bluuebunny/crossref_metadata_2025 huggingface dataset:
Nicotiana attenuata MPK4 suppresses a novel jasmonic acid (JA) signaling‐independent defense pathway against the specialist insect Manduca sexta, but is not required for the resistance to the generalist Spodoptera littoralis
Authors: Hettenhausen Christian , Baldwin Ian T. , Wu Jianqiang
Published: May 2013

How plants tailor their defense responses to attack from different insects remains largely unknown. Here, we studied the role of a mitogen‐activated protein kinase (MAPK), MPK4, in the resistance of a wild tobacco Nicotiana attenuata to two herbivores, the specialist Manduca sexta and the generalist Spodoptera littoralis.

Stably transformed N. attenuata plants silenced in MPK4 (irMPK4) were generated and characterized for traits important for defense against herbivores.

Only the oral secretions (OS) from M. sexta, but not the OS from S. littoralis or mechanical wounding, induced elevated levels of jasmonic acid (JA) in irMPK4 plants relative to the wild‐type plants. Moreover, silencing of MPK4 strongly increased the resistance of N. attenuata to M. sexta in a fashion that was independent of COI1 (CORONATINE INSENSITIVE1)‐mediated JA signaling. Untargeted metabolomic screening identified several new MPK4‐dependent putative defensive compounds against M. sexta. By contrast, silencing of MPK4 did not affect the growth of the generalist insect S. littoralis, and we propose that this was because of the very low levels of fatty acid–amino acid conjugates (FACs) in S. littoralis OS.

Thus, MPK4 is likely to be a key signaling element that enables plants to tailor defense responses to different attackers.
OakContigDF159.1, a reference library for studying differential gene expression in Quercus robur during controlled biotic interactions: use for quantitative transcriptomic profiling of oak roots in ectomycorrhizal symbiosis
Authors: Tarkka Mika T. , Herrmann Sylvie , Wubet Tesfaye , Feldhahn Lasse , Recht Sabine , Kurth Florence , Mailänder Sarah , Bönn Markus , Neef Maren , Angay Oguzhan , Bacht Michael , Graf Marcel , Maboreke Hazel , Fleischmann Frank , Grams Thorsten E. E. , Ruess Liliane , Schädler Martin , Brandl Roland , Scheu Stefan , Schrey Silvia D. , Grosse Ivo , Buscot François
Published: May 2013

Oaks (Quercus spp.), which are major forest trees in the northern hemisphere, host many biotic interactions, but molecular investigation of these interactions is limited by fragmentary genome data. To date, only 75 oak expressed sequence tags (ESTs) have been characterized in ectomycorrhizal (EM) symbioses.

We synthesized seven beneficial and detrimental biotic interactions between microorganisms and animals and a clone (DF159) of Quercus robur. Sixteen 454 and eight Illumina cDNA libraries from leaves and roots were prepared and merged to establish a reference for RNA‐Seq transcriptomic analysis of oak EMs with Piloderma croceum.

Using the Mimicking Intelligent Read Assembly (MIRA) and Trinity assembler, the OakContigDF159.1 hybrid assembly, containing 65 712 contigs with a mean length of 1003 bp, was constructed, giving broad coverage of metabolic pathways. This allowed us to identify 3018 oak contigs that were differentially expressed in EMs, with genes encoding proline‐rich cell wall proteins and ethylene signalling‐related transcription factors showing up‐regulation while auxin and defence‐related genes were down‐regulated.

In addition to the first report of remorin expression in EMs, the extensive coverage provided by the study permitted detection of differential regulation within large gene families (nitrogen, phosphorus and sugar transporters, aquaporins). This might indicate specific mechanisms of genome regulation in oak EMs compared with other trees.
Immunoprofiling of oral squamous cell carcinomas reveals high p63 and survivin expression
Authors: Lauxen IS , Oliveira MG , Rados PV , Lingen MW , Nör JE , Sant'Ana Filho M
Published: May 2013

Background

Cancer is a multifactorial disease composed of cells that show somatic mutations and epigenetic changes. The aim of this study was to investigate the expression of proteins involved in the development and maintenance of epithelia, cell cycle regulation, and apoptosis in human oral squamous cell carcinoma (OSCC) tissue samples.

Methods

A tissue microarray containing 65 primary human OSCC specimens was immunolabeled for bcl‐2, survivin, epidermal growth factor receptor (EGFR), p21, p53, p63, and cleaved caspase‐3.

Results

Samples were scored for percentage of positively stained tumor cells and staining intensity. A total immunostaining score was also calculated, using the product of percentage and intensity scores. All specimens showed high scores, > 75%, for p63 and survivin, and 75.4% of the specimens also presented high EGFR expression. All cases showed p53‐positive cells. p21 showed a diffuse staining pattern. The percentage of cells positive for cleaved caspase‐3 and bcl‐2 was low.

Conclusions

The high frequency of tumor cells expressing p63 and survivin highlights the role of these proteins in the malignant transformation of oral epithelium. Collectively, our results suggest that p63 and survivin may constitute attractive targets for cancer therapy in patients with OSCC.
Oxymetazoline and hypertensive crisis in a child: can we prevent it?
Authors: Latham Gregory J. , Jardine David S.
Published: May 2013

Background

Oxymetazoline nasal spray is not FDA approved for use in children less than 6 years; however, its safety and efficacy are widely accepted, and it is in widespread use in children prior to procedures that may lead to epistaxis. We report a case of intraoperative oxymetazoline toxicity in a 4‐year‐old boy that led to a hypertensive crisis. While examining the possible causes for this problem, we became aware that the method of drug delivery led to an unanticipated overdose. The position in which the bottle is held causes pronounced variation in the quantity of oxymetazoline dispensed.

