bluuebunny/crossref_metadata_2025 huggingface dataset:
Human platelets pathogen reduced with riboflavin and ultraviolet light do not cause acute lung injury in a two‐event SCID mouse model
Authors: Chi Xuan , Zhi Li , Vostal Jaroslav G.
Published: May 2013

Background

Pathogen reduction technologies (PRTs) can induce platelet (PLT) lesions that reduce PLT survival and recovery from circulation and may be associated with acute lung injury (ALI).

Study Design and Methods

Human PLTs (hPLTs) in plasma with or without single or multiple Mirasol PRT treatments were assessed in vitro by aggregation and percentage of P‐selectin expression. In vivo studies included PLT recovery in SCID mice and assessment of ALI in a two‐event mouse model in which the sensitizing event was lipopolysaccharide injection and the second event was infusion of Mirasol‐treated hPLTs.

Results

A single‐dose Mirasol treatment (5 J/cm2) did not induce any change in aggregation in response to adenosine 5′‐diphosphate (ADP) while a five‐times‐repeat Mirasol treatment (5×) increased aggregation response to low concentration of ADP. Mirasol PLTs (1×‐5×) had increased percentage of P‐selectin–positive PLTs after treatment and decreased aggregation with TRAP as the agonist. In vivo recovery in SCID mice was reduced extensively with Mirasol treatments (1× and 5×). In the two‐event model of ALI, only the 5× Mirasol PLTs accumulated in the lung and this was not accompanied by changes in lung histology or increases in MIP‐2 levels in bronchoalveolar lavage fluid.

Conclusions

Mirasol PRT treatment induced PLT activation and reduced in vivo recovery in a SCID mouse model of transfusion. In our two‐event mouse model of ALI, the 5× Mirasol hPLTs accumulated in the lung, but did not cause signs of ALI. The 1× Mirasol treatment did not lead to PLT lung accumulation or ALI in this model.
Analyses of Extreme Wave Heights in the Gulf of Mexico for Offshore Engineering Applications
Authors: Panchang Vijay , Kwon Jeong Chan , Demirbilek Zeki
Published: May 2013

The 2004–2008 hurricane season in the Gulf of Mexico (GOM) saw several exceedances of what was regarded, prior to that period, as the 100-year significant wave heights (SWHs) that are used for the design of offshore oil and gas facilities. As a result, these facilities sustained considerable damage and disrupted U.S. energy supplies. The wave climatology in the GOM is therefore studied in detail. A 51-year database of SWHs was constructed by using a combination of wind and wave models, and both individual wave heights and statistical measures were validated, to the extent possible, using buoy data. Analyses of the modeled data show that there is an increasing trend in the annual maximum SWHs in the eastern part of the GOM; the maximum trend is approximately 5.6 cm/year, which is of the same magnitude as that reported for the U.S. west coast. The western part; on the other hand, shows a decreasing trend. The maximum estimated 100-year SWHs (denoted by SWH100) are 19.1 m, 22.6 m and 26.7 m for the Gumbel, Weibull, and the GEV distributions, respectively. The estimates obtained here using the Weibull distribution are comparable to those obtained independently by API (API—American Petroleum Institute, 2007, “Interim Guidance on Hurricane Conditions in the Gulf of Mexico,” API Bulletin No. 2INT-MET). However, the use of objective criteria to identify the optimal distribution suggests that the GEV estimates are to be preferred if the engineer wishes to emphasize the upper tail where extremes are likely to occur. The maximum increase in the SWH100 due to the 2004–2008 season is of the order of 0.9 m to 2.7 m (depending as the distribution). Information generated here is intended to supplement the design recommendations provided by API (American Petroleum Institute, 2007, “Interim Guidance on Hurricane Conditions in the Gulf of Mexico,” API Bulletin No. 2INT-MET).
Return Value Estimation of Significant Wave Heights With Maximum Entropy Distribution
Authors: Dong S. , Liu W. , Zhang L. Z. , Guedes Soares C.
Published: May 2013

The maximum entropy distribution is proposed to fit the long term and extreme distribution of significant wave heights from which return value estimates are derived. The maximum entropy distribution is applied to data from two sites of different characteristics, namely from Japan characterized by the occurrence of typhoons and from the North Sea with continuous variation of sea state intensity. The compound distribution, Poisson-maximum entropy distribution, is described and adopted to model the data from these two locations. It is shown that in the case of continuous data from the North Sea, this model does not bring any advantage over the direct application of the maximum entropy distribution to adjust the significant wave heights larger than different thresholds. For this case the maximum entropy distribution provides good fits.
Thermomechanical Characterization of Low Density Foams for the ATLAS Upgrade
Authors: Bonad Isaac , Bates Richard , Batter Craig , MacEwan Fiona , Canfer Simon , Locket Cyrill
Published: May 2013

The increase of the luminosity of the Large Hadron Collider (LHC) by 2020 requires the upgrade of the ATLAS inner tracker experiment. Expected to be used as support structures in the design of the inner tracker, the thermal and mechanical properties of POCOFOAM and ALLLCOMP foam needed to be well understood and dimensionally stable in order to allow efficient cooling and accurate track reconstruction. Thermal conductivities of these foams were measured experimentally together with the Young's modulus, yield, and shear stresses of POCOFOAM at low stress. Thermomechanical measurements of POCOFOAM were also achieved. This paper describes briefly the measurement systems used and reports the results obtained.
Part Load Efficiency Enhancement of an Automotive Engine Via a Direct Methanol Fuel Cell-Internal Combustion Engine Hybrid System
Authors: Suslu Osman Sinan , Becerik Ipek
Published: May 2013

