bluuebunny/crossref_metadata_2025 huggingface dataset:
Near-Field Interference for the Unidirectional Excitation of Electromagnetic Guided Modes
Authors: Rodríguez-Fortuño Francisco J. , Marino Giuseppe , Ginzburg Pavel , O’Connor Daniel , Martínez Alejandro , Wurtz Gregory A. , Zayats Anatoly V.
Published: April 2013

Controlling Light Propagation

Surface plasmons are light-induced collective electronic excitations in a metal that offer the possibility of manufacturing optoelectronic devices at nanometer scale. Before such shrinking can be achieved, the propagation direction and lifetime of the plasmonic excitations have to be controlled (see the Perspective by

Miroshnichenko and Kivshar

).

Rodríguez-Fortuño
et al.

(p.
328
) show how this is done using polarized light. Alternatively, using an array of metallic nanoantennae (in this case, slits) patterned into a thin gold film,

Lin
et al.

(p.
331
) present a further improvement on current plasmonic coupling schemes that has the potential to encode information contained in both the intensity and polarization of light.
Representation of Three-Dimensional Space in the Hippocampus of Flying Bats
Authors: Yartsev Michael M. , Ulanovsky Nachum
Published: April 2013

Bats, Grids, and Oscillations

Nearly all animals move around in a three-dimensional (3D) world; however, very little is known about the neural circuitry underlying the representation of 3D space (see the Perspective by

Barry and Doeller

). Using whole-cell patch recordings in slices of entorhinal cortex,

Heys
et al.

(p.
363
) found that bat entorhinal stellate cells must generate grid patterns without theta-frequency oscillatory mechanisms. In another study,
Yartsev and Ulanovsky
(p.
367
) used telemetry to record activity from the hippocampus of bats while they were flying around. They found that active pyramidal cells—or place cells—in hippocampal area CA1 fired in positions, depending on where the animals were in the room.
Driven by Diversity
Authors: Ferrini-Mundy Joan
Published: April 2013

Evidence is growing on benefits, and approaches, to increase diversity in the science and engineering workforce.
Pursuing Near-Zero Response
Authors: Engheta Nader
Published: April 2013

A class of metamaterials designed with low permittivity provides a platform for developing optical devices with unconventional properties.
Prioritizing Science Education
Authors: Alberts Bruce
Published: April 2013

This special issue of
Science
explores “Grand Challenges in Science Education,” a critical set of the problems and exciting opportunities now facing science education on a global level. The 20 Challenges, addressed by a team of education experts, range from “Enable students to build on their own enduring, science-related interests” to “Shift incentives to encourage education research on the real problems of practice as they exist in school settings.” Here I propose three additional Grand Challenges. These focus on harnessing the wisdom of teachers, helping the business community promote new directions in precollege science education, and—last but not least—catalyzing major changes in the way we teach college-level science.
Rare Cancer Successes Spawn ‘Exceptional’ Research Efforts
Authors: Kaiser Jocelyn
Published: April 2013

The U.S. National Cancer Institute announced that it is casting a wide net for such "exceptional responders" to experimental cancer drugs that are often shelved.
Transformation Is Possible if a University Really Cares
Authors: Mervis Jeffrey
Published: April 2013

The same attention to scientific detail that led to his Nobel Prize is helping Carl Wieman improve how undergraduates learn science.
Evaluation of RevA, a Fibronectin-Binding Protein of Borrelia burgdorferi, as a Potential Vaccine Candidate for Lyme Disease
Authors: Floden Angela M. , Gonzalez Tammy , Gaultney Robert A. , Brissette Catherine A.
Published: April 2013

Previous studies indicated that the Lyme disease spirochete
Borrelia burgdorferi
expresses the RevA outer surface protein during mammalian infection. As an adhesin that promotes bacterial interaction with fibronectin, RevA appears to be a good target for preventive therapies. RevA proteins are highly conserved across all Lyme borreliae, and antibodies against RevA protein are cross-reactive among RevA proteins from diverse strains. Mice infected with
B. burgdorferi
mounted a rapid IgM response to RevA, followed by a strong IgG response that generally remained elevated for more than 12 months, suggesting continued exposure of RevA protein to the immune system. RevA antibodies were bactericidal
in vitro
. To evaluate the RevA antigen as a potential vaccine, mice were vaccinated with recombinant RevA and challenged with
B. burgdorferi
by inoculation with a needle or by a tick bite. Cultured tissues from all treatment groups were positive for
B. burgdorferi
. Vaccinated animals also appeared to have similar levels of
B. burgdorferi
DNA compared to nonvaccinated controls. Despite its antigenicity, surface expression, and the production of bactericidal antibodies against it, RevA does not protect against
Borrelia burgdorferi
infection in a mouse model. However, passive immunization with anti-RevA antibodies did prevent infection, suggesting the possible utility of RevA-based immunotherapeutics or vaccine.
PCR-Electrospray Ionization Mass Spectrometry for Direct Detection of Pathogens and Antimicrobial Resistance from Heart Valves in Patients with Infective Endocarditis
Authors: Brinkman Cassandra L. , Vergidis Paschalis , Uhl James R. , Pritt Bobbi S. , Cockerill Franklin R. , Steckelberg James M. , Baddour Larry M. , Maleszewski Joseph J. , Edwards William D. , Sampath Rangarajan , Patel Robin
Published: April 2013

