bluuebunny/crossref_metadata_2025 huggingface dataset:
Meganucleases and Their Biomedical Applications
Authors: Molina Rafael , Montoya Guillermo , Prieto Jesús
Published: January 2011

Homing endonucleases and zinc‐finger nucleases are double‐stranded meganucleases that target large
deoxyribonucleic acid
(DNA) recognition sites, a feature that means only a few such sites are likely to be present in a mammalian‐sized genome. Several homing endonucleases have been used as templates to engineer tools that cleave DNA sequences other than their original wild‐type targets. Indeed, zinc‐finger nucleases have been designed to recognise specific genes. These custom meganucleases can be used to stimulate double‐strand break homologous recombination in cells, thereby inducing the repair of defective genes with very low toxicity levels. The use of tailored meganucleases opens up new possibilities for gene therapy in patients with monogenic diseases that can be treated

ex vivo

. This review provides an overview of recent advances in this field.

Key Concepts:

Meganucleases are double‐stranded DNAses that target large recognition sites.

Meganucleases promote efficient gene targeting through double‐strand‐break‐induced homologous recombination.

Homologous recombination and nonhomologous end joining are the two pathways that can be used to repair DNA double‐strand breaks.

Meganucleases encompass homing endonucleases and zinc‐finger nucleases.

Meganucleases are ideal scaffolds to engineer enzymes that accurately cleave DNA and induce recombination.

Meganucleases can recognise unique sites of cleavage within a genome, permitting their use for therapeutic purposes in human diseases.

X‐ray diffraction of crystallised proteins allows us to understand the relationship between the structure and function of biomolecules.
Carbocupration of Alkynes
Authors: Chemla Fabrice , Ferreira Franck
Published: January 2011

General Introduction

Carbocupration of Acetylene

Carbocupration of Substituted Alkynes

Conclusion
Oxidation of Organocopper Compounds
Authors: Aves Sarah J. , Spring David R.
Published: January 2011

Introduction

Formation of
C

C
Bonds

Formation of
C

N
Bonds

Conclusion
Copper‐Mediated and Copper‐Catalyzed Addition and Substitution Reactions of Extended Multiple Bond Systems
Authors: Krause Norbert , Aksin‐Artok Özge
Published: January 2011

Introduction

Copper‐Mediated and Copper‐Catalyzed Addition Reactions to Extended Michael Acceptors

Copper‐Mediated and Copper‐Catalyzed Substitution Reactions of Extended Substrates

Conclusion
Increases in global tropospheric ozone following an El Niño event: examining stratospheric ozone variability as a potential driver
Authors: Voulgarakis A. , Hadjinicolaou P. , Pyle J. A.
Published: January 2011

The stratosphere can strongly influence the interannual variability of tropospheric ozone. It has been discussed previously that tropospheric ozone can increase following an El Niño event, due to enhanced stratosphere/troposphere exchange (STE) of ozone. Here, we run a chemical‐transport model for 5 years, covering a period including a strong El Niño event (1997–1998), and find that variability of ozone in the stratosphere is an almost negligible driver of modelled post‐El Niño increases of ozone STE and tropospheric ozone abundances. Changes in the dynamics, affecting the cross‐tropopause air‐mass flux, may be far more important in driving these anomalies. Copyright © 2011 Royal Meteorological Society
Stereoselective Single (Copper) or Double (Platinum) Boronation of Alkynes Catalyzed by Magnesia‐Supported Copper Oxide or Platinum Nanoparticles
Authors: Grirrane Abdessamad , Corma Avelino , Garcia Hermenegildo
Published: January 2011

Copper(II) oxide nanoparticles supported on magnesia have been prepared from CuII supported on magnesia by hydrogen reduction at 400 °C followed by storage under ambient conditions. X‐ray photoelectron spectroscopy of the material clearly shows that immediately after the reduction copper(0)–metal nanoparticles are present on the magnesia support, but they undergo fast oxidation to copper oxide upon contact with the ambient for a short time. TEM images show that the catalytically active CuO/MgO material is formed of well‐dispersed copper oxide nanoparticles supported on fibrous MgO. CuO/MgO exhibits a remarkable catalytic activity for the monoborylation of aromatic, aliphatic, terminal, and internal alkynes, the products being formed with high regio‐ (borylation at the less substituted carbon) and stereoselectivity (trans‐configured). CuO/MgO exhibits complete chemoselectivity towards the monoborylation of alkynes in the presence of alkenes. Other metal nanoparticles such as gold or palladium are inactive towards borylation, but undergo undesirable oligomerization or partial hydrogenation of the CC triple bond. In contrast, platinum, either supported on magnesia or on nanoparticulate ceria, efficiently promotes the stereoselective diborylation of alkynes to yield a cis‐configured diboronate alkene. By using platinum as the catalyst we have developed a tandem diborylation/hydrogenation reaction that gives vic‐diboronated alkanes from alkynes in one pot.
How does macroinvertebrate taxonomic resolution influence ecohydrological relationships in riverine ecosystems
Authors: Monk Wendy A. , Wood Paul J. , Hannah David M. , Extence Chris A. , Chadd Richard P. , Dunbar Michael J.
Published: January 2011

