bluuebunny/crossref_metadata_2025 huggingface dataset:
Rehabilitating Seagrass by Facilitating Recruitment: Improving Chances for Success
Authors: Irving Andrew D. , Tanner Jason E. , Collings Greg J.
Published: June 2013

Attempts to arrest seagrass loss through numerous rehabilitation methods have traditionally produced inconsistent results. On Australia's southern coast, hessian bags made from biodegradable jute fibers show promise for rehabilitating Amphibolis antarctica by facilitating recruitment of seedlings in situ. Testing ways to improve the performance of bags (i.e. increasing seagrass recruitment and establishment) showed that bags with a coarse outer weave of hessian facilitated greater seedling densities (approximately 1700 individuals/m2) than bags with a fine outer weave, but the content of bags (sand vs. sand and rubble mixture) had little effect. Isolated bags facilitated greater longer term densities than bags grouped together, while similar densities were sampled up to 80 m away from a natural meadow. Lastly, bags that had spent less time in situ initially facilitated more recruits than older bags, but longer term (21–32 months) retention was similar among bag ages. Collectively, the results suggest hessian bags can be a relatively simple, cost‐effective, and environmentally friendly method for rehabilitating Amphibolis seagrass, with few considerations in their use other than their physical architecture and arrangement (e.g. isolated coarse‐weave bags).
Tectono‐stratigraphic history of the southern Junggar basin: seismic profiling evidences
Authors: Wang Sheng‐Li , Chen Yan , Charreau Julien , Wei Dong‐Tao , Jia Dong
Published: June 2013

The modern Tianshan is an active intracontinental range in central Asia. Its initial timing is poorly known and still hotly debated. As the subsidence of foreland basins is intrinsically coupled with the uplift of orogenic wedges, the foreland sedimentary records may accurately constrain the Tianshan uplifting history. To better address the question, we analyse a seismic profile across the southern Junggar foreland basin to decipher its tectonic and stratigraphic history. Four structural layers can be identified in an ascending order: the Permian – Lower Jurassic transtension‐related layer, the Jurassic – Cretaceous thermal‐subsistence layer, the Palaeogene layer and the Miocene – Quaternary foreland sedimentary layer. The oldest sedimentary sequence in the foreland succession is of the Shawan Formation deposited at ~24 Ma based on magnetostratigraphic constraints. This indicates that foreland deformation in the northern Tianshan and uplifting of the modern Tianshan probably initiated at the beginning of the Miocene.
Effect of topical naltrexone 0.3% on corneal sensitivity and tear parameters in normal brachycephalic dogs
Authors: Arnold Trevor S. , Wittenburg Luke A. , Powell Cynthia C.
Published: June 2013

Objective

To determine the effect of topical naltrexone 0.3% on tear production, corneal sensitivity, and tear film stability in normal brachycephalic dogs.

Animals Studied

Twenty‐two normal brachycephalic dogs.

Procedures

Measurements of tear production (Schirmer tear test I and II), intraocular pressure (IOP), central corneal sensitivity (CS), and tear film breakup time (TFBUT) were collected at time 0, 1, and 24 h after administration of either naltrexone (NTX) 0.3% or placebo (SV). Naltrexone or SV was then administered once daily for 1 week, and the above measurements were repeated at 7 days, then again 7 days after discontinuing medication. Owners scored the degree of comfort, redness, rubbing, squinting, and tearing. Serum was collected at time 0, 1, 24 h, and 7 days to determine systemic concentrations.

Results

Owners reported no significant change in the degree of comfort, redness, rubbing, squinting, or tearing. Naltrexone was detected in serum of all treated dogs 1‐h postadministration (average: 908 pg/mL, range: 319–1570 pg/mL) and in two dogs at the 1‐week time point. Naltrexone was not detected at the 24‐h time point. There was no significant effect of NTX on STT1, STT2, IOP, CS, or TFBUT.

Conclusions

Naltrexone 0.3% is well tolerated and safe when applied topically to the eye once daily. Naltrexone 0.3% did not show any significant effects on corneal parameters as measured in this study. At once, daily dosing NTX is systemically absorbed; however, the degree of systemic absorption is not likely to be clinically significant.
Secondary prophylaxis vs. on‐demand treatment to improve quality of life in severe adult haemophilia A patients: a prospective study in a single centre
Authors: Aznar J. A. , García‐Dasí M. , Pérez‐Alenda S. , Marco A. , Jaca M. , Moret A. , Querol F.
Published: June 2013

Background

Retrospective publications show a decrease in the bleeding frequency and an improvement in the quality of life (QoL) in severe adult haemophilia A (SAHA) after switching from the on‐demand treatment (DT) to secondary prophylaxis (SP). But there are no prospective studies which demonstrate, using a haemophilia‐specific questionnaire, an improvement in the QoL after such treatment change. The main objective of this study is to prospectively compare the QoL and the musculoskeletal assessment after switching from DT to SP in SAHA using the A36 Hemofilia‐QoL®. As secondary objective, we compare the haemarthrosis frequency and factor VIII consumption in DT and SP during a similar period of time (12 months) after switching.

Materials and Methods

We have designed a prospective study including SAHA who have been under DT and were changed to a protocol, which combines SP (biweekly administration of factor VIII) with individualized physiotherapy programme.

Results

Twelve months after switching to SP, the QoL was significantly improved (P = 0·005). Musculoskeletal assessment of pathologic irreversible joints and joints with a reversible alteration was generally improved, although in only a few joints, this improvement was statistically significant. Haemarthrosis was strongly reduced (12·60–1·42, P < 0·001).