Microbiological diagnosis is pivotal to the appropriate management and treatment of infective endocarditis. We evaluated PCR-electrospray ionization mass spectrometry (PCR/ESI-MS) for bacterial and candidal detection using 83 formalin-fixed paraffin-embedded heart valves from subjects with endocarditis who had positive valve and/or blood cultures, 63 of whom had positive valvular Gram stains. PCR/ESI-MS yielded 55% positivity with concordant microbiology at the genus/species or organism group level (e.g., viridans group streptococci), 11% positivity with discordant microbiology, and 34% with no detection. PCR/ESI-MS detected all antimicrobial resistance encoded by
mecA
or
vanA
/
B
and identified a case of
Tropheryma whipplei
endocarditis not previously recognized.
Results of External Quality Assessment for Proviral DNA Testing of HIV Tropism in the Maraviroc Switch Collaborative Study
Authors: Tu Elise , Swenson Luke C. , Land Sally , Pett Sarah , Emery Sean , Marks Kat , Kelleher Anthony D. , Kaye Steve , Kaiser Rolf , Schuelter Eugene , Harrigan Richard
Published: April 2013

The
Mar
aviroc Swit
ch
collaborative study (MARCH) is a study in aviremic patients on stable antiretroviral therapy and utilizes population-based sequencing of proviral DNA to determine HIV tropism and susceptibility to maraviroc. An external quality assessment (EQA) program was implemented to ensure competency in assessing the tropism of clinical samples conducted by MARCH laboratories (
n
= 14). The MARCH EQA has three prestudy phases assessing V3 loop sequencing and tropism determination using the bioinformatic algorithm geno2pheno, which generates a false-positive rate (FPR). DNA sequences with low FPRs are more likely to be from CXCR4-using (X4) viruses. Phase 1 of the EQA involved chromatogram interpretation. Phases 2, 2/3, and 3 involved patient and clonal samples. Clinical samples used in these phases were from treatment-experienced HIV-infected volunteers; 18/20 had viral loads of <50 copies/ml, and 10/15 were CXCR4-tropic on prior phenotyping. All samples were tested in triplicate, and any replicate with a geno2pheno FPR of <10% was designated X4. Performance was deemed adequate if ≤2 R5 and ≤1 X4 specimens were miscalled. For several clinical samples in the EQA, triplicate testing revealed marked DNA variability (FPR range, 0 to 96.7%). Therefore, a consensus-based approach was employed for each sample, i.e., a median FPR across laboratories was used to define sample tropism. Further sequencing analysis showed mixed viral populations in the clinical samples, explaining the differences in tropism predictions. All laboratories passed the EQA after achieving predefined competence thresholds in either of the phase 2 rounds. The use of clinical samples from patients resembling those who were likely to be screened in the MARCH, coupled with triplicate testing, revealed inherent DNA variability that might have been missed if single or duplicate testing and/or clonal samples alone were used. These data highlight the importance of intensive EQA of tropism laboratories before embarking on clinical studies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01384682 [
http://www.clinicaltrials.gov/ct2/show/study/NCT01384682?term=NCT01384682&rank=1
].)
Influence of Clinical Breakpoint Changes from CLSI 2009 to EUCAST 2011 Antimicrobial Susceptibility Testing Guidelines on Multidrug Resistance Rates of Gram-Negative Rods
Authors: Hombach Michael , Wolfensberger Aline , Kuster Stefan P. , Böttger Erik C.
Published: April 2013

Multidrug resistance (MDR) rates of Gram-negative rods were analyzed comparing CLSI 2009 and EUCAST 2011 antibiotic susceptibility testing guidelines. After EUCAST 2011 was applied, the MDR rates increased for
Klebsiella pneumoniae
(2.2%),
Enterobacter cloacae
(1.1%),
Pseudomonas aeruginosa
(0.7%), and
Escherichia coli
(0.4%). A total of 24% of
Enterobacteriaceae
MDR isolates and 12% of
P. aeruginosa
MDR isolates were categorized as MDR due to breakpoint changes.
The Structure of the Herpes Simplex Virus DNA-Packaging Terminase pUL15 Nuclease Domain Suggests an Evolutionary Lineage among Eukaryotic and Prokaryotic Viruses
Authors: Selvarajan Sigamani Sundaresan , Zhao Haiyan , Kamau Yvonne N. , Baines Joel D. , Tang Liang
Published: April 2013

Herpes simplex virus 1 (HSV-1), the prototypic member of herpesviruses, employs a virally encoded molecular machine called terminase to package the viral double-stranded DNA (dsDNA) genome into a preformed protein shell. The terminase contains a large subunit that is thought to cleave concatemeric viral DNA during the packaging initiation and completion of each packaging cycle and supply energy to the packaging process via ATP hydrolysis. We have determined the X-ray structure of the C-terminal domain of the terminase large-subunit pUL15 (pUL15C) from HSV-1. The structure shows a fold resembling those of bacteriophage terminases, RNase H, integrases, DNA polymerases, and topoisomerases, with an active site clustered with acidic residues. Docking analysis reveals a DNA-binding surface surrounded by flexible loops, indicating considerable conformational changes upon DNA binding.
In vitro
assay shows that pUL15C possesses non-sequence-specific, Mg
2+
-dependent nuclease activity. These results suggest that pUL15 uses an RNase H-like, metal ion-mediated catalysis mechanism for cleavage of viral concatemeric DNA. The structure reveals extra structural elements in addition to the RNase H-like fold core and variations in local architecture of the nuclease active site, which are conserved in herpesvirus terminases and bear great similarity to the phage T4 gp17 but are distinct from podovirus and siphovirus orthologs and cellular RNase H, delineating a new evolutionary lineage among a large family of eukaryotic viruses and simple and complex prokaryotic viruses.
Identification of a Pegivirus (GB Virus-Like Virus) That Infects Horses
Authors: Kapoor Amit , Simmonds Peter , Cullen John M. , Scheel Troels K. H. , Medina Jan L. , Giannitti Federico , Nishiuchi Eiko , Brock Kenny V. , Burbelo Peter D. , Rice Charles M. , Lipkin W. Ian
Published: April 2013

