bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial DNA nanostructure detection using solution-processed In-Ga-Zn-O thin-film transistors
Authors: Kim Si Joon , Kim Byeonghoon , Jung Joohye , Yoon Doo Hyun , Lee Junwye , Park Sung Ha , Kim Hyun Jae
Published: March 2012

A method for detecting artificial DNA using solution-processed In-Ga-Zn-O (IGZO) thin-film transistors (TFTs) was developed. The IGZO TFT had a field-effect mobility (μFET) of 0.07 cm2/Vs and an on-current (Ion) value of about 2.68 μA. A dry-wet method was employed to immobilize double-crossover (DX) DNA onto the IGZO surface. After DX DNA immobilization, significant decreases in μFET (0.02 cm2/Vs) and Ion (0.247 μA) and a positive shift of threshold voltage were observed. These results were attributed to the negatively charged phosphate groups on the DNA backbone, which generated electrostatic interactions in the TFT device.
Phase transition behaviors in relaxor ferroelectric [001]-poled Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 single crystals studied by Brillouin light scattering and dielectric spectroscopies
Authors: Hyun Kim Tae , Kojima Seiji , Ko Jae-Hyeon
Published: March 2012

Phase transition behaviors of [001]-oriented Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 (PIN-PMN-PT) single crystals were studied under unpoled and [001]-poled conditions by Brillouin light scattering and dielectric spectroscopies. The unpoled crystal showed a diffused elastic anomaly accompanied by substantial dielectric dispersion, which were associated with the temperature evolution of polar nanoregions represented by the excitation of strong central peaks. The poled crystal exhibited two-step changes in both dielectric and elastic properties, which were attributed to the successive phase transitions from rhombohedral to tetragonal, and then from tetragonal to cubic phase upon heating. The high-temperature tetragonal-cubic phase transition remained diffused with dielectric dispersion due to local random fields inherent in relaxors. The transverse acoustic mode disappeared at the rhombohedral-tetragonal phase transition indicating a clear symmetry change.
Patterning graphene nanoribbons using copper oxide nanowires
Authors: Sinitskii Alexander , Tour James M.
Published: March 2012

We present a fabrication technique for graphene nanoribbons (GNRs) that employs copper oxide nanowires as the etch masks. We demonstrate that these etch masks have numerous advantages: they can be synthesized simply by heating a copper foil in air, deposited on graphene from a solution, they are inert to oxygen plasma, and can be removed from the substrate by dissolution in mild acids. We fabricated GNRs in the device configuration and tested their electrical properties. Depending on the duration of the plasma etching, GNR devices exhibiting either standard ambipolar electric field effects or p-type transistor behaviors with ON-OFF ratios > 50 can be fabricated. The resulting devices based on narrow GNRs are demonstrated to exhibit promising electronic properties, which can be exploited in studies where GNR devices are required.
Photoluminescence of Nd-doped SnO2 thin films
Authors: Rinnert H. , Miska P. , Vergnat M. , Schmerber G. , Colis S. , Dinia A. , Muller D. , Ferblantier G. , Slaoui A.
Published: March 2012

Structural, optical, and electrical properties of Nd-doped SnOx thin films are reported. The atomic structure was characterized by x-ray diffraction and infrared absorption spectrometry. Investigation of the photoluminescence properties revealed Nd-related bands at 920 and 1100 nm for samples annealed at 700 °C, which present the tetragonal structure of the SnO2 rutile phase. Nd3+ ions can be indirectly excited and no concentration quenching was observed up to 3 at. %. It is concluded that Nd3+ ions are efficient optically active dopants in addition to be responsible of the observed electric conductivity improvement. These materials are then interesting for solar cell applications.
Measurements of electron density and temperature in the H-1 heliac plasma by helium line intensity ratios
Authors: Ma Shuiliang , Howard John , Blackwell Boyd D. , Thapar Nandika
Published: March 2012

Electron density and temperature distributions in the H-1 heliac plasma are measured using the helium line intensity ratio technique based on a collisional–radiative model. An inversion approach with minimum Fisher regularization is developed to reconstruct the ratios of the local emission radiances from detected line-integrated intensities. The electron density and temperature inferred from the He I 667.8/728.1 and He I 728.1/706.5 nm line ratios are in good agreement with those from other diagnostic techniques in the inner region of the plasma. The electron density and temperature values appear to be a little high in the outer region of the plasma. Some possible causes of the discrepancy in the outer region are discussed.
Induction of alternative fate other than default neuronal fate of embryonic stem cells in a membrane-based two-chambered microbioreactor by cell-secreted BMP4
Authors: Mahfuz Chowdhury Mohammad , Kimura Hiroshi , Fujii Teruo , Sakai Yasuyuki
Published: March 2012

