bluuebunny/crossref_metadata_2025_split huggingface dataset:
EU Foreign Investment Law
Authors: Dimopoulos Angelos 
Published: January 2012

AbstractRegulation of foreign investment presents one of the most topical and controversial subjects in EU law and international investment law. The introduction of EU competence over foreign direct investment (FDI) in Article 207 TFEU after the Lisbon Treaty as well as the recent successful challenge of Member States Bilateral Investment Treaties (BITs) regarding their compatibility with EU law, indicate the emerging importance of EU foreign investment law. Within this framework, the purpose of this book is to identify whether and to what extent the EU has become an international actor in the field of foreign investment. Exploring the existing legal framework on the scope and exercise of EU competence and its legal effects, it examines the foundations upon which EU investment policy is based and will be based in the future. The book examines EU foreign investment law firstly from an EU law perspective. It addresses questions relating to the definition of foreign investment, the scope of EU competences, the actual exercise of EU powers, the substantive content of existing and future EU International Investment Agreements (EU IIAs), the objectives of EU investment policy and its EU law effects, in particular as regards the compatibility of Member States BITs with EU law. Secondly, the book examines the influence that the EU exerts on international law and regulation of foreign investment. Specific attention is paid to the substantive content and orientation of EU IIAs, taking a comparative approach to the content of BITs, as well as to the ramifications of EU foreign investment regulation for international law, especially with regard to the EU's international responsibility. Taking into account the recent developments in this field, this book addresses the legal, practical and political concerns that the creation of an EU common investment policy creates.
medpie: an information extraction package for medical message board posts
Authors: Benton A. , Holmes J. H. , Hill S. , Chung A. , Ungar L. 
Published: January 2012

Abstract
Summary: We have developed medpie, a software package for preparing medical message board corpora and extracting patient mentions and statistics for drugs, herbs and adverse effects experienced from them. The package is divided into web-crawling, HTML-cleaning, de-identification and information extraction modules. It also includes a sample controlled vocabulary of drugs, herbs and adverse effect terms.
Availability: http://www.cis.upenn.edu/~ungar/medpie.zip
Dependencies: Python 2.6 or 2.7
Contact: ungar@cis.upenn.edu; adrianb@mail.med.upenn.edu
Regional métier definition: a comparative investigation of statistical methods using a workflow applied to international otter trawl fisheries in the North Sea
Authors: Deporte Nicolas , Ulrich Clara , Mahévas Stéphanie , Demanèche Sébastien , Bastardie Francois 
Published: January 2012

Abstract
Deporte, N., Ulrich, C., Mahévas, S., Demanèche, S., and Bastardie, F. 2012. Regional métier definition: a comparative investigation of statistical methods using a workflow applied to international otter trawl fisheries in the North Sea. – ICES Journal of Marine Science, 69: 331–342. The European Common Fisheries Policy recognizes the importance of accounting for heterogeneity in fishing practices, and métier-based sampling is now at the core of the EU Data Collection Framework. The implementation of such an approach would require Member States to agree on the standard regional métier definitions and on practical rules to categorize logbook records into métiers. Several alternative approaches have been used in the past to categorize landings profiles, but no consensus has yet emerged. A generic open-source workflow is developed to test and compare a selection of methods, including principal components analysis (PCA), hierarchical agglomerative clustering (HAC), K-means, and Clustering LARge Applications (CLARA), and to provide simple allocation rules. This workflow is applied to a unique regional dataset consisting of bottom-trawl logbooks of five North Sea countries. No method proved to be infallible, but combining PCA with either CLARA or HAC performed best. For 2008, a hierarchical classification with 14 species assemblages is proposed. Discriminant analysis proved more robust than simple ordination methods for allocating a new logbook record into an existing métier. The whole approach is directly operational and could contribute to defining more objective and consistent métiers across European fisheries.
Feeding the world: what role for fisheries?
Authors: Frid Chris L. J. , Paramor Odette A. L. 
Published: January 2012

