E10, but it appeared not to bind phospholipids and might target the untriggered envelope spikes, raising the hope that the MPER could be harnessed for vaccine design without major immunological concerns. Here, we show by three independent approaches that 10E8 indeed binds lipid bilayers through two hydrophobic residues in its CDR H3 (third heavy-chain complementarity-determining region). Its weak affinity for membranes in general and preference for cholesterol-rich membranes may account for its great neutralization potency, as it is less likely than other MPER-specific antibodies to bind cellular membranes nonspecifically. 10E8 binds with high affinity to a construct mimicking the fusion intermediate of gp41 but fails to recognize the envelope trimers representing the untriggered conformation. Moreover, we can improve the potency of 4E10 without affecting its binding to gp41 by a modification of its lipid-interacting CDR H3. These results reveal a general mechanism of HIV-1 neutralization by MPER-specific antibodies that involves interactions with viral lipids.
Characterization of the Noncoding Regions of the 1918 Influenza A H1N1 Virus
Authors: Wang Ruixue , Taubenberger Jeffery K.
Published: November 2013

The terminal noncoding region (NCR) sequences of the eight gene segments of the influenza A/Brevig Mission/1/1918 (H1N1) virus were determined by rapid amplification of cDNA ends (RACE). Chimeric viruses encoding the open reading frames of the 1918 virus but flanked by either the wild-type 1918 NCR sequences or the NCR sequences of two other H1N1 virus strains, A/WSN/1933 and A/New York/312/2001, were produced. No growth differences between the NCR variant 1918 influenza viruses were noted.
Can foster care ever be justified for weight management?
Authors: Williams G M G , Bredow Maria , Barton John , Pryce Rebekah , Shield J P H
Published: November 2013

Article nine of the UN Convention of the Rights of the Child states that ‘Children must not be separated from their parents unless it is in the best interests of the child.’ We describe the impact that placing a child into care can have on long-standing and intractable obesity when this is a component of a child safeguarding strategy. Significant weight loss was documented in a male adolescent following his placement into foster care due to emotional harm and neglect within his birth family. The child's body mass index (BMI) dropped from a peak of 45.6 to 35 over 18 months. We provide brief details of two further similar cases and outcomes. Childhood obesity is often not the sole concern during safeguarding proceedings. Removal from an ‘obesogenic’ home environment should be considered if failure by the parents/carers to address the obesity is a major cause for concern. It is essential that all other avenues have been explored before removing a child from his birth family. However, in certain circumstances we feel it may be justified.
Feasibility, acceptability and outcomes at a 12-month follow-up of a novel community-based intervention to prevent type 2 diabetes in adults at high risk: mixed methods pilot study
Authors: Penn Linda , Ryan Vicky , White Martin
Published: November 2013

Objectives and design

Lifestyle interventions can prevent type 2 diabetes (T2D) in adults with impaired glucose tolerance. In a mixed methods pilot study, we aimed to assess the feasibility, acceptability and outcomes at a 12-month follow-up of a behavioural intervention for adults at risk of T2D.

Participants

Adults aged 45–65 years with a Finnish Diabetes Risk Score (FINDRISC) ≥11.

Setting

The intervention was delivered in leisure and community settings in a local authority that ranks in the 10 most socioeconomically deprived in England.

Intervention

A 10-week supported programme to promote increased physical activity (PA), healthy eating and weight loss was delivered by fitness trainers as twice-weekly group PA or cookery sessions, each followed by behavioural counselling with support to 12 months.

Outcome measures

We assessed feasibility and acceptability of the intervention, and change in behavioural and health-related outcomes at 6 and 12 months.

Results

From 367 registers of interest, 218 participants were recruited to the programme with baseline mean (SD): age 53.6 (6) years, FINDRISC 13.9 (3.1), body mass index 33.5 (5.9) kg/m2, waist circumference 108.1 (13.7) cm, PA levels (self-report): daily total 49.1 (5.9) metabolic-equivalent (MET) h/day. Follow-up at 12 months was completed by 134 (61%) participants, with an estimated mean (95% CI) change from baseline in weight −5.7 (−7.8 to −2.8); −2.8 (−3.8 to −1.9) kg, waist circumference −7.2 (−9.2 to −5.2); −6.0 (−7.1 to −5.0) cm, and PA level 7.9 (5.8 to 10.1); 6.7 (5.2 to 8.2) MET h/day equivalent, for men and women, respectively (from covariance pattern mixed models). Participants reported an enjoyable, sociable and supportive intervention experience.