Cell-secreted soluble factor signaling in a diffusion dominant microenvironment plays an important role on early stage differentiation of pluripotent stem cells in vivo. In this study, we utilized a membrane-based two-chambered microbioreactor (MB) to differentiate mouse embryonic stem cells (mESCs) in a diffusion dominant microenvironment of the top chamber while providing enough nutrient through the bottom chamber. Speculating that accumulated FGF4 in the small top chamber will augment neuronal differentiation in the MB culture, we first differentiated mESCs for 8 days by using a chemically optimized culture medium for neuronal induction. However, comparison of cellular morphology and expression of neuronal markers in the MB with that in the 6-well plate (6WP) indicated relatively lower neuronal differentiation in the MB culture. Therefore, to investigate whether microenvironment in the MB facilitates non-neuronal differentiation, we differentiated mESCs for 8 days by using chemically defined basal medium. In this case, differentiated cell morphology differed markedly between the MB and 6WP cultures: epithelial sheet-like morphology in the MB, whereas rosette morphology in the 6WP. Expression of markers from the three germ layers indicated lower neuronal but higher meso- and endo-dermal differentiation of mESCs in the MB than the 6WP culture. Moreover, among various cell-secreted soluble factors, BMP4 expression was remarkably upregulated in the MB culture. Inhibition of BMP4 signaling demonstrated that enhanced effect of upregulated BMP4 was responsible for the prominent meso- and endo-dermal differentiation in the MB. However, in the 6WP, downregulated BMP4 had a minimal influence on the differentiation behavior. Our study demonstrated utilization of a microbioreactor to modulate the effect of cell-secreted soluble factors by autoregulation and thereby inducing alternative self-capability of mESCs. Understanding and implementation of autoregulation of soluble factors similar to this study will lead to the development of robust culture systems to control ESC behavior.
Production, properties and processing of American bison (Bison bison) wool grown in southern Australia
Authors: McGregor B. A.
Published: March 2012

American bison grow a thick coat of fibres which assists them to withstand severe climatic conditions. Bison fibre was traditionally used in textiles by native North Americans. This study aimed to quantify the production, fibre attributes and dehairing processing of bison fibre produced from bison grazed in north-eastern Victoria. Three age/sex classes were sampled (n = 16) at seven body positions in spring. The fibre growing area was measured. Fibre was tested for diameter distribution, clean washing yield, proportion of fine fibres <36 µm and fine fibre length, and processed by cashmere dehairing. Bison were 1–2 years of age, liveweights 160–450 kg and had mean fibre growing area of 1.4 m2. They produced an average 1184 g (range 530–1640 g) of fine fibre with mean fibre diameter 18.5 µm, clean washing yield 76.5%, wax content 9.8%, suint content 14.5%, clean fine fibre yield 56.4%, fine fibre length 37 mm and fibre curvature was 93°/mm. Mid-side fibre had a crimp frequency of 6.5/cm and mean resistance to compression of 6.6 kPa. Fibre had a tenacity of 8.7 cN/tex and an extension of 39.3%. Restricted maximum likelihood mixed model analysis showed age/sex class and sampling site significantly affected all fibre attributes. Finer and longer fibre was produced in anterior sites and in younger bison. Fibre curvature declined 5.3°/mm for each 1-µm increase in mean fibre diameter. Dehaired fibre had a mean fibre diameter of 17.8 µm and mid-length of 28 mm, suitable for woollen spinning. The production by bison of coats containing significant amounts of fibre indicates that careful harvesting of fibre could form an important source of income in bison enterprises.
Autonomous self-pollination and insect visitation in a saprophytic orchid, Epipogium roseum (D.Don) Lindl.
Authors: Zhou X. , Lin H. , Fan X.-L. , Gao J.-Y.
Published: March 2012

Reproductive biology of saprophytic plants has been poorly studied. Epipogium roseum (D.Don) Lindl. is a small saprophytic orchid that is widely distributed in tropical and subtropical Asia, Australia and Africa. The floral biology and insect visitation of E. roseum were studied in Xishuangbanna, south Yunnan Province, China. E. roseum possesses an obligate self-pollination system, in which the degenerative rostellum has lost its function as a physical barrier separating the stigma and stamens (pollinia), allowing contact between the stigmatic secretions and the pollinia during bud development. Flowers of E. roseum usually open and successfully attract insect visitors. The Asian honey bee (Apis cerana cerana) was the only visitor observed, and regularly visited flowers of E. roseum for nectar. However, these bees did not carry pollinia away after visiting the flowers due to the absence of a viscid disk in E. roseum; the results of experiments also indicated that the Asian honey bee does not contribute to fruit set in E. roseum. The visiting frequency of Asian honey bees to flowers of E. roseum varied both spatially and temporally. E. roseum does not undergo outcrossing mediated by insects and is adapted to obligate self-pollination. We suggest that this may have evolved because of the uncertainty of pollinator services associated with its saprophytic lifestyle. Our current studies do not support the hypothesis that obligate autogamy is favoured by myco-heterotrophic plants due to resource limitations.
N-Heterocyclic Carbene Adducts of Cyclopalladated Ferrocenylpyridazine: Synthesis, Structural Characterization, and Application in ?-Arylation of Ketones with Aryl Chlorides
Authors: Xu Chen , Li Hong-Mei , Wang Zhi-Qiang , Fu Wei-Jun , Zhang Yu-Qing , Ji Bao-Ming
Published: March 2012

A new ferrocene-based ligand 3-chloro-6-pyridazinylferrocene 1 and its N-heterocyclic carbene adducts 2–3 were synthesized and characterized by 1H NMR and IR spectroscopy, ESI-MS, and elemental analysis. Additionally, detailed structures of complexes 2–3 have been determined by single-crystal X-ray analysis. Complex 3 exhibited high catalytic activity for α-arylation of ketones with aryl chlorides. Typically, using 1 mol % catalyst in the presence of 1.5 equivalents of tBuOK as base in dioxane at 100°C provided coupled products in good yields.
The fibroblast growth factor family: involvement in the regulation of folliculogenesis
Authors: Chaves Roberta Nogueira , Tavares de Matos Maria Helena , Buratini José , Ricardo de Figueiredo José
Published: March 2012