The recent identification of nonprimate hepaciviruses in dogs and then in horses prompted us to look for pegiviruses (GB virus-like viruses) in these species. Although none were detected in canines, we found widespread natural infection of horses by a novel pegivirus. Unique genomic features and phylogenetic analyses confirmed that the tentatively named equine pegivirus (EPgV) represents a novel species within the
Pegivirus
genus. We also determined that EPgV causes persistent viremia whereas its clinical significance is undetermined.
Comprehensive Analysis of Varicella-Zoster Virus Proteins Using a New Monoclonal Antibody Collection
Authors: Lenac Roviš Tihana , Bailer Susanne M. , Pothineni Venkata R. , Ouwendijk Werner J. D. , Šimić Hrvoje , Babić Marina , Miklić Karmela , Malić Suzana , Verweij Marieke C. , Baiker Armin , Gonzalez Orland , von Brunn Albrecht , Zimmer Ralf , Früh Klaus , Verjans Georges M. G. M. , Jonjić Stipan , Haas Jürgen
Published: April 2013

Varicella-zoster virus (VZV) is the etiological agent of chickenpox and shingles. Due to the virus's restricted host and cell type tropism and the lack of tools for VZV proteomics, it is one of the least-characterized human herpesviruses. We generated 251 monoclonal antibodies (MAbs) against 59 of the 71 (83%) currently known unique VZV proteins to characterize VZV protein expression
in vitro
and
in situ
. Using this new set of MAbs, 44 viral proteins were detected by Western blotting (WB) and indirect immunofluorescence (IF); 13 were detected by WB only, and 2 were detected by IF only. A large proportion of viral proteins was analyzed for the first time in the context of virus infection. Our study revealed the subcellular localization of 46 proteins, 14 of which were analyzed in detail by confocal microscopy. Seven viral proteins were analyzed in time course experiments and showed a cascade-like temporal gene expression pattern similar to those of other herpesviruses. Furthermore, selected MAbs tested positive on human skin lesions by using immunohistochemistry, demonstrating the wide applicability of the MAb collection. Finally, a significant portion of the VZV-specific antibodies reacted with orthologs of simian varicella virus (SVV), thus enabling the systematic analysis of varicella in a nonhuman primate model system. In summary, this study provides insight into the potential function of numerous VZV proteins and novel tools to systematically study VZV and SVV pathogenesis.
Inhibition of the HIV-1 Spike by Single-PG9/16-Antibody Binding Suggests a Coordinated-Activation Model for Its Three Protomeric Units
Authors: Löving Robin , Sjöberg Mathilda , Wu Shang-Rung , Binley James M. , Garoff Henrik
Published: April 2013

The HIV-1 spike is composed of three protomeric units, each containing a peripheral gp120 and a transmembrane gp41 subunit. Binding to the CD4 and the chemokine receptors triggers them to mediate virus entry into cells by membrane fusion. The spikes also represent the major target for neutralizing antibodies (Abs) against the virus. We have studied how two related broadly neutralizing Abs, PG9 and PG16, react with the spike. Unexpectedly, this also suggested how the functions of the individual protomers in the spike depend on each other. The Abs have been shown to bind the V1/V2 loops of gp120, located at the top of the spike. Using blue native-polyacrylamide gel electrophoresis (BN-PAGE), we show that only single Abs or antigen-binding fragments could bind to the spikes of HIV-1 virus-like particles. Apparently, binding to one gp120 sterically interferes with binding to the other two subunits in the spike top. Despite this constraint, all of the protomers of the spike became resistant to CD4 binding and subsequent formation of the coreceptor binding site. These activities were measured by monitoring the sequential complex formation of the spike first with Abs and then with soluble 2d- or 4d-CD4 or with soluble CD4 and the CD4 inducible coreceptor binding site Ab 17b in BN-PAGE. The inhibition of the spike by single-Ab binding suggested that the activation reactions of the individual protomeric units are linked to each other in a coordinated activation process.
Simultaneous Neutralization and Innate Immune Detection of a Replicating Virus by TRIM21
Authors: Watkinson R. E. , Tam J. C. H. , Vaysburd M. J. , James L. C.
Published: April 2013

Tripartite motif-containing 21 (TRIM21) is a cytosolic immunoglobulin receptor that mediates antibody-dependent intracellular neutralization (ADIN). Here we show that TRIM21 potently inhibits the spreading infection of a replicating cytopathic virus and activates innate immunity. We used a quantitative PCR (qPCR)-based assay to measure
in vitro
replication of mouse adenovirus type 1 (MAV-1), a virus that causes dose-dependent hemorrhagic encephalitis in mice. Using this assay, we show that genetic ablation of TRIM21 or chemical inhibition of either the AAA ATPase p97/valosin-containing protein (VCP) or the proteasome results in a >1,000-fold increase in the relative level of infection in the presence of immune serum. Moreover, the TRIM21-mediated ability of antisera to block replication was a consistent feature of the humoral immune response in immunized mice. In the presence of immune sera and upon infection, TRIM21 also activates a proinflammatory response, resulting in secretion of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). These results demonstrate that TRIM21 provides a potent block to spreading infection and induces an antiviral state.
Differing Effects of Herpes Simplex Virus 1 and Pseudorabies Virus Infections on Centrosomal Function
Authors: Pasdeloup David , Labetoulle Marc , Rixon Frazer J.
Published: April 2013

