bluuebunny/crossref_metadata_2025 huggingface dataset:
EEG delta oscillations index inhibitory control of contextual novelty to both irrelevant distracters and relevant task‐switch cues
Authors: Prada Laura , Barceló Francisco , Herrmann Christoph S. , Escera Carles
Published: March 2014

Delta oscillations contribute to the human P300 event‐related potential evoked by oddball targets, although it is unclear whether they index contextual novelty (event oddballness, novelty P3, nP3), or target‐related processes (event targetness, target P3b). To examine this question, the electroencephalogram (EEG) was recorded during a cued task‐switching version of the Wisconsin card‐sorting test. Each target card was announced by a tone cueing either to switch or repeat the task. Novel sound distracters were interspersed among trials. Time‐frequency EEG analyses revealed bursts of delta (2–4 Hz) power associated with enhanced nP3 amplitudes to both task‐switch cues and novel distracters—but no association with target P3b. These findings indicate that the P300‐delta response indexes contextual novelty regardless of whether novelty emanates from endogenous (new task rules) or exogenous (novel distracters) sources of information.
A Case Series of Real‐Time Hemodynamic Assessment of High Output Heart Failure as a Complication of Arteriovenous Access in Dialysis Patients
Authors: Singh Sarguni , Elramah Mohsen , Allana Salman S. , Babcock Michael , Keevil Jon G. , Johnson Maryl R. , Yevzlin Alexander S. , Chan Micah R.
Published: March 2014

Congestive heart failure (CHF) is an important source of morbidity and mortality in end‐stage renal disease patients. Although CHF is commonly associated with low cardiac output (CO), it may also occur in high CO states. Multiple conditions are associated with increased CO including congenital or acquired arteriovenous fistulae or arteriovenous grafts. Increased CO resulting from permanent AV access in dialysis patients has been shown to induce structural and functional cardiac changes, including the development of eccentric left ventricle hypertrophy. Often, the diagnosis of high output heart failure requires invasive right heart monitoring in the acute care setting such as a medical or cardiac intensive care unit. The diagnosis of an arteriovenous access causing high output heart failure is usually confirmed after the access is ligated surgically. We present for the first time, a case for real‐time hemodynamic assessment of high output heart failure due to AV access by interventional nephrology in the cardiac catheterization suite.
Cytotoxic reaction mediators: granzymes A and B in women with ovarian cancer
Authors: Mielczarek‐Palacz A. , Sikora J. , Kondera‐Anasz Z. , Bednarek I.
Published: March 2014

The purpose of this work was the assessment of cytotoxic reaction mediators – granzymes A and B in the serum of women with ovarian tumors. The study included 120 women with proven ovarian tumors. The control group consisted of 60 healthy women in whom no pathological changes within the reproductive system were detected. Concentrations of granzymes A and B were measured by enzyme‐linked immunosorbent (ELISA) assay. The highest concentrations of the studied parameters were observed in serum of women with ovarian cancer. Moreover, the concentrations of granzymes A and B in patients with ovarian cancer were substantially increased in comparison to concentrations in patients with ovarian cystadenomas (P < 0.0001) or ovarian teratomas (P < 0.0001).
Drivers of Export Demand: A Focus on the GIIPS Countries
Authors: Algieri Bernardina
Published: March 2014

This study investigates the drivers of export demand in the peripheral economies of the Euro Area, namely Greece, Ireland, Italy, Portugal, and Spain (GIIPS), for the period between 1980 and 2012. Recently, several authors have pointed out that changes in trade export shares are not associated with major terms of trade disturbances; rather, they are the result of other underlying factors commonly defined as ‘non‐price competitiveness’. Starting from this premise, the study extends the traditional imperfect substitute trade model to include a measure of non‐price competitiveness: real capital stock. The latter is a measure of a country's total resource base and captures the presence of product differentiation and product innovation. The results show a significant link between export demand and cumulative investments. In the short‐term, GIIPS exports are dominated by the movements of worldwide real income, while changes in price and non‐competitiveness take longer to affect export performance. In the long‐run, all three variables play a significant role in pushing exports.
Heat Transfer and Pressure Loss Measurements in a Turbulated High Aspect Ratio Channel With Large Reynolds Number Flows
Authors: Mhetras Shantanu , Han Je-Chin , Huth Michael
Published: March 2014

Experiments to investigate heat transfer and pressure loss are performed in a rectangular channel with an aspect ratio of 6 at very high Reynolds numbers under compressible flow conditions. Reynolds numbers up to 1.3 × 106 are tested. The presence of a turbulated wall and the resultant heat transfer enhancement against a smooth surface is investigated. Three dimpled configurations including spherical and cylindrical dimples are studied on one wide wall of the channel. The presence of discrete ribs on the same wide wall is also investigated. A steady state heat transfer measurement method is used to obtain the heat transfer coefficients while pressure taps located at several streamwise locations in the channel walls are used to record the static pressures on the surface. Experiments are performed for a wide range of Reynolds numbers from the incompressible (Re = 100,000–500,000; Mach = 0.04–0.19) to compressible flow regimes (Re = 900,000–1,300,000, Mach = 0.35–0.5). Results for low Reynolds numbers are compared to existing heat transfer data available in open literature for similar configurations. Heat transfer enhancement is found to decrease at high Re with the discrete rib configurations providing the best enhancement but highest pressure losses. However, the small spherical dimples show the best thermal performance. Results can be used for the combustor liner back side cooling at high Reynolds number flow conditions. Local measurements using the steady state, hue-detection based liquid crystal technique are also performed in the fully developed region for case 1 with large spherical dimples. Good comparison is obtained between averaged local heat transfer coefficient measurements and from thermocouple measurements.
An Efficient Static Analysis of Continuum Robots
Authors: Hasanzadeh Shahir , Janabi-Sharifi Farrokh
Published: March 2014