Abstract
Frid, C. L. J., and Paramor, O. A. L. 2012. Feeding the world: what role for fisheries? – ICES Journal of Marine Science, 69: 145–150. Fisheries (wild capture and aquaculture) deliver more than 110 million tonnes of food and around 15% of the dietary protein to the 7 billion people currently living on the planet. With the global population expected to peak at 9 billion by 2050, and >80% of global fish stocks currently fully or overexploited (and aquaculture is at least in part dependent on capture fisheries), the contribution of fisheries looks set to decline. The challenge is therefore determining how better management, an ecosystem perspective, and more efficient utilization of fisheries waste can support fisheries products continuing to contribute significantly to “feeding the world” up to and beyond the population peak.
Molecular characterization of macrolide resistance mechanisms among Streptococcus pneumoniae and Streptococcus pyogenes isolated from the PROTEKT 1999-2000 study
Authors: Farrell D. J. , Morrissey I. , Bakker S. , Felmingham D. 
Published: January 2012

Abstract
In this study, the distribution of macrolide resistance mechanisms was determined for isolates of Streptococcus pneumoniae and Streptococcus pyogenes obtained from the PROTEKT 1999–2000 study (a global, longitudinal study of the antibacterial susceptibility of bacterial pathogens associated with community-acquired lower respiratory tract infections). The global macrolide resistance mechanism distribution results for 1043 macrolide-resistant S. pneumoniae isolates collected from 25 countries were as follows: 35.3% mef (A) , 56.2% erm (B) , 6.8% both mef (A) and erm (B) , 0.2% erm (A) subclass erm (TR) and 1.5% negative for mechanisms tested. Mechanisms of macrolide resistance were found to vary widely between countries and different geographical regions with mef (A) predominating in North America and erm(B) in Europe. Approximation of genotype from macrolide MIC without molecular determination of the mechanism of resistance resulted in an error of 10.2% (106 isolates). Overall, for 143 macrolide-resistant S. pyogenes isolates, 46.1% of the isolates tested were mef (A), 30.8% were erm (B), 23.1% were erm (A) subclass erm (TR) and no isolates were negative for all the genetic markers tested. Again, the distribution varied widely between countries and geographical regions. This study provides valuable baseline data for the continued monitoring of the evolution of macrolide resistance development in these important respiratory tract pathogens. The ketolide telithromycin retained excellent anti-pneumococcal activity irrespective of macrolide resistance mechanism, having a MIC 90 of 0.25, 0.5 and 0.5 mg/L against mef (A), erm (B) and mef (A)+ erm (B) macrolide-resistant S. pneumoniae , respectively. It also exhibited potent activity against S. pyogenes that had become resistant to macrolides via either mef (A), (MIC 90 0.5 mg/L) or erm (TR), (MIC 90 0.03 mg/L).
The need for antimicrobial resistance surveillance
Authors: Felmingham David 
Published: January 2012

Abstract
Although antimicrobial agents drastically reduced patient morbidity and mortality, bacterial resistance to these agents developed shortly after their introduction. Because the laboratory diagnosis of respiratory tract infection (RTI) is not always possible, and rarely of immediate use, treatment success or failure often depends upon the availability of reliable susceptibility information at the time of therapeutic decision-making. Hence, the need for accurate, up-to-date and timely data is obvious. This information can also be used to help determine the cause of antimicrobial resistance and how it spreads. Desired components of a global RTI surveillance study fall into four categories: programme design, methodology, clinical and dissemination of information. PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) is an RTI surveillance study designed to fulfil these requirements. PROTEKT includes all of the features of other successful RTI surveillance studies (e.g. the Alexander Project, SENTRY) and improves on these studies by the addition of other desirable features, such as the determination of resistance mechanisms and the availability of up-to-date local data that can be downloaded to hand-held computers via the worldwide web for use at the bedside.
Molecular Changes Induced in Rat Liver by Hemorrhage and Effects of Melanocortin Treatment
Authors: Lonati Caterina , Sordi Andrea , Giuliani Daniela , Spaccapelo Luca , Leonardi Patrizia , Carlin Andrea , Ottani Alessandra , Galantucci Maria , Grieco Paolo , Catania Anna , Guarini Salvatore 
Published: January 2012

Background
Melanocortin peptides improve hemodynamic parameters and prevent death during severe hemorrhagic shock. In the present research we determined influences of a synthetic melanocortin 1/4 receptor agonist on the molecular changes that occur in rat liver during hemorrhage.