Several growth factors have been identified as local regulators of follicle development and ovulation. Fibroblast growth factor (FGF) family members are potent mitogens and are involved in cell differentiation, cell migration and angiogenesis in many tissues and organs. In addition to FGF-2, which is the most-studied FGF, other important members are FGF-1, -5, -7, -8, -9 and -10. A number of studies have indicated that FGFs play important roles in regulating the initiation of primordial follicle growth, oocyte and follicle survival, granulosa and theca cell proliferation and differentiation, corpus luteum formation, steroidogenesis and angiogenesis. The purpose of this review is to highlight the importance of the FGFs on mammalian female reproduction, providing a better understanding of the roles of this family in ovarian physiology and female fertility.
Control of protein signaling using a computationally designed GTPase/GEF orthogonal pair
Authors: Kapp Gregory T. , Liu Sen , Stein Amelie , Wong Derek T. , Reményi Attila , Yeh Brian J. , Fraser James S. , Taunton Jack , Lim Wendell A. , Kortemme Tanja
Published: March 2012

Signaling pathways depend on regulatory protein-protein interactions; controlling these interactions in cells has important applications for reengineering biological functions. As many regulatory proteins are modular, considerable progress in engineering signaling circuits has been made by recombining commonly occurring domains. Our ability to predictably engineer cellular functions, however, is constrained by complex crosstalk observed in naturally occurring domains. Here we demonstrate a strategy for improving and simplifying protein network engineering: using computational design to create orthogonal (non-crossreacting) protein-protein interfaces. We validated the design of the interface between a key signaling protein, the GTPase Cdc42, and its activator, Intersectin, biochemically and by solving the crystal structure of the engineered complex. The designed GTPase (
ortho
Cdc42) is activated exclusively by its engineered cognate partner (
ortho
Intersectin), but maintains the ability to interface with other GTPase signaling circuit components in vitro. In mammalian cells,
ortho
Cdc42 activity can be regulated by
ortho
Intersectin, but not wild-type Intersectin, showing that the designed interaction can trigger complex processes. Computational design of protein interfaces thus promises to provide specific components that facilitate the predictable engineering of cellular functions.
Promiscuous binding of extracellular peptides to cell surface class I MHC protein
Authors: Eisen Herman N. , Hou Xun Helen , Shen Chase , Wang Kaidi , Tanguturi Varsha Keelara , Smith Crysela , Kozyrytska Katerina , Nambiar Lakshmi , McKinley Carol A. , Chen Jianzhu , Cohen Richard J.
Published: March 2012

Algorithms derived from measurements of short-peptide (8–10 mers) binding to class I MHC proteins suggest that the binding groove of a class I MHC protein, such asKb, can bind well over 1 million different peptides with significant affinity (<500 nM), a level of ligand-binding promiscuity approaching the level of heat shock protein binding of unfolded proteins. MHC proteins can, nevertheless, discriminate between similar peptides and bind many of them with high (nanomolar) affinity. Some insights into this high-promiscuity/high-affinity behavior and its impact on immunodominant peptides in T-cell responses to some infections and vaccination are suggested by results obtained here from testing a model developed to predict the number of cell surface peptide–MHC complexes that form on cells exposed to extracellular (exogenous) peptides.
Walking the leadership tightrope: building community cohesiveness and social capital in schools in highly disadvantaged urban communities
Authors: Riley Kathryn A.
Published: March 2012

School leaders in highly disadvantaged urban communities across the globe walk a tightrope, caught between the needs of communities and the requirements of national policies. This article aims to enrich our understanding of the potential of school–community relationships. It examines the policy discourse on urban schools and the practice of community leadership. The policy context is one of UK and international concerns about divisions in society and the rise of political extremism: concerns which, in the UK, have led to a policy focus on community cohesion. The article offers a conceptual framework—a theory of action—as a possible road map for school leaders to manage through this complex and evolving arena of policy and practice. The template— developed through earlier work on urban schools—is underpinned by a focus on trust (as the lubricant to link communities together) and social capital (as a way of harnessing the ‘social energy’ of communities for positive good). The template is tested against the leadership of two school principals in challenging contexts in London and Greater Manchester. The author concludes that there is potential for schools to create space for the voices of the marginalised and disenfranchised to be heard. This analysis will resonate with school leaders serving disadvantaged communities in many international contexts and signals a new departure for leadership.
Innovative or imitative? Technology firms in China
Authors: Zheng Connie , Wang Bai Xuan
Published: March 2012

This paper has two aims. First, we clarify the belief that many Chinese firms have operated quite successfully both onshore and offshore by following cost-cutting strategies, through process efficiency rather than innovation. Second, we explain the reasons why Chinese firms are not all innovative by means of a review of empirical studies, as well as our own examination of two technology companies. We argue that there might be a dynamic sort of innovation that combines strategic costing with organisational and technological changes, and which has contributed to the fast growth and business success of some Chinese firms on the global stage in recent years. We use institutional theory and a resource-based view of the firm to explain why firms follow either innovative or imitative strategies. In analysing the three areas of innovation in two technology-based firms, we detect both innovative and imitative behaviour in Chinese firms. Our conclusion is that not all Chinese firms are innovative. Most Chinese firms follow an imitative strategy because of an imperfect institutional environment which diminishes the protection of intellectual property rights, which we regard as a prerequisite for innovation. Where Chinese firms do exhibit innovative behaviour, this is still predominantly strategic cost innovation, not innovation as it is commonly perceived and understood by researchers in the West.
Effect of paddle grip on segmental fluid distribution in elite slalom paddlers
Authors: Bílý Milan , Baláš Jiří , Martin Andrew John , Cochrane Darryl , Coufalová Klára , Süss Vladimír
Published: March 2012