Conclusions

This prospective study has demonstrated a statistically significant improvement in the QoL after 1 year from switching patients from DT to SP. The musculoskeletal assessment after 1 year was maintained similar or slightly improved. When we compared retrospective DT and prospective SP, haemarthrosis where strongly reduced requiring a slight increase in the consumption of factor VIII concentrates.
A Cross‐Sectional Study Examining Campylobacter and Other Zoonotic Enteric Pathogens in Dogs that Frequent Dog Parks in Three Cities in South‐Western Ontario and Risk Factors for Shedding of Campylobacter spp.
Authors: Procter T. D. , Pearl D. L. , Finley R. L. , Leonard E. K. , Janecko N. , Reid‐Smith R. J. , Weese J. S. , Peregrine A. S. , Sargeant J. M.
Published: June 2013

An estimated 6 million pet dogs live in Canadian households with the potential to transmit zoonotic pathogens to humans. Dogs have been identified as carriers of Salmonella, Giardia and Campylobacter spp., particularly Campylobacter upsaliensis, but little is known about the prevalence and risk factors for these pathogens in pet dogs that visit dog parks. This study examined the prevalence of these organisms in the faeces of dogs visiting dog parks in three cities in south‐western Ontario, as well as risk factors for shedding Campylobacter spp. and C. upsaliensis. From May to August 2009, canine faecal samples were collected at ten dog parks in the cities of Guelph and Kitchener‐Waterloo, Ontario, Canada. Owners were asked to complete a questionnaire related to pet characteristics and management factors including age, diet and activities in which the dog participates. Faecal samples were collected from 251 dogs, and 189 questionnaires were completed. Salmonella, Giardia and Campylobacter spp. were present in 1.2%, 6.4% and 43.0% of faecal samples, respectively. Of the Campylobacter spp. detected, 86.1% were C. upsaliensis, 13% were C. jejuni and 0.9% were C. coli. Statistically significant sparing factors associated with the shedding of Campylobacter spp. included the feeding of a commercial dry diet and the dog's exposure to compost. Age of dog had a quadratic effect, with young dogs and senior dogs having an increased probability of shedding Campylobacter spp. compared with adult dogs. The only statistically significant risk factor for shedding C. upsaliensis was outdoor water access including lakes and ditches, while dogs >1 year old were at a lower risk than young dogs. Understanding the pet‐related risk factors for Campylobacter spp. and C. upsaliensis shedding in dogs may help in the development of awareness and management strategies to potentially reduce the risk of transmitting this pathogen from dogs to humans.
Study of Flow Boiling Characteristics of a Microchannel Using High Speed Visualization
Authors: Ali Rashid , Palm Björn , Martin-Callizo Claudi , Maqbool Mohammad H.
Published: June 2013

This paper presents the visualization results obtained for an experimental study of R134a during flow boiling in a horizontal microchannel. The microchannel used was a fused silica tube having an internal diameter of 781 μm, a heated length of 191 mm, and was coated with a thin, transparent, and electrically conductive layer of indium-tin-oxide (ITO) on the outer surface. The operating parameters during the experiments were: mass flux 100–400 kg/m2 s, heat flux 5–45 kW/m2, saturation temperatures 25 and 30 °C, corresponding to saturation pressures of 6.65 bar and 7.70 bar and reduced pressures of 0.163 and 0.189, respectively. A high speed camera with a close up lens was used to capture the flow patterns that evolved along the channel. Flow pattern maps are presented in terms of the superficial gas and liquid velocity and in terms of the Reynolds number and vapor quality plots. The results are compared with some flow pattern maps for conventional and micro scale channels available in the literature. Rigorous boiling and increased coalescence rates were observed with an increase in the heat flux.
Structure and Thermal Conductivity of Nanostructured Hafnia-Based Thermal Barrier Coating Grown on SS-403
Authors: Noor-A-Alam M. , Choudhuri A. R. , Ramana C. V.
Published: June 2013

Yttria-stabilized hafnia (YSH) coatings were grown onto stainless steel 403 (SS-403) and Si substrates. The deposition was made at various growth temperatures ranging from room temperature (RT) to 500 °C. The microstructure and thermal properties of the YSH coatings were evaluated employing grazing incidence X-ray diffraction (GIXRD), scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDS), and photoacoustic measurements. GIXRD studies indicate that the coatings crystalize in cubic structure with a (111) texturing. Well-grown triangular dense morphology was evident in SEM data. EDS analysis indicates the composition stability of YSH coatings. The grain size increases with the increasing growth temperature. Thermal conductivity measurements indicate lower thermal conductivity of YSH coatings compared to either pure hafnia or yttria-stabilized zirconia.
A Bio-Inspired Condylar Hinge for Robotic Limbs
Authors: Etoundi Appolinaire C. , Burgess Stuart C. , Vaidyanathan Ravi
Published: June 2013