An efficient yet accurate model of the continuum robot is the main component for its real-time control, simulation as well as localization. Previous models of the continuum robot, based on rod theory, suffer from high computational burden. The models also require a priori knowledge of the robot environment. This paper presents an efficient static model for the planar continuum robot that experiences external forces at the tip as a result of contact with its surroundings (measured by the built-in force sensors), thus no a priori information about the environment is required. The typical example of such robots is steerable catheters used in medical operations. The proposed approach involves discretizing the robot backbone curve to elastic arc elements. After deriving the equilibrium equations for the infinitesimal elements, a recursive algorithm with the time complexity of O(n) is proposed for realizing the shape of the robot as a result of the external force. Accuracy of the proposed method is evaluated both theoretically and experimentally for a case study, i.e., an intracardiac ablation catheter. Results validate the accuracy and time-efficiency of the proposed approach for real-time applications.
Three-Dimensional Thermohydrodynamic Morton Effect Analysis—Part II: Parametric Studies
Authors: Suh Junho , Palazzolo Alan
Published: March 2014

This paper presents simulation results corresponding with the theoretical Morton effect model explained in Part I, where the 3D finite element models of bearing, shaft, and fluid film are adopted. In addition, it explains how thermal bow induced imbalance force develops in the spinning journal with time and how the vibration level is affected by the thermal bow vector. Shaft asymmetric thermal expansion induced by nonuniform journal heating is simulated, which is one of the unique contributions of this research. The effect of changes in: (1) thermal boundary condition around the pad, (2) lubricant supply temperature, (3) initial mechanical imbalance, (4) pivot stiffness, (5) film clearance, and (6) pad material are studied. Cooling the pad and the lubricant, using a pad with a low thermal expansion coefficient, soft pivot, and reducing the initial imbalance are found to be the best remedies for the thermal induced synchronous rotor instability problem.
A Multi-Tier Design Methodology for Reconfigurable Milling Machines
Authors: Azulay Hay , Mills James K. , Benhabib Beno
Published: March 2014

Reconfigurable Machine Tools (RMTs) have been developed in response to agile flexible manufacturing demands. Current design methodologies for RMTs support modular reconfigurability in which a machine configuration is assembled for a given part. In this paper, on the other hand, reconfigurability relies on redundancy, namely, a desired RMT configuration is obtained through topological reconfiguration by locking/unlocking degrees-of-freedom (dof). Thus, in order to design a Redundant Reconfigurable Machine Tool (RRMT) with all of its dof already included, a new multi–tier optimization based design methodology was developed. The design is formulated for the efficient selection of the best architecture from a set of serial/parallel/hybrid solutions, while considering the redundant reconfigurability effect on performance. The viability of the methodology is demonstrated herein via a design test case of a Parallel Kinematic Mechanism (PKM)-based Redundant Reconfigurable meso-Milling Machine Tool (RRmMT) that can attain high stiffness at the high feed-rate required in meso-milling.
Nonlinear System Identification and Modeling of a New Fatigue Testing Rig Based on Inertial Forces
Authors: Falco Michael , Liu Ming , Hai Nguyen Son , Chelidze David
Published: March 2014

A novel fatigue testing rig based on inertial forces is introduced. The test rig has capacity to mimic various loading conditions including high frequency loads. The rig design allows reconfigurations to accommodate a range of specimen sizes, and changes in structural elements and instrumentation. It is designed to be used as a platform to study the interaction between fatigue crack propagation and structural dynamics. As the first step to understand this interaction, a numerical model of testing rig is constructed using nonlinear system identification approaches. Some initial testing results also are reported.
Sample size requirements for estimating effective dose from computed tomography using solid‐state metal‐oxide‐semiconductor field‐effect transistor dosimetry
Authors: Trattner Sigal , Cheng Bin , Pieniazek Radoslaw L. , Hoffmann Udo , Douglas Pamela S. , Einstein Andrew J.
Published: March 2014

Purpose:

Effective dose (ED) is a widely used metric for comparing ionizing radiation burden between different imaging modalities, scanners, and scan protocols. In computed tomography (CT), ED can be estimated by performing scans on an anthropomorphic phantom in which metal‐oxide‐semiconductor field‐effect transistor (MOSFET) solid‐state dosimeters have been placed to enable organ dose measurements. Here a statistical framework is established to determine the sample size (number of scans) needed for estimating ED to a desired precision and confidence, for a particular scanner and scan protocol, subject to practical limitations.

Methods:

The statistical scheme involves solving equations which minimize the sample size required for estimating ED to desired precision and confidence. It is subject to a constrained variation of the estimated ED and solved using the Lagrange multiplier method. The scheme incorporates measurement variation introduced both by MOSFET calibration, and by variation in MOSFET readings between repeated CT scans. Sample size requirements are illustrated on cardiac, chest, and abdomen–pelvis CT scans performed on a 320‐row scanner and chest CT performed on a 16‐row scanner.