Efficient intracellular transport of the capsid of alphaherpesviruses, such as herpes simplex virus 1 (HSV-1), is known to be dependent upon the microtubule (MT) network. Typically, the MT network radiates from an MT-organizing center (MTOC), which is, in most cases, the centrosome. During herpesvirus egress, it has been assumed that capsids travel first from the nucleus to the centrosome and then from the centrosome to the site of envelopment. Here we report that the centrosome is no longer a primary MTOC in HSV-1-infected cells, but it retains this function in cells infected by another alphaherpesvirus, pseudorabies virus (PrV). As a result, MTs formed at late times after infection with PrV grow from a major, centralized MTOC, while those formed after HSV-1 infection arise from dispersed locations in the cytoplasm, indicating the presence of alternative and minor MTOCs. Thus, loss of the principal MT nucleating center in cells following HSV-1 infection raises questions about the mechanism of HSV-1 capsid egress. It is possible that, rather than passing via the centrosome, capsids may travel directly to the site of envelopment after exiting the nucleus. We suggest that, in HSV-1-infected cells, the disruption of centrosomal functions triggers reorganization of the MT network to favor noncentrosomal MTs and promote efficient viral spread.
Interleukin-22 Reduces Lung Inflammation during Influenza A Virus Infection and Protects against Secondary Bacterial Infection
Authors: Ivanov Stoyan , Renneson Joelle , Fontaine Josette , Barthelemy Adeline , Paget Christophe , Fernandez Elodie Macho , Blanc Fany , De Trez Carl , Van Maele Laurye , Dumoutier Laure , Huerre Michel-René , Eberl Gérard , Si-Tahar Mustapha , Gosset Pierre , Renauld Jean Christophe , Sirard Jean Claude , Faveeuw Christelle , Trottein François
Published: April 2013

Interleukin-22 (IL-22) has redundant, protective, or pathogenic functions during autoimmune, inflammatory, and infectious diseases. Here, we addressed the potential role of IL-22 in host defense and pathogenesis during lethal and sublethal respiratory H3N2 influenza A virus (IAV) infection. We show that IL-22, as well as factors associated with its production, are expressed in the lung tissue during the early phases of IAV infection. Our data indicate that retinoic acid receptor-related orphan receptor-γt (RORγt)-positive αβ and γδ T cells, as well as innate lymphoid cells, expressed enhanced
Il22
transcripts as early as 2 days postinfection. During lethal or sublethal IAV infections, endogenous IL-22 played no role in the control of IAV replication and in the development of the IAV-specific CD8
+
T cell response. During lethal infection, where wild-type (WT) mice succumbed to severe pneumonia, the lack of IL-22 did not accelerate or delay IAV-associated pathogenesis and animal death. In stark contrast, during sublethal IAV infection, IL-22-deficient animals had enhanced lung injuries and showed a lower airway epithelial integrity relative to WT littermates. Of importance, the protective effect of endogenous IL-22 in pulmonary damages was associated with a more controlled secondary bacterial infection. Indeed, after challenge with
Streptococcus pneumoniae
, IAV-experienced
Il22
−/−
animals were more susceptible than WT controls in terms of survival rate and bacterial burden in the lungs. Together, IL-22 plays no major role during lethal influenza but is beneficial during sublethal H3N2 IAV infection, where it limits lung inflammation and subsequent bacterial superinfections.
Attenuated and Replication-Competent Vaccinia Virus Strains M65 and M101 with Distinct Biology and Immunogenicity as Potential Vaccine Candidates against Pathogens
Authors: Sánchez-Sampedro Lucas , Gómez Carmen Elena , Mejías-Pérez Ernesto , Pérez-Jiménez Eva , Oliveros Juan Carlos , Esteban Mariano
Published: April 2013

Replication-competent poxvirus vectors with an attenuation phenotype and with a high immunogenic capacity of the foreign expressed antigen are being pursued as novel vaccine vectors against different pathogens. In this investigation, we have examined the replication and immunogenic characteristics of two vaccinia virus (VACV) mutants, M65 and M101. These mutants were generated after 65 and 101 serial passages of persistently infected Friend erythroleukemia (FEL) cells. In cultured cells of different origins, the mutants are replication competent and have growth kinetics similar to or slightly reduced in comparison with those of the parental Western Reserve (WR) virus strain. In normal and immune-suppressed infected mice, the mutants showed different levels of attenuation and pathogenicity in comparison with WR and modified vaccinia Ankara (MVA) strains. Wide genome analysis after deep sequencing revealed selected genomic deletions and mutations in a number of viral open reading frames (ORFs). Mice immunized in a DNA prime/mutant boost regimen with viral vectors expressing the LACK (
Leishmania
homologue for receptors of activated C kinase) antigen of
Leishmania infantum
showed protection or a delay in the onset of cutaneous leishmaniasis. Protection was similar to that triggered by MVA-LACK. In immunized mice, both polyfunctional CD4
+
and CD8
+
T cells with an effector memory phenotype were activated by the two mutants, but the DNA-LACK/M65-LACK protocol preferentially induced CD4
+
whereas DNA-LACK/M101-LACK preferentially induced CD8
+
T cell responses. Altogether, our findings showed the adaptive changes of the WR genome during long-term virus-host cell interaction and how the replication competency of M65 and M101 mutants confers distinct biological properties and immunogenicity in mice compared to those of the MVA strain. These mutants could have applicability for understanding VACV biology and as potential vaccine vectors against pathogens and tumors.
HIV-1 Envelope Glycoprotein Trimers Display Open Quaternary Conformation When Bound to the gp41 Membrane-Proximal External-Region-Directed Broadly Neutralizing Antibody Z13e1
Authors: Harris Audray K. , Bartesaghi Alberto , Milne Jacqueline L. S. , Subramaniam Sriram
Published: April 2013