This paper presents a novel condylar hinge for robotic limbs which was inspired by the human knee joint. The ligaments in the human knee joint can be modeled as an inverted parallelogram four-bar mechanism. The knee joint also has a condylar cam mechanism between the femur and tibia bones. The bio-inspired joint mimics the four-bar mechanism and the cam mechanism of the human knee joint. The bio-inspired design has the same desirable features of a human knee joint including compactness, high mechanical advantage, high strength, high stiffness and locking in the upright position. These characteristics are important for robotic limbs where there are often tight space and mass limitations. A prototype hinge joint similar in size to the human knee joint has been designed and tested. Experimental tests have shown that the new condylar hinge joint has superior performance to a pin-jointed hinge in terms of mechanical advantage and stiffness. The prototype hinge has a mechanical advantage that is greater than a pin-jointed hinge by up to 35% which leads to a corresponding reduction in the peak force of the actuator of up to 35% for a squatting movement. The paper also presents a five-step design procedure to produce a combined inverted parallelogram mechanism with a cam mechanism.
Influence of Surface Roughness Lay Directionality on Scuffing Failure of Lubricated Point Contacts
Authors: Li S.
Published: June 2013

The influence of roughness lay directionality on scuffing failure is studied considering different roughness lay direction combinations of the contacting surfaces of a ball-on-disk contact. Using a recently developed scuffing model Li et al., (2013, “A Model to Predict Scuffing Failures of a Ball-On-Disk Contact,” Tribol. Int., 60, pp. 233–245)., the bulk temperature and flash temperature are predicted for each roughness lay combination within the load range from 0.76 GPa to 2.47 GPa in a step-wise manner under the rolling velocity of 10 m/s and slide-to-roll ratio of −0.5 to show substantial impacts of roughness lay directionality on scuffing resistance performance (SRP). It is found (i) the lay direction combination that results into contacts of asperities with small contact radii leads to increased local contact pressures and frictional heat flux, reducing SRP; (ii) the continuous asperity contact along the sliding direction leads to continuous surface temperature rise and lowers SRP; and (iii) the lubricant side leakage caused by the pressure gradient in the direction normal to the sliding direction leads to reduced SRP. With these main mechanisms in effect, the SRP of a contact decreases as the deviation between the roughness texture orientations of the two surfaces increases. The surfaces with their roughness lay directions both perpendicular to the sliding direction exhibits best SRP. The surfaces with one roughness lay direction positioned in line with the direction of sliding and the other positioned perpendicular to the sliding direction shows worst SRP.
Dynamic Programming-Informed Equivalent Cost Minimization Control Strategies for Hybrid-Electric Vehicles
Authors: Pei Dekun , Leamy Michael J.
Published: June 2013

This paper presents a direct mathematical approach for determining the state of charge (SOC)-dependent equivalent cost factor in hybrid-electric vehicle (HEV) supervisory control problems using globally optimal dynamic programming (DP). It therefore provides a rational basis for designing equivalent cost minimization strategies (ECMS) which achieve near optimal fuel economy (FE). The suggested approach makes use of the Pareto optimality criterion that exists in both ECMS and DP, and as such predicts the optimal equivalence factor for a drive cycle using DP marginal cost. The equivalence factor is then further modified with corrections based on battery SOC, with the aim of making the equivalence factor robust to drive cycle variations. Adaptive logic is also implemented to ensure battery charge sustaining operation at the desired SOC. Simulations performed on parallel and power-split HEV architectures demonstrate the cross-platform applicability of the DP-informed ECMS approach. Fuel economy data resulting from the simulations demonstrate that the robust controller consistently achieves FE within 1% of the global optimum prescribed by DP. Additionally, even when the equivalence factor deviates substantially from the optimal value for a drive cycle, the robust controller can still produce FE within 1–2% of the global optimum. This compares favorably with a traditional ECMS controller based on a constant equivalence factor, which can produce FE 20–30% less than the global optimum under the same conditions. As such, the controller approach detailed should result in ECMS supervisory controllers that can achieve near optimal FE performance, even if component parameters vary from assumed values (e.g., due to manufacturing variation, environmental effects or aging), or actual driving conditions deviate largely from standard drive cycles.
From Gas to Stars Over Cosmic Time
Authors: Mac Low Mordecai-Mark
Published: June 2013

Background

Immediately after the Big Bang, the universe was uniform, homogeneous, and completely free of stars. The gravitational collapse of dark matter gathered gas with it that cooled, collapsed further, and formed stars. Observations over the past 20 years have revealed the dynamic star-formation history of the universe. The star-formation rate peaked 10 billion years ago, when stars formed an order of magnitude faster than in the modern universe. Deep observations have begun to reveal the early history of star formation, but how quickly star formation started remains controversial, with results from observations of early galaxies suggesting a slower start than distributions of distant gamma-ray bursts that trace young stars. However, simulations using standard prescriptions for energetic feedback from star formation (from stellar explosions and ionizing radiation) have tended to predict a substantially earlier peak than either of these methods shows.

Advances

Energetic feedback drives turbulence in diffuse gas that both promotes and inhibits star formation, with inhibition dominating over promotion, so that star formation does not efficiently trigger further star formation. Insufficient numerical resolution in simulations causes unphysical radiative cooling to occur in multiple ways, reducing the effectiveness of feedback in driving turbulence. Other mechanisms—such as magnetorotational instability, radiative heating, or accretion from the intergalactic medium—must also contribute to the observed gas velocity dispersions. Radiation pressure appears likely to be only modestly effective because of Rayleigh-Taylor instability in gas accelerated by it. Observed correlations between gas surface density and star-formation rate surface density can be reproduced by models including gravitational instability. Molecule formation may occur as a result of gravitational collapse rather than initiating it. Thus, gravitational instability seems to determine star formation, with the level of turbulence setting the critical density for instability.