Results:

Sample sizes for estimating ED vary considerably between scanners and protocols. Sample size increases as the required precision or confidence is higher and also as the anticipated ED is lower. For example, for a helical chest protocol, for 95% confidence and 5% precision for the ED, 30 measurements are required on the 320‐row scanner and 11 on the 16‐row scanner when the anticipated ED is 4 mSv; these sample sizes are 5 and 2, respectively, when the anticipated ED is 10 mSv.

Conclusions:

Applying the suggested scheme, it was found that even at modest sample sizes, it is feasible to estimate ED with high precision and a high degree of confidence. As CT technology develops enabling ED to be lowered, more MOSFET measurements are needed to estimate ED with the same precision and confidence.
A Physical Model to Help Explain Evaporation
Authors: Branca M. , Soletta I.
Published: March 2014

One of the basic ideas when studying science is that matter is composed of particles (atoms or molecules) and these are in a constant state of agitation. In the solid or liquid state the molecules are attracted to each other, while in the gaseous state they have sufficient energy to overcome the forces of cohesion and can move away from one another.
Nickel Curie point engine
Authors: Chiaverina Chris , Lisensky George
Published: March 2014

Ferromagnetic materials such as nickel, iron, or cobalt lose the electron alignment that makes them attracted to a magnet when sufficient thermal energy is added. The temperature at which this change occurs is called the “Curie temperature,” or “Curie point.” Nickel has a Curie point of 627 K, so a candle flame is a sufficient heat source. A simple but elegant device illustrates this phenomenon beautifully.
A Different Class of Planets
Authors: Brandeker Alexis
Published: March 2014

Detection of a carbon dioxide gas cloud suggests the presence of an exoplanet further out from its host star than usual.

[Also see Report by

Dent
et al.

]
A Hardbound Information Revolution
Visions of Science
Books and Readers at the Dawn of the Victorian Age

by James A. Secord

Oxford University Press, Oxford, 2014. 328 pp. £18.99. ISBN 9780199675265.
Authors: Lightman Bernard
Published: March 2014

Secord surveys the reception of eight books published in the United Kingdom around 1830 that "offered comprehensive perspectives on science and its meaning for human life."
Next Steps for Citizen Science
Authors: Bonney Rick , Shirk Jennifer L. , Phillips Tina B. , Wiggins Andrea , Ballard Heidi L. , Miller-Rushing Abraham J. , Parrish Julia K.
Published: March 2014

Strategic investments and coordination are needed for citizen science to reach its full potential.
Cancer Suppression by the Chromosome Custodians, BRCA1 and BRCA2
Authors: Venkitaraman Ashok R.
Published: March 2014

Germline mutations in
BRCA1
and
BRCA2
predispose to common human malignancies, most notably tumors of the breast and ovaries. The proteins encoded by these genes have been implicated in a plethora of biochemical interactions and biological functions, confounding attempts to coherently explain how their inactivation promotes carcinogenesis. Here, I argue that tumor suppression by BRCA1 and BRCA2 originates from their fundamental role in controlling the assembly and activity of macromolecular complexes that monitor chromosome duplication, maintenance, and segregation across the cell cycle. A tumor-suppressive role for the BRCA proteins as “chromosome custodians” helps to explain the clinical features of cancer susceptibility after their inactivation, provides foundations for the rational therapy of BRCA-deficient cancers, and offers general insights into the mechanisms opposing early steps in human carcinogenesis.
Cholesterol and Cancer, in the Balance
Authors: Silvente-Poirot Sandrine , Poirot Marc
Published: March 2014

Cholesterol metabolites can promote or suppress breast cancer, raising questions about how therapies might disrupt this balance.
Pioneering Womb Transplant Trial Highlights Risks and Ethical Dilemmas
Authors: Orange Richard
Published: March 2014

Scientists hope that womb transplants can give women with a dysfunctional or missing uterus the option of bearing their own children, but the procedure is fraught with unique challenges and ethical dilemmas.
Search for Martian Life Clears Another Hurdle
Authors: Kerr Richard A.
Published: March 2014

Curiosity rover team members are now reasonably confident that contaminants brought from Earth cannot entirely explain certain carbon compounds Curiosity spotted in martian rock.
The 'Other' Breast Cancer Genes
Authors: Kean Sam
Published: March 2014

Since the discovery of
BRCA1
and
BRCA2
, dozens more breast cancer genes have come to light. But what risk they pose—and what to tell women who carry them—remain quandaries.
Refilling the Drug Discovery Pipeline: The Role of New Technologies
Authors: Rees Stephen , Belcher Paul
Published: March 2014

The ultimate aim of most scientific research is the creation of therapies that will cure or extend the life of patients. In recent years, though, the flow of new drugs in the development pipeline seems to have slowed, despite increased R&D budgets and the concerted efforts of researchers. The reasons for this are hotly debated, including the suggestion that the "easy" targets have already been found, or that increasing regulatory demands are stifling progress. Another possibility is that, as a result of the proliferation of technologies intended to enable drug discovery, the basic biological questions are being overlooked or ignored. Technological development in high throughput target identification, screening, library synthesis, and validation have their place, but they are essentially just tools, and a clear understanding of the underlying biology is paramount. This webinar will take a critical look at what role technology plays in helping researchers understand molecular pathways and characterize signaling cascades, to better predict the efficacy, and potential toxicity, of new drugs.
Seroprevalence of Canine Norovirus in 14 European Countries
Authors: Mesquita João R. , Delgado Inês , Costantini Veronica , Heenemann Kristin , Vahlenkamp Thomas W. , Vinjé Jan , Nascimento Maria S. J.
Published: March 2014