Methods

To examine the impact that bottle position has on the volume delivered, we measured the volume of oxymetazoline dispensed with the bottle in the upright and inverted position. We also measured the volume of a drop of oxymetazoline dispensed from the bottle. Because an additional source of oxymetazoline exposure is from packing the nares with surgical pledgets, we analyzed the volume of oxymetazoline absorbed by each pledget.

Results

Squeezing the bottle in the upright position results in a fine spray of fluid that averaged 28.9 ± 6.8 μl and was largely independent of effort. This volume is nearly identical to the measured volume of a drop of oxymetazoline, which was 30 μl. However, squeezing the bottle in the inverted position resulted in a steady stream of fluid, and the volume administered was completely effort dependent. Multiple tests in the inverted position demonstrated an average volume of 1037 ± 527 μl, with a range of 473–2196 μl. Lastly, the volume of oxymetazoline absorbed by each surgical pledget was 1511 ± 184 μl.

Discussion

Our testing indicates that bottle position during oxymetazoline administration can cause up to a 75‐fold increase in intended drug administration.
The mouse ruby‐eye 2d (ru2d/Hps5ru2‐d) allele inhibits eumelanin but not pheomelanin synthesis
Authors: Hirobe Tomohisa , Ito Shosuke , Wakamatsu Kazumasa
Published: May 2013

The novel mutation named ru2d/Hps5ru2‐d, characterized by light‐colored coats and ruby‐eyes, prohibits differentiation of melanocytes by inhibiting tyrosinase (Tyr) activity, expression of Tyr, Tyr‐related protein 1 (Tyrp1), Tyrp2, and Kit. However, it is not known whether the ru2d allele affects pheomelanin synthesis in recessive yellow (e/Mc1re) or in pheomelanic stage in agouti (A) mice. In this study, effects of the ru2d allele on pheomelanin synthesis were investigated by chemical analysis of melanin present in dorsal hairs of 5‐week‐old mice from F2 generation between C57BL/10JHir (B10)‐co‐isogenic ruby‐eye 2d and B10‐congenic recessive yellow or agouti. Eumelanin content was decreased in ruby‐eye 2d and ruby‐eye 2d agouti mice, whereas pheomelanin content in ruby‐eye 2d recessive yellow and ruby‐eye 2d agouti mice did not differ from the corresponding Ru2d/‐ mice, suggesting that the ru2d allele inhibits eumelanin but not pheomelanin synthesis.
A Prospective Two‐Year Assessment of Miconazole Resistance in Candida Spp. with Repeated Treatment with 0.25% Miconazole Nitrate Ointment in Neonates and Infants with Moderate to Severe Diaper Dermatitis Complicated by Cutaneous Candidiasis
Authors: Blanco Daisy , van Rossem Koen
Published: May 2013

A petrolatum and zinc oxide–based ointment containing 0.25% miconazole nitrate is reported to be effective and well tolerated in the treatment of diaper dermatitis complicated by cutaneous candidiasis (DDCC). This prospective, multicenter, open‐label, long‐term, phase IV study investigated the potential resistance of Candida spp. to repeated topical use of 0.25% miconazole nitrate in infants age 15 months and younger with moderate to severe DDCC. For initial and recurring episodes of DDCC over the 2‐year study period, subjects were treated with a 7‐day course of 0.25% miconazole nitrate ointment (active components: miconazole nitrate 0.25%, zinc oxide 15%, and white petrolatum 81.35%) with a 7‐day follow‐up. Clinical and mycologic evaluations were conducted before treatment (day 0) and 7 days after treatment (day 14). Potential resistance to miconazole was defined using an arbitrary breakpoint of minimum inhibitory concentration of 2 μg/mL. There was no evidence of resistance to miconazole in Candida spp. after single or repeated treatment courses of 0.25% miconazole nitrate ointment. For the initial episode of DDCC, 83 of 168 subjects (49.4%) achieved a clinical cure, 77 (45.8%) achieved a mycologic cure, and 49 (29.2%) achieved an overall cure (clinical and mycologic). The overall cure rate for recurrent episodes of DDCC was similar to or numerically greater than rates observed for the initial episode. Treatment of DDCC with 0.25% miconazole nitrate ointment was effective and generally well tolerated. No evidence of the development of resistance to miconazole in Candida spp. was observed.
Vertical Integration under Competition: Forward, Backward, or No Integration?
Authors: Lin Yen‐Ting , Parlaktürk Ali K. , Swaminathan Jayashankar M.
Published: May 2013

We consider two competing supply chains, each consisting of supplier, a manufacturer, and a retailer. The suppliers exert effort to improve product quality, and the retailers sell products competitively. Each manufacturer chooses one of the three strategies: forward integration, backward integration, or no vertical integration. We seek for a subgame perfect Nash equilibrium and study the resulting market structure. Moreover, we characterize the effect of vertical integration on profitability, product price, and quality in a competitive setting. Existing literature has shown that, when manufacturers consider only forward integration, they may choose not to vertically integrate in equilibrium. In contrast, we find that, when both forward and backward integration options are considered, disintegration cannot be an equilibrium outcome. In this case, both manufacturers either forward or backward integrate, and the degree of product perishability, cost of quality, and how much consumers value quality are critical for the chosen direction of integration. Furthermore, competition increases attractiveness of backward integration relative to forward integration. We show that, while integrating backward unilaterally is always beneficial, unilateral forward integration can harm a manufacturer's profitability. Finally, vertical integration can result in a better quality product sold at a lower price.
Resistance against Botrytis cinerea in smooth leaf pruning wounds of tomato does not depend on major disease signalling pathways
Authors: Beyers T. , Vos C. , Aerts R. , Heyens K. , Vogels L. , Seels B. , Höfte M. , Cammue B. P. A. , De Coninck B.
Published: May 2013

