VO: Vaccine Ontology

Vaccine research, as well as the development, testing, clinical trials, and commercial uses of vaccines involve complex processes with various biological data that include gene and protein expression, analysis of molecular and cellular interactions, study of tissue and whole body responses, and extensive epidemiological modeling. Although many data resources are available to meet different aspects of vaccine needs, it remains a challenge how we are to standardize vaccine annotation, integrate data about varied vaccine types and resources, and support advanced vaccine data analysis and inference. To address these problems, the community-based Vaccine Ontology (VO, "http://www.violinet.org/vaccineontology":http://www.violinet.org/vaccineontology) has been developed through collaboration with vaccine researchers and many national and international centers and programs, including the National Center for Biomedical Ontology (NCBO), the Infectious Disease Ontology (IDO) Initiative, and the Ontology for Biomedical Investigations (OBI). VO utilizes the Basic Formal Ontology (BFO) as the top ontology and the Relation Ontology (RO) for definition of term relationships. VO is represented in the Web Ontology Language (OWL) and edited using the Protégé-OWL. Currently VO contains more than 2000 terms and relationships. VO emphasizes on classification of vaccines and vaccine components, vaccine quality and phenotypes, and host immune response to vaccines. These reflect different aspects of vaccine composition and biology and can thus be used to model individual vaccines. More than 200 licensed vaccines and many vaccine candidates in research or clinical trials have been modeled in VO. VO is being used for vaccine literature mining through collaboration with the National Center for Integrative Biomedical Informatics (NCIBI). Multiple VO applications will be presented.
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VO: Vaccine Ontology

Vaccine research, as well as the development, testing, clinical trials, and commercial uses of vaccines involve complex processes with various biological data that include gene and protein expression, analysis of molecular and cellular interactions, study of tissue and whole body responses, and extensive epidemiological modeling. Although many data resources are available to meet different aspects of vaccine needs, it remains a challenge how we are to standardize vaccine annotation, integrate data about varied vaccine types and resources, and support advanced vaccine data analysis and inference. To address these problems, the community-based Vaccine Ontology (VO) has been developed through collaboration with vaccine researchers and many national and international centers and programs, including the National Center for Biomedical Ontology (NCBO), the Infectious Disease Ontology (IDO) Initiative, and the Ontology for Biomedical Investigations (OBI). VO utilizes the Basic Formal Ontology (BFO) as the top ontology and the Relation Ontology (RO) for definition of term relationships. VO is represented in the Web Ontology Language (OWL) and edited using the Protégé-OWL. Currently VO contains more than 2000 terms and relationships. VO emphasizes on classification of vaccines and vaccine components, vaccine quality and phenotypes, and host immune response to vaccines. These reflect different aspects of vaccine composition and biology and can thus be used to model individual vaccines. More than 200 licensed vaccines and many vaccine candidates in research or clinical trials have been modeled in VO. VO is being used for vaccine literature mining through collaboration with the National Center for Integrative Biomedical Informatics (NCIBI). Multiple VO applications will be presented

VO: Vaccine Ontology

The collaborative, community-based Vaccine Ontology (VO) was developed to promote vaccine data standardization, integration, and computer-assisted reasoning. Currently VO covers a variety of aspects of the vaccine domain, with an emphasis on classification of vaccines and vaccine components, and on host immune response to vaccines. VO can be used for a number of applications, e.g., ontology-based vaccine literature mining through collaboration with the National Center for Integrative Biomedical Informatics (NCIBI)