The operation of a direct methanol fuel cell with an internal combustion engine in a hybrid system is investigated in terms of fuel efficiency. The following work shows a potential for fuel saving because the engine's waste heat is utilized in preconditioning of methanol for the fuel cell and in postconditioning of the cell's anode exhaust for the engine. The low activity of methanol oxidation catalysts and methanol crossover are the main drawbacks of direct methanol fuel cells. H3PO4-doped polybenzimidazole membranes have lower methanol crossover, and allow a higher operational temperature and methanol concentration compared to Nafion membranes. The operation of the cell at higher temperature with polybenzimidazole membranes improves catalyst activity and mass transfer increasing cell efficiency. But the fuel feed to this type of membrane must be in vapor phase. Methanol solution can be evaporated by the engine coolant. Unutilized methanol in the anode exhaust is converted to H2 rich product gas in a reactor before feeding into the engine. The endothermic reaction enthalpy for this conversion is recovered from engine's exhaust gas. The system efficiency increases with the cell's fuel utilization, as long as the cell's efficiency is higher than the engine's efficiency. In order to increase the system efficiency with load, the current density of the fuel cell should not be increased beyond the point where the cell and engine efficiency meet. Beyond that, the product gas should be substituted with liquid methanol to meet the rest of the load because the engine charge's energy density can be increased with liquid methanol injection into the engine. If the engine charge is comprised of fuel cell exhaust only and the engine's indicated efficiency is 20%, the efficiency of the hybrid system will be 25.5% at a cell voltage of 0.4 V and a cell fuel utilization of 40%. This corresponds to a fuel saving of 28% compared to the internal combustion engine. The hybrid system efficiency will increase to 28.5% at this operating point, if the fuel cell's anode exhaust is further decomposed in a reactor prior to combustion in the engine. The addition of the reactor to the hybrid system corresponds to a fuel saving of 43% compared to the engine and a fuel saving of 12% compared to the hybrid system without the reactor.
Effect of the Ratio Spread of CVU in Automotive Kinetic Energy Recovery Systems
Authors: Bottiglione F. , Mantriota G.
Published: May 2013

The Kinetic Energy Recovery Systems (KERS) are being considered as promising short-range solution to improve the fuel economy of road vehicles. The key element of a mechanical hybrid is a Continuously Variable Unit (CVU), which is used to drive the power from the flywheel to the wheels and vice versa by varying the speed ratio. The performance of the KERS is very much affected by the efficiency of the CVU in both direct and reverse operation, and the ratio spread. However, in real Continuously Variable Transmissions (CVT), the ratio spread is limited (typical value is 6) to keep acceptable efficiency and to minimize wear. Extended range shunted CVT (Power Split CVT or PS-CVT), made of one CVT, one fixed-ratio drive and one planetary gear drive, permit the designer to arrange a CVU with a larger ratio spread than the CVT or to improve its basic efficiency. For these reasons, in the literature they are sometimes addressed as devices for proficient application to KERS. In this paper, two performance indexes have been defined to quantify the effect of the ratio spread of PS-CVT on the energy recovery capabilities and overall round-trip efficiency of KERS. It is found that no substantial benefit is achieved with the use of PS-CVT instead of direct drive CVT, because the extension of the speed ratio range is paid with a loss of efficiency. It is finally discussed if new generation high-efficiency CVTs can change the scenario.
Experimental Analysis of the Start-Up Torque of a Mildly Loaded Foil Thrust Bearing1
Authors: Balducchi Franck , Arghir Mihaï , Gauthier Romain , Renard Emelyne
Published: May 2013

The paper deals with the experimental analysis of the torque and of the lift-off velocity of a foil thrust bearing. The geometric characteristics of the foil thrust bearing follow the design recently proposed by Dykas et al. (2009, “Design, Fabrication, and Performance of Foil Gas Thrust Bearings for Microturbomachinery Applications,” ASME J. Eng. Gas Turbines Power, 131(1), p. 012301-1). A dedicated test rig was developed and enables the measurement of the speed, the torque, and temperatures under the foils. The measurements underlined the importance of managing heat transfer in a foil thrust bearing. Results are presented for mild static loads ranging from 5 to 60 N and rotation speeds comprised between 20 and 35 krpm. The value of the start-up torque was validated by comparisons with results obtained with a rapid camera.
Efficient Simulation of Gear Contacts Including Transient Elastohydrodynamic Effects
Authors: Fietkau Peter , Bertsche Bernd
Published: May 2013

This paper describes an efficient transient elastohydrodynamic simulation method for gear contacts. The model uses oil films and elastic deformations directly in the multibody simulation, and is based on the Reynolds equation including squeeze and wedge terms as well as an elastic half-space. Two transient solutions to this problem, an analytical and a numerical one, were developed. The analytical solution is accomplished using assumptions for the gap shape and the pressure in the middle of the gap. The numerical problem is solved using multilevel multi-integration algorithms. With this approach, tooth impacts during gear rattling as well as highly loaded power-transmitting gear contacts can be investigated and lubrication conditions like gap heights or type of friction may be determined. The method was implemented in the multibody simulation environment SIMPACK. Therefore it is easy to transfer the developed element to other models and use it for a multitude of different engineering problems. A detailed three-dimensional elastic multibody model of an experimental transmission is used to validate the developed method. Important values of the gear contact like normal and tangential forces, proportion of dry friction, and minimum gap heights are calculated and studied for different conditions. In addition, pressure distributions on tooth flanks as well as gap forms are determined based on the numerical solution method. Finally, the simulation approach is validated with measurements and shows good consistency. The simulation model is therefore capable of predicting transient gear contact under different operating conditions such as load vibrations or gear rattling. Simulations of complete transmissions are possible and therefore a direct determination of transmission vibration behavior and structure-borne noise as well as of forces and lubrication conditions can be done.
Identifying a temporal threshold of tolerance for silent gaps after requests
Authors: Roberts Felicia , Francis Alexander L.
Published: May 2013

