bluuebunny/crossref_metadata_2025 huggingface dataset:
The M33 G Protein-Coupled Receptor Encoded by Murine Cytomegalovirus Is Dispensable for Hematogenous Dissemination but Is Required for Growth within the Salivary Gland
Authors: Bittencourt Fabiola M. , Wu Shu-En , Bridges James P. , Miller William E.
Published: August 2014

Human cytomegalovirus (HCMV) is a pathogen found worldwide and is a serious threat to immunocompromised individuals and developing fetuses. Due to the species specificity of cytomegaloviruses, murine cytomegalovirus (MCMV) has been used as a model for
in vivo
studies of HCMV pathogenesis. The MCMV genome, like the genomes of other beta- and gammaherpesviruses, encodes G protein-coupled receptors (GPCRs) that modulate host signaling pathways presumably to facilitate viral replication and dissemination. Among these viral receptors, the M33 GPCR carried by MCMV is an activator of CREB, NF-κB, and phospholipase C-β signaling pathways and has been implicated in aspects of pathogenesis
in vivo
, including persistence in the salivary glands of BALB/c mice. In this study, we used immunocompetent
n
on
o
bese
d
iabetic (NOD) and immunocompromised
N
OD-
s
cid-
g
amma (NSG) mice to further investigate the salivary gland defect exhibited by M33 deficiency. Interestingly, we demonstrate that virus with an M33 deletion (ΔM33) can replicate in the salivary gland of immunocompromised animals, albeit with a 400-fold growth defect compared with the growth of wild-type virus. Moreover, we determined that M33 does not have a role in cell-associated hematogenous dissemination but is required for viral amplification once the virus reaches the salivary gland. We conclude that the reduced replicative capacity of the ΔM33 virus is due to a specific defect occurring within the localized environment of the salivary gland. Importantly, since the salivary gland represents a site essential for persistence and horizontal transmission, an understanding of the mechanisms of viral replication within this site could lead to the generation of novel therapeutics useful for the prevention of HCMV spread.

IMPORTANCE
Human cytomegalovirus infects the majority of the American people and can reside silently in infected individuals for the duration of their lives. Under a number of circumstances, the virus can reactivate, leading to a variety of diseases in both adults and developing babies, and therefore, identifying the function of viral proteins is essential to understand how the virus spreads and causes disease. We aim to utilize animal models to study the function of an important class of viral proteins termed G protein-coupled receptors with the ultimate goal of developing inhibitors to these proteins that could one day be used to prevent viral spread.
Mutagenesis of the Catalytic and Cleavage Site Residues of the Hypovirus Papain-Like Proteases p29 and p48 Reveals Alternative Processing and Contributions to Optimal Viral RNA Accumulation
Authors: Jensen Kenneth S. , Nuss Donald L.
Published: August 2014

The positive-stranded RNA genome of the prototypic virulence-attenuating hypovirus CHV-1/EP713 contains two open reading frames (ORF), each encoding an autocatalytic papain-like leader protease. Protease p29, derived from the N-terminal portion of ORF A, functions as a suppressor of RNA silencing, while protease p48, derived from the N-terminal portion of ORF B, is required for viral RNA replication. The catalytic and cleavage site residues required for autoproteolytic processing have been functionally mapped
in vitro
for both proteases but not confirmed in the infected fungal host. We report here the mutagenesis of the CHV-1/EP713 infectious cDNA clone to define the requirements for p29 and p48 cleavage and the role of autoproteolysis in the context of hypovirus replication. Mutation of the catalytic cysteine and histidine residues for either p29 or p48 was tolerated but reduced viral RNA accumulation to ca. 20 to 50% of the wild-type level. Mutation of the p29 catalytic residues caused an accumulation of unprocessed ORF A product p69. Surprisingly, the release of p48 from the ORF B-encoded polyprotein was not prevented by mutation of the p48 catalytic and cleavage site residues and was independent of p29. The results show that, while dispensable for hypovirus replication, the autocatalytic processing of the leader proteases p29 and p48 contributes to optimal virus RNA accumulation. The role of the predicted catalytic residues in autoproteolytic processing of p29 was confirmed in the infected host, while p48 was found to also undergo alternative processing independent of the encoded papain-like protease activities.

IMPORTANCE
Hypoviruses are positive-strand RNA mycoviruses that attenuate virulence of their pathogenic fungal hosts. The prototypic hypovirus CHV-1/EP713, which infects the chestnut bight fungus
Cryphonetria parasitica
, encodes two papain-like autocatalytic leader proteases, p29 and p48, that also have important functions in suppressing the RNA silencing antiviral defense response and in viral RNA replication, respectively. The mutational analyses of the CHV-1/EP713 infectious cDNA clone, reported here, define the requirements for p29 and p48 cleavage and the functional importance of autoproteolysis in the context of hypovirus replication and exposed an alternative p48 processing pathway independent of the encoded papain-like protease activities. These findings provide additional insights into hypovirus gene expression, replication, and evolution and inform ongoing efforts to engineer hypoviruses for interrogating and modulating fungal virulence.
Influenza A Virus Acquires Enhanced Pathogenicity and Transmissibility after Serial Passages in Swine
Authors: Wei Kai , Sun Honglei , Sun Zhenhong , Sun Yipeng , Kong Weili , Pu Juan , Ma Guangpeng , Yin Yanbo , Yang Hanchun , Guo Xin , Chang Kin-Chow , Liu Jinhua
Published: August 2014