The taxonomic resolution of macroinvertebrate community data needs careful consideration, to ensure that research objectives in pure and applied freshwater scientific research are met. The level of taxonomy used may be driven by time and financial restrictions associated with the increasing resources and effort needed to identify organisms to a lower taxonomic resolution. This paper aims to assess the influence of taxonomic resolution on the understanding of long‐term (1985–2006) benthic macroinvertebrate community response to changes in the hydrological regime. There were marked differences in the number of taxa included in the analysis when comparing ‘species’‐ and ‘family’‐level data used to derive lotic‐invertebrate index for flow evaluation (LIFE) scores, particularly among species rich orders, such as Ephemeroptera, Plecoptera, Trichoptera and Coleoptera. The performance of the partial least squares (PLS) regression models of hydrological variables and the LIFE scores derived for different taxonomic levels were compared. Coefficients of determination were higher for species‐level LIFE data than for the same data resolved to family level. Results demonstrate that the species‐level LIFE data produced significant model components while those derived from family‐level data were not; although both models indicated the dominance of hydrological indices quantifying the duration and magnitude of the hydrological events. We conclude that there is a growing need to resolve faunal data to species level to adequately fulfil operational and legislative obligations for river management and conservation purposes. Copyright © 2011 John Wiley & Sons, Ltd.
Design of neo‐glycoconjugates that target the mannose receptor and enhance TLR‐independent cross‐presentation and Th1 polarization
Authors: Singh Satwinder Kaur , Streng‐Ouwehand Ingeborg , Litjens Manja , Kalay Hakan , Burgdorf Sven , Saeland Eirikur , Kurts Christian , Unger Wendy W. , van Kooyk Yvette
Published: January 2011

Cross‐presentation is an important mechanism by which DCs present exogenous antigens on MHC‐I molecules, and activate CD8+ T cells, cells that are crucial for the elimination of tumors. We investigated the feasibility of exploiting the capacity of the mannose receptor (MR) to improve both cross‐presentation of tumor antigens and Th polarization, processes that are pivotal for the anti‐tumor potency of cytotoxic T cells. To this end, we selected two glycan ligands of the MR, 3‐sulfo‐LewisA and tri‐GlcNAc (N‐acetylglucosamine), to conjugate to the model antigen OVA and assessed in vitro the effect on antigen presentation and Th differentiation. Our results demonstrate that conjugation of either 3‐sulfo‐LewisA or tri‐GlcNAc specifically directs antigen to the MR. Both neo‐glycoconjugates showed, even at low doses, improved uptake as compared with native OVA, resulting in enhanced cross‐presentation. Using MR−/− and MyD88‐TRIFF−/− bone marrow‐derived DCs (BMDCs), we show that the cross‐presentation of the neo‐glycoconjugates is dependent on MR and independent of TLR‐mediated signaling. Whereas proliferation of antigen‐specific CD4+ T cells was unchanged, stimulation with neo‐glycoconjugate‐loaded DCs enhanced the generation of IFN‐γ‐producing T cells. We conclude that modification of antigen with either 3‐sulfo‐LewisA or tri‐GlcNAc enhances cross‐presentation and permits Th1 skewing, through specific targeting of the MR, which may be beneficial for DC‐based vaccination strategies to treat cancer.
IL‐22 is produced by γC‐independent CD25+ CCR6+ innate murine spleen cells upon inflammatory stimuli and contributes to LPS‐induced lethality
Authors: Dumoutier Laure , de Heusch Magali , Orabona Ciriana , Satoh‐Takayama Naoko , Eberl Gerard , Sirard Jean‐Claude , Di Santo James P. , Renauld Jean‐Christophe
Published: January 2011

IL‐22 is a Th17 cytokine that plays a key role in immune responses against extracellular bacteria. In mucosal lymphoid tissues, IL‐22 production is mainly due to an IL‐23‐responsive NK‐like cell subset that shares some markers with lymphoid tissue inducer (LTi) cells. Here, we identified a new spleen cell population responsible for IL‐22 production upon either in vitro stimulation by anti‐CD3 antibodies or in vivo stimulation by lipopolysaccharide (LPS) via IL‐2‐ and an IL‐23‐dependent mechanisms, respectively. These cells represent 1% of spleen cells from recombination activating gene (Rag2)‐deficient mice, and correspond to a discrete innate lymphoid cell population expressing CD25, CCR6 and IL‐7R. This population comprises 60–70% CD4+ cells, which produce IL‐22, and are still present in common γ chain‐deficient mice; the CD4− subset coexpresses IL‐22 and IL‐17, and is common γ chain‐dependent. The importance of IL‐22 production for the LPS‐triggered response is highlighted by the fact that IL‐22‐deficient mice are more resistant to LPS‐induced mortality.
The high‐frequency limit of usable response spectral ordinates from filtered analogue and digital strong‐motion accelerograms
Authors: Akkar Sinan , Kale Özkan , Yenier Emrah , Bommer Julian J.
Published: January 2011

The range of response frequencies for which spectral ordinates obtained from accelerograms may be considered reliable is limited by several factors, primary among them being the effects of filters that are routinely applied to remove noise from the records. Considerable attention has been focused on the low‐frequency limit of the usable spectral ordinates because of various engineering applications requiring long‐period spectral accelerations or displacements but only recently have rational approaches to selecting the high‐frequency limit been proposed. Since there are applications for which the high‐frequency spectral ordinates are important, the approaches to this issue presented in the recent studies are reviewed and their application to the ground‐motion database from Europe and the Middle East is explored. On the basis of the results of these analyses, it is concluded that a large proportion of this dataset can be used to provide reliable estimates of response spectral ordinates at much shorter periods than may have previously been considered feasible. Copyright © 2011 John Wiley & Sons, Ltd.
Seismic reliability of traditional and innovative concentrically braced frames
Authors: Giugliano Maria Teresa , Longo Alessandra , Montuori Rosario , Piluso Vincenzo
Published: January 2011

