UNSUPERVISED INDEXING OF MEDLINE ARTICLES THROUGH GRAPH-BASED RANKING

The biomedical literature is extensively catalogued and indexed in MEDLINE. MEDLINE indexing is done by trained human indexers, who identify the most important concepts in each article, and is expensive and inconsistent. Automating the indexing task is difficult: the National Library of Medicine produces the Medical Text Indexer (MTI), which suggests potential indexing terms to the indexers. MTI’s output is not good enough to work unattended. In my thesis, I propose a different way to approach the indexing task called MEDRank. MEDRank creates graphs representing the concepts in biomedical articles and their relationships within the text, and applies graph-based ranking algorithms to identify the most important concepts in each article. I evaluate the performance of several automated indexing solutions, including my own, by comparing their output to the indexing terms selected by the human indexers. MEDRank outperformed all other evaluated indexing solutions, including MTI, in general indexing performance and precision. MEDRank can be used to cluster documents, index any kind of biomedical text with standard vocabularies, or could become part of MTI itself.

Occupational therapy articles in serial publications: an analysis of sources.

This study was designed to locate and document serial literature on occupational therapy published since 1900. Emphasis is placed on finding articles on occupational therapy or by occupational therapists from sources other than those normally associated with the professional journals. Multiple sources were used including print indexes, online databases, occupational therapy bibliographies, and tables of contents or yearly indexes. Almost 7,000 articles were identified, not including those published in foreign journals. Occupational therapy publications have increased steadily since 1900, with the most rapid increase during the 1970s and 1980s when five new occupational therapy journals were initiated. Suggestions for formulating search strategies are included.

Evolutionary conservation of residues in vertebrate DNA polymerase N conferring low fidelity and bypass activity.

POLN is a nuclear A-family DNA polymerase encoded in vertebrate genomes. POLN has unusual fidelity and DNA lesion bypass properties, including strong strand displacement activity, low fidelity favoring incorporation of T for template G and accurate translesion synthesis past a 5S-thymine glycol (5S-Tg). We searched for conserved features of the polymerase domain that distinguish it from prokaryotic pol I-type DNA polymerases. A Lys residue (679 in human POLN) of particular interest was identified in the conserved 'O-helix' of motif 4 in the fingers sub-domain. The corresponding residue is one of the most important for controlling fidelity of prokaryotic pol I and is a nonpolar Ala or Thr in those enzymes. Kinetic measurements show that K679A or K679T POLN mutant DNA polymerases have full activity on nondamaged templates, but poorly incorporate T opposite template G and do not bypass 5S-Tg efficiently. We also found that a conserved Tyr residue in the same motif not only affects sensitivity to dideoxynucleotides, but also greatly influences enzyme activity, fidelity and bypass. Protein sequence alignment reveals that POLN has three specific insertions in the DNA polymerase domain. The results demonstrate that residues have been strictly retained during evolution that confer unique bypass and fidelity properties on POLN.

Synthesis and incorporation into DNA of a chemically stable, functional abasic site analogue

[reaction: see text] The abasic site building block 7 for DNA synthesis, containing a methylenephosphinic acid group at C3', was prepared in six steps and was incorporated into DNA via a combination of H-phosphonate and phosphoramidite chemistry. Corresponding oligodeoxynucleotides were shown to be chemically stable under basic conditions and fully functional at the respective hemiacetal center

Polychlorinated Biphenyls in Glaciers. 2. Model Results of Deposition and Incorporation Processes

In previous work, Alpine glaciers have been identified as a secondary source of persistent organic pollutants (POPs). However, detailed understanding of the processes organic chemicals undergo in a glacial system was missing. Here, we present results from a chemical fate model describing deposition and incorporation of polychlorinated biphenyls (PCBs) into an Alpine glacier (Fiescherhorn, Switzerland) and an Arctic glacier (Lomonosovfonna, Norway). To understand PCB fate and dynamics, we investigate the interaction of deposition, sorption to ice and particles in the atmosphere and within the glacier, revolatilization, diffusion and degradation, and discuss the effects of these processes on the fate of individual PCB congeners. The model is able to reproduce measured absolute concentrations in the two glaciers for most PCB congeners. While the model generally predicts concentration profiles peaking in the 1970s, in the measurements, this behavior can only be seen for higher-chlorinated PCB congeners on Fiescherhorn glacier. We suspect seasonal melt processes are disturbing the concentration profiles of the lower-chlorinated PCB congeners. While a lower-chlorinated PCB congener is mainly deposited by dry deposition and almost completely revolatilized after deposition, a higher-chlorinated PCB congener is predominantly transferred to the glacier surface by wet deposition and then is incorporated into the glacier ice. The incorporated amounts of PCBs are higher on the Alpine glacier than on the Arctic glacier due to the higher precipitation rate and aerosol particle concentration on the former. Future studies should include the effects of seasonal melt processes, calculate the quantities of PCBs incorporated into the entire glacier surface, and estimate the quantity of chemicals released from glaciers to determine the importance of glaciers as a secondary source of organic chemicals to remote aquatic ecosystems.

