WorldWideScience

Sample records for searching candidate biomarkers

  1. Testing of the OMERACT 8 draft validation criteria for a soluble biomarker reflecting structural damage in rheumatoid arthritis: a systematic literature search on 5 candidate biomarkers

    DEFF Research Database (Denmark)

    Syversen, Silje W; Landewe, Robert; van der Heijde, Désirée

    2009-01-01

    OBJECTIVE: To test the OMERACT 8 draft validation criteria for soluble biomarkers by assessing the strength of literature evidence in support of 5 candidate biomarkers. METHODS: A systematic literature search was conducted on the 5 soluble biomarkers RANKL, osteoprotegerin (OPG), matrix...... metalloprotease (MMP-3), urine C-telopeptide of types I and II collagen (U-CTX-I and U CTX-II), focusing on the 14 OMERACT 8 criteria. Two electronic voting exercises were conducted to address: (1) strength of evidence for each biomarker as reflecting structural damage according to each individual criterion...

  2. Multiomics Data Triangulation for Asthma Candidate Biomarkers and Precision Medicine.

    Science.gov (United States)

    Pecak, Matija; Korošec, Peter; Kunej, Tanja

    2018-06-01

    Asthma is a common complex disorder and has been subject to intensive omics research for disease susceptibility and therapeutic innovation. Candidate biomarkers of asthma and its precision treatment demand that they stand the test of multiomics data triangulation before they can be prioritized for clinical applications. We classified the biomarkers of asthma after a search of the literature and based on whether or not a given biomarker candidate is reported in multiple omics platforms and methodologies, using PubMed and Web of Science, we identified omics studies of asthma conducted on diverse platforms using keywords, such as asthma, genomics, metabolomics, and epigenomics. We extracted data about asthma candidate biomarkers from 73 articles and developed a catalog of 190 potential asthma biomarkers (167 human, 23 animal data), comprising DNA loci, transcripts, proteins, metabolites, epimutations, and noncoding RNAs. The data were sorted according to 13 omics types: genomics, epigenomics, transcriptomics, proteomics, interactomics, metabolomics, ncRNAomics, glycomics, lipidomics, environmental omics, pharmacogenomics, phenomics, and integrative omics. Importantly, we found that 10 candidate biomarkers were apparent in at least two or more omics levels, thus promising potential for further biomarker research and development and precision medicine applications. This multiomics catalog reported herein for the first time contributes to future decision-making on prioritization of biomarkers and validation efforts for precision medicine in asthma. The findings may also facilitate meta-analyses and integrative omics studies in the future.

  3. Candidate immune biomarkers for radioimmunotherapy.

    Science.gov (United States)

    Levy, Antonin; Nigro, Giulia; Sansonetti, Philippe J; Deutsch, Eric

    2017-08-01

    Newly available immune checkpoint blockers (ICBs), capable to revert tumor immune tolerance, are revolutionizing the anticancer armamentarium. Recent evidence also established that ionizing radiation (IR) could produce antitumor immune responses, and may as well synergize with ICBs. Multiple radioimmunotherapy combinations are thenceforth currently assessed in early clinical trials. Past examples have highlighted the need for treatment personalization, and there is an unmet need to decipher immunological biomarkers that could allow selecting patients who could benefit from these promising but expensive associations. Recent studies have identified potential predictive and prognostic immune assays at the cellular (tumor microenvironment composition), genomic (mutational/neoantigen load), and peripheral blood levels. Within this review, we collected the available evidence regarding potential personalized immune biomarker-directed radiation therapy strategies that might be used for patient selection in the era of radioimmunotherapy. Copyright © 2017. Published by Elsevier B.V.

  4. Major depressive disorder: insight into candidate cerebrospinal fluid protein biomarkers from proteomics studies.

    Science.gov (United States)

    Al Shweiki, Mhd Rami; Oeckl, Patrick; Steinacker, Petra; Hengerer, Bastian; Schönfeldt-Lecuona, Carlos; Otto, Markus

    2017-06-01

    Major Depressive Disorder (MDD) is the leading cause of global disability, and an increasing body of literature suggests different cerebrospinal fluid (CSF) proteins as biomarkers of MDD. The aim of this review is to summarize the suggested CSF biomarkers and to analyze the MDD proteomics studies of CSF and brain tissues for promising biomarker candidates. Areas covered: The review includes the human studies found by a PubMed search using the following terms: 'depression cerebrospinal fluid biomarker', 'major depression biomarker CSF', 'depression CSF biomarker', 'proteomics depression', 'proteomics biomarkers in depression', 'proteomics CSF biomarker in depression', and 'major depressive disorder CSF'. The literature analysis highlights promising biomarker candidates and demonstrates conflicting results on others. It reveals 42 differentially regulated proteins in MDD that were identified in more than one proteomics study. It discusses the diagnostic potential of the biomarker candidates and their association with the suggested pathologies. Expert commentary: One ultimate goal of finding biomarkers for MDD is to improve the diagnostic accuracy to achieve better treatment outcomes; due to the heterogeneous nature of MDD, using bio-signatures could be a good strategy to differentiate MDD from other neuropsychiatric disorders. Notably, further validation studies of the suggested biomarkers are still needed.

  5. Integrative analysis to select cancer candidate biomarkers to targeted validation

    Science.gov (United States)

    Heberle, Henry; Domingues, Romênia R.; Granato, Daniela C.; Yokoo, Sami; Canevarolo, Rafael R.; Winck, Flavia V.; Ribeiro, Ana Carolina P.; Brandão, Thaís Bianca; Filgueiras, Paulo R.; Cruz, Karen S. P.; Barbuto, José Alexandre; Poppi, Ronei J.; Minghim, Rosane; Telles, Guilherme P.; Fonseca, Felipe Paiva; Fox, Jay W.; Santos-Silva, Alan R.; Coletta, Ricardo D.; Sherman, Nicholas E.; Paes Leme, Adriana F.

    2015-01-01

    Targeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS-based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Three feature selection algorithms, namely, Beta-binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS. PMID:26540631

  6. Multiplexed mass spectrometry monitoring of biomarker candidates for osteoarthritis.

    Science.gov (United States)

    Fernández-Puente, Patricia; Calamia, Valentina; González-Rodríguez, Lucía; Lourido, Lucía; Camacho-Encina, María; Oreiro, Natividad; Ruiz-Romero, Cristina; Blanco, Francisco J

    2017-01-30

    The methods currently available for the diagnosis and monitoring of osteoarthritis (OA) are very limited and lack sensitivity. Being the most prevalent rheumatic disease, one of the most disabling pathologies worldwide and currently untreatable, there is a considerable interest pointed in the verification of specific biological markers for improving its diagnosis and disease progression studies. Considering the remarkable development of targeted proteomics methodologies in the frame of the Human Proteome Project, the aim of this work was to develop and apply a MRM-based method for the multiplexed analysis of a panel of 6 biomarker candidates for OA encoded by the Chromosome 16, and another 8 proteins identified in previous shotgun studies as related with this pathology, in specimens derived from the human joint and serum. The method, targeting 35 different peptides, was applied to samples from human articular chondrocytes, healthy and osteoarthritic cartilage, synovial fluid and serum. Subsequently, a verification analysis of the biomarker value of these proteins was performed by single point measurements on a set of 116 serum samples, leading to the identification of increased amounts of Haptoglobin and von Willebrand Factor in OA patients. Altogether, the present work provides a tool for the multiplexed monitoring of 14 biomarker candidates for OA, and verifies for the first time the increased amount of two of these circulating markers in patients diagnosed with this disease. We have developed an MRM method for the identification and relative quantification of a panel of 14 protein biomarker candidates for osteoarthritis. This method has been applied to analyze human articular chondrocytes, articular cartilage, synovial fluid, and finally a collection of 116 serum samples from healthy controls and patients suffering different degrees of osteoarthritis, in order to verify the biomarker usefulness of the candidates. HPT and VWF were validated as increased in OA

  7. Proteomics for discovery of candidate colorectal cancer biomarkers

    Science.gov (United States)

    Álvarez-Chaver, Paula; Otero-Estévez, Olalla; Páez de la Cadena, María; Rodríguez-Berrocal, Francisco J; Martínez-Zorzano, Vicenta S

    2014-01-01

    Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in Europe and other Western countries, mainly due to the lack of well-validated clinically useful biomarkers with enough sensitivity and specificity to detect this disease at early stages. Although it is well known that the pathogenesis of CRC is a progressive accumulation of mutations in multiple genes, much less is known at the proteome level. Therefore, in the last years many proteomic studies have been conducted to find new candidate protein biomarkers for diagnosis, prognosis and as therapeutic targets for this malignancy, as well as to elucidate the molecular mechanisms of colorectal carcinogenesis. An important advantage of the proteomic approaches is the capacity to look for multiple differentially expressed proteins in a single study. This review provides an overview of the recent reports describing the different proteomic tools used for the discovery of new protein markers for CRC such as two-dimensional electrophoresis methods, quantitative mass spectrometry-based techniques or protein microarrays. Additionally, we will also focus on the diverse biological samples used for CRC biomarker discovery such as tissue, serum and faeces, besides cell lines and murine models, discussing their advantages and disadvantages, and summarize the most frequently identified candidate CRC markers. PMID:24744574

  8. Candidate Biomarkers in Children with Autism Spectrum Disorder: A Review of MRI Studies

    Institute of Scientific and Technical Information of China (English)

    Dongyun Li; Hans-Otto Karnath; Xiu Xu

    2017-01-01

    Searching for effective biomarkers is one of the most challenging tasks in the research field of Autism Spectrum Disorder (ASD).Magnetic resonance imaging (MRI) provides a non-invasive and powerful tool for investigating changes in the structure,function,maturation,connectivity,and metabolism of the brain of children with ASD.Here,we review the more recent MRI studies in young children with ASD,aiming to provide candidate biomarkers for the diagnosis of childhood ASD.The review covers structural imaging methods,diffusion tensor imaging,resting-state functional MRI,and magnetic reso nance spectroscopy.Future advances in neuroimaging techniques,as well as cross-disciplinary studies and largescale collaborations will be needed for an integrated approach linking neuroimaging,genetics,and phenotypic data to allow the discovery of new,effective biomarkers.

  9. Candidate proteomic biomarkers for non-alcoholic fatty liver disease (steatosis and non-alcoholic steatohepatitis) discovered with mass-spectrometry: a systematic review.

    Science.gov (United States)

    Lădaru, Anca; Bălănescu, Paul; Stan, Mihaela; Codreanu, Ioana; Anca, Ioana Alina

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver which is accompanied by a series of metabolic deregulations. There are sustained research efforts focusing upon biomarker discovery for NAFLD diagnosis and its prognosis in order investigate and follow-up patients as minimally invasive as possible. The objective of this study is to critically review proteomic studies that used mass spectrometry techniques and summarize relevant proteomic NAFLD candidate biomarkers. Medline and Embase databases were searched from inception to December 2014. A final number of 22 records were included that identified 251 candidate proteomic biomarkers. Thirty-three biomarkers were confirmed - 14 were found in liver samples, 21 in serum samples, and two from both serum and liver samples. Some of the biomarkers identified have already been extensively studied regarding their diagnostic and prognostic capacity. However, there are also more potential biomarkers that still need to be addressed in future studies.

  10. Biomarkers of tolerance: searching for the hidden phenotype.

    Science.gov (United States)

    Perucha, Esperanza; Rebollo-Mesa, Irene; Sagoo, Pervinder; Hernandez-Fuentes, Maria P

    2011-08-01

    Induction of transplantation tolerance remains the ideal long-term clinical and logistic solution to the current challenges facing the management of renal allograft recipients. In this review, we describe the recent studies and advances made in identifying biomarkers of renal transplant tolerance, from study inceptions, to the lessons learned and their implications for current and future studies with the same goal. With the age of biomarker discovery entering a new dimension of high-throughput technologies, here we also review the current approaches, developments, and pitfalls faced in the subsequent statistical analysis required to identify valid biomarker candidates.

  11. Mass spectrometry imaging enriches biomarker discovery approaches with candidate mapping.

    Science.gov (United States)

    Scott, Alison J; Jones, Jace W; Orschell, Christie M; MacVittie, Thomas J; Kane, Maureen A; Ernst, Robert K

    2014-01-01

    Integral to the characterization of radiation-induced tissue damage is the identification of unique biomarkers. Biomarker discovery is a challenging and complex endeavor requiring both sophisticated experimental design and accessible technology. The resources within the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Consortium, Medical Countermeasures Against Radiological Threats (MCART), allow for leveraging robust animal models with novel molecular imaging techniques. One such imaging technique, MALDI (matrix-assisted laser desorption ionization) mass spectrometry imaging (MSI), allows for the direct spatial visualization of lipids, proteins, small molecules, and drugs/drug metabolites-or biomarkers-in an unbiased manner. MALDI-MSI acquires mass spectra directly from an intact tissue slice in discrete locations across an x, y grid that are then rendered into a spatial distribution map composed of ion mass and intensity. The unique mass signals can be plotted to generate a spatial map of biomarkers that reflects pathology and molecular events. The crucial unanswered questions that can be addressed with MALDI-MSI include identification of biomarkers for radiation damage that reflect the response to radiation dose over time and the efficacy of therapeutic interventions. Techniques in MALDI-MSI also enable integration of biomarker identification among diverse animal models. Analysis of early, sublethally irradiated tissue injury samples from diverse mouse tissues (lung and ileum) shows membrane phospholipid signatures correlated with histological features of these unique tissues. This paper will discuss the application of MALDI-MSI for use in a larger biomarker discovery pipeline.

  12. SEARCHES FOR MILLISECOND PULSAR CANDIDATES AMONG THE UNIDENTIFIED FERMI OBJECTS

    Energy Technology Data Exchange (ETDEWEB)

    Hui, C. Y.; Park, S. M. [Department of Astronomy and Space Science, Chungnam National University, Daejeon (Korea, Republic of); Hu, C. P. [Graduate Institute of Astronomy, National Central University, Jhongli 32001, Taiwan (China); Lin, L. C. C. [Institute of Astronomy and Astrophysics, Academia Sinica, Taiwan (China); Li, K. L.; Kong, A. K. H.; Jin, Ruolan; Yen, T.-C. [Institute of Astronomy and Department of Physics, National Tsing Hua University, Hsinchu, Taiwan (China); Tam, P. H. T. [Institute of Astronomy and Space Science, Sun Yat-Sen University, Guangzhou 510275 (China); Takata, J.; Cheng, K. S. [Department of Physics, University of Hong Kong, Pokfulam Road, Hong Kong (China); Kim, Chunglee, E-mail: cyhui@cnu.ac.kr [Yonsei University Observatory, Yonsei University, Seoul (Korea, Republic of)

    2015-08-10

    Here we report the results of searching millisecond pulsar (MSP) candidates from the Fermi LAT second source catalog (2FGL). Seven unassociated γ-ray sources in this catalog are identified as promising MSP candidates based on their γ-ray properties. Through the X-ray analysis, we have detected possible X-ray counterparts, localized to an arcsecond accuracy. We have systematically estimated their X-ray fluxes and compared them with the corresponding γ-ray fluxes. The X-ray to γ-ray flux ratios for 2FGL J1653.6-0159 and 2FGL J1946.4-5402 are comparable with the typical value for pulsars. For 2FGL J1625.2-0020, 2FGL J1653.6-0159, and 2FGL J1946.4-5402, their candidate X-ray counterparts are bright enough to perform a detailed spectral and temporal analysis to discriminate their thermal/non-thermal nature and search for the periodic signal. We have also searched for possible optical/IR counterparts at the X-ray positions. For the optical/IR source coincident with the brightest X-ray object associated with 2FGL J1120.0-2204, its spectral energy distribution is comparable with a late-type star. Evidence for the variability has also been found by examining its optical light curve. All the aforementioned 2FGL sources resemble a pulsar in one or more aspects, making them promising targets for follow-up investigations.

  13. MFAP4: a candidate biomarker for hepatic and pulmonary fibrosis?

    Science.gov (United States)

    Mölleken, Christian; Poschmann, Gereon; Bonella, Francesco; Costabel, Ulrich; Sitek, Barbara; Stühler, Kai; Meyer, Helmut E; Schmiegel, Wolff H; Marcussen, Niels; Helmer, Michael; Nielsen, Ole; Hansen, Søren; Schlosser, Anders; Holmskov, Uffe; Sorensen, Grith Lykke

    2016-03-29

    Several comparable mechanisms have been identified for hepatic and pulmonary fibrosis. The human microfibrillar associated glycoprotein 4 (MFAP4), produced by activated myofibroblasts, is a ubiquitous protein playing a potential role in extracellular matrix (ECM) turnover and was recently identified as biomarker for hepatic fibrosis in hepatitis C patients. The current study aimed to evaluate serum levels of MFAP4 in patients with pulmonary fibrosis in order to test its potential as biomarker in clinical practice. A further aim was to determine whether MFAP4 deficiency in mice affects the formation of pulmonary fibrosis in the bleomycin model of lung fibrosis. 91 patients with idiopathic pulmonary fibrosis (IPF), 23 with hypersensitivity pneumonitis (HP) and 31 healthy subjects were studied. In the mouse model, C57BL/6 Mfap4+/+ and Mfap4-/- mice between 6-8 weeks of age were studied. Serum levels of MFAP4 were measured by ELISA in patients and in mice. Surfactant protein D (SP-D) and LDH were measured as comparison biomarkers in patients with pulmonary fibrosis. Morphometric assessment and the Sircol kit were used to determine the amount of collagen in the lung tissue in the mouse model. Serum levels of MFAP4 were not elevated in lung fibrosis - neither in the patients with IPF or HP nor in the animal model. Furthermore no significant correlations with pulmonary function tests of IPF patients could be found for MFAP4. MFAP4 levels were increased in BAL of bleomycin treated mice with pulmonary fibrosis. MFAP4 is not elevated in sera of patients with pulmonary fibrosis or bleomycin treated mice with pulmonary fibrosis. This may be due to different pathogenic mechanisms of liver and lung fibrogenesis. MFAP4 seems to be useful as serum biomarker for hepatic but not for lung fibrosis.