Issues of high levels of muscular asymmetry have been associated with injury risk, and therefore have potential implications for decremental performance at the elite sport level. The aim of this current study was to assess the relationship between the segmental fluid distribution and the paddle grip in elite male and female slalom kayakers and canoeists. Eighty‐four world‐cup competitors (61 males and 23 females) took part in the study. Impedance analysis was used to assess segmental fluid asymmetry. The effect of paddle grip (loose/fixed hand in kayakers, lower/upper hand in canoeists), morphological dominance (dominant/non‐dominant) and discipline (canoe/kayak) were evaluated by repeated measures ANOVA. The findings indicated a significant effect of paddle grip in canoeists on morphological asymmetry in upper limbs (arm of lower paddle hand mean fluid distribution 3.28, s=0.43 litres; arm of upper paddle hand mean fluid distribution 3.19, s=0.41 litres; P=0.000, =0.33). The sternmen demonstrated higher asymmetry between the arms of upper and lower paddle hand (mean 0.11, s=0.04 litres, P=0.000, =0.80) than the bowmen (mean 0.04, s=0.06 litres, P=0.015, =0.44) in double‐canoes. Significant morphological asymmetry was found also in kayakers but the effect of paddle grip was not substantial. The use of segmental impedance analysis may be a suitable diagnostic tool for assessing morphological changes, which can be related to paddling training. Likewise muscular asymmetry is associated with injury risk; the evaluation of morphological changes during the training process may be considered by sport trainers and physical therapists.
The effects of running a 308 km ultra‐marathon on cardiac markers
Authors: Kim Young‐Joo , Shin Young‐Oh , Lee Jeong‐Beom , Lee Yoon‐Hee , Shin Kyung‐A , Kim Al‐Chan , Goh Choong‐Won , Kim Chul , Oh Jae‐Keun , Min Young‐Ki , Yang Hun‐Mo
Published: March 2012

The aim of this study was to investigate the expression of cardiac strain and damage in 18 male marathoners with average age of 52.8±5.0 years running at a 308 km ultra‐marathon. Blood samples were collected at pre‐race, 100 km, 200 km and 308 km check points for the analysis of cardiac muscle injury markers, creatine kinase (CK), creatine kinase–myocardial band (CK–MB), cardiac troponin I (cTnI) and cardiac muscle strain marker, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP). The CK levels increased 1127.2±507.9 IU/L, 5133.8±2492.7 IU/L and 4958.4±2087.9 IU/L at 100 km, 200 km and 308 km, respectively, compared to the pre‐race levels. The CK–MB levels increased 20.2±11.2 ng/mL, 73.3±35.6 ng/mL and 68.6±42.6 ng/mL at 100, 200 and 308 km, respectively, compared to the pre‐race levels. The CK–MB/CK ratio showed that the CK–MB mass index was within the normal range (<2.5%) at 100 km, 200 km and 308 km. The cTnI levels showed no significant difference in all check points. The NT‐proBNP levels increased 146.55±92.7 pg/mL, 167.95±111.9 pg/mL and 241.23±121.2 pg/mL at 100, 200 and 308 km, respectively, compared to the pre‐race levels. The normal CK–MB mass index (<5.0 ng/mL) and the absence of an increase in the cTnI levels during the 308 km ultra‐marathon suggested that no myocardial injury despite an elevation in CK–MB. The increase in NT‐proBNP levels probably resulted from continuous hemodynamic cardiac stress and represents a transient physiological myocardial protective response.
Processing natural language arguments with the  platform
Authors: Saint-Dizier Patrick
Published: March 2012

In this article, we first present the  platform and the Dislog language, designed for discourse analysis with a logic and linguistic perspective. The platform has now reached a certain level of maturity which allows the recognition of a large diversity of discourse structures including general-purpose rhetorical structures as well as domain-specific discourse structures. The Dislog language is based on linguistic considerations and includes knowledge access and inference capabilities. Functionalities of the language are presented together with a method for writing discourse analysis rules. Efficiency and portability of the system over domains and languages are investigated to conclude this first part. In a second part, we analyse the different types of arguments found in several document genres, most notably: procedures, didactic texts and requirements. Arguments form a large class of discourse relations. A generic and frequently encountered form emerges from our analysis: ‘reasons for conclusion’ which constitutes a homogeneous family of arguments from a language, functional and conceptual point of view. This family can be viewed as a kind of proto-argument. We then elaborate its linguistic structure and show how it is implemented in . We then investigate the cooperation between explanation and arguments, in particular in didactic texts where they are particularly rich and elaborated. This article ends with a prospective section that develops current and potential uses of this work and how it can be extended to the recognition of other forms of arguments.
A three-component mechanism for fibroblast migration with a contractile cell body that couples a myosin II–independent propulsive anterior to a myosin II–dependent resistive tail
Authors: Guo Wei-hui , Wang Yu-li
Published: March 2012