Structural engineering problems are always affected by many sources of uncertainty, such as aleatory of material properties, applied loads and earthquake intensity, therefore, seismic assessment of structures should be based on probabilistic methods. Since PBSD (Performance‐based Seismic Design) philosophy was formulated, many researches have been conducted in this field in order to develop simple and accurate procedures for evaluating structural reliability. An important contribution has been provided by Jalayer and Cornell, who have developed a closed‐form expression to evaluate the mean annual frequency of exceeding a defined limit state. In this paper, by assuming the record‐to‐record variability as the only source of uncertainty, the seismic reliability of concentrically braced frames designed according to traditional and innovative methodologies is investigated, and a comparison between their performances is presented. In particular, two design methodologies have been applied: Eurocode 8 provisions and a new design methodology based on a rigorous application of ‘capacity design’ criteria. The innovative reduced section solution strategy, based on the reduction of cross sections at bracing member ends, has also been analysed. Copyright © 2011 John Wiley & Sons, Ltd.
Control of Noise in Chemical and Biochemical Information Processing
Authors: Privman Vladimir
Published: January 2011

We review models and approaches for error control in order to prevent the buildup of noise when gates for digital chemical and biomolecular computing based on (bio)chemical reaction processes are utilized to realize stable, scalable networks for information processing. Solvable rate equation models illustrate several recently developed methodologies for gate‐function optimization. We also survey future challenges and possible new research avenues.
Prostate‐derived Ets transcription factor (PDEF) is a potential prognostic marker in patients with prostate cancer
Authors: Ghadersohi Ali , Sharma Satish , Zhang Shaozeng , Azrak Rami G. , Wilding Gregory E. , Manjili Masoud H. , Li Fengzhi
Published: January 2011

BACKGROUND

Reduced expression of prostate‐derived Ets transcription factor (PDEF) leads to morphologic change as well as increased migration and invasiveness of prostate cancer cells. However, the clinical relevance of PDEF expression and its relationship to anti‐apoptotic protein survivin is yet to be determined.

METHODS

Tissue microarrays of 73 prostate carcinomas and their adjacent benign prostate tissue, as well as 50 benign prostates were evaluated for PDEF expression by immunohistochemistry. Results were confirmed in available tumor tissues using Western blot and RT‐PCR. Expression of survivin in prostate carcinoma and benign tissues were determined using Western blot. Results and correlation with clinical data were statistically analyzed.

RESULTS

Patients' specimens with low Gleason scores (GS < 5) expressed higher levels of PDEF protein and lower levels of survivin protein when compared with moderate‐to‐high GS tumors (GS > 6). Patients with PDEF‐positive tumor survived significantly longer (P < 0.0001) than patients with PDEF‐negative tumor, and the 8‐year survival rate was 94% and 40%, respectively. PDEF expression was detected at the highest levels in benign tissues and was down‐regulated or lost in 30 recently diagnosed prostate carcinomas. Re‐expression of PDEF in prostate cancer cells inhibited survivin expression. Treatment of prostate cancer cells with methylseleninic acid resulted in restoration of PDEF expression, down‐regulation of survivin, and inhibition of tumor cell growth when compared with untreated controls (P < 0.05).

CONCLUSIONS

These studies demonstrated an inverse correlation between PDEF and survivin expression, and that up‐regulation of PDEF was associated with a favorable prognosis in patients with clinically localized prostate cancer. Prostate 71:1178–1188, 2011. © 2011 Wiley‐Liss, Inc.
Resistive memory switching in layered oxides: AnBnO3n+2 perovskite derivatives and Bi2Sr2CaCu2O8+δ high‐Tc superconductor
Authors: Koval Y. , Chowdhury F. , Jin X. , Simsek Y. , Lichtenberg F. , Pentcheva R. , Müller P.
Published: January 2011

Resistive memory switching was investigated in titanates and niobates of the type AnBnO3n+2 and in the high‐Tc superconductor Bi2Sr2CaCu2O8+δ. We studied the switching by current injection perpendicular to the layers. Both dc and pulsed measurements were performed. Out‐of‐plane transport properties were investigated by measurements of the resistance and current–voltage characteristics (IVs) vs. temperature for different resistive states. The critical temperature of superconducting transition and the critical current of intrinsic Josephson junctions were also analyzed for different resistive states in Bi2Sr2CaCu2O8+δ. The resistive memory switching was explained in terms of doping of the conducting layers, which is induced by trapped charges in the insulating layers. The charged insulating layers act as a floating gate and reduce or increase the carrier concentration in the conducting layers, respectively. We found that all studied materials demonstrate a different type of non‐persistent resistive switching at low temperatures. This type of switching shows up in a specific form of current–voltage characteristics with a pronounced back‐bending often called s‐shaped IV. Both types of resistive switching with and without memory effect were analyzed in terms of electron overheating. We examine the role of hot electrons and discuss additional factors, which might lead to persistent resistive states.
Development and clinical evaluation of medical robot assisted photodynamic therapy of port wine stains
Authors: Wang Xing‐tao , Duan Xing‐guang , Huang Qiang , Bian Gui‐bin , Zhao Hong‐hua , Huang Nai‐yan , Gu Ying , Tang Xiao‐ying
Published: January 2011

Background

Port wine stains (PWS) are a kind of skin disease for which photodynamic therapy (PDT) has already achieved good results. With manual operation of clinical PDT, the laser density is uneven and laser irradiation of the lesion is arbitrary and non‐uniform. In addition, lengthy manual operation tires doctors; thus a robot system has been developed to assist them.