Genetic and phylogenetic analyses suggest that the pandemic H1N1/2009 virus was derived from well-established swine influenza lineages; however, there is no convincing evidence that the pandemic virus was generated from a direct precursor in pigs. Furthermore, the evolutionary dynamics of influenza virus in pigs have not been well documented. Here, we subjected a recombinant virus (rH1N1) with the same constellation makeup as the pandemic H1N1/2009 virus to nine serial passages in pigs. The severity of infection sequentially increased with each passage. Deep sequencing of viral quasispecies from the ninth passage found five consensus amino acid mutations: PB1 A469T, PA 1129T, NA N329D, NS1 N205K, and NEP T48N. Mutations in the hemagglutinin (HA) protein, however, differed greatly between the upper and lower respiratory tracts. Three representative viral clones with the five consensus mutations were selected for functional evaluation. Relative to the parental virus, the three viral clones showed enhanced replication and polymerase activity
in vitro
and enhanced replication, pathogenicity, and transmissibility in pigs, guinea pigs, and ferrets
in vivo
. Specifically, two mutants of rH1N1 (PB1 A469T and a combination of NS1 N205K and NEP T48N) were identified as determinants of transmissibility in guinea pigs. Crucially, one mutant viral clone with the five consensus mutations, which also carried D187E, K211E, and S289N mutations in its HA, additionally was able to infect ferrets by airborne transmission as effectively as the pandemic virus. Our findings demonstrate that influenza virus can acquire viral characteristics that are similar to those of the pandemic virus after limited serial passages in pigs.

IMPORTANCE
We demonstrate here that an engineered reassortant swine influenza virus, with the same gene constellation pattern as the pandemic H1N1/2009 virus and subjected to only nine serial passages in pigs, acquired greatly enhanced virulence and transmissibility. In particular, one representative pathogenic passaged virus clone, which carried three mutations in the HA gene and five consensus mutations in PB1, PA, NA, NS1, and NEP genes, additionally was able to confer respiratory droplet transmission as effectively as the pandemic H1N1/2009 virus. Our findings suggest that pigs can readily induce adaptive mutational changes to a precursor pandemic-like virus to transform it into a highly virulent and infectious form akin to that of the pandemic H1N1/2009 virus, which underlines the potential direct role of pigs in promoting influenza A virus pathogenicity and transmissibility.
A Chimeric Virus-Mouse Model System for Evaluating the Function and Inhibition of Papain-Like Proteases of Emerging Coronaviruses
Authors: Deng Xufang , Agnihothram Sudhakar , Mielech Anna M. , Nichols Daniel B. , Wilson Michael W. , StJohn Sarah E. , Larsen Scott D. , Mesecar Andrew D. , Lenschow Deborah J. , Baric Ralph S. , Baker Susan C.
Published: August 2014

To combat emerging coronaviruses, developing safe and efficient platforms to evaluate viral protease activities and the efficacy of protease inhibitors is a high priority. Here, we exploit a biosafety level 2 (BSL-2) chimeric Sindbis virus system to evaluate protease activities and the efficacy of inhibitors directed against the papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus (SARS-CoV), a biosafety level 3 (BSL-3) pathogen. We engineered Sindbis virus to coexpress PLpro and a substrate, murine interferon-stimulated gene 15 (ISG15), and found that PLpro mediates removal of ISG15 (deISGylation) from cellular proteins. Mutation of the catalytic cysteine residue of PLpro or addition of a PLpro inhibitor blocked deISGylation in virus-infected cells. Thus, deISGylation is a marker of PLpro activity. Infection of alpha/beta interferon receptor knockout (IFNAR
−/−
) mice with these chimeric viruses revealed that PLpro deISGylation activity removed ISG15-mediated protection during viral infection. Importantly, administration of a PLpro inhibitor protected these mice from lethal infection, demonstrating the efficacy of a coronavirus protease inhibitor in a mouse model. However, this PLpro inhibitor was not sufficient to protect the mice from lethal infection with SARS-CoV MA15, suggesting that further optimization of the delivery and stability of PLpro inhibitors is needed. We extended the chimeric-virus platform to evaluate the papain-like protease/deISGylating activity of Middle East respiratory syndrome coronavirus (MERS-CoV) to provide a small-animal model to evaluate PLpro inhibitors of this recently emerged pathogen. This platform has the potential to be universally adaptable to other viral and cellular enzymes that have deISGylating activities.

IMPORTANCE
Evaluating viral protease inhibitors in a small-animal model is a critical step in the path toward antiviral drug development. We modified a biosafety level 2 chimeric virus system to facilitate evaluation of inhibitors directed against highly pathogenic coronaviruses. We used this system to demonstrate the
in vivo
efficacy of an inhibitor of the papain-like protease of severe acute respiratory syndrome coronavirus. Furthermore, we demonstrate that the chimeric-virus system can be adapted to study the proteases of emerging human pathogens, such as Middle East respiratory syndrome coronavirus. This system provides an important tool to rapidly assess the efficacy of protease inhibitors targeting existing and emerging human pathogens, as well as other enzymes capable of removing ISG15 from cellular proteins.
Effect of Formaldehyde Inactivation on Poliovirus
Authors: Wilton Thomas , Dunn Glynis , Eastwood David , Minor Philip D. , Martin Javier
Published: August 2014