This study addresses whether there is a threshold, some particular length of silent gap between two speakers' turns, at which negative social attributions emerge. The effect of such inter-turn silence was tested by constructing dialogues where responses to requests were identical and affirmative so that study participants' (n = 380) ratings about “willingness” would be colored by lag time, not semantics. 100 ms intervals between 200 and 1200 ms were tested in a between groups design. There was a notable drop-off in ratings at 600 ms and a statistically significant difference in ratings between 700 and 800 ms.
Enhanced Role of Transition Metal Ion Catalysis During In-Cloud Oxidation of SO
2
Authors: Harris Eliza , Sinha Bärbel , van Pinxteren Dominik , Tilgner Andreas , Fomba Khanneh Wadinga , Schneider Johannes , Roth Anja , Gnauk Thomas , Fahlbusch Benjamin , Mertes Stephan , Lee Taehyoung , Collett Jeffrey , Foley Stephen , Borrmann Stephan , Hoppe Peter , Herrmann Hartmut
Published: May 2013

Dust in the Clouds

Sulfate aerosols have the greatest radiative impact on climate systems.

Harris
et al.

(p.
727
) report that the oxidation of sulfur dioxide gas, catalyzed by natural transition metal ions mostly on the surface of coarse mineral dust, is the dominant pathway for sulfate production in clouds. In view of the growing sulfur dioxide emissions from large, industrializing countries, including this process in climate models should improve the agreement between models and observations.
Cellular Self-Defense: How Cell-Autonomous Immunity Protects Against Pathogens
Authors: Randow Felix , MacMicking John D. , James Leo C.
Published: May 2013

Defense and Counter-Defense

Provided a pathogen can enter the body and survive coughing and spluttering, peristalsis, and mucus, the first active responses the host evokes to an invading organism will be at the level of the first cell encountered, well before classical cellular immunity and antibody responses are initiated.

Randow
et al.

(p.
701
) review the range of intracellular defenses against incoming pathogens and describe how compartmental boundaries within the cell provide multiple levels at which pathogens can be thwarted in their attempts to subjugate the cell to do their bidding.

Baxt
et al.

(p.
697
) review the range of evasion tactics that bacterial pathogens can summon to counter host repulsion and establish a niche in which to replicate and ensure onward transmission.
Comment on “Evidence of Abundant Purifying Selection in Humans for Recently Acquired Regulatory Functions”
Authors: Green Phil , Ewing Brent
Published: May 2013

Ward and Kellis (Reports, 28 September 2012, p. 1675; published online 5 September 2012) found altered patterns of human polymorphism in biochemically active but non–mammalian-conserved genomic regions relative to control regions and interpreted this as due to lineage-specific purifying selection. We find on closer inspection of their data that the polymorphism trends are primarily attributable to mutational variation and technical artifacts rather than selection.
Networks of bZIP Protein-Protein Interactions Diversified Over a Billion Years of Evolution
Authors: Reinke Aaron W. , Baek Jiyeon , Ashenberg Orr , Keating Amy E.
Published: May 2013

bZIPping Through Evolution

The basic region-leucine zipper (bZIP) transcription factors are found in many species and can form complexes that bind to DNA and affect transcription.

Reinke
et al.

(p.
730
) analyzed interactions for over 3000 bZIPs within and among five metazoan and two unicellular species. The results reveal differences within bZIP interactive networks that have accumulated over time and identify plasticity among interactions and changes in binding specificity that relate to specific amino acid residue changes.
Compartmentalization of GABAergic Inhibition by Dendritic Spines
Authors: Chiu Chiayu Q. , Lur Gyorgy , Morse Thomas M. , Carnevale Nicholas T. , Ellis-Davies Graham C. R. , Higley Michael J.
Published: May 2013

Dendritic Precision Strikes

The effects of excitatory synaptic inputs are considered to be highly compartmentalized because of the biophysical properties of dendritic spines. Individual inhibitory synapses, however, are thought to affect dendritic integration in a more extended spatial region. Combining optogenetic stimulation of dendrite-targeting γ-aminobutyric acid—mediated interneurons with two-photon calcium imaging in postsynaptic pyramidal cell dendrites,

Chiu
et al.

(p.
759
) challenge this latter view. The findings suggest that the effect of an inhibitory synapse can be as compartmentalized as that of an excitatory synapse, provided that the synapses are localized on spine heads.
Feathers Before Flight
Authors: Clarke Julia
Published: May 2013

Fossil data indicate that feathers and their precursors may have evolved over a much longer span than previously thought.
Why Adults Need New Brain Cells
Authors: Bergmann Olaf , Frisén Jonas
Published: May 2013

Neurogenesis and gliogenesis shape connectivity in the adult brain, influencing plasticity and repair.

[Also see Report by

Freund
et al.

]
A Fresh Start for Foam Physics
Authors: Weaire Denis
Published: May 2013

A numerical simulation moves beyond explaining the static structure of foams and describes their temporal evolution.

