bluuebunny/crossref_metadata_2025 huggingface dataset:
Solution based prompt inorganic condensation and atomic layer deposition of Al2O3 films: A side-by-side comparison
Authors: Smith Sean W. , Wang Wei , Keszler Douglas A. , Conley John F.
Published: May 2014

A comparison was made of Al2O3 films deposited on Si via prompt inorganic condensation (PIC) and atomic layer deposition (ALD). Current–voltage measurements as a function of annealing temperature indicate that the solution-processed PIC films, annealed at 500 °C, exhibit lower leakage and roughly equivalent breakdown strength in comparison to ALD films. PIC films are less dense than as-deposited ALD films and capacitance–voltage measurements indicate a lower relative dielectric constant. On the basis of x-ray photoelectron spectroscopy, transmission electron microscopy, and energy dispersive x-ray spectroscopy, it is found that the 500 °C anneal results in the formation of a ∼6 nm thick interfacial SiO2 layer at the Si interface. This SiO2 interfacial layer significantly affects the electrical performance of PIC Al2O3 films deposited on Si.
Physicochemical perspective on “polydopamine” and “poly(catecholamine)” films for their applications in biomaterial coatings (Review)
Authors: Ball Vincent
Published: May 2014

Bioinspired poly(catecholamine) based coatings, mostly "polydopamine," were conceived based on the chemistry used by mussels to adhere strongly to the surface of stones and wood in water and to remain attached to their substrates even under conditions of strong shear stresses. These kinds of films can in turn be easily modified with a plethora of molecules and inorganic (nano)materials. This review shows that poly(catecholamine) based coatings are an ideal film forming method for applications in the field of biomaterials. It is written from a physicochemical and a materials science perspective and discusses optical, chemical, electrochemical, and mechanical properties of polydopamine films. It further demonstrates that a better understanding of the polydopamine film deposition mechanism is warranted to improve the properties of these coatings even further.
A critical gel fluid with high extensibility: The rheology of chewing gum
Authors: Martinetti Luca , Mannion Alexander M. , Voje William E. , Xie Renxuan , Ewoldt Randy H. , Morgret Leslie D. , Bates Frank S. , Macosko Christopher W.
Published: May 2014

Chewing gum provides an excellent everyday example of viscoelastic behavior, and understanding its rheological properties is important for application purposes. Here, we compare the rheological behavior of selected commercial chewing gums and bubble gums. Small amplitude oscillatory shear, shear creep, and steady shear demonstrated that both chewing and bubble gums behave like power-law critical gels in the linear regime. Nonlinear viscoelastic behavior was investigated using large amplitude oscillatory shear, shear creep, and start-up flows (in shear and uniaxial extension). Bubble gums showed more pronounced strain hardening and greater stresses to break in start-up of steady uniaxial extension than chewing gums. We argue that this combination of rheological signatures is sufficient to provide a new robust definition of chewing gum that is independent of specific molecular composition. There are potentially many different formulations and design routes that can achieve this distinctive rheological fingerprint.
Sound Strategies for Hearing Restoration
Authors: Géléoc Gwenaëlle S. G. , Holt Jeffrey R.
Published: May 2014

Hearing Aid

Many millions of people across the globe are subject to hearing loss.
Géléoc and Holt
(
10.1126/science.1241062
) review recent developments in potential therapeutic strategies to restore inner-ear function in patients with acquired or genetic forms of deafness. While challenges remain, fundamental research in molecular, gene, and stem-cell therapies has enabled progress toward developing alternatives to conventional, sound amplification–based prostheses.
Spatially Distributed Local Fields in the Hippocampus Encode Rat Position
Authors: Agarwal Gautam , Stevenson Ian H. , Berényi Antal , Mizuseki Kenji , Buzsáki György , Sommer Friedrich T.
Published: May 2014

Extracting Spatial Information

The location of a rat can be deciphered from hippocampal activity by detecting the firing of individual place-selective neurons. In contrast, the local field potential (LFP), which arises from the coherent voltage fluctuations of large hippocampal cell populations, has been hard to decode.

Agarwal
et al.

(p.
626
) worked out how to recover positional information exclusively from multiple-site LFP measurements in the rat hippocampus. The information was as precise as that derived from spiking place cells. The approach might also be applicable more generally for deciphering information from coherent population activity anywhere in the brain.
Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer
Authors: Tran Eric , Turcotte Simon , Gros Alena , Robbins Paul F. , Lu Yong-Chen , Dudley Mark E. , Wunderlich John R. , Somerville Robert P. , Hogan Katherine , Hinrichs Christian S. , Parkhurst Maria R. , Yang James C. , Rosenberg Steven A.
Published: May 2014

T Cells for Epithelial Tumors

Malignant tumors harbor genetic alterations. Recently, adoptive T cell therapies have taken advantage of this: T cells specific for mutations in tumors are infused into patients to generate an antitumor immune response. Although therapeutic benefit has been seen for melanomas, effectiveness against more common epithelial tumors is unclear. Using whole-exome sequencing,

Tran
et al.

(p.
641
) identified tumor-infiltrating CD4+ T cells specific for a mutated antigen expressed by a tumor from a patient with metastatic cholangiocarcinoma. Infusion of this patient with an expanded-population, mutation-specific T cell resulted in tumor regression and stabilization of disease.
Restoration of Large Damage Volumes in Polymers
Authors: White S. R. , Moore J. S. , Sottos N. R. , Krull B. P. , Santa Cruz W. A. , Gergely R. C. R.
Published: May 2014

Self-Healing Larger Wounds

By loading a polymer with pockets of monomer, it is possible to heal small cracks in a sample through the polymerization of the monomer following the formation of a crack. However, large holes are much harder to repair.