Pediatric primary intramedullary spinal cord glioblastoma

Spinal cord tumors in pediatric patients are rare, representing less than 1% of all central nervous system tumors. Two cases of pediatric primary intramedullary spinal cord glioblastoma at ages 14 and 8 years are reported. Both patients presented with rapid onset paraparesis and quadraparesis. Magnetic resonance imaging in both showed heterogeneously enhancing solitary mass lesions localized to lower cervical and upper thoracic spinal cord parenchyma. Histopathologic diagnosis was glioblastoma. Case #1 had a small cell component (primitive neuroectodermal tumor-like areas), higher Ki67, and p53 labeling indices, and a relatively stable karyotype with only minimal single copy losses involving regions: Chr8;pter-30480019, Chr16;pter-29754532, Chr16;56160245–88668979, and Chr19;32848902-qter on retrospective comparative genomic hybridization using formalin-fixed, paraffin-embedded samples. Case #2 had relatively bland histomorphology and negligible p53 immunoreactivity. Both underwent multimodal therapy including gross total resection, postoperative radiation and chemotherapy. However, there was no significant improvement in neurological deficits, and overall survival in both cases was 14 months.This report highlights the broad histological spectrum and poor overall survival despite multi modality therapy. The finding of relatively unique genotypic abnormalities resembling pediatric embryonal tumors in one case may highlight the value of genome-wide profiling in development of effective therapy. The differences in management with intracranial and low-grade spinal cord gliomas and current management issues are discussed

Ex vivo drug sensitivity screening predicts response to temozolomide in glioblastoma patients and identifies candidate biomarkers

Background: Patient-derived glioma stem-like cells (GSCs) have become the gold-standard in neuro-oncological research; however, it remains to be established whether loss of in situ microenvironment affects the clinically-predictive value of this model. We implemented a GSC monolayer system to investigate in situ-in vitro molecular correspondence and the relationship between in vitro and patient response to temozolomide (TMZ). Methods: DNA/RNA-sequencing was performed on 56 glioblastoma tissues and 19 derived GSC cultures. Sensitivity to TMZ was screened across 66 GSC cultures. Viability readouts were related to clinical parameters of corresponding patients and whole-transcriptome data. Results: Tumour DNA and RNA sequences revealed strong similarity to corresponding GSCs despite loss of neuronal and immune interactions. In vitro TMZ screening yielded three response categories which significantly correlated with patient survival, therewith providing more specific prediction than the binary MGMT marker. Transcriptome analysis identified 121 genes related to TMZ sensitivity of which 21were validated in external datasets. Conclusion:GSCs retain patient-unique hallmark gene expressions despite loss of their natural environment. Drug screening using GSCs predicted patient response to TMZ more specifically than MGMT status, while transcriptome analysis identified potential biomarkers for this response. GSC drug screening therefore provides a tool to improve drug development and precision medicine for glioblastoma.</p

Copy Number Variation across European Populations

Genome analysis provides a powerful approach to test for evidence of genetic variation within and between geographical regions and local populations. Copy number variants which comprise insertions, deletions and duplications of genomic sequence provide one such convenient and informative source. Here, we investigate copy number variants from genome wide scans of single nucleotide polymorphisms in three European population isolates, the island of Vis in Croatia, the islands of Orkney in Scotland and the South Tyrol in Italy. We show that whereas the overall copy number variant frequencies are similar between populations, their distribution is highly specific to the population of origin, a finding which is supported by evidence for increased kinship correlation for specific copy number variants within populations

Bedform migration in a mixed sand and cohesive clay intertidal environment and implications for bed material transport predictions

Many coastal and estuarine environments are dominated by mixtures of non-cohesive sand and cohesive mud. The migration rate of bedforms, such as ripples and dunes, in these environments is important in determining bed material transport rates to inform and assess numerical models of sediment transport and geomorphology. However, these models tend to ignore parameters describing the physical and biological cohesion (resulting from clay and extracellular polymeric substances, EPS) in natural mixed sediment, largely because of a scarcity of relevant laboratory and field data. To address this gap in knowledge, data were collected on intertidal flats over a spring-neap cycle to determine the bed material transport rates of bedforms in biologically-active mixed sand-mud. Bed cohesive composition changed from below 2 vol% up to 5.4 vol% cohesive clay, as the tide progressed from spring towards neap. The amount of EPS in the bed sediment was found to vary linearly with the clay content. Using multiple linear regression, the transport rate was found to depend on the Shields stress parameter and the bed cohesive clay content. The transport rates decreased with increasing cohesive clay and EPS content, when these contents were below 2.8 vol% and 0.05 wt%, respectively. Above these limits, bedform migration and bed material transport was not detectable by the instruments in the study area. These limits are consistent with recently conducted sand-clay and sand-EPS laboratory experiments on bedform development. This work has important implications for the circumstances under which existing sand-only bedform migration transport formulae may be applied in a mixed sand-clay environment, particularly as 2.8 vol% cohesive clay is well within the commonly adopted definition of “clean sand”