Inactivated polio vaccines, which have been used in many countries for more than 50 years, are produced by treating live poliovirus (PV) with formaldehyde. However, the molecular mechanisms underlying virus inactivation are not well understood. Infection by PV is initiated by virus binding to specific cell receptors, which results in viral particles undergoing sequential conformational changes that generate altered structural forms (135S and 80S particles) and leads to virus cell entry. We have analyzed the ability of inactivated PV to bind to the human poliovirus receptor (hPVR) using various techniques such as ultracentrifugation, fluorescence-activated cell sorting flow cytometry and real-time reverse transcription-PCR (RT-PCR). The results showed that although retaining the ability to bind to hPVR, inactivated PV bound less efficiently in comparison to live PV. We also found that inactivated PV showed resistance to structural conversion
in vitro
, as judged by measuring changes in antigenicity, the ability to bind to hPVR, and viral RNA release at high temperature. Furthermore, viral RNA from inactivated PV was shown to be modified, since cDNA yields obtained by RT-PCR amplification were severely reduced and no infectious virus was recovered after RNA transfection into susceptible cells.

IMPORTANCE
This study represents a novel insight into the molecular mechanisms responsible for poliovirus inactivation. We show that inactivation with formaldehyde has an effect on early steps of viral replication as it reduces the ability of PV to bind to hPVR, decreases the sensitivity of PV to convert to 135S particles, and abolishes the infectivity of its viral RNA. These changes are likely responsible for the loss of infectivity shown by PV following inactivation. Techniques used in this study represent new approaches for the characterization of inactivated PV products and could be useful in developing improved methods for the production and quality control testing of inactivated polio vaccines. Measuring the antigenicity, capsid stability, and RNA integrity of inactivated PV samples could help establishing the optimal balance between the loss of infectivity and the preservation of virus antigenicity during inactivation.
Coinfection with Streptococcus pneumoniae Modulates the B Cell Response to Influenza Virus
Authors: Wolf Amaya I. , Strauman Maura C. , Mozdzanowska Krystyna , Whittle James R. R. , Williams Katie L. , Sharpe Arlene H. , Weiser Jeffrey N. , Caton Andrew J. , Hensley Scott E. , Erikson Jan
Published: August 2014

Pathogen-specific antibodies (Abs) protect against respiratory infection with influenza A virus (IAV) andStreptococcus pneumoniaeand are the basis of effective vaccines. Sequential or overlapping coinfections with both pathogens are common, yet the impact of coinfection on the generation and maintenance of Ab responses is largely unknown. We report here that the B cell response to IAV is altered in mice coinfected with IAV andS. pneumoniaeand that this response differs, depending on the order of pathogen exposure. In mice exposed toS. pneumoniaeprior to IAV, the initial virus-specific germinal center (GC) B cell response is significantly enhanced in the lung-draining mediastinal lymph node and spleen, and there is an increase in CD4+T follicular helper (TFH) cell numbers. In contrast, secondaryS. pneumoniaeinfection exaggerates early antiviral antibody-secreting cell formation, and at later times, levels of GCs, TFH cells, and antiviral serum IgG are elevated. Mice exposed toS. pneumoniaeprior to IAV do not maintain the initially robust GC response in secondary lymphoid organs and exhibit reduced antiviral serum IgG with diminished virus neutralization activity a month after infection. Our data suggest that the history of pathogen exposures can critically affect the generation of protective antiviral Abs and may partially explain the differential susceptibility to and disease outcomes from IAV infection in humans.

IMPORTANCERespiratory tract coinfections, specifically those involving influenza A viruses andStreptococcus pneumoniae, remain a top global health burden. We sought to determine howS. pneumoniaecoinfection modulates the B cell immune response to influenza virus since antibodies are key mediators of protection.
Hepatitis E Virus Inhibits Type I Interferon Induction by ORF1 Products
Authors: Nan Yuchen , Yu Ying , Ma Zexu , Khattar Sunil K. , Fredericksen Brenda , Zhang Yan-Jin
Published: August 2014

Hepatitis E virus (HEV) causes both endemic and epidemic human hepatitis by fecal-oral transmission in many parts of the world. Zoonotic transmission of HEV from animals to humans has been reported. Due to the lack of an efficient cell culture system, the molecular mechanisms of HEV infection remain largely unknown. In this study, we found that HEV replication in hepatoma cells inhibited poly(I·C)-induced beta interferon (IFN-β) expression and that the HEV open reading frame 1 (ORF1) product was responsible for this inhibition. Two domains, X and the papain-like cysteine protease domain (PCP), of HEV ORF1 were identified as the putative IFN antagonists. When overexpressed in HEK293T cells, the X domain (or macro domain) inhibited poly(I·C)-induced phosphorylation of interferon regulatory factor 3 (IRF-3), which is the key transcription factor for IFN induction. The PCP domain was shown to have deubiquitinase activity for both RIG-I and TBK-1, whose ubiquitination is a key step in their activation in poly(I·C)-induced IFN induction. Furthermore, replication of a HEV replicon containing green fluorescent protein (GFP) (E2-GFP) in hepatoma cells led to impaired phosphorylation of IRF-3 and reduced ubiquitination of RIG-I and TBK-1, which confirmed our observations of X and PCP inhibitory effects in HEK293T cells. Altogether, our study identified the IFN antagonists within the HEV ORF1 polyprotein and expanded our understanding of the functions of several of the HEV ORF1 products, as well as the mechanisms of HEV pathogenesis.