Methods
Controlled-volume hemorrhage was performed in adult rats under general anesthesia by a stepwise blood withdrawal until mean arterial pressure fell to 40 mmHg. Then rats received either saline or the synthetic melanocortin 1/4 receptor agonist Butir-His-D-Phe-Arg-Trp-Sar-NH2 (Ro27-3225; n = 6-8 per group). Hemogasanalysis was performed throughout a 60-min period. Gene expression in liver samples was determined at 1 or 3 h using quantitative real-time polymerase chain reaction.

Results
At 1 h, in saline-treated shocked rats, there were significant increases in activating transcription factor 3 (Atf3), early growth response 1 (Egr1), heme oxygenase (decycling) 1 (Hmox1), FBJ murine osteosarcoma viral oncogene homolog (Fos), and jun oncogene (Jun). These changes were prevented by Ro27-3225 (mean ± SEM: Atf3 152.83 ± 58.62 vs. 579.00 ± 124.13, P = 0.002; Egr1 13.21 ± 1.28 vs. 26.63 ± 1.02, P = 0.001; Hmox1 3.28 ± 0.31 vs. 166.54 ± 35.03, P = 0.002; Fos 4.36 ± 1.03 vs. 14.90 ± 3.44, P < 0.001; Jun 6.62 ± 1.93 vs. 15.07 ± 2.09, P = 0.005; respectively). Increases in alpha-2-macroglobulin (A2m), heat shock 70kD protein 1A (Hspa1a), erythropoietin (Epo), and interleukin-6 (Il6) occurred at 3 h in shocked rats and were prevented by Ro27-3225 treatment (A2m 6.90 ± 0.82 vs. 36.73 ± 4.00, P < 0.001; Hspa1a 10.34 ± 3.28 vs. 25.72 ± 3.64, P = 0.001; Epo 0.49 ± 0.13 vs. 2.37 ± 0.73, P = 0.002; Il6 1.05 ± 0.15 vs. 1.88 ± 0.23, P < 0.001; respectively). Further, at 3 h in shocked rats treated with Ro27-3225 there were significant increases in tight junction protein 1 (Tjp1; 27.30 ± 2.43 vs. 5.03 ± 1.68, P < 0.001) and nuclear receptor subfamily 4, group A, member 1 (Nr4a1; 91.03 ± 16.20 vs. 30.43 ± 11.0, P = 0.01) relative to sham animals. Treatment with Ro27-3225 rapidly restored blood pressure, hemogasanalysis parameters, and lactate blood levels.

Conclusions
Melanocortin treatment significantly prevents most of the systemic and hepatic detrimental changes induced by hemorrhage.
Comparison of Fecal Elastase‐1 and Pancreatic Function Testing in Children
Authors: Wali Prateek D. , Loveridge‐Lenza Beth , He Zhaoping , Horvath Karoly 
Published: January 2012

ABSTRACTObjectives:The fecal pancreatic elastase‐1 (FE‐1) test is considered a simple, noninvasive, indirect measure of pancreatic function. We aimed to evaluate the performance of the FE‐1 test compared with the direct pancreatic function test (PFT) with secretin stimulation in children.Methods:Data of 70 children (6 months–17 years of age) who had both FE‐1 test and PFT were analyzed.Results:The average FE‐1 concentration was 403 ± 142 μg/g. Eleven children had concentrations below 200 μg/g, 23 between 201 to 500 μg/g, and 36 were above 500 μg/g. The average pancreatic elastase activity measured on direct stimulation was 49.1 ± 38.6 μmol · min−1 · ml−1 and 11 children had activity below the established cutoff (10.5 μmol · min−1 · ml−1). Among the 11 children with pathologic PFT, 7 had normal FE‐1, 4 were in the intermediate range (201–500 μg/g), and none were in the low range (<200 μg/g). Among the 59 children with normal direct PFT 11 (19%) had pathologic (<200 μg/g) and 19 (32%) had intermediate FE‐1 tests. Twenty‐nine children had both normal FE‐1 concentration and normal PFT, giving a negative predictive value of 80%. The correlation between pancreatic elastase activity and FE‐1 concentration was poor (r = 0.190). The sensitivity of the FE‐1 test was found to be 41.7%, whereas the specificity was 49.2%. The positive predictive value of the FE‐1 test was only 14%.Conclusions:The FE‐1 test is a simple, noninvasive, indirect method; however, ordering physicians should be aware of its limitations. It can give false‐positive results and has low sensitivity in children with mild pancreatic insufficiency without cystic fibrosis and in those with isolated pancreatic enzyme deficiencies.
Accuracy of Diagnostic Antibody Tests for Coeliac Disease in Children
Authors: Giersiepen Klaus , Lelgemann Monika , Stuhldreher Nina , Ronfani Luca , Husby Steffen , Koletzko Sibylle , Korponay‐Szabó Ilma R. ,   ESPGHAN Working Group on Coeliac Disease Diagnosis
Published: January 2012