White
et al.

(p.
620
; see the Perspective by

Zhao and Arruda

) developed a vascular-like repair system involving a dual-stage strategy to self-heal epoxy thermosets. After injecting a damaged site with precursors, a gel with reversible cross-links rapidly formed, so the material stayed in place that then solidified further upon cross-linking. The approach successfully patched holes larger than 3 centimeters in diameter.
Comment on “Revealing Nature’s Cellulase Diversity: The Digestion Mechanism of
Caldicellulosiruptor bescii
CelA”
Authors: Gusakov Alexander V.
Published: May 2014

Brunecky
et al
. (Reports, 20 December 2013, p. 1513) compared the cellulolytic activity of bacterial multimodular cellulase CelA with fungal Cel7A (cellobiohydrolase I from
Trichoderma reesei
). If more active Cel7A from another fungus were used as a reference enzyme under optimal conditions with β-glucosidase added, the reported difference between bacterial and fungal enzymes would be less dramatic.
New Sites Bring the Earliest Americans Out of the Shadows
Authors: Gibbons Ann
Published: May 2014

Archaeologists are finding new evidence that Paleoindians spread throughout North and South America earlier than long believed—and even camped high in the Andes Mountains.
'Sea Butterflies' Are a Canary for Ocean Acidification
Authors: Kintisch Eli
Published: May 2014

The shells of sea snails off the Pacific coast are dissolving, scientists report, raising new questions about the severity of ocean acidification.
The Importance of Bioinformatics in NGS: Breaking the Bottleneck in Data Interpretation
Authors: Funari Vincent , Canosa Sandra J.
Published: May 2014

Unprecedented advances have been made in the speed and throughput of next generation sequencing (NGS) platforms over the last decade. This progress has imposed increasingly high demands on the bioinformatics tools necessary for analysis of the data generated, which has grown exponentially. Although hundreds of thousands of samples have been sequenced, our ability to find, associate, and implicate genetic variants and candidate disease genes far outstrips our ability to understand them. Many researchers are comfortable with NGS technology, but encounter difficulties with the bioinformatics portion of their workflow, rendering NGS a less attractive option as their primary sequencing platform. However, once clear bioinformatics procedures are established and optimized this bottleneck can be removed, resulting in smooth and routine data interpretation processes and expedited research discoveries. During this webinar, our expert speakers will discuss their bioinformatics strategies and applications in range of fields of clinical research.
Neisseria Adhesin A Variation and Revised Nomenclature Scheme
Authors: Bambini Stefania , De Chiara Matteo , Muzzi Alessandro , Mora Marirosa , Lucidarme Jay , Brehony Carina , Borrow Ray , Masignani Vega , Comanducci Maurizio , Maiden Martin C. J. , Rappuoli Rino , Pizza Mariagrazia , Jolley Keith A.
Published: May 2014

Neisseriaadhesin A (NadA), involved in the adhesion and invasion ofNeisseria meningitidisinto host tissues, is one of the major components of Bexsero, a novel multicomponent vaccine licensed for protection against meningococcal serogroup B in Europe, Australia, and Canada. NadA has been identified in approximately 30% of clinical isolates and in a much lower proportion of carrier isolates. Three protein variants were originally identified in invasive meningococci and named NadA-1, NadA-2, and NadA-3, whereas most carrier isolates either lacked the gene or harbored a different variant, NadA-4. Further analysis of isolates belonging to the sequence type 213 (ST-213) clonal complex identified NadA-5, which was structurally similar to NadA-4, but more distantly related to NadA-1, -2, and -3. At the time of this writing, more than 89 distinctnadAallele sequences and 43 distinct peptides have been described. Here, we present a revised nomenclature system, taking into account the complete data set, which is compatible with previous classification schemes and is expandable. The main features of this new scheme include (i) the grouping of the previously named NadA-2 and NadA-3 variants into a single NadA-2/3 variant, (ii) the grouping of the previously assigned NadA-4 and NadA-5 variants into a single NadA-4/5 variant, (iii) the introduction of an additional variant (NadA-6), and (iv) the classification of the variants into two main groups, named groups I and II. To facilitate querying of the sequences and submission of new allele sequences, the nucleotide and amino acid sequences are available athttp://pubmlst.org/neisseria/NadA/.
Expansion and Evolution of a Virulent, Extensively Drug-Resistant (Polymyxin B-Resistant), QnrS1-, CTX-M-2-, and KPC-2-Producing Klebsiella pneumoniae ST11 International High-Risk Clone
Authors: Andrade Leonardo Neves , Vitali Lúcia , Gaspar Gilberto Gambero , Bellissimo-Rodrigues Fernando , Martinez Roberto , Darini Ana Lúcia Costa
Published: May 2014