We describe cryo-electron microscopic studies of the interaction between the ectodomain of the trimeric HIV-1 envelope glycoprotein (Env) and Z13e1, a broadly neutralizing antibody that targets the membrane-proximal external region (MPER) of the gp41 subunit. We show that Z13e1-bound Env displays an open quaternary conformation similar to the CD4-bound conformation. Our results support the idea that MPER-directed antibodies, such as Z13e1, block viral entry by interacting with Env at a step after CD4 activation.
Bulge in the tonsillar fossa. Is it a quinsy?
Authors: Vijendren Ananth , Eladawy Iman , Kothari Prasad
Published: April 2013

A young girl presented to the ENT acute clinic with a persistent cough and a bulge in the left oropharynx. As there were no clinical signs suggestive of a quinsy, an MRI was performed that showed a large mass extending from the base of the skull to the epiglottis medialising the lateral and posterior pharyngeal walls. The patient subsequently underwent an excision biopsy which demonstrated a ganglioneuroma, however developed a left-sided Horner's syndrome and mild vocal cord palsy after.
Itraconazole as ‘bridge therapy’ to anti-IgE in a patient with severe asthma with fungal sensitisation
Authors: Pizzimenti Stefano , Bussolino Claudia , Badiu Iuliana , Rolla Giovanni
Published: April 2013

Sensitisation to fungi has been reported to play an important role in a particular phenotype of severe asthma, the so-called severe asthma with fungal sensitisation, characterised by high levels of total IgE, which may be an obstacle to anti-IgE therapy. We describe here the case of a polysensitised woman with refractory asthma, sensitised toAspergillus fumigatuswith high total IgE values (1793 kUA/l), but without the diagnostic criteria for allergic bronchopulmonary aspergillosis. Additional therapy with itraconazole leads to the decrease of total IgE to the limits recommended for proper omalizumab dosing (30–1500 kUA/l). Itraconazole, used as bridge therapy, provided us the opportunity to start anti-IgE treatment in a patient with high levels of total IgE, beyond the upper limits recommended for proper prescription of omalizumab.
Acute cord compression secondary to spinal relapse of testicular seminomas
Authors: Ng Yau Hong , Ho Henry Sun Sien , Kumar Naresh Satyanarayan
Published: April 2013

This is the first-reported case of an isolated thoracic spine relapse of a stage 1 testicular seminoma more than 1 year after surgery and radiotherapy. We report a 38-year-old gentleman, who underwent radical orchidectomy and adjuvant retroperitoneal irradiation for a pure testicular seminoma, presenting with acute cord compression from an isolated T8 relapse 14 months after the index surgery. Decompressive laminectomy with instrumentation was performed with adjuvant chemoradiotherapy. The patient gained full neurological recovery and has remained disease-free for 4 years. Testicular seminomas rarely relapse in the spine after treatment with surgery and radiotherapy, and it is usually the lumbar spine that is involved. Spinal relapse also commonly presents with pain rather than acute cord compression. This case report discusses the unique behaviour of testicular seminomas and their presentation in vertebral relapse. We also present a summary of the available literature on isolated thoracic spine relapse of testicular seminomas.
Emergence of co-trimoxazole resistantNocardia brasiliensiscausing fatal pneumonia
Authors: Khare Vineeta , Gupta Prashant , D Himanshu , Kumar Deepak
Published: April 2013

An 85-year-old man was admitted to the medical intensive care unit with a 10-day history of severe breathlessness, fever and cough. The patient was known to have chronic obstructive pulmonary disease and had been receiving corticosteroids in the preceding 18 months. He had been treated for tuberculosis 2.5 years previously. On examination he was febrile, tachycardic with a respiratory rate of 46/min. Auscultation revealed bilateral crepitation's and wheeze. Chest radiograph revealed patchy infiltrates on right lung. The patient developed respiratory depression and was mechanically ventilated. His sputum and endotracheal aspirates revealedNocardia brasiliensison culture which was found to be co-trimoxazole resistant. Once this became known imipenem was substituted for co-trimoxazole but unfortunately condition of the patient did not improve and he died following a cardiac arrest.
Intraduct papillary mucinous neoplasm of the pancreas: a tumour linked with IgG4-related disease?
Authors: Bateman Adrian C , Culver Emma L , Sommerlad Matthew , Chetty Runjan
Published: April 2013

Objectives

Intraduct papillary mucinous neoplasm (IPMN) is a pancreatic tumour that is often associated with chronic pancreatitis (CP) in the surrounding pancreas. Type 1 autoimmune pancreatitis (AIP) is a fibro-inflammatory condition with characteristic histological features and prominent IgG4+ plasma cells and is part of the spectrum of IgG4-related disease (IgG4-RD). The aim of this study was to determine whether CP associated with pancreatic IPMN commonly represents AIP.

Methods

We identified two consecutive ‘index’ cases of pancreatic IPMN during routine reporting in which the adjacent pancreas showed morphological features suggestive of AIP. These cases were investigated using the Boston criteria for the histopathological diagnosis of IgG4-RD and the HISORt criteria for the clinical and histopathological diagnosis of AIP. Using the same criteria, we proceeded to a clinical review of 12 extra cases of IPMN in which the tumour or the surrounding pancreas showed significant lymphoplasmacytic inflammation and/or fibrosis.

Results

Both of the ‘index’ cases fulfilled the HISORt criteria for AIP and both had morphological features characteristic of IgG4-RD using the Boston criteria, although only one possessed features ‘highly suggestive of IgG4-RD’ after immunohistochemistry. Additionally, both ‘index’ cases had radiological features that could represent extrapancreatic manifestations. Review of the 12 additional cases of IPMN revealed no further examples showing co-existent AIP.