In high‐tech, heated tomato glasshouses, stem infections caused by Botrytis cinerea usually end up girdling the stem, resulting in plant death and consequently high economic losses. Such infections originate primarily from wounds created during leaf pruning, a common cultural practice in which it is intended to remove leaves completely, resulting in smooth stem wounds. However, hasty leaf pruning often results in numerous petiole stubs accidentally left behind. In this study analysis of disease incidences clearly proved that pruning leaves flush to the stem resulted in absolute resistance of the stem wounds, whereas petiole stubs displayed a high level of susceptibility to B. cinerea. Postponing inoculation of wounds after pruning indicated that development of nearly complete resistance occurs within 48 h after deleafing. Monitoring of the wound wetness period showed that drying of the wound surface is not the cause of the decreased susceptibility, contrary to what was commonly believed. Tomato mutants deficient in disease signalling showed altered phenotypes for susceptibility to B. cinerea, indicating that defences against this pathogen in petiole stubs depend on ethylene signalling. Additionally, the decreased susceptibility of mutants deficient in the biosynthesis of jasmonates and abscisic acid suggest an antagonistic effect of these signal molecules. On the other hand, resistance of smooth stem wounds could not be altered by disruption of salicylic acid, ethylene, jasmonate or abscisic acid signalling. This indicates that this remarkable absolute resistance to B. cinerea does not depend on the major disease signalling pathways.
Phylogenetic revision of the North American Asidini (Coleoptera: Tenebrionidae)
Authors: SMITH AARON D.
Published: May 2013

The asidine darkling beetles (Coleoptera: Tenebrionidae: Asidini) are a morphologically diverse tribe of flightless tenebrionids found in many arid and sub‐arid habitats around the world. The 260 currently described North American species are contained in 27 genera, all of which are restricted to the western half of the continent. Evolutionary relationships within and between the North American Asidini (Coleoptera: Tenebrionidae) genera were reconstructed using partial sequences of mitochondrial cytochrome c oxidase I (COI) (660 bp) and nuclear ribosomal 28S (D2 region) (492 bp), and 100 phenotypic characters for 50 North American asidine species, representing 20 of the 27 currently described genera and 1 new genus. Species from two additional tenebrionid tribes (Branchini and Coniontini) and the South American asidine genus Cardigenius were chosen as outgroups. Analyses were performed using maximum parsimony and Bayesian inference methods. Clade support was inferred based on the posterior probability distribution of tree topologies, nonparametric bootstrap analysis, and partitioned Bremer support indices. The generic classification of the North American Asidini is revised based on the results, with ten genera recognized. Seven current genera: Craniotus LeConte, Heterasida Casey, Litasida Casey, Microschatia Solier, Pelecyphorus Solier, Philolithus Lacordaire, Stenomorpha Solier, are redescribed, and Ardamimicus Smith gen.n., Ferveoventer Smith gen.n. and Micrasida Smith gen.n. are described, including Ardamimicus cognatoi Smith sp.n., Ferveoventer browni Smith sp.n. and Micrasida obrienorum Smith sp.n. Twenty current genera are treated as subgenera pending further analyses: Philolithus Lacordaire with subgenera Glyptasida Casey, Gonasida Casey, Herthasida Wilke and Tisamenes Champion; Pelecyphorus Solier, with subgenera: Astrotus LeConte, Parasida Casey (= Plesiasida nom.n), Poliorcetes Champion, Sicharbas Champion, Stenosides Solier, Ucalegon Champion and Zaleucus Champion, and Stenomorpha Solier with subgenera Asidina Casey, Asidopsis Casey, Bothrasida Casey, Megasida Casey, Notiasida Casey, Platasida Casey, Pycnomorpha Motschulsky, Stethasida Casey and Trichiasida Casey; all stat.rev.
Hospital‐based transfusion error tracking from 2005 to 2010: identifying the key errors threatening patient transfusion safety
Authors: Maskens Carolyn , Downie Helen , Wendt Alison , Lima Ana , Merkley Lisa , Lin Yulia , Callum Jeannie
Published: May 2013

Background

This report provides a comprehensive analysis of transfusion errors occurring at a large teaching hospital and aims to determine key errors that are threatening transfusion safety, despite implementation of safety measures.

Study Design and Methods

Errors were prospectively identified from 2005 to 2010. Error data were coded on a secure online database called the Transfusion Error Surveillance System. Errors were defined as any deviation from established standard operating procedures. Errors were identified by clinical and laboratory staff. Denominator data for volume of activity were used to calculate rates.

Results

A total of 15,134 errors were reported with a median number of 215 errors per month (range, 85‐334). Overall, 9083 (60%) errors occurred on the transfusion service and 6051 (40%) on the clinical services. In total, 23 errors resulted in patient harm: 21 of these errors occurred on the clinical services and two in the transfusion service. Of the 23 harm events, 21 involved inappropriate use of blood. Errors with no harm were 657 times more common than events that caused harm. The most common high‐severity clinical errors were sample labeling (37.5%) and inappropriate ordering of blood (28.8%). The most common high‐severity error in the transfusion service was sample accepted despite not meeting acceptance criteria (18.3%). The cost of product and component loss due to errors was $593,337.

Conclusion

Errors occurred at every point in the transfusion process, with the greatest potential risk of patient harm resulting from inappropriate ordering of blood products and errors in sample labeling.
Lung sparing and dose escalation in a robust‐inspired IMRT planning method for lung radiotherapy that accounts for intrafraction motion
Authors: McCann Claire , Purdie Thomas , Hope Andrew , Bezjak Andrea , Bissonnette Jean‐Pierre
Published: May 2013

Purpose:

To test the efficacy of a simple, robust‐inspired intensity modulated radiotherapy (IMRT) planning strategy for lung radiotherapy designed to reduce lung dose and escalate tumor dose using realistic dose accumulation tools.