In this study, we report the early expansion, evolution, and characterization of a multiresistant
Klebsiella pneumoniae
clone that was isolated with increasing frequency from inpatients in a tertiary-care university hospital in Brazil. Seven carbapenem- and quinolone-resistant and polymyxin B-susceptible or -resistant
K. pneumoniae
isolates isolated between December 2012 and February 2013 were investigated. Beta-lactamase- and plasmid-mediated quinolone resistance (PMQR)-encoding genes and the genetic environment were investigated using PCR, sequencing, and restriction fragment length polymorphism (RFLP). Clonal relatedness was established using XbaI–pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and phylogenetic group characterization. Plasmid analyses included PCR-based replicon typing (PBRT) and hybridization of the
S1
-PFGE product, plasmid MLST, and conjugation experiments. Virulence potential was assessed by PCR by searching for 10 virulence factor-encoding genes (
ureA
,
fimH
,
kfuBC
,
uge
,
wabG
,
magA
,
mrkD
,
allS
,
rmpA
, and
cf29a
) and by phenotypic tests to analyze the hypermucoviscous phenotype. The genetic context of a multidrug-resistant and extensively drug-resistant
K. pneumoniae
ST11-KpI clone harboring IncFIIk-Tn
4401a-bla
KPC-2
,
qnrS1
, and
bla
CTX-M-2
was found. Moreover, three isolates displayed high resistance to polymyxin B (MICs = 32, 32, and 128 mg/liter) as well as mucous and hypermucoviscous phenotypes. These bacteria also harbored
ureA
,
fimH
,
uge
,
wabG
, and
mrkD
, which code for virulence factors associated with binding, biofilm formation, and the ability to colonize and escape from phagocytosis. Our study describes the association of important coresistance and virulence factors in the
K. pneumoniae
ST11 international high-risk clone, which makes this pathogen successful at infections and points to the quick expansion and evolution of this multiresistant and virulent clone, leading to a pandrug-resistant phenotype and persistent bacteria in a Brazilian hospital.
Utility of
rpoB
Gene Sequencing for Identification of Nontuberculous Mycobacteria in the Netherlands
Authors: de Zwaan Rina , van Ingen Jakko , van Soolingen Dick
Published: May 2014

In the Netherlands, clinical isolation of nontuberculous mycobacteria (NTM) has increased over the past decade. Proper identification of isolates is important, as NTM species differ strongly in clinical relevance. Most of the currently applied identification methods cannot distinguish between all different
Mycobacterium
species and complexes within species.
rpoB
gene sequencing exhibits a promising level of discrimination among rapidly and slowly growing mycobacteria, including the
Mycobacterium avium
complex. In this study, we prospectively compared
rpoB
gene sequencing with our routine algorithm of reverse line blot identification combined with partial 16S rRNA gene sequencing of 455 NTM isolates.
rpoB
gene sequencing identified 403 isolates to species level as 45 different known species and identified 44 isolates to complex level, and eight isolates remained unidentifiable to species level. In contrast, our reference reverse line blot assay with adjunctive 16S rRNA gene sequencing identified 390 isolates to species level (30 distinct species) and identified 56 isolates to complex level, and nine isolates remained unidentified. The higher discriminatory power of
rpoB
gene sequencing results largely from the distinction of separate species within complexes and subspecies. Also,
Mycobacterium gordonae
,
Mycobacterium kansasii
, and
Mycobacterium interjectum
were separated into multiple groupings with relatively low sequence similarity (98 to 94%), suggesting that these are complexes of closely related species. We conclude that
rpoB
gene sequencing is a more discriminative identification technique than the combination of reverse line blot and 16S rRNA gene sequencing and could introduce a major improvement in clinical care of NTM disease and the research on the epidemiology and clinical relevance of NTM.
Evaluation of Three Rapid Diagnostic Methods for Direct Identification of Microorganisms in Positive Blood Cultures
Authors: Martinez Raquel M. , Bauerle Elizabeth R. , Fang Ferric C. , Butler-Wu Susan M.
Published: May 2014

The identification of organisms from positive blood cultures generally takes several days. However, recently developed rapid diagnostic methods offer the potential for organism identification within only a few hours of blood culture positivity. In this study, we evaluated the performance of three commercial methods to rapidly identify organisms directly from positive blood cultures:
Quick
FISH (AdvanDx, Wolburn, MA), Verigene Gram-Positive Blood Culture (BC-GP; Nanosphere, Northbrook, IL), and matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) with Sepsityper processing (Bruker Daltonics, Billerica, MA). A total of 159 blood cultures (VersaTREK Trek Diagnostic Systems, Cleveland, OH) positive for Gram-positive and Gram-negative bacteria as well as yeast were analyzed with
Quick
FISH and MALDI-TOF MS. In all, 102 blood cultures were analyzed using the BC-GP assay. For monomicrobial cultures, we observed 98.0% concordance with routine methods for both
Quick
FISH (143/146) and the BC-GP assay (93/95). MALDI-TOF MS demonstrated 80.1% (117/146) and 87.7% (128/146) concordance with routine methods to the genus and species levels, respectively. None of the methods tested were capable of consistently identifying polymicrobial cultures in their entirety or reliably differentiating
Streptococcus pneumoniae
from viridans streptococci. Nevertheless, the methods evaluated in this study are convenient and accurate for the most commonly encountered pathogens and have the potential to dramatically reduce turnaround time for the provision of results to the treating physician.
Description of Dientamoeba fragilis Cyst and Precystic Forms from Human Samples
Authors: Stark D. , Garcia L. S. , Barratt J. L. N. , Phillips O. , Roberts T. , Marriott D. , Harkness J. , Ellis J. T.
Published: May 2014

Dientamoeba fragilis
is a common enteropathogen of humans. Recently a cyst stage of the parasite was described in an animal model; however, no cyst stage has been described in detail from clinical samples. We describe both cyst and precystic forms from human clinical samples.
“Meet the Expert Interviews,” an Integrative Learning Experience for Microbiology and Anatomy & Physiology Undergraduate Students
Authors: Davis Barbara D. , Flannery Mary , Lowe Marty , Payne Jeannie S.
Published: May 2014

An important goal of higher education is to encourage students to integrate learning and apply skills to different situations. In the “Meet the Expert Interviews” students interviewed authors of research papers on Shiga Toxin Producing E. coli (STEC) outbreaks. Students attended seminars, analyzed STEC publications, created questions, and interviewed authors. We hypothesized that the project would enhance student understanding of STEC and encourage students to integrate and apply information to real world problems.