Conclusions

Participants’ views indicated a high level of intervention acceptability. High retention and positive outcomes at 12 months provide encouraging indications of the feasibility and potential effectiveness of the intervention. A definitive trial of this intervention is warranted.
Long-term prediction of major coronary or ischaemic stroke event in a low-incidence Southern European population: model development and evaluation of clinical utility
Authors: Veronesi Giovanni , Gianfagna Francesco , Chambless Lloyd E , Giampaoli Simona , Mancia Giuseppe , Cesana Giancarlo , Ferrario Marco M
Published: November 2013

Objective

To develop a long-term prediction model of first major cardiovascular event and to assess its clinical utility in a low-incidence European population.

Setting

Four independent population-based cohorts enrolled between 1986 and 1993 in Northern Italy.

Participants and methods

N=5247 35-year-old to 69-year-old men and women free of cardiovascular disease at baseline. Absolute 20-year risk of first fatal or non-fatal coronary or ischaemic stroke event (monitoring trends and determinants in cardiovascular disease (MONICA) validated) was estimated from gender-specific Cox models.

Main outcome measures

Model discrimination (area under the receiver operating characteristic (ROC)-curve, AUC). ‘High-risk’ subjects were identified based on several threshold values for the 20-year predicted risk. Clinical utility was defined in terms of fraction of missed events (events among those considered at low-risk) and unnecessary treatment (false:true positive ratio). A net benefit curve was also provided.

Results

Kaplan-Meier 20-year risk was 16.1% in men (315 events) and 6.1% in women (123 events). Model discrimination (AUC=0.737 in men, 0.801 in women) did not change significantly as compared to 10-year prediction time interval. In men, with respect to risk stratification based on the number of risk factors, a 20% predicted risk cut-off would miss less events (36% vs 50%) and reduce unnecessary treatment (false:true positive ratio 2.2 vs 3.0); the net benefit was higher over the whole range of threshold values. Similar considerations hold for women.

Conclusions

Long-term prediction has good discrimination ability and is clinically useful for risk stratification in primary prevention. A clinical utility analysis is recommended to identify the optimal stratification according to different public health goals.
Pre-hospital spinal immobilisation: an initial consensus statement
Authors: Connor D , Greaves I , Porter K , Bloch M ,   On behalf of the consensus group, Faculty of Pre-Hospital Care
Published: November 2013

This paper reviews the current evidence available on the practice of spinal immobilisation in the prehospital environment. Following this, initial conclusions from a consensus meeting held by the Faculty of Pre-hospital Care, Royal College of Surgeons of Edinburgh in March 2012 are presented.
A short history of providing medical history within the British medical undergraduate curriculum
Authors: Metcalfe N H , Stuart E
Published: November 2013

This article aims to discuss the history of medical history in the British medical undergraduate curriculum and it reviews the main characters and organisations that have attempted to earn it a place in the curriculum. It also reviews the arguments for and against the study of the subject that have been used over the last 160 years.
Prevalence and characteristics in coding, classification and diagnosis of diabetes in primary care
Authors: Seidu Samuel , Davies Melanie J , Mostafa Samiul , de Lusignan Simon , Khunti Kamlesh
Published: November 2013

Introduction

Approximately 366 million people worldwide live with diabetes and this figure is expected to rise. Among the correct diagnosis, there will be errors in the diagnosis, classification and coding, resulting in adverse health and financial implications.

Aim

To determine the prevalence and characteristics of diagnostic errors in people with diabetes managed in primary care settings.

Methods

We conducted a cross-sectional study in nine general practices in Leicester, UK, from May to August 2011, using a validated electronic toolkit. Searches identified cases with potential errors which were manually checked for accuracy.

Results

There were 54 088 patients and 2434 (4.5%) diagnosed with diabetes. Out of 316 people identified with potential errors with the toolkit, 180 (57%) had confirmed errors after manually reviewing the records, resulting in an error prevalence of 7.4%. Correctly coded people on registers had significantly greater glycated haemoglobin (HbA1c) reductions. There were no significant differences between patients with and without errors in their HbA1C, body mass index, age and size of practice. There was also no significant association of the errors with pay-for-performance initiatives; however, those patients not on disease register had worse glycaemic control.