To investigate the prevalence of the recently described genogroup VI canine noroviruses (CNVs) in dogs in Europe, we tested 510 serum samples from dogs in 14 European countries for anti-IgG CNV antibodies. Seropositive dogs were found throughout Europe. Dogs with antibodies against human noroviruses were also found.
Performance of a Cytomegalovirus IgG Enzyme Immunoassay Kit Modified To Measure Avidity
Authors: Prince Harry E. , Lapé-Nixon Mary , Novak-Weekley Susan M.
Published: March 2014

The measurement of cytomegalovirus (CMV) IgG avidity accurately discriminates recent and past CMV infections. We sought to determine if the Wampole Laboratories CMV IgG enzyme immunoassay (EIA) could be modified to measure avidity. The evaluation panel consisted of 156 serum samples we used in 2002 to validate a laboratory-developed EIA, in which 78 serum samples exhibited low avidity, 7 exhibited intermediate avidity, and 71 exhibited high avidity. The qualitative agreement between the two avidity assays was 94% (147/156); all 9 sera with discordant results exhibited intermediate avidity in one of the assays. The avidity index (AI) values in the two assays showed excellent correlation (
r
= 0.96,
P
< 0.0001). The definition of high avidity was verified for the Wampole assay by demonstrating high avidity in 91/93 (98%) recently collected CMV IgG-positive/IgM-negative serum samples. The performance of the Wampole avidity assay in a reference laboratory setting was assessed using 470 consecutive serum samples submitted for CMV IgG avidity testing. Surprisingly, 101 serum samples were negative when screened for CMV IgG using the Wampole kit per the package insert; 98 of these 101 serum samples were tested using a CMV IgG chemiluminescent immunoassay, and only 5 were positive. Of the 369 CMV IgG-positive samples, 6% exhibited low IgG avidity, 6% exhibited intermediate avidity, and 88% exhibited high avidity; CMV IgM detection rates were inversely related to AI levels. These findings show that (i) the Wampole CMV IgG EIA can be modified to measure CMV IgG avidity, (ii) many samples are apparently submitted for avidity testing without knowledge of their CMV IgG status, and (iii) most CMV IgG-positive sera submitted for avidity testing exhibit high avidity.
Novel DNA Chip Based on a Modified DigiTag2 Assay for High-Throughput Species Identification and Genotyping of Mycobacterium tuberculosis Complex Isolates
Authors: Srilohasin Prapaporn , Chaiprasert Angkana , Tokunaga Katsushi , Nao Nishida , Prammananan Therdsak
Published: March 2014

A multipurpose high-throughput genotyping tool for the assessment of recent epidemiological data and evolutional pattern in
Mycobacterium tuberculosis
complex (MTBC) clinical isolates was developed in this study. To facilitate processing, 51 highly informative single nucleotide polymorphisms (SNPs) were selected for discriminating the clinically most relevant MTBC species and genotyping
M. tuberculosis
into its principle genetic groups (PGGs) and SNP cluster groups (SCGs). Because of the high flexibility of the DigiTag2 assay, the identical protocol and DNA array containing the identical set of probes were applied to the highly GC-rich mycobacterial genome. The specific primers with multiplex amplification and hybridization conditions based on the DigiTag2 principle were optimized and evaluated with 14 MTBC reference strains, 4 nontuberculous mycobacteria (NTM) isolates, and 322 characterized
M. tuberculosis
clinical isolates. The DNA chip that was developed revealed a 99.85% call rate, a 100% conversion rate, and 99.75% reproducibility. For the accuracy rate, 98.94% of positive calls were consistent with previous molecular characterizations. Our cost-effective technology was capable of simultaneously identifying the MTBC species and the genotypes of 96
M. tuberculosis
clinical isolates within 6 h using only simple instruments, such as a thermal cycler, a hybridization oven, and a DNA chip scanner, and less technician skill was required than for other techniques. We demonstrate this approach's potential as a simple, flexible, and rapid tool for providing clearer information regarding circulating MTBC isolates.
Ability of Two Commercially Available Assays (Abbott RealTi
m
e HIV-1 and Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 Version 2.0) To Quantify Low HIV-1 RNA Levels (<1,000 Copies/Milliliter): Comparison with Clinical Samples and NIBSC Working Reagent for Nucleic Acid Testing Assays
Authors: Amendola Alessandra , Marsella Patrizia , Bloisi Maria , Forbici Federica , Angeletti Claudio , Capobianchi Maria R.
Published: March 2014