Outlook

Determining the early history of star formation will require the efforts of the largest ground and space-based telescopes under construction, such as the James Webb Space Telescope
,
the European Extremely Large Telescope, and the Large Synoptic Survey Telescope. Progress in models requires both better algorithms and larger computers. Adaptive meshes, both structured and unstructured, will play a critical role, as will hybrid algorithms that can take full advantage of the shared memory nodes of massively parallel computer clusters. A clear picture of star formation will underpin our understanding of the evolution of galaxies, including our own Milky Way, and of the history of the production and distribution of the elements heavier than helium, including those necessary for planet formation and for life.
Elongation Factor G Bound to the Ribosome in an Intermediate State of Translocation
Authors: Tourigny David S. , Fernández Israel S. , Kelley Ann C. , Ramakrishnan V.
Published: June 2013

Revealed in Translation

The ribosome, with the help of transfer RNAs (tRNAs), converts the triple genetic code in messenger RNA (mRNA) into protein. Upon decoding of a codon, the mRNA and associated tRNAs must be moved through the ribosome, so that the next codon can be read, with a new charged tRNA taken in at the A (aminoacyl-tRNA) site, the newly extended peptidyl-tRNA moved into the P (peptidyl-tRNA) site, and the deacylated tRNA removed from the exit site in the ribosome (see the Perspective by

Rodnina

). Crystal structures from

Tourigny
et al.

(p.
1235490
),
Pulk and Cate
(p.
1235970
), and

Zhou
et al.

(p.
1236086
), variously capture the prokaryotic ribosome during this translocation phase, revealing the hybrid states of the tRNAs and the substantial motions of the 30S ribosomal subunit during the process, the role of elongation factor G, and suggest how the direction and reading frame of the mRNA is maintained.
Control of Ribosomal Subunit Rotation by Elongation Factor G
Authors: Pulk Arto , Cate Jamie H. D.
Published: June 2013

Revealed in Translation

The ribosome, with the help of transfer RNAs (tRNAs), converts the triple genetic code in messenger RNA (mRNA) into protein. Upon decoding of a codon, the mRNA and associated tRNAs must be moved through the ribosome, so that the next codon can be read, with a new charged tRNA taken in at the A (aminoacyl-tRNA) site, the newly extended peptidyl-tRNA moved into the P (peptidyl-tRNA) site, and the deacylated tRNA removed from the exit site in the ribosome (see the Perspective by

Rodnina

). Crystal structures from

Tourigny
et al.

(p.
1235490
),
Pulk and Cate
(p.
1235970
), and

Zhou
et al.

(p.
1236086
), variously capture the prokaryotic ribosome during this translocation phase, revealing the hybrid states of the tRNAs and the substantial motions of the 30S ribosomal subunit during the process, the role of elongation factor G, and suggest how the direction and reading frame of the mRNA is maintained.
Crystal Structures of EF-G–Ribosome Complexes Trapped in Intermediate States of Translocation
Authors: Zhou Jie , Lancaster Laura , Donohue John Paul , Noller Harry F.
Published: June 2013

Introduction:
One of the most critical and complex steps of protein synthesis is the coupled translocation of mRNA and tRNAs (mRNA and tRNAs) through the ribosome, catalyzed by the guanosine triphosphatase (GTPase) elongation factor EF-G. Although several of the main steps have been identified, the underlying molecular mechanisms of translocation are poorly understood. A central question is how structural rearrangements in the ribosome are coupled to movement of mRNA and tRNA.

Methods:
We trapped and crystallized complexes of
Thermus thermophilus
ribosomes bound with EF-G, mRNA, and tRNA, using the antibiotic fusidic acid (which prevents release of EF-G after GTP hydrolysis) or the nonhydrolyzable GTP analog GDPNP, in intermediate states of translocation. Their crystal structures were determined to resolutions from 3.5 to 4.1 Å.

Results:
The structures of the fusidic acid complex (Fus) and two GDPNP complexes (GDPNP-I and GDPNP-II) reveal conformational changes occurring during intermediate states of translocation, including large-scale (15° to 18°) rotation of the 30
S
subunit head and 3° to 5° rotation of the 30
S
body. In all complexes, the tRNA acceptor end has moved from the 50
S
subunit P site to the 50
S
E site, while the anticodon stem loop (ASL) and mRNA move with the head of the 30
S
subunit to positions between the P and E sites, forming chimeric pe*/E intermediate states. The elongated, mobile domain IV of EF-G moves to contact the head of the 30
S
subunit and the backbone of the mRNA. Two universally conserved bases of 16
S
rRNA that intercalate between bases of the mRNA may act as “pawls” of a translocational ratchet. In the GDPNP complexes, structuring of the conserved switch loop I segment, which was disordered in previous structures, completes the cage that encloses GDPNP and fixes the relative geometry of EF-G domains I, III, and V. In the Fus complex, the position of fusidic acid overlaps that of switch loop I, stabilizing contacts between domains I and III that are normally made by the structured switch loop.