[Also see Report by
Saye and Sethian
]
Simple Genetics for a Complex Disease
Authors: Cohen Jonathan C. , Hobbs Helen H.
Published: May 2013

Low-frequency alleles with large phenotypic effects may guide the development of therapeutics and treatments.
The NIH BRAIN Initiative
Authors: Insel Thomas R. , Landis Story C. , Collins Francis S.
Published: May 2013

The NIH BRAIN Initiative will build on recent successes in neuroscience to create and apply new tools for understanding brain activity.
Amid Heightened Concerns, New Name for Novel Coronavirus Emerges
Authors: Enserink Martin
Published: May 2013

Pathogen to be christened Middle East respiratory syndrome coronavirus, or MERS-CoV.
Lack of Serum Antibodies against Borrelia burgdorferi in Children with Autism
Authors: Burbelo Peter D. , Swedo Susan E. , Thurm Audrey , Bayat Ahmad , Levin Andrew E. , Marques Adriana , Iadarola Michael J.
Published: May 2013

It has been proposed thatBorrelia burgdorferiinfection is present in ∼25% of children with autism spectrum disorders. In this study, antibodies againstBorrelia burgdorferiwere assessed in autistic (n= 104), developmentally delayed (n= 24), and healthy control (n= 55) children. No seropositivity againstBorrelia burgdorferiwas detected in the children with and without autism. There was no evidence of an association between Lyme disease and autism.
Clinical Bovine Piroplasmosis Caused by Babesia occultans in Italy
Authors: Decaro Nicola , Larocca Vittorio , Parisi Antonio , Losurdo Michele , Lia Riccardo Paolo , Greco Maria Fiorella , Miccolis Antonio , Ventrella Gianpiero , Otranto Domenico , Buonavoglia Canio
Published: May 2013

A clinical outbreak of bovine piroplasmosis was reported in Italy. The etiological agent was characterized as
Babesia occultans
, a parasite regarded as apathogenic and never detected before in continental Europe. This report paves the way for further studies to assess the occurrence of this tick-transmitted protozoan in other European regions.
Use of Colorimetric Culture Methods for Detection of Mycobacterium tuberculosis Complex Isolates from Sputum Samples in Resource-Limited Settings
Authors: Boum Yap , Orikiriza Patrick , Rojas-Ponce Gabriel , Riera-Montes Margarita , Atwine Daniel , Nansumba Margaret , Bazira Joel , Tuyakira Eleanor , De Beaudrap Pierre , Bonnet Maryline , Page Anne-Laure
Published: May 2013

Despite recent advances, tuberculosis (TB) diagnosis remains imperfect in resource-limited settings due to its complexity and costs, poor sensitivity of available tests, or long times to reporting. We present a report on the use of colorimetric methods, based on the detection of mycobacterial growth using colorimetric indicators, for the detection of
Mycobacterium tuberculosis
in sputum specimens. We evaluated the nitrate reductase assay (NRA), a modified NRA using
para
-nitrobenzoic acid (PNB) (NRAp), and the resazurin tube assay using PNB (RETAp) to differentiate tuberculous and nontuberculous mycobacteria. The performances were assessed at days 18 and 28 using mycobacterium growth indicator tube (MGIT) and Löwenstein-Jensen (LJ) medium culture methods as the reference standards. We enrolled 690 adults with suspected pulmonary tuberculosis from a regional referral hospital in Uganda between March 2010 and June 2011. At day 18, the sensitivities and specificities were 84.6% and 90.0% for the NRA, 84.1% and 92.6% for the NRAp, and 71.2% and 99.3% for the RETAp, respectively. At day 28, the sensitivity of the RETAp increased to 82.6%. Among smear-negative patients with suspected TB, sensitivities at day 28 were 64.7% for the NRA, 61.3% for the NRAp, and 50% for the RETAp. Contamination rates were found to be 5.4% for the NRA and 6.7% for the RETAp, compared with 22.1% for LJ medium culture and 20.4% for MGIT culture. The median times to positivity were 10, 7, and 25 days for colorimetric methods, MGIT culture, and LJ medium culture,respectively. Whereas the low specificity of the NRA/NRAp precludes it from being used for TB diagnosis, the RETAp might provide an alternative to LJ medium culture to decrease the time to culture results in resource-poor settings.
Virus Detection and Semiquantitation in Explanted Heart Tissues of Idiopathic Dilated Cardiomyopathy Adult Patients by Use of PCR Coupled with Mass Spectrometry Analysis
Authors: Nguyen Yohan , Renois Fanny , Leveque Nicolas , Giusti Delphine , Picard-Maureau Marcus , Bruneval Patrick , Fornes Paul , Andreoletti Laurent
Published: May 2013