IMPORTANCE
Type I interferons (IFNs) are important components of innate immunity and play a crucial role against viral infection. They also serve as key regulators to evoke an adaptive immune response. Virus infection can induce the synthesis of interferons; however, viruses have evolved many strategies to antagonize the induction of interferons. There is little knowledge about how hepatitis E virus (HEV) inhibits induction of host IFNs, though the viral genome was sequenced more than 2 decades ago. This is the first report of identification of the potential IFN antagonists encoded by HEV. By screening all the domains in the open reading frame 1 (ORF1) polyprotein, we identified two IFN antagonists and performed further research to determine how and at which step in the IFN induction pathway they antagonize host IFN induction. Our work provides valuable information about HEV-cell interaction and pathogenesis.
A surprising cause of acute right upper quadrant pain
Authors: Stitt Rodger Scott , Greenwood Robert , Laczek Jeffrey
Published: August 2014

A 42 year-old African-American woman was admitted for severe acute right upper quadrant pain. Her liver function tests showed a cholestatic pattern of hepatitis. She had no known history of liver disease or sarcoidosis. Imaging of her liver and biliary tree did not reveal any apparent cause for her right upper quadrant pain. A liver biopsy was performed which showed granulomatous disease. This prompted a CT chest that showed mediastinal lymphadenopathy. Biopsy of the mediastinal lymphnode revealed non-caseating granulomas. Despite having no pulmonary symptoms or history of pulmonary sarcoidosis, she was diagnosed with systemic pulmonary sarcoidosis. She was treated with corticosteroids and had complete resolution of symptoms over the next several weeks.
Fracture of mandible during yawning in a patient with osteogenesis imperfecta
Authors: Ram Hari , Shadab Mohammad , Vardaan Ajay , Aga Pallavi
Published: August 2014

Osteogenesis imperfecta is a genetic disorder characterised by fragility and multiple fractures of bones. Clinical signs and symptoms vary depending on the type of disease. Fractures of facial bones are rare compared with load-bearing long bones. We report a case of fracture of the mandible during yawning which was managed by open reduction and internal fixation.
Family-based interventions to increase physical activity in children: a meta-analysis and realist synthesis protocol
Authors: Brown Helen Elizabeth , Atkin Andrew J , Panter Jenna , Corder Kirsten , Wong Geoff , Chinapaw Mai J M , van Sluijs Esther
Published: August 2014

Introduction

Despite the established relationship between physical activity and health, data suggest that many children are insufficiently active, and that levels decline into adolescence. Engaging the family in interventions may increase and maintain children's physical activity levels at the critical juncture before secondary school. Synthesis of existing evidence will inform future studies, but the heterogeneity in target populations recruited, behaviour change techniques and intervention strategies employed, and measurement conducted, may require a multifaceted review method. The primary objective of this work will therefore be to synthesis evidence from intervention studies that explicitly engage the family unit to increase children's physical activity using an innovative dual meta-analysis and realist approach.

Methods and analysis

Peer-reviewed studies will be independently screened by two authors for inclusion based on (1) including ‘healthy’ participants aged 5–12 years; (2) having a substantive intervention aim of increasing physical activity, by engaging the family and (3) reporting on physical activity. Duplicate data extraction and quality assessment will be conducted using a specially designed proforma and the Effective Public Health Practice Project Quality Assessment Tool respectively. STATA software will be used to compute effect sizes for meta-analyses, with subgroup analyses conducted to identify moderating characteristics. Realist syntheses will be conducted according to RAMESES quality and publication guidelines, including development of a programme theory and evidence mapping.

Dissemination

This review will be the first to use the framework of a traditional review to conduct a dual meta-analysis and realist synthesis, examining interventions that engage the family to increase physical activity in children. The results will be disseminated through peer-reviewed publications, conferences, formal presentations to policy makers and practitioners and informal meetings. Evidence generated from this synthesis will also be used to inform the development of theory-driven, evidence-based interventions aimed at engaging the family to increase physical activity levels in children.

Protocol registration

International Prospective Register for Systematic Reviews (PROSPERO): number CRD42013005780.
Transvenous approach for the treatment of direct carotid cavernous fistula following Pipeline embolization of cavernous carotid aneurysm: a report of two cases and review of the literature
Authors: Lin Li-Mei , Colby Geoffrey P , Jiang Bowen , Pero Guglielmo , Boccardi Edoardo , Coon Alexander L
Published: August 2014

Flow diverters are increasingly used for the endovascular treatment of cerebral aneurysms. A rare complication from flow diversion is delayed aneurysm rupture, which can lead to carotid–cavernous fistula (CCF) in the setting of cavernous carotid aneurysms (CCAs). Direct CCFs pose unique management challenges, given the lack of transarterial access to the fistula. We present two cases of direct CCFs following treatment of CCAs with the Pipeline embolization device (PED). Case 1 was a middle-aged patient with a symptomatic 10 mm wide-necked left CCA. Six weeks after PED treatment the patient developed diplopia secondary to direct CCF. Case 2 was a middle-aged patient with a symptomatic 17 mm left CCA treated with PED. One-month follow-up angiography demonstrated a direct CCF. Both patients underwent successful coil embolization of the CCF through a transvenous approach. Direct CCF formation following PED deployment for CCA is a rare complication. Parent vessel sacrifice may be avoided with transvenous occlusion of the fistula.
Non-vitamin K antagonist oral anticoagulants (NOACs): clinical evidence and therapeutic considerations
Authors: Saraf Karan , Morris Paul , Garg Pankaj , Sheridan Paul , Storey Robert
Published: August 2014