To understand the mechanism of cell migration, we cultured fibroblasts on micropatterned tracks to induce persistent migration with a highly elongated morphology and well-defined polarity, which allows microfluidic pharmacological manipulations of regional functions. The function of myosin II was probed by applying inhibitors either globally or locally. Of interest, although global inhibition of myosin II inhibited tail retraction and caused dramatic elongation of the posterior region, localized inhibition of the cell body inhibited nuclear translocation and caused elongation of the anterior region. In addition, local application of cytochalasin D at the tip inhibited frontal extension without inhibiting forward movement of the cell nucleus, whereas local treatment posterior to the nucleus caused reversal of nuclear movement. Imaging of cortical dynamics indicated that the region around the nucleus is a distinct compression zone where activities of anterior and posterior regions converge. These observations suggest a three-component model of cell migration in which a contractile middle section is responsible for the movement of a bulky cell body and the detachment/retraction of a resistive tail, thereby allowing these regions to undergo coordinated movement with a moving anterior region that carries little load.
Source Diversification and Import Price Risk
Authors: Muhammad Andrew
Published: March 2012

In this article, I present a theoretical framework and derive an empirical model that relates import price risk to the allocation of an import across exporting sources (source diversification). A differential approach to expected utility theory and firm demand is used to derive a model comparable to more popular demand systems such as the Rotterdam and AIDS models. The model is used in estimating carnation demand in the United Kingdom. Results show that while total carnation imports, expected prices and seasonality are important determinants of import demand by source, there is significant information loss when price risk is not considered.
Mirroring co-evolving trees in the light of their topologies
Authors: Hajirasouliha Iman , Schönhuth Alexander , de Juan David , Valencia Alfonso , Sahinalp S. Cenk
Published: March 2012

Motivation: Determining the interaction partners among protein/domain families poses hard computational problems, in particular in the presence of paralogous proteins. Available approaches aim to identify interaction partners among protein/domain families through maximizing the similarity between trimmed versions of their phylogenetic trees. Since maximization of any natural similarity score is computationally difficult, many approaches employ heuristics to evaluate the distance matrices corresponding to the tree topologies in question. In this article, we devise an efficient deterministic algorithm which directly maximizes the similarity between two leaf labeled trees with edge lengths, obtaining a score-optimal alignment of the two trees in question.

Results: Our algorithm is significantly faster than those methods based on distance matrix comparison: 1 min on a single processor versus 730 h on a supercomputer. Furthermore, we outperform the current state-of-the-art exhaustive search approach in terms of precision, while incurring acceptable losses in recall.

Availability: A C implementation of the method demonstrated in this article is available at http://compbio.cs.sfu.ca/mirrort.htm

Contact:  imanh@sfu.ca; cenk@sfu.ca; as@cwi.nl
Multiple Trajectories of Successful Aging of Older and Younger Cohorts
Authors: Hsu Hui-Chuan , Jones Bobby L.
Published: March 2012

Purpose:

The purpose of this study was to apply group-based trajectory analysis to identify multiple successful aging trajectories by multiple indicators and to examine the factors related to successful aging among the elderly population in Taiwan.

Design and Methods:

Nation-representative longitudinal data collected from 1993 to 2007 and consisting of 2 cohorts were used, and the trajectories of the following 6 successful aging indicators were analyzed: chronic diseases, physical function difficulties, depressive symptoms, social support, social participation, and economic satisfaction.

Results:

Members of the cohorts fell into 4 groups: successful aging, usual aging (the older cohort)/insecure aging (the younger cohort), health declining, and care demanding. Successful aging trajectories reflected differences in self-rated health and life satisfaction.

Implications:

This study provides empirical findings of the heterogeneity of successful aging trajectories in multidimensional indicators.
Prevalence and phylogenetic analysis of the current porcine circovirus 2 genotypes after implementation of widespread vaccination programmes in the USA
Authors: Shen Hui-Gang , Halbur Patrick G. , Opriessnig Tanja
Published: March 2012

To determine the prevalence of porcine circovirus 2 (PCV2) genotypes in the USA during 2010–2011, 5 years after widespread PCV2 vaccination, serum samples from clinically normal pigs that were PCV2 vaccinated (n = 1177), non-vaccinated (n = 378) or of unknown vaccination status (n = 120), and 100 lung samples from pigs diagnosed with PCV-associated disease (PCVAD) were tested. The presence of PCV2, PCV1, PCV1-2a and porcine parvovirus (PPV) DNA was determined by PCR. Determination of the PCV2 genotype was done by differential PCR and sequencing. The prevalence of PCV2a and PCV2b in serum samples was 7.7 % (129/1675) and 8.4 % (141/1675), respectively. PCV2a DNA was only detected in non-vaccinated pigs. For the 100 PCVAD pigs, the prevalence of PCV2a and PCV2b in lung tissues was 13.0 and 65.0 %, respectively. Partial PCV2 ORF2 sequences (9–563 nt) were obtained from 85 PCV2 DNA-positive samples (24 normal pigs and 61 PCVAD cases). Phylogenetic analysis revealed that 12.9 % (11/85) of the sequences belonged to the 2E clade and the PCV2a genotype and 87.1 % (74/85) belonged to the 1B clade and the PCV2b genotype. The alignment of putative PCV2 capsid amino acid sequences revealed possible recombination or mutation between PCV2a and PCV2b genotypes. Chimeric PCV1-2a was not detected in any of the samples and the prevalence rates of PCV1 and PPV were low. Our results suggest PCV2b is more prevalent than PCV2a in PCVAD cases and in vaccinated herds PCV2b circulation is common. The data generated in this study provide novel information on the distribution of PCV2 genotypes in vaccinated pig populations.
West Nile virus-induced disruption of the blood–brain barrier in mice is characterized by the degradation of the junctional complex proteins and increase in multiple matrix metalloproteinases
Authors: Roe Kelsey , Kumar Mukesh , Lum Stephanie , Orillo Beverly , Nerurkar Vivek R. , Verma Saguna
Published: March 2012