Viral detection in heart tissues has become a central issue for the diagnosis and exploration of the pathogenesis of idiopathic dilated cardiomyopathy (IDCM). In the present study, common cardiotropic viruses in 67 explanted heart samples of 31 IDCM adult patients were detected and semiquantified by using for the first time a new technology based on PCR assay coupled to electrospray ionization-time of flight mass spectrometry analysis (PCR-MS), with comparison to reference quantitative real-time PCR (RT-qPCR) assay. PCR-MS identified single or mixed enterovirus (EV) and parvovirus B19 (PVB19) infections in 27 (40.2%) of 67 samples, corresponding to 15 (48.3%) of the 31 patients, whereas RT-qPCR identified viral infections in 26 (38.8%) samples, corresponding to 16 (51.6%) of the patients. The PCR-MS results correlated well with EV and PVB19 detection by RT-qPCR (kappa = 0.85 [95% confidence interval {CI}, 0.72 to 1.00] and kappa = 0.82 [95% CI, 0.66 to 0.99], respectively). The levels of EV RNA (median, 550 [range, 178 to 3,200] copies/μg of total extracted nucleic acids) and of PVB19 DNA (median, 486 [range, 80 to 1,157] copies/μg of total extracted nucleic acids) were measured using PCR-MS and correlated with those obtained by RT-qPCR (
r
2
= 0.57,
P
= 0.002 and
r
2
= 0.64,
P
< 0.001 for EV and PVB19, respectively). No viruses other than EV and PVB19 strains were detected using the new PCR-MS technology, which is capable of simultaneously identifying 84 known human viruses in one assay. In conclusion, we identified single or mixed EV and PVB19 cardiac infections as potential causes of IDCM. The PCR-MS analysis appeared to be a valuable tool to rapidly detect and semiquantify common viruses in cardiac tissues and may be of major interest to better understand the role of viruses in unexplained cardiomyopathies.
Helicobacter cinaedi and Helicobacter fennelliae Transmission in a Hospital from 2008 to 2012
Authors: Rimbara Emiko , Mori Shigetarou , Kim Hyun , Matsui Mari , Suzuki Satowa , Takahashi Shunji , Yamamoto Satoshi , Mukai Masaya , Shibayama Keigo
Published: May 2013

Forty-six
Helicobacter cinaedi
isolates from the same hospital were analyzed by multilocus sequence typing. Most
H. cinaedi
isolates exhibited clonal complex 9 and were mainly isolated from immunocompromised patients in the same ward. Three
Helicobacter fennelliae
isolates were obtained from the same ward and exhibited the same pulsed-field gel electrophoresis patterns. All isolates were resistant to clarithromycin and ciprofloxacin.
H. cinaedi
and
H. fennelliae
must be carefully monitored to prevent nosocomial infection.
Protection by Immunoglobulin Dual-Affinity Retargeting Antibodies against Dengue Virus
Authors: Brien James D. , Sukupolvi-Petty Soila , Williams Katherine L. , Lam Chia-Ying Kao , Schmid Michael A. , Johnson Syd , Harris Eva , Diamond Michael S.
Published: May 2013

Dengue viruses are the most common arthropod-transmitted viral infection, with an estimated 390 million human infections annually and ∼3.6 billion people at risk. Currently, there are no approved vaccines or therapeutics available to control the global dengue virus disease burden. In this study, we demonstrate the binding, neutralizing activity, and therapeutic capacity of a novel bispecific
d
ual-
a
ffinity
r
e
t
argeting molecule (DART) that limits infection of all four serotypes of dengue virus.
The Resistance Protein Tm-1 Inhibits Formation of a Tomato Mosaic Virus Replication Protein-Host Membrane Protein Complex
Authors: Ishibashi Kazuhiro , Ishikawa Masayuki
Published: May 2013

The
Tm-1
gene of tomato confers resistance to
Tomato mosaic virus
(ToMV).
Tm-1
encodes a protein that binds ToMV replication proteins and inhibits the RNA-dependent RNA replication of ToMV. The replication proteins of resistance-breaking mutants of ToMV do not bind Tm-1, indicating that the binding is important for inhibition. In this study, we analyzed how Tm-1 inhibits ToMV RNA replication in a cell-free system using evacuolated tobacco protoplast extracts. In this system, ToMV RNA replication is catalyzed by replication proteins bound to membranes, and the RNA polymerase activity is unaffected by treatment with 0.5 M NaCl-containing buffer and remains associated with membranes. We show that in the presence of Tm-1, negative-strand RNA synthesis is inhibited; the replication proteins associate with membranes with binding that is sensitive to 0.5 M NaCl; the viral genomic RNA used as a translation template is not protected from nuclease digestion; and host membrane proteins TOM1, TOM2A, and ARL8 are not copurified with the membrane-bound 130K replication protein. Deletion of the polymerase read-through domain or of the 3′ untranslated region (UTR) of the genome did not prevent the formation of complexes between the 130K protein and the host membrane proteins, the 0.5 M NaCl-resistant binding of the replication proteins to membranes, and the protection of the genomic RNA from nucleases. These results indicate that Tm-1 binds ToMV replication proteins to inhibit key events in replication complex formation on membranes that precede negative-strand RNA synthesis.
Polarized Cell Migration during Cell-to-Cell Transmission of Herpes Simplex Virus in Human Skin Keratinocytes
Authors: Abaitua Fernando , Zia F. Rabiya , Hollinshead Michael , O'Hare Peter
Published: May 2013

In addition to transmission involving extracellular free particles, a generally accepted model of virus propagation is one wherein virus replicates in one cell, producing infectious particles that transmit to the next cell via cell junctions or induced polarized contacts. This mechanism of spread is especially important in the presence of neutralizing antibody, and the concept underpins analysis of virus spread, plaque size, viral and host functions, and general mechanisms of virus propagation. Here, we demonstrate a novel process involved in cell-to-cell transmission of herpes simplex virus (HSV) in human skin cells that has not previously been appreciated. Using time-lapse microscopy of fluorescent viruses, we show that HSV infection induces the polarized migration of skin cells into the site of infection. In the presence of neutralizing antibody, uninfected skin cells migrate to the initial site of infection and spread over infected cells to become infected in a spatially confined cluster containing hundreds of cells. The cells in this cluster do not undergo cytocidal cell lysis but harbor abundant enveloped particles within cells and cell-free virus within interstitial regions below the cluster surface. Cells at the base and outside the cluster were generally negative for virus immediate-early expression. We further show, using spatially separated monolayer assays, that at least one component of this induced migration is the paracrine stimulation of a cytotactic response from infected cells to uninfected cells. The existence of this process changes our concept of virus transmission and the potential functions, virus, and host factors involved.
Infectious Virion Capture by HIV-1 gp120-Specific IgG from RV144 Vaccinees
Authors: Liu Pinghuang , Yates Nicole L. , Shen Xiaoying , Bonsignori Mattia , Moody M. Anthony , Liao Hua-Xin , Fong Youyi , Alam S. Munir , Overman R. Glenn , Denny Thomas , Ferrari Guido , Ochsenbauer Christina , Kappes John C. , Polonis Victoria R. , Pitisuttithum Punnee , Kaewkungwal Jaranit , Nitayaphan Sorachai , Rerks-Ngarm Supachai , Montefiori David C. , Gilbert Peter , Michael Nelson L. , Kim Jerome H. , Haynes Barton F. , Tomaras Georgia D.
Published: May 2013