TIPIT: A randomised controlled trial of thyroxine in preterm infants under 28 weeks gestation: Magnetic Resonance Imaging and Magnetic Resonance Angiography protocol

<p>Abstract </p> <p>Background</p> <p>Infants born at extreme prematurity are at high risk of developmental disability. A major risk factor for disability is having a low level of thyroid hormone described as hypothyroxinaemia, which is recognised to be a frequent phenomenon in these infants. Derangements of critical thyroid function during the sensitive window in prematurity when early development occurs, may have a range of long term effects for brain development. Further research in preterm infants using neuroimaging techniques will increase our understanding of the specificity of the effects of hypothyroxinaemia on the developing foetal brain. This is an explanatory double blinded randomised controlled trial which is aimed to assess the effect of thyroid hormone supplementation on brain size, key brain structures, extent of myelination, white matter integrity and vessel morphology, somatic growth and the hypothalamic-pituitary-adrenal axis.</p> <p>Methods</p> <p>The study is a multi-centred double blinded randomised controlled trial of thyroid hormone supplementation in babies born below 28 weeks' gestation. All infants will receive either levothyroxine or placebo until 32 weeks corrected gestational age. The primary outcomes will be width of the sub-arachnoid space measured using cranial ultrasound and head circumference at 36 weeks corrected gestational age. The secondary outcomes will be thyroid hormone concentrations, the hypothalamic pituitary axis status and auxological data between birth and expected date of delivery; thyroid gland volume, brain size, volumes of key brain structures, extent of myelination and brain vessel morphology at expected date of delivery and markers of morbidity which include duration of mechanical ventilation and/or oxygen requirement and chronic lung disease.</p> <p><b>Trial registration</b></p> <p>Current Controlled Trials ISRCTN89493983</p

Respatialization and local protest strategy formation: Investigating high-speed rail megaproject development in the UK

Understanding spatial conceptions is critical to the analysis of local protest strategy formation. Spatialities provoke inquiry into the drivers that may prompt local actors to adhere to particular strategies, and the implications this has on forms of contestation and the way protest is organized. It is argued that local protest can ‘respatialize’ when actors are embedded in social movements and translocal assemblages associated with controversy over development, and that this warrants reconsidering the role of ‘place’. A case study of a proposed megaproject framed in the national interest – a high-speed rail network called HS2, in the United Kingdom – is used to investigate local protest respatialization. Fieldwork was conducted in the Chilterns, an area of high scenic beauty which will be adversely impacted by HS2. The results show how the perceived need to respatialize protest away from the local to the national domain reconfigures debate to focus primarily on economic issues. Respatialization also has implications for the dynamics of protest assemblages with unlikely alliances developing around a need to engage with or engender debate in the national polity. It is concluded that local actors may opt to respatialize their protest in response to their interaction with social movements and protest assemblages that disengage from specific place-based interests. The paper recommends that future research on the geographies of social action take forward spatialization as a powerful lens for investigating protest strategy formation

Search for Neutral Heavy Leptons Produced in Z Decays

Weak isosinglet Neutral Heavy Leptons ($\nu_m$) have been searched for using data collected by the DELPHI detector corresponding to $3.3\times 10^{6}$ hadronic~Z$^{0}$ decays at LEP1. Four separate searches have been performed, for short-lived $\nu_m$ production giving monojet or acollinear jet topologies, and for long-lived $\nu_m$ giving detectable secondary vertices or calorimeter clusters. No indication of the existence of these particles has been found, leading to an upper limit for the branching ratio $BR($Z$^0\rightarrow \nu_m \overline{\nu})$ of about $1.3\times10^{-6}$ at 95\% confidence level for $\nu_m$ masses between 3.5 and 50 GeV/$c^2$. Outside this range the limit weakens rapidly with the $\nu_m$ mass. %Special emphasis has been given to the search for monojet--like topologies. One event %has passed the selection, in agreement with the expectation from the reaction: %$e^+e^- \rightarrow\ell \bar\ell \nu\bar\nu$. The results are also interpreted in terms of limits for the single production of excited neutrinos