West Nile virus (WNV) encephalitis is characterized by neuroinflammation, neuronal loss and blood–brain barrier (BBB) disruption. However, the mechanisms associated with the BBB disruption are unclear. Complex interactions between the tight junction proteins (TJP) and the adherens junction proteins (AJP) of the brain microvascular endothelial cells are responsible for maintaining the BBB integrity. Herein, we characterized the relationship between the BBB disruption and expression kinetics of key TJP, AJP and matrix metalloproteinases (MMPs) in the mice brain. A dramatic increase in the BBB permeability and extravasation of IgG was observed at later time points of the central nervous system (CNS) infection and did not precede virus–CNS entry. WNV-infected mice exhibited significant reduction in the protein levels of the TJP ZO-1, claudin-1, occludin and JAM-A, and AJP β-catenin and vascular endothelial cadherin, which correlated with increased levels of MMP-1, -3 and -9 and infiltrated leukocytes in the brain. Further, intracranial inoculation of WNV also demonstrated increased extravasation of IgG in the brain, suggesting the role of virus replication in the CNS in BBB disruption. These data suggest that altered expression of junction proteins is a pathological event associated with WNV infection and may explain the molecular basis of BBB disruption. We propose that WNV initially enters CNS without altering the BBB integrity and later virus replication in the brain initiates BBB disruption, allowing enhanced infiltration of immune cells and contribute to virus neuroinvasion via the ‘Trojan-horse’ route. These data further implicate roles of multiple MMPs in the BBB disruption and strategies to interrupt this process may influence the WNV disease outcome.
Identification of novel causative genes determining the complex trait of high ethanol tolerance in yeast using pooled-segregant whole-genome sequence analysis
Authors: Swinnen Steve , Schaerlaekens Kristien , Pais Thiago , Claesen Jürgen , Hubmann Georg , Yang Yudi , Demeke Mekonnen , Foulquié-Moreno María R. , Goovaerts Annelies , Souvereyns Kris , Clement Lieven , Dumortier Françoise , Thevelein Johan M.
Published: March 2012

High ethanol tolerance is an exquisite characteristic of the yeast Saccharomyces cerevisiae, which enables this microorganism to dominate in natural and industrial fermentations. Up to now, ethanol tolerance has only been analyzed in laboratory yeast strains with moderate ethanol tolerance. The genetic basis of the much higher ethanol tolerance in natural and industrial yeast strains is unknown. We have applied pooled-segregant whole-genome sequence analysis to map all quantitative trait loci (QTL) determining high ethanol tolerance. We crossed a highly ethanol-tolerant segregant of a Brazilian bioethanol production strain with a laboratory strain with moderate ethanol tolerance. Out of 5974 segregants, we pooled 136 segregants tolerant to at least 16% ethanol and 31 segregants tolerant to at least 17%. Scoring of SNPs using whole-genome sequence analysis of DNA from the two pools and parents revealed three major loci and additional minor loci. The latter were more pronounced or only present in the 17% pool compared to the 16% pool. In the locus with the strongest linkage, we identified three closely located genes affecting ethanol tolerance: MKT1, SWS2, and APJ1, with SWS2 being a negative allele located in between two positive alleles. SWS2 and APJ1 probably contained significant polymorphisms only outside the ORF, and lower expression of APJ1 may be linked to higher ethanol tolerance. This work has identified the first causative genes involved in high ethanol tolerance of yeast. It also reveals the strong potential of pooled-segregant sequence analysis using relatively small numbers of selected segregants for identifying QTL on a genome-wide scale.
Technology and Flexibility: Enablers of Collaboration and Time‐Based Logistics Quality
Authors: Richey R. Glenn , Adams Frank G. , Dalela Vivek
Published: March 2012

Collaboration has been cited as one of the most important elements in leveraging supply chains to achieve competitive advantage. Literature in the field of collaboration tends to focus on strategic level initiatives; this research examines the benefits of implementing collaborative approaches at the logistics operations level. We find that leading strategic indicators, including technological innovativeness, technological complementarity, and flexibility are positively related to higher levels of collaboration and logistics service quality at the operational level in retail firms.
C4.4A is associated with tumor budding and epithelial–mesenchymal transition of colorectal cancer
Authors: Oshiro Ryota , Yamamoto Hirofumi , Takahashi Hidekazu , Ohtsuka Masahisa , Wu Xin , Nishimura Junichi , Takemasa Ichiro , Mizushima Tsunekazu , Ikeda Masataka , Sekimoto Mitsugu , Matsuura Nariaki , Doki Yuichiro , Mori Masaki
Published: March 2012