The detailed examination of the antibody repertoire from RV144 provides a unique template for understanding potentially protective antibody functions. Some potential immune correlates of protection were untested in the correlates analyses due to inherent assay limitations, as well as the need to keep the correlates analysis focused on a limited number of endpoints to achieve statistical power. In an RV144 pilot study, we determined that RV144 vaccination elicited antibodies that could bind infectious virions (including the vaccine strains HIV-1 CM244 and HIV-1 MN and an HIV-1 strain expressing transmitted/founder Env, B.WITO.c). Among vaccinees with the highest IgG binding antibody profile, the majority (78%) captured the infectious vaccine strain virus (CM244), while a smaller proportion of vaccinees (26%) captured HIV-1 transmitted/founder Env virus. We demonstrated that vaccine-elicited HIV-1 gp120 antibodies of multiple specificities (V3, V2, conformational C1, and gp120 conformational) mediated capture of infectious virions. Although capture of infectious HIV-1 correlated with other humoral immune responses, the extent of variation between these humoral responses and virion capture indicates that virion capture antibodies occupy unique immunological space.
Assessment of the Protective Effect of Imvamune and Acam2000 Vaccines against Aerosolized Monkeypox Virus in Cynomolgus Macaques
Authors: Hatch Graham J. , Graham Victoria A. , Bewley Kevin R. , Tree Julia A. , Dennis Mike , Taylor Irene , Funnell Simon G. P. , Bate Simon R. , Steeds Kimberley , Tipton Thomas , Bean Thomas , Hudson Laura , Atkinson Deborah J. , McLuckie Gemma , Charlwood Melanie , Roberts Allen D. G. , Vipond Julia
Published: May 2013

To support the licensure of a new and safer vaccine to protect people against smallpox, a monkeypox model of infection in cynomolgus macaques, which simulates smallpox in humans, was used to evaluate two vaccines, Acam2000 and Imvamune, for protection against disease. Animals vaccinated with a single immunization of Imvamune were not protected completely from severe and/or lethal infection, whereas those receiving either a prime and boost of Imvamune or a single immunization with Acam2000 were protected completely. Additional parameters, including clinical observations, radiographs, viral load in blood, throat swabs, and selected tissues, vaccinia virus-specific antibody responses, immunophenotyping, extracellular cytokine levels, and histopathology were assessed. There was no significant difference (
P
> 0.05) between the levels of neutralizing antibody in animals vaccinated with a single immunization of Acam2000 (132 U/ml) and the prime-boost Imvamune regime (69 U/ml) prior to challenge with monkeypox virus. After challenge, there was evidence of viral excretion from the throats of 2 of 6 animals in the prime-boost Imvamune group, whereas there was no confirmation of excreted live virus in the Acam2000 group. This evaluation of different human smallpox vaccines in cynomolgus macaques helps to provide information about optimal vaccine strategies in the absence of human challenge studies.
DNA Topoisomerase 1 Facilitates the Transcription and Replication of the Ebola Virus Genome
Authors: Takahashi Kei , Halfmann Peter , Oyama Masaaki , Kozuka-Hata Hiroko , Noda Takeshi , Kawaoka Yoshihiro
Published: May 2013

Ebola virus (EBOV) protein L (EBOL) acts as a viral RNA-dependent RNA polymerase. To better understand the mechanisms underlying the transcription and replication of the EBOV genome, we sought to identify cellular factors involved in these processes via their coimmunoprecipitation with EBOL and by mass spectrometry. Of 65 candidate proteins identified, we focused on DNA topoisomerase 1 (TOP1), which localizes to the nucleus and unwinds helical DNA. We found that in the presence of EBOL, TOP1 colocalizes and interacts with EBOL in the cytoplasm, where transcription and replication of the EBOV genome occur. Knockdown of TOP1 markedly reduced virus replication and viral polymerase activity. We also found that the phosphodiester bridge-cleaving and recombination activities of TOP1 are required for the polymerase activity of EBOL. These results demonstrate that TOP1 is an important cellular factor for the transcription and replication of the EBOV genome and, as such, plays a key role in the EBOV life cycle.
Nocardia cyriacigeorgicaintracavitary lung colonization: first report of an actinomycetic rather than fungal ball in bronchiectasis
Authors: Severo Cecília Bittencourt , Oliveira Flávio de Mattos , Hochhegger Bruno , Severo Luiz Carlos
Published: May 2013