Conclusion:
Our structures capture intermediate states of the rate-limiting step of translocation, in which movement of the tRNA ASL and mRNA is coupled to rotational movement of the 30
S
subunit head. Slippage of the translational reading frame during reverse rotation of the head during translocation may be prevented by intercalation of bases C1397 and A1503 of 16
S
rRNA, which project from the body of the 30
S
subunit, between mRNA bases. The antibiotic fusidic acid appears to stabilize binding of EF-G to the ribosome in the GDP state by mimicking the structure of the conserved core of switch loop I of EF-G in the GTP state.
Terabit-Scale Orbital Angular Momentum Mode Division Multiplexing in Fibers
Authors: Bozinovic Nenad , Yue Yang , Ren Yongxiong , Tur Moshe , Kristensen Poul , Huang Hao , Willner Alan E. , Ramachandran Siddharth
Published: June 2013

A Twist on the Capacity Crunch

The rate at which data can be transmitted down optic fibers is approaching a limit because of nonlinear optical effects. Multiplexing allows data to be encoded in different modes of light such as polarization, wavelength, amplitude, and phase and to be sent down the fibers in parallel. Optical angular momentum (OAM) can provide another degree of freedom whereby the photons are given a well-defined twist or helicity.

Bozinovic
et al.

(p.
1545
) were able to transmit high-bandwidth data using OAM modes in long lengths of optical fibers, thus providing a possible route to get yet more capacity through optic fiber networks.
Fe-S Cluster Biosynthesis Controls Uptake of Aminoglycosides in a ROS-Less Death Pathway
Authors: Ezraty Benjamin , Vergnes Alexandra , Banzhaf Manuel , Duverger Yohann , Huguenot Allison , Brochado Ana Rita , Su Shu-Yi , Espinosa Leon , Loiseau Laurent , Py Béatrice , Typas Athanasios , Barras Frédéric
Published: June 2013

Unreactive Death

A controversial proposal that all bactericidal antibiotics kill by reactive oxygen species (ROS) and not by their primary cell target has recently attracted high-profile refutations. The ROS-death pathway implicated overstimulation of the electron transport in respiratory chains; a malfunction that leads to ROS releasing Fe from Fe-S clusters and causing cell death via Fenton chemistry.

Ezraty
et al.

(p.
1583
) show that electron transport chains and Fe-S clusters are key to killing by aminoglycoside antibiotics but not for the reasons envisioned in the ROS theory. Fe-S clusters are essential for killing because they mature the respiratory chains that produce the necessary proton motive force for the energized uptake of aminoglycosides. Consequently, iron chelators protect against aminoglycosides, not because they scavenge the iron from Fenton chemistry, but because they block aminoglycoside uptake.
Dinitrogen Cleavage and Hydrogenation by a Trinuclear Titanium Polyhydride Complex
Authors: Shima Takanori , Hu Shaowei , Luo Gen , Kang Xiaohui , Luo Yi , Hou Zhaomin
Published: June 2013

Titanium Cleaver

A century after its discovery, the Haber Bosch process is still used to produce ammonia from nitrogen for fertilizer. Nonetheless, the process requires high temperature and pressure, and chemists continue to look for synthetic analogs to microbial nitrogenase enzymes, which have managed to slice through the N2 triple bond under ambient conditions for millennia. Most efforts in this vein have relied on a boost from the reducing power of alkali metals.

Shima
et al.

(p.
1549
; see the Perspective by

Fryzuk

) instead explored the reactivity of a titanium hydride cluster, which cleanly slices through N
2
at room temperature and incorporates the separated N atoms into its framework. Though ammonia was not produced, the system offers hope in the search for mild nitrogen reduction catalysts.
Translocation in Action
Authors: Rodnina Marina V.
Published: June 2013

Structures of translocation intermediates reveal how transfer RNA molecules move through the ribosome during protein synthesis.

[Also see Research Articles by

Tourigny
et al.

,

Zhou
et al.

, and
Pulk and Cate
]
Scientists Bristle at Canadian Leader's Applied Research Push
Authors: Kondro Wayne
Published: June 2013

Prime Minister Stephen Harper has drawn criticism for an autocratic style and cuts to environmental research, but supporters applaud his focus on commercialization.
An Inactivated, Adjuvanted Whole Virion Clade 2.2 H5N1 (A/Chicken/Astana/6/05) Influenza Vaccine Is Safe and Immunogenic in a Single Dose in Humans
Authors: Sansyzbay Abylay R. , Erofeeva Marianna K. , Khairullin Berik M. , Sandybayev Nurlan T. , Kydyrbayev Zhailaubay K. , Mamadaliyev Seidigapbar M. , Kassenov Markhabat M. , Sergeeva Maria V. , Romanova Julia R. , Krivitskaya Vera Z. , Kiselev Oleg I. , Stukova Marina A.
Published: June 2013

In this study, we assessed in humans the immunogenicity and safety of one dose (7.5 or 15 μg of hemagglutinin [HA]) of a whole-virion inactivated prepandemic influenza vaccine adjuvanted with aluminum hydroxide. The vaccine strain was made by reverse genetics from the highly pathogenic avian A/Chicken/Astana/6/05 (H5N1) clade 2.2 strain isolated from a dead bird in Kazakhstan. The humoral immune response was evaluated after a single vaccination by hemagglutination inhibition (HI) and microneutralization (MN) assays. The vaccine was safe and immunogenic, inducing seroconversion in 55% of the evaluated patients, with a geometric mean titer (GMT) of 17.1 and a geometric mean increase (GMI) of 3.42 after a dose of 7.5 μg in the HI test against the vaccine strain. The rate of seroconversion increased up to 70% when the dose of 15 μg was used. The percentages of individuals achieving anti-HA titers of ≥1:40 were 52.5% and 57.5% for the 7.5- and 15-μg dose groups, respectively. Similar results were obtained when antibodies were analyzed in an MN test. Substantial cross-neutralization titers (seroconversion in 35% and 52.5% of subjects in the two dose groups, respectively) were detected against heterologous clade 1 strain NIBRG14 (H5N1). Thus, one dose of this whole-virion prepandemic vaccine adjuvanted with aluminum has the potential to be effective against H5N1 viruses of different clades.
Recombinant Secreted Antigens from Mycoplasma hyopneumoniae Delivered as a Cocktail Vaccine Enhance the Immune Response of Mice
Authors: Galli Vanessa , Simionatto Simone , Marchioro Silvana Beutinger , Klabunde Gustavo Henrique Ferrero , Conceição Fabricio Rochedo , Dellagostin Odir Antônio
Published: June 2013

