bluuebunny/crossref_metadata_2025 huggingface dataset:
-constraints for the total descendant potential of a simple singularity
Authors: Bakalov Bojko , Milanov Todor
Published: February 2013

Simple, or Kleinian, singularities are classified by Dynkin diagrams of type $ADE$. Let $\mathfrak {g}$ be the corresponding finite-dimensional Lie algebra, and $W$ its Weyl group. The set of $\mathfrak {g}$-invariants in the basic representation of the affine Kac–Moody algebra $\hat {\mathfrak {g}}$ is known as a $\mathcal {W}$-algebra and is a subalgebra of the Heisenberg vertex algebra $\mathcal {F}$. Using period integrals, we construct an analytic continuation of the twisted representation of $\mathcal {F}$. Our construction yields a global object, which may be called a $W$-twisted representation of $\mathcal {F}$. Our main result is that the total descendant potential of the singularity, introduced by Givental, is a highest-weight vector for the $\mathcal {W}$-algebra.
Consensus Analysis and Formation Control of Second-Order Multiagent Systems Via Nonlinear Protocol
Authors: Pan Huan , Nian Xiaohong , Guo Ling
Published: February 2013

This paper mainly investigates consensus and formation control of second-order multiagent system with undirected communication graph. A nonlinear protocol is proposed as an extension of general linear protocols that have been widely studied. In order to achieve formation control, a formation control strategy corresponding to the nonlinear protocol is designed too. The sufficient conditions of consensus and formation are derived based on LaSalle's invariance principle. Simulation examples are provided to illustrate that the second-order multiagent with the nonlinear protocol can achieve consensus and formation.
Is Europe Evolving Toward an Integrated Research Area?
Authors: Chessa A. , Morescalchi A. , Pammolli F. , Penner O. , Petersen A. M. , Riccaboni M.
Published: February 2013

Despite efforts to integrate across borders, Europe remains a collection of national innovation systems.
Stress State in the Largest Displacement Area of the 2011 Tohoku-Oki Earthquake
Authors: Lin Weiren , Conin Marianne , Moore J. Casey , Chester Frederick M. , Nakamura Yasuyuki , Mori James J. , Anderson Louise , Brodsky Emily E. , Eguchi Nobuhisa ,   Expedition 343 Scientists, Cook Becky , Jeppson Tamara , Wolfson-Schwehr Monica , Sanada Yoshinori , Saito Saneatsu , Kido Yukari , Hirose Takehiro , Behrmann Jan H. , Ikari Matt , Ujiie Kohtaro , Rowe Christie , Kirkpatrick James , Bose Santanu , Regalla Christine , Remitti Francesca , Toy Virginia , Fulton Patrick , Mishima Toshiaki , Yang Tao , Sun Tianhaozhe , Ishikawa Tsuyoshi , Sample James , Takai Ken , Kameda Jun , Toczko Sean , Maeda Lena , Kodaira Shuichi , Hino Ryota , Saffer Demian
Published: February 2013

Stressed Out

Large seismic events such as the 2011 magnitude 9.0 Tohoku-Oki earthquake can have profound effects not just on the severity of ground motion and tsunami generation, but also on the overall state of the crust in the surrounding regions.

Lin
et al.

(p.
687
) analyzed the stress 1 year after the Tohoku-Oki earthquake and compared it with the estimated stress state before the earthquake. In situ resistivity images were analyzed from three boreholes drilled into the crust across the plate interface where the earthquake occurred. Stress values indicate a nearly complete drop in stress following the earthquake such that the type of faulting above the plate boundary has changed substantially. These findings are consistent with observations that the sea floor moved nearly 50 meters during the earthquake.
Proton Donor Acidity Controls Selectivity in Nonaromatic Nitrogen Heterocycle Synthesis
Authors: Duttwyler Simon , Chen Shuming , Takase Michael K. , Wiberg Kenneth B. , Bergman Robert G. , Ellman Jonathan A.
Published: February 2013

Acid-Derived Diversity

Compounds with nitrogen-bearing rings have proven rather promising in pharmaceutical research, spurring the need for improved synthetic methods to access structurally diverse variants of this motif.

Duttwyler
et al.

(p.
678
) show that applying acids of different strengths to a dihydropyridine intermediate leads to selective protonation at either of two sites, depending on whether the reaction proceeds under kinetic or thermodynamic (that is, equilibrated) control. The protonations in turn activate the rings for addition of various carbon nucleophiles to the periphery, thereby affording multiple different substitution patterns for use in screening studies.
A Functional [NiFe]Hydrogenase Mimic That Catalyzes Electron and Hydride Transfer from H
2
Authors: Ogo Seiji , Ichikawa Koji , Kishima Takahiro , Matsumoto Takahiro , Nakai Hidetaka , Kusaka Katsuhiro , Ohhara Takashi
Published: February 2013

Mimicking Hydrogenase

Hydrogenase enzymes possess unusual bimetallic active sites that cleave H
2
. The enzymes make use of abundant metals (iron and sometimes nickel), in contrast to the often expensive synthetic catalysts that rely on rarer elements such as ruthenium or platinum.

Ogo
et al.