Methods:

A deformable image registration tool was used to plan and accumulate dose over all phases of the breathing cycle for conventional and robust‐inspired IMRT strategies of eight nonsmall cell lung cancer patients exhibiting peak‐to‐peak respiratory motion with amplitudes ranging from 1 to 2 cm in the craniocaudal direction. The authors’ robust‐inspired plans were designed to have smaller beam apertures based on target location during exhale, combined with edge‐enhanced intensity maps to ensure target coverage during inspiration. For these, a new planning target volume defined as the rPTV was generated from a 5‐mm isotropic expansion of the clinical target volume (CTV) on end‐exhale combined with a boost volume, set to 110% of the prescription dose. Plans were evaluated in terms of (i) lung sparing and (ii) dose escalation for mean lung dose (MLD) isotoxicity. CTV and planning target volumes (PTV) coverage and lung dose were compared to the conventional IMRT approach.

Results:

Robust‐inspired plans showed potential lung dose reductions in seven out of eight patients. For non‐GTV lung, percent reductions of 3%–14% in MLD and 6%–15% in V20 were observed. For seven of eight cases, the robust‐like approach yielded increased accumulated doses to CTV. Isotoxicity studies for MLD showed increased dose to the CTV and the rPTV, in the range of 104%–118% and 95%–114% of prescription dose, respectively.

Conclusions:

A 4D dose calculation based on deformable image registration was used to evaluate a robust‐inspired planning strategy for lung radiotherapy. This method offers notable reductions to lung dose while improving tumor coverage through the use of reduced geometric margins combined with edge enhancements.
Ultrasound assessment of polymer-shelled magnetic microbubbles used as dual contrast agents
Authors: Sciallero Claudia , Trucco Andrea
Published: May 2013

This letter describes an ultrasound imaging assessment of novel contrast agents that are detectable by both medical ultrasound and magnetic resonance imaging. Such agents are created by including superparamagnetic particles in polymer-shelled microbubbles through two different approaches. The reduced echogenicity and nonlinearity of the microbubbles are observed, depending on the strategy used to include the particles and the resulting density. The best results are obtained using imaging techniques that exploit the third-order nonlinear term, which is especially true when the microbubbles are excited by means of chirp pulses.
Comment on "Stress in Puberty Unmasks Latent Neuropathological Consequences of Prenatal Immune Activation in Mice"
Authors: Lazic Stanley E.
Published: May 2013

Giovanoliet al. (Reports, 1 March 2013, p. 1095) applied an immune challenge to pregnant females, and therefore to all offspring, and subsequently applied stress to offspring on a per cage basis. The data, however, were analyzed as a completely randomized design, which is inappropriate given these restrictions on randomization. This will increase both false positives and false negatives.
Engineering Blood Vessels Through Geometry
Authors: Balcells Mercedes
Published: May 2013

Providing endothelial cells with a prefixed template enhances neovessel formation and promotes integration within engineered tissues.
Induction of Dendritic Cell Production of Type I and Type III Interferons by Wild-Type and Vaccine Strains of Measles Virus: Role of Defective Interfering RNAs
Authors: Shivakoti Rupak , Siwek Martina , Hauer Debra , Schultz Kimberly L. W. , Griffin Diane E.
Published: May 2013

The innate immune response to viral infection frequently includes induction of type I interferons (IFN), but many viruses have evolved ways to block this response and increase virulence.
In vitro
studies of IFN production after infection of susceptible cells with measles virus (MeV) have often reported greater IFN synthesis after infection with vaccine than with wild-type strains of MeV. However, the possible presence in laboratory virus stocks of 5′ copy-back defective interfering (DI) RNAs that induce IFN independent of the standard virus has frequently confounded interpretation of data from these studies. To further investigate MeV strain-dependent differences in IFN induction and the role of DI RNAs, monocyte-derived dendritic cells (moDCs) were infected with the wild-type Bilthoven strain and the vaccine Edmonston-Zagreb strain with and without DI RNAs. Production of type I IFN, type III IFN, and the interferon-stimulated genes (ISGs) Mx and ISG56 by infected cells was assessed with a flow cytometry-based IFN bioassay, quantitative reverse transcriptase PCR (RT-PCR), and immunoassays. Bilthoven infected moDCs less efficiently than Edmonston-Zagreb. Presence of DI RNAs in vaccine stocks resulted in greater maturation of moDCs, inhibition of virus replication, and induction of higher levels of IFN and ISGs. Production of type I IFN, type III IFN, and ISG mRNA and protein was determined by both the level of infection and the presence of DI RNAs. At the same levels of infection and in the absence of DI RNA, IFN induction was similar between wild-type and vaccine strains of MeV.
Adaptor Protein 1 Promotes Cross-Presentation through the Same Tyrosine Signal in Major Histocompatibility Complex Class I as That Targeted by HIV-1
Authors: Kulpa Deanna A. , Del Cid Natasha , Peterson Kirsten A. , Collins Kathleen L.
Published: May 2013