  14. Neutrophils, a candidate biomarker and target for radiation therapy?

    Science.gov (United States)

    Schernberg, Antoine; Blanchard, Pierre; Chargari, Cyrus; Deutsch, Eric

    2017-11-01

    Neutrophils are the most abundant blood-circulating white blood cells, continuously generated in the bone marrow. Growing evidence suggests they regulate the innate and adaptive immune system during tumor evolution. This review will first summarize the recent findings on neutrophils as a key player in cancer evolution, then as a potential biomarker, and finally as therapeutic targets, with respective focuses on the interplay with radiation therapy. A complex interplay: Neutrophils have been associated with tumor progression through multiple pathways. Ionizing radiation has cytotoxic effects on cancer cells, but the sensitivity to radiation therapy in vivo differ from isolated cancer cells in vitro, partially due to the tumor microenvironment. Different microenvironmental states, whether baseline or induced, can modulate or even attenuate the effects of radiation, with consequences for therapeutic efficacy. Inflammatory biomarkers: Inflammation-based scores have been widely studied as prognostic biomarkers in cancer patients. We have performed a large retrospective cohort of patients undergoing radiation therapy (1233 patients), with robust relationship between baseline blood neutrophil count and 3-year's patient's overall survival in patients with different cancer histologies. (Pearson's correlation test: p = .001, r = -.93). Therapeutic approaches: Neutrophil-targeting agents are being developed for the treatment of inflammatory and autoimmune diseases. Neutrophils either can exert antitumoral (N1 phenotype) or protumoral (N2 phenotype) activity, depending on the Tumor Micro Environment. Tumor associated N2 neutrophils are characterized by high expression of CXCR4, VEGF, and gelatinase B/MMP9. TGF-β within the tumor microenvironment induces a population of TAN with a protumor N2 phenotype. TGF-β blockade slows tumor growth through activation of CD8 + T cells, macrophages, and tumor associated neutrophils with an antitumor N1 phenotype. This supports

  15. Piezo2: A Candidate Biomarker for Visceral Hypersensitivity in Irritable Bowel Syndrome?

    OpenAIRE

    Bai, Tao; Li, Ying; Xia, Jing; Jiang, Yudong; Zhang, Lei; Wang, Huan; Qian, Wei; Song, Jun; Hou, Xiaohua

    2017-01-01

    Background/Aims Currently, there exists no biomarker for visceral hypersensitivity in irritable bowel syndrome (IBS). Piezo proteins have been proven to play an important role in the mechanical stimulation to induce visceral pain in other tissues and may also be a biomarker candidate. The aim of this study was to test the expressions of Piezo1 and Piezo2 proteins in the intestinal epithelial cells from different intestinal segments and to explore the correlation between Piezo proteins express...

  16. Validation of biomarkers of food intake − critical assessment of candidate biomarkers

    DEFF Research Database (Denmark)

    Dragsted, Lars Ove; Gao, Qian; Scalbert, Augustin

    2018-01-01

    Biomarkers of food intake (BFIs) are a promising tool for limiting misclassification in nutrition research where more subjective dietary assessment instruments are used. They may also be used to assess compliance to dietary guidelines or to a dietary intervention. Biomarkers therefore hold promis...

  17. Resolving breast cancer heterogeneity by searching reliable protein cancer biomarkers in the breast fluid secretome

    International Nuclear Information System (INIS)

    Mannello, Ferdinando; Ligi, Daniela

    2013-01-01

    One of the major goals in cancer research is to find and evaluate the early presence of biomarkers in human fluids and tissues. To resolve the complex cell heterogeneity of a tumor mass, it will be useful to characterize the intricate biomolecular composition of tumor microenvironment (the so called cancer secretome), validating secreted proteins as early biomarkers of cancer initiation and progression. This approach is not broadly applicable because of the paucity of well validated and FDA-approved biomarkers and because most of the candidate biomarkers are mainly organ-specific rather than tumor-specific. For these reasons, there is an urgent need to identify and validate a panel of biomarker combinations for early detection of human tumors. This is especially important for breast cancer, the cancer spread most worldwide among women. It is well known that patients with early diagnosed breast cancer live longer, require less extensive treatment and fare better than patients with more aggressive and/or advanced disease. In the frame of searching breast cancer biomarkers (especially using nipple aspirate fluid mirroring breast microenvironment), studies have highlighted an optimal combination of well-known biomarkers: uPA + PAI-1 + TF. When individually investigated they did not show perfect accuracy in predicting the presence of breast cancer, whereas the triple combination has been demonstrated to be highly predictive of pre-cancer and/or cancerous conditions, approaching 97-100% accuracy. Despite the heterogeneous composition of breast cancer and the difficulties to find specific breast cancer biomolecules, the noninvasive analysis of the nipple aspirate fluid secretome may significantly improve the discovery of promising biomarkers, helping also the differentiation among benign and invasive breast diseases, opening new frontiers in early oncoproteomics

  18. Validation of Candidate Serum Ovarian Cancer Biomarkers for Early Detection

    Directory of Open Access Journals (Sweden)

    Feng Su

    2007-01-01

    Full Text Available Objective: We have previously analyzed protein profi les using Surface Enhanced Laser Desorption and Ionization Time-Of-Flight Mass Spectroscopy (SELDI-TOF-MS [Kozak et al. 2003, Proc. Natl. Acad. Sci. U.S.A. 100:12343–8] and identified 3 differentially expressed serum proteins for the diagnosis of ovarian cancer (OC [Kozak et al. 2005, Proteomics, 5:4589–96], namely, apolipoprotein A-I (apoA-I, transthyretin (TTR and transferin (TF. The objective of the present study is to determine the efficacy of the three OC biomarkers for the detection of early stage (ES OC, in direct comparison to CA125.Methods: The levels of CA125, apoA-I, TTR and TF were measured in 392 serum samples [82 women with normal ovaries (N, 24 women with benign ovarian tumors (B, 85 women with ovarian tumors of low malignant potential (LMP, 126 women with early stage ovarian cancer (ESOC, and 75 women with late stage ovarian cancer (LSOC], obtained through the GOG and Cooperative Human Tissue Network. Following statistical analysis, multivariate regression models were built to evaluate the utility of the three OC markers in early detection.Results: Multiple logistic regression models (MLRM utilizing all biomarker values (CA125, TTR, TF and apoA-I from all histological subtypes (serous, mucinous, and endometrioid adenocarcinoma distinguished normal samples from LMP with 91% sensitivity (specifi city 92%, and normal samples from ESOC with a sensitivity of 89% (specifi city 92%. MLRM, utilizing values of all four markers from only the mucinous histological subtype showed that collectively, CA125, TTR, TF and apoA-I, were able to distinguish normal samples from mucinous LMP with 90% sensitivity, and further distinguished normal samples from early stage mucinous ovarian cancer with a sensitivity of 95%. In contrast, in serum samples from patients with mucinous tumors, CA125 alone was able to distinguish normal samples from LMP and early stage ovarian cancer with a sensitivity of

  19. Neuropathological biomarker candidates in brain tumors: key issues for translational efficiency.

    Science.gov (United States)

    Hainfellner, J A; Heinzl, H

    2010-01-01

    Brain tumors comprise a large spectrum of rare malignancies in children and adults that are often associated with severe neurological symptoms and fatal outcome. Neuropathological tumor typing provides both prognostic and predictive tissue information which is the basis for optimal postoperative patient management and therapy. Molecular biomarkers may extend and refine prognostic and predictive information in a brain tumor case, providing more individualized and optimized treatment options. In the recent past a few neuropathological brain tumor biomarkers have translated smoothly into clinical use whereas many candidates show protracted translation. We investigated the causes of protracted translation of candidate brain tumor biomarkers. Considering the research environment from personal, social and systemic perspectives we identified eight determinants of translational success: methodology, funding, statistics, organization, phases of research, cooperation, self-reflection, and scientific progeny. Smoothly translating biomarkers are associated with low degrees of translational complexity whereas biomarkers with protracted translation are associated with high degrees. Key issues for translational efficiency of neuropathological brain tumor biomarker research seem to be related to (i) the strict orientation to the mission of medical research, that is the improval of medical practice as primordial purpose of research, (ii) definition of research priorities according to clinical needs, and (iii) absorption of translational complexities by means of operatively beneficial standards. To this end, concrete actions should comprise adequate scientific education of young investigators, and shaping of integrative diagnostics and therapy research both on the local level and the level of influential international brain tumor research platforms.

  20. Candidate protein biomarkers as rapid indicators of radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Horn, Simon, E-mail: sjh.horn@gmail.com [Health Protection Agency, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Oxfordshire OX11 0RQ (United Kingdom); Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast BT9 7BL (United Kingdom); Rothkamm, Kai [Health Protection Agency, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Oxfordshire OX11 0RQ (United Kingdom)

    2011-09-15

    For large scale exposures of the human population to ionising radiation, there is a need for cost-effective high throughput assessment of radiation exposure levels from biological samples to allow triage decisions to be made. Here we assess the usefulness of H2AX phosphorylation, 53BP1 foci formation, p53 induction and caspase activation as tools for biological dosimetry. Peripheral blood lymphocytes from healthy donors were isolated and exposed to X-rays. Cells were fixed, permeabilised and then stained with primary antibodies for {gamma}-H2AX and/or 53BP1, p53 or FLICA caspase detection kit followed by fluorescently tagged secondary antibodies. Cell nuclei were DAPI or propidium iodide counterstained for microscopy or cytometry respectively. Average {gamma}-H2AX/53BP1 foci numbers and {gamma}-H2AX fluorescence intensities increased with dose. Foci loss occurred over a period of 24 h post exposure with foci levels remaining above baseline levels for at least 24 h following exposure to 0.5 Gy or more of X-rays. p53 levels increased with dose and over time, peaking at 48 h post exposure. Apoptotic cells were highlighted with greatly increased levels of activated caspases. A single dose of 4 Gy increased the percentage of apoptotic lymphocytes to over 60% at 96 h post exposure. The finding that the biomarkers analysed here have different temporal dynamics following radiation exposure suggests that they could be combined to enable detection of exposures over a period of hours to several days after a radiation incident to help facilitate rapid triage.

  1. [Identification of candidate genes and expression profiles, as doping biomarkers].

    Science.gov (United States)

    Paparini, A; Impagnatiello, F; Pistilli, A; Rinaldi, M; Gianfranceschi, G; Signori, E; Stabile, A M; Fazio, V; Rende, M; Romano Spica, V

    2007-01-01

    Administration of prohibited substances to enhance athletic performance represents an emerging medical, social, ethical and legal issue. Traditional controls are based on direct detection of substances or their catabolites. However out-of-competition doping may not be easily revealed by standard analytical methods. Alternative indirect control strategies are based on the evaluation of mid- and long-term effects of doping in tissues. Drug-induced long-lasting changes of gene expression may be taken as effective indicators of doping exposure. To validate this approach, we used real-time PCR to monitor the expression pattern of selected genes in human haematopoietic cells exposed to nandrolone, insulin-like growth factor I (IGF-I) or growth hormone (GH). Some candidate genes were found significantly and consistently modulated by treatments. Nandrolone up-regulated AR, ESR2 and PGR in K562 cells, and SRD5A1, PPARA and JAK2 in Jurkat cells; IGF-I up-regulated EPOR and PGR in HL60 cells, and SRD5A1 in Jurkat; GH up-regulated SRD5A1 and GHR in K562. GATA1 expression was down-regulated in IGF-1-treated HL60, ESR2 was down-regulated in nandrolone-treated Jurkat, and AR and PGR were down-regulated in GH-treated Jurkat. This pilot study shows the potential of molecular biology-based strategies in anti-doping controls.

  2. Metabolomics-based promising candidate biomarkers and pathways in Alzheimer's disease.

    Science.gov (United States)

    Kang, Jian; Lu, Jingli; Zhang, Xiaojian

    2015-05-01

    Pathologically, loss of synapses and neurons, extracellular senile plaques and intracellular neurofibrillary tangles (NFTs) are observed in the brains of patients with Alzheimer's disease (AD). These features are associated with changes Aβ (amyloid β) 40, Aβ42, total tau and phosphorylated tau (p-tau), which are as definitely biomarkers for severe AD state. However, biomarkers for effectively diagnosing AD in the pre-clinical state for directing therapeutic strategies are lacking. Metabolic profiling as a powerful tool to identify new biomarkers is receiving increasing attention in AD. This review will focus on metabolomics-based detection of promising candidate biomarkers and pathways in AD to facilitate the discovery of new medicines and disease pathways.

  3. Enrichment of MCI and early Alzheimer's disease treatment trials using neurochemical and imaging candidate biomarkers.

    LENUS (Irish Health Repository)

    Hampel, H

    2012-02-01

    In the earliest clinical stages of Alzheimer\\'s Disease (AD), when symptoms are mild, clinical diagnosis will still be difficult. AD related molecular mechanisms precede symptoms. Biological markers can serve as early diagnostic indicators, as markers of preclinical pathological change, e.g. underlying mechanisms of action (MoA). Hypothesis based candidates are derived from structural and functional neuroimaging as well as from cerebrospinal fluid (CSF) and plasma. Unbiased exploratory approaches e.g. proteome analysis or rater independent fully automated imaging post-processing methods yield novel candidates. Recent progress in the validation of core feasible imaging and neurochemical biomarkers for functions such as early detection, classification, progression and prediction of AD is summarized. Single core feasible biomarkers can already be used to enrich populations at risk for AD and may be further enhanced using distinct combinations. Some biomarkers are currently in the process of implementation as primary or secondary outcome variables into regulatory guideline documents, e.g. regarding phase II in drug development programs as outcome measures in proof of concept or dose finding studies. There are specific biomarkers available depending on the hypothesized mechanism of action of a medicinal product, e.g. impact on the amyloidogenic cascade or on tauhyperphosphorylation. Ongoing large-scale international controlled multi-center trials will provide further validation of selected core feasible imaging and CSF biomarker candidates as outcome measures in early AD for use in phase III clinical efficacy trials. There is a need of rigorous co-development of biological trait- and statemarker candidates facilitated through planned synergistic collaboration between academic, industrial and regulatory partners.

  4. Guidelines for Biomarker of Food Intake Reviews (BFIRev): how to conduct an extensive literature search for biomarker of food intake discovery.

    Science.gov (United States)

    Praticò, Giulia; Gao, Qian; Scalbert, Augustin; Vergères, Guy; Kolehmainen, Marjukka; Manach, Claudine; Brennan, Lorraine; Pedapati, Sri Harsha; Afman, Lydia A; Wishart, David S; Vázquez-Fresno, Rosa; Lacueva, Cristina Andres; Garcia-Aloy, Mar; Verhagen, Hans; Feskens, Edith J M; Dragsted, Lars O

    2018-01-01

    Identification of new biomarkers of food and nutrient intake has developed fast over the past two decades and could potentially provide important new tools for compliance monitoring and dietary intake assessment in nutrition and health science. In recent years, metabolomics has played an important role in identifying a large number of putative biomarkers of food intake (BFIs). However, the large body of scientific literature on potential BFIs outside the metabolomics area should also be taken into account. In particular, we believe that extensive literature reviews should be conducted and that the quality of all suggested biomarkers should be systematically evaluated. In order to cover the literature on BFIs in the most appropriate and consistent manner, there is a need for appropriate guidelines on this topic. These guidelines should build upon guidelines in related areas of science while targeting the special needs of biomarker methodology. This document provides a guideline for conducting an extensive literature search on BFIs, which will provide the basis to systematically validate BFIs. This procedure will help to prioritize future work on the identification of new potential biomarkers and on validating these as well as other biomarker candidates, thereby providing better tools for future studies in nutrition and health.