Conclusion

While pancreatic IPMN and AIP may co-exist, most CP associated with IPMN does not represent AIP.
Chemical reactivity and biological activity of dihydro-1,4-dithiin tetraoxides
Authors: Chee Gaik-Lean , Bhattarai Bharat , Nash Jordan D. , Madec Kim , Hasinoff Brian B. , Brewer A. David
Published: April 2013

Certain dihydro-1,4-dithiin tetraoxides such as dimethipin, a commercial plant growth regulant, have been reported to exhibit highly selective biological activities depending on the type and number of substitutions on the α,β-unsaturated bond in the dithiin ring. Despite the abundant reports on this class of compounds, the study of chemical reactivity of the α,β-unsaturated bond in the dithiin ring has not been reported and the factors governing the biological selectivity of these compounds are still unknown. In this study, the reactivity of eight dithiin compounds substituted in varying degrees at the α,β-unsaturated bond towards biologically important nucleophilic groups at pH 7.4 were investigated using UV-vis, fluorescence, and1H NMR spectroscopies. Their reactivity towards glutathione correlated strongly with their cell growth inhibitory activity and inhibition of DNA topoisomerase II, an enzyme containing critical sulfhydryl groups. On this basis, the mechanism by which these dithiins achieve the biological selectivity previously reported was proposed. Excellent correlations between glutathione reactivity and Taft’s polar substituent constants or electrostatic atomic charges of the dithiins were also demonstrated, suggesting that these descriptors might be useful for predicting the reactivity of other dithiins towards sulfhydryl nucleophiles.
A density functional theory approach to the magnetic properties of a coupled single-molecule magnet (Mn7)2 complex — An entangled qubit pair candidate
Authors: Gómez-Coca Silvia , Ruiz Eliseo
Published: April 2013

The exchange coupling constants of a Mn14 complex constituted by two weakly coupled Mn7 moieties were calculated using two different density functional theory (DFT) approaches: the Perdew–Burke–Ernzerhof (PBE) functional with a numerical basis set and the hybrid Becke, three-parameter Lee–Yang–Parr (B3LYP) functional employed with a Gaussian basis set. The sign and relative strength of the exchange coupling constants calculated with both methods were consistent; as expected, the values calculated with the PBE functional were slightly overestimated, as corroborated by comparison with the experimental magnetic susceptibility curve. Both methods gave a ground spin configuration of S = 3/2 for the Mn7 moiety, which was weakly antiferromagnetically coupled with the other Mn7 fragment, leading to an S = 0 ground spin configuration for the entire Mn14 complex.
Albanerpetontid amphibians from the Late Cretaceous (Santonian) of Iharkút, Hungary, with remarks on regional differences in Late Cretaceous Laurasian amphibian assemblages
Authors: Szentesi Zoltán , Gardner James D. , Venczel Márton
Published: April 2013

Since its discovery in 2000, the Iharkút fossil locality in the Upper Cretaceous (Santonian) Csehbánya Formation of western Hungary has yielded a taxonomically diverse assemblage of terrestrial and freshwater vertebrates that continue to provide insights into the diversity, paleobiogeography, and paleoecology of Late Cretaceous vertebrates in Europe. Albanerpetontidae, an extinct group of superficially salamander-like amphibians that were widespread across Laurasia during the latter part of the Mesozoic, are represented at Iharkút by 16 fragmentary jaws. Here we describe and figure these specimens as Albanerpetontidae genus and species indeterminate. Based on the age of the Iharkút locality, several premaxillary features, the known distribution (late Early Cretaceous – late Pliocene) of the type genus Albanerpeton, and an unusually large dentary specimen, we suggest that the Iharkút albanerpetontid may pertain to a previously unrecognized species of Albanerpeton, but verification of that must await the recovery of more diagnostically informative specimens, such as frontals and more nearly complete premaxillae. The Iharkút lissamphibian assemblage contains a mixture of taxa with Laurasian (the albanerpetontid and a discoglossid anuran) and Gondwanan (a neobatrachian anuran) affinities. Intriguing higher level differences are evident among Late Cretaceous Laurasian assemblages; for example, urodeles are scarce or absent (as at Iharkút) in Europe, whereas albanerpetontids are scarce in Middle Asia.
R-MATRICES AND HAMILTONIAN STRUCTURES FOR CERTAIN LAX EQUATIONS
Authors: WU CHAO-ZHONG
Published: April 2013

In this paper a list of R-matrices on a certain coupled Lie algebra is obtained. With one of these R-matrices, we construct infinitely many bi-Hamiltonian structures for each of the two-component BKP and the Toda lattice hierarchies. We also show that, when such two hierarchies are reduced to their subhierarchies, these bi-Hamiltonian structures are reduced correspondingly.
HYDRODYNAMIC MODELING OF HEAVY-ION COLLISIONS
Authors: GALE CHARLES , JEON SANGYONG , SCHENKE BJÖRN
Published: April 2013

We review progress in the hydrodynamic description of heavy-ion collisions, focusing on recent developments in modeling the fluctuating initial state and event-by-event viscous hydrodynamic simulations. We discuss how hydrodynamics can be used to extract information on fundamental properties of quantum chromodynamics from experimental data, and review successes and challenges of the hydrodynamic framework.
HALF-CIRCULAR PILLAR IN A SUPERCONDUCTING SAMPLE
Authors: BARBA-ORTEGA J. , HIGUERA SINDY J. , AGUIAR J. ALBINO
Published: April 2013