Warfarin, a vitamin K antagonist, is the most widely used oral anticoagulant in the world. It is cheap and effective, but its use is limited in many patients by unpredictable levels of anticoagulation, which increases the risk of thromboembolic or haemorrhagic complications. It also requires regular blood monitoring and dose adjustment. New classes of drugs, non-vitamin K antagonist oral anticoagulants (NOACs), are now supported as alternatives to warfarin. Three NOACs are licensed: dabigatran, a direct thrombin inhibitor, and rivaroxaban and apixaban, antagonists of factor Xa. NOACs do not require routine blood monitoring or dose adjustment. They have a rapid onset and offset of action and fewer food and drug interactions. Current indications include treatment and prophylaxis of venous thromboembolism and prevention of cardioembolic disease in non-valvular atrial fibrillation. Effective antidotes are lacking and some caution must be used in severe renal impairment, but favourable trial evidence has led to their widespread adoption. Research is ongoing, and an increase in their use and indications is expected in the coming years.
Angular propulsion–the rotational analog of rocket motion
Authors: Polihronov Jeliazko G. , Straatman Anthony G.
Published: August 2014

In a recent publication it has been shown that vortex cooling takes place as rotational work is extracted from pressurized gas (Polihronov and Straatman. Phys. Rev. Lett. 109, 054504 (2012)). We show that such rotating systems can be treated as systems with variable mass and thus introduce a rotational analog of the familiar rectilinear rocket motion. In this manner, such propulsion systems are analogous to radial inflow turbines.
On the history of the strong interaction
Authors: Leutwyler H.
Published: August 2014

These notes recall the conceptual developments which led from the discovery of the neutron to our present understanding of strong interaction physics.
QFT and unification of knot theories
Authors: Sleptsov Alexey
Published: August 2014

We discuss relation between knot theory and topological quantum field theory. Also it is considered a theory of superpolynomial invariants of knots which generalizes all other known theories of knot invariants. We discuss a possible generalization of topological quantum field theory with the help of superpolynomial invariants.
SEMICONDUCTOR OPTICAL AMPLIFIER BASED FREQUENCY ENCODED LOGIC GATES EXPLOITING NONLINEAR POLARIZATION ROTATION ONLY
Authors: MUKHERJEE KOUSIK
Published: August 2014

All optical frequency encoded logic gates NOT, OR and AND are proposed and described using polarization rotation in semiconductor optical amplifiers (SOAs). The switching power of the logic gates are very low and have capability to speed of 320 Gbps. The gates are easily integrable, simple in hardware and compatible to optical network. The input and output power requirement is included.
X-RAY PHOTOEMISSION ELECTRON MICROSCOPE DETERMINATION OF ORIGINS OF ROOM TEMPERATURE FERROMAGNETISM AND PHOTOLUMINESCENCE IN HIGHCo-CONTENTCoxZn1-xOFILMS
Authors: CAO WEI , PANKRATOV VLADIMIR , HUTTULA MARKO , SHIRMANE LIANA , NIU YU RAN , WANG FENG
Published: August 2014

In this paper, we reported on the X-ray photoemission electron microscope (XPEEM) determination of magnetic and luminescence origins for two CoxZn1-xO films. The cobalt fraction x of radio frequency co-sputtered samples were 0.86(2) and 0.92(2), respectively. Films were ferromagnetic and semiconductive. Unique narrow green color lines beside the ZnO intrinsic emissions were found with a decay time in microsecond range at room temperature. Origins of magnetic and luminescence properties were determined with XPEEM. The X-ray absorption near edge structure at the Co  L3-edge denoted that Co was partially oxidized, and phase-contrast images together with chemical composition identification further proved that Co and CoO co-existed in the samples. The ferromagnetism was attributed to ferromagnetism of Co clusters partially canceled by the antiferromagnetism of its oxide, and the photoluminescence to bound exciton in ZnO nanoclusters and defect related centers of ZnO nanoclusters in a Co -rich matrix. Present results show possibilities for adjusting magnetic and luminescence properties of Co – ZnO compounds by changing the cobalt concentration.
Compliance Control and Human–Robot Interaction: Part II — Experimental Examples
Authors: Khan Said G. , Herrmann Guido , Lenz Alexander , Al Grafi Mubarak , Pipe Tony , Melhuish Chris
Published: August 2014

Compliance control is highly relevant to human safety in human–robot interaction (HRI). This paper presents multi-dimensional compliance control of a humanoid robot arm. A dynamic model-free adaptive controller with an anti-windup compensator is implemented on four degrees of freedom (DOF) of a humanoid robot arm. The paper is aimed to compliment the associated review paper on compliance control. This is a model reference adaptive compliance scheme which employs end-effector forces (measured via joint torque sensors) as a feedback. The robot's body-own torques are separated from external torques via a simple but effective algorithm. In addition, an experiment of physical human robot interaction is conducted employing the above mentioned adaptive compliance control along with a speech interface. The experiment is focused on passing an object (a cup) between a human and a robot. Compliance is providing an immediate layer of safety for this HRI scenario by avoiding pushing, pulling or clamping and minimizing the effect of collisions with the environment.
Characteristics, bicharacteristics and geometric singularities of solutions of PDEs
Authors: Vitagliano Luca
Published: August 2014