  5. Guidelines for Biomarker of Food Intake Reviews (BFIRev: how to conduct an extensive literature search for biomarker of food intake discovery

    Directory of Open Access Journals (Sweden)

    Giulia Praticò

    2018-02-01

    Full Text Available Abstract Identification of new biomarkers of food and nutrient intake has developed fast over the past two decades and could potentially provide important new tools for compliance monitoring and dietary intake assessment in nutrition and health science. In recent years, metabolomics has played an important role in identifying a large number of putative biomarkers of food intake (BFIs. However, the large body of scientific literature on potential BFIs outside the metabolomics area should also be taken into account. In particular, we believe that extensive literature reviews should be conducted and that the quality of all suggested biomarkers should be systematically evaluated. In order to cover the literature on BFIs in the most appropriate and consistent manner, there is a need for appropriate guidelines on this topic. These guidelines should build upon guidelines in related areas of science while targeting the special needs of biomarker methodology. This document provides a guideline for conducting an extensive literature search on BFIs, which will provide the basis to systematically validate BFIs. This procedure will help to prioritize future work on the identification of new potential biomarkers and on validating these as well as other biomarker candidates, thereby providing better tools for future studies in nutrition and health.

  6. Identification of plasma biomarker candidates in glioblastoma using an antibody-array-based proteomic approach

    International Nuclear Information System (INIS)

    Zupancic, Klemen; Blejec, Andrej; Herman, Ana; Veber, Matija; Verbovsek, Urska; Korsic, Marjan; Knezevic, Miomir; Rozman, Primoz; Turnsek, Tamara Lah; Gruden, Kristina; Motaln, Helena

    2014-01-01

    Glioblastoma multiforme (GBM) is a brain tumour with a very high patient mortality rate, with a median survival of 47 weeks. This might be improved by the identification of novel diagnostic, prognostic and predictive therapy-response biomarkers, preferentially through the monitoring of the patient blood. The aim of this study was to define the impact of GBM in terms of alterations of the plasma protein levels in these patients. We used a commercially available antibody array that includes 656 antibodies to analyse blood plasma samples from 17 healthy volunteers in comparison with 17 blood plasma samples from patients with GBM. We identified 11 plasma proteins that are statistically most strongly associated with the presence of GBM. These proteins belong to three functional signalling pathways: T-cell signalling and immune responses; cell adhesion and migration; and cell-cycle control and apoptosis. Thus, we can consider this identified set of proteins as potential diagnostic biomarker candidates for GBM. In addition, a set of 16 plasma proteins were significantly associated with the overall survival of these patients with GBM. Guanine nucleotide binding protein alpha (GNAO1) was associated with both GBM presence and survival of patients with GBM. Antibody array analysis represents a useful tool for the screening of plasma samples for potential cancer biomarker candidates in small-scale exploratory experiments; however, clinical validation of these candidates requires their further evaluation in a larger study on an independent cohort of patients

  7. Evaluation of candidate biomarkers to predict cancer cell sensitivity or resistance to PARP-1 inhibitor treatment

    DEFF Research Database (Denmark)

    Oplustilova, L.; Wolanin, K.; Bartkova, J.

    2012-01-01

    combinations with camptothecin or ionizing radiation. Furthermore, monitoring pARsylation and Rad51 foci formation as surrogate markers for PARP activity and HR, respectively, supported their candidacy for biomarkers of PARP-1i responses. As to resistance mechanisms, we confrmed the role of the multidrug......(ADp-ribose) polymerase-1 (PARP-1), an enzyme critical for repair pathways alternative to HR. While promising, treatment with PARP-1 inhibitors (PARP-1i) faces some hurdles, including (1) acquired resistance, (2) search for other sensitizing, non-BRCA1/2 cancer defects and (3) lack of biomarkers to predict response...

  8. Searching for Clinically Relevant Biomarkers in Geriatric Oncology.

    Science.gov (United States)

    Katsila, Theodora; Patrinos, George P; Kardamakis, Dimitrios

    2018-01-01

    Ageing, which is associated with a progressive decline and functional deterioration in multiple organ systems, is highly heterogeneous, both inter- and intraindividually. For this, tailored-made theranostics and optimum patient stratification become fundamental, when decision-making in elderly patients is considered. In particular, when cancer incidence and cancer-related mortality and morbidity are taken into account, elderly patient care is a public health concern. In this review, we focus on oncogeriatrics and highlight current opportunities and challenges with an emphasis on the unmet need of clinically relevant biomarkers in elderly cancer patients. We performed a literature search on PubMed and Scopus databases for articles published in English between 2000 and 2017 coupled to text mining and analysis. Considering the top insights, we derived from our literature analysis that information knowledge needs to turn into knowledge growth in oncogeriatrics towards clinically relevant biomarkers, cost-effective practices, updated educational schemes for health professionals (in particular, geriatricians and oncologists), and awareness of ethical issues. We conclude with an interdisciplinary call to omics, geriatricians, oncologists, informatics, and policy-makers communities that Big Data should be translated into decision-making in the clinic.

  9. Secure searching of biomarkers through hybrid homomorphic encryption scheme.

    Science.gov (United States)

    Kim, Miran; Song, Yongsoo; Cheon, Jung Hee

    2017-07-26

    As genome sequencing technology develops rapidly, there has lately been an increasing need to keep genomic data secure even when stored in the cloud and still used for research. We are interested in designing a protocol for the secure outsourcing matching problem on encrypted data. We propose an efficient method to securely search a matching position with the query data and extract some information at the position. After decryption, only a small amount of comparisons with the query information should be performed in plaintext state. We apply this method to find a set of biomarkers in encrypted genomes. The important feature of our method is to encode a genomic database as a single element of polynomial ring. Since our method requires a single homomorphic multiplication of hybrid scheme for query computation, it has the advantage over the previous methods in parameter size, computation complexity, and communication cost. In particular, the extraction procedure not only prevents leakage of database information that has not been queried by user but also reduces the communication cost by half. We evaluate the performance of our method and verify that the computation on large-scale personal data can be securely and practically outsourced to a cloud environment during data analysis. It takes about 3.9 s to search-and-extract the reference and alternate sequences at the queried position in a database of size 4M. Our solution for finding a set of biomarkers in DNA sequences shows the progress of cryptographic techniques in terms of their capability can support real-world genome data analysis in a cloud environment.

  10. Search for Binary Black Hole Candidates from the VLBI Images of ...

    Indian Academy of Sciences (India)

    2016-01-27

    Jan 27, 2016 ... We have searched the core-jet pairs in the VLBI scales (< 1 kpc), from several VLBI catalogues, and found out 5 possible Binary Black Hole (BBH) candidates. We present here the search results and analyse the candidates preliminarily. We plan to study with multi-band VLBI observation. We also plan to ...

  11. Candidate biomarker discovery and selection for ‘Granny Smith' superficial scald risk management and diagnosis, poster board

    Science.gov (United States)

    Discovery of candidate biomarkers for superficial scald, a peel disorder that develops during storage of susceptible apple cultivars, is part of a larger project aimed at developing biomarker-based risk-management and diagnostic tools for multiple apple postharvest disorders (http://www.tfrec.wsu.ed...

  12. Proteomic candidate biomarkers of drug-induced nephrotoxicity in the rat.

    Directory of Open Access Journals (Sweden)

    Rodney Rouse

    Full Text Available Improved biomarkers of acute nephrotoxicity are coveted by the drug development industry, regulatory agencies, and clinicians. In an effort to identify such biomarkers, urinary peptide profiles of rats treated with two different nephrotoxins were investigated. 493 marker candidates were defined that showed a significant response to cis-platin comparing a cis-platin treated cohort to controls. Next, urine samples from rats that received three consecutive daily doses of 150 or 300 mg/kg gentamicin were examined. 557 potential biomarkers were initially identified; 108 of these gentamicin-response markers showed a clear temporal response to treatment. 39 of the cisplatin-response markers also displayed a clear response to gentamicin. Of the combined 147 peptides, 101 were similarly regulated by gentamicin or cis-platin and 54 could be identified by tandem mass spectrometry. Most were collagen type I and type III fragments up-regulated in response to gentamicin treatment. Based on these peptides, classification models were generated and validated in a longitudinal study. In agreement with histopathology, the observed changes in classification scores were transient, initiated after the first dose, and generally persistent over a period of 10-20 days before returning to control levels. The data support the hypothesis that gentamicin-induced renal toxicity up-regulates protease activity, resulting in an increase in several specific urinary collagen fragments. Urinary proteomic biomarkers identified here, especially those common to both nephrotoxins, may serve as a valuable tool to investigate potential new drug candidates for the risk of nephrotoxicity.

  13. Can interoception improve the pragmatic search for biomarkers in psychiatry?

    Directory of Open Access Journals (Sweden)

    Sahib S Khalsa

    2016-07-01

    Full Text Available Disrupted interoception is a prominent feature of the diagnostic classification of several psychiatric disorders. However, progress in understanding the interoceptive basis of these disorders has been incremental and the application of interoception in clinical treatment is currently limited to panic disorder. To examine the degree to which the scientific community has recognized interoception as a construct of interest, we identified and individually screened all articles published in the English language on interoception and associated root terms in Pubmed, Psychinfo and ISI Web of Knowledge. This search revealed that interoception is a multifaceted process that is being increasingly studied within the fields of psychiatry, psychology, neuroscience and biomedical science. To illustrate the multifaceted nature of interoception we provide a focused review of one of the most commonly studied interoceptive channels, the cardiovascular system, and give a detailed comparison of the most popular methods used to study cardiac interoception. We subsequently review evidence of interoceptive dysfunction in panic disorder, depression, somatic symptom disorders, anorexia nervosa, and bulimia nervosa. For each disorder, we suggest how interoceptive predictions constructed by the brain may erroneously bias individuals to express key symptoms and behaviors, and outline questions that are suitable for the development of neuroscience-based mental health interventions. We conclude that interoception represents a viable avenue for clinical and translational research in psychiatry, with a well-established conceptual framework, a neural basis, measurable biomarkers, interdisciplinary appeal, and transdiagnostic targets for understanding and improving mental health outcomes.

  14. NeuroRDF: semantic integration of highly curated data to prioritize biomarker candidates in Alzheimer's disease.

    Science.gov (United States)

    Iyappan, Anandhi; Kawalia, Shweta Bagewadi; Raschka, Tamara; Hofmann-Apitius, Martin; Senger, Philipp

    2016-07-08

    Neurodegenerative diseases are incurable and debilitating indications with huge social and economic impact, where much is still to be learnt about the underlying molecular events. Mechanistic disease models could offer a knowledge framework to help decipher the complex interactions that occur at molecular and cellular levels. This motivates the need for the development of an approach integrating highly curated and heterogeneous data into a disease model of different regulatory data layers. Although several disease models exist, they often do not consider the quality of underlying data. Moreover, even with the current advancements in semantic web technology, we still do not have cure for complex diseases like Alzheimer's disease. One of the key reasons accountable for this could be the increasing gap between generated data and the derived knowledge. In this paper, we describe an approach, called as NeuroRDF, to develop an integrative framework for modeling curated knowledge in the area of complex neurodegenerative diseases. The core of this strategy lies in the usage of well curated and context specific data for integration into one single semantic web-based framework, RDF. This increases the probability of the derived knowledge to be novel and reliable in a specific disease context. This infrastructure integrates highly curated data from databases (Bind, IntAct, etc.), literature (PubMed), and gene expression resources (such as GEO and ArrayExpress). We illustrate the effectiveness of our approach by asking real-world biomedical questions that link these resources to prioritize the plausible biomarker candidates. Among the 13 prioritized candidate genes, we identified MIF to be a potential emerging candidate due to its role as a pro-inflammatory cytokine. We additionally report on the effort and challenges faced during generation of such an indication-specific knowledge base comprising of curated and quality-controlled data. Although many alternative approaches

  15. A Proteomic Approach Identifies Candidate Early Biomarkers to Predict Severe Dengue in Children.

    Directory of Open Access Journals (Sweden)

    Dang My Nhi

    2016-02-01

    Full Text Available Severe dengue with severe plasma leakage (SD-SPL is the most frequent of dengue severe form. Plasma biomarkers for early predictive diagnosis of SD-SPL are required in the primary clinics for the prevention of dengue death.Among 63 confirmed dengue pediatric patients recruited, hospital based longitudinal study detected six SD-SPL and ten dengue with warning sign (DWS. To identify the specific proteins increased or decreased in the SD-SPL plasma obtained 6-48 hours before the shock compared with the DWS, the isobaric tags for relative and absolute quantification (iTRAQ technology was performed using four patients each group. Validation was undertaken in 6 SD-SPL and 10 DWS patients.Nineteen plasma proteins exhibited significantly different relative concentrations (p<0.05, with five over-expressed and fourteen under-expressed in SD-SPL compared with DWS. The individual protein was classified to either blood coagulation, vascular regulation, cellular transport-related processes or immune response. The immunoblot quantification showed angiotensinogen and antithrombin III significantly increased in SD-SPL whole plasma of early stage compared with DWS subjects. Even using this small number of samples, antithrombin III predicted SD-SPL before shock occurrence with accuracy.Proteins identified here may serve as candidate predictive markers to diagnose SD-SPL for timely clinical management. Since the number of subjects are small, so further studies are needed to confirm all these biomarkers.

  16. Biomarkers Discovery for Colorectal Cancer: A Review on Tumor Endothelial Markers as Perspective Candidates

    Directory of Open Access Journals (Sweden)

    Łukasz Pietrzyk

    2016-01-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer in the world. The early detection of CRC, during the promotion/progression stages, is an enormous challenge for a successful outcome and remains a fundamental problem in clinical approach. Despite the continuous advancement in diagnostic and therapeutic methods, there is a need for discovery of sensitive and specific, noninvasive biomarkers. Tumor endothelial markers (TEMs are associated with tumor-specific angiogenesis and are potentially useful to discriminate between tumor and normal endothelium. The most promising TEMs for oncogenic signaling in CRC appeared to be the TEM1, TEM5, TEM7, and TEM8. Overexpression of TEMs especially TEM1, TEM7, and TEM8 in colorectal tumor tissue compared to healthy tissue suggests their role in tumor blood vessels formation. Thus TEMs appear to be perspective candidates for early detection, monitoring, and treatment of CRC patients. This review provides an update on recent data on tumor endothelial markers and their possible use as biomarkers for screening, diagnosis, and therapy of colorectal cancer patients.

  17. Biomarkers Discovery for Colorectal Cancer: A Review on Tumor Endothelial Markers as Perspective Candidates.

    Science.gov (United States)

    Pietrzyk, Łukasz

    2016-01-01

    Colorectal cancer (CRC) is the third most common cancer in the world. The early detection of CRC, during the promotion/progression stages, is an enormous challenge for a successful outcome and remains a fundamental problem in clinical approach. Despite the continuous advancement in diagnostic and therapeutic methods, there is a need for discovery of sensitive and specific, noninvasive biomarkers. Tumor endothelial markers (TEMs) are associated with tumor-specific angiogenesis and are potentially useful to discriminate between tumor and normal endothelium. The most promising TEMs for oncogenic signaling in CRC appeared to be the TEM1, TEM5, TEM7, and TEM8. Overexpression of TEMs especially TEM1, TEM7, and TEM8 in colorectal tumor tissue compared to healthy tissue suggests their role in tumor blood vessels formation. Thus TEMs appear to be perspective candidates for early detection, monitoring, and treatment of CRC patients. This review provides an update on recent data on tumor endothelial markers and their possible use as biomarkers for screening, diagnosis, and therapy of colorectal cancer patients.

  18. In search of the cancer candidate: can lay epidemiology help?

    Science.gov (United States)

    Macdonald, Sara; Watt, Graham; Macleod, Una

    2013-05-01

    First published in 1991, the ideas embedded in 'Lay epidemiology and the prevention paradox' offered a novel and rational explanation for the lay public's failure to fully engage with the lifestyle messages offered by health educators. During the course of a large ethnographic study in South Wales, Davison and colleagues described the emergence of what they termed the coronary candidate. Candidacy provides a 'cultural mechanism' that facilitates the estimation of risk for coronary heart disease. The model has rarely been applied to other major illnesses. This article presents findings from a study that sought to explore the lay epidemiology model, candidacy and cancer. In a series of in-depth individual interviews, members of the lay public discussed their ideas about cancer, and what emerged was an explanatory hierarchy to account for cancer events. Yet the random and unpredictable nature of cancer was emphasised as well as a general reluctance to accept the idea of cancer candidacy. © 2012 The Authors. Sociology of Health & Illness © 2012 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

  19. LOS ALAMOS: Candidate events in a search for neutrino oscillations

    International Nuclear Information System (INIS)

    Anon.