The project was assessed by student surveys. The majority of 129 students surveyed agreed or strongly agreed that the seminar enhanced their understanding of E.coli transmission, diagnosis, and treatment; that the interview enhanced their understanding of epidemiology; and made them more aware of the steps involved in determining the cause of the outbreak. The project was engaging for students and faculty and provided a unique way for professional outreach to biology students. The project is an innovative example of an integrative method to enhance student learning and interaction with microbiology and epidemiology professionals.
Making Heads or Tails: Planarian Stem Cells in the Classroom
Authors: Srougi Melissa C. , Thomas-Swanik Jackie , Chan John D. , Marchant Jonathan S. , Carson Susan
Published: May 2014

Stem cells hold great promise in the treatment of diseases ranging from cancer to dementia. However, as rapidly as the field of stem cell biology has emerged, heated political debate has followed, scrutinizing the ethical implications of stem cell use. It is therefore imperative to promote scientific literacy by educating students about stem cell biology. Yet, there is a definite lack of material to engage students in this subject at the basic science level. Therefore, we have developed and implemented a hands-on introductory laboratory module that introduces students to stem cell biology and can be easily incorporated into existing curricula. Students learn about stem cell biology using an
in vivo
planarian model system in which they down-regulate two genes important in stem cell differentiation using RNA interference and then observe the regenerative phenotype. The module was piloted at the high school, community college, and university levels. Here, we report that introductory biology students enrolled at a community college were able to demonstrate gains in learning after completion of a one-hour lecture and four 45-minute laboratory sessions over the course of three weeks. These gains in learning outcomes were objectively evaluated both before and after its execution using a student quiz and experimental results. Furthermore, students’ self-assessments revealed increases in perceived knowledge as well as a general interest in stem cells. Therefore, these data suggest that this module is a simple, useful way to engage and to teach students about stem cell biology.
The Ups and Downs of Emerging Infectious Diseases at Your FingertipsReview of:	Emerging Infectious Diseases: A Guide to Diseases, Causative Agents, and Surveillance;	BeltzLisa A; (	2011).	Jossey-Bass, John Wiley & Sons,	San Francisco, CA.	734 pages.
Authors: Jandu Narveen
Published: May 2014

Review of:
Emerging Infectious Diseases: A Guide to Diseases, Causative Agents, and Surveillance;
Lisa A Beltz; (2011). Jossey-Bass, John Wiley & Sons, San Francisco, CA. 734 pages.
A Weekly Spark for Progressive Educators: Annie Murphy Paul’s Brilliant Blog and Newsletter
Authors: Hines Stephen A.
Published: May 2014

Review of:
Annie Murphy Paul: Brilliant: The Science of Smart. A newsletter bringing you the latest intelligence on learning.
http://anniemurphypaul.com/
Proteolytic Activation of the Porcine Epidemic Diarrhea Coronavirus Spike Fusion Protein by Trypsin in Cell Culture
Authors: Wicht Oliver , Li Wentao , Willems Lione , Meuleman Tom J. , Wubbolts Richard W. , van Kuppeveld Frank J. M. , Rottier Peter J. M. , Bosch Berend Jan
Published: May 2014

Isolation of porcine epidemic diarrhea coronavirus (PEDV) from clinical material in cell culture requires supplementation of trypsin. This may relate to the confinement of PEDV natural infection to the protease-rich small intestine of pigs. Our study focused on the role of protease activity on infection by investigating the spike protein of a PEDV isolate (wtPEDV) using a reverse genetics system based on the trypsin-independent cell culture-adapted strain DR13 (caPEDV). We demonstrate that trypsin acts on the wtPEDV spike protein after receptor binding. We mapped the genetic determinant for trypsin-dependent cell entry to the N-terminal region of the fusion subunit of this class I fusion protein, revealing a conserved arginine just upstream of the putative fusion peptide as the potential cleavage site. Whereas coronaviruses are typically processed by endogenous proteases of the producer or target cell, PEDV S protein activation strictly required supplementation of a protease, enabling us to study mechanistic details of proteolytic processing.

IMPORTANCE
Recurring PEDV epidemics constitute a serious animal health threat and an economic burden, particularly in Asia but, as of recently, also on the North-American subcontinent. Understanding the biology of PEDV is critical for combatting the infection. Here, we provide new insight into the protease-dependent cell entry of PEDV.
The Varicella-Zoster Virus Portal Protein Is Essential for Cleavage and Packaging of Viral DNA
Authors: Visalli Melissa A. , House Brittany L. , Selariu Anca , Zhu Hua , Visalli Robert J.
Published: May 2014