C4.4A is a glycolipid‐anchored membrane protein expressed in several human malignancies. The aim of this study was to explore the association between C4.4A expression at the invasion front of colorectal cancer (CRC) and tumor budding, a putative hallmark of cell invasion of CRC. Advanced CRCs (T2–4, n = 126) had a budding count of 3.66 ± 5.66, which was significantly higher than that of T1 early CRCs (1.75 ± 2.78, n = 87). C4.4A‐positive CRC specimens showed a larger budding cell number than C4.4A‐negative CRC specimens in T1 CRCs, and especially advanced CRCs (9.45 ± 5.83 vs 1.60 ± 3.93). Furthermore, we found a correlation between the percentage of C4.4A‐positive cases and budding count in advanced CRC. Multivariate analysis for patients' survival showed that C4.4A was superior to tumor budding as a prognostic factor. With siRNA treatment, C4.4A levels were associated with cell invasion, but not with proliferation, in HCT116 and DLD1 cell lines. An immunohistochemical study in a subset of CRCs showed no relationship between C4.4A and Ki‐67 proliferation marker. In vitro assays using HCT116 indicated that C4.4A levels correlated well with epithelial–mesenchymal transition (EMT) with regard to cell morphology and alterations of EMT markers including E‐cadherin, vimentin, and partially N‐cadherin. We also found that C4.4A expression was significantly associated with loss of E‐cadherin and gain of β‐catenin in clinical CRC tissue samples. These findings suggest that a tight association between C4.4A and tumor budding may, in part, be due to C4.4A promoting EMT at the invasive front of CRC. (Cancer Sci 2012; 103: 1155–1164)
Review article: bismuth‐based therapy for Helicobacter pylori eradication in children
Authors: Pacifico L. , Osborn J. F. , Anania C. , Vaira D. , Olivero E. , Chiesa C.
Published: March 2012

Background

Because of the decrease in the Helicobacter pylori eradication rate after standard triple therapy with a proton pump inhibitor and two antibiotics, bismuth‐based therapy has recently been recommended as alternate first‐line regimen in children.

Aim

To comprehensively review the clinical, pharmacologic and microbiologic properties of bismuth salts, and to summarise the evidence for the therapeutic efficacy of bismuth‐based therapy for H. pylori eradication in children.

Methods

Bibliographical searches were performed in MEDLINE. Results on the efficacy of bismuth‐containing regimens on H. pylori eradication were combined using the inverse variance method.

Results

Bismuth monotherapy showed a very low efficacy. Overall, the mean eradication rate with bismuth‐based dual therapy was 68% (95% CI, 60–76%) (intention‐to‐treat analysis‐ITT) and 73% (95% CI, 64–81%) (per protocol‐PP). In case series, the overall percentages of children with successful eradication for triple therapy containing bismuth were 82% (95% CI, 76–88%) and 86% (95% CI, 80–92%) according to ITT and PP respectively. In comparative studies, H. pylori eradication rates ranged between 69% and 85% according to ITT and between 74% and 96% PP. Side effects included dark stools, urine discoloration, black tongue, burning tongue, and marked darkness of the gums.

Conclusions

The evidence in favour of bismuth compounds for treating infected children is still not clear. Well‐designed, randomised, multi‐centre studies of H. pylori eradication trials in children comparing bismuth‐based triple therapy with the best available recommended first‐line therapies are needed. The evidence obtained from audited case series that produce an eradication rate of >95% on PP analysis should also be considered.
Symmetrical analysis of risk–benefit
Authors: Warren John B. , Day Simon , Feldschreiber Peter
Published: March 2012

To quantify the value of a medical therapy the benefits are weighed against the risks. Effectiveness is defined by objective evidence from predefined endpoints. This benefit is offset against the disadvantage of adverse events. The safety assessment is usually a subjective summary of concerns that can often be neither confirmed nor dismissed. But sometimes a clinical database is so large that a parameter common to both efficacy and safety can be quantified with reasonable certainty: myocardial infarction (MI) is used here as an example. Recently the Food and Drug Administration (FDA) proposed set limits for the incidence of MI as a safety threshold for diabetes treatment. Setting a threshold before something is considered as a safety concern opens the possibility of setting a threshold for clinically important efficacy. When a parameter is common to both safety and efficacy, then logically a unit change in either direction should be of equal weight in the risk and benefit analysis. For example, a doubling in the incidence of myocardial infarction as a safety signal should be given equal weight to the halving of the incidence of myocardial infarction as an efficacy signal. Similarly, if FDA guidance suggests that a less than a 30% increase in the incidence of MI as a safety parameter is considered acceptable, for example for diabetes treatment, when there is no other major toxicity, this opens a debate about a possible inverse threshold for clinical benefit for drugs that reduce a risk factor, such as antihypertensives.
Engaging parents of suicidal youth in a rural environment
Authors: Slovak Karen , Singer Jonathan B.
Published: March 2012

Engaging caregivers is an essential component of service for at‐risk youth. Engagement has been described as specific behaviours (e.g. treatment participation) and attitudes (e.g. therapeutic alliance). Although best practices for working with suicidal youth includes involving parents in the assessment and crisis plan, there has been almost no research on the process that clinicians in outpatient settings use to engage parents of youth who exhibit risk for suicide. The purpose of this study was to document how clinicians in outpatient mental‐health settings engaged parents following a youth suicide assessment. Twenty‐four clinicians from the rural Midwestern USA took part in two focus groups to discuss typical interactions with parents following a suicide assessment. Analyses suggested that clinicians' engagement with parents included five major elements: (i) presenting difficult information; (ii) responding to parents' reactions; (iii) joining with parents; (iv) moving the parents towards concrete actions; and (v) addressing rural gun culture. The results are discussed within the context of Staudt's conceptual framework of engagement with caregivers of at‐risk children. Implications for practice and research are discussed.
Carrier‐bound Alt a 1 peptides without allergenic activity for vaccination against Alternaria alternata allergy
Authors: Twaroch T. E. , Focke M. , Fleischmann K. , Balic N. , Lupinek C. , Blatt K. , Ferrara R. , Mari A. , Ebner C. , Valent P. , Spitzauer S. , Swoboda I. , Valenta R.
Published: March 2012

Background

The mould Alternaria alternata is a major elicitor of allergic asthma. Diagnosis and specific immunotherapy (SIT) of Alternaria allergy are often limited by the insufficient quality of natural mould extracts.