    1995-01-01

    In the past several years, a number of experiments have searched for neutrino oscillations,where a neutrino of one type (say muon-antineutrinos) spontaneously transforms into a neutrino of another type (say electron antineutrinos). For this phenomenon to occur, neutrinos must be massive and the apparent conservation law of lepton families must be violated. At this time, there is no broadly accepted evidence for neutrino oscillations from a terrestrial experiment. The Liquid Scintillator Neutrino Detector (LSND) experiment (July 1993, page 10) at the Los Alamos Meson Physics facility (LAMPF) is designed to search with high sensitivity for muon-antineutrino electronantineutrino oscillations from positive muon decay at rest. The collaboration consists of groups from the University of California at Riverside, San Diego and Santa Barbara, the University California Intercampus Institute for Research at Particle Accelerators, Embry Riddle Aeronautical University, Linfield College, Los Alamos National Laboratory, Louisiana State University, Louisiana Tech University, the University of New Mexico, Southern University, and Temple University. LAMPF is an intense source of low energy neutrinos due to its 1 mA proton intensity and 800 MeV energy. The neutrino source is well understood because almost all neutrinos arise from positive pion or muon decay; negative muons and pions are readily captured in the iron of the shielding and copper of the beam stop. The production of kaons and heavier mesons is negligible at these energies. The electron-antineutrino rate is calculated to be only 4 x 10 -4 that of muon-antineutrinos in the neutrino energy range between 36 and 52.8 MeV, so that the observation of a significant electronantineutrino rate would be evidence for muon-antineutrino electronantineutrino oscillations. The LSND detector consists of an approximately cylindrical tank 8.3 m long by 5.7 m in diameter. The centre of the detector is 30 m from the neutrino source. On the

  20. Plasma Dihydroceramides Are Diabetes Susceptibility Biomarker Candidates in Mice and Humans

    Directory of Open Access Journals (Sweden)

    Leonore Wigger

    2017-02-01

    Full Text Available Summary: Plasma metabolite concentrations reflect the activity of tissue metabolic pathways and their quantitative determination may be informative about pathogenic conditions. We searched for plasma lipid species whose concentrations correlate with various parameters of glucose homeostasis and susceptibility to type 2 diabetes (T2D. Shotgun lipidomic analysis of the plasma of mice from different genetic backgrounds, which develop a pre-diabetic state at different rates when metabolically stressed, led to the identification of a group of sphingolipids correlated with glucose tolerance and insulin secretion. Quantitative analysis of these and closely related lipids in the plasma of individuals from two population-based prospective cohorts revealed that specific long-chain fatty-acid-containing dihydroceramides were significantly elevated in the plasma of individuals who will progress to diabetes up to 9 years before disease onset. These lipids may serve as early biomarkers of, and help identify, metabolic deregulation in the pathogenesis of T2D. : Wigger et al. find that several sphingolipids in mouse plasma correlate with glucose tolerance and insulin secretion. Quantitative analysis of these and closely related lipids in human plasma from two cohorts reveal that dihydroceramides are significantly elevated in individuals progressing to diabetes, up to 9 years before disease onset. Keywords: diabetes, T2D, ceramides, dihydroceramides, biomarkers, lipidomics, prognostic, mouse, human, high-fat diet, metabolic challenge, glucose intolerance, insulin sensitivity, prospective cohort

  1. Identification of Candidate Biomarkers Associated with Response to Vedolizumab in Inflammatory Bowel Disease.

    Science.gov (United States)

    Boden, Elisa K; Shows, Donna M; Chiorean, Michael V; Lord, James D

    2018-01-25

    Vedolizumab is an anti-α4β7 monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). This exploratory study aimed to identify biomarkers associated with vedolizumab response. Twenty-six IBD patients (15 with Crohn's, 11 with ulcerative or indeterminate colitis) initiating vedolizumab at a single center between 2014 and 2016 underwent sampling of serum and peripheral blood mononuclear cells (PBMCs) before and during vedolizumab therapy. Response was defined as steroid-free improvement in endoscopic score or Harvey-Bradshaw index/simple clinical colitis activity index (reduction greater than 3 or total less than 3). PBMCs were evaluated for immunophenotype and expression of α4β7 integrin on lymphocytes before and during vedolizumab therapy. Serum vedolizumab levels and α4β7 saturation were measured serially after induction. Fourteen out of 26 (54%) patients treated with vedolizumab responded to therapy. Pretreatment α4β7 expression was higher in responders on multiple subsets of T, B, and NK cells, with terminal effector memory (p = .0009 for CD4 and .0043 for CD8) and NK cells (p = .0047) best discriminating between responders and nonresponders. During therapy, log 10 serum vedolizumab levels at trough were higher in responders than nonresponders (p = .0007). Conversely, the percentage of effector memory T cells with free α4β7 at trough was lower in responders than nonresponders (p < .0001). However, loss of α4β7 saturation with vedolizumab was more sensitive to low serum vedolizumab in nonresponders. Pretreatment α4β7 expression and α4β7 receptor saturation during maintenance therapy were identified as candidate biomarkers for vedolizumab response.

  2. Discovery of prognostic biomarker candidates of lacunar infarction by quantitative proteomics of microvesicles enriched plasma.

    Directory of Open Access Journals (Sweden)

    Arnab Datta

    Full Text Available Lacunar infarction (LACI is a subtype of acute ischemic stroke affecting around 25% of all ischemic stroke cases. Despite having an excellent recovery during acute phase, certain LACI patients have poor mid- to long-term prognosis due to the recurrence of vascular events or a decline in cognitive functions. Hence, blood-based biomarkers could be complementary prognostic and research tools.Plasma was collected from forty five patients following a non-disabling LACI along with seventeen matched control subjects. The LACI patients were monitored prospectively for up to five years for the occurrence of adverse outcomes and grouped accordingly (i.e., LACI-no adverse outcome, LACI-recurrent vascular event, and LACI-cognitive decline without any recurrence of vascular events. Microvesicles-enriched fractions isolated from the pooled plasma of four groups were profiled by an iTRAQ-guided discovery approach to quantify the differential proteome. The data have been deposited to the ProteomeXchange with identifier PXD000748. Bioinformatics analysis and data mining revealed up-regulation of brain-specific proteins including myelin basic protein, proteins of coagulation cascade (e.g., fibrinogen alpha chain, fibrinogen beta chain and focal adhesion (e.g., integrin alpha-IIb, talin-1, and filamin-A while albumin was down-regulated in both groups of patients with adverse outcome.This data set may offer important insight into the mechanisms of poor prognosis and provide candidate prognostic biomarkers for validation on larger cohort of individual LACI patients.

  3. HD 91669B: A NEW BROWN DWARF CANDIDATE FROM THE MCDONALD OBSERVATORY PLANET SEARCH

    International Nuclear Information System (INIS)

    Wittenmyer, Robert A.; Endl, Michael; Cochran, William D.; Ramirez, Ivan; MacQueen, Phillip J.; Shetrone, Matthew; Reffert, Sabine

    2009-01-01

    We report the detection of a brown dwarf candidate orbiting the metal-rich K dwarf HD 91669, based on radial-velocity data from the McDonald Observatory Planet Search. HD 91669b is a substellar object in an eccentric orbit (e = 0.45) at a separation of 1.2 AU. The minimum mass of 30.6M Jup places this object firmly within the brown dwarf desert for inclinations i ∼> 23 0 . This is the second rare close-in brown dwarf candidate discovered by the McDonald planet search program.

  4. Searching for new biomarkers in ovarian cancer patients

    DEFF Research Database (Denmark)

    Hentze, Julie L.; Høgdall, Claus; Kjær, Susanne K.

    2017-01-01

    , by predicting which patients will benefit from specific treatment strategies. The Mermaid III project is consisting of 3 parts including “Early detection, screening and long-term survival,” “Biomarkers and/or prognostic markers” and “The infection theory.” The present paper gives an overview of the part...

  5. Integrative analysis of gene expression and DNA methylation using unsupervised feature extraction for detecting candidate cancer biomarkers.

    Science.gov (United States)

    Moon, Myungjin; Nakai, Kenta

    2018-04-01

    Currently, cancer biomarker discovery is one of the important research topics worldwide. In particular, detecting significant genes related to cancer is an important task for early diagnosis and treatment of cancer. Conventional studies mostly focus on genes that are differentially expressed in different states of cancer; however, noise in gene expression datasets and insufficient information in limited datasets impede precise analysis of novel candidate biomarkers. In this study, we propose an integrative analysis of gene expression and DNA methylation using normalization and unsupervised feature extractions to identify candidate biomarkers of cancer using renal cell carcinoma RNA-seq datasets. Gene expression and DNA methylation datasets are normalized by Box-Cox transformation and integrated into a one-dimensional dataset that retains the major characteristics of the original datasets by unsupervised feature extraction methods, and differentially expressed genes are selected from the integrated dataset. Use of the integrated dataset demonstrated improved performance as compared with conventional approaches that utilize gene expression or DNA methylation datasets alone. Validation based on the literature showed that a considerable number of top-ranked genes from the integrated dataset have known relationships with cancer, implying that novel candidate biomarkers can also be acquired from the proposed analysis method. Furthermore, we expect that the proposed method can be expanded for applications involving various types of multi-omics datasets.

  6. Blood-Based Biomarker Candidates of Cerebral Amyloid Using PiB PET in Non-Demented Elderly

    Science.gov (United States)

    Westwood, Sarah; Leoni, Emanuela; Hye, Abdul; Lynham, Steven; Khondoker, Mizanur R.; Ashton, Nicholas J.; Kiddle, Steven J.; Baird, Alison L.; Sainz-Fuertes, Ricardo; Leung, Rufina; Graf, John; Hehir, Cristina Tan; Baker, David; Cereda, Cristina; Bazenet, Chantal; Ward, Malcolm; Thambisetty, Madhav; Lovestone, Simon

    2018-01-01

    Increasingly, clinical trials for Alzheimer’s disease (AD) are being conducted earlier in the disease phase and with biomarker confirmation using in vivo amyloid PET imaging or CSF tau and Aβ measures to quantify pathology. However, making such a pre-clinical AD diagnosis is relatively costly and the screening failure rate is likely to be high. Having a blood-based marker that would reduce such costs and accelerate clinical trials through identifying potential participants with likely pre-clinical AD would be a substantial advance. In order to seek such a candidate biomarker, discovery phase proteomic analyses using 2DGE and gel-free LC-MS/MS for high and low molecular weight analytes were conducted on longitudinal plasma samples collected over a 12-year period from non-demented older individuals who exhibited a range of 11C-PiB PET measures of amyloid load. We then sought to extend our discovery findings by investigating whether our candidate biomarkers were also associated with brain amyloid burden in disease, in an independent cohort. Seven plasma proteins, including A2M, Apo-A1, and multiple complement proteins, were identified as pre-clinical biomarkers of amyloid burden and were consistent across three time points (p biomarker signature indicative of AD pathology at a stage long before the onset of clinical disease manifestation. As in previous studies, acute phase reactants and inflammatory markers dominate this signature. PMID:27031486

  7. Surfactant Protein D is a candidate biomarker for subclinical tobacco smoke-induced lung damage

    DEFF Research Database (Denmark)

    Lock Johansson, Sofie; Tan, Qihua; Holst, Rene

    2014-01-01

    Variation in Surfactant Protein D (SP-D) is associated with lung function in tobacco smoke-induced chronic respiratory disease. We hypothesized that the same association exists in the general population and could be used to identify individuals sensitive to smoke-induced lung damage. The associat......Variation in Surfactant Protein D (SP-D) is associated with lung function in tobacco smoke-induced chronic respiratory disease. We hypothesized that the same association exists in the general population and could be used to identify individuals sensitive to smoke-induced lung damage...... or haplotypes, and expiratory lung function were assessed using twin study methodology and mixed-effects models. Significant inverse associations were evident between sSP-D and the forced expiratory volume in 1 second and forced vital capacity in the presence of current tobacco smoking but not in non...... with lung function measures in interaction with tobacco smoking. The obtained data suggest sSP-D as a candidate biomarker in risk assessments for subclinical tobacco smoke-induced lung damage. The data and derived conclusion warrant confirmation in a longitudinal population following chronic obstructive...

  8. Candidate proteins, metabolites and transcripts in the Biomarkers for Spinal Muscular Atrophy (BforSMA clinical study.

    Directory of Open Access Journals (Sweden)

    Richard S Finkel

    Full Text Available Spinal Muscular Atrophy (SMA is a neurodegenerative motor neuron disorder resulting from a homozygous mutation of the survival of motor neuron 1 (SMN1 gene. The gene product, SMN protein, functions in RNA biosynthesis in all tissues. In humans, a nearly identical gene, SMN2, rescues an otherwise lethal phenotype by producing a small amount of full-length SMN protein. SMN2 copy number inversely correlates with disease severity. Identifying other novel biomarkers could inform clinical trial design and identify novel therapeutic targets.To identify novel candidate biomarkers associated with disease severity in SMA using unbiased proteomic, metabolomic and transcriptomic approaches.A cross-sectional single evaluation was performed in 108 children with genetically confirmed SMA, aged 2-12 years, manifesting a broad range of disease severity and selected to distinguish factors associated with SMA type and present functional ability independent of age. Blood and urine specimens from these and 22 age-matched healthy controls were interrogated using proteomic, metabolomic and transcriptomic discovery platforms. Analyte associations were evaluated against a primary measure of disease severity, the Modified Hammersmith Functional Motor Scale (MHFMS and to a number of secondary clinical measures.A total of 200 candidate biomarkers correlate with MHFMS scores: 97 plasma proteins, 59 plasma metabolites (9 amino acids, 10 free fatty acids, 12 lipids and 28 GC/MS metabolites and 44 urine metabolites. No transcripts correlated with MHFMS.In this cross-sectional study, "BforSMA" (Biomarkers for SMA, candidate protein and metabolite markers were identified. No transcript biomarker candidates were identified. Additional mining of this rich dataset may yield important insights into relevant SMA-related pathophysiology and biological network associations. Additional prospective studies are needed to confirm these findings, demonstrate sensitivity to change with

  9. Seminal plasma as a source of prostate cancer peptide biomarker candidates for detection of indolent and advanced disease.

    Directory of Open Access Journals (Sweden)

    Jochen Neuhaus

    for primary PCa diagnosis. Our findings warrant further prospective validation to confirm the diagnostic potential of identified seminal biomarker candidates.

  10. In search of biomarkers for autism: scientific, social and ethical challenges.

    Science.gov (United States)

    Walsh, Pat; Elsabbagh, Mayada; Bolton, Patrick; Singh, Ilina

    2011-09-20

    There is widespread hope that the discovery of valid biomarkers for autism will both reveal the causes of autism and enable earlier and more targeted methods for diagnosis and intervention. However, growing enthusiasm about recent advances in this area of autism research needs to be tempered by an awareness of the major scientific challenges and the important social and ethical concerns arising from the development of biomarkers and their clinical application. Collaborative approaches involving scientists and other stakeholders must combine the search for valid, clinically useful autism biomarkers with efforts to ensure that individuals with autism and their families are treated with respect and understanding.

  11. Searching for new biomarkers in ovarian cancer patients

    DEFF Research Database (Denmark)

    Hentze, Julie L.; Høgdall, Claus; Kjær, Susanne K.

    2017-01-01

    , will be examined. Relevant microRNAs and DNA methylation patterns will be investigated using array technology. Patient exomes will be fully sequenced, and identified genetic variations will be validated with Next Generation Sequencing. In all cases, data will be correlated with clinical information on the patient...... of cancer and the discovery of new drugs. Moreover, biomarkers are a prerequisite for the development of precision medicine. This study will attack the ovarian cancer problem from several angles, thereby increasing the chance of successfully contributing to saving lives....

  12. Biomarker candidate discovery in Atlantic cod (Gadus morhua) continuously exposed to North Sea produced water from egg to fry

    DEFF Research Database (Denmark)

    Bohne-Kjersem, Anneli; Bache, Nicolai; Meier, Sonnich

    2010-01-01

    were able to compare the induced changes by PW to the mode of action of oestrogens. Changes in the proteome in response to exposure in whole cod fry (approximately 80 days post-hatching, dph) were detected by two-dimensional gel electrophoresis and image analysis and identified by MALDI-ToF-ToF mass...... spectrometry, using a newly developed cod EST database and the NCBI database. Many of the protein changes occurred at low levels (0.01% and 0.1% PW) of exposure, indicating putative biological responses at lower levels than previously detected. Using discriminant analysis, we identified a set of protein...... changes that may be useful as biomarker candidates of produced water (PW) and oestradiol exposure in Atlantic cod fry. The biomarker candidates discovered in this study may, following validation, prove effective as diagnostic tools in monitoring exposure and effects of discharges from the petroleum...

  13. Ongoing search for diagnostic biomarkers in idiopathic normal pressure hydrocephalus.

    Science.gov (United States)

    Tarnaris, Andrew; Toma, Ahmed K; Kitchen, Neil D; Watkins, Laurence D

    2009-12-01

    Idiopathic normal pressure hydrocephalus is a syndrome, which typically has a clinical presentation of gait/balance disturbance, often accompanied by cognitive decline and/or urinary incontinence. Its diagnosis is based on relevant history and clinical examination, appropriate imaging findings and physiological testing. The clinical picture of idiopathic normal pressure hydrocephalus may occasionally be difficult to distinguish from that of Alzheimer's dementia, subcortical ischemic vascular dementia and Parkinson's disease. The aim of this article is to systematically review the literature from the last 29 years in order to identify cerebrospinal fluid (CSF) or imaging biomarkers that may aid in the diagnosis of the syndrome. The authors concluded that no CSF or imaging biomarker is currently fulfilling the criteria required to aid in the diagnosis of the condition. However, a few studies have revealed promising CSF and imaging markers that need to be verified by independent groups. The reasons that the progress in this field has been slow so far is also commented on, as well as steps required to apply the current evidence in the design of future studies within the field.

  14. Prediction potential of candidate biomarker sets identified and validated on gene expression data from multiple datasets

    Directory of Open Access Journals (Sweden)

    Karacali Bilge

    2007-10-01

    learning approaches. These findings are relevant to the use of molecular profiling for the identification of candidate biomarker panels.