Methods

First, a novel medical manipulator consisting of five passive joints (robot arm) and two active joints (robot wrist) was developed to automatically improve the uniformity of laser irradiation. Second, image processing of the lesion was introduced. Third, kinematics and path planning of the robot were analysed, and safety precautions were introduced. Then, accuracy tests of the robot wrist and robot system were conducted separately before clinical application. Finally, a total of 50 PWS cases were treated using the robot system. The clinical outcomes and comparison of non‐parametric values were employed to evaluate the robot system.

Results

The accuracies of the robot wrist and robot system were shown to meet the requirements of clinical PDT treatment. The robot system performed successfully in 50 PWS cases. Doctors can devote more energy to clinical judgments during treatment with the assistance of the robot system. All the PWS have shown different degrees of improvement. The results show that the robot system is useful in assisting doctors for the PDT treatment of PWS.

Conclusions

The experiments show the feasibility and usefulness of the robot system in assisting doctors giving PDT treatment for PWS. The robot system can lighten the load on doctors and improve the therapeutic effect. Copyright © 2011 John Wiley & Sons, Ltd.
Patient-reported outcomes in congenital cardiac disease: are they as good as you think they are?
Authors: Moons Philip
Published: January 2011

Patient-reported outcomes are “any outcome based on data provided by patients or patient proxy as opposed to data provided from other sources”. Examples of patient-reported outcomes are quality of life, well-being, functional status, symptoms, adherence to treatment, satisfaction with treatment, and utility or preference-based measures. The main question of this manuscript is whether patient-reported outcomes in patients with congenital cardiac disease are as good as we think they are. In general, we could say yes, because numerous studies show that patients with congenital cardiac disease have an excellent quality of life. By contrast, we could say no, because patients generally overestimate their functioning, and up to two out of three patients are not compliant with the prescribed therapy or recommendations for follow-up. However, most importantly, we have to say that we do not know whether the patient-reported outcomes are good, because research with patient-reported outcomes in congenital cardiac disease is limited. Hence, patient-reported outcomes should be a priority on the agenda for research in the domain of congenital cardiac disease.
NONVANISHING OF JACOBI POINCARÉ SERIES
Authors: DAS SOUMYA
Published: January 2011

We prove that, under suitable conditions, a Jacobi Poincaré series of exponential type of integer weight and matrix index does not vanish identically. For the classical Jacobi forms, we construct a basis consisting of the ‘first’ few Poincaré series, and also give conditions, both dependent on and independent of the weight, that ensure the nonvanishing of a classical Jacobi Poincaré series. We also obtain a result on the nonvanishing of a Jacobi Poincaré series when an odd prime divides the index.
Remapping for visual stability
Authors: Hall Nathan J. , Colby Carol L.
Published: January 2011

Visual perception is based on both incoming sensory signals and information about ongoing actions. Recordings from single neurons have shown that corollary discharge signals can influence visual representations in parietal, frontal and extrastriate visual cortex, as well as the superior colliculus (SC). In each of these areas, visual representations are remapped in conjunction with eye movements. Remapping provides a mechanism for creating a stable, eye-centred map of salient locations. Temporal and spatial aspects of remapping are highly variable from cell to cell and area to area. Most neurons in the lateral intraparietal area remap stimulus traces, as do many neurons in closely allied areas such as the frontal eye fields the SC and extrastriate area V3A. Remapping is not purely a cortical phenomenon. Stimulus traces are remapped from one hemifield to the other even when direct cortico-cortical connections are removed. The neural circuitry that produces remapping is distinguished by significant plasticity, suggesting that updating of salient stimuli is fundamental for spatial stability and visuospatial behaviour. These findings provide new evidence that a unified and stable representation of visual space is constructed by redundant circuitry, comprising cortical and subcortical pathways, with a remarkable capacity for reorganization.
The Botrytis cinerea phytotoxin botcinic acid requires two polyketide synthases for production and has a redundant role in virulence with botrydial
Authors: DALMAIS BÉRENGÈRE , SCHUMACHER JULIA , MORAGA JAVIER , LE PÊCHEUR PASCAL , TUDZYNSKI BETTINA , COLLADO ISIDRO GONZALEZ , VIAUD MURIEL
Published: January 2011