ABSTRACTObjective:The aim of this study was to summarise the evidence from 2004 to September 2009 on the performance of laboratory‐based serological and point of care (POC) tests for diagnosing coeliac disease (CD) in children using histology as reference standard.Patients and Methods:We searched MEDLINE and EMBASE for studies reporting on children for tests based on IgA and IgG anti‐gliadin (AGA), endomysial (EmA), anti‐transglutaminase‐2 (TG2), and anti‐deamidated gliadin peptides (DGP) antibodies or POC tests. For inclusion, histological analysis of duodenal biopsies and sensitivity and specificity for index tests had to be reported. Data were pooled and summary measures calculated for sensitivity, specificity, positive and negative likelihood ratios (“LR+”, “LR−”), and diagnostic odds ratios (DOR). In case of elevated statistical heterogeneity, studies reaching 90% sensitivity or specificity were reported.Results:A total of 2510 articles were reviewed; 16 entered meta‐analysis, reporting on 3110 patients (1876 with CD, 1234 without CD). For IgA‐EmA, sensitivity was ≥90% in 7/11 studies and pooled specificity 98.2%. For IgA‐anti‐TG2, 11/15 studies yielded sensitivities ≥90% and 13/15 specificities ≥90%. For IgA‐DGP, sensitivity ranged between 80.7% and 95.1% (specificity 86.3%–93.1%); for IgG‐DGP between 80.1% and 98.6% (specificity 86.0–96.9%). IgA‐EmA had the highest pooled DOR (554) and LR+ (31.8) for a laboratory test, followed by IgA‐anti‐TG2, IgG‐DGP, IgA‐DGP and IgA‐AGA. POC tests showed a pooled sensitivity of 96.4% for IgA‐TG2 (specificity 97.7%).Conclusions:IgA‐EmA and IgA‐anti‐TG2 tests appear highly accurate to diagnose CD. IgG‐anti‐DGP tests may help in excluding CD. IgA‐AGA and IgA‐DGP tests show inferior accuracy. POC tests may achieve high accuracy in the hands of experienced readers, but IgA‐anti‐TG2/EmA were superior.
Structures of new crystal forms ofMycobacterium tuberculosispeptidyl-tRNA hydrolase and functionally important plasticity of the molecule
Authors: Selvaraj M. , Ahmad Rais , Varshney Umesh , Vijayan M. 
Published: January 2012

The X-ray structures of new crystal forms of peptidyl-tRNA hydrolase fromM. tuberculosisreported here and the results of previous X-ray studies of the enzyme from different sources provide a picture of the functionally relevant plasticity of the protein molecule. The new X-ray results confirm the connection deduced previously between the closure of the lid at the peptide-binding site and the opening of the gate that separates the peptide-binding and tRNA-binding sites. The plasticity of the molecule indicated by X-ray structures is in general agreement with that deduced from the available solution NMR results. The correlation between the lid and the gate movements is not, however, observed in the NMR structure.
Distribution of aldehyde dehydrogenase 1‐positive stem cells in benign mammary tissue from women with and without breast cancer
Authors: Isfoss Björn L , Holmqvist Bo , Alm Per , Olsson Håkan 
Published: January 2012