The varicella-zoster virus (VZV) open reading frame 54 (ORF54) gene encodes an 87-kDa monomer that oligomerizes to form the VZV portal protein, pORF54. pORF54 was hypothesized to perform a function similar to that of a previously described herpes simplex virus 1 (HSV-1) homolog, pUL6. pUL6 and the associated viral terminase are required for processing of concatemeric viral DNA and packaging of individual viral genomes into preformed capsids. In this report, we describe two VZV bacterial artificial chromosome (BAC) constructs with ORF54 gene deletions, Δ54L (full ORF deletion) and Δ54S (partial internal deletion). The full deletion of ORF54 likely disrupted essential adjacent genes (ORF53 and ORF55) and therefore could not be complemented on an ORF54-expressing cell line (ARPE54). In contrast, Δ54S was successfully propagated in ARPE54 cells but failed to replicate in parental, noncomplementing ARPE19 cells. Transmission electron microscopy confirmed the presence of only empty VZV capsids in Δ54S-infected ARPE19 cell nuclei. Similar to the HSV-1 genome, the VZV genome is composed of a unique long region (U
L
) and a unique short region (U
S
) flanked by inverted repeats. DNA from cells infected with parental VZV (VZV
LUC
strain) contained the predicted U
L
and U
S
termini, whereas cells infected with Δ54S contained neither. This result demonstrates that Δ54S is not able to process and package viral DNA, thus making pORF54 an excellent chemotherapeutic target. In addition, the utility of BAC constructs Δ54L and Δ54S as tools for the isolation of site-directed ORF54 mutants was demonstrated by recombineering single-nucleotide changes within ORF54 that conferred resistance to VZV-specific portal protein inhibitors.

IMPORTANCE
Antivirals with novel mechanisms of action would provide additional therapeutic options to treat human herpesvirus infections. Proteins involved in the herpesviral DNA encapsidation process have become promising antiviral targets. Previously, we described a series of
N
-α-methylbenzyl-
N
′-aryl thiourea analogs that target the VZV portal protein (pORF54) and prevent viral replication
in vitro
. To better understand the mechanism of action of these compounds, it is important to define the structural and functional characteristics of the VZV portal protein. In contrast to HSV, no VZV mutants have been described for any of the seven essential DNA encapsidation genes. The VZV ORF54 deletion mutant described in this study represents the first VZV encapsidation mutant reported to date. We demonstrate that the deletion mutant can serve as a platform for the isolation of portal mutants via recombineering and provide a strategy for more in-depth studies of VZV portal structure and function.
Identification of Amino Acid Substitutions with Compensational Effects in the Attachment Protein of Canine Distemper Virus
Authors: Sattler Ursula , Khosravi Mojtaba , Avila Mislay , Pilo Paola , Langedijk Johannes P. , Ader-Ebert Nadine , Alves Lisa A. , Plattet Philippe , Origgi Francesco C.
Published: May 2014

The hemagglutinin (H) gene of canine distemper virus (CDV) encodes the receptor-binding protein. This protein, together with the fusion (F) protein, is pivotal for infectivity since it contributes to the fusion of the viral envelope with the host cell membrane. Of the two receptors currently known for CDV (nectin-4 and the signaling lymphocyte activation molecule [SLAM]), SLAM is considered the most relevant for host susceptibility. To investigate how evolution might have impacted the host-CDV interaction, we examined the functional properties of a series of missense single nucleotide polymorphisms (SNPs) naturally accumulating within the H-gene sequences during the transition between two distinct but related strains. The two strains, a wild-type strain and a consensus strain, were part of a single continental outbreak in European wildlife and occurred in distinct geographical areas 2 years apart. The deduced amino acid sequence of the two H genes differed at 5 residues. A panel of mutants carrying all the combinations of the SNPs was obtained by site-directed mutagenesis. The selected mutant, wild type, and consensus H proteins were functionally evaluated according to their surface expression, SLAM binding, fusion protein interaction, and cell fusion efficiencies. The results highlight that the most detrimental functional effects are associated with specific sets of SNPs. Strikingly, an efficient compensational system driven by additional SNPs appears to come into play, virtually neutralizing the negative functional effects. This system seems to contribute to the maintenance of the tightly regulated function of the H-gene-encoded attachment protein.

IMPORTANCE
To investigate how evolution might have impacted the host-canine distemper virus (CDV) interaction, we examined the functional properties of naturally occurring single nucleotide polymorphisms (SNPs) in the hemagglutinin gene of two related but distinct strains of CDV. The hemagglutinin gene encodes the attachment protein, which is pivotal for infection. Our results show that few SNPs have a relevant detrimental impact and they generally appear in specific combinations (molecular signatures). These drastic negative changes are neutralized by compensatory mutations, which contribute to maintenance of an overall constant bioactivity of the attachment protein. This compensational mechanism might reflect the reaction of the CDV machinery to the changes occurring in the virus following antigenic variations critical for virulence.
Analysis of Recombinant H7N9 Wild-Type and Mutant Viruses in Pigs Shows that the Q226L Mutation in HA Is Important for Transmission
Authors: Liu Qinfang , Zhou Bin , Ma Wenjun , Bawa Bhupinder , Ma Jingjiao , Wang Wei , Lang Yuekun , Lyoo Young , Halpin Rebecca A. , Lin Xudong , Stockwell Timothy B. , Webby Richard , Wentworth David E. , Richt Juergen A.
Published: May 2014