In this paper, we solve the Ginzburg–Landau equations for a circular geometry containing a half-circular pillar. We consider the surface of the sample in a complete normal state (|ψ| surface = 0), this choice, leading to take the extrapolation de Gennes length equal to zero (b = 0). Our results point out that the critical fields, magnetization and vorticity, depend on the chosen boundary condition.
EFFECT OF FINITE AMPLIFIER BANDWIDTH AND EXCESS LOOP DELAY IN A PARALLEL CT ΔΣ ADC FOR OFDM UWB RECEIVERS
Authors: QUINTANILLA L. , ARIAS J. , SEGUNDO J. , ENRIQUEZ L. , HERNANDEZ-MANGAS J. M. , VICENTE J.
Published: April 2013

A comprehensive analysis of the impact of the finite gain-bandwidth product (GBW) in amplifiers and the excess loop delay on a parallel multibit CT ΔΣ ADC for an orthogonal frequency division multiplexing OFDM ultra-wideband (UWB) receiver has been carried out in this paper. The overall converter consists of two CT ΔΣ modulators covering two sub-bands (each of them implemented by a third and a fourth order CT ΔΣ modulator) that are arranged to operate in parallel. Our study was based on the dependence of the noise transfer function (NTF) poles and zeroes locus in the z-plane on these two nonideal effects for both modulators from a theoretical approach. The corresponding STFs were also analytically evaluated. System-level simulations have been accomplished too. Amplifiers were modeled according to a single-pole transfer function. Using the modified Z-transform method the dependence of the NTF poles and zeroes locus in the z-plane on the finite GBW and on excess loop delay was obtained when the DAC pulse end occurs in the current ("early") or in the following ("late") clock cycle. NTF poles and zeroes loci were evaluated as a function of the two nonideal effects considered separately or combined.
A FINITE ELEMENT PLATE FORMULATION FOR THE ACOUSTICAL INVESTIGATION OF THIN AIR LAYERS
Authors: RONG PING , ESTORFF OTTO VON , NAGLER LORIS , SCHANZ MARTIN
Published: April 2013

Double wall systems consisting of thin plates separated by an air gap are common light-weighted wall structures with high transmission loss. Generally, these plate-like structures are modeled in a finite element analysis with shell elements and volume elements for the air (fluid) layer. An alternative approach is presented in this paper, using shell elements for the air layer as well. First, the element stiffness matrix is obtained by removing the thickness dependence of the variational form of the Helmholtz equation by use of a power series. Second, the coupling between the acoustical shell element and the elastic structure is described. To verify the new shell element, a simple double wall system is considered. Comparing the predicted sound field with the results from a commercial FE software (with a single layer of volume elements) a very good agreement is observed. At the same time, employing the new elements with a third-order power series (4 DOFs per node), the calculation time is reduced.
A NEW APPROACH FOR CONVERGENCE ACCELERATION OF ITERATIVE METHODS IN STRUCTURAL ANALYSIS
Authors: SAFFARI HAMED , BAGHLANI ABDOLHOSSEIN , MIRZAI NADIA M. , MANSOURI IMAN
Published: April 2013

In this paper, a new approach is presented to accelerate the nonlinear analysis of structures with low computational cost. The method is essentially based on Newton–Raphson method, which has been improved in each iteration to achieve faster convergence. The normal flow algorithm has been employed to pass successfully through the limit points and through the entire equilibrium path. Subsequently, numerical examples are performed to demonstrate the efficiency of the formulation. The results show better performance, accuracy and rate of convergence of the present method to deal with nonlinear analysis of structures.
NUMERICAL ANALYSIS OF IDEALLY-EXPANDED SUPERSONIC JETS WITH NONEQUILIBRIUM HOMOGENEOUS CONDENSATION
Authors: ALAM M. M. A. , SETOGUCHI T. , MATSUO S.
Published: April 2013

Steam or moist air is used as working gas in a wide range of engineering applications of supersonic jets. In these cases, nonequilibrium homogeneous condensation may occur at the downstream of nozzle throat. The surrounding gas will be heated by the release of latent heat of condensation, and may results a change in the flowfield. The present report will describe numerical investigations predicting the effect of nonequilibrium condensation on the flow characteristics of ideally-expanded supersonic free jets. A TVD numerical method is applied to solve RANS and droplet growth equations. The predicted results are compared with the experimental data.
Downregulation of core clock gene Bmal1 attenuates expression of progesterone and prostaglandin biosynthesis-related genes in rat luteinizing granulosa cells
Authors: Chen Huatao , Zhao Lijia , Kumazawa Makoto , Yamauchi Nobuhiko , Shigeyoshi Yasufumi , Hashimoto Seiichi , Hattori Masa-aki
Published: April 2013

Ovarian circadian oscillators have been implicated in the reproductive processes of mammals. However, there are few reports regarding the detection of ovarian clock-controlled genes (CCGs). The present study was designed to unravel the mechanisms through which CCG ovarian circadian oscillators regulate fertility, primarily using quantitative RT-PCR and RNA interference against Bmal1 in rat granulosa cells. Mature granulosa cells were prepared from mouse Per2-destabilized luciferase ( dLuc) reporter gene transgenic rats. A real-time monitoring system of Per2 promoter activity was employed to detect Per2-dLuc oscillations. The cells exposed to luteinizing hormone (LH) displayed clear Per2-dLuc oscillations and a rhythmic expression of clock genes ( Bmal1, Per1, Per2, Rev-erbα, and Dbp). Meanwhile, the examined ovarian genes ( Star, Cyp19a1, Cyp11a1, Ptgs2, Lhcgr, and p53) showed rhythmic transcript profiles except for Hsd3b2, indicating that these rhythmic expression genes may be CCGs. Notably, Bmal1 small interfering (si)RNA treatment significantly decreased both the amplitude of Per2-dLuc oscillations and Bmal1 mRNA levels compared with nonsilencing RNA treatment in luteinizing granulosa cells. Depletion of Bmal1 by siRNA decreased the transcript levels of clock genes ( Per1, Per2, Rev-erbα, and Dbp) and examined ovarian genes ( Star, Cyp19a1, Cyp11a1, Ptgs2, Hsd3b2, and Lhcgr). Accordingly, knockdown of Bmal1 also inhibited the synthesis of progesterone and prostaglandin E2, which are associated with crucial reproductive processes. Collectively, these data suggest that ovarian circadian oscillators regulate the synthesis of steroid hormones and prostaglandins through ovarian-specific CCGs in response to LH stimuli. The present study provides new insights into the physiologic significance of Bmal1 related to fertility in ovarian circadian oscillators.
Impact of fasting on the rhythmic expression of myogenic and metabolic factors in skeletal muscle of adult mice
Authors: Shavlakadze T. , Anwari T. , Soffe Z. , Cozens G. , Mark P. J. , Gondro C. , Grounds M. D.
Published: April 2013