Isfoss B L, Holmqvist B, Alm P & Olsson H  (2012) Histopathology 60, 617–633 Distribution of aldehyde dehydrogenase 1‐positive stem cells in benign mammary tissue from women with and without breast cancerAims:  Aldehyde dehydrogenase 1 (ALDH1) in female breast tissue has been linked to stem cells, but little is known about the benign cellular organization in situ. We investigated the distribution of ALDH1‐immunoreactive (ALDH1+) cells in histomorphologically benign breast tissue from 28 women with or without breast cancer.Methods and results:  ALDH1+ cells were detected in benign tissue of women aged 20–72 years, located most commonly at the luminal and intermediate ductular levels and in the stroma. ALDH1+ cell populations and Ki67+ cell populations were present in separate ductules, both cell types rarely showing epithelial differentiation. ALDH1+ cells were non‐reactive to Ki67 and oestrogen receptor. Stromal round/oval ALDH1+ non‐leukocyte cells in both age groups expressed contractile protein. There was a lower concentration of luminal and intermediate ductular ALDH1+ cells in postmenopausal women than in premenopausal women, and in cancer patients than in non‐cancer patients, and a higher concentration in women receiving exogenous hormones.Conclusions:  This study provides further evidence for the stem cell character of ALDH1+ cells, here in benign breast tissue of cancer and non‐cancer patients throughout non‐lactating adult life, and contributes evidence of benign stromal ALDH1+ cells. The distribution of ductular ALDH1+ stem cells appears to be influenced by hormonal status.
The pathway of cross‐presentation is influenced by the particle size of phagocytosed antigen
Authors: Mant Alexandra , Chinnery Fay , Elliott Tim , Williams Anthony P. 
Published: January 2012

SummaryCross‐presentation is the presentation by MHC class I of antigenic peptides from exogenous proteins that have been internalized and processed by professional antigen‐presenting cells, e.g. dendritic cells. We have investigated the influence of particle size and antigen load on cross‐presentation following antigen delivery on microspheres (MS). Cross‐presentation from small particles (0·8‐μm) is sensitive to proteasome inhibition and the blockade of endoplasmic reticulum‐resident MHC class I complex export, whereas cross‐presentation from larger particles (aggregated clumps of 0·8‐μm MS) is resistant to these antagonists. This observation may have been overlooked previously, because of the heterogeneity of particle size and MS uptake in unsorted dendritic cell populations. Larger particles carry more antigen, but we show that antigen load does not influence the cross‐presentation pathway used. Whereas early endosome autoantigen 1 (EEA1) could be observed in all phagosomes, we observed endoplasmic reticulum SNARE of molecular weight 24 000 (ERS24) and cathepsin S in association with 3·0‐μm and aggregated 0·8‐μm MS, but not individual 0·8‐μm MS. A potential mechanism underlying our observations may be the activation of β‐catenin by disruption of E‐cadherin‐mediated adhesion. Activated β‐catenin was detected in the cytoplasm of cells after phagocytosis of MS (highest levels for the largest particles). We propose that particle size can direct the use of different pathways for the cross‐presentation of an identical antigen. Furthermore, these pathways have differing yields of MHC class I–peptide complexes, which is an important variable in designing vaccination strategies for maximal antigen expression and CD8+ T‐cell priming.
Toll‐like receptor (TLR) 3 immune modulation by unformulated small interfering RNA or DNA and the role of CD14 (in TLR‐mediated effects)
Authors: Weber Cordula , Müller Christian , Podszuweit Anja , Montino Carmen , Vollmer Jörg , Forsbach Alexandra 
Published: January 2012

SummaryThe Toll‐like receptors (TLRs) 3, 7, 8 and 9 stimulate innate immune responses upon recognizing pathogen‐derived nucleic acids. TLR3 is located on the cell surface and in cellular endosomes and recognizes double‐stranded viral RNA or the synthetic mimic poly rI:rC. Recently, unformulated small interfering RNA (siRNA) has been reported as ligand for surface‐expressed murine TLR3. Blockage of TLR3 is achieved by single‐stranded DNA. We confirm and expand the observation that poly rI:rC‐mediated TLR3 immune activation is blocked in a sequence‐, length‐, backbone‐ and CpG‐dependent manner. However, human TLR3 is not activated by siRNA, which may be the result of differences in the amino acid composition of the TLR3 loop 1 of mice and humans. Although CD14 was previously described as a co‐receptor for murine TLR3 and other nucleic acid‐recognizing TLRs, human CD14 acts only as co‐receptor to human TLR9, but not TLR3, TLR7 or TLR8. We show that CD14 up‐regulates the TLR9 immune response of A, B and C‐class oligodeoxynucleotides but down‐regulates the phosphoro‐diester version of B‐class oligodeoxynucleotides.