Certain antigen-presenting cells (APCs) process and present extracellular antigen with major histocompatibility complex class I (MHC-I) molecules to activate naive CD8
+
T cells in a process termed cross-presentation. We used insights gained from HIV immune evasion strategies to demonstrate that the clathrin adaptor protein adaptor protein 1 (AP-1) is necessary for cross-presentation by MHC-I molecules containing a cytoplasmic tail tyrosine signal (murine MHC-I molecules, human MHC-I HLA-A and HLA-B allotypes). In contrast, AP-1 activity was not needed for cross-presentation by MHC-I molecules containing a human MHC-I HLA-C cytoplasmic tail, which does not contain a tyrosine signal. AP-1 activity was also dispensable for presentation of endogenous antigens by MHC-I via the classical pathway. In APCs, we show that HIV Nef disrupts cross-presentation by MHC-I containing the tyrosine signal but does not affect cross-presentation by MHC-I containing the HLA-C cytoplasmic tail. Thus, we provide evidence for two separable cross-presentation pathways, only one of which is targeted by HIV.
Analysis of the Role of Vaccinia Virus H7 in Virion Membrane Biogenesis with an H7-Deletion Mutant
Authors: Meng Xiangzhi , Wu Xiang , Yan Bo , Deng Junpeng , Xiang Yan
Published: May 2013

Essential vaccinia virus genes are often studied with conditional-lethal inducible mutants. Here, we constructed a deletion mutant lacking the essential H7R gene (the ΔH7 mutant) with an H7-expressing cell line. Compared to an inducible H7 mutant, the ΔH7 mutant showed a defect at an earlier step of virion membrane biogenesis, before the development of short crescent-shaped precursors of the viral envelope. Our studies refine the role of H7 in virion membrane biogenesis and highlight the values of analyzing deletion mutants.
Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus Entry That Act by Three Distinct Mechanisms
Authors: Adedeji Adeyemi O. , Severson William , Jonsson Colleen , Singh Kamalendra , Weiss Susan R. , Sarafianos Stefan G.
Published: May 2013

Severe acute respiratory syndrome (SARS) is an infectious and highly contagious disease that is caused by SARS coronavirus (SARS-CoV) and for which there are currently no approved treatments. We report the discovery and characterization of small-molecule inhibitors of SARS-CoV replication that block viral entry by three different mechanisms. The compounds were discovered by screening a chemical library of compounds for blocking of entry of HIV-1 pseudotyped with SARS-CoV surface glycoprotein S (SARS-S) but not that of HIV-1 pseudotyped with vesicular stomatitis virus surface glycoprotein G (VSV-G). Studies on their mechanisms of action revealed that the compounds act by three distinct mechanisms: (i) SSAA09E2 {
N
-[[4-(4-methylpiperazin-1-yl)phenyl]methyl]-1,2-oxazole-5-carboxamide} acts through a novel mechanism of action, by blocking early interactions of SARS-S with the receptor for SARS-CoV, angiotensin converting enzyme 2 (ACE2); (ii) SSAA09E1 {[(
Z
)-1-thiophen-2-ylethylideneamino]thiourea} acts later, by blocking cathepsin L, a host protease required for processing of SARS-S during viral entry; and (iii) SSAA09E3 [
N
-(9,10-dioxo-9,10-dihydroanthracen-2-yl)benzamide] also acts later and does not affect interactions of SARS-S with ACE2 or the enzymatic functions of cathepsin L but prevents fusion of the viral membrane with the host cellular membrane. Our work demonstrates that there are at least three independent strategies for blocking SARS-CoV entry, validates these mechanisms of inhibition, and introduces promising leads for the development of SARS therapeutics.
Epstein-Barr Virus-Encoded MicroRNA BART15-3p Promotes Cell Apoptosis Partially by Targeting BRUCE
Authors: Choi Hoyun , Lee Hanna , Kim Sae Rom , Gho Yong Song , Lee Suk Kyeong
Published: May 2013

Epstein-Barr Virus (EBV) generates a variety of viral microRNAs (miRNAs) by processing the BHRF1 and BamHI A rightward (BART) transcripts. BART miRNAs are expressed in all cells latently infected with EBV, but the functions of most BART miRNAs remain unknown. The results of a cell proliferation assay revealed that miR-BART15-3p inhibited cell proliferation. Fluorescence-activated cell sorting following staining with annexin V or propidium iodide showed that miR-BART15-3p promoted apoptosis. Furthermore, the inhibitor for miR-BART15-3p increased cell growth and reduced apoptosis in EBV-infected cells. Using bioinformatic analyses, we predicted that miR-BART15-3p may target the antiapoptotic B-cell lymphoma 2 (BCL2), BCL2L2, DEAD (Asp-Glu-Ala-Asp) box polypeptide 42 (DDX42), and baculovirus inhibitor of apoptosis repeat-containing ubiquitin-conjugating enzyme (BRUCE) mRNAs. The luciferase reporter assay showed that only the 3′ untranslated region (UTR) of BRUCE was affected by miR-BART15-3p. Two putative seed-matched sites for miR-BART15-3p were evident on the BRUCE 3′ UTR. The results of a mutation study indicated that miR-BART15-3p hybridized only with the first seed-matched site on the BRUCE 3′ UTR. miR-BART15-3p downregulated the BRUCE protein in EBV-negative cells, while the inhibitor for miR-BART15-3p upregulated the BRUCE protein in EBV-infected cells without affecting the BRUCE mRNA level. miR-BART15-3p was secreted from EBV-infected gastric carcinoma cells, and the level of miR-BART15-3p was 2- to 16-fold higher in exosomes than in the corresponding cells. Our data suggest that miR-BART15-3p can induce apoptosis partially by inhibiting the translation of the apoptosis inhibitor BRUCE. Further study is warranted to understand the role of miR-BART15-3p in the EBV life cycle.
Phosphorylation of Kaposi's Sarcoma-Associated Herpesvirus Processivity Factor ORF59 by a Viral Kinase Modulates Its Ability To Associate with RTA and
ori
Lyt
Authors: McDowell Maria E. , Purushothaman Pravinkumar , Rossetto Cyprian C. , Pari Gregory S. , Verma Subhash C.
Published: May 2013