Many physical systems are described by partial differential equations (PDEs). Determinism then requires the Cauchy problem to be well-posed. Even when the Cauchy problem is well-posed for generic Cauchy data, there may exist characteristic Cauchy data. Characteristics of PDEs play an important role both in Mathematics and in Physics. I will review the theory of characteristics and bicharacteristics of PDEs, with a special emphasis on intrinsic aspects, i.e. those aspects which are invariant under general changes of coordinates. After a basically analytic introduction, I will pass to a modern, geometric point of view, presenting characteristics within the jet space approach to PDEs. In particular, I will discuss the relationship between characteristics and singularities of solutions and observe that: "wave-fronts are characteristic surfaces and propagate along bicharacteristics". This remark may be understood as a mathematical formulation of the wave/particle duality in optics and/or quantum mechanics. The content of the paper reflects the three-hour mini-course that I gave at the XXII International Fall Workshop on Geometry and Physics, September 2–5, 2013, Évora, Portugal.
On Kossakowski Construction of Positive Maps on Matrix Algebras
Authors: Chruściński Dariusz
Published: August 2014

We provide the continuation of an analysis of a class of positive maps proposed ten years ago by Kossakowski. In particular, we propose a new parametrization which reveals an elegant geometric structure and an interesting interplay between group theory and a certain class of positive maps.
Comment on 'Effective Dielectric Constant of BaTiO3-PVDF Systems'
Authors: Muralidhar C.
Published: August 2014

The authors have measured the dielectric constant of BaTiO3 after compression and observed the low values of dielectric constant to that of ordinary BaTiO3 ceramics and attributed the discrepancy to the small size of BaTiO3 particles. We have suggested that the discrepancy is due to a compressed BaTiO3 pellet which is not sintered. It is not due to the small particle size since the BaTiO3 powder has a diameter of less than 100 µm.
Dynamic elastic characterization of carbonate rocks used as building materials in the historical city centre of Cagliari (Italy)
Authors: Cuccuru F. , Fais S. , Ligas P.
Published: August 2014

This paper focuses on the dynamic characterization approach to evaluate the conservation state of carbonate building stones of monumental structures. In particular, we report the use of elastic waves at an ultrasonic frequency of 54 kHz to define quantitatively some dynamic properties of carbonate rock types used as building materials. Measurements of compressional and shear wave velocities have been carried out and the relationship between some physical properties of the investigated rocks and these geophysical measurements have been evaluated. The ultrasonic data were also supplemented by a petrographical study of these rocks to correlate their petrophysical features with the elastic ones. Based on the results of the laboratory measurements,
in situ
applications on a significant monumental structure have been also carried out to check zones of weakness and to assess the state of deterioration of the investigated stones. A comparison of laboratory and
in situ
results confirms that dynamic characterization is a useful approach.
Transcriptional regulation of α1H T-type calcium channel under hypoxia
Authors: Sellak Hassan , Zhou Chun , Liu Bainan , Chen Hairu , Lincoln Thomas M. , Wu Songwei
Published: August 2014

The low-voltage-activated T-type Ca2+ channels play an important role in mediating the cellular responses to altered oxygen tension. Among three T-type channel isoforms, α1G, α1H, and α1I, only α1H was found to be upregulated under hypoxia. However, mechanisms underlying such hypoxia-dependent isoform-specific gene regulation remain incompletely understood. We, therefore, studied the hypoxia-dependent transcriptional regulation of α1G and α1H gene promoters with the aim to identify the functional hypoxia-response elements (HREs). In rat pulmonary artery smooth muscle cells (PASMCs) and pheochromocytoma (PC12) cells after hypoxia (3% O2) exposure, we observed a prominent increase in α1H mRNA at 12 h along with a significant rise in α1H-mediated T-type current at 24 and 48 h. We then cloned two promoter fragments from the 5′-flanking regions of rat α1G and α1H gene, 2,000 and 3,076 bp, respectively, and inserted these fragments into a luciferase reporter vector. Transient transfection of PASMCs and PC12 cells with these recombinant constructs and subsequent luciferase assay revealed a significant increase in luciferase activity from the reporter containing the α1H, but not α1G, promoter fragment under hypoxia. Using serial deletion and point mutation analysis strategies, we identified a functional HRE at site −1,173cacgc−1,169 within the α1H promoter region. Furthermore, an electrophoretic mobility shift assay using this site as a DNA probe demonstrated an increased binding activity to nuclear protein extracts from the cells after hypoxia exposure. Taken together, these findings indicate that hypoxia-induced α1H upregulation involves binding of hypoxia-inducible factor to an HRE within the α1H promoter region.
Silencing Bruton's tyrosine kinase in alveolar neutrophils protects mice from LPS/immune complex-induced acute lung injury
Authors: Krupa Agnieszka , Fol Marek , Rahman Moshiur , Stokes Karen Y. , Florence Jon M. , Leskov Igor L. , Khoretonenko Mikhail V. , Matthay Michael A. , Liu Kathleen D. , Calfee Carolyn S. , Tvinnereim Amy , Rosenfield Gabriel R. , Kurdowska Anna K.
Published: August 2014

Previous observations made by our laboratory indicate that Bruton's tyrosine kinase (Btk) may play an important role in the pathophysiology of local inflammation in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). We have shown that there is cross talk between FcγRIIa and TLR4 in alveolar neutrophils from patients with ALI/ARDS and that Btk mediates the molecular cooperation between these two receptors. To study the function of Btk in vivo we have developed a unique two-hit model of ALI: LPS/immune complex (IC)-induced ALI. Furthermore, we conjugated F(ab)2fragments of anti-neutrophil antibodies (Ly6G1A8) with specific siRNA for Btk to silence Btk specifically in alveolar neutrophils. It should be stressed that we are the first group to perform noninvasive transfections of neutrophils, both in vitro and in vivo. Importantly, our present findings indicate that silencing Btk in alveolar neutrophils has a dramatic protective effect in mice with LPS/IC-induced ALI, and that Btk regulates neutrophil survival and clearance of apoptotic neutrophils in this model. In conclusion, we put forward a hypothesis that Btk-targeted neutrophil specific therapy is a valid goal of research geared toward restoring homeostasis in lungs of patients with ALI/ARDS.
Cardiac macrophages and apoptosis after myocardial infarction: effects of central MR blockade
Authors: Rafatian Naimeh , Westcott Katherine V. , White Roselyn A. , Leenen Frans H. H.
Published: August 2014