The fact that there have been more than 300 human infections with a novel avian H7N9 virus in China indicates that this emerging strain has pandemic potential. Furthermore, many of the H7N9 viruses circulating in animal reservoirs contain putative mammalian signatures in the HA and PB2 genes that are believed to be important in the adaptation of other avian strains to humans. To date, the definitive roles of these mammalian-signature substitutions in transmission and pathogenesis of H7N9 viruses remain unclear. To address this we analyzed the biological characteristics, pathogenicity, and transmissibility of A/Anhui/1/2013 (H7N9) virus and variants
in vitro
and
in vivo
using a synthetically created wild-type virus (rAnhui-WT) and two mutants (rAnhui-HA-226Q and rAnhui-PB2-627E). All three viruses replicated in lungs of intratracheally inoculated pigs, yet nasal shedding was limited. The rAnhui-WT and rAnhui-PB2-627E viruses were transmitted to contact animals. In contrast, the rAnhui-HA-226Q virus was not transmitted to sentinel pigs. Deep sequencing of viruses from the lungs of infected pigs identified substitutions arising in the viral population (e.g., PB2-T271A, PB2-D701N, HA-V195I, and PB2-E627K reversion) that may enhance viral replication in pigs. Collectively, the results demonstrate that critical mutations (i.e., HA-Q226L) enable the H7N9 viruses to be transmitted in a mammalian host and suggest that the myriad H7N9 genotypes circulating in avian species in China and closely related strains (e.g., H7N7) have the potential for further adaptation to human or other mammalian hosts (e.g., pigs), leading to strains capable of sustained human-to-human transmission.

IMPORTANCE
The genomes of the zoonotic avian H7N9 viruses emerging in China have mutations in critical genes (PB2-E627K and HA-Q226L) that may be important in their pandemic potential. This study shows that (i) HA-226L of zoonotic H7N9 strains is critical for binding the α-2,6-linked receptor and enables transmission in pigs; (ii) wild-type A/Anhui/1/2013 (H7N9) shows modest replication, virulence, and transmissibility in pigs, suggesting that it is not well adapted to the mammalian host; and (iii) both wild-type and variant H7N9 viruses rapidly develop additional mammalian-signature mutations in pigs, indicating that they represent an important potential intermediate host. This is the first study analyzing the phenotypic effects of specific mutations within the HA and PB2 genes of the novel H7N9 viruses created by reverse genetics in an important mammalian host model. Finally, this study illustrates that loss-of-function mutations can be used to effectively identify residues critical to zoonosis/transmission.
Hijacking of Host Calreticulin Is Required for the White Spot Syndrome Virus Replication Cycle
Authors: Watthanasurorot Apiruck , Guo Enen , Tharntada Sirinit , Lo Chu-Fang , Söderhäll Kenneth , Söderhäll Irene
Published: May 2014

We have previously shown that multifunctional calreticulin (CRT), which resides in the endoplasmic reticulum (ER) and is involved in ER-associated protein processing, responds to infection with white spot syndrome virus (WSSV) by increasing mRNA and protein expression and by forming a complex with gC1qR and thereby delaying apoptosis. Here, we show that CRT can directly interact with WSSV structural proteins, including VP15 and VP28, during an early stage of virus infection. The binding of VP28 with CRT does not promote WSSV entry, and CRT-VP15 interaction was detected in the viral genome in virally infected host cells and thus may have an effect on WSSV replication. Moreover, CRT was detected in the viral envelope of purified WSSV virions. CRT was also found to be of high importance for proper oligomerization of the viral structural proteins VP26 and VP28, and when CRT glycosylation was blocked with tunicamycin, a significant decrease in both viral replication and assembly was detected. Together, these findings suggest that CRT confers several advantages to WSSV, from the initial steps of WSSV infection to the assembly of virions. Therefore, CRT is required as a “vital factor” and is hijacked by WSSV for its replication cycle.

IMPORTANCE
White spot syndrome virus (WSSV) is a double-stranded DNA virus and the cause of a serious disease in a wide range of crustaceans that often leads to high mortality rates. We have previously shown that the protein calreticulin (CRT), which resides in the endoplasmic reticulum (ER) of the cell, is important in the host response to the virus. In this report, we show that the virus uses this host protein to enter the cell and to make the host produce new viral structural proteins. Through its interaction with two viral proteins, the virus “hijacks” host calreticulin and uses it for its own needs. These findings provide new insight into the interaction between a large DNA virus and the host protein CRT and may help in understanding the viral infection process in general.
Recombinant Covalently Closed Circular Hepatitis B Virus DNA Induces Prolonged Viral Persistence in Immunocompetent Mice
Authors: Qi Zhihua , Li Gaiyun , Hu Hao , Yang Chunhui , Zhang Xiaoming , Leng Qibin , Xie Youhua , Yu Demin , Zhang Xinxin , Gao Yueqiu , Lan Ke , Deng Qiang
Published: May 2014

It remains crucial to develop a laboratory model for studying hepatitis B virus (HBV) chronic infection. We hereby produced a recombinant covalently closed circular DNA (rcccDNA) in view of the key role of cccDNA in HBV persistence. AloxP-chimeric intron was engineered into a monomeric HBV genome in a precursor plasmid (prcccDNA), which was excised using Cre/loxP-mediated DNA recombination into a 3.3-kb rcccDNA in the nuclei of hepatocytes. The chimeric intron was spliced from RNA transcripts without interrupting the HBV life cycle. In cultured hepatoma cells, cotransfection of prcccDNA and pCMV-Cre (encoding Cre recombinase) resulted in accumulation of nuclear rcccDNA that was heat stable and epigenetically organized as a minichromosome. A mouse model of HBV infection was developed by hydrodynamic injection of prcccDNA. In the presence of Cre recombinase, rcccDNA was induced in the mouse liver with effective viral replication and expression, triggering a compromised T-cell response against HBV. Significant T-cell hyporesponsiveness occurred in mice receiving 4 μg prcccDNA, resulting in prolonged HBV antigenemia for up to 9 weeks. Persistent liver injury was observed as elevated alanine transaminase activity in serum and sustained inflammatory infiltration in the liver. Although a T-cell dysfunction was induced similarly, mice injected with a plasmid containing a linear HBV replicon showed rapid viral clearance within 2 weeks. Collectively, our study provides an innovative approach for producing a cccDNA surrogate that established HBV persistence in immunocompetent mice. It also represents a useful model systemin vitroandin vivofor evaluating antiviral treatments against HBV cccDNA.