Mycoplasma hyopneumoniae
is the etiological agent of porcine enzootic pneumonia (EP), which is a respiratory disease responsible for huge economic losses in the pig industry worldwide. The commercially available vaccines provide only partial protection and are expensive. Thus, the development of alternatives for the prophylaxis of EP is critical for improving pig health. The use of multiple antigens in the same immunization may represent a promising alternative. In the present study, seven secreted proteins of
M. hyopneumoniae
were cloned, expressed in
Escherichia coli
, and evaluated for antigenicity using serum from naturally and experimentally infected pigs. In addition, the immunogenicity of the seven recombinant proteins delivered individually or in protein cocktail vaccines was evaluated in mice. In Western blot assays and enzyme-linked immunosorbent assays, most of the recombinant proteins evaluated were recognized by convalescent-phase serum from the animals, indicating that they are expressed during the infectious process. The recombinant proteins were also immunogenic, and most induced a mixed IgG1/IgG2a humoral immune response. The use of these proteins in a cocktail vaccine formulation enhanced the immune response compared to their use as antigens delivered individually, providing evidence of the efficacy of the multiple-antigen administration strategy for the induction of an immune response against
M. hyopneumoniae
.
Immunogenicity Analysis of Staphylococcus aureus Clumping Factor A Genetic Variants
Authors: Brady Rebecca A. , Mocca Christopher P. , Burns Drusilla L.
Published: June 2013

The staphylococcal adhesin clumping factor A (ClfA) has a variant amino acid sequence, generating the potential for alterations in epitope structure and immunogenicity of this vaccine candidate. We demonstrated for two recombinant ClfA
40–531
(a slightly truncated version of the fibrinogen-binding domain of ClfA containing amino acids 40 to 531) genetic variants that strain-specific epitopes are immunodominant. This work indicates that immune responses elicited by ClfA may, at least in part, be dependent on the strain of origin of the ClfA.
Increased Sensitivity in Diagnosis of Tuberculosis in HIV-Positive Patients through the Small-Membrane-Filter Method of Microscopy
Authors: Quincó Patrícia , Bührer-Sékula Samira , Brandão Walber , Monte Rossiclea , Souza Silvia Leopoldina , Saraceni Valeria , Palaci Moises , Dietze Reynaldo , Cordeiro-Santos Marcelo
Published: June 2013

The sensitivity of microscopy for the diagnosis of tuberculosis (TB) is around 50% but decreases by about 15% in patients with suspected TB who are coinfected with HIV. Here, we compared the accuracies of three microscopy methods for processing sputum smears (concentration by centrifugation with or without
N
-acetyl-
l
-cysteine [NALC] and concentration by filtration on a polycarbonate membrane) to that of culture on Ogawa-Kudoh medium as the gold standard method. Sputum samples were obtained from 432 patients with suspected pulmonary TB, of whom 60% were infected with HIV. Analysis was performed using the first specimen. Compared to the gold standard culture, the small-membrane-filter (SMF) method was the most sensitive microscopic method. In HIV-infected TB patients, the sensitivity of the SMF method was significantly higher than those for centrifugation of sputum samples with or without NALC treatment (61.9%, 47.6%, and 45.2%, respectively;
P
= 0.001). Similarly, in TB patients without HIV infection, the sensitivity of the SMF method was significantly higher than those for centrifugation of sputum samples with or without NALC treatment (81.8%, 63.6%, and 57.5%, respectively;
P
= 0.001). In the two study groups, TB patients with or without HIV, no significant differences between the specificities of the three methods were observed. Handling of the second sputum sample similarly by centrifugation with or without NALC and by the SMF method increased positivities by 13%, 11%, and 4%, respectively. The overall agreement between microscopy and culture was above 90% for all groups. Microscopic evaluation of the sputum samples treated with NALC compared to those not treated with NALC did not show any increase in sensitivity. Altogether, the sensitivity of the SMF method is higher than those of the other two microscopic methods studied without a loss of specificity.
Algorithm-Based Prediction of HIV-1 Subtype D Coreceptor Use
Authors: Dina Julia , Raymond Stephanie , Maillard Anne , Le Guillou-Guillemette Helene , Rodalec Audrey , Beby-Defaux Agnes , Giraudeau Genevieve , Vallet Sophie , Mourez Thomas , Payan Christopher , Vabret Astrid , Ruffault Annick , Ferre Virginie , Izopet Jacques , Plantier Jean-Christophe
Published: June 2013