  15. The use of mineral crystals as bio-markers in the search for life on Mars

    Science.gov (United States)

    Schwartz, D. E.; Mancinelli, R. L.; Kaneshiro, E. S.

    1992-01-01

    It is proposed that minerals resulting from biologically controlled mineralization processes be utilized as biomarkers because of their favorable qualities. Universal signatures of life (biomarkers) are discussed in terms of their terrestrial forms and hypothetical Martian counterparts including organics, suites of specific inorganic and organic compounds, and isotopic ratios. It is emphasized that minerals produced under biologic control have morphological and isotopic compositions that are not found in their abiotic counterparts. Other biomarkers are not necessarily indicative of biological origin and are therefore unreliable resources for scientific study. Mineral crystals are also stable over long geological periods, and the minerals from Martian fluvial features can therefore be employed to search for fossils and biomarkers of early biological activity.

  16. Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort.

    Science.gov (United States)

    Church, Rachel J; Kullak-Ublick, Gerd A; Aubrecht, Jiri; Bonkovsky, Herbert L; Chalasani, Naga; Fontana, Robert J; Goepfert, Jens C; Hackman, Frances; King, Nicholas M P; Kirby, Simon; Kirby, Patrick; Marcinak, John; Ormarsdottir, Sif; Schomaker, Shelli J; Schuppe-Koistinen, Ina; Wolenski, Francis; Arber, Nadir; Merz, Michael; Sauer, John-Michael; Andrade, Raul J; van Bömmel, Florian; Poynard, Thierry; Watkins, Paul B

    2018-01-22

    Current blood biomarkers are suboptimal in detecting drug-induced liver injury (DILI) and predicting its outcome. We sought to characterize the natural variabilty and performance characteristics of fourteen promising DILI biomarker candidates. Serum or plasma from multiple cohorts of healthy volunteers (n=192 and =81), subjects who safely took potentially hepatotoxic drugs without adverse effects (n=55 and =92) and DILI patients (n=98, =28, and =143) were assayed for microRNA-122 (miR-122), glutamate dehydrogenase (GLDH), total keratin 18 (K18), caspase cleaved K18 (ccK18), glutathione S-transferase alpha (GSTα), alpha fetoprotein (AFP), arginase-1 (ARG1), osteopontin (OPN), sorbitol dehydrogenase (SDH), fatty acid binding protein (FABP1), cadherin-5 (CDH5), macrophage colony stimulating factor receptor (MCSFR), paraoxonase 1 (PON1, normalized to prothrombin protein), and leucocyte cell-derived chemotaxin-2 (LECT2). Most candidate biomarkers were significantly altered in DILI cases compared to healthy volunteers. GLDH correlated more closely with gold standard alanine aminotransferase (ALT) than miR-122 and there was a surprisingly wide inter- and intra-individual variability of miR-122 levels among the healthy volunteers. Serum K18, OPN, and MCSFR levels were most strongly associated with liver-related death or transplant within 6 months of DILI-onset. Prediction of prognosis among DILI patients using Model for End-stage Liver Disease (MELD) was improved by incorporation of K18 and MCSFR levels. GLDH appears to be more useful than miR-122 in identifying DILI patients. K18, OPN and MCSFR are promising candidates for prediction of prognosis during an acute DILI event. Serial assessment of these biomarkers in large prospective studies will help further delineate their role in DILI diagnosis and management. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  17. Quantitative proteomic analysis by iTRAQ® for the identification of candidate biomarkers in ovarian cancer serum

    Directory of Open Access Journals (Sweden)

    Higgins LeeAnn

    2010-06-01

    Full Text Available Abstract Background Ovarian cancer is the most lethal gynecologic malignancy, with the majority of cases diagnosed at an advanced stage when treatments are less successful. Novel serum protein markers are needed to detect ovarian cancer in its earliest stage; when detected early, survival rates are over 90%. The identification of new serum biomarkers is hindered by the presence of a small number of highly abundant proteins that comprise approximately 95% of serum total protein. In this study, we used pooled serum depleted of the most highly abundant proteins to reduce the dynamic range of proteins, and thereby enhance the identification of serum biomarkers using the quantitative proteomic method iTRAQ®. Results Medium and low abundance proteins from 6 serum pools of 10 patients each from women with serous ovarian carcinoma, and 6 non-cancer control pools were labeled with isobaric tags using iTRAQ® to determine the relative abundance of serum proteins identified by MS. A total of 220 unique proteins were identified and fourteen proteins were elevated in ovarian cancer compared to control serum pools, including several novel candidate ovarian cancer biomarkers: extracellular matrix protein-1, leucine-rich alpha-2 glycoprotein-1, lipopolysaccharide binding protein-1, and proteoglycan-4. Western immunoblotting validated the relative increases in serum protein levels for several of the proteins identified. Conclusions This study provides the first analysis of immunodepleted serum in combination with iTRAQ® to measure relative protein expression in ovarian cancer patients for the pursuit of serum biomarkers. Several candidate biomarkers were identified which warrant further development.

  18. Cross-study and cross-omics comparisons of three nephrotoxic compounds reveal mechanistic insights and new candidate biomarkers

    International Nuclear Information System (INIS)

    Matheis, Katja A.; Com, Emmanuelle; Gautier, Jean-Charles; Guerreiro, Nelson; Brandenburg, Arnd; Gmuender, Hans; Sposny, Alexandra; Hewitt, Philip; Amberg, Alexander; Boernsen, Olaf; Riefke, Bjoern; Hoffmann, Dana; Mally, Angela; Kalkuhl, Arno; Suter, Laura; Dieterle, Frank; Staedtler, Frank

    2011-01-01

    The European InnoMed-PredTox project was a collaborative effort between 15 pharmaceutical companies, 2 small and mid-sized enterprises, and 3 universities with the goal of delivering deeper insights into the molecular mechanisms of kidney and liver toxicity and to identify mechanism-linked diagnostic or prognostic safety biomarker candidates by combining conventional toxicological parameters with 'omics' data. Mechanistic toxicity studies with 16 different compounds, 2 dose levels, and 3 time points were performed in male Crl: WI(Han) rats. Three of the 16 investigated compounds, BI-3 (FP007SE), Gentamicin (FP009SF), and IMM125 (FP013NO), induced kidney proximal tubule damage (PTD). In addition to histopathology and clinical chemistry, transcriptomics microarray and proteomics 2D-DIGE analysis were performed. Data from the three PTD studies were combined for a cross-study and cross-omics meta-analysis of the target organ. The mechanistic interpretation of kidney PTD-associated deregulated transcripts revealed, in addition to previously described kidney damage transcript biomarkers such as KIM-1, CLU and TIMP-1, a number of additional deregulated pathways congruent with histopathology observations on a single animal basis, including a specific effect on the complement system. The identification of new, more specific biomarker candidates for PTD was most successful when transcriptomics data were used. Combining transcriptomics data with proteomics data added extra value.

  19. Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

    Science.gov (United States)

    Coiffier, Bertrand; Li, Weimin; Henitz, Erin D; Karkera, Jayaprakash D; Favis, Reyna; Gaffney, Dana; Shapiro, Alice; Theocharous, Panteli; Elsayed, Yusri A; van de Velde, Helgi; Schaffer, Michael E; Osmanov, Evgenii A; Hong, Xiaonan; Scheliga, Adriana; Mayer, Jiri; Offner, Fritz; Rule, Simon; Teixeira, Adriana; Romejko-Jarosinska, Joanna; de Vos, Sven; Crump, Michael; Shpilberg, Ofer; Zinzani, Pier Luigi; Cakana, Andrew; Esseltine, Dixie-Lee; Mulligan, George; Ricci, Deborah

    2013-05-01

    Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G allele, low CD68 expression (≤50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab. ©2013 AACR.

  20. A Selected Reaction Monitoring Mass Spectrometry Protocol for Validation of Proteomic Biomarker Candidates in Studies of Psychiatric Disorders.

    Science.gov (United States)

    Reis-de-Oliveira, Guilherme; Garcia, Sheila; Guest, Paul C; Cassoli, Juliana S; Martins-de-Souza, Daniel

    2017-01-01

    Most biomarker candidates arising from proteomic studies of psychiatric disorders have not progressed for use in clinical studies due to insufficient validation steps. Here we describe a selective reaction monitoring mass spectrometry (SRM-MS) approach that could be used as a follow-up validation tool of proteins identified in blood serum or plasma. This protocol specifically covers the stages of peptide selection and optimization. The increasing application of SRM-MS should enable fast, sensitive, and robust methods with the potential for use in clinical studies involving sampling of serum or plasma. Understanding the molecular mechanisms and identifying potential biomarkers for risk assessment, diagnosis, prognosis, and prediction of drug response goes toward the implementation of translational medicine strategies for improved treatment of patients with psychiatric disorders and other debilitating diseases.

  1. Proteomics analysis after traumatic brain injury in rats: the search for potential biomarkers

    Directory of Open Access Journals (Sweden)

    Jun Ding

    2015-04-01

    Full Text Available Many studies of protein expression after traumatic brain injury (TBI have identified biomarkers for diagnosing or determining the prognosis of TBI. In this study, we searched for additional protein markers of TBI using a fluid perfusion impact device to model TBI in S-D rats. Two-dimensional gel electrophoresis and mass spectrometry were used to identify differentially expressed proteins. After proteomic analysis, we detected 405 and 371 protein spots within a pH range of 3-10 from sham-treated and contused brain cortex, respectively. Eighty protein spots were differentially expressed in the two groups and 20 of these proteins were identified. This study validated the established biomarkers of TBI and identified potential biomarkers that could be examined in future work.

  2. Quantitative iTRAQ-Based Proteomic Identification of Candidate Biomarkers for Diabetic Nephropathy in Plasma of Type 1 Diabetic Patients

    DEFF Research Database (Denmark)

    Overgaard, Anne Julie; Thingholm, Tine Engberg; Larsen, Martin R

    2010-01-01

    INTRODUCTION: As part of a clinical proteomics programme focused on diabetes and its complications, it was our goal to investigate the proteome of plasma in order to find improved candidate biomarkers to predict diabetic nephropathy. METHODS: Proteins derived from plasma from a cross-sectional co...... nephropathy; however, they need to be confirmed in a longitudinal cohort. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12014-010-9053-0) contains supplementary material, which is available to authorized users....

  3. Upper-Lower Bounds Candidate Sets Searching Algorithm for Bayesian Network Structure Learning

    Directory of Open Access Journals (Sweden)

    Guangyi Liu

    2014-01-01

    Full Text Available Bayesian network is an important theoretical model in artificial intelligence field and also a powerful tool for processing uncertainty issues. Considering the slow convergence speed of current Bayesian network structure learning algorithms, a fast hybrid learning method is proposed in this paper. We start with further analysis of information provided by low-order conditional independence testing, and then two methods are given for constructing graph model of network, which is theoretically proved to be upper and lower bounds of the structure space of target network, so that candidate sets are given as a result; after that a search and scoring algorithm is operated based on the candidate sets to find the final structure of the network. Simulation results show that the algorithm proposed in this paper is more efficient than similar algorithms with the same learning precision.

  4. Searching for white dwarfs candidates in Sloan Digital Sky Survey Data

    International Nuclear Information System (INIS)

    Nalezyty, Miroslaw; Majczyna, Agnieszka; Ciechanowska, Anna; Madej, Jerzy

    2009-01-01

    Large amount of observational spectroscopic data are recently available from different observational projects, like Sloan Digital Sky Survey. It's become more urgent to identify white dwarfs stars based on data itself i.e. without modelling white dwarf atmospheres. In particular, existing methods of white dwarfs identification presented in Kleinman et al. (2004) and in Eisenstein et al. (2006) did not allow to find all the white dwarfs in examined data. We intend to test various criteria of searching for white dwarf candidates, based on photometric and spectral features.

  5. Urinary and Blood MicroRNA-126 and -770 are Potential Noninvasive Biomarker Candidates for Diabetic Nephropathy: a Meta-Analysis.

    Science.gov (United States)

    Park, Sungjin; Moon, SeongRyeol; Lee, Kiyoung; Park, Ie Byung; Lee, Dae Ho; Nam, Seungyoon

    2018-01-01

    Diabetic nephropathy (DN), a major diabetic microvascular complication, has a long and growing list of biomarkers, including microRNA biomarkers, which have not been consistent across preclinical and clinical studies. This meta-analysis aims to identify significant blood- and urine-incident microRNAs as diagnostic/prognostic biomarker candidates for DN. PubMed, Web of Science, and Cochrane Library were searched from their earliest records through 12th Dec 2016. Relevant publications for the meta-analysis included (1) human participants; (2) microRNAs in blood and urine; (3) DN studies; and (4) English language. Four reviewers, including two physicians, independently and blindly extracted published data regarding microRNA profiles in blood and/or urine from subjects with diabetic nephropathy. A random-effect model was used to pool the data. Statistical associations between diabetic nephropathy and urinary or blood microRNA expression levels were assessed. Fourteen out of 327 studies (n=2,747 patients) were selected. Blood or urinary microRNA expression data of diabetic nephropathy were pooled for this analysis. The hsa-miR-126 family was significantly (OR: 0.57; 95% CI: 0.44-0.74; p-value diabetic kidney disease, while its urinary level was upregulated (OR: 2931.12; 95% CI: 9.96-862623.21; p-value = 0.0059). The hsa-miR-770 family microRNA were significantly (OR: 10.24; 95% CI: 2.37-44.25; p-value = 0.0018) upregulated in both blood and urine from patients with diabetic nephropathy. Our meta-analysis suggests that hsa-miR-126 and hsa-miR-770 family microRNA may have important diagnostic and pathogenetic implications for DN, which warrants further systematic clinical studies. © 2018 The Author(s). Published by S. Karger AG, Basel.

  6. Is there Progress? An Overview of Selecting Biomarker Candidates for Major Depressive Disorder

    Science.gov (United States)

    Young, Juan Joseph; Silber, Tim; Bruno, Davide; Galatzer-Levy, Isaac Robert; Pomara, Nunzio; Marmar, Charles Raymond

    2016-01-01

    Major depressive disorder (MDD) contributes to a significant worldwide disease burden, expected to be second only to heart disease by 2050. However, accurate diagnosis has been a historical weakness in clinical psychiatry. As a result, there is a demand for diagnostic modalities with greater objectivity that could improve on current psychiatric practice that relies mainly on self-reporting of symptoms and clinical interviews. Over the past two decades, literature on a growing number of putative biomarkers for MDD increasingly suggests that MDD patients have significantly different biological profiles compared to healthy controls. However, difficulty in elucidating their exact relationships within depression pathology renders individual markers inconsistent diagnostic tools. Consequently, further biomarker research could potentially improve our understanding of MDD pathophysiology as well as aid in interpreting response to treatment, narrow differential diagnoses, and help refine current MDD criteria. Representative of this, multiplex assays using multiple sources of biomarkers are reported to be more accurate options in comparison to individual markers that exhibit lower specificity and sensitivity, and are more prone to confounding factors. In the future, more sophisticated multiplex assays may hold promise for use in screening and diagnosing depression and determining clinical severity as an advance over relying solely on current subjective diagnostic criteria. A pervasive limitation in existing research is heterogeneity inherent in MDD studies, which impacts the validity of biomarker data. Additionally, small sample sizes of most studies limit statistical power. Yet, as the RDoC project evolves to decrease these limitations, and stronger studies with more generalizable data are developed, significant advances in the next decade are expected to yield important information in the development of MDD biomarkers for use in clinical settings. PMID:27199779

  7. Translational database selection and multiplexed sequence capture for up front filtering of reliable breast cancer biomarker candidates.

    Directory of Open Access Journals (Sweden)

    Patrik L Ståhl

    Full Text Available Biomarker identification is of utmost importance for the development of novel diagnostics and therapeutics. Here we make use of a translational database selection strategy, utilizing data from the Human Protein Atlas (HPA on differentially expressed protein patterns in healthy and breast cancer tissues as a means to filter out potential biomarkers for underlying genetic causatives of the disease. DNA was isolated from ten breast cancer biopsies, and the protein coding and flanking non-coding genomic regions corresponding to the selected proteins were extracted in a multiplexed format from the samples using a single DNA sequence capture array. Deep sequencing revealed an even enrichment of the multiplexed samples and a great variation of genetic alterations in the tumors of the sampled individuals. Benefiting from the upstream filtering method, the final set of biomarker candidates could be completely verified through bidirectional Sanger sequencing, revealing a 40 percent false positive rate despite high read coverage. Of the variants encountered in translated regions, nine novel non-synonymous variations were identified and verified, two of which were present in more than one of the ten tumor samples.

  8. A proteomic analysis identifies candidate early biomarkers to predict ovarian hyperstimulation syndrome in polycystic ovarian syndrome patients.