Concordance between molecular assays may be suboptimal at low HIV-1 viremia levels (<1,000 copies/ml); therefore, it may be difficult to define and compare virologic endpoints for successful and failed therapy. We compared two commercial assays (the Abbott RealTi
m
e HIV-1 and the Roche Cobas AmpliPrep/TaqMan HIV-1 version 2.0) for their ability to detect and quantify low viral loads. A comparison was performed using 167 residual clinical samples (with values ranging from “not detected” to 1,000 copies/ml, as measured by the Abbott assay) and the National Institute and Biological Standards and Control (NIBSC) HIV-1 RNA working reagent 1 for nucleic acid amplification techniques (NAT) assays (serially diluted to a range from 1 to 1,000 copies/ml). Quantitative results were compared using Lin's concordance correlation coefficient and a Bland-Altman plot. Concordance with the qualitative results was measured by Cohen's kappa statistic. With clinical samples, the degree of interassay concordance of the qualitative results at a 40-copies/ml HIV-1 RNA threshold was substantial (κ = 0.762); the correlation among the quantified samples was suboptimal (concordance correlation coefficient, 0.728;
P
< 0.0001); the mean difference of the values between the Roche and Abbott assays was 0.193 log
10
copies/ml. Using the HIV-1 RNA working reagent 1 for NAT assays, the results provided by the Roche assay were, on average, 3 times higher than expected, while the Abbott assay showed high accuracy. The Roche assay was highly sensitive, being able to detect a level as low as 3.5 copies/ml HIV-1 RNA with 95% probability. The performance characteristics of each molecular assay should be taken into account when HIV-1 RNA threshold values for “virologic suppression,” “virologic failure,” “persistent low viral loads,” etc., are defined and indicated in the support of clinical decisions.
Molecular Epidemiology of
sil
Locus in Clinical Streptococcus pyogenes Strains
Authors: Plainvert Céline , Dinis Márcia , Ravins Miriam , Hanski Emanuel , Touak Gérald , Dmytruk Nicolas , Fouet Agnès , Poyart Claire
Published: March 2014

Streptococcus pyogenes
(group A
Streptococcus
[GAS]) causes a wide variety of diseases, ranging from mild noninvasive to severe invasive infections. Mutations in regulatory components have been implicated in the switch from colonization to invasive phenotypes. The inactivation of the
sil
locus, composed of six genes encoding a quorum-sensing complex, gives rise to a highly invasive strain. However, studies conducted on limited collections of GAS strains suggested that
sil
prevalence is around 15%; furthermore, whereas a correlation between the presence of
sil
and the genetic background was suggested, no link between the presence of a functional
sil
locus and the invasive status was assessed. We established a collection of 637 nonredundant strains covering all
emm
genotypes present in France and of known clinical history; 68%, 22%, and 10% were from invasive infections, noninvasive infections, and asymptomatic carriage, respectively. Among the 637 strains, 206 were
sil
positive. The prevalence of the
sil
locus varied according to the
emm
genotype, being present in >85% of the
emm4
,
emm18
,
emm32
,
emm60
,
emm87
, and
emm90
strains and absent from all
emm1
,
emm28
, and
emm89
strains. A random selection based on 2009 French epidemiological data indicated that 16% of GAS strains are
sil
positive. Moreover, due to mutations leading to truncated proteins, only 9% of GAS strains harbor a predicted functional
sil
system. No correlation was observed between the presence or absence of a functional
sil
locus and the strain invasiveness status.
Multiplex Nucleic Acid Amplification Test for Diagnosis of Dengue Fever, Malaria, and Leptospirosis
Authors: Waggoner Jesse J. , Abeynayake Janaki , Balassiano Ilana , Lefterova Martina , Sahoo Malaya K. , Liu Yuanyuan , Vital-Brazil Juliana Magalhães , Gresh Lionel , Balmaseda Angel , Harris Eva , Banaei Niaz , Pinsky Benjamin A.
Published: March 2014

Dengue, leptospirosis, and malaria are among the most common etiologies of systemic undifferentiated febrile illness (UFI) among travelers to the developing world, and these pathogens all have the potential to cause life-threatening illness in returned travelers. The current study describes the development of an internally controlled multiplex nucleic acid amplification test for the detection of dengue virus (DENV) and
Leptospira
and
Plasmodium
species, with a specific callout for
Plasmodium falciparum
(referred to as the UFI assay). During analytical evaluation, the UFI assay displayed a wide dynamic range and a sensitive limit of detection for each target, including all four DENV serotypes. In a clinical evaluation including 210 previously tested samples, the sensitivities of the UFI assay were 98% for DENV (58/59 samples detected) and 100% for
Leptospira
and malaria (65/65 and 20/20 samples, respectively). Malaria samples included all five
Plasmodium
species known to cause human disease. The specificity of the UFI assay was 100% when evaluated with a panel of 66 negative clinical samples. Furthermore, no amplification was observed when extracted nucleic acids from related pathogens were tested. Compared with whole-blood samples, the UFI assay remained positive for
Plasmodium
in 11 plasma samples from patients with malaria (parasitemia levels of 0.0037 to 3.4%). The syndrome-based design of the UFI assay, combined with the sensitivities of the component tests, represents a significant improvement over the individual diagnostic tests available for these pathogens.
Typing and Clustering of Yersinia pseudotuberculosis Isolates by Restriction Fragment Length Polymorphism Analysis Using Insertion Sequences
Authors: Voskresenskaya E. , Savin C. , Leclercq A. , Tseneva G. , Carniel E.
Published: March 2014