The grey mould fungus Botrytis cinerea produces two major phytotoxins, the sesquiterpene botrydial, for which the biosynthesis gene cluster has been characterized previously, and the polyketide botcinic acid. We have identified two polyketide synthase (PKS) encoding genes, BcPKS6 and BcPKS9, that are up‐regulated during tomato leaf infection. Gene inactivation and analysis of the secondary metabolite spectra of several independent mutants demonstrated that both BcPKS6 and BcPKS9 are key enzymes for botcinic acid biosynthesis. We showed that BcPKS6 and BcPKS9 genes, renamed BcBOA6 and BcBO9 (for B. cinerea botcinic acid biosynthesis), are located at different genomic loci, each being adjacent to other putative botcinic acid biosynthetic genes, named BcBOA1 to BcBOA17. Putative orthologues of BcBOA genes are present in the closely related fungus Sclerotinia sclerotiorum, but the cluster organization is not conserved between the two species. As for the botrydial biosynthesis genes, the expression of BcBOA genes is co‐regulated by the Gα subunit BCG1 during both in vitro and in planta growth. The loss of botcinic acid production does not affect virulence on bean and tomato leaves. However, double mutants that do not produce botcinic acid or botrydial (bcpks6Δbcbot2Δ) exhibit markedly reduced virulence. Hence, a redundant role of botrydial and botcinic acid in the virulence of B. cinerea has been demonstrated.
Adherence to treatment guidelines and long‐term survival in hospitalized patients with chronic obstructive pulmonary disease
Authors: Sarc Irena , Jeric Tina , Ziherl Kristina , Suskovic Stanislav , Kosnik Mitja , Anker Stefan D. , Lainscak Mitja
Published: January 2011

Rationale and aims  Adherence to treatment guidelines in chronic obstructive pulmonary disease (COPD) has been shown to be less than optimal over the COPD continuum. This retrospective study aimed to assess the implementation of COPD guidelines and potential association with long‐term mortality in patients with COPD.

Methods  All consecutive patient discharges in the period of February 2002–June 2007 from the University Clinic of Pulmonary and Allergic Diseases Golnik, Slovenia, were screened for a primary discharge diagnosis of COPD.

Results  Data on 1185 patients (mean age 70 ± 9 years, 72% men, 64% GOLD stage III/IV) were analysed. In the discharge letters 62% of patients had three or more drugs prescribed; 3% had no regular prescription. Most patients were discharged with short‐acting (91%) and long‐acting β2‐agonists (LABAs, 65%) and inhaled corticosteroids (61%), and 23% received long‐term oxygen therapy. Prescription rates of LABAs, tiotropium and inhaled corticosteroids increased over the disease continuum (P < 0.001). In total, 48% of patients died during a median follow‐up of 1149 days. Deceased patients had been less often treated with LABAs, inhaled corticosteroids and tiotropium. In multivariate Cox proportional‐hazards analysis, advanced age, current smoking status, lower body mass index, longer hospital stay and cancer were associated with higher mortality (P < 0.05 for all), and inhaled corticosteroids predicted lower mortality (hazard ratio 0.72, 95% confidence interval 0.55–0.94).

Conclusion  Implementation of guideline‐recommended therapy was not optimal, particularly in patients who died during follow‐up. The high long‐term mortality calls for careful risk assessment and appropriate adherence to treatment guidelines.
Prolonged, wireless pH‐studies have a high diagnostic yield in patients with reflux symptoms and negative 24‐h catheter‐based pH‐studies
Authors: Sweis R. , Fox M. , Anggiansah A. , Wong T.
Published: January 2011

Background  Catheter‐based esophageal pH‐monitoring is used to evaluate patients with suspected gastro‐esophageal reflux disease (GERD); however false‐negative results may occur due to poor tolerance of the catheter with reduced oral intake and activity, or high day‐to‐day variation in reflux and symptom events. We assessed diagnostic yield and clinical impact of prolonged, wireless pH‐monitoring in patients with negative results from 24‐h catheter‐based studies and ongoing symptoms.

Methods  Esophageal acid exposure (percentage time pH <4), Symptom Index, and Symptom Association Probability (SAP) were calculated. Diagnostic yield was assessed using Average (mean) and Worst Day (24‐h period with highest acid exposure or symptom load) analyses. Outcome data were assessed 6–36 months (median 24) after initiation of definitive therapy based on physiologic testing.

Key Results  Data from prolonged pH‐monitoring up to 96‐h (median 72‐h) were available from 38 patients. Using Average and Worst Day analysis, esophageal acid exposure was pathologic in 37% and 47%, whereas SAP was positive in 34% and 63% of patients, respectively. Overall using Average and Worst Day analyses, 61% and 76% patients were diagnosed with GERD based on either pathologic acid exposure or positive symptom association. Of 12 patients that underwent antireflux surgery, 10(83%) reported a good outcome at a median 24 months follow‐up.

Conclusions & Inferences  Prolonged, wireless pH‐monitoring increases test sensitivity and diagnostic yield in patients with continuing esophageal symptoms despite negative 24‐h catheter‐based pH‐studies. Without a definitive diagnosis, many would not have received effective treatment.
Gene expression analysis of wounding‐induced root‐to‐shoot communication in Arabidopsis thaliana
Authors: HASEGAWA SATOKO , SOGABE YUSUKE , ASANO TOMOYA , NAKAGAWA TOMOYUKI , NAKAMURA HARUNA , KODAMA HIROAKI , OHTA HIROYUKI , YAMAGUCHI KAZUO , MUELLER MARTIN J. , NISHIUCHI TAKUMI
Published: January 2011