Circadian rhythms and metabolism are tightly integrated, and rhythmic expression of metabolic factors is common in homeostatic processes. We measured the temporal changes in the expression of myogenic regulatory factors and expression and activity level of molecules involved in protein metabolism in skeletal muscles and livers in mice and examined the impact of fasting. Tissues were collected over 24 h (at zeitgeber times ZT1, ZT5, ZT9, ZT13, ZT17, ZT21, and ZT1 the following day) from adult male C57Bl/6J mice that had been either freely fed or fasted for 24 h. In skeletal muscle, there was a robust rise in the mRNA expression of the myogenic regulatory factors MyoD and myogenin during dark hours which was strongly suppressed by fasting. Circadian pattern was observed for mRNA of MuRF1, Akt1, and ribosomal protein S6 in muscles in fed and fasted mice and for Fbxo32 in fed mice. Activity (phosphorylation) levels of Akt(Ser473) displayed temporal regulation in fasted (but not fed) mice and were high at ZT9. Fasting caused significant reductions in phosphorylation for both Akt and S6 in muscles, indicative of inactivation. Hepatic phosphorylated Akt(Ser473) and S6(Ser235/236) proteins did not exhibit daily rhythms. Fasting significantly reduced hepatic Akt(473) phosphorylation compared with fed levels, although (unlike in muscle) it did not affect S6(Ser235/236) phosphorylation. This in vivo circadian study addresses for the first time the signaling activities of key molecules related to protein turnover and their possible cross-regulation of expression of genes related to protein degradation.
Interleukin-19 decreases leukocyte-endothelial cell interactions by reduction in endothelial cell adhesion molecule mRNA stability
Authors: England Ross N. , Preston Kyle J. , Scalia Rosario , Autieri Michael V.
Published: April 2013

Vascular endothelial cell (EC) inflammation is a key event in the pathogenesis of multiple vascular diseases. We tested the hypothesis that interleukin-19 (IL-19), an anti-inflammatory Th2 interleukin, could have a direct anti-inflammatory effect on ECs to decrease inflammation. IL-19 can significantly decrease tumor necrosis factor (TNF)-α-driven intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 mRNA and protein abundance in cultured human coronary artery ECs ( P < 0.01). IL-19 treatment of ECs, but not monocytes, significantly reduced monocyte adhesion to EC monolayers ( P < 0.01). In vivo, systemic administration of IL-19 could significantly reduce TNF-α-induced leukocyte rolling and adhesion in wild-type mice as assayed by intravital microscopy ( P < 0.05). IL-19 does not reduce TNF-α-stimulated NF-κB activation in ECs but does decrease serine phosphorylation and cytoplasmic translocation of the mRNA stability factor HuR and significantly reduces stability of ICAM-1 and VCAM-1 mRNA ( P < 0.01). These data are the first to report that IL-19 can reduce leukocyte-endothelial cell adhesion and the first to propose reduction in HuR-mediated mRNA stability of ICAM-1 and VCAM-1 as a mechanism. Expression of IL-19 by ECs may represent a protective mechanism to promote resolution of the vascular response to inflammation. Function of IL-19 outside of the immune system is a novel concept, suggesting that resident vascular cells can adopt a Th2 phenotype, and has important ramifications for numerous inflammatory diseases.
A role for tricellulin in the regulation of gill epithelium permeability
Authors: Kolosov Dennis , Kelly Scott P.
Published: April 2013

The apical-most region of cell-to-cell contact in a vertebrate epithelium is the tight junction (TJ) complex. It is composed of bicellular TJs (bTJs) that bridge two adjacent epithelial cells and tricellular TJs (tTJs) that are points of contact between three adjoining epithelial cells. Tricellulin (TRIC) is a transmembrane TJ protein of vertebrates that is found in the tTJ complex. Full-length cDNA encoding rainbow trout TRIC was cloned and sequenced. In silico analysis of rainbow trout TRIC revealed a tetraspannin protein with several putative posttranslational modification sites. TRIC mRNA was broadly expressed in rainbow trout tissues and exhibited moderately greater abundance in the gill. In a primary cultured gill epithelium, TRIC localized to tTJs and TRIC protein abundance increased in association with corticosteroid-induced reductions in paracellular permeability. Sodium caprate was used to compromise cultured gill epithelium integrity by disrupting the tTJ complex. Sodium caprate treatment caused a reversible reduction in transepithelial resistance, caused an increase in paracellular permeability (as measured by [3H]PEG-4000 flux), and displaced TRIC from tTJs while leaving bTJs intact. Data from this study support the view that tTJs and the TJ protein TRIC 1) play a role in maintaining gill epithelium integrity and 2) contribute to the regulation of gill epithelium permeability.