Automated annotation of chemical names in the literature with tunable accuracy

<p>Abstract</p> <p>Background</p> <p>A significant portion of the biomedical and chemical literature refers to small molecules. The accurate identification and annotation of compound name that are relevant to the topic of the given literature can establish links between scientific publications and various chemical and life science databases. Manual annotation is the preferred method for these works because well-trained indexers can understand the paper topics as well as recognize key terms. However, considering the hundreds of thousands of new papers published annually, an automatic annotation system with high precision and relevance can be a useful complement to manual annotation.</p> <p>Results</p> <p>An automated chemical name annotation system, MeSH Automated Annotations (MAA), was developed to annotate small molecule names in scientific abstracts with tunable accuracy. This system aims to reproduce the MeSH term annotations on biomedical and chemical literature that would be created by indexers. When comparing automated free text matching to those indexed manually of 26 thousand MEDLINE abstracts, more than 40% of the annotations were false-positive (FP) cases. To reduce the FP rate, MAA incorporated several filters to remove "incorrect" annotations caused by nonspecific, partial, and low relevance chemical names. In part, relevance was measured by the position of the chemical name in the text. Tunable accuracy was obtained by adding or restricting the sections of the text scanned for chemical names. The best precision obtained was 96% with a 28% recall rate. The best performance of MAA, as measured with the F statistic was 66%, which favorably compares to other chemical name annotation systems.</p> <p>Conclusions</p> <p>Accurate chemical name annotation can help researchers not only identify important chemical names in abstracts, but also match unindexed and unstructured abstracts to chemical records. The current work is tested against MEDLINE, but the algorithm is not specific to this corpus and it is possible that the algorithm can be applied to papers from chemical physics, material, polymer and environmental science, as well as patents, biological assay descriptions and other textual data.</p

FAS-dependent cell death in α-synuclein transgenic oligodendrocyte models of multiple system atrophy

Multiple system atrophy is a parkinsonian neurodegenerative disorder. It is cytopathologically characterized by accumulation of the protein p25α in cell bodies of oligodendrocytes followed by accumulation of aggregated α-synuclein in so-called glial cytoplasmic inclusions. p25α is a stimulator of α-synuclein aggregation, and coexpression of α-synuclein and p25α in the oligodendroglial OLN-t40-AS cell line causes α-synuclein aggregate-dependent toxicity. In this study, we investigated whether the FAS system is involved in α-synuclein aggregate dependent degeneration in oligodendrocytes and may play a role in multiple system atrophy. Using rat oligodendroglial OLN-t40-AS cells we demonstrate that the cytotoxicity caused by coexpressing α-synuclein and p25α relies on stimulation of the death domain receptor FAS and caspase-8 activation. Using primary oligodendrocytes derived from PLP-α-synuclein transgenic mice we demonstrate that they exist in a sensitized state expressing pro-apoptotic FAS receptor, which makes them sensitive to FAS ligand-mediated apoptosis. Immunoblot analysis shows an increase in FAS in brain extracts from multiple system atrophy cases. Immunohistochemical analysis demonstrated enhanced FAS expression in multiple system atrophy brains notably in oligodendrocytes harboring the earliest stages of glial cytoplasmic inclusion formation. Oligodendroglial FAS expression is an early hallmark of oligodendroglial pathology in multiple system atrophy that mechanistically may be coupled to α-synuclein dependent degeneration and thus represent a potential target for protective intervention

A precision study of the fine tuning in the DiracNMSSM

Recently the DiracNMSSM has been proposed as a possible solution to reduce the fine tuning in supersymmetry. We determine the degree of fine tuning needed in the DiracNMSSM with and without non-universal gaugino masses and compare it with the fine tuning in the GNMSSM. To apply reasonable cuts on the allowed parameter regions we perform a precise calculation of the Higgs mass. In addition, we include the limits from direct SUSY searches and dark matter abundance. We find that both models are comparable in terms of fine tuning, with the minimal fine tuning in the GNMSSM slightly smaller.Comment: 20 pages + appendices, 10 figure

A comparison of physicians and medical assistants in interpreting verbal autopsy interviews for allocating cause of neonatal death in Matlab, Bangladesh: can medical assistants be considered an alternative to physicians?