Root‐to‐shoot communication plays an important role in the adaptation to environmental stress. In this study, we established a model system for root‐to‐shoot signalling to observe global gene expression in Arabidopsis thaliana. The roots of Arabidopsis seedlings were wounded and the expression in the shoots of 68 and 5 genes was up‐regulated threefold at 30 min and 6 h post‐injury, respectively. These genes were designated early and late Root‐to‐Shoot responsive (RtS) genes, respectively. Many of the early RtS genes were found to encode transcription factors such as AtERFs, whereas others were associated with jasmonic acid (JA) and ethylene (ET). Some of the late RtS genes were shown to be regulated by 12‐oxo‐phytodienoic acid (OPDA). In fact, elevated levels of JA and OPDA were detected in the shoots of seedlings 30 min and 6 h, respectively, after wounding of the roots. A mutant analysis revealed that JA and ET are involved in the expression of the early RtS genes. Thus, root‐to‐shoot communication for many RtS genes is associated with the systemic production of JA, OPDA and possibly ET.
Sucrose transporter plays a role in phloem loading in CMV‐infected melon plants that are defined as symplastic loaders
Authors: Gil Lidor , Yaron Imry , Shalitin Dror , Sauer Norbert , Turgeon Robert , Wolf Shmuel
Published: January 2011

Based on the high density of plasmodesmata interconnecting the intermediary cells and their neighboring phloem parenchyma or bundle‐sheath cells, and based on the insensitivity to the sucrose transport inhibitor p‐chloromercuribenzenesulfonic acid (PCMBS), cucurbits have been concluded to be symplastic loaders. In the present study, we identified and characterized the full‐length sequence of sucrose transporter gene (CmSUT1) from melon (Cucumis melo L. cv. Hale’s best jumbo). In vitro experiments confirmed that the identified gene product has sucrose transporter activity in baker’s yeast. Healthy and cucumber mosaic virus (CMV)‐infected melon plants were employed to examine sucrose transporter activity in planta. Pretreatment with PCMBS inhibited loading of newly fixed 14CO2 into minor veins of CMV‐infected plants. Moreover, CMV infection caused significant increase in CmSUT1 transcripts expression, mainly in vascular bundles of minor veins, which was associated with elevated sucrose content in phloem sap collected from source‐leaf petioles. We propose that cucurbit plants contain the machinery for apoplastic phloem loading and that CMV infection causes a quantitative shift in the mode by which photoassimilates are loaded into the sieve tube.
Slow photosynthetic induction and low photosynthesis in Paphiopedilum armeniacum are related to its lack of guard cell chloroplast and peculiar stomatal anatomy
Authors: Zhang Shi‐Bao , Guan Zhi‐Jie , Chang Wei , Hu Hong , Yin Qing , Cao Kun‐Fang
Published: January 2011

Paphiopedilum and Cypripedium are close relatives in the subfamily Cypripedioideae. Cypripedium leaves contain guard cell chloroplasts, whereas Paphiopedilum do not. It is unclear whether the lack of guard cell chloroplasts affects photosynthetic induction, which is important for understory plants to utilize sunflecks. To understand the role of guard cell chloroplasts in photosynthetic induction of Paphiopedilum and Cypripedium, the stomatal anatomy and photosynthetic induction of Paphiopedilum armeniacum and Cypripedium flavum were investigated at different ratios of red to blue light. The highest stomatal opening and photosynthesis of intact leaves in P. armeniacum were induced by irradiance enriched with blue light. Its stomatal opening could be induced by red light 250 µmol m−2 s−1, but the magnitude of stomatal opening was lower than those at the other light qualities. However, the stomatal opening and photosynthesis of C. flavum were highly induced by mixed blue and red light rather than pure blue or red light. The two orchid species did not differ in stomatal density, but P. armeniacum had smaller stomatal size than C. flavum. The stomata of P. armeniacum were slightly sunken into the leaf epidermis, while C. flavum protruded above the leaf surface. The slower photosynthetic induction and lower photosynthetic rate of P. armeniacum than C. flavum were linked to the lack of guard cell chloroplasts and specific stomatal structure, which reflected an adaptation of Paphiopedilum to periodic water deficiency in limestone habitats. These results provide evidence for the morphological and physiological evolution of stomata relation for water conservation under natural selection.
Comparison of the bacterial isolates and antibiotic resistance patterns of elderly nursing home and general community patients
Authors: Xie C. , Taylor D. McD. , Howden B. P. , Charles P. G. P.
Published: January 2011

Background:  Nursing home‐acquired infections may differ from general community‐acquired infections in bacteriology and antibiotic resistance. However, there are currently limited data on this topic in the Australian setting.

Aims:  To compare bacterial isolates and antibiotic resistance patterns, from pathology specimens of nursing home and community patients, and to comment on the suitability of empiric antibiotic guidelines for nursing home‐acquired infection.

Methods:  This was a retrospective cohort study of patients, aged ≥65 years, who resided in either nursing homes or the general community. Patients with a hospital admission in the previous 28 days were excluded. Positive specimen cultures, collected between July 2003 and June 2008 in the Emergency Department and Outpatient Clinics of the Austin Hospital (Melbourne), were examined. The main outcome measures were the bacterial isolates, and their antibiotic resistance patterns, of patients from nursing homes and the general community.

Results:  Specimens of blood (638), sputum (425), urine (4044) and wound cultures (785) were examined. The bacteriology of blood culture isolates did not differ between the two groups (P= 0.3). However, the bacteriology of sputum, urine and wound cultures differed significantly between the groups (P= 0.025, P < 0.001, P= 0.004 respectively). There were also higher proportions of antibiotic resistance among some bacteria in nursing home patients, especially methicillin resistance among Staphylococcus aureus isolates across all specimen types, and resistance to several empiric antibiotics among Enterobacteriaceae isolates in urine cultures.