ORF59 of Kaposi's sarcoma-associated herpesvirus (KSHV) plays an essential role in viral lytic replication by providing DNA processivity activity to the viral DNA polymerase (ORF9). ORF59 forms a homodimer in the cytoplasm and binds and translocates ORF9 into the nucleus, where it secures ORF9 to the origin of lytic DNA replication (
ori
Lyt) in order to synthesize long DNA fragments during replication. ORF59 binds to
ori
Lyt through an immediate early protein, replication and transcription activator (RTA). Here, we show that viral kinase (ORF36) phosphorylates serines between amino acids 376 and 379 of ORF59 and replacement of the Ser378 residue with alanine significantly impairs phosphorylation. Although mutating these serine residues had no effect on binding between ORF59 and ORF9, viral polymerase, or ORF36, the viral kinase, it significantly reduced the ability of ORF59 to bind to RTA. The results for the mutant in which Ser376 to Ser379 were replaced by alanine showed that both Ser378 and Ser379 contribute to binding to RTA. Additionally, the Ser376, Ser378, and Ser379 residues were found to be critical for binding of ORF59 to
ori
Lyt and its processivity function. Ablation of these phosphorylation sites reduced the production of virion particles, suggesting that phosphorylation is critical for ORF59 activity and viral DNA synthesis.
Reninoma: a rare cause of curable hypertension
Authors: Venkateswaran Ramanathan , Hamide Abdoul , Dorairajan Lalgudi Narayanan , Basu Debdatta
Published: May 2013

A 25-year-old lady presented with hypertensive encephalopathy. She also had chronic refractory hypertension for the past 7  years. Workup revealed persistent hypokalaemia with metabolic alkalosis suggesting hyperaldosteronism. Hyperaldosteronic states such as renal artery stenosis, Conn's syndrome and Liddle's syndrome were ruled out. Her plasma renin activity was high. Contrast-enhanced CT of the abdomen showed a 1.9×2 cm heterogeneously enhancing lesion in the anterior aspect of the right kidney suggesting a possibility of reninoma. The benign tumour was resected by a nephron-sparing surgery. Histopathology suggested a juxtaglomerular cell tumour. Anti-hypertensive drugs were completely withdrawn postoperatively.
Presacral tumours: a rare case of a dermoid cyst in a paediatric patient
Authors: Jones Matthew , Khosa Japinder
Published: May 2013

Presacral tumours are considered very rare tumours with their incidence being around 1:40 000. Presacral dermoid tumours, part of the family of presacral tumours, usually present in the female adult population. They are benign tumours arising from all the three germ cell layers. Presentation in a paediatric population, defined as an individual under the age of 18 years, is extremely rare. A 15-year-old girl presented with abdominal pain present for 5 years diagnosed as a somatisation disorder. Upon further investigation with abdominal CT and MRI a diagnosis of a presacral mass was made. A laparoscopic-assisted transabdominal excision of the mass was performed and histopathology confirmed the radiological suspicion of a presacral dermoid cyst. As there are no reports of a presacral dermoid cysts being excised and reported in the paediatric surgical literature, we hope to highlight this pathology as a potential cause of abdominal pain in the paediatric population.
Active haemorrhage of a renal allograft detected on portable ultrasound
Authors: Ricketts James , Pang Chun Lap , Dissanayake Prageeth , Hutchinson Rachel , Gutteridge Catherine
Published: May 2013

Function of a renal allograft relies on the integrity of its vascular anatomy. Renal biochemistry, ultrasound and percutaneous biopsy are used in combination to determine allograft function. Biopsy is not without risk, and in this case study we demonstrate a rare but a potentially life-threatening complication of renal allograft biopsy.
Addressing the human resources crisis: a case study of Cambodia’s efforts to reduce maternal mortality (1980–2012)
Authors: Fujita Noriko , Abe Kimiko , Rotem Arie , Tung Rathavy , Keat Phuong , Robins Ann , Zwi Anthony B
Published: May 2013

Objective

To identify factors that have contributed to the systematic development of the Cambodian human resources for health (HRH) system with a focus on midwifery services in response to high maternal mortality in fragile resource-constrained countries.

Design

Qualitative case study. Review of the published and grey literature and in-depth interviews with key informants and stakeholders using an HRH system conceptual framework developed by the authors (‘House Model’; Fujita et al, 2011). Interviews focused on the perceptions of respondents regarding their contributions to strengthening midwifery services and the other external influences which may have influenced the HRH system and reduction in the maternal mortality ratio (MMR).

Setting

Three rounds of interviews were conducted with senior and mid-level managers of the Ministries of Health (MoH) and Education, educational institutes and development partners.

Participants

A total of 49 interviewees, who were identified through a snowball sampling technique.

Main outcome measures

Scaling up the availability of 24 h maternal health services at all health centres contributing to MMR reduction.

Results

The incremental development of the Cambodian HRH system since 2005 focused on the production, deployment and retention of midwives in rural areas as part of a systematic strategy to reduce maternal mortality. The improved availability and access to midwifery services contributed to significant MMR reduction. Other contributing factors included improved mechanisms for decision-making and implementation; political commitment backed up with necessary resources; leadership from the top along with a growing capacity of mid-level managers; increased MoH capacity to plan and coordinate; and supportive development partners in the context of a conducive external environment.