We report the first case of an isolated endobronchial mass caused byNocardia cyriacigeorgicain an immunocompetent patient with a history of lung surgery; this is a rare presentation of an emerging opportunistic pathogen. The infection was successfully eradicated by surgery. Microbiologists and clinicians should pay more attention to this group of filamentous bacteria, which in the past have often been neglected by medical personnel.
Malignant neuroendocrine tumour of the gallbladder with elevated carcinoembryonic antigen: case report and literature review
Authors: Furrukh Muhammad , Qureshi Asim , Saparamadu Anna , Kumar Shiyam
Published: May 2013

A 58-year-old woman presented to a tertiary care centre with signs and symptoms of acute cholecystitis, cholelithiasis and diagnoses of a high-grade neuroendocrine tumour of the gallbladder primarily with peritoneal and liver metastases. She had a liver abscess secondary toSalmonellaandEnterococcus fecalisthat was drained and treated with appropriate antibiotics. Interestingly, the serum chromogranin A levels were within normal limits, but carcinoembryonic antigen was elevated, which helped evaluate responses and pick progression. She was treated with 10 cycles of palliative chemotherapy when malignancy associated complications started to recur, that is, cholangitis, worsening pain, cachexia, intestinal obstruction, etc leading to chemotherapy delays. Her disease progressed during these times with rapid deterioration of performance status. She died of septic complications postlaparotomy for intestinal obstruction. Her progression-free survival remained for 8 months with subjective and objective improvements, and her overall survival remained at 13 months. We describe the course of her illness and give a brief review of the literature.
Nodular secondary syphilis in a woman
Authors: Glatz M , Achermann Y , Kerl K , Bosshard P P , Cozzio A
Published: May 2013

We report the case of a 21-year-old woman with symmetrically distributed, ulcerated nodules and plaques on the face, neck and arms. Initial differential diagnoses included pyoderma or sarcoidosis based on the clinical presentation and histopathology with non-caseating granulomas. After inefficient treatment with topical and systemic fusidic acid and steroids, we diagnosed nodular secondary syphilis owing to positive serology and immunohistochemical staining ofTreponema pallidumin lesional skin. After treatment with benzathine penicillin, skin lesions improved and antibody titres declined significantly within 3 months. Nodular skin lesions in secondary syphilis are rare with 15 reported cases within the last 20 years. Furthermore, the granulomatous histology is often misleading. Our patient's case suggests that the physicians should be aware of syphilis as a possible differential diagnosis also in patients outside a high-risk population for sexually transmitted diseases and with an unusual clinical presentation.
Mucopolysaccharidosis type IIIB (MPS IIIB) masquerading as a behavioural disorder
Authors: Brady Jacqueline , Trehan Aditi , Landis Dennis , Toro Camilo
Published: May 2013

Inborn errors of metabolism (IEMs) that manifest primarily as psychiatric and behavioural symptoms in childhood are often mistaken for idiopathic primary psychiatric disorders. The pathophysiological basis of these symptoms may be overlooked until later in the disease course when neurological deficits become dominant; this results in a significant delay in establishing a proper diagnosis. To illustrate this, we describe two siblings who presented with behavioural issues and mild learning disabilities in childhood, and were consequently given multiple psychiatric diagnoses. In early adulthood, however, they manifested a rapid cognitive decline. Subsequent cranial MRI imaging revealed progressive brain iron accumulation in deep brain nuclei. Whole exome sequencing and biochemical investigation confirmed the diagnosis of mucopolysaccharidosis type IIIB. Their long diagnostic odyssey illustrates the importance of considering IEMs when assessing individuals with behavioural abnormalities and cognitive impairment.
Randomised controlled trial of an education and support package for stroke patients and their carers
Authors: Eames Sally , Hoffmann Tammy , Worrall Linda , Read Stephen , Wong Andrew
Published: May 2013

Objective

Tailoring stroke information and providing reinforcement opportunities are two strategies proposed to enhance the effectiveness of education. This study aimed to evaluate the effects of an education package which utilised both strategies on the knowledge, health and psychosocial outcomes of stroke patients and carers.

Design

Multisite, randomised trial comparing usual care with an education and support package.

Setting

Two acute stroke units.

Participants

Patients and their carers (N=138) were randomised (control n=67, intervention n=71) of which data for 119 participants (control n=59, intervention n=60) were analysed.

Intervention

The package consisted of a computer-generated, tailored written information booklet and verbal reinforcement provided prior to, and for 3 months following, discharge.

Outcome measures

Outcome measures were administered prior to hospital discharge and at 3-month follow-up by blinded assessors. The primary outcome was stroke knowledge (score range: 0–25). Secondary outcomes were: self-efficacy (1–10), anxiety and depression (0–21), ratings of importance of information (1–10), feelings of being informed (1–10), satisfaction with information (1–10), caregiver burden (carers) (0–13) and quality of life (patients) (1–5).

Results

Intervention group participants reported better: self-efficacy for accessing stroke information (adjusted mean difference (MD) of 1.0, 95% CI 0.3 to 1.7, p=0.004); feeling informed (MD 0.9, 95% CI 0.2 to 1.6, p=0.008); and satisfaction with medical (MD 2.0, 95% CI 1.1 to 2.8, p<0.001); practical (MD 1.1, 95% CI 0.3 to 1.9, p=0.008), services and benefits (MD 0.9, 95% CI 0.1 to 1.8, p=0.036) and secondary prevention information (MD 1.7, 95% CI 0.9 to 2.5, p<0.001). There was no significant effect on other outcomes.

Conclusions

Intervention group participants had improved self-efficacy for accessing stroke information and satisfaction with information, but other outcomes were not significantly affected. Evaluation of a more intensive intervention in a trial with a larger sample size is required to establish the value of an educational intervention that uses tailoring and reinforcement strategies.