Yersinia pseudotuberculosis
is an enteropathogen that has an animal reservoir and causes human infections, mostly in temperate and cold countries. Most of the methods previously used to subdivide
Y. pseudotuberculosis
were performed on small numbers of isolates from a specific geographical area. One aim of this study was to evaluate the typing efficiency of restriction fragment length polymorphism of insertion sequence hybridization patterns (IS-RFLP) compared to other typing methods, such as serotyping, ribotyping, and multilocus sequence typing (MLST), on the same set of 80 strains of
Y. pseudotuberculosis
of global origin. We found that IS
100
was not adequate for IS-RFLP but that both IS
285
and IS
1541
efficiently subtyped
Y. pseudotuberculosis
. The discriminatory index (DI) of IS
1541
-RFLP (0.980) was superior to those of IS
285
-RFLP (0.939), ribotyping (0.944), MLST (0.861), and serotyping (0.857). The combination of the two IS (2IS-RFLP) further increased the DI to 0.998. Thus, IS-RFLP is a powerful tool for the molecular typing of
Y. pseudotuberculosis
and has the advantage of exhibiting well-resolved banding patterns that allow for a reliable comparison of strains of worldwide origin. The other aim of this study was to assess the clustering power of IS-RFLP. We found that 2IS-RFLP had a remarkable capacity to group strains with similar genotypic and phenotypic markers, thus identifying robust populations within
Y. pseudotuberculosis
. Our study thus demonstrates that 2IS- and even IS
1541
-RFLP alone might be valuable tools for the molecular typing of global isolates of
Y. pseudotuberculosis
and for the analysis of the population structure of this species.
Intestinal Epithelial Barrier Disruption through Altered Mucosal MicroRNA Expression in Human Immunodeficiency Virus and Simian Immunodeficiency Virus Infections
Authors: Gaulke Christopher A. , Porter Matthew , Han Yan-Hong , Sankaran-Walters Sumathi , Grishina Irina , George Michael D. , Dang Angeline T. , Ding Shou-Wei , Jiang Guochun , Korf Ian , Dandekar Satya
Published: March 2014

Epithelial barrier dysfunction during human immunodeficiency virus (HIV) infection has largely been attributed to the rapid and severe depletion of CD4
+
T cells in the gastrointestinal (GI) tract. Although it is known that changes in mucosal gene expression contribute to intestinal enteropathy, the role of small noncoding RNAs, specifically microRNA (miRNA), has not been investigated. Using the simian immunodeficiency virus (SIV)-infected nonhuman primate model of HIV pathogenesis, we investigated the effect of viral infection on miRNA expression in intestinal mucosa. SIV infection led to a striking decrease in the expression of mucosal miRNA compared to that in uninfected controls. This decrease coincided with an increase in 5′-3′-exoribonuclease 2 protein and alterations in DICER1 and Argonaute 2 expression. Targets of depleted miRNA belonged to molecular pathways involved in epithelial proliferation, differentiation, and immune response. Decreased expression of several miRNA involved in maintaining epithelial homeostasis in the gut was localized to the proliferative crypt region of the intestinal epithelium. Our findings suggest that SIV-induced decreased expression of miRNA involved in epithelial homeostasis, disrupted expression of miRNA biogenesis machinery, and increased expression of XRN2 are involved in the development of epithelial barrier dysfunction and gastroenteropathy.

IMPORTANCE
MicroRNA (miRNA) regulate the development and function of intestinal epithelial cells, and many viruses disrupt normal host miRNA expression. In this study, we demonstrate that SIV and HIV disrupt expression of miRNA in the small intestine during infection. The depletion of several key miRNA is localized to the proliferative crypt region of the gut epithelium. These miRNA are known to control expression of genes involved in inflammation, cell death, and epithelial maturation. Our data indicate that this disruption might be caused by altered expression of miRNA biogenesis machinery during infection. These findings suggest that the disruption of miRNA in the small intestine likely plays a role in intestinal enteropathy during HIV infection.
Nuclear Magnetic Resonance Structure Revealed that the Human Polyomavirus JC Virus Agnoprotein Contains an α-Helix Encompassing the Leu/Ile/Phe-Rich Domain
Authors: Coric Pascale , Saribas A. Sami , Abou-Gharbia Magid , Childers Wayne , White Martyn K. , Bouaziz Serge , Safak Mahmut
Published: March 2014

Agnoprotein is a small multifunctional regulatory protein required for sustaining the productive replication of JC virus (JCV). It is a mostly cytoplasmic protein localizing in the perinuclear area and forms highly stable dimers/oligomers through a Leu/Ile/Phe-rich domain. There have been no three-dimensional structural data available for agnoprotein due to difficulties associated with the dynamic conversion from monomers to oligomers. Here, we report the first nuclear magnetic resonance (NMR) structure of a synthetic agnoprotein peptide spanning amino acids Thr17 to Glu55 where Lys23 to Phe39 encompassing the Leu/Ile/Phe-rich domain forms an amphipathic α-helix. On the basis of these structural data, a number of Ala substitution mutations were made to investigate the role of the α-helix in the structure and function of agnoprotein. Single L29A and L36A mutations exhibited a significant negative effect on both protein stability and viral replication, whereas the L32A mutation did not. In addition, the L29A mutant displayed a highly nuclear localization pattern, in contrast to the pattern for the wild type (WT). Interestingly, a triple mutant, the L29A+L32A+L36A mutant, yielded no detectable agnoprotein expression, and the replication of this JCV mutant was significantly reduced, suggesting that Leu29 and Leu36 are located at the dimer interface, contributing to the structure and stability of agnoprotein. Two other single mutations, L33A and E34A, did not perturb agnoprotein stability as drastically as that observed with the L29A and L36A mutations, but they negatively affected viral replication, suggesting that the role of these residues is functional rather than structural. Thus, the agnoprotein dimerization domain can be targeted for the development of novel drugs active against JCV infection.