Conclusions

Lessons from this case study point to the importance of a systemic and comprehensive approach to health and HRH system strengthening and of ongoing capacity enhancement and leadership development to ensure effective planning, implementation and monitoring of HRH policies and strategies.
Dry blood spot testing for hepatitis C in people who injected drugs: reaching the populations other tests cannot reach
Authors: Tait J M , Stephens Brian P , McIntyre Paul G , Evans Morgan , Dillon John F
Published: May 2013

Objective

The aim of the study was to evaluate the effectiveness of Dry Blood Spot testing (DBST) for hepatitis C within a geographical area.

Design

This is a prospective cohort study of all individuals living in Tayside who had received a hepatitis C virus (HCV) DBST between 2009 and 2011.

Results

During the study, 1123 DBSTs were carried out. 946 individuals had one test. 295 (31.2%) of these individuals were HCV antibody positive on their first test. Overall, 94.3% (902/956) individuals returned for the results of their test. During the course of the study 177 individuals were retested and 29 new cases of hepatitis C were detected. 249 individuals attended for further follow-up, and 164 (65.5%) were PCR positive. All 164 PCR-positive individuals were offered referral into specialist HCV services for further assessment. Data showed 62.5% were genotype 3, 65.1% had a low viral load (<600 000 iu/ml) and 77.5% had a Fibroscan score below 7 KPa. To date, 40 have commenced treatment and a further 16 are currently in the assessment period. Overall, we have retained in services or treated 63.6% (105/164) of patients who were initially referred and with effective support mechanisms in place we have achieved sustained viral response rates of 90%.

Conclusions

The study has shown that DBST is a complementary technique to conventional venepuncture for the diagnosis of HCV. The majority of patients have low viral loads and low fibrosis scores, so that while this group of patients may be difficult to reach and may be challenging to maintain in therapy, they are easier to cure.
Comparison of heart and respiratory rate variability measures using an intermittent incremental submaximal exercise model
Authors: Barrera-Ramirez Juliana , Bravi Andrea , Green Geoffrey , Seely Andrew J. , Kenny Glen P.
Published: May 2013

To better understand the alterations in cardiorespiratory variability during exercise, the present study characterized the patterns of change in heart rate variability (HRV), respiratory rate variability (RRV), and combined cardiorespiratory variability (HRV–RRV) during an intermittent incremental submaximal exercise model. Six males and six females completed a submaximal exercise protocol consisting of an initial baseline resting period followed by three 10-min bouts of exercise at 20%, 40%, and 60% of maximal aerobic capacity (V̇O2max). The R–R interval and interbreath interval variability were measured at baseline rest and throughout the submaximal exercise. A group of 93 HRV, 83 RRV, and 28 HRV–RRV measures of variability were tracked over time through a windowed analysis using a 5-min window size and 30-s window step. A total of 91 HRV measures were able to detect the presence of exercise, whereas only 46 RRV and 3 HRV–RRV measures were able to detect the same stimulus. Moreover, there was a loss of overall HRV and RRV, loss of complexity of HRV and RRV, and loss of parasympathetic modulation of HRV (up to 40% V̇O2max) with exercise. Conflicting changes in scale-invariant structure of HRV and RRV with increases in exercise intensity were also observed. In summary, in this simultaneous evaluation of HRV and RRV, we found more consistent changes across HRV metrics compared with RRV and HRV–RRV.
Damage to industrial structures due to the 27 February 2010 Chile earthquake
Authors: Tremblay Robert , Mitchell Denis , Tinawi René
Published: May 2013

This paper provides a summary of the damage to industrial facilities in the Mw 8.8 Chile earthquake of 27 February 2010. The types of damage observed include failure of elevated tanks, collapse and cracking of concrete silos, buckling of steel silos, collapse of conveyor systems, failure of steel bins, and failure of anchor rods. Damage to industrial buildings included buckling of bracing members, failure of brace connections, shear failures of reinforced concrete columns, and shear failures of heavily loaded steel girders. Aspects of the current Chilean design code for industrial structures are reviewed and discussed. Recommendations are proposed for the development of Canadian seismic design provisions for industrial structures.
Spectrum of a microcavity with single quantum nonlinearity
Authors: Guo Xiaoyong , An Liqun , Ren Xiaobin , Ren Zhongzhou
Published: May 2013

In this paper, we investigate the emission spectrum of a nonlinear microcavity at the level of individual quantum. The physical system consists of one coherently pumped microcavity in which a self-interacting bosonic matter field strongly couples with the cavity field. By the master equation treatment, we obtain an analytical expression for the emission spectrum of the cavity. It is found that when the strength of the bosonic nonlinear effect is greater than a critical level, the spectrum of the single-mode cavity field is divided into doublet peaks. Furthermore, we also study the influence of the detuning between cavity field and matter field on the emission property. We show that the emission intensity is enhanced by negative detuning and suppressed by positive detuning.
EVIDENCE ON TWO-WAY RELATIONSHIPS BETWEEN FOREIGN DIRECT INVESTMENT INFLOWS AND COUNTRY-LEVEL INDIVIDUAL GOVERNANCE INDICATORS
Authors: FAROOQUE OMAR AL , YARRAM SUBBA REDDY
Published: May 2013

This paper investigates the interactions between foreign direct investment (FDI) and country-level individual governance indicators for a sample of 173 countries from 1996 to 2007, and also the effect of legal origin, international financial reporting standards (IFRS) and ownership diffusion on them. We find evidence of positively significant two-way relationships between each of the six individual governance indicators and lagged FDI inflows scaled by lagged GDP to confirm that governance is a function of FDI inflows and vice-versa. The overall interpretation of the results is that FDI inflows, IFRS, ownership diffusion and legal framework of a country 'matter' for macro-level governance in a competitive global business environment while FDI inflows are dependent on individual governance indicators and other macro-economic variables to a large extent. Both IFRS and legal origin have no direct link to FDI inflow. These findings have policy implications for individual governments and international donor organizations to undertake tenable actions for the improvement of country-level individual governance indicators to attract more FDI inflow.
INVESTIGATION OF MECHANICAL DAMPING CHARACTERISTIC IN SHORT FIBERGLASS REINFORCED POLYCARBONATE COMPOSITES
Authors: CHO MYOUNG-RAE , KIM HYUNG-ICK , JANG JAE-SOON , SUHR JONGHWAN , PRATE DEVIN R. , CHUN DAVID
Published: May 2013