Objective. This study assessed the agreement between medical physicians in their interpretation of verbal autopsy (VA) interview data for identifying causes of neonatal deaths in rural Bangladesh. Methods. The study was carried out in Matlab, a rural sub-district in eastern Bangladesh. Trained persons conducted the VA interview with the mother or another family member at the home of the deceased. Three physicians and a medical assistant independently reviewed the VA interviews to assign causes of death using the International Classification of Diseases - Tenth Revision (ICD-10) codes. A physician assigned cause was decided when at least two physicians agreed on a cause of death. Cause-specific mortality fraction (CSMF), kappa (k) statistic, sensitivity, specificity, and positive predictive values were applied to compare agreement between the reviewers.Results. Of the 365 neonatal deaths reviewed, agreement on a direct cause of death was reached by at least two physicians in 339 (93%) of cases. Physician and medical assistant reviews of causes of death demonstrated the following levels of diagnostic agreement for the main causes of deaths: for birth asphyxia the sensitivity was 84%, specificity 93%, and kappa 0.77. For prematurity/low birth weight, the sensitivity, specificity, and kappa statistics were, respectively, 53%, 96%, and 0.55, for sepsis/meningitis they were 48%, 98%, and 0.53, and for pneumonia they were 75%, 94%, and 0.51. Conclusion. This study revealed a moderate to strong agreement between physician- assigned and medical assistant- assigned major causes of neonatal death. A well-trained medical assistant could be considered an alternative for assigning major causes of neonatal deaths in rural Bangladesh and in similar settings where physicians are scarce and their time costs more. A validation study with medically confirmed diagnosis will improve the performance of VA for assigning cause of neonatal death

Biomass fuel use, burning technique and reasons for the denial of improved cooking stoves by Forest User Groups of Rema-Kalenga Wildlife Sanctuary, Bangladesh

This is an electronic version of an article published in International Journal of Sustainable Development & World Ecology, 1745-2627, 18(1) 2011, 88-97. International Journal of Sustainable Development & World Ecology is available online at: http://www.informaworld.com/smpp/content~db=all~content=a933218896~frm=titlelinkUse of biomass fuel in traditional cooking stoves (TCS) is a long-established practice that has incomplete combustion and generates substances with global warming potential (GWP). Improved cooking stoves (ICS) have been developed worldwide as an alternative household fuel burning device, as well as a climate change mitigation. A study was conducted among female Forest User Groups (FUGs) of Rema-Kalenga Wildlife Sanctuary, Bangladesh, to assess the status of ICS disseminated by the Forest Department (FD) under the Nishorgo (2009) Support Project, along with the community's biomass fuel consumption pattern. Wood consumption was highest (345kg month-1 household-1) followed by agricultural residues (60kg month-1 household-1), tree leaves (51kg month-1 household-1) and cow dung (25kg month-1 household-1). Neighbouring forests of the sanctuary was the core source for wood fuel, with little or no reduction in the extraction even after joining the FUG. Twenty-two species, both indigenous and introduced, were preferred as wood fuel. None of the respondents were found willing to use ICS although 43% owned one; either as a status symbol or to meet the conditions of the FD for membership in FUG. Seven negative features of the disseminated ICS were identified by households, which made them unwilling to use them further. Manufacturing faults may be responsible for some ICS demerits, while the FD failed to convince the community of the benefits. A proper examination of the disseminated ICS efficacy is crucial, with active involvement of community members. The Sustainable Energy Triangle Strategy (SETS) could be implemented for this purpose. Findings of the study are of immense importance in designing a strategy for the introduction of ICS into Bangladesh.ArticleINTERNATIONAL JOURNAL OF SUSTAINABLE DEVELOPMENT AND WORLD ECOLOGY. 18(1):88-97 (2011)journal articl

Physical growth during the first year of life. A longitudinal study in rural and urban areas of Hanoi, Vietnam

<p>Abstract</p> <p>Background</p> <p>Good infant growth is important for future health. Assessing growth is common in pediatric care all over the world, both at the population and individual level. There are few studies of birth weight and growth studies comparing urban and rural communities in Vietnam. The first aim is to describe and compare the birth weight distributions and physical growth (weight and length) of children during their first year in one rural and one urban area of Hanoi Vietnam. The second aim is to study associations between the anthropometric outcomes and indicators of the economic and educational situations.</p> <p>Methods</p> <p>Totally 1,466 children, born from 1^stMarch, 2009 to June 2010, were followed monthly from birth to 12 months of age in two Health and Demographic Surveillance Sites; one rural and one urban. In all, 14,199 measurements each of weight and length were made. Birth weight was recorded separately. Information about demographic conditions, education, occupation and economic conditions of persons and households was obtained from household surveys. Fractional Polynomial models and standard statistical methods were used for description and analysis.</p> <p>Results</p> <p>Urban infants have higher birth weight and gain weight faster than rural infants. The mean birth weight for urban boys and girls were 3,298 grams and 3,203 grams as compared to 3,105 grams and 3,057 grams for rural children. At 90 days, the urban boys were estimated to be 4.1% heavier than rural boys. This difference increased to 7.2% at 360 days. The corresponding difference for girls was 3.4% and 10.5%. The differences for length were comparatively smaller. Both birth weight and growth were statistically significantly and positively associated with economic conditions and mother education.</p> <p>Conclusion</p> <p>Birth weight was lower and the growth, weight and length, considerably slower in the rural area, for boys as well as for girls. The results support the hypothesis that the rather drastic differences in maternal education and economic conditions lead to poor nutrition for mothers and children in turn causing inferior birth weight and growth.</p