We compared the coreceptor tropism-predicting performance of a specific genotypic algorithm for HIV-1 subtype D and that of the geno2pheno algorithm with different cutoffs. The D-specific algorithm and geno2pheno with a false-positivity rate cutoff of 2.5% had the same concordance with the phenotypic determination. The geno2pheno algorithm with a false-positivity rate cutoff of 2.5%, more sensitive but slightly less specific, seems to be an appropriate alternative.
Evaluation of Cycloserine-Cefoxitin Fructose Agar (CCFA), CCFA with Horse Blood and Taurocholate, and Cycloserine-Cefoxitin Mannitol Broth with Taurocholate and Lysozyme for Recovery of Clostridium difficile Isolates from Fecal Samples
Authors: Tyrrell Kerin L. , Citron Diane M. , Leoncio Eliza S. , Merriam C. Vreni , Goldstein Ellie J. C.
Published: June 2013

Cycloserine-cefoxitin fructose agar (CCFA), CCFA with horse blood and taurocholate (CCFA-HT), and cycloserine-cefoxitin mannitol broth with taurocholate and lysozyme (CCMB-TAL) were compared for recovery ofClostridium difficilefrom 120 stool specimens. Compared to CCFA, CCFA-HT enhancedC. difficilegrowth and improved recovery by 4%. In a separate study, 9% (8/91) of stool samples previouslyC. difficilenegative on plate medium wereC. difficilepositive when cultured in CCMB-TAL.
Epidemiological and Microbiological Characteristics of an Outbreak Caused by OXA-48-Producing Enterobacteriaceae in a Neonatal Intensive Care Unit in Jerusalem, Israel
Authors: Adler Amos , Solter Ester , Masarwa Samira , Miller-Roll Tamar , Abu-Libdeh Bassam , Khammash Hatem , Najem Khalil , Dekadek Susan , Stein-Zamir Chen , Nubani Nafez , Kunbar Amin , Assous Marc Victor , Carmeli Yehuda , Schwaber Mitchell J.
Published: June 2013

This study describes the course of an OXA-48-producing
Enterobacteriaceae
(OPE) outbreak that started in March 2012 in a neonatal intensive care unit (NICU) in Jerusalem, Israel. During the peak of the outbreak (January to August 2012), there were 49 patients who had proven or suspected acquisition of OPE in the NICU, including 16 with invasive infections, out of a total of 156 patients who were hospitalized during that period. Three children hospitalized in the pediatric ICU were identified as carriers of OPE. Three patients with a previous stay in the affected NICU were identified as OPE carriers upon admission to another hospital. The Ministry of Health was notified and then intervened in July 2012. Intervention included cohorting colonized patients, conducting frequent rectal-culture surveillance, and improving the implementation of infection control practices. As a result, the incidence of OPE acquisition declined to 5 cases in the first 4 months, followed by no new cases in the next 3 months. Thirty-one patient-unique isolates were available for analysis: 29
Klebsiella pneumoniae
isolates, all belonging to a single clone (sequence type 39 [ST39]), and 2 isolates from
Enterobacter cloacae
. All isolates possessed the
bla
OXA-48
and
bla
CTX-M-14
genes, which are located on the same plasmid. This plasmid, similar to the global
bla
OXA-48
-harboring vector, has now acquired
bla
CTX-M-14
, leading to resistance to all β-lactam agents.
The Bracovirus Genome of the Parasitoid Wasp
Cotesia congregata
Is Amplified within 13 Replication Units, Including Sequences Not Packaged in the Particles
Authors: Louis Faustine , Bézier Annie , Periquet Georges , Ferras Cristina , Drezen Jean-Michel , Dupuy Catherine
Published: June 2013

The relationship between parasitoid wasps and polydnaviruses constitutes one of the few known mutualisms between viruses and eukaryotes. Viral particles are injected with the wasp eggs into parasitized larvae, and the viral genes thus introduced are used to manipulate lepidopteran host physiology. The genome packaged in the particles is composed of 35 double-stranded DNA (dsDNA) circles produced in wasp ovaries by amplification of viral sequences from proviral segments integrated in tandem arrays in the wasp genome. These segments and their flanking regions within the genome of the wasp
Cotesia congregata
were recently isolated, allowing extensive mapping of amplified sequences. The bracovirus DNAs packaged in the particles were found to be amplified within more than 12 replication units. Strikingly, the nudiviral cluster, the genes of which encode particle structural components, was also amplified, although not encapsidated. Amplification of bracoviral sequences was shown to involve successive head-to-head and tail-to-tail concatemers, which was not expected given the nudiviral origin of bracoviruses.
Coagulation Factor Binding Orientation and Dimerization May Influence Infectivity of Adenovirus-Coagulation Factor Complexes
Authors: Irons Eric E. , Flatt Justin W. , Doronin Konstantin , Fox Tara L. , Acchione Mauro , Stewart Phoebe L. , Shayakhmetov Dmitry M.
Published: June 2013