The focus of this study is to experimentally investigate the effect of debonding stress, the interface between the fibers and the polymer matrix, on the damping properties of the short fiberglass reinforced polymer composites. In this study, short fiberglass reinforced polycarbonate composite materials were fabricated and characterized for their tensile properties by varying the fiberglass loading fraction. The debonding stress was evaluated by coupling the acoustic emission technique with the tensile testing. After the determination of the debonding stress was completed, dynamic cyclic testing was performed in order to investigate the effect of debonding on the damping properties of the polymer composites. It was experimentally observed in this study that the debonding can facilitate the stick-slip friction under cyclic loadings, which then gives rise to better damping performance in the fiberglass composites.
A GALLERY OF LORENZ-LIKE AND CHEN-LIKE ATTRACTORS
Authors: WANG XIONG , CHEN GUANRONG
Published: May 2013

In this article, three-dimensional autonomous chaotic systems with two quadratic terms, similar to the Lorenz system in their algebraic forms, are studied. An attractor with two clearly distinguishable scrolls similar to the Lorenz attractor is referred to as a Lorenz-like attractor, while an attractor with more intertwine between the two scrolls similar to the Chen attractor is referred to as a Chen-like attractor. A gallery of Lorenz-like attractors and Chen-like attractors are presented. For several different families of such systems, through tuning only one real parameter gradually, each of them can generate a spectrum of chaotic attractors continuously changing from a Lorenz-like attractor to a Chen-like attractor. Some intrinsic relationships between the Lorenz system and the Chen system are revealed and discussed. Some common patterns of the Lorenz-like and Chen-like attractors are found and analyzed, which suggest that the instability of the two saddle-foci of such a system somehow determines the shape of its chaotic attractor. These interesting observations on the general dynamic patterns hopefully could shed some light for a better understanding of the intrinsic relationships between the algebraic structures and the geometric attractors of these kinds of chaotic systems.
INTEGRABILITY AND BIFURCATIONS OF LIMIT CYCLES IN A CUBIC KOLMOGOROV SYSTEM
Authors: LI FENG
Published: May 2013

We investigate the planar cubic Kolmogorov systems with three invariant algebraic curves which have a equilibrium at (1,1). With the help of computer algebra system MATHEMATICA, we prove that five limit cycles can be bifurcated from a critical point in the first quadrant. Moreover, the necessary conditions of center are obtained, by technical transformation, and its sufficiencies are proved.
COMPLEX DYNAMICS AND FAST-SLOW SCALE INSTABILITY IN CURRENT-MODE CONTROLLED BUCK CONVERTER WITH CONSTANT CURRENT LOAD
Authors: ZHOU GUOHUA , BAO BOCHENG , XU JIANPING
Published: May 2013

The complex dynamics and coexisting fast-slow scale instability in current-mode controlled buck converter with constant current load (CCL), operating in both continuous conduction mode (CCM) and discontinuous conduction mode (DCM), are investigated in this paper. Via cycle-by-cycle computer simulation and experimental measurement of current-mode controlled buck converter with CCL, it is found that a unique fast-slow scale instability exists in the second-order switching converter. It is also found that a unique period-doubling accompanied by Neimark–Sacker bifurcation exists in this simple second-order converter, which is different from period-doubling or Neimark–Sacker bifurcations reported previously. Based on a nonlinear discrete-time model and the corresponding Jacobian, the effects of CCL and input voltage on the dynamics of current-mode controlled buck converter are investigated and verified theoretically. Fixed point analysis for slow-scale low-frequency oscillation is also given to verify the dynamics and the coexisting fast-slow scale instability.
LOWER BOUNDS FOR THE MAXIMUM NUMBER OF LIMIT CYCLES OF DISCONTINUOUS PIECEWISE LINEAR DIFFERENTIAL SYSTEMS WITH A STRAIGHT LINE OF SEPARATION
Authors: LLIBRE J. , TEIXEIRA M. A. , TORREGROSA J.
Published: May 2013

In this paper, we provide a lower bound for the maximum number of limit cycles of planar discontinuous piecewise linear differential systems defined in two half-planes separated by a straight line. Here, we only consider nonsliding limit cycles. For those systems, the interior of any limit cycle only contains a unique equilibrium point or a unique sliding segment. Moreover, the linear differential systems that we consider in every half-plane can have either a focus (F), or a node (N), or a saddle (S), these equilibrium points can be real or virtual. Then, we can consider six kinds of planar discontinuous piecewise linear differential systems: FF, FN, FS, NN, NS, SS. We provide for each of these types of discontinuous differential systems examples with two limit cycles.
ON THE DEHN COMPLEX OF VIRTUAL LINKS
Authors: BYRD RACHEL , HARLANDER JENS
Published: May 2013

A virtual link comes with a variety of link complements. This paper is concerned with the Dehn space, a pseudo-manifold with boundary, and the Dehn complex, a two-dimensional spine of the Dehn space. In the classical case where the link is planar, the Dehn space is the link complement in the 3-sphere. We study topological and geometric properties of the Dehn complex of a virtual link. Among other things, we show that every finitely presented group is the fundamental group of a Dehn complex, and that the Dehn complex of any alternating triple of an alternating virtual link is a non-positively curved squared complex.