    Science.gov (United States)

    Wu, Lan; Sun, Yazhou; Wan, Jun; Luan, Ting; Cheng, Qing; Tan, Yong

    2017-07-01

    Ovarian hyperstimulation syndrome (OHSS) is a potentially life‑threatening, iatrogenic complication that occurs during assisted reproduction. Polycystic ovarian syndrome (PCOS) significantly increases the risk of OHSS during controlled ovarian stimulation. Therefore, a more effective early prediction technique is required in PCOS patients. Quantitative proteomic analysis of serum proteins indicates the potential diagnostic value for disease. In the present study, the authors revealed the differentially expressed proteins in OHSS patients with PCOS as new diagnostic biomarkers. The promising proteins obtained from liquid chromatography‑mass spectrometry were subjected to ELISA and western blotting assay for further confirmation. A total of 57 proteins were identified with significant difference, of which 29 proteins were upregulated and 28 proteins were downregulated in OHSS patients. Haptoglobin, fibrinogen and lipoprotein lipase were selected as candidate biomarkers. Receiver operating characteristic curve analysis demonstrated all three proteins may have potential as biomarkers to discriminate OHSS in PCOS patients. Haptoglobin, fibrinogen and lipoprotein lipase have never been reported as a predictive marker of OHSS in PCOS patients, and their potential roles in OHSS occurrence deserve further studies. The proteomic results reported in the present study may gain deeper insights into the pathophysiology of OHSS.

  9. The MCP-4/MCP-1 ratio in plasma is a candidate circadian biomarker for chronic post-traumatic stress disorder

    Science.gov (United States)

    Dalgard, C; Eidelman, O; Jozwik, C; Olsen, C H; Srivastava, M; Biswas, R; Eudy, Y; Rothwell, S W; Mueller, G P; Yuan, P; Drevets, W C; Manji, H K; Vythlingam, M; Charney, D S; Neumeister, A; Ursano, R J; Jacobowitz, D M; Pollard, H B; Bonne, O

    2017-01-01

    Post-traumatic stress disorder (PTSD) is psychiatric disease, which can occur following exposure to traumatic events. PTSD may be acute or chronic, and can have a waxing and waning course of symptoms. It has been hypothesized that proinflammatory cytokines and chemokines in the cerebrospinal fluid (CSF) or plasma might be mediators of the psychophysiological mechanisms relating a history of trauma exposure to changes in behavior and mental health disorders, and medical morbidity. Here we test the cytokine/chemokine hypothesis for PTSD by examining levels of 17 classical cytokines and chemokines in CSF, sampled at 0900 hours, and in plasma sampled hourly for 24 h. The PTSD and healthy control patients are from the NIMH Chronic PTSD and healthy control cohort, initially described by Bonne et al. (2011), in which the PTSD patients have relatively low comorbidity for major depressive disorder (MDD), drug or alcohol use. We find that in plasma, but not CSF, the bivariate MCP4 (CCL13)/ MCP1(CCL2) ratio is ca. twofold elevated in PTSD patients compared with healthy controls. The MCP-4/MCP-1 ratio is invariant over circadian time, and is independent of gender, body mass index or the age at which the trauma was suffered. By contrast, MIP-1β is a candidate biomarker for PTSD only in females, whereas TARC is a candidate biomarker for PTSD only in males. It remains to be discovered whether these disease-specific differences in circadian expression for these specific immune signaling molecules are biomarkers, surrogates, or drivers for PTSD, or whether any of these analytes could contribute to therapy. PMID:28170001

  10. Systematic Search for Rings around Kepler Planet Candidates: Constraints on Ring Size and Occurrence Rate

    Science.gov (United States)

    Aizawa, Masataka; Masuda, Kento; Kawahara, Hajime; Suto, Yasushi

    2018-05-01

    We perform a systematic search for rings around 168 Kepler planet candidates with sufficient signal-to-noise ratios that are selected from all of the short-cadence data. We fit ringed and ringless models to their light curves and compare the fitting results to search for the signatures of planetary rings. First, we identify 29 tentative systems, for which the ringed models exhibit statistically significant improvement over the ringless models. The light curves of those systems are individually examined, but we are not able to identify any candidate that indicates evidence for rings. In turn, we find several mechanisms of false positives that would produce ringlike signals, and the null detection enables us to place upper limits on the size of the rings. Furthermore, assuming the tidal alignment between axes of the planetary rings and orbits, we conclude that the occurrence rate of rings larger than twice the planetary radius is less than 15%. Even though the majority of our targets are short-period planets, our null detection provides statistical and quantitative constraints on largely uncertain theoretical models of the origin, formation, and evolution of planetary rings.

  11. Expressed prostatic secretion biomarkers improve stratification of NCCN active surveillance candidates: performance of secretion capacity and TMPRSS2:ERG models.

    Science.gov (United States)

    Whelan, Christopher; Kawachi, Mark; Smith, David D; Linehan, Jennifer; Babilonia, Gail; Mejia, Rosa; Wilson, Timothy; Smith, Steven S

    2014-01-01

    Active surveillance is a viable patient option for prostate cancer provided that a clinical determination of low risk and presumably organ confined disease can be made. To standardize risk stratification schemes the NCCN (National Comprehensive Cancer Network®) provides guidelines for the active surveillance option. We determined the effectiveness of expressed prostatic secretion biomarkers for detecting occult risk factors in NCCN active surveillance candidates. Expressed prostatic secretion specimens were obtained before robot-assisted radical prostatectomy. Secretion capacity biomarkers, including total RNA and expressed prostatic secretion specimen volume, were measured by standard techniques. RNA expression biomarkers, including TXNRD1 mRNA, prostate specific antigen mRNA, TMPRSS2:ERG fusion mRNA and PCA3 mRNA, were measured by quantitative reverse-transcription polymerase chain reaction. Of the 528 patients from whom expressed prostatic secretions were collected 216 were eligible for active surveillance under NCCN guidelines. Variable selection on logistic regression identified 2 models, including one featuring types III and VI TMPRSS2:ERG variants, and one featuring 2 secretion capacity biomarkers. Of the 2 high performing models the secretion capacity model was most effective for detecting cases in this group that were up-staged or up-staged plus upgraded. It decreased the risk of up-staging in patients with a negative test almost eightfold and decreased the risk of up-staging plus upgrading about fivefold while doubling the prevalence of up-staging in the positive test group. Noninvasive expressed prostatic secretion testing may improve patient acceptance of active surveillance by dramatically reducing the presence of occult risk factors among those eligible for active surveillance under NCCN guidelines. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  12. Identification of 10 Candidate Biomarkers Distinguishing Tuberculous and Malignant Pleural Fluid by Proteomic Methods

    OpenAIRE

    Lee, Chang Youl; Hong, Ji Young; Lee, Myung-Goo; Suh, In-Bum

    2017-01-01

    Purpose Pleural effusion, an accumulation of fluid in the pleural space, usually occurs in patients when the rate of fluid formation exceeds the rate of fluid removal. The differential diagnosis of tuberculous pleurisy and malignant pleural effusion is a difficult task in high tuberculous prevalence areas. The aim of the present study was to identify novel biomarkers for the diagnosis of pleural fluid using proteomics technology. Materials and Methods We used samples from five patients with t...

  13. Identification of candidate diagnostic serum biomarkers for Kawasaki disease using proteomic analysis

    Science.gov (United States)

    Kimura, Yayoi; Yanagimachi, Masakatsu; Ino, Yoko; Aketagawa, Mao; Matsuo, Michie; Okayama, Akiko; Shimizu, Hiroyuki; Oba, Kunihiro; Morioka, Ichiro; Imagawa, Tomoyuki; Kaneko, Tetsuji; Yokota, Shumpei; Hirano, Hisashi; Mori, Masaaki

    2017-01-01

    Kawasaki disease (KD) is a systemic vasculitis and childhood febrile disease that can lead to cardiovascular complications. The diagnosis of KD depends on its clinical features, and thus it is sometimes difficult to make a definitive diagnosis. In order to identify diagnostic serum biomarkers for KD, we explored serum KD-related proteins, which differentially expressed during the acute and recovery phases of two patients by mass spectrometry (MS). We identified a total of 1,879 proteins by MS-based proteomic analysis. The levels of three of these proteins, namely lipopolysaccharide-binding protein (LBP), leucine-rich alpha-2-glycoprotein (LRG1), and angiotensinogen (AGT), were higher in acute phase patients. In contrast, the level of retinol-binding protein 4 (RBP4) was decreased. To confirm the usefulness of these proteins as biomarkers, we analyzed a total of 270 samples, including those collected from 55 patients with acute phase KD, by using western blot analysis and microarray enzyme-linked immunosorbent assays (ELISAs). Over the course of this experiment, we determined that the expression level of these proteins changes specifically in the acute phase of KD, rather than the recovery phase of KD or other febrile illness. Thus, LRG1 could be used as biomarkers to facilitate KD diagnosis based on clinical features. PMID:28262744

  14. Building a gold standard to construct search filters: a case study with biomarkers for oral cancer.

    Science.gov (United States)

    Frazier, John J; Stein, Corey D; Tseytlin, Eugene; Bekhuis, Tanja

    2015-01-01

    To support clinical researchers, librarians and informationists may need search filters for particular tasks. Development of filters typically depends on a "gold standard" dataset. This paper describes generalizable methods for creating a gold standard to support future filter development and evaluation using oral squamous cell carcinoma (OSCC) as a case study. OSCC is the most common malignancy affecting the oral cavity. Investigation of biomarkers with potential prognostic utility is an active area of research in OSCC. The methods discussed here should be useful for designing quality search filters in similar domains. The authors searched MEDLINE for prognostic studies of OSCC, developed annotation guidelines for screeners, ran three calibration trials before annotating the remaining body of citations, and measured inter-annotator agreement (IAA). We retrieved 1,818 citations. After calibration, we screened the remaining citations (n = 1,767; 97.2%); IAA was substantial (kappa = 0.76). The dataset has 497 (27.3%) citations representing OSCC studies of potential prognostic biomarkers. The gold standard dataset is likely to be high quality and useful for future development and evaluation of filters for OSCC studies of potential prognostic biomarkers. The methodology we used is generalizable to other domains requiring a reference standard to evaluate the performance of search filters. A gold standard is essential because the labels regarding relevance enable computation of diagnostic metrics, such as sensitivity and specificity. Librarians and informationists with data analysis skills could contribute to developing gold standard datasets and subsequent filters tuned for their patrons' domains of interest.

  15. The search for neuroimaging biomarkers of Alzheimer's disease with advanced MRI techniques

    Energy Technology Data Exchange (ETDEWEB)

    Li, Tie-Qiang (Karolinska Huddinge - Medical Physics, Stockholm (Sweden)), email: tieqiang.li@karolinska.se; Wahlund, Lars-Olof (Dept. of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm (Sweden))

    2011-02-15

    The aim of this review is to examine the recent literature on using advanced magnetic resonance imaging (MRI) techniques for finding neuroimaging biomarkers that are sensitive to the detection of risks for Alzheimer's disease (AD). Since structural MRI techniques, such as brain structural volumetry and voxel based morphometry (VBM), have been widely used for AD studies and extensively reviewed, we will only briefly touch on the topics of volumetry and morphometry. The focus of the current review is about the more recent developments in the search for AD neuroimaging biomarkers with functional MRI (fMRI), resting-state functional connectivity MRI (fcMRI), diffusion tensor imaging (DTI), arterial spin-labeling (ASL), and magnetic resonance spectroscopy (MRS)

  16. The search for neuroimaging biomarkers of Alzheimer's disease with advanced MRI techniques

    International Nuclear Information System (INIS)

    Li, Tie-Qiang; Wahlund, Lars-Olof

    2011-01-01

    The aim of this review is to examine the recent literature on using advanced magnetic resonance imaging (MRI) techniques for finding neuroimaging biomarkers that are sensitive to the detection of risks for Alzheimer's disease (AD). Since structural MRI techniques, such as brain structural volumetry and voxel based morphometry (VBM), have been widely used for AD studies and extensively reviewed, we will only briefly touch on the topics of volumetry and morphometry. The focus of the current review is about the more recent developments in the search for AD neuroimaging biomarkers with functional MRI (fMRI), resting-state functional connectivity MRI (fcMRI), diffusion tensor imaging (DTI), arterial spin-labeling (ASL), and magnetic resonance spectroscopy (MRS)

  17. Heptadecanoylcarnitine (C17) a novel candidate biomarker for propionic and methylmalonic acidemias during expanded newborn screening

    Science.gov (United States)

    Malvagia, Sabrina; Haynes, Christopher A.; Grisotto, Laura; Ombrone, Daniela; Funghini, Silvia; Moretti, Elisa; McGreevy, Kathleen; Buggeri, Annibale; Guerrini, Renzo; Yahyaoui, Raquel; Garg, Uttam; Seeterlin, Mary; Chace, Donald; De Jesus, Victor; la Marca, Giancarlo

    2017-01-01

    Background 3-hydroxypalmitoleoyl-carnitine (C16:1-OH) was recently reported to be elevated in acylcarnitine profile of propionic acidemia (PA) or methylmalonic acidemia (MMA) patients during expanded newborn screening (NBS). High levels of C16:1-OH, combined with other hydroxylated long chain acylcarnitines are related to long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). Methods The acylcarnitine profile of two LCHADD patients was evaluated using liquid chromatography-tandem mass spectrometric method. A specific retention time was reported for each hydroxylated long chain acylcarnitine. The same method was applied to some neonatal dried blood spots (DBS) from PA and MMA patients presenting abnormal C16:1-OH concentrations. Results The final retention time of the peak corresponding to C16:1-OH in LCHADD patients differed from those in MMA and PA patients. Heptadecanoylcarnitine (C17) has been identified as the novel biomarker specific for PA and MMA patients through high resolution mass spectrometry (Orbitrap) experiments. We found that 21 out of 23 neonates (22 MMA, and 1PA) diagnosed through the Tuscany region NBS program had significantly higher levels of C17 compared to levels detected in controls. Twenty-three maternal deficiencies (21 vitamin B12 deficiency, 1 homocystinuria and 1 gastrin deficiency) and 82 false positive for propionylcarnitine (C3) results were also analyzed. Conclusions This paper reports on the characterization of a novel biomarker able to detect propionate disorders during expanded newborn screening (NBS). The use of this new biomarker may improve the analytical performances of NBS programs especially in laboratories where second tier tests are not performed. PMID:26368264

  18. Heptadecanoylcarnitine (C17) a novel candidate biomarker for newborn screening of propionic and methylmalonic acidemias.

    Science.gov (United States)

    Malvagia, Sabrina; Haynes, Christopher A; Grisotto, Laura; Ombrone, Daniela; Funghini, Silvia; Moretti, Elisa; McGreevy, Kathleen S; Biggeri, Annibale; Guerrini, Renzo; Yahyaoui, Raquel; Garg, Uttam; Seeterlin, Mary; Chace, Donald; De Jesus, Victor R; la Marca, Giancarlo

    2015-10-23

    3-Hydroxypalmitoleoyl-carnitine (C16:1-OH) has recently been reported to be elevated in acylcarnitine profiles of patients with propionic acidemia (PA) or methylmalonic acidemia (MMA) during expanded newborn screening (NBS). High levels of C16:1-OH, combined with other hydroxylated long chain acylcarnitines are related to long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and trifunctional protein (TFP) deficiency. The acylcarnitine profile of two LCHADD patients was evaluated using liquid chromatography-tandem mass spectrometric method. A specific retention time was determined for each hydroxylated long chain acylcarnitine. The same method was applied to some neonatal dried blood spots (DBSs) from PA and MMA patients presenting abnormal C16:1-OH concentrations. The retention time of the peak corresponding to C16:1-OH in LCHADD patients differed from those in MMA and PA patients. Heptadecanoylcarnitine (C17) has been identified as the novel biomarker specific for PA and MMA patients through high resolution mass spectrometry (Orbitrap) experiments. We found that 21 out of 23 neonates (22 MMA, and 1PA) diagnosed through the Tuscany region NBS program exhibited significantly higher levels of C17 compared to controls. Twenty-three maternal deficiency (21 vitamin B12 deficiency, 1 homocystinuria and 1 gastrin deficiency) samples and 82 false positive for elevated propionylcarnitine (C3) were also analyzed. We have characterized a novel biomarker able to detect propionate disorders during expanded newborn screening (NBS). The use of this new biomarker may improve the analytical performances of NBS programs especially in laboratories where second tier tests are not performed. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Identification of a candidate biomarker from perfusion MRI to anticipate glioblastoma progression after chemoradiation

    Energy Technology Data Exchange (ETDEWEB)

    Khalifa, J. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Radiation Oncology, Toulouse (France); Tensaouti, F. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); Chaltiel, L. [Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Biostatistics, Toulouse (France); Lotterie, J.A. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); CHU Rangueil, Department of Nuclear Medicine, Toulouse (France); Catalaa, I. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); CHU Rangueil, Department of Radiology, Toulouse (France); Sunyach, M.P. [Centre Leon Berard, Department of Radiation Oncology, Lyon (France); Ibarrola, D. [CERMEP - Imagerie du Vivant, Lyon (France); Noel, G. [EA 3430, University of Strasbourg, Department of Radiation Oncology, Centre Paul Strauss, Strasbourg (France); Truc, G. [Centre Georges-Francois Leclerc, Department of Radiation Oncology, Dijon (France); Walker, P. [University of Burgundy, Laboratory of Electronics, Computer Science and Imaging (Le2I), UMR 6306 CNRS, Dijon (France); Magne, N. [Institut de cancerologie Lucien-Neuwirth, Department of Radiation Oncology, Saint-Priest-en-Jarez (France); Charissoux, M. [Department of Radiation Oncology, Institut du Cancer de Montpellier, Montpellier (France); Ken, S. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Medical Physics, Toulouse (France); Peran, P. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); Universite Toulouse III Paul Sabatier, UMR 1214, Toulouse (France); Berry, I. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); CHU Rangueil, Department of Nuclear Medicine, Toulouse (France); Universite Toulouse III Paul Sabatier, UMR 1214, Toulouse (France); Moyal, E.C. [Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Radiation Oncology, Toulouse (France); Universite Toulouse III Paul Sabatier, Toulouse (France); INSERM U1037, Centre de Recherches contre le Cancer de Toulouse, Toulouse (FR); Laprie, A. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (FR); Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Radiation Oncology, Toulouse (FR); Universite Toulouse III Paul Sabatier, Toulouse (FR)

    2016-11-15

    To identify relevant relative cerebral blood volume biomarkers from T2* dynamic-susceptibility contrast magnetic resonance imaging to anticipate glioblastoma progression after chemoradiation. Twenty-five patients from a prospective study with glioblastoma, primarily treated by chemoradiation, were included. According to the last follow-up MRI confirmed status, patients were divided into: relapse group (n = 13) and control group (n = 12). The time of last MR acquisition was t{sub end}; MR acquisitions performed at t{sub end-2M}, t{sub end-4M} and t{sub end-6M} (respectively 2, 4 and 6 months before t{sub end}) were analyzed to extract relevant variations among eleven perfusion biomarkers (B). These variations were assessed through R(B), as the absolute value of the ratio between ∇B from t{sub end-4M} to t{sub end-2M} and ∇B from t{sub end-6M} to t{sub end-4M}. The optimal cut-off for R(B) was determined using receiver-operating-characteristic curve analysis. The fraction of hypoperfused tumor volume (F{sub h}P{sub g}) was a relevant biomarker. A ratio R(F{sub h}P{sub g}) ≥ 0.61 would have been able to anticipate relapse at the next follow-up with a sensitivity/specificity/accuracy of 92.3 %/63.6 %/79.2 %. High R(F{sub h}Pg) (≥0.61) was associated with more relapse at t{sub end} compared to low R(F{sub h}Pg) (75 % vs 12.5 %, p = 0.008). Iterative analysis of F{sub h}P{sub g} from consecutive examinations could provide surrogate markers to predict progression at the next follow-up. (orig.)