(p.
682
; see the Perspective by

Armstrong

) now report a bimetallic coordination compound of iron and nickel that can catalyze electron and hydride transfers from H
2
in a manner analogous to the corresponding enzyme and characterize the structure of an intermediate with bound hydride.
Carl R. Woese (1928–2012)
Authors: Goldenfeld Nigel , Pace Norman R.
Published: February 2013

A visionary microbiologist focused on evolution and discovered a third domain of life, archaea.
Investing in Distant Rewards
Authors: Press William H.
Published: February 2013

Would you spend money today to make the world a substantially better place for your children and grandchildren? Most of us would. But what if the benefit would accrue only to your great-great-great-great-grandchildren, not born until the 22nd century? That's an awfully distant time horizon for most people. Many would probably spend today's resources on more immediate concerns.
Archaeologist Hammers Away At 'Modern' Behavior
Authors: Balter Michael
Published: February 2013

Stone tools suggest that the earliest modern humans were as smart as we are—they just had different problems to solve, an archaeologist argues.
Immunization with Pneumococcal Polysaccharide Serotype 3 and Lipopolysaccharide Modulates Lung and Liver Inflammation during a Virulent Streptococcus pneumoniae Infection in Mice
Authors: Restori Katherine H. , Kennett Mary J. , Ross A. Catharine
Published: February 2013

Vaccination reduces morbidity and mortality from pneumonia, but its effect on the tissue-level response to infection is still poorly understood. We evaluated pneumonia disease progression, acute-phase response, and lung gene expression profiles in mice inoculated intranasally with virulent Gram-positiveStreptococcus pneumoniaeserotype 3 (ST 3) with and without prior immunization with pneumococcal polysaccharide ST 3 (PPS3) or after coimmunization with PPS3 and a low dose of lipopolysaccharide (PPS3+LPS). Pneumonia severity was assessed in the acute phase at 5, 12, 24 and 48 h postinoculation (p.i.) and in the resolution phase at 7 days p.i. Primary PPS3-specific antibody production was upregulated, and IgM binding to pneumococci increased in PPS3-immunized mice. Immunizations with PPS3 or PPS3+LPS decreased bacterial recovery in the lung and blood at 24 and 48 h and increased survival. Microarray analysis of whole-lung RNA revealed significant changes in the acute-phase protein serum amyloid A (SAA) levels between noninfected and infected mice, and these changes were attenuated by immunization. SAA transcripts were higher in the liver and lungs of infected controls, and SAA protein was elevated in serum but decreased in PPS3-immunized mice. Thus, during a virulent pneumonia infection, prior immunization with PPS3 in an IgM-dependent manner as well as immunization with PPS3+LPS attenuated pneumonia severity and promoted resolution of infection, concomitant with significant regulation of cytokine gene expression levels in the lungs and acute-phase proteins in the lungs, liver, and serum.
Cell-Mediated and Humoral Immune Responses after Immunization of Calves with a Recombinant Multiantigenic Mycobacterium avium subsp. paratuberculosis Subunit Vaccine at Different Ages
Authors: Thakur Aneesh , Aagaard Claus , Stockmarr Anders , Andersen Peter , Jungersen Gregers
Published: February 2013

Neonates and juvenile ruminants are very susceptible to paratuberculosis infection. This is likely due to a high degree of exposure from their dams and an immature immune system. To test the influence of age on vaccine-induced responses, a cocktail of recombinantMycobacterium aviumsubsp.paratuberculosisproteins (MAP0217, MAP1508, MAP3701c, MAP3783, and MAP1609c/Ag85B) was formulated in a cationic liposome adjuvant (CAF01) and used to vaccinate animals of different ages. Male jersey calves were divided into three groups that were vaccinated at 2, 8, or 16 weeks of age and boosted twice at weeks 4 and 12 relative to the first vaccination. Vaccine-induced immune responses, the gamma interferon (IFN-γ) cytokine secretion and antibody responses, were followed for 20 weeks. In general, the specific responses were significantly elevated in all three vaccination groups after the first booster vaccination with no or only a minor effect from the second booster. However, significant differences were observed in the immunogenicity levels of the different proteins, and it appears that the older age group produced a more consistent IFN-γ response. In contrast, the humoral immune response is seemingly independent of vaccination age as we found no difference in the IgG1 responses when we compared the three vaccination groups. Combined, our results suggest that an appropriate age of vaccination should be considered in vaccination protocols and that there is a possible interference of vaccine-induced immune responses with weaning (week 8).
Changes in Streptococcus pneumoniae Serotype 19A Invasive Infections in Children from 1993 to 2011
Authors: Hulten Kristina G. , Kaplan Sheldon L. , Lamberth Linda B. , Barson William J. , Romero José R. , Lin Philana Ling , Bradley John S. , Givner Laurence B. , Tan Tina Q. , Hoffman Jill A. , Mason Edward O.
Published: February 2013

Among 594
Streptococcus pneumoniae
serotype 19A invasive pneumococcal disease (IPD) isolates collected from 1993 to 2011, we identified 85 sequence types by multilocus sequence typing. CC320 was associated with multidrug resistance and reduced susceptibility to penicillin and ceftriaxone and still predominated among declining serotype 19A IPD isolates following PCV13 introduction.
Quantification of Viral Loads Lower than 50 Copies per Milliliter by Use of the Cobas AmpliPrep/Cobas TaqMan HIV-1 Test, Version 2.0, Can Predict the Likelihood of Subsequent Virological Rebound to >50 Copies per Milliliter
Authors: Álvarez Estévez Marta , Chueca Porcuna Natalia , Guillot Suay Vicente , Peña Monge Alejandro , García García Fernando , Muñoz Medina Leopoldo , Vinuesa García David , Parra Ruiz Jorge , Hernández-Quero Jose , García García Federico
Published: February 2013