After myocardial infarction (post-MI), inflammation and apoptosis contribute to progressive cardiac remodeling and dysfunction. Cardiac mineralocorticoid receptor (MR) and β-adrenergic signaling promote apoptosis and inflammation. Post-MI, MR activation in the brain contributes to sympathetic hyperactivity and an increase in cardiac aldosterone. In the present study, we assessed the time course of macrophage infiltration and apoptosis in the heart as detected by both terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and active caspase-3 immunostaining in both myocytes and nonmyocytes, as well as the effects of central MR blockade by intracerebroventricular infusion of eplerenone at 5 μg/day on peak changes in macrophage infiltration and apoptosis post-MI. Macrophage numbers were markedly increased in the infarct and peri-infarct zones and to a minor extent in the noninfarct part of the left ventricle at 10 days post-MI and decreased over the 3-mo study period. Apoptosis of both myocytes and nonmyocytes was clearly apparent in the infarct and peri-infarct areas at 10 days post-MI. For TUNEL, the increases persisted at 4 and 12 wk, but the number of active caspase-3-positive cells markedly decreased. Central MR blockade significantly decreased CD80-positive proinflammatory M1 macrophages and increased CD163-positive anti-inflammatory M2 macrophages in the infarct. Central MR blockade also reduced apoptosis of myocytes by 40–50% in the peri-infarct and to a lesser extent of nonmyocytes in the peri-infarct and infarct zones. These findings indicate that MR activation in the brain enhances apoptosis both in myocytes and nonmyocytes in the peri-infarct and infarct area post-MI and contributes to the inflammatory response.
Guanylin peptides regulate electrolyte and fluid transport in the Gulf toadfish (Opsanus beta) posterior intestine
Authors: Ruhr Ilan M. , Bodinier Charlotte , Mager Edward M. , Esbaugh Andrew J. , Williams Cameron , Takei Yoshio , Grosell Martin
Published: August 2014

The physiological effects of guanylin (GN) and uroguanylin (UGN) on fluid and electrolyte transport in the teleost fish intestine have yet to be thoroughly investigated. In the present study, the effects of GN, UGN, and renoguanylin (RGN; a GN and UGN homolog) on short-circuit current ( Isc) and the transport of Cl−, Na+, bicarbonate (HCO3−), and fluid in the Gulf toadfish ( Opsanus beta) intestine were determined using Ussing chambers, pH-stat titration, and intestinal sac experiments. GN, UGN, and RGN reversed the Iscof the posterior intestine (absorptive-to-secretory), but not of the anterior intestine. RGN decreased baseline HCO3−secretion, but increased Cl−and fluid secretion in the posterior intestine. The secretory response of the posterior intestine coincides with the presence of basolateral NKCC1 and apical cystic fibrosis transmembrane conductance regulator (CFTR), the latter of which is lacking in the anterior intestine and is not permeable to HCO3−in the posterior intestine. However, the response to RGN by the posterior intestine is counterintuitive given the known role of the marine teleost intestine as a salt- and water-absorbing organ. These data demonstrate that marine teleosts possess a tissue-specific secretory response, apparently associated with seawater adaptation, the exact role of which remains to be determined.
Sex- and limb-specific differences in the nitric oxide-dependent cutaneous vasodilation in response to local heating
Authors: Stanhewicz Anna E. , Greaney Jody L. , Larry Kenney W. , Alexander Lacy M.
Published: August 2014

Local heating of the skin is commonly used to assess cutaneous microvasculature function. Controversy exists as to whether there are limb or sex differences in the nitric oxide (NO)-dependent contribution to this vasodilation, as well as the NO synthase (NOS) isoform mediating the responses. We tested the hypotheses that 1) NO-dependent vasodilation would be greater in the calf compared with the forearm; 2) total NO-dependent dilation would not be different between sexes within limb; and 3) women would exhibit greater neuronal NOS (nNOS)-dependent vasodilation in the calf. Two microdialysis fibers were placed in the skin of the ventral forearm and the calf of 19 (10 male and 9 female) young (23 ± 1 yr) adults for the local delivery of Ringer solution (control) or 5 mM Nω-propyl-l-arginine (NPLA; nNOS inhibition). Vasodilation was induced by local heating (42°C) at each site, after which 20 mM NG-nitro-l-arginine methyl ester (l-NAME) was perfused for within-site assessment of NO-dependent vasodilation. Cutaneous vascular conductance (CVC) was calculated as laser-Doppler flux/mean arterial pressure and normalized to maximum (28 mM sodium nitroprusside, 43°C). Total NO-dependent vasodilation in the calf was lower compared with the forearm in both sexes (Ringer: 42 ± 5 vs. 62 ± 4%; P < 0.05; NPLA: 37 ± 3 vs. 59 ± 5%; P < 0.05) and total NO-dependent vasodilation was lower in the forearm for women (Ringer: 52 ± 6 vs. 71 ± 4%; P < 0.05; NPLA: 47 ± 6 vs. 68 ± 5%; P < 0.05). NPLA did not affect total or NO-dependent vasodilation across limbs in either sex ( P > 0.05). These data suggest that the NO-dependent component of local heating-induced cutaneous vasodilation is lower in the calf compared with the forearm. Contrary to our original hypothesis, there was no contribution of nNOS to NO-dependent vasodilation in either limb during local heating.
Social stress induces changes in urinary bladder function, bladder NGF content, and generalized bladder inflammation in mice
Authors: Mingin Gerald C. , Peterson Abbey , Erickson Cuixia Shi , Nelson Mark T. , Vizzard Margaret A.
Published: August 2014