IMPORTANCE(i) Unlike plasmids that contain a linear HBV replicon, rcccDNA established HBV persistence with sustained liver injury in immunocompetent mice. This method could be a prototype for developing a mouse model of chronic HBV infection. (ii) An exogenous intron was engineered into the HBV genome for functionally seamless DNA recombination. This original approach could be also extended to other viral studies. (iii) rcccDNA was substantially induced in the nuclei of hepatocytes and could be easily distinguished by its exogenous intron using PCR. This convenient model system affords the opportunity to test antivirals directly targeting HBV cccDNA.
Xanthogranulomatous cholecystitis mimicking gallbladder cancer
Authors: Ewelukwa Ofor , Ali Omair , Akram Salma
Published: May 2014

Xanthogranulomatous cholecystitis (XGC) is a benign, uncommon variant of chronic cholecystitis characterised by focal or diffuse destructive inflammatory process of the gallbladder (GB). Macroscopically, it appears like yellowish tumour-like masses in the wall of the GB. This article reports on a 74-year-old woman with XGC mimicking GB cancer.
Acute kidney injury in a diabetic haemophiliac: one step at a time
Authors: Althaf Mohammed Mahdi , Hussein Maged Hassan , Abdelsalam Mohamed Said , Amer Sadiq Mohammed
Published: May 2014

We present a young man with type 1 diabetes mellitus and haemophilia A; who presented with oliguric acute kidney injury (AKI). He is also known to have chronic hepatitis C virus infection. On presentation, he had an active urinary sediment warranting a renal biopsy for definitive diagnosis and management. Although he was at high risk for bleeding we elected for renal biopsy with appropriate factor VIII supplementation and monitoring. Ultrasound-guided percutaneous renal biopsy was successful with no immediate or long-term complications. Biopsy revealed advanced diabetic glomerulosclerosis with mild chronic interstitial inflammation.
Contusio cordis, not an innocent diagnosis
Authors: Driessen Roel , Doodeman Inge , Bogaard Kjell , Reichert Stan
Published: May 2014

This report demonstrates two cases of traumatic valvular lesions of the heart. The first is a patient with severe mitral regurgitation after a blunt chest trauma and the second a severe aortic regurgitation due to rupture of a coronary cusp after a motor cycle accident. Both patients underwent successful surgery and recovered. Valvular lesions are a rare complication after blunt chest trauma. Physicians should always consider a traumatic valvular lesion as a possible cause of pulmonary oedema or haemodynamic instability after a blunt chest trauma.
Clinical evaluation of small animal cancer patients
Authors: Elliott James
Published: May 2014

It is important to take a holistic approach to cancer patients and remember that there is a patient attached to every tumour. Considering the whole patient, and not just the tumour in isolation, is likely to ensure that no important underlying causes, comorbidities or paraneoplastic diseases are missed. These may themselves require specific management in addition to treatment of the primary cancer. An important part of this initial patient approach is tumour staging, which allows assessment of the extent of disease and allows the formulation of an appropriate therapeutic plan and prognosis. This article discusses clinical examination of dogs and cats.
Artificial insemination in dogs and cats 3. Semen preservation and artificial insemination in cats
Authors: England Gary C. W. , Russo Marco
Published: May 2014

This article, the last in a series of three discussing artificial insemination in dogs and cats, aims to provide a comprehensive but practical review of the purpose, techniques and likely outcomes of artificial insemination in cats. The first two articles in the series discussed the benefits of artificial insemination in dogs, explaining how to collect and preserve semen and the practicalities of performing the procedure (In Practice, February 2014, vol 36, pp 77‐84; April 2014, vol 36, pp 183‐190).
Management of the surgical equine colic patient following hospital discharge
Authors: Findley Judith , Archer Debra
Published: May 2014

Surgical treatment is required in around nine per cent of equine colic cases seen in first opinion practice. Veterinary practitioners play an important role in the early diagnosis of these cases and in the care of these horses following hospital discharge. This article discusses the management of the colic patient in the postoperative period and outlines possible complications, with a particular focus on the identification and management of complications that may occur immediately after hospital discharge. It also discusses measures that can be taken to reduce the risk of recurrence of colic in these cases.
A new look at the Lake Superior biomass size spectrum
Authors: Yurista Peder M. , Yule Daniel L. , Balge Matt , VanAlstine Jon D. , Thompson Jo A. , Gamble Allison E. , Hrabik Tom R. , Kelly John R. , Stockwell Jason D. , Vinson Mark R.
Published: May 2014