  20. Metabolomics Identifies Multiple Candidate Biomarkers to Diagnose and Stage Human African Trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Isabel M Vincent

    2016-12-01

    Full Text Available Treatment for human African trypanosomiasis is dependent on the species of trypanosome causing the disease and the stage of the disease (stage 1 defined by parasites being present in blood and lymphatics whilst for stage 2, parasites are found beyond the blood-brain barrier in the cerebrospinal fluid (CSF. Currently, staging relies upon detecting the very low number of parasites or elevated white blood cell numbers in CSF. Improved staging is desirable, as is the elimination of the need for lumbar puncture. Here we use metabolomics to probe samples of CSF, plasma and urine from 40 Angolan patients infected with Trypanosoma brucei gambiense, at different disease stages. Urine samples provided no robust markers indicative of infection or stage of infection due to inherent variability in urine concentrations. Biomarkers in CSF were able to distinguish patients at stage 1 or advanced stage 2 with absolute specificity. Eleven metabolites clearly distinguished the stage in most patients and two of these (neopterin and 5-hydroxytryptophan showed 100% specificity and sensitivity between our stage 1 and advanced stage 2 samples. Neopterin is an inflammatory biomarker previously shown in CSF of stage 2 but not stage 1 patients. 5-hydroxytryptophan is an important metabolite in the serotonin synthetic pathway, the key pathway in determining somnolence, thus offering a possible link to the eponymous symptoms of "sleeping sickness". Plasma also yielded several biomarkers clearly indicative of the presence (87% sensitivity and 95% specificity and stage of disease (92% sensitivity and 81% specificity. A logistic regression model including these metabolites showed clear separation of patients being either at stage 1 or advanced stage 2 or indeed diseased (both stages versus control.

  1. Comparative Tissue Proteomics of Microdissected Specimens Reveals Novel Candidate Biomarkers of Bladder Cancer*

    Science.gov (United States)

    Chen, Chien-Lun; Chung, Ting; Wu, Chih-Ching; Ng, Kwai-Fong; Yu, Jau-Song; Tsai, Cheng-Han; Chang, Yu-Sun; Liang, Ying; Tsui, Ke-Hung; Chen, Yi-Ting

    2015-01-01

    More than 380,000 new cases of bladder cancer are diagnosed worldwide, accounting for ∼150,200 deaths each year. To discover potential biomarkers of bladder cancer, we employed a strategy combining laser microdissection, isobaric tags for relative and absolute quantitation labeling, and liquid chromatography-tandem MS (LC-MS/MS) analysis to profile proteomic changes in fresh-frozen bladder tumor specimens. Cellular proteins from four pairs of surgically resected primary bladder cancer tumor and adjacent nontumorous tissue were extracted for use in two batches of isobaric tags for relative and absolute quantitation experiments, which identified a total of 3220 proteins. A DAVID (database for annotation, visualization and integrated discovery) analysis of dysregulated proteins revealed that the three top-ranking biological processes were extracellular matrix organization, extracellular structure organization, and oxidation-reduction. Biological processes including response to organic substances, response to metal ions, and response to inorganic substances were highlighted by up-expressed proteins in bladder cancer. Seven differentially expressed proteins were selected as potential bladder cancer biomarkers for further verification. Immunohistochemical analyses showed significantly elevated levels of three proteins—SLC3A2, STMN1, and TAGLN2—in tumor cells compared with noncancerous bladder epithelial cells, and suggested that TAGLN2 could be a useful tumor tissue marker for diagnosis (AUC = 0.999) and evaluating lymph node metastasis in bladder cancer patients. ELISA results revealed significantly increased urinary levels of both STMN1 and TAGLN2 in bladder cancer subgroups compared with control groups. In comparisons with age-matched hernia urine specimens, urinary TAGLN2 in bladder cancer samples showed the largest fold change (7.13-fold), with an area-under-the-curve value of 0.70 (p < 0.001, n = 205). Overall, TAGLN2 showed the most significant

  2. The extracellular domain of neurotrophin receptor p75 as a candidate biomarker for amyotrophic lateral sclerosis.

    Science.gov (United States)

    Shepheard, Stephanie R; Chataway, Tim; Schultz, David W; Rush, Robert A; Rogers, Mary-Louise

    2014-01-01

    Objective biomarkers for amyotrophic lateral sclerosis would facilitate the discovery of new treatments. The common neurotrophin receptor p75 is up regulated and the extracellular domain cleaved from injured neurons and peripheral glia in amyotrophic lateral sclerosis. We have tested the hypothesis that urinary levels of extracellular neurotrophin receptor p75 serve as a biomarker for both human motor amyotrophic lateral sclerosis and the SOD1(G93A) mouse model of the disease. The extracellular domain of neurotrophin receptor p75 was identified in the urine of amyotrophic lateral sclerosis patients by an immuno-precipitation/western blot procedure and confirmed by mass spectrometry. An ELISA was established to measure urinary extracellular neurotrophin receptor p75. The mean value for urinary extracellular neurotrophin receptor p75 from 28 amyotrophic lateral sclerosis patients measured by ELISA was 7.9±0.5 ng/mg creatinine and this was significantly higher (pneurotrophin receptor p75 was also readily detected in SOD1(G93A) mice by immuno-precipitation/western blot before the onset of clinical symptoms. These findings indicate a significant relation between urinary extracellular neurotrophin receptor p75 levels and disease progression and suggests that it may be a useful marker of disease activity and progression in amyotrophic lateral sclerosis.

  3. CXCL14 is a candidate biomarker for Hedgehog signalling in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Jia, Guiquan; Chandriani, Sanjay; Abbas, Alexander R; DePianto, Daryle J; N'Diaye, Elsa N; Yaylaoglu, Murat B; Moore, Heather M; Peng, Ivan; DeVoss, Jason; Collard, Harold R; Wolters, Paul J; Egen, Jackson G; Arron, Joseph R

    2017-09-01

    Idiopathic pulmonary fibrosis (IPF) is associated with aberrant expression of developmental pathways, including Hedgehog (Hh). As Hh signalling contributes to multiple pro-fibrotic processes, Hh inhibition may represent a therapeutic option for IPF. However, no non-invasive biomarkers are available to monitor lung Hh activity. We assessed gene and protein expression in IPF and control lung biopsies, mouse lung, fibroblasts stimulated in vitro with sonic hedgehog (SHh), and plasma in IPF patients versus controls, and cancer patients before and after treatment with vismodegib, a Hh inhibitor. Lung tissue from IPF patients exhibited significantly greater expression of Hh-related genes versus controls. The gene most significantly upregulated in both IPF lung biopsies and fibroblasts stimulated in vitro with SHh was CXCL14 , which encodes a soluble secreted chemokine whose expression is inhibited in vitro by the addition of vismodegib. CXCL14 expression was induced by SHh overexpression in mouse lung. Circulating CXCL14 protein levels were significantly higher in plasma from IPF patients than controls. In cancer patients, circulating CXCL14 levels were significantly reduced upon vismodegib treatment. CXCL14 is a systemic biomarker that could be used to identify IPF patients with increased Hh pathway activity and monitor the pharmacodynamic effects of Hh antagonist therapy in IPF. Post-results, NCT00968981. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Two novel blood-based biomarker candidates measuring degradation of tau are associated with dementia: A prospective study

    DEFF Research Database (Denmark)

    Neergaard, Jesper Skov; Dragsbæk, Katrine; Christiansen, Claus

    2018-01-01

    fragments were detected in serum of 5,309 women from the Prospective Epidemiological Risk Factor study. The study was an observational, prospective study of Danish postmenopausal women. Subjects were followed with registry-linkage for up to 15 years (median follow-up time 13.7 years). Cox regression......Truncated tau appears to be specifically related to disease pathology and recent studies have shown the presence and elevation of several truncated tau species in Cerebrospinal fluid (CSF) of subjects with Alzheimer's disease (AD); however, the relevance of truncated Tau measurements in blood...... is still being studied. The aim of the current study was to assess the longitudinal associations between baseline levels of two novel blood biomarker candidates measuring truncated tau, Tau-A and Tau-C, and the risk of incident dementia and AD in elderly women. Using solid phase competitive ELISA, two tau...

  5. Science-Driven Candidate Search for New Scintillator Materials FY 2013 Annual Report

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Fei; Kerisit, Sebastien N.; Xie, YuLong; Wu, Dangxin; Prange, Micah P.; Van Ginhoven, Renee M.; Campbell, Luke W.; Wang, Zhiguo

    2013-10-01

    This annual report presents work carried out during Fiscal Year (FY) 2013 at Pacific Northwest National Laboratory (PNNL) under the project entitled “Science-Driven Candidate Search for New Scintillator Materials” (Project number: PL13-SciDriScintMat-PD05) and led by Dr. Fei Gao. This project is divided into three tasks, namely (1) Ab initio calculations of electronic properties, electronic response functions and secondary particle spectra; (2) Intrinsic response properties, theoretical light yield, and microscopic description of ionization tracks; and (3) Kinetics and efficiency of scintillation: nonlinearity, intrinsic energy resolution, and pulse shape discrimination. Detailed information on the findings and insights obtained in each of these three tasks are provided in this report. Additionally, papers published this fiscal year or currently in review are included in Appendix together with presentations given this fiscal year.

  6. Near-infrared Variability in the 2MASS Calibration Fields: A Search for Planetary Transit Candidates

    Science.gov (United States)

    Plavchan, Peter; Jura, M.; Kirkpatrick, J. Davy; Cutri, Roc M.; Gallagher, S. C.

    2008-01-01

    The Two Micron All Sky Survey (2MASS) photometric calibration observations cover approximately 6 square degrees on the sky in 35 'calibration fields,' each sampled in nominal photometric conditions between 562 and 3692 times during the 4 years of the 2MASS mission. We compile a catalog of variables from the calibration observations to search for M dwarfs transited by extrasolar planets. We present our methods for measuring periodic and nonperiodic flux variability. From 7554 sources with apparent K(sub s) magnitudes between 5.6 and 16.1, we identify 247 variables, including extragalactic variables and 23 periodic variables. We have discovered three M dwarf eclipsing systems, including two candidates for transiting extrasolar planets.

  7. Glutathione transferase (GST) as a candidate molecular-based biomarker for soil toxin exposure in the earthworm Lumbricus rubellus

    International Nuclear Information System (INIS)

    LaCourse, E. James; Hernandez-Viadel, Mariluz; Jefferies, James R.; Svendsen, Claus; Spurgeon, David J.; Barrett, John; John Morgan, A.; Kille, Peter; Brophy, Peter M.

    2009-01-01

    The earthworm Lumbricus rubellus (Hoffmeister, 1843) is a terrestrial pollution sentinel. Enzyme activity and transcription of phase II detoxification superfamily glutathione transferases (GST) is known to respond in earthworms after soil toxin exposure, suggesting GST as a candidate molecular-based pollution biomarker. This study combined sub-proteomics, bioinformatics and biochemical assay to characterise the L. rubellus GST complement as pre-requisite to initialise assessment of the applicability of GST as a biomarker. L. rubellus possesses a range of GSTs related to known classes, with evidence of tissue-specific synthesis. Two affinity-purified GSTs dominating GST protein synthesis (Sigma and Pi class) were cloned, expressed and characterised for enzyme activity with various substrates. Electrospray ionisation mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) following SDS-PAGE were superior in retaining subunit stability relative to two-dimensional gel electrophoresis (2-DE). This study provides greater understanding of Phase II detoxification GST superfamily status of an important environmental pollution sentinel organism. - This study currently provides the most comprehensive view of the Phase II detoxification enzyme superfamily of glutathione transferases within the important environmental pollution sentinel earthworm Lumbricus rubellus.

  8. Glutathione transferase (GST) as a candidate molecular-based biomarker for soil toxin exposure in the earthworm Lumbricus rubellus

    Energy Technology Data Exchange (ETDEWEB)

    LaCourse, E. James, E-mail: james.la-course@liverpool.ac.u [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom); Hernandez-Viadel, Mariluz; Jefferies, James R. [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom); Svendsen, Claus; Spurgeon, David J. [Centre for Ecology and Hydrology, Huntingdon PE28 2LS (United Kingdom); Barrett, John [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom); John Morgan, A.; Kille, Peter [Biosciences, University of Cardiff, Cardiff CF10 3TL (United Kingdom); Brophy, Peter M. [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom)

    2009-08-15

    The earthworm Lumbricus rubellus (Hoffmeister, 1843) is a terrestrial pollution sentinel. Enzyme activity and transcription of phase II detoxification superfamily glutathione transferases (GST) is known to respond in earthworms after soil toxin exposure, suggesting GST as a candidate molecular-based pollution biomarker. This study combined sub-proteomics, bioinformatics and biochemical assay to characterise the L. rubellus GST complement as pre-requisite to initialise assessment of the applicability of GST as a biomarker. L. rubellus possesses a range of GSTs related to known classes, with evidence of tissue-specific synthesis. Two affinity-purified GSTs dominating GST protein synthesis (Sigma and Pi class) were cloned, expressed and characterised for enzyme activity with various substrates. Electrospray ionisation mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) following SDS-PAGE were superior in retaining subunit stability relative to two-dimensional gel electrophoresis (2-DE). This study provides greater understanding of Phase II detoxification GST superfamily status of an important environmental pollution sentinel organism. - This study currently provides the most comprehensive view of the Phase II detoxification enzyme superfamily of glutathione transferases within the important environmental pollution sentinel earthworm Lumbricus rubellus.

  9. The extracellular domain of neurotrophin receptor p75 as a candidate biomarker for amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Stephanie R Shepheard

    Full Text Available Objective biomarkers for amyotrophic lateral sclerosis would facilitate the discovery of new treatments. The common neurotrophin receptor p75 is up regulated and the extracellular domain cleaved from injured neurons and peripheral glia in amyotrophic lateral sclerosis. We have tested the hypothesis that urinary levels of extracellular neurotrophin receptor p75 serve as a biomarker for both human motor amyotrophic lateral sclerosis and the SOD1(G93A mouse model of the disease. The extracellular domain of neurotrophin receptor p75 was identified in the urine of amyotrophic lateral sclerosis patients by an immuno-precipitation/western blot procedure and confirmed by mass spectrometry. An ELISA was established to measure urinary extracellular neurotrophin receptor p75. The mean value for urinary extracellular neurotrophin receptor p75 from 28 amyotrophic lateral sclerosis patients measured by ELISA was 7.9±0.5 ng/mg creatinine and this was significantly higher (p<0.001 than 12 controls (2.6±0.2 ng/mg creatinine and 19 patients with other neurological disease (Parkinson's disease and Multiple Sclerosis; 4.1±0.2 ng/mg creatinine. Pilot data of disease progression rates in 14 MND patients indicates that p75NTR(ECD levels were significantly higher (p = 0.0041 in 7 rapidly progressing patients as compared to 7 with slowly progressing disease. Extracellular neurotrophin receptor p75 was also readily detected in SOD1(G93A mice by immuno-precipitation/western blot before the onset of clinical symptoms. These findings indicate a significant relation between urinary extracellular neurotrophin receptor p75 levels and disease progression and suggests that it may be a useful marker of disease activity and progression in amyotrophic lateral sclerosis.