Objective

To investigate whether recombinant Alt a 1 can be used for reliable diagnosis of Alternaria alternata allergy and to develop a safe, non‐allergenic vaccine for SIT of Alternaria allergy.

Methods

The qualitative sensitization profile of 80 Alternaria‐allergic patients from Austria and Italy was investigated using an allergen micro‐array and the amount of Alternaria‐specific IgE directed to rAlt a 1 was quantified by ImmunoCAP measurements. Peptides spanning regions of predicted high surface accessibility of Alt a 1 were synthesized and tested for IgE reactivity and allergenic activity, using sera and basophils from allergic patients. Carrier‐bound peptides were studied for their ability to induce IgG antibodies in rabbits which recognize Alt a 1 and inhibit allergic patients’ IgE reactivity to Alt a 1.

Results

rAlt a 1 allowed diagnosis of Alternaria allergy in all tested patients, bound the vast majority (i.e. >95%) of Alternaria‐specific IgE and elicited basophil activation already at a concentration of 0.1 ng/mL. Four non‐allergenic peptides were synthesized which, after coupling to the carrier protein keyhole limpet hemocyanin, induced Alt a 1‐specific IgG and inhibited allergic patients’ IgE binding to Alt a 1.

Conclusions and clinical relevance

rAlt a 1 is a highly allergenic molecule allowing sensitive diagnosis of Alternaria allergy. Carrier‐bound non‐allergenic Alt a 1 peptides are candidates for safe SIT of Alternaria allergy.
Quality of life in adult patients with haemophilia – a single centre experience from Sweden
Authors: LINDVALL K. , Von MACKENSEN S. , BERNTORP E.
Published: March 2012

Summary.  Increased or maintained health and quality of life (HRQoL) are essential goals in health care among patients with a chronic disease. To gain an understanding of HRQoL in patients with haemophilia at the Haemophilia Treatment Centre in Malmö, Sweden, patients seen from 2004–2008 were asked to complete the Short form Health Survey, SF‐36, also answering to what extent haemophilia, physically and mentally, interferes with their daily life at their annual check‐up. Data were extracted from the UMAS Haemophilia Database. Interference of haemophilia in daily life was estimated using a Visual Analogue Scale. A total of 105/144 haemophilia patients were included in the study (73%); 28 mildly, 21 moderately and 56 severely affected. The median age of patients at study entry was 44.0 years (range 18–84 years). The comparison of SF‐36 data of Swedish haemophilia patients with the general Swedish male population yielded no significant differences in age groups 15–24, 25–34 and 65–74 years. Patients in age groups 35–44 years, 45–54 years and 55–64 years were significantly impaired in some of their HRQoL domains. For severely affected patients who filled in SF‐36 over a period of 5 years no statistical differences in HRQoL were found. For patients undergoing orthopaedic surgery HRQoL increased in most SF‐36 domains. Patients reported in general on the VAS that they feel ‘somehow’ interfered in their daily life due to haemophilia. The results indicate a need for continuous monitoring of HRQoL to identify an increased need of care in the ageing haemophilia population.
Fracture resistance and mode of failure of various types of root filled teeth
Authors: Castro C. G. , Santana F. R. , Roscoe M. G. , Simamoto P. C. , Santos‐Filho P. C. F. , Soares C. J.
Published: March 2012

Castro CG, Santana FR, Roscoe MG, Simamoto Jr PC, Santos‐Filho PCF, Soares CJ. Fracture resistance and mode of failure of various types of root filled teeth. International Endodontic Journal, 45, 840–847, 2012.

Aim  To investigate ex vivo the influence of the post system on fracture resistance and failure mode of root filled incisor, canine, premolar and molar teeth.

Methodology  Eighty human teeth were divided into eight groups (n = 10) resulting from the interaction between the two study factors: post system (glass fibre post; cast Ni–Cr alloy post and core) and type of tooth (maxillary incisors, maxillary canines, maxillary premolars and mandibular molars). All roots were prepared with a 2‐mm ferrule and restored with metal crown. Fracture resistance (N) was assessed in a mechanical testing device, and the data were analysed by two‐way anova (4 × 2) followed by Tukey’s test (α = 0.05). The failure mode was evaluated using an optical stereomicroscope and classified according to the location of the failure. Failure mode data were analysed by two‐factor anova and Student–Newman–Keuls (SNK) tests (α = 0.05). Correlation between fracture resistance and failure mode was analysed by linear regression.

Results  Glass fibre and cast posts and cores had similar fracture resistance, regardless of the type of tooth. Canines and molars had significantly higher fracture resistance (P < 0.001) than premolars. Incisors teeth had significantly lower fracture resistance (P < 0.001) than premolars. The fracture mode for incisors, premolars and molars was more amenable to restoration when the teeth were restored with glass fibre posts. Fracture resistance had no correlation with fracture mode, regardless of the post system and type of tooth analysed.

Conclusions  Post system had no significant effect on fracture resistance, regardless of the type of tooth. The mode of fracture was more restorable with glass fibre posts.