Social stress may play a role in urinary bladder dysfunction in humans, but the underlying mechanisms are unknown. In the present study, we explored changes in bladder function caused by social stress using mouse models of stress and increasing stress. In the stress paradigm, individual submissive FVB mice were exposed to C57BL/6 aggressor mice directly/indirectly for 1 h/day for 2 or 4 wk. Increased stress was induced by continuous, direct/indirect exposure of FVB mice to aggressor mice for 2 wk. Stressed FVB mice exhibited nonvoiding bladder contractions and a decrease in both micturition interval (increased voiding frequency) and bladder capacity compared with control animals. ELISAs demonstrated a significant increase in histamine protein expression with no change in nerve growth factor protein expression in the urinary bladder compared with controls. Unlike stressed mice, mice exposed to an increased stress paradigm exhibited increased bladder capacities and intermicturition intervals (decreased voiding frequency). Both histamine and nerve growth factor protein expression were significantly increased with increased stress compared with control bladders. The change in bladder function from increased voiding frequency to decreased voiding frequency with increased stress intensity suggests that changes in social stress-induced urinary bladder dysfunction are context and duration dependent. In addition, changes in the bladder inflammatory milieu with social stress may be important contributors to changes in urinary bladder function.
Systemic stiffening of mouse tail tendon is related to dietary advanced glycation end products but not high-fat diet or cholesterol
Authors: Eriksen C. , Svensson R. B. , Scheijen J. , Hag A. M. F. , Schalkwijk C. , Praet S. F. E. , Schjerling P. , Kjær M. , Magnusson S. P. , Couppé C.
Published: August 2014

Tendon pathology is related to metabolic disease and mechanical overloading, but the effect of metabolic disease on tendon mechanics is unknown. This study investigated the effect of diet and apolipoprotein E deficiency (ApoE−/−) on mechanical properties and advanced glycation end product (AGE) cross-linking of non-weight-bearing mouse tail tendons. Twenty ApoE−/− male mice were used as a model for hypercholesterolemia along with 26 wild-type (WT) mice. One-half of the mice from each group was fed a normal diet (ND) and the other half was fed a high-fat diet (HFD) to induce obesity. All were killed at 40 wk, and tail tendon fascicles were mechanically tested to failure and analyzed for AGEs. Diets were also analyzed for AGEs. ApoE−/− mice displayed a 14% increase in plateau modulus compared with WT mice ( P < 0.05), whereas HFD mice displayed a 13% decrease in plateau modulus ( P < 0.05) and a 12% decrease in total modulus ( P < 0.05) compared with ND mice. Tail tendons of HFD mice had significantly lower concentrations of AGEs [carboxymethyllysine (CML): 26%, P < 0.0001; methylglyoxal-derived hydroimidazolone 1 (MG-H1): 15%, P < 0.005; pentosidine: 13%, P < 0.0005]. The HFD had ∼44-fold lower content of CML ( P < 0.01), ∼29-fold lower content of carboxyethyllysine ( P < 0.005), and ∼16-fold lower content of MG-H1 ( P < 0.05) compared with ND. ApoE−/− increased, whereas HFD decreased mouse tail tendon stiffness. Dietary AGE content may be a crucial determinant for accumulation of AGE cross-links in tendons and for tissue compliance. The results demonstrate how systemic metabolic factors may influence tendon health.
On Conservation Forms and Invariant Solutions for Classical Mechanics Problems of Liénard Type
Authors: Gün Polat Gülden , Özer Teoman
Published: August 2014

In this study we apply partial Noether andλ-symmetry approaches to a second-order nonlinear autonomous equation of the formy′′+fyy′+g(y)=0, called Liénard equation corresponding to some important problems in classical mechanics field with respect tof(y)andg(y)functions. As a first approach we utilize partial Lagrangians and partial Noether operators to obtain conserved forms of Liénard equation. Then, as a second approach, based on theλ-symmetry method, we analyzeλ-symmetries for the case thatλ-function is in the form ofλ(x,y,y′)=λ1(x,y)y′+λ2(x,y). Finally, a classification problem for the conservation forms and invariant solutions are considered.
Cephalexin Induced Cholestatic Jaundice
Authors: Agrawal Abhinav , Rao Mana , Jasdanwala Sarfaraz , Mathur Ajay , Eng Margaret
Published: August 2014

Cephalexin is a very commonly prescribed orally administered antibiotic which has many potential side effects. Amongst these cholestatic jaundice has been infrequently reported as an adverse reaction. We present a case of a 57-year-old male who exhibited features of cholestatic jaundice including elevated liver function tests (LFTs) after taking cephalexin and showed improvement on removal of the offending agent. During this time he was symptomatically treated with cholestyramine. Complete resolution of LFTs was seen in four weeks. Cephalexin induced cholestasis is rare and hence requires a high degree of clinical suspicion for prompt diagnosis and treatment.