  10. Identification of 10 Candidate Biomarkers Distinguishing Tuberculous and Malignant Pleural Fluid by Proteomic Methods.

    Science.gov (United States)

    Lee, Chang Youl; Hong, Ji Young; Lee, Myung Goo; Suh, In Bum

    2017-11-01

    Pleural effusion, an accumulation of fluid in the pleural space, usually occurs in patients when the rate of fluid formation exceeds the rate of fluid removal. The differential diagnosis of tuberculous pleurisy and malignant pleural effusion is a difficult task in high tuberculous prevalence areas. The aim of the present study was to identify novel biomarkers for the diagnosis of pleural fluid using proteomics technology. We used samples from five patients with transudative pleural effusions for internal standard, five patients with tuberculous pleurisy, and the same numbers of patients having malignant effusions were enrolled in the study. We analyzed the proteins in pleural fluid from patients using a technique that combined two-dimensional liquid-phase electrophoresis and matrix assisted laser desorption/ionization-time of flight-mass spectrometry. We identified a total of 10 proteins with statistical significance. Among 10 proteins, trasthyretin, haptoglobin, metastasis-associated protein 1, t-complex protein 1, and fibroblast growth factor-binding protein 1 were related with malignant pleural effusions and human ceruloplasmin, lysozyme precursor, gelsolin, clusterin C complement lysis inhibitor, and peroxirexdoxin 3 were expressed several times or more in tuberculous pleural effusions. Highly expressed proteins in malignant pleural effusion were associated with carcinogenesis and cell growth, and proteins associated with tuberculous pleural effusion played a role in the response to inflammation and fibrosis. These findings will aid in the development of novel diagnostic tools for tuberculous pleurisy and malignant pleural effusion of lung cancer. © Copyright: Yonsei University College of Medicine 2017

  11. Soluble αKlotho as a candidate for the biomarker of aging.

    Science.gov (United States)

    Koyama, Daisuke; Sato, Yu; Aizawa, Masato; Maki, Takumi; Kurosawa, Masaki; Kuro-o, Makoto; Furukawa, Yusuke

    2015-11-27

    Although the Klotho gene has been recognized as an aging-suppressor gene, the significance of its soluble product, soluble αKlotho (sKlotho), in aging remains to be elucidated. To address this issue, we conducted a single-centered cross-sectional study in a region with a high prevalence of aging. We compared sKlotho levels with the patient characteristics from medical records and laboratory measurements, including fibroblast growth factor 23 (FGF23), intact parathyroid hormone, activated vitamin D3 and factors associated with mineral bone metabolism, in 52 outpatients with a mean age of 78.2 years. Serum sKlotho levels significantly decreased with age, but were not associated with the stage of chronic kidney disease (CKD). Serum FGF23 levels increased as CKD stages advanced, but were not associated with aging. Univariate analyses revealed that sKlotho levels positively correlated with glomerular filtration rate, and negatively with age and serum levels of FGF23 and phosphorus. In a multivariable linear regression analysis, sKlotho significantly correlated with aging and lower FGF23 levels. Only osteoporosis affected sKlotho and FGF23 levels among the various complications and patient status including medication. In summary, serum sKlotho levels inversely correlated with age and FGF23, and were significantly reduced in patients with osteoporosis. sKlotho may serve as a biomarker of aging independent of renal function. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. AZU-1: A Candidate Breast Tumor Suppressor and Biomarker for Tumor Progression

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Huei-Mei; Schmeichel, Karen L; Mian, I. Saira; Lelie`vre, Sophie; Petersen, Ole W; Bissell, Mina J

    2000-02-04

    To identify genes misregulated in the final stages of breast carcinogenesis, we performed differential display to compare the gene expression patterns of the human tumorigenic mammary epithelial cells, HMT-3522-T4-2, with those of their immediate premalignant progenitors, HMT-3522-S2. We identified a novel gene, called anti-zuai-1 (AZU-1), that was abundantly expressed in non- and premalignant cells and tissues but was appreciably reduced in breast tumor cell types and in primary tumors. The AZU-1 gene encodes an acidic 571-amino-acid protein containing at least two structurally distinct domains with potential protein-binding functions: an N-terminal serine and proline-rich domain with a predicted immunoglobulin-like fold and a C-terminal coiled-coil domain. In HMT-3522 cells, the bulk of AZU-1 protein resided in a detergent-extractable cytoplasmic pool and was present at much lower levels in tumorigenic T4-2 cells than in their nonmalignant counterparts. Reversion of the tumorigenic phenotype of T4-2 cells, by means described previously, was accompanied by the up-regulation of AZU-1. In addition, reexpression of AZU-1 in T4-2 cells, using viral vectors, was sufficient to reduce their malignant phenotype substantially, both in culture and in vivo. These results indicate that AZU-1 is a candidate breast tumor suppressor that may exert its effects by promoting correct tissue morphogenesis.

  13. Potential candidate genomic biomarkers of drug induced vascular injury in the rat

    International Nuclear Information System (INIS)

    Dalmas, Deidre A.; Scicchitano, Marshall S.; Mullins, David; Hughes-Earle, Angela; Tatsuoka, Kay; Magid-Slav, Michal; Frazier, Kendall S.; Thomas, Heath C.

    2011-01-01

    Drug-induced vascular injury is frequently observed in rats but the relevance and translation to humans present a hurdle for drug development. Numerous structurally diverse pharmacologic agents have been shown to induce mesenteric arterial medial necrosis in rats, but no consistent biomarkers have been identified. To address this need, a novel strategy was developed in rats to identify genes associated with the development of drug-induced mesenteric arterial medial necrosis. Separate groups (n = 6/group) of male rats were given 28 different toxicants (30 different treatments) for 1 or 4 days with each toxicant given at 3 different doses (low, mid and high) plus corresponding vehicle (912 total rats). Mesentery was collected, frozen and endothelial and vascular smooth muscle cells were microdissected from each artery. RNA was isolated, amplified and Affymetrix GeneChip® analysis was performed on selectively enriched samples and a novel panel of genes representing those which showed a dose responsive pattern for all treatments in which mesenteric arterial medial necrosis was histologically observed, was developed and verified in individual endothelial cell- and vascular smooth muscle cell-enriched samples. Data were confirmed in samples containing mesentery using quantitative real-time RT-PCR (TaqMan™) gene expression profiling. In addition, the performance of the panel was also confirmed using similarly collected samples obtained from a timecourse study in rats given a well established vascular toxicant (Fenoldopam). Although further validation is still required, a novel gene panel has been developed that represents a strategic opportunity that can potentially be used to help predict the occurrence of drug-induced mesenteric arterial medial necrosis in rats at an early stage in drug development. -- Highlights: ► A gene panel was developed to help predict rat drug-induced mesenteric MAN. ► A gene panel was identified following treatment of rats with 28

  14. Pairwise protein expression classifier for candidate biomarker discovery for early detection of human disease prognosis

    Directory of Open Access Journals (Sweden)

    Kaur Parminder

    2012-08-01

    Full Text Available Abstract Background An approach to molecular classification based on the comparative expression of protein pairs is presented. The method overcomes some of the present limitations in using peptide intensity data for class prediction for problems such as the detection of a disease, disease prognosis, or for predicting treatment response. Data analysis is particularly challenging in these situations due to sample size (typically tens being much smaller than the large number of peptides (typically thousands. Methods based upon high dimensional statistical models, machine learning or other complex classifiers generate decisions which may be very accurate but can be complex and difficult to interpret in simple or biologically meaningful terms. A classification scheme, called ProtPair, is presented that generates simple decision rules leading to accurate classification which is based on measurement of very few proteins and requires only relative expression values, providing specific targeted hypotheses suitable for straightforward validation. Results ProtPair has been tested against clinical data from 21 patients following a bone marrow transplant, 13 of which progress to idiopathic pneumonia syndrome (IPS. The approach combines multiple peptide pairs originating from the same set of proteins, with each unique peptide pair providing an independent measure of discriminatory power. The prediction rate of the ProtPair for IPS study as measured by leave-one-out CV is 69.1%, which can be very beneficial for clinical diagnosis as it may flag patients in need of closer monitoring. The “top ranked” proteins provided by ProtPair are known to be associated with the biological processes and pathways intimately associated with known IPS biology based on mouse models. Conclusions An approach to biomarker discovery, called ProtPair, is presented. ProtPair is based on the differential expression of pairs of peptides and the associated proteins. Using mass

  15. Red blood cell populations and membrane levels of peroxiredoxin 2 as candidate biomarkers to reveal blood doping.

    Science.gov (United States)

    Marrocco, Cristina; Pallotta, Valeria; D'alessandro, Angelo; Alves, Gilda; Zolla, Lello

    2012-05-01

    Blood doping represents one main trend in doping strategies. Blood doping refers to the practice of boosting the number of red blood cells (RBCs) in the bloodstream in order to enhance athletic performance, by means of blood transfusions, administration of erythropoiesis-stimulating substances, blood substitutes, natural or artificial altitude facilities, and innovative gene therapies. While detection of recombinant EPO and homologous transfusion is already feasible through electrophoretic, mass spectrometry or flow cytometry-based approaches, no method is currently available to tackle doping strategies relying on autologous transfusions. We exploited an in vitro model of autologous transfusion through a 1:10 dilution of concentrated RBCs after 30 days of storage upon appropriate dilution in freshly withdrawn RBCs from the same donor. Western blot towards membrane Prdx2 and Percoll density gradients were exploited to assess their suitability as biomarkers of transfusion. Membrane Prdx2 was visible in day 30 samples albeit not in day 0, while it was still visible in the 1:10 dilution of day 30 in day 0 RBCs. Cell gradients also highlighted changes in the profile of the RBC subpopulations upon dilution of stored RBCs in the fresh ones. From this preliminary in vitro investigation it emerges that Prdx2 and RBC populations might be further tested as candidate biomarkers of blood doping through autologous transfusion, though it is yet to be assessed whether the kinetics in vivo of Prdx2 exposure in the membrane of transfused RBCs will endow a sufficient time-window to allow reliable anti-doping testing.

  16. Identification of candidate biomarkers of the exposure to PCBs in contaminated cattle: A gene expression- and proteomic-based approach.

    Science.gov (United States)

    Girolami, F; Badino, P; Spalenza, V; Manzini, L; Renzone, G; Salzano, A M; Dal Piaz, F; Scaloni, A; Rychen, G; Nebbia, C

    2018-05-28

    Dioxins and polychlorinated biphenyls (PCBs) are widespread and persistent contaminants. Through a combined gene expression/proteomic-based approach, candidate biomarkers of the exposure to such environmental pollutants in cattle subjected to a real eco-contamination event were identified. Animals were removed from the polluted area and fed a standard ration for 6 months. The decontamination was monitored by evaluating dioxin and PCB levels in pericaudal fat two weeks after the removal from the contaminated area (day 0) and then bimonthly for six months (days 59, 125 and 188). Gene expression measurements demonstrated that CYP1B1 expression was significantly higher in blood lymphocytes collected in contaminated animals (day 0), and decreased over time during decontamination. mRNA levels of interleukin 2 showed an opposite quantitative trend. MALDI-TOF-MS polypeptide profiling of serum samples ascertained a progressive decrease (from day 0 to 188) of serum levels of fibrinogen β-chain and serpin A3-7-like fragments, apolipoprotein (APO) C-II and serum amyloid A-4 protein, along with an augmented representation of transthyretin isoforms, as well as APOC-III and APOA-II proteins during decontamination. When differentially represented species were combined with serum antioxidant, acute phase and proinflammatory protein levels already ascertained in the same animals (Cigliano et al., 2016), bioinformatics unveiled an interaction network linking together almost all components. This suggests the occurrence of a complex PCB-responsive mechanism associated with animal contamination/decontamination, including a cohort of protein/polypeptide species involved in blood redox homeostasis, inflammation and lipid transport. All together, these results suggest the use in combination of such biomarkers for identifying PCB-contaminated animals, and for monitoring the restoring of their healthy condition following a decontamination process. Copyright © 2018 Elsevier B.V. All

  17. Evaluation of the biomarker candidate MFAP4 for non-invasive assessment of hepatic fibrosis in hepatitis C patients.

    Science.gov (United States)

    Bracht, Thilo; Mölleken, Christian; Ahrens, Maike; Poschmann, Gereon; Schlosser, Anders; Eisenacher, Martin; Stühler, Kai; Meyer, Helmut E; Schmiegel, Wolff H; Holmskov, Uffe; Sorensen, Grith L; Sitek, Barbara

    2016-07-04

    The human microfibrillar-associated protein 4 (MFAP4) is located to extracellular matrix fibers and plays a role in disease-related tissue remodeling. Previously, we identified MFAP4 as a serum biomarker candidate for hepatic fibrosis and cirrhosis in hepatitis C patients. The aim of the present study was to elucidate the potential of MFAP4 as biomarker for hepatic fibrosis with a focus on the differentiation of no to moderate (F0-F2) and severe fibrosis stages and cirrhosis (F3 and F4, Desmet-Scheuer scoring system). MFAP4 levels were measured using an AlphaLISA immunoassay in a retrospective study including n = 542 hepatitis C patients. We applied a univariate logistic regression model based on MFAP4 serum levels and furthermore derived a multivariate model including also age and gender. Youden-optimal cutoffs for binary classification were determined for both models without restrictions and considering a lower limit of 80 % sensitivity (correct classification of F3 and F4), respectively. To assess the generalization error, leave-one-out cross validation (LOOCV) was performed. MFAP4 levels were shown to differ between no to moderate fibrosis stages F0-F2 and severe stages (F3 and F4) with high statistical significance (t test on log scale, p value <2.2·10(-16)). In the LOOCV, the univariate classification resulted in 85.8 % sensitivity and 54.9 % specificity while the multivariate model yielded 81.3 % sensitivity and 61.5 % specificity (restricted approaches). We confirmed the applicability of MFAP4 as a novel serum biomarker for assessment of hepatic fibrosis and identification of high-risk patients with severe fibrosis stages in hepatitis C. The combination of MFAP4 with existing tests might lead to a more accurate non-invasive diagnosis of hepatic fibrosis and allow a cost-effective disease management in the era of new direct acting antivirals.

  18. Science-Driven Candidate Search for New Scintillator Materials: FY 2014 Annual Report

    Energy Technology Data Exchange (ETDEWEB)

    Kerisit, Sebastien N.; Gao, Fei; Xie, YuLong; Campbell, Luke W.; Wu, Dangxin; Prange, Micah P.

    2014-10-01

    This annual reports presents work carried out during Fiscal Year (FY) 2014 at Pacific Northwest National Laboratory (PNNL) under the project entitled “Science-Driven Candidate Search for New Scintillator Materials” (Project number: PL13-SciDriScintMat-PD05) and led by Drs. Fei Gao and Sebastien N. Kerisit. This project is divided into three tasks: 1) Ab initio calculations of electronic properties, electronic response functions and secondary particle spectra; 2) Intrinsic response properties, theoretical light yield, and microscopic description of ionization tracks; and 3) Kinetics and efficiency of scintillation: nonproportionality, intrinsic energy resolution, and pulse shape discrimination. Detailed information on the results obtained in each of the three tasks is provided in this Annual Report. Furthermore, peer-reviewed articles published this FY or currently under review and presentations given this FY are included in Appendix. This work was supported by the National Nuclear Security Administration, Office of Nuclear Nonproliferation Research and Development (DNN R&D/NA-22), of the U.S. Department of Energy (DOE).

  19. Searching for New Biomarkers and the Use of Multivariate Analysis in Gastric Cancer Diagnostics.

    Science.gov (United States)

    Kucera, Radek; Smid, David; Topolcan, Ondrej; Karlikova, Marie; Fiala, Ondrej; Slouka, David; Skalicky, Tomas; Treska, Vladislav; Kulda, Vlastimil; Simanek, Vaclav; Safanda, Martin; Pesta, Martin

    2016-04-01

    The first aim of this study was to search for new biomarkers to be used in gastric cancer diagnostics. The second aim was to verify the findings presented in literature on a sample of the local population and investigate the risk of gastric cancer in that population using a multivariant statistical analysis. We assessed a group of 36 patients with gastric cancer and 69 healthy individuals. We determined carcinoembryonic antigen, cancer antigen 19-9, cancer antigen 72-4, matrix metalloproteinases (-1, -2, -7, -8 and -9), osteoprotegerin, osteopontin, prothrombin induced by vitamin K absence-II, pepsinogen I, pepsinogen II, gastrin and Helicobacter pylori for each sample. The multivariate stepwise logistic regression identified the following biomarkers as the best gastric cancer predictors: CEA, CA72-4, pepsinogen I, Helicobacter pylori presence and