ACTRN12608000469314
An observational study of nurse staffing ratios and hospital readmission among children admitted for common conditions
Authors: Tubbs-Cooley Heather L , Cimiotti Jeannie P , Silber Jeffrey H , Sloane Douglas M , Aiken Linda H
Published: May 2013

Background

Hospital patient-to-nurse staffing ratios are associated with quality outcomes in adult patient populations but little is known about how these factors affect paediatric care. We examined the relationship between staffing ratios and all-cause readmission (within 14 days, 15–30 days) among children admitted for common medical and surgical conditions.

Methods

We conducted an observational cross-sectional study of readmissions of children in 225 hospitals by linking nurse surveys, inpatient discharge data and information from the American Hospital Association Annual Survey. Registered Nurses (N=14 194) providing direct patient care in study hospitals (N=225) and children hospitalised for common conditions (N=90 459) were included.

Results

Each one patient increase in a hospital's average paediatric staffing ratio increased a medical child's odds of readmission within 15–30 days by a factor of 1.11, or by 11% (95% CI 1.02 to 1.20) and a surgical child's likelihood of readmission within 15–30 days by a factor of 1.48, or by 48% (95% CI 1.27 to 1.73). Children treated in hospitals with paediatric staffing ratios of 1 : 4 or less were significantly less likely to be readmitted within 15–30 days. There were no significant effects of nurse staffing ratios on readmissions within 14 days.

Discussion

Children with common conditions treated in hospitals in which nurses care for fewer patients each are significantly less likely to experience readmission between 15 and 30 days after discharge. Lower patient-to-nurse ratios hold promise for preventing unnecessary hospital readmissions for children through more effective predischarge monitoring of patient conditions, improved discharge preparation and enhanced quality improvement success.
Oral supplementation with the rutin improves cardiovagal baroreflex sensitivity and vascular reactivity in hypertensive rats
Authors: Mendes-Junior Leônidas das Graças , Monteiro Matheus Morais de Oliveira , Carvalho Alynne dos Santos , Queiroz Thyago Moreira de , Braga Valdir de Andrade
Published: May 2013

The hypothesis that oral supplementation with the flavonoid rutin improves baroreflex sensitivity and vascular reactivity in hypertensive (2-kidney-1-clip (2K1C)) rats was tested. Sixty-four rats were divided in 4 groups: sham + saline; sham + rutin; 2K1C + saline, and 2K1C + rutin. Six weeks after 2K1C surgery, the animals were treated with saline or rutin (40 mg·kg−1·day−1) by gavage for 7 days. Baroreflex sensitivity test using phenylephrine (8 μg·kg−1, iv) and sodium nitroprusside (25 μg·kg−1, iv), vascular reactivity, and thiobarbituric acid reactive substances assay were performed. Baroreflex sensitivity in hypertensive rats was impaired and compared with sham (−2.77 ± 0.15 vs. –1.53 ± 0.27 beats·min−1·mm Hg−1; n = 8; p < 0.05). Oral supplementation with rutin restored baroreflex sensitivity in 2K1C rats (−2.40 ± 0.24 vs. –2.77 ± 0.15 beats·min−1·mm Hg−1; n = 8; p > 0.05). Besides, hypertensive rats have greater contraction to phenylephrine (129.49% ± 4.46% vs. 99.50% ± 11.36%; n = 8; p < 0.05), which was restored by rutin (99.10% ± 1.77% vs. 99.50% ± 11.36%; n = 8; p > 0.05). Furthermore, vasorelaxation to acetylcholine was diminished in hypertensive rats (96.42% ± 2.80% vs. 119.35% ± 5.60%; n = 8; p < 0.05), which was also restored by rutin (117.55% ± 6.94% vs. 119.35% ± 5.60%; n = 8; p > 0.05). Finally, oxidative stress was greater in hypertensive rats (1.54 ± 0.12 vs. 0.53 ± 0.12 nmol MDA·mL−1; n = 8; p < 0.05) and rutin supplementation significantly decreased oxidative stress in those animals (0.70 ± 0.13 vs. 1.54 ± 0.12 nmol MDA·mL−1; n = 8; p < 0.05). We concluded that oral supplementation with rutin restores impaired baroreflex sensitivity and vascular reactivity in hypertensive rats by decreasing oxidative stress.
Probabilistic identification of underground soil stratification using cone penetration tests
Authors: Wang Yu , Huang Kai , Cao Zijun
Published: May 2013

This paper develops Bayesian approaches for underground soil stratum identification and soil classification using cone penetration tests (CPTs). The uncertainty in the CPT-based soil classification using the Robertson chart is modeled explicitly in the Bayesian approaches, and the probability that the soil belongs to one of the nine soil types in the Robertson chart based on a set of CPT data is formulated using the maximum entropy principle. The proposed Bayesian approaches contain two major components: a Bayesian model class selection approach to identify the most probable number of underground soil layers and a Bayesian system identification approach to simultaneously estimate the most probable layer thicknesses and classify the soil types. Equations are derived for the Bayesian approaches, and the proposed approaches are illustrated using a real-life CPT performed at the National Geotechnical Experimentation Site (NGES) at Texas A&M University, USA. It has been shown that the proposed approaches properly identify the underground soil stratification and classify the soil type of each layer. In addition, as the number of model classes increases, the Bayesian model class selection approach identifies the soil layers progressively, starting from the statistically most significant boundary and gradually zooming into less significant ones with improved resolution. Furthermore, it is found that the evolution of the identified soil strata as the model class increases provides additional valuable information for assisting in the interpretation of CPT data in a rational and transparent manner.