High Incorrect Use of the Standard Error of the Mean (SEM) in Original Articles in Three Cardiovascular Journals Evaluated for 2012.

RATIONALE In biomedical journals authors sometimes use the standard error of the mean (SEM) for data description, which has been called inappropriate or incorrect. OBJECTIVE To assess the frequency of incorrect use of SEM in articles in three selected cardiovascular journals. METHODS AND RESULTS All original journal articles published in 2012 in Cardiovascular Research, Circulation: Heart Failure and Circulation Research were assessed by two assessors for inappropriate use of SEM when providing descriptive information of empirical data. We also assessed whether the authors state in the methods section that the SEM will be used for data description. Of 441 articles included in this survey, 64% (282 articles) contained at least one instance of incorrect use of the SEM, with two journals having a prevalence above 70% and "Circulation: Heart Failure" having the lowest value (27%). In 81% of articles with incorrect use of SEM, the authors had explicitly stated that they use the SEM for data description and in 89% SEM bars were also used instead of 95% confidence intervals. Basic science studies had a 7.4-fold higher level of inappropriate SEM use (74%) than clinical studies (10%). LIMITATIONS The selection of the three cardiovascular journals was based on a subjective initial impression of observing inappropriate SEM use. The observed results are not representative for all cardiovascular journals. CONCLUSION In three selected cardiovascular journals we found a high level of inappropriate SEM use and explicit methods statements to use it for data description, especially in basic science studies. To improve on this situation, these and other journals should provide clear instructions to authors on how to report descriptive information of empirical data.

Incorporation of RANKL promotes osteoclast formation and osteoclast activity on β-TCP ceramics.

β-Tricalcium phosphate (β-TCP) ceramics are approved for the repair of osseous defects. In large defects, however, the substitution of the material by authentic bone is inadequate to provide sufficient long-term mechanical stability. We aimed to develop composites of β-TCP ceramics and receptor activator of nuclear factor κ-B ligand (RANKL) to enhance the formation of osteoclasts and promote cell mediated calcium phosphate resorption. RANKL was adsorbed superficially onto β-TCP ceramics or incorporated into a crystalline layer of calcium phosphate by the use of a co-precipitation technique. Murine osteoclast precursors were seeded onto the ceramics. After 15 days, the formation of osteoclasts was quantified cytologically and colorimetrically with tartrate-resistant acidic phosphatase (TRAP) staining and TRAP activity measurements, respectively. Additionally, the expression of transcripts encoding the osteoclast gene products cathepsin K, calcitonin receptor, and of the sodium/hydrogen exchanger NHA2 were quantified by real-time PCR. The activity of newly formed osteoclasts was evaluated by means of a calcium phosphate resorption assay. Superficially adsorbed RANKL did not induce the formation of osteoclasts on β-TCP ceramics. When co-precipitated onto β-TCP ceramics RANKL supported the formation of mature osteoclasts. The development of osteoclast lineage cells was further confirmed by the increased expression of cathepsin K, calcitonin receptor, and NHA2. Incorporated RANKL stimulated the cells to resorb crystalline calcium phosphate. Our in vitro study shows that RANKL incorporated into β-TCP ceramics induces the formation of active, resorbing osteoclasts on the material surface. Once formed, osteoclasts mediate the release of RANKL thereby perpetuating their differentiation and activation. In vivo, the stimulation of osteoclast-mediated resorption may contribute to a coordinated sequence of material resorption and bone formation. Further in vivo studies are needed to confirm the current in vitro findings.