IMPORTANCE
Agnoprotein is a small regulatory protein of JC virus (JCV) and is required for the successful completion of the viral replication cycle. It forms highly stable dimers and oligomers through its hydrophobic (Leu/Ile/Phe-rich) domain, which has been shown to play essential roles in the stability and function of the protein. In this work, the Leu/Ile/Phe-rich domain has been further characterized by NMR studies using an agnoprotein peptide spanning amino acids T17 to Q54. Those studies revealed that the dimerization domain of the protein forms an amphipathic α-helix. Subsequent NMR structure-based mutational analysis of the region highlighted the critical importance of certain amino acids within the α-helix for the stability and function of agnoprotein. In conclusion, this study provides a solid foundation for developing effective therapeutic approaches against the dimerization domain of the protein to inhibit its critical roles in JCV infection.
Cryo-Electron Microscopy Study of Insect Cell-Expressed Enterovirus 71 and Coxsackievirus A16 Virus-Like Particles Provides a Structural Basis for Vaccine Development
Authors: Gong Minqing , Zhu Hongtao , Zhou Jun , Yang Chunting , Feng Jing , Huang Xiaojun , Ji Gang , Xu Honglin , Zhu Ping
Published: March 2014

Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two most common etiological agents responsible for the epidemics of hand, foot, and mouth disease (HFMD), a childhood illness with occasional severe neurological complications. A number of vaccine candidates against EV71 or CA16 have been reported; however, no vaccine is currently available for clinical use. Here, we generated a secreted version of EV71 and CA16 virus-like particles (VLPs) using a baculovirus-insect cell expression system and reconstructed the three-dimensional (3D) structures of both VLPs by cryo-electron microscopy (cryo-EM) single-particle analysis at 5.2-Å and 5.5-Å resolutions, respectively. The reconstruction results showed that the cryo-EM structures of EV71 and CA16 VLPs highly resemble the recently published crystal structures for EV71 natural empty particles and CA16 135S-like expanded particles, respectively. Our cryo-EM analysis also revealed that the majority of previously identified linear neutralizing epitopes are well preserved on the surface of EV71 and CA16 VLPs. In addition, both VLPs were able to induce efficiently neutralizing antibodies against various strains of EV71 and CA16 viruses in mouse immunization. These studies provide a structural basis for the development of insect cell-expressed VLP vaccines and for a potential bivalent VLP vaccine against both EV71- and CA16-associated HFMD.

IMPORTANCE
The recent outbreaks of hand, foot, and mouth disease (HFMD) in the Asia Pacific region spurred the search for effective vaccines against EV71 and CA16 viruses, the two most common etiological agents responsible for HFMD. In this paper, we show that secreted versions of EV71 and CA16 VLPs generated in the baculovirus-insect cell expression system highly resemble the crystal structures of their viral conterparts and that the majority of previously identified linear neutralizing epitopes are well preserved on the VLP surfaces. In addition, the generated VLPs can efficiently induce neutralizing antibodies against various strains of EV71 and CA16 viruses in mouse immunization. These studies provide a structural basis for the development of insect cell-expressed VLP vaccines and for a potential bivalent VLP vaccine against both EV71- and CA16-associated HFMD.
The Tripartite Virions of the Brome Mosaic Virus Have Distinct Physical Properties That Affect the Timing of the Infection Process
Authors: Vaughan Robert , Tragesser Brady , Ni Peng , Ma Xiang , Dragnea Bogdan , Kao C. Cheng
Published: March 2014

The three subsets of virions that comprise the Brome mosaic virus (BMV) were previously thought to be indistinguishable. This work tested the hypothesis that distinct capsid-RNA interactions in the BMV virions allow different rates of viral RNA release. Several results support distinct interactions between the capsid and the BMV genomic RNAs. First, the deletion of the first eight residues of the BMV coat protein (CP) resulted in the RNA1-containing particles having altered morphologies, while those containing RNA2 were unaffected. Second, subsets of the BMV particles separated by density gradients into a pool enriched for RNA1 (B1) and for RNA2 and RNA3/4 (B2.3/4) were found to have different physiochemical properties. Compared to the B2.3/4 particles, the B1 particles were more sensitive to protease digestion and had greater resistivity to nanoindentation by atomic force microscopy and increased susceptibility to nuclease digestion. Mapping studies showed that portions of the arginine-rich N-terminal tail of the CP could interact with RNA1. Mutational analysis in the putative RNA1-contacting residues severely reduced encapsidation of BMV RNA1 without affecting the encapsidation of RNA2. Finally, during infection of plants, the more easily released RNA1 accumulated to higher levels early in the infection.

IMPORTANCE
Viruses with genomes packaged in distinct virions could theoretically release the genomes at different times to regulate the timing of gene expression. Using an RNA virus composed of three particles, we demonstrated that the RNA in one of the virions is released more easily than the other two
in vitro
. The differential RNA release is due to distinct interactions between the viral capsid protein and the RNAs. The ease of RNA release is also correlated with the more rapid accumulation of that RNA in infected plants. Our study identified a novel role for capsid-RNA interactions in the regulation of a viral infection.
Hormone dependency in metastatic low-grade leiomyosarcoma following uterine smooth muscle tumour of uncertain malignant potential
Authors: Serrano Cesar , Nucci Marisa R , Tirumani Sree H , Raut Chandrajit P , George Suzanne
Published: March 2014