Conclusion:  Empiric antibiotic guidelines appear adequate to treat nursing home‐acquired septicaemia and pneumonia. However, guidelines for urinary tract infections and wound infections may need to be refined.
REALIZING BENEFIT SHARING – THE CASE OF POST‐STUDY OBLIGATIONS
Authors: SCHROEDER DORIS , GEFENAS EUGENIJUS
Published: January 2011

In 2006, the Indonesian government decided to withhold avian flu samples from the World Health Organization. They argued that even though Indonesian samples were crucial to the development of vaccines, the results of vaccine research would be unaffordable for its citizens. Commentaries on the case varied from alleging blackmail to welcoming this strong stance against alleged exploitation. What is clear is that the concern expressed is related to benefit sharing.

Benefit sharing requires resource users to return benefits to resource providers in order to achieve justice. One benefit sharing tool within health research is the duty to provide a health care intervention which has been proven to be beneficial (or alternative benefits) to research participants after a study has been concluded. This duty is generally known as a post‐study obligation. It was enshrined in the Declaration of Helsinki in 2000 and re‐emphasized in 2008. Yet, there are few, if any, examples of good practice.

In this article, we analyse the obstacles to giving more bite to benefit sharing provisions in health research through ethical review. We conclude that the provision of post‐study access to healthcare interventions is not a promising mechanism when monitored through research ethics committees. Alternative benefit provision is preferable if one focuses on achieving compliance. However, even the latter faces challenges, which we address in specific recommendations.
Is there an Expectations Gap in the Roles of Independent Directors? An Explorative Study of Listed Chinese Companies
Authors: Li Pingli , Parsa Sepideh , Tang Guliang , Xiao Jason Zezhong
Published: January 2011

This paper investigates whether an expectations gap exists in the control, strategic and resource provision roles that independent directors play in the corporate governance of listed Chinese firms and the factors that affect their performance of these roles. For this purpose, we interviewed Chinese executive directors, independent directors, institutional investors and stock exchange regulators. We find a performance gap but no reasonableness gap with respect to the control and strategic roles. The results suggest that the performance gap may be attributed to such factors as the ill‐defined roles, independent directors' limited amount of time commitment and their lack of competence and objectivity. Interestingly, there is disagreement over the protection of minority interest as the objective of the control role. We find no consensus on the desirability, reasonableness and effectiveness of independent directors' resource provision role, perhaps because of a pejorative interpretation of this role as an exercise of guanxi.
Does Mobility Matter for Attitudes to Europe? A Multi-level Analysis of Immigrants' Attitudes to European Unification
Authors: Roeder Antje
Published: January 2011

Support for Europe is largely argued to be based on the self-interest of individuals as well as being influenced by their national identity. Relatively little is known, however, about the attitudes of immigrants regarding Europe, although they form a growing part of the European population and are strongly affected by European policies. In this article, attitudes of immigrants towards European unification are analysed to determine how far they differ from the native population and between immigrants from different regions. The main theories on attitudes towards Europe would predict overall more positive attitudes. First, self-interest should lead migrants to evaluate Europe more favourably, as certain groups in particular have gained from it in the past mainly in terms of enhanced mobility and legal rights as immigrants, and can realistically expect to gain more in the future. Secondly, being an immigrant as opposed to a native citizen can be expected to have an impact on national identities, with the supranational level likely to be more attractive to people with multiple national affiliations. Findings confirm this, and highlight that migration status, region of origin and citizenship status are important predictors of attitudes. Furthermore, explanatory factors related to economic interests, which have been shown to be of major importance for natives, matter less for immigrants. It would appear that issues related to mobility and a less exclusively defined national identity may be of more importance for immigrants' attitudes than socio-economic position.
Innovation and evaluation: taming and unleashing telecare technology
Authors: Pols Jeannette , Willems Dick
Published: January 2011

Telecare is advocated in most European countries with great, if not grandiose, promises: improving healthcare, lowering costs, solving workforce shortage. This paper does not so much question these specific promises, but rather the ‘register of promising’ as such, by comparing the promises with actual processes of incorporating technologies in healthcare practices. The case we study is the use of webcams in follow‐up care from a Dutch rehabilitation clinic for people with severe chronic obstructive pulmonary disease (COPD). This process shows many changes and contingencies, and corresponding shifts in goals and aims. The conclusion is that when innovative technologies such as telecare are actually put to work, ‘the same’ technology will perform differently. In order to function at all, technology has to be tamed, it has to be tinkered with to fit the practices of the users. The technology, however, is not meekly put to use (tamed), but is unleashed as well, affecting care practices in unforeseen ways. The untenability of pre‐given promises and the fluidity of locally evolving goals has important implications for the way in which innovations are promoted, as well as for the way innovative technologies may be evaluated.
E47 retroviral rescue of intrinsic B‐cell defects in senescent mice
Authors: Landin Ana M. , Frasca Daniela , Harrison Patrick , Scallan Martina , Riley Richard L. , Blomberg Bonnie B.
Published: January 2011