After 1 year of follow-up, patients on HAART with a baseline viral load (VL) of <20 copies/ml showed significantly lower odds of virological rebound to two consecutive VLs of >50 copies/ml than those with baseline VLs of 20 to 39 and 40 to 49 (
P
< 0.001). The time to virological rebound was also significantly shorter (
P
< 0.001) for the groups with baseline VLs of 20 to 39 and 40 to 49.
Varicella-Like Cutaneous Toxoplasmosis in a Patient with Aplastic Anemia
Authors: Zimmermann Stefan , Hadaschik Eva , Dalpke Alexander , Hassel Jessica C. , Ajzenberg Daniel , Tenner-Racz Klara , Lehners Nicola , Kapaun Annette , Schnitzler Paul
Published: February 2013

A 60-year-old patient with aplastic anemia presented with vesicular varicella-like skin lesions on her face, arms, legs, back, and abdomen. However, diagnosis for herpetic infection was negative. Findings of a skin biopsy led to a tentative histologic diagnosis of toxoplasmosis, and infection with
Toxoplasma gondii
was confirmed by immunohistochemistry and PCR. Cutaneous toxoplasmosis is a rare finding in immunocompromised patients and might mimic other infectious diseases, and vesicular lesions associated with toxoplasmosis have not been reported previously.
Controlled Multicenter Evaluation of a Bacteriophage-Based Method for Rapid Detection of Staphylococcus aureus in Positive Blood Cultures
Authors: Bhowmick T. , Mirrett S. , Reller L. B. , Price C. , Qi C. , Weinstein M. P. , Kirn T. J.
Published: February 2013

Staphylococci are a frequent cause of bloodstream infections (BSIs). Appropriate antibiotic treatment for BSIs may be delayed because conventional laboratory testing methods take 48 to 72 h to identify and characterize isolates from positive blood cultures. We evaluated a novel assay based on bacteriophage amplification that identifies
Staphylococcus aureus
and differentiates between methicillin-susceptible and methicillin-resistant
S. aureus
(MSSA and MRSA, respectively) in samples taken directly from signal-positive Bactec blood culture bottles within 24 h of positive signal, with results available within 5 h. The performance of the MicroPhage KeyPath MRSA/MSSA blood culture test was compared to conventional identification and susceptibility testing methods. At four sites, we collectively tested a total of 1,165 specimens, of which 1,116 were included in our analysis. Compared to standard methods, the KeyPath MRSA/MSSA blood culture test demonstrated a sensitivity, specificity, positive predictive value, and negative predictive value of 91.8%, 98.3%, 96.3%, and 96.1%, respectively, for correctly identifying
S. aureus
. Of those correctly identified as
S. aureus
(
n
= 334), 99.1% were correctly categorized as either MSSA or MRSA. Analysis of a subset of the data revealed that the KeyPath MRSA/MSSA blood culture test delivered results a median of 30 h sooner than conventional methods (a median of 46.9 h versus a median of 16.9 h). Although the sensitivity of the test in detecting
S. aureus
-positive samples is not high, its accuracy in determining methicillin resistance and susceptibility among positives is very high. These characteristics may enable earlier implementation of appropriate antibiotic treatment for many
S. aureus
BSI patients.
Molecular Characterization of Enterotoxigenic Escherichia coli Isolates Recovered from Children with Diarrhea during a 4-Year Period (2007 to 2010) in Bolivia
Authors: Gonzales Lucia , Sanchez Samanta , Zambrana Silvia , Iñiguez Volga , Wiklund Gudrun , Svennerholm Ann-Mari , Sjöling Åsa
Published: February 2013

Enterotoxigenic
Escherichia coli
(ETEC) is an important cause of childhood diarrhea. This study aimed to characterize ETEC strains isolated from Bolivian children aged <5 years according to enterotoxin profile, colonization factors (CFs), suggested virulence genes, and severity of disease. A total of 299 ETEC isolates recovered from children with diarrhea and 55 ETEC isolates from children without diarrhea (controls) were isolated over a period of 4 years. Strains expressing heat-labile toxin (LT) or heat-stable toxin (ST) alone were about equally common and twice as common as ETEC producing both toxins (20%). ETEC strains expressing human ST (STh) were more common in children aged <2 years, while ETEC strains expressing LT plus STh (LT/STh) were more frequent in 2- to 5-year-old children. Severity of disease was not related to the toxin profile of the strains. CF-positive isolates were more frequently identified in diarrheal samples than in control samples (
P
= 0.02). The most common CFs were CFA/I and CS14. CFA/I ETEC strains were more frequent in children aged <2 years than CS1+CS3 isolates and CS14 isolates, which were more prevalent in 2- to 5-year-old children. The presence of suggested ETEC virulence genes (
clyA
,
eatA
,
tia
,
tibC
,
leoA
, and
east-1
) was not associated with disease. However,
east-1
was associated with LT/STh strains (
P
< 0.001),
eatA
with STh strains (
P
< 0.001), and
tia
with LT/STh strains (
P
< 0.001). A minor seasonal peak of ETEC infections was identified in May during the cold-dry season and coincided with the peak of rotavirus infections; this pattern is unusual for ETEC and may be important for vaccination strategies in Bolivia.
Evaluation of Quantification of HIV-1 RNA Viral Load in Plasma and Dried Blood Spots by Use of the Semiautomated Cobas Amplicor Assay and the Fully Automated Cobas Ampliprep/TaqMan Assay, Version 2.0, in Kisumu, Kenya
Authors: Ouma Kenneth N. , Basavaraju Sridhar V. , Okonji Jully A. , Williamson John , Thomas Timothy K. , Mills Lisa A. , Nkengasong John N. , Zeh Clement
Published: February 2013

In Kenya, HIV-1 viral load monitoring is commonly performed with the Cobas Amplicor using plasma specimens. Interest is growing in transitioning to real-time PCR (RT-PCR), such as the Cobas Ampliprep/Cobas TaqMan (CAP/CTM), using dried blood spots (DBS). Before implementation, direct evaluation of the two assays using DBS field specimens is required. This study compares the sensitivity, specificity, negative and positive predictive values (NPV and PPV, respectively), concordance, and agreement between HIV-1 viral load measurements using plasma and DBS specimens obtained from 512 HIV-1-infected pregnant females enrolled in the Kisumu Breastfeeding Study and tested with the Cobas Amplicor and CAP/CTM assays. The sensitivity and NPV of viral load detection in DBS specimens were higher with CAP/CTM (sensitivity, 100%; 95% confidence interval [CI], 99.1 to 100.0%; NPV, 100%; 95% CI, 59.0 to 100.0%) than the Cobas Amplicor (sensitivity, 96.6%; 95% CI, 94.3 to 98.1%; NPV, 58.8%; 95% CI, 40.7 to 75.4%). The PPVs were comparable between both assays when using DBS. The specificity of viral load detection in DBS specimens was lower with CAP/CTM (77.8%; 95% CI, 40.0 to 97.2%) than that of the Cobas Amplicor (95.2%; 95% CI, 76.2 to 99.9%). Good concordance and agreement were observed when paired plasma and DBS specimens were tested with both assays. Lower specificity with the CAP/CTM is likely due to proviral HIV-1 DNA amplification and lower detection limits with RT-PCR. However, the CAP/CTM has better sensitivity and higher throughput than the Cobas Amplicor. These findings suggest that DBS may be a suitable alternative to plasma when using RT-PCR, which could increase access to viral load monitoring in resource-limited settings.
Evaluation of Methods for Testing the Susceptibility of Clinical Mycobacterium tuberculosis Isolates to Pyrazinamide
Authors: Cui Zhenling , Wang Jie , Lu Junmei , Huang Xiaochen , Zheng Ruijuan , Hu Zhongyi
Published: February 2013

Pyrazinamide (PZA) is a first-line antituberculosis (anti-TB) drug capable of killing nonreplicating, persistent
Mycobacterium tuberculosis
. However, reliable testing of the susceptibility of
M. tuberculosis
to PZA is challenging. Using 432 clinical
M. tuberculosis
isolates, we compared the performances of five methods for the determination of
M. tuberculosis
susceptibility to PZA: the MGIT 960 system, the molecular drug susceptibility test (mDST), the pyrazinamidase (PZase) activity assay, the resazurin microtiter assay (REMA), and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction test. The sensitivities of the MGIT 960 system, the PZase activity assay, the mDST, the REMA, and the MTT assay were 98.8%, 88.8%, 90.5%, 98.8%, and 98.2%, respectively. The sensitivities of the PZase activity assay and the mDST were lower than those of the other three methods (
P
< 0.05). The specificities of the MGIT 960 system, the PZase activity assay, the mDST, the REMA and the MTT assays were 99.2%, 98.9%, 90.9%, 98.5%, and 100%, respectively. The specificity of the mDST was lower than those of the other four methods (
P
< 0.05). In conclusion, the MGIT 960 system, the MTT assay, and the REMA are superior to the PZase activity assay and the mDST in determining the susceptibility of
M. tuberculosis
to PZA. The MTT assay and the REMA might serve as alternative methods for clinical laboratories without access to the MGIT 960 system. For rapid testing in well-equipped laboratories, the mDST might be the best choice, particularly for small quantities of
M. tuberculosis
. The PZase activity assay has no obvious advantage in the assessment of
M. tuberculosis
susceptibility to PZA, as it is less accurate and requires larger quantities of bacteria.
USP4 Positively Regulates RIG-I-Mediated Antiviral Response through Deubiquitination and Stabilization of RIG-I
Authors: Wang Lijuan , Zhao Wei , Zhang Meng , Wang Peng , Zhao Kai , Zhao Xueying , Yang Shangru , Gao Chengjiang
Published: February 2013

Protein ubiquitination plays an essential role in the regulation of retinoic acid-inducible gene I (RIG-I) activation and the antiviral immune response. However, the function of the opposite process of deubiquitination in RIG-I activation remains elusive. In this study, we have identified the deubiquitinating enzyme ubiquitin-specific protease 4 (USP4) as a new regulator for RIG-I activation through deubiquitination and stabilization of RIG-I. USP4 expression was attenuated after virus-induced RIG-I activation. Overexpression of USP4 significantly enhanced RIG-I protein expression and RIG-I-triggered beta interferon (IFN-β) signaling and, at the same time, inhibited vesicular stomatitis virus (VSV) replication. Small interfering RNA (siRNA) knockdown of USP4 expression had an opposite effect. Furthermore, USP4 was found to interact with RIG-I and remove K48-linked polyubiquitination chains from RIG-I. Therefore, we identified USP4 as a new positive regulator for RIG-I that acts through deubiquitinating K48-linked ubiquitin chains and stabilizing RIG-I.
3C Protease of Enterovirus 68: Structure-Based Design of Michael Acceptor Inhibitors and Their Broad-Spectrum Antiviral Effects against Picornaviruses
Authors: Tan Jinzhi , George Shyla , Kusov Yuri , Perbandt Markus , Anemüller Stefan , Mesters Jeroen R. , Norder Helene , Coutard Bruno , Lacroix Céline , Leyssen Pieter , Neyts Johan , Hilgenfeld Rolf
Published: February 2013

We have determined the cleavage specificity and the crystal structure of the 3C protease of enterovirus 68 (EV68 3C
pro
). The protease exhibits a typical chymotrypsin fold with a Cys...His...Glu catalytic triad; its three-dimensional structure is closely related to that of the 3C
pro
of rhinovirus 2, as well as to that of poliovirus. The phylogenetic position of the EV68 3C
pro
between the corresponding enzymes of rhinoviruses on the one hand and classical enteroviruses on the other prompted us to use the crystal structure for the design of irreversible inhibitors, with the goal of discovering broad-spectrum antiviral compounds. We synthesized a series of peptidic α,β-unsaturated ethyl esters of increasing length and for each inhibitor candidate, we determined a crystal structure of its complex with the EV68 3C
pro
, which served as the basis for the next design round. To exhibit inhibitory activity, compounds must span at least P3 to P1′; the most potent inhibitors comprise P4 to P1′. Inhibitory activities were found against the purified 3C protease of EV68, as well as with replicons for poliovirus and EV71 (50% effective concentration [EC
50
] = 0.5 μM for the best compound). Antiviral activities were determined using cell cultures infected with EV71, poliovirus, echovirus 11, and various rhinovirus serotypes. The most potent inhibitor, SG85, exhibited activity with EC
50
s of ≈180 nM against EV71 and ≈60 nM against human rhinovirus 14 in a live virus–cell-based assay. Even the shorter SG75, spanning only P3 to P1′, displayed significant activity (EC
50
= 2 to 5 μM) against various rhinoviruses.
Methyltransferase PRMT1 Is a Binding Partner of HBx and a Negative Regulator of Hepatitis B Virus Transcription
Authors: Benhenda Shirine , Ducroux Aurélie , Rivière Lise , Sobhian Bijan , Ward Michael D. , Dion Sarah , Hantz Olivier , Protzer Ulrike , Michel Marie-Louise , Benkirane Monsef , Semmes Oliver J. , Buendia Marie-Annick , Neuveut Christine
Published: February 2013

The hepatitis B virus X protein (HBx) is essential for virus replication and has been implicated in the development of liver cancer. HBx is recruited to viral and cellular promoters and activates transcription by interacting with transcription factors and coactivators. Here, we purified HBx-associated factors in nuclear extracts from HepG2 hepatoma cells and identified protein arginine methyltransferase 1 (PRMT1) as a novel HBx-interacting protein. We showed that PRMT1 overexpression reduced the transcription of hepatitis B virus (HBV), and this inhibition was dependent on the methyltransferase function of PRMT1. Conversely, depletion of PRMT1 correlated with increased HBV transcription. Using a quantitative chromatin immunoprecipitation assay, we found that PRMT1 is recruited to HBV DNA, suggesting a direct effect of PRMT1 on the regulation of HBV transcription. Finally, we showed that HBx expression inhibited PRMT1-mediated protein methylation. Downregulation of PRMT1 activity was further observed in HBV-replicating cells in an
in vivo
animal model. Altogether, our results support the notion that the binding of HBx to PRMT1 might benefit viral replication by relieving the inhibitory activity of PRMT1 on HBV transcription.
An Attenuated Listeria monocytogenes Vector Primes More Potent Simian Immunodeficiency Virus-Specific Mucosal Immunity than DNA Vaccines in Mice
Authors: Im Eung-Jun , Borducchi Erica N. , Provine Nicholas M. , McNally Anna G. , Li Sufen , Frankel Fred R. , Barouch Dan H.
Published: February 2013

A human immunodeficiency virus type 1 (HIV-1) vaccine that induces potent immune responses in the gastrointestinal mucosa would be highly desirable. Here we show that attenuated recombinant
Listeria monocytogenes
, administered orally utilizing its natural route of infection, induces potent mucosal as well as systemic immune responses in mice. Moreover, these responses can be boosted efficiently with replication-incompetent adenoviral vectors.
L. monocytogenes
elicited more potent simian immunodeficiency virus (SIV) Gag-specific CD8
+
T lymphocyte responses in mucosal compartments than DNA vaccines.
The Frequency of CD127
+
Hepatitis C Virus (HCV)-Specific T Cells but Not the Expression of Exhaustion Markers Predicts the Outcome of Acute HCV Infection
Authors: Shin Eui-Cheol , Park Su-Hyung , Nascimbeni Michelina , Major Marian , Caggiari Laura , de Re Valli , Feinstone Stephen M. , Rice Charles M. , Rehermann Barbara
Published: February 2013

T cells are exhausted and overexpress inhibitory molecules in chronic hepatitis C virus (HCV) infection. It is unclear whether this is the cause or consequence of HCV persistence. By studying serial blood and liver samples of chimpanzees during acute infection, we demonstrate that the early expression of the memory precursor marker CD127 on HCV-specific T cells, but not the expression of inhibitory molecules on those T cells or their ligands in the liver, predicts the outcome of acute infection.
Kaposi's Sarcoma-Associated Herpesvirus Latency in Endothelial and B Cells Activates Gamma Interferon-Inducible Protein 16-Mediated Inflammasomes
Authors: Singh Vivek Vikram , Kerur Nagaraj , Bottero Virginie , Dutta Sujoy , Chakraborty Sayan , Ansari Mairaj Ahmed , Paudel Nitika , Chikoti Leela , Chandran Bala
Published: February 2013

Kaposi's sarcoma-associated herpesvirus (KSHV) infections of endothelial and B cells are etiologically linked with Kaposi's sarcoma (KS) and primary effusion B-cell lymphoma (PEL), respectively. KS endothelial and PEL B cells carry multiple copies of the nuclear episomal latent KSHV genome and secrete a variety of inflammatory cytokines, including interleukin-1β (IL-1β) and IL-18. The maturation of IL-1β and IL-18 depends upon active caspase-1, which is regulated by a multiprotein inflammasome complex induced by sensing of danger signals. During primary KSHV infection of endothelial cells, acting as a nuclear pattern recognition receptor, gamma interferon-inducible protein 16 (IFI16) colocalized with the KSHV genome in the nuclei and interacted with ASC and procaspase-1 to form a functional inflammasome (Kerur N et al., Cell Host Microbe 9:363-375, 2011). Here, we demonstrate that endothelial telomerase-immortalized human umbilical cells (TIVE) supporting KSHV stable latency (TIVE-LTC cells) and PEL (cavity-based B-cell lymphoma 1 [BCBL-1]) cells show evidence of inflammasome activation, such as the activation of caspase-1 and cleavage of pro-IL-1β and pro-IL-18. Interaction of ASC with IFI16 but not with AIM2 or NOD-like receptor P3 (NLRP3) was detected. The KSHV latency-associated viral FLIP (vFLIP) gene induced the expression of IL-1β, IL-18, and caspase-1 mRNAs in an NF-κB-dependent manner. IFI16 and cleaved IL-1β were detected in the exosomes released from BCBL-1 cells. Exosomal release could be a KSHV-mediated strategy to subvert IL-1β functions. In fluorescent
in situ
hybridization analyses, IFI16 colocalized with multiple copies of the KSHV genome in BCBL-1 cells. IFI16 colocalization with ASC was also detected in lung PEL sections from patients. Taken together, these findings demonstrated the constant sensing of the latent KSHV genome by IFI16-mediated innate defense and unraveled a potential mechanism of inflammation induction associated with KS and PEL lesions.
Myxoma and Vaccinia Viruses Bind Differentially to Human Leukocytes
Authors: Chan Winnie M. , Bartee Eric C. , Moreb Jan S. , Dower Ken , Connor John H. , McFadden Grant
Published: February 2013

Myxoma virus (MYXV) and vaccinia virus (VACV), two distinct members of the family
Poxviridae
, are both currently being developed as oncolytic virotherapeutic agents. Recent studies have demonstrated that
ex vivo
treatment with MYXV can selectively recognize and kill contaminating cancerous cells from autologous bone marrow transplants without perturbing the engraftment of normal CD34
+
hematopoietic stem and progenitor cells. However, the mechanism(s) by which MYXV specifically recognizes and eliminates the cancer cells in the autografts is not understood. While little is known about the cellular attachment factor(s) exploited by MYXV for entry into any target cells, VACV has been shown to utilize cell surface glycosaminoglycans such as heparan sulfate (HS), the extracellular matrix protein laminin, and/or integrin β1. We have constructed MYXV and VACV virions tagged with the Venus fluorescent protein and compared their characteristics of binding to various human cancer cell lines as well as to primary human leukocytes. We report that the binding of MYXV or VACV to some adherent cell lines could be partially inhibited by heparin, but laminin blocked only VACV binding. In contrast to cultured fibroblasts, the binding of MYXV and VACV to a wide spectrum of primary human leukocytes could not be competed by either HS or laminin. Additionally, MYXV and VACV exhibited very different binding characteristics against certain select human leukocytes, suggesting that the two poxviruses utilize different cell surface determinants for the attachment to these cells. These results indicate that VACV and MYXV can exhibit very different oncolytic tropisms against some cancerous human leukocytes.
Uterine rupture complicating sequential curettage and Bakri balloon tamponade to control secondary PPH
Authors: Ajayi Olukunle Adegboye , Sant Manjusha , Ikhena Sunday , Bako Abdumalik
Published: February 2013

A 20-year-old para 2 woman had a preterm delivery at 25 weeks and 6 days, readmitted to the hospital 25 days after delivery with severe secondary postpartum haemorrhage (PPH). Uncontrolled by initial conservative management, she underwent uterine curettage followed by Bakri balloon tamponade. She later had laparotomy for continued bleeding. She was found to have uterine rupture and hysterectomy was carried out as a life-saving measure. She was transfused in total with 14 units of blood, 1 unit of platelet, 2 units of cryoprecipitate and 3 units of fresh frozen plasma. The patient had intensive therapy unit  care and was discharged home on the sixth postoperative day. The histology report showed ectatic non-constricted vessels as the cause of the secondary PPH. No myometrial tissue, products of conception or evidence of endometritis. The sequential use of uterine curettage and balloon tamponade in the aetiology of uterine rupture is a rare occurrence.
Syphilitic limbic encephalitis revealed by status epilepticus
Authors: Derouich Ilhame , Messouak Ouafae , Belahsen Mohammed Faouzi
Published: February 2013

Limbic encephalitis (LE) is an inflammatory disorder of the limbic system; the clinical features are diverse, characterised by the development of neuropsychiatric symptoms, its aetiologies are various; syphilis is a rare entity. We report the case of a 50-year-old-man with syphilitic LE revealed by an inaugural status epilepticus. Diagnosis was made considering clinical, biological and radiological arguments. The patient received specific treatment for neurosyphilis. Evolution was marked by improved neuropsychological symptoms, the negativity of venereal disease research laboratory test in blood and cerebrospinal fluid and regression of the mesiotemporal signal abnormalities on MRI.
Multilobed mesiodens: a supernumerary tooth with unusual morphology
Authors: Dave Bhavna , Patel Jalark , Swadas Milan , Mallikarjuna Rachappa
Published: February 2013

An 8-year-old boy came with a chief complaint of an abnormally shaped tooth situated in upper front teeth region. On examination a supernumerary tooth with multiple lobes was present palatally to the maxillary right permanent central incisor. The morphology of the tooth crown was found to be unusual due to the presence of five lobes in the crown portion. Because of the supernumerary tooth, the permanent right central incisor was displaced labially. Radiographic examination showed a completely formed supernumerary tooth with dilacerated root. On the basis of clinical and radiographic examination, the supernumerary tooth was diagnosed as multilobed mesiodens. Since patient expressed dissatisfaction with the presence of supernumerary tooth, it was decided to extract this mesiodens followed by orthodontic treatment for alignment of labially placed maxillary right permanent central incisor.
Phenibut dependence
Authors: Samokhvalov Andriy V , Paton-Gay C Lindsay , Balchand Kam , Rehm Jürgen
Published: February 2013

Phenibut is a γ-aminobutyric acid (GABA) agonist designed and used as an anxiolytic in Russia. In Western countries, phenibut is not a registered medication but is available through online stores as a supplement. We present a case of a patient who used phenibut to self-medicate anxiety, insomnia and cravings for alcohol. While phenibut was helpful initially, the patient developed dependence including tolerance, significant withdrawal symptoms within 3–4 h of last use and failure to fulfil his roles at work and at home. He finally sought medical assistance in our addictions clinic. We have gradually, over the course of 9 weeks, substituted phenibut with baclofen, which has similar pharmacological properties, and then successfully tapered the patient off baclofen. This required approximately 10 mg of baclofen for each gram of phenibut.
Safety of AS03-adjuvanted split-virion H1N1 (2009) pandemic influenza vaccine: a prospective cohort study
Authors: Nazareth Irwin , Tavares Fernanda , Rosillon Dominique , Haguinet François , Bauchau Vincent
Published: February 2013

Objectives

To assess the safety of an AS03-adjuvanted split virion H1N1 (2009) vaccine (Pandemrix) in persons vaccinated during the national pandemic influenza vaccination campaign in the UK.

Design

Prospective, cohort, observational, postauthorisation safety study.

Setting

87 general practices forming part of the Medical Research Council General Practice Research Framework and widely distributed throughout England.

Participants

A cohort of 9143 individuals aged 7 months to 97 years who received at least one dose of the AS03-adjuvanted H1N1 pandemic vaccine during the national pandemic influenza vaccination campaign in the UK was enrolled. 94% completed the 6-month follow-up. Exclusion criteria were previous vaccination with other H1N1 pandemic vaccine and any child in care.

Primary and secondary outcome measures

Medically attended adverse events (MAEs) occurring within 31 days after any dose, serious adverse events (SAEs) and adverse events of special interest (AESIs) following vaccination were collected for all participants. Solicited adverse events (AEs) were assessed in a subset of participants.

Results

MAEs were reported in 1219 participants and SAEs in 113 participants during the 31-day postvaccination period. The most frequently reported MAEs and SAEs were consistent with events expected to be reported during the winter season in this population: lower respiratory tract infections, asthma and pneumonia. The most commonly reported solicited AEs were irritability in young children aged <5 years (61.8%), muscle aches in children aged 5–17 years (61.9%) and adults (46.9%). 18 AESIs, experienced by 14 patients, met the criteria to be considered for the observed-to-expected analyses. AESIs above the expected number were neuritis (1 case within 31 days) and convulsions (8 cases within 181 days). There were 41 deaths during the 181-day period after vaccination, fewer than expected.

Conclusions

Results indicate that the AS03-adjuvanted H1N1 pandemic vaccine showed a clinically acceptable reactogenicity and safety profile in all age and risk groups studied.

Trial registration

ClinicalTrials.gov,NCT00996853.
How big does the effect of an intervention have to be? Application of two novel methods to determine the smallest worthwhile effect of a fall prevention programme: a study protocol
Authors: Franco Marcia Rodrigues , Ferreira Manuela L , Howard Kirsten , Sherrington Catherine , Rose John , Haines Terry P , Ferreira Paulo
Published: February 2013

Introduction

This project concerns the identification of the smallest worthwhile effect (SWE) of exercise-based programmes to prevent falls in older people. The SWE is the smallest effect that justifies the costs, risks and inconveniences of an intervention and is used to inform the design and interpretation of systematic reviews and randomised clinical trials.

Methods and analysis

This study will comprise two different methodological approaches: the benefit-harm trade-off method and the discrete choice experiment to estimate the SWE of exercise interventions to prevent falls in older people. In the benefit-harm trade-off method, hypothetical scenarios with the benefits, costs, risks and inconveniences associated with the intervention will be presented to each participant. Then, assuming a treatment effect of certain magnitude, the participant will be asked if he or she would choose to have the intervention. The size of the hypothetical benefit will be varied up and down until it is possible to identify the SWE for which the participant would choose to have the intervention. In the discrete choice experiment, the same attributes (benefits, costs, risks and inconveniences) with varying levels will be presented as choice sets, and participants will be asked to choose between these choice sets. With this approach, we will determine the probability that a person will consider the effects of an intervention to be worthwhile, given the particular costs, risks and inconveniences. For each of the two approaches, participants will be interviewed in person and on different occasions. A subsample of the total cohort will participate in both interviews.

Ethics and dissemination

This project has received Ethics Approval from the University of Sydney Human Ethics Committee (Protocol number: 14404). Findings will be disseminated through conference presentations, seminars and peer-reviewed scientific journals.
Radiography and radiology of the carpus and proximal aspect of the metacarpus of the horse
Authors: Butler Jan
Published: February 2013

The carpus is a complex joint and interpretation of radiographs can be challenging. Pathology in this region may result from stress‐induced damage, or from acute injury. Stress‐induced osteochondral damage occurs at predictable sites, especially in the racehorse, but acute trauma leading to osteochondral changes or soft tissue injury may occur at non‐predictive sites in any horse. Although facilities for scintigraphy, computed tomography and magnetic resonance imaging are becoming increasing available, radiography, together with ultrasonography, is the main imaging modality available in practice. This article describes the radiographic projections for this region and highlights the conditions commonly seen radiographically in practice.
Comments on the dilemma in the January issue: ‘A corneal cat‐astrophe?’
Authors: Mullan Siobhan
Published: February 2013

In the January issue, a cat with a corneal laceration and protruding iris tissues was brought into your practice. Despite its injuries, it did not seem to show any signs of discomfort. A colleague believed that, based on the Animal Welfare Act 2006, the only viable treatment choices were immediate surgery to repair the cornea, enucleation of the eye or, barring these two options, euthanasia to prevent unnecessary suffering. The owner could not afford to pay for any surgery (In Practice, January 2013, volume 35, pages 46‐47). David Williams suggested that the first thing to evaluate was whether the cat was actually in pain, as its behaviour appeared normal, and decide how this might affect the Act's interpretation and the definition of ‘suffering’. Second, he wondered whether there was a fourth option available to the cat, taking into account that the ‘best’ treatment might entail a compromise between its well‐being and the financial cost to its owner. Based on this, he suggested prescribing an oral, non‐steroidal anti‐inflammatory analgesic and a topical antibiotic that would allow the laceration to heal by itself – a treatment that the owner could afford. While admittedly not ideal, as the situation would need to be kept under review in case complications arose, the cat could still live a long life pain‐free.
Internet shopping: challenges and opportunities for practices
Authors: Barabas Stephen
Published: February 2013

It can be hard to keep up with the internet sales revolution and the massive changes it has made to the way clients buy goods. But rather than avoid it and be left behind, Stephen Barabas argues that practices should embrace these changes and the opportunities they present. Here, he outlines things to consider when setting up an online shop, emphasising the importance of careful planning.
Next generation telecoms for crisis management
Authors: Grossart Dawn , Greenshaw John
Published: February 2013

Client communications and effective telecoms are practice essentials. However, with many businesses being served by older phone systems, it's easy to miss out on developments which can make significant improvements to the practice's business continuity, efficiency and the quality of client contact, as Dawn Grossart and John Greenshaw explain.
Chronic nasal discharge and sneezing in cats
Authors: Sturgess Kit
Published: February 2013

Sneezing and nasal discharge are a relatively common presentation in cats, often accompanied by involvement of the sinuses and the middle ear. Common associated clinical signs are noisy breathing and inappetence/weight loss. The best outcome for the patient occurs when a specific, treatable cause is identified; however, in a significant number of cases the nasal discharge is the chronic sequel to a respiratory virus infection. In such cases squamous metaplasia of the nasal mucosa means that complete resolution is unlikely, making good long‐term management the goal. This article discusses the various causes of sneezing and chronic nasal discharge in the cat, and suggests diagnostic routes and therapeutic options.
Angiographic warning of hemorrhagic transformation after stent retriever thrombectomy procedure
Authors: Vollman Andrew T , Bruno Charles A , Dumeer Shifali , Malone Hani , Meyers Philip M
Published: February 2013

This study reports cerebral angiographic findings observed after stent retriever thrombectomy that is suggestive of a higher risk of hemorrhagic transformation (HT). A woman aged 65–75 presented with a right middle cerebral artery syndrome confirmed by non-contrast CT brain scan. Endovascular revascularization using the Solitaire device was placed across the thromboembolic occlusion and thromboembolectomy was performed. Angiography showed complete recanalization of the left internal carotid artery, anterior and middle cerebral artery branches. Twelve hours following the procedure the patient had a hemorrhagic conversion of the ischemic infarct with significant mass effect causing herniation. Despite surgical intervention (hemicraniectomy) the patient died. The angiographic features following revascularization of the vessels distal to the occlusion showed subtle dilations which were visualized at the branch points of the vessels. This may be a warning sign of increased risk of HT.
An analysis of the current educational status and future training needs of China's rural doctors in 2011
Authors: Li Xingming , Liu Juyuan , Huang Jianshi , Qian Yunliang , Che Lu
Published: February 2013

Objectives

To analyse the educational status and future training needs of China's rural doctors and provide a basis to improve their future training.

Methods

A cross-sectional epidemiological survey was used for the analysis, and 17 954 rural doctors chosen randomly from the eastern, central and western regions of China in 2009–2010 were surveyed to ascertain their average training time and the methods used for and content of their training.

Results

In general, 8671/17 778 (48.77%) of respondents received less than 12 days of training in a year. Conference sessions seemed to be the major route of training, with 10 150/17 925 respondents (56.62%). Clinical skills, with a response rate of 14 441/17 926 (80.56%), seemed to be the most popular training content. With regard to the general needs for training time received, 6547/18 255 (35.86%) of respondents hoped the average training time received a year would be less than 12 days; on-site guidance from a senior doctor was the most popular training method with response rate of 10 109/17 976 (56.24%), and clinical skills was what rural doctors wished to study the most, with a positive response of 16 744/17 962 (93.22%). Statistically significant differences existed in the current status and training time, training method and training content needs of China's rural doctors.

Conclusions

Our results suggest that the training status and needs of China's rural doctors are still disjointed; measures including the introduction of remote education and clinical further education, extended training time and more clinical skills training should be adopted.
DECAY COUPLING CONSTANT SUM RULES FOR TETRAQUARKS $T[(\bar{Q}q)(Q\bar{q})]$ WITH BROKEN SU(3) SYMMETRY
Authors: GUPTA V. , SÁNCHEZ-COLÓN G. , RAJPOOT S.
Published: February 2013

For tetraquarks of the form [Formula: see text] we give sum rules for their decay coupling constants, taking into account the SU(3) symmetry breaking interactions to first-order.