The Jews in India and Far East : (being a reprint of articles contributed to "Church and Synagoge" with appendices)

by J. Henry Lord

How political economies affect immigrants' socio-economic incorporation. A comparative analysis of immigrants’ poverty risks across advanced industrialised countries

Immigration and the resulting increasing ethnic diversity have become an important characteristic of advanced industrialised countries. At the same time, the majority of the countries in question are confronted with structural transformation such as deindustrialisation and changes in family structures as well as economic downturn, which limit the capacities of nation-states in addressing rising inequality and supporting those individuals at the margins of the society. This paper addresses both issues, immigration and inequality, by focusing on immigrants’ socio-economic incorporation into the receiving societies of advanced industrialised countries. The aim of this paper is to explain cross-national variation in immigrants’ poverty risks. Drawing on the political economy as well as the migration literature, the paper develops a theoretical framework that considers how the impact of the national labour market and welfare system on immigrants’ poverty risks is moderated by the integration policies, which regulate immigrants’ access to the labour market and social programs (or immigrants’ economic and social rights). The empirical analysis draws on income surveys as well as a newly collected data set on economic and social rights of immigrants in 19 advanced industrialised countries, including European countries as well as Australia, and North America, for the year 2007. As the results from multilevel analysis show, integration policies concerning immigrants’ access to the labour market and social programs can partly explain cross-national variations in immigrants’ poverty risks. In line with the hypothesis, stricter labour market regulations such as minimum wage setting reduce immigrants’ poverty risks stronger in countries where they are granted easier access to the labour market. However, concerning the impact of more generous social programs the reductive poverty effect is stronger in countries with less inclusive access of immigrants to social programs. The paper concludes by discussing possible explanations for this puzzling finding.

Synthesis and Incorporation into PNA of Fluorinated Olefinic PNA (F-OPA) Monomers

A fluorinated OPA monomer containing the base thymine ((Z)-t-F-OPA) was synthesized in 12 steps, featuring a highly selective allylic over homoallylic Mitsunobu substitution for the introduction of the nucleobase. F-OPA modified PNA decamers were prepared by the MMTr/acyl protection strategy. The thermal stability of duplexes of PNA decamers containing (Z)-t-F-OPA units with antiparallel complementary DNA was measured. We found a strong dependence of stability from the sequential position of the (Z)-t-F-OPA units, ranging from ¢Tm of +2.4 to -8.1 °C/modification relative to unmodified PNA.

Mechanical Loading Promoted Discogenic Differentiation of Human Mesenchymal Stem Cells Incorporated in 3D-PEG Scaffolds with RhGDF5 and RGD

Hydrogels have been described as ideal scaffolds for cells of 3D tissue constructs and hold strong promises with respect to in vitro 3D-cell-culture, where cells are isolated from native extracellular matrix (ECM). Synthesized polyethyleneglycol (PEG) hydrogels are appealing with regard to potential for cell therapy or as vehicles for drug delivery or even to regenerate tissue with similar hydrogel-like properties such as the nucleus pulposus of the intervertebral disc (IVD). Here, we tested whether incorporation of RGD motive would hinder discogenic differentiation of primary bone marrow-derived human mesenchymal stem cells (hMSCs) but favor proliferation of undifferentiated hMSCs. HMSCs were embedded in +RGD containing or without RGD PEG hydrogel and pre-conditioned with or without growth and differentiation factor-5 (rhGDF-5) for 13 days. Afterwards, all hMSCs-PEG gels were subsequently cyclically loaded (15% strain, 1Hz) for 5 consecutive days in a bioreactor to generate an IVD-like phenotype. Higher metabolic activity (resazurin assay) was found in groups with rhGDF5 in both gel types with and without RGD. Cell viability and morphology measured by confocal laser microscopy and DNA content showed decreased values (~60%) after 18 days of culture. Real-time RT-PCR of an array of 15 key genes suspected to be distinctive for IVD cells revealed moderate response to rhGDF5 and mechanical loading as also shown by histology staining. Preconditioning and mechanical loading showed relatively moderate responses revealed from both RT-PCR and histology although hMSCs were demonstrated to be potent to differentiate into chondrocyte-progenitor cells in micro- mass and 3D alginate bead culture.

Synthesis and incorporation into a-DNA of a novel conformationally constrained alpha-nucleoside analogue

We describe the synthesis and incorporation into alpha-DNA of a novel conformationally constrained alpha-nucleoside analogue. The carbohydrate part of this analogue was prepared in 4 steps from the known bicyclic precursor 1 via a stereospecific, intramolecular, Et 3B mediated radical addition to a keto-function as the key step. The thus obtained intermediate 4 was transformed stereoselectively into the corresponding alpha-nucleoside analogues 7 and 8 containing the bases adenine and thymine, and were further elaborated into the phosphoramidite building blocks 11 and 12 . Both building blocks were incorporated into alpha-oligodeoxynucleotides and their pairing behavior to parallel complementary DNA studied by UV-melting experiments. Single substitutions of alpha-deoxyribnucleoside units by the new analogues in the center of duplexes were found to be thermally destabilizing by only -0.8 to -3.1›C.