Adenoviruses (Ads) are promising vectors for therapeutic interventions in humans. When injected into the bloodstream, Ad vectors can bind several vitamin K-dependent blood coagulation factors, which contributes to virus sequestration in the liver by facilitating transduction of hepatocytes. Although both coagulation factors FVII and FX bind the hexon protein of human Ad serotype 5 (HAdv5) with a very high affinity, only FX appears to play a role in mediating Ad-hepatocyte transduction
in vivo
. To understand the discrepancy between efficacy of FVII binding to hexon and its apparently poor capacity for supporting virus cell entry, we analyzed the HAdv5-FVII complex by using high-resolution cryo-electron microscopy (cryo-EM) followed by molecular dynamic flexible fitting (MDFF) simulations. The results indicate that although hexon amino acids T423, E424, and T425, identified earlier as critical for FX binding, are also involved in mediating binding of FVII, the FVII GLA domain sits within the surface-exposed hexon trimer depression in a different orientation from that found for FX. Furthermore, we found that when bound to hexon, two proximal FVII molecules interact via their serine protease (SP) domains and bury potential heparan sulfate proteoglycan (HSPG) receptor binding residues within the dimer interface. In contrast, earlier cryo-EM studies of the Ad-FX interaction showed no evidence of dimer formation. Dimerization of FVII bound to Ad may be a contributing mechanistic factor for the differential infectivity of Ad-FX and Ad-FVII complexes, despite high-affinity binding of both these coagulation factors to the virus.
The Role of Protein Kinase A Regulation of the E6 PDZ-Binding Domain during the Differentiation-Dependent Life Cycle of Human Papillomavirus Type 18
Authors: Delury Craig P. , Marsh Elizabeth K. , James Claire D. , Boon Siaw Shi , Banks Lawrence , Knight Gillian L. , Roberts Sally
Published: June 2013

Human papillomavirus (HPV) E6 proteins of high-risk alpha types target a select group of PSD95/DLG1/ZO1 (PDZ) domain-containing proteins by using a C-terminal PDZ-binding motif (PBM), an interaction that can be negatively regulated by phosphorylation of the E6 PBM by protein kinase A (PKA). Here, we have mutated the canonical PKA recognition motif that partially overlaps with the E6 PBM in the HPV18 genome (E6153PKA) and compared the effect of this mutation on the HPVl8 life cycle in primary keratinocytes with the wild-type genome and with a second mutant genome that lacks the E6 PBM (E6ΔPDZ). Loss of PKA recognition of E6 was associated with increased growth of the genome-containing cells relative to cells carrying the wild-type genome, and upon stratification, a more hyperplastic phenotype, with an increase in the number of S-phase competent cells in the upper suprabasal layers, while the opposite was seen with the E6ΔPDZ genome. Moreover, the growth of wild-type genome-containing cells was sensitive to changes in PKA activity, and these changes were associated with increased phosphorylation of the E6 PBM. In marked contrast to E6ΔPDZ genomes, the E6153PKA mutation exhibited no deleterious effects on viral genome amplification or expression of late proteins. Our data suggest that the E6 PBM function is differentially regulated by phosphorylation in the HPV18 life cycle. We speculate that perturbation of protein kinase signaling pathways could lead to changes in E6 PBM function, which in turn could have a bearing on tumor promotion and progression.
Interferon Regulatory Factor 4 Is Activated through c-Src-Mediated Tyrosine Phosphorylation in Virus-Transformed Cells
Authors: Wang Ling , Ning Shunbin
Published: June 2013

The importance of the oncogenic transcription factor interferon regulatory factor 4 (IRF4) in hematological malignancies has been increasingly recognized. We have previously identified the B cell integration cluster (BIC), the gene encoding miR-155, as the first microRNA (miRNA)-encoding gene transcriptionally targeted by IRF4 in virus-transformed cancer cells. Activation of IRFs is prerequisite for their functions. However, how IRF4 is activated in cancer is an open question. Our phosphoproteome profiling has identified several tyrosine phosphorylation sites on IRF4 in Epstein-Barr virus (EBV)-transformed cells. Further, we show here that c-Src dramatically stimulates IRF4 phosphorylation and activity and that Y61 and Y124 are two key sites responding to c-Src-mediated activation. Consistently, c-Src is constitutively expressed and active in EBV-transformed cells. However, c-Src is unlikely to be a direct kinase for IRF4. Furthermore, we have a polyclonal antibody specific to phospho-IRF4(Y121/124) developed in rabbit. We have further shown that inhibition of c-Src activity reduces p-IRF4(Y121/124) and significantly represses transcription of the IRF4 target BIC in EBV-transformed cells. Our results therefore, for the first time, demonstrate that IRF4 is phosphorylated and activated through a c-Src-mediated pathway in virus-transformed cells. These findings will improve our understanding of IRF4 in neoplasia and will provide profound insights into the interaction of oncogenic viruses with IRF4 in the development of hematological malignancies.
Chronic traumatic encephalopathy in sport: a systematic review
Authors: Gardner Andrew , Iverson Grant L , McCrory Paul
Published: June 2013

Objective

To provide a critical review of chronic traumatic encephalopathy (CTE) by considering the range of clinical presentations, neuropathology and the strength of evidence for CTE as a distinct syndrome.

Data sources

Seven electronic databases were searched using a combination of MeSH terms and key words to identify relevant articles.

Review methods

Specific inclusion and exclusion criteria were used to select studies for review. Data extracted where present included study population, exposure/outcome measures, clinical data, neurological examination findings, cognitive assessment, investigation results and neuropathology results.

Results

The data from 158 published case studies were reviewed. Critical differences between the older descriptions of CTE (the ‘classic’ syndrome) and the recent descriptions (the ‘modern’ syndrome) exist in the age of onset, natural history, clinical features, pathological findings and diagnostic criteria, which suggests that modern CTE is a different syndrome. The methodology of the current studies does not allow determination of aetiology or risk factors.

Conclusions

The clinicopathological differences between the ‘classic’ CTE syndrome and the ‘modern’ syndrome suggest that the new syndrome needs a different nomenclature. Further research is required to clearly define the clinical phenotype of the modern CTE syndrome and establish the underlying aetiology. Future research needs to address these issues through large-scale, prospective clinicopathological studies.