Uterine leiomyosarcoma (ULMS) usually follows an aggressive clinical course, although a small proportion of ULMS exhibit a more indolent course, which in turn reflects heterogeneity within this disease and the need to identify and characterise this distinct subgroup. The role of hormone therapy in ULMS is yet to be elucidated. We report a patient with well-differentiated metastatic ULMS on hormone replacement therapy (HRT) at the time of the diagnosis. The withdrawal of the HRT led to a significant decrease in the tumour burden and symptomatic improvement. The patient further benefited from aromatase inhibitor treatment once the benefit from the HRT withdrawal reached a plateau. The present case report describes for the first time hormone-dependency for tumour growth in a ULMS. We propose that a subset of ULMS that follow a protracted/indolent course might depend on hormone stimulation for tumour proliferation, and antihormone treatment can therefore be useful in these patients.
Individualisation of drug treatments for patients with long-term conditions: a review of concepts
Authors: Denford S , Frost J , Dieppe P , Cooper Chris , Britten N
Published: March 2014

Objectives

Patients and policy makers advocate that drug treatments should be individualised. However, the term is used in a variety of ways. We set out to identify the range of related terminology and concepts in the general field of individualisation, map out the relationships between these concepts and explore how patients’ perspectives are considered.

Design

We consulted members of an established patient and public involvement group about their experience of medicine taking for long-term conditions and their ideas about individualisation. We then conducted a scoping review of the literature to explore how terms surrounding individualisation of drug treatment are used and defined in the literature, and to explore the extent to which patients’ perspectives are represented, with a view to informing future recommendations as to how individualisation can be operationalised.

Methods

We identified relevant literature using a range of search strategies. Two researchers independently extracted definitions of terms using a template. Inductive and deductive methods were used to explore the data.

Results

Definitions were categorised according to the following themes: medical management; pharmacogenetics, the patient's perspective; interactions between the healthcare provider and patient and management of long-term conditions.

Conclusions

Within the literature reviewed, the involvement of patients in the ongoing management of drug treatment was largely absent. We propose the use of a new term ‘mutually agreed tailoring’ (MAT). This describes the ongoing pharmacological management of conditions that incorporates patients’ specific needs, experiences and existing strategies for using their medications, and the professionals’ clinical judgement. This usually includes patients monitoring their symptoms and, with the support of the professional, making appropriate product, dose or timing adjustments as necessary. Our previous work suggests that many patients and doctors are successfully practising MAT, so we suggest that a formal description may facilitate wider utilisation of strategies that will improve patient outcomes.
Is gauge-invariant complete decomposition of the nucleon spin possible?
Authors: Wakamatsu Masashi
Published: March 2014

Is gauge-invariant complete decomposition of the nucleon spin possible? Although it is a difficult theoretical question which has not reached a complete consensus yet, a general agreement now is that there are at least two physically inequivalent gauge-invariant decompositions (I) and (II) of the nucleon. In these two decompositions, the intrinsic spin parts of quarks and gluons are just common. What discriminate these two decompositions are the orbital angular momentum parts. The orbital angular momenta of quarks and gluons appearing in the decomposition (I) are the so-called "mechanical" orbital angular momenta, while those appearing in the decomposition (II) are the generalized (gauge-invariant) "canonical" ones. By this reason, these decompositions are also called the "mechanical" and "canonical" decompositions of the nucleon spin, respectively. A crucially important question is which decomposition is more favorable from the observational viewpoint. The main objective of this concise review is to try to answer this question with careful consideration of recent intensive researches on this problem.
REVIEW ON ELECTROLESS PLATING Ni–P COATINGS FOR IMPROVING SURFACE PERFORMANCE OF STEEL
Authors: ZHANG HONGYAN , ZOU JIAOJUAN , LIN NAIMING , TANG BIN
Published: March 2014

Electroless plating has been considered as an effective approach to provide protection and enhancement for metallic materials with many excellent properties in engineering field. This paper begins with a brief introduction of the fundamental aspects underlying the technological principles and conventional process of electroless nickel–phosphorus ( Ni – P ) coatings. Then this paper discusses different electroless nickel plating, including binary plating, ternary composite plating and nickel plating with nanoparticles and rare earth, with the intention of improving the surface performance on steel substrate in recent years in detail. Based on different coating process, the varied features depending on the processing parameters are highlighted. Separately, diverse preparation techniques aiming at improvement of plating efficiency are summarized. Moreover, in view of the outstanding performance, such as corrosion resistance, abrasive resistance and fatigue resistance, this paper critically reviews the behaviors and features of various electroless coatings under different conditions.
Self-organized one-dimensional columns of benzo[b]thiophene-fused tetraazaporphyrins
Authors: Suzuki Hiroyuki , Yamada Naoya , Nakayama Ken-ichi , Kimura Mutsumi
Published: March 2014

Ring-expanded metallophthalocyanines fused with thiophene rings 1–4 have been synthesized by ring closing reaction from the o-chloroethynylbenzene substructures with Na 2 S 9 H 2 O . The self-organizing properties of these compounds have been studied by UV-vis spectroscopy in solution, π-A isotherms at air-water interface, X-ray diffraction (XRD) patterns of a solid, and atomic force microscopy (AFM). Whereas all compounds exhibit good solubility in organic solvents, thiophene-fused phthalocyanines form stable aggregates through strong intermolecular π–π interaction. Copper phthalocynaine Cu -2 possessing phenyl spacers produced long nano-fibrous assemblies from solution.