In aging, immune responses are dramatically impaired, specifically the ability to produce protective antibodies. We previously showed that with age there is a B‐cell intrinsic decrease in class switch recombination (CSR) because of a decrease in activation‐induced cytidine deaminase (AID). One mechanism we have demonstrated for decreased AID includes increased mRNA degradation of the transcription factor E47, critical for AID transcription. Here, we show by means of a retroviral construct containing the DsRED reporter and the 3′UTR of E47 that the 3′UTR lowers mRNA expression, and particularly in B cells from old mice. This is the first demonstration that the E47 3′UTR directly regulates its degradation. The AID mRNA was not differentially regulated by degradation in aging. Therefore, we have here further established critical components for decreased AID with age. The major aim of this study was to establish conditions for the rescue of the intrinsic defect of aged B cells with retroviral addition of the coding region of E47 in splenic B cells to restore their ability to produce optimal AID and class switch to IgG. In this study, we show that young and old primary B cells overexpressing a stable E47 mRNA up‐regulate E47, AID, and CSR and improve B‐cell immune responses in senescent murine B cells. Our results provide a proof of principle for the rescue of intrinsic B‐cell defects and the humoral immune response in senescence.
Predictors of the risk of cognitive deficiency in very preterm infants: the EPIPAGE prospective cohort
Authors: Beaino Ghada , Khoshnood Babak , Kaminski Monique , Marret Stéphane , Pierrat Véronique , Vieux Rachel , Thiriez Gérard , Matis Jacqueline , Picaud Jean‐Charles , Rozé Jean‐Christophe , Alberge Corine , Larroque Béatrice , Bréart Gérard , Ancel Pierre‐Yves ,   for the EPIPAGE Study Group
Published: January 2011

Aim:  To assess cerebral lesions and other medical as well as social characteristics as predictors of risk of mild and severe cognitive deficiencies in very preterm infants.

Methods:  As part of the EPIPAGE population‐based prospective cohort study, perinatal data and cognitive outcome at 5 years of age were recorded for 1503 infants born before 33 weeks of gestation in nine regions of France in 1997. Mild cognitive deficiency was defined as a Mental Processing Composite score on the Kaufman Assessment Battery for Children test of between 70 and 84, and severe cognitive deficiency as a score of <70.

Results:  After controlling for cerebral lesions and other medical as well as social factors, low parental socio‐economic status and lack of breastfeeding were significant predictors of mild and severe cognitive deficiencies, whereas presence of cerebral lesions, being small for gestational age and having a large number of siblings were predictors of severe cognitive deficiency.

Conclusion:  Predictors of poor cognitive outcome in very preterm infants are low social status, lack of breastfeeding, presence of cerebral lesions on ultrasound scan, being born small for gestational age and having a high number of siblings. Social factors predicted both mild and severe cognitive deficiencies, whereas medical factors predicted mostly severe cognitive deficiencies.
In Vitro Antifungal and Antibacterial Activities of Pentacycloundecane Tetra‐Amines
Authors: Onajole Oluseye K. , Coovadia Yacoob , Govender Thavendran , Kruger Hendrik G. , Maguire Glenn E. M. , Naidu Dianithi , Singh Nisha , Govender Patrick
Published: January 2011

The antifungal and antimicrobial activities of three pentacycloundecane (PCU) tetra‐amine derivatives are reported herein. The in vitro activity of these PCU derivatives against yeasts (Candida albicans and non‐albicans species) and filamentous fungi was evaluated using the Clinical and Laboratory Standards Institute (CLSI) M27‐A2 and M38‐A2 guidelines and the 2H‐tetrazolium salt, (MTS) colorimetric method. The minimum inhibitory concentration against most of the tested clinical fungal strains for GKM8 and GKM9 derivatives ranges from 15.6 to 62.5 μg/mL while GKM11 ranged from 3.9 to 7.8 μg/mL. The GKM11 derivative was also active against fluconazole‐resistant strains of fungi. The GKM11 derivative also exhibited promising activity against filamentous fungi in that it was 2.5 times more active than amphotericin B against Sporothrix schenckii. Antibacterial activity was determined using the broth microdilution method (BMM) and the iodonitrotetrazolium chloride (INT) colorimetric method. The GKM11 derivative was mainly active against Gram‐positive bacteria with MIC ranging from 3.9 to 7.8 μg/mL. Activity against Gram‐negative bacteria tested was limited to Escherichia coli and Elizabethkingia meningoseptica (MIC of 31 μg/mL).
Mise à l'évidence et cinématique de la faille de La Guadeloupe, Appalaches du sud du Québec
Authors: Tremblay Alain , St-Julien Pierre , Labbé Jean-Yves
Published: January 2011

In the Appalachians of southern Quebec, the contact between Siluro-Devonian rocks of the Connecticut Valley – Gaspé Synclinorium and the Cambro-Ordovician rocks of the Dunnage Zone is marked by an important thrust fault striking northwest, La Guadeloupe fault. This fault separates two stratigraphically distinct domains, but the regional deformations are related to the same orogenic period. In the Sherbrooke and Weedon areas, different structural features show evidence of La Guadeloupe fault and reveal its kinematics. The exposed rocks near the fault exhibit structures that indicate a strong deformation zone. The deformation includes well-developed stretching lineations and shearing zones. The ductile deformation is restricted to the Cambro-Ordovician rocks. Macroscopic and microscopic studies of samples from the shear zones related to La Guadeloupe fault reveal, systematically, a tectonic transport from southwest to northwest. This interpretation is supported by the quartz crystallographic c-axis orientation. In New England, La Guadeloupe fault seems to coincide with the Taconic unconformity, though a bifurcation of the pre-Silurian units exposed on the western side of this unconformity remains possible. In Quebec, the correlation and kinematics of La Guadeloupe fault extension towards the northeast are not completely understood. [Journal Translation]