Conclusions

A high prevalence of diabetic diagnostic errors was confirmed using medication, biochemical and demographic data. Larger studies are needed to more accurately assess the scale of this problem. Automation of these processes might be possible, which would allow searches to be even more user friendly.
Ultrasound‐guided atlanto‐occipital puncture for cerebrospinal fluid analysis on the standing horse
Authors: Depecker M. , Bizon‐Mercier C. , Couroucé‐Malblanc A.
Published: November 2013

The atlanto‐occipital site (AO) is convenient for retrieving an adequate volume and quality of cerebrospinal fluid (CSF) in the diagnosis of neurological disease in horses. However, general anaesthesia is not always possible for horses displaying severe neurological signs, or for economical reasons. The objectives of the present work were to determine the feasibility and safety of ultrasound‐guided CSF puncture at the AO site on the standing horse. Seven horses (six healthy and one mildly ataxic) were sedated with acepromazine (0.02 mg/kg bodyweight intravenously or 0.04 mg/kg bodyweight intramuscularly) and detomidine (0.01 mg/kg bodyweight intravenously), and placed in stocks or in a recovery stall with the head kept on a headstand. Puncture was performed by ultrasonographic guidance with a parasagittal technique, as previously described, using a 20 g, 3.5 inch spinal needle. In all horses, no adverse reaction was observed when crossing the dura mater and 20 ml of CSF was rapidly retrieved without any blood contamination. Ultrasound‐guided CSF puncture can be performed easily at the AO site on a healthy standing horse. Regarding the potential risk of this procedure, safety measures and close observation are essential. Further studies on a larger amount of ataxic horses are also required before considering this technique as an alternative option for CSF puncture.
PROTEIN DYNAMICS IN PHOSPHORYLATION-MEDIATED ALLOSTERY PROBED BY AMIDE EXCHANGE MASS SPECTROMETRY
Authors: GHOSH MADHUBRATA , ANAND GANESH S.
Published: November 2013

A major goal of molecular biology is to correlate molecular structure with function. Since most enzymes and biological catalysts are proteins, the focus for correlating 'form' with 'function' has been entirely on protein macromolecular structure. It is obvious that any understanding of protein function must come through an understanding protein dynamics. Furthermore, all of the regulatory reactions are through changes in dynamics brought about by post-translational modifications, the most important of which is phosphorylation. This review highlights the important role of covalent phosphorylation and noncovalent phosphates in regulating allosteric effects and function through a study of protein dynamics. Mass spectrometry is a relatively new and increasingly important tool for describing protein dynamics. All examples described in this review have been studied by amide hydrogen/deuterium exchange mass spectrometry.
Geochemical data management – issues and solutions
Authors: Adcock Stephen W. , Spirito Wendy A. , Garrett Robert G.
Published: November 2013

Geochemical data are complex, and becoming more so as analytical techniques advance. This complexity gives rise to many data management issues that have no simple solutions. The Geological Survey of Canada (GSC) has a long history of collecting and managing geochemical data. The challenges of managing the data are continuously evolving. The emergence of the WWW is causing a revolution in how scientific data are delivered. This paper documents how one group within the GSC is responding to this rapidly changing environment.
Predicting Archaean volcanogenic massive sulphide deposit potential from lithogeochemistry: application to the Abitibi Greenstone Belt
Authors: Grunsky E.C.
Published: November 2013

Archaean greenstone belts are prime exploration targets for volcanogenic massive sulphide deposits and the use of lithogeochemistry plays an important role in detecting and mapping hydrothermal alteration zones and in recognizing the massive sulphide potential of volcanic assemblages. This study reviews the state of existing lithogeochemical databases and the use of new geochemical analyses for the identification of alteration associated with massive sulphide deposits. This paper also provides a new methodology for the prediction of missing values in geochemical compositions. Through the application of statistical methods, combined sets of lithogeochemical data can be used to create predictive maps of prospective massive sulphide successions. Predictive maps are created through the use of multivariate statistical methods, lithogeochemical alteration indices and normative minerals from which areas of multi-element enrichment and depletion are defined. These indices, when combined in an exploration programme, are potentially useful for massive sulphide discovery. Additionally, the use of rare earth elements can be used to characterize differences in the various supracrustal assemblages and provide a better regional understanding of potential metal endowment.

Supplementary material:

Provides details on the datasets selected in this study and is available at
http://www.geolsoc.org.uk/SUP18712