Cleavage of von Willebrand Factor by Granzyme M Destroys Its Factor VIII Binding Capacity

Von Willebrand factor (VWF) is a pro-hemostatic multimeric plasma protein that promotes platelet aggregation and stabilizes coagulation factor VIII (FVIII) in plasma. The metalloproteinase ADAMTS13 regulates the platelet aggregation function of VWF via proteolysis. Severe deficiency of ADAMTS13 is associated with thrombotic thrombocytopenic purpura, but does not always correlate with its clinical course. Therefore, other proteases could also be important in regulating VWF activity. In the present study, we demonstrate that VWF is cleaved by the cytotoxic lymphocyte granule component granzyme M (GrM). GrM cleaved both denaturated and soluble plasma-derived VWF after Leu at position 276 in the D3 domain. GrM is unique in that it did not affect the multimeric size and pro-hemostatic platelet aggregation ability of VWF, but instead destroyed the binding of VWF to FVIII in vitro. In meningococcal sepsis patients, we found increased plasma GrM levels that positively correlated with an increased plasma VWF/FVIII ratio in vivo. We conclude that, next to its intracellular role in triggering apoptosis, GrM also exists extracellularly in plasma where it could play a physiological role in controlling blood coagulation by determining plasma FVIII levels via proteolytic processing of its carrier VWF

Nicotinic Receptor Alpha7 Expression during Tooth Morphogenesis Reveals Functional Pleiotropy

The expression of nicotinic acetylcholine receptor (nAChR) subtype, alpha7, was investigated in the developing teeth of mice that were modified through homologous recombination to express a bi-cistronic IRES-driven tau-enhanced green fluorescent protein (GFP); alpha7GFP) or IRES-Cre (alpha7Cre). The expression of alpha7GFP was detected first in cells of the condensing mesenchyme at embryonic (E) day E13.5 where it intensifies through E14.5. This expression ends abruptly at E15.5, but was again observed in ameloblasts of incisors at E16.5 or molar ameloblasts by E17.5–E18.5. This expression remains detectable until molar enamel deposition is completed or throughout life as in the constantly erupting mouse incisors. The expression of alpha7GFP also identifies all stages of innervation of the tooth organ. Ablation of the alpha7-cell lineage using a conditional alpha7Cre×ROSA26-LoxP(diphtheria toxin A) strategy substantially reduced the mesenchyme and this corresponded with excessive epithelium overgrowth consistent with an instructive role by these cells during ectoderm patterning. However, alpha7knock-out (KO) mice exhibited normal tooth size and shape indicating that under normal conditions alpha7 expression is dispensable to this process. The function of ameloblasts in alpha7KO mice is altered relative to controls. High resolution micro-computed tomography analysis of adult mandibular incisors revealed enamel volume of the alpha7KO was significantly reduced and the organization of enamel rods was altered relative to controls. These results demonstrate distinct and varied spatiotemporal expression of alpha7 during tooth development, and they suggest that dysfunction of this receptor would have diverse impacts upon the adult organ

Directed Evaluation of Enterotoxigenic Escherichia coli Autotransporter Proteins as Putative Vaccine Candidates

Diarrheal diseases are responsible for more than 1.5 million deaths annually in developing countries. Enterotoxigenic E. coli (ETEC) are among the most common bacterial causes of diarrhea, accounting for an estimated 300,000–500,000 deaths each year, mostly in young children. There unfortunately is not yet a vaccine that can offer sustained, broad-based protection against ETEC. While most vaccine development effort has focused on plasmid-encoded finger-like ETEC adhesin structures known as colonization factors, additional effort is needed to identify conserved target antigens. Epidemiologic studies suggest that immune responses to uncharacterized, chromosomally encoded antigens could contribute to protection resulting from repeated infections. Earlier studies of immune responses to ETEC infection had identified a class of surface-expressed molecules known as autotransporters (AT). Therefore, available ETEC genome sequences were examined to identify conserved ETEC autotransporters not shared by the commensal E. coli HS strain, followed by studies of the immune response to these antigens, and tests of their utility as vaccine components. Two chromosomally encoded ATs, identified in ETEC, but not in HS, were found to be immunogenic and protective in an animal model, suggesting that conserved AT molecules contribute to protective immune responses that follow natural ETEC infection and offering new potential targets for vaccines