We synthesized data from multiple sampling programs and years to describe the Lake Superior pelagic biomass size structure. Data consisted of Coulter counts for phytoplankton, optical plankton counts for zooplankton, and acoustic surveys for pelagic prey fish. The size spectrum was stable across two time periods separated by 5 years. The primary scaling or overall slope of the normalized biomass size spectra for the combined years was −1.113, consistent with a previous estimate for Lake Superior (−1.10). Periodic dome structures within the overall biomass size structure were fit to polynomial regressions based on the observed sub-domes within the classical taxonomic positions (algae, zooplankton, and fish). This interpretation of periodic dome delineation was aligned more closely with predator–prey size relationships that exist within the zooplankton (herbivorous, predacious) and fish (planktivorous, piscivorous) taxonomic positions. Domes were spaced approximately every 3.78 log10 units along the axis and with a decreasing peak magnitude of −4.1 log10 units. The relative position of the algal and herbivorous zooplankton domes predicted well the subsequent biomass domes for larger predatory zooplankton and planktivorous prey fish.
H7N9: A killer in the making or a false alarm?
Authors: Nailwal Himani , Kamra Komal , Lal Sunil K.
Published: May 2014

Influenza virus remains one of the most important disease-causing viruses owing to its high adaptability and even higher contagious nature. Thus, it poses a constant threat of pandemic, engulfing a large population within the smallest possible time interval. A similar threat was anticipated with the identification of the novel H7N9 virus in China on 30 March 2013. Detection of transmission of the virus between humans has caused a stir with the identification of family clusters along with sporadic infections all across China. In this review we analyze the potential of the novel H7N9 virus as a probable cause of a pandemic and the possible consequences thereof.
Exploring cylindrical solutions in modified f(G) gravity
Authors: Houndjo M.J.S. , Rodrigues M.E. , Momeni D. , Myrzakulov R.
Published: May 2014

We present detailed cylindrically symmetric solutions for a type of Gauss–Bonnet gravity. We derive the full system of field equations and show that there exist seven families of exact solutions for three forms of viable models. By applying the method based on the effective fluid energy momentum tensor components, we evaluate the mass per unit length for the solutions. From a dynamical point of the view, by evaluating the null energy condition for these configurations, we show that in some cases the azimuthal pressure breaks the energy condition. This violation of the null energy condition predicts the existence of a cylindrical wormhole.
The “graviton picture”: a Bohr model for gravitation on galactic scales?
Authors: Trippe Sascha
Published: May 2014

Modified Newtonian dynamics (MOND) provides a successful description of stellar and galactic dynamics on almost all astronomical scales. A key feature of MOND is the transition function from Newtonian to modified dynamics, which corresponds to the empirical mass discrepancy–acceleration (MDA) relation. However, the functional form of the MDA relation does not follow from theory in a straightforward manner; in general, empirical MDA relations are inserted ad hoc into analyses of stellar dynamics. I revisit the possibility of gravity being mediated by massive virtual particles, gravitons. Under certain reasonable assumptions, the resulting “graviton picture” implies a MDA relation that is equivalent to the — empirical — “simple μ” function of MOND, which is in very good agreement with observations. I conclude that the “graviton picture” offers a simple description of gravitation on galactic scales, potentially playing a role for gravitation analogous to the role played by Bohr’s model for atomic physics.
A NEW MIXED MODE FULL-WAVE RECTIFIER REALIZATION WITH CURRENT DIFFERENCING TRANSCONDUCTANCE AMPLIFIER
Authors: KAÇAR FIRAT , BAŞAK MUHAMMED EMIN
Published: May 2014

In this paper, a new mixed mode full-wave rectifier which consists of a current differencing transconductance amplifier (CDTA), resistor and two complementary MOS transistor is presented. The proposed circuit is called as mixed mode because it can be used as current-, voltage-, transimpedance- and transconductance-mode rectifier depending on how the resistor is connected to the input or output of the circuit. The presented circuit has an appropriate zero crossing performance, linearity, low component count, and can be adapted to modern IC technologies. It is also suitable for monolithic integrated implementation. LTSPICE simulations with 0.18 μm CMOS model obtained through TMSC are included to verify the workability of the proposed circuit. We also performed noise and Monte Carlo analyses. Various simulation results are presented to show the effectiveness of the proposed circuit.
Double-Λ hypernuclei within a Skyrme–Hartree–Fock approach
Authors: Guleria Neelam , Dhiman Shashi K. , Shyam Radhey
Published: May 2014

We extend our Skyrme–Hartree–Fock (SHF) approach, which was used earlier to describe successfully the single-Λ hypernuclei, to investigate the binding and the ΛΛ bond energies of the double-Λ hypernuclei. The nucleon–nucleon (NN) and Λ-nucleon (ΛN) interactions are taken from our previous study. For the ΛΛ force, several Skyrme-like potentials available in the literature have been used. We discuss the sensitivity of the calculated ΛΛ binding and bond energies to the ΛΛ and ΛN force parameters. It is found that the existing ΛΛ hypernuclear data do not allow to distinguish between various ΛΛ force parameter sets used by us. However, they show some selectivity for a particular set of the ΛN potential determined in our previous work.
Real-Time Profitability of Published Anomalies: An Out-of-Sample Test
Authors: Huang Jing-Zhi , Huang Zhijian
Published: May 2014

Empirical evidence on the out-of-sample performance of asset-pricing anomalies is mixed so far and arguably is often subject to data-snooping bias. This paper proposes a method that can significantly reduce this bias. Specifically, we consider a long-only strategy that involves only published anomalies and non-forward-looking filters and that each year recursively picks the best past-performer among such anomalies over a given training period. We find that this strategy can outperform the equity market even after transaction costs. Overall, our results suggest that published anomalies persist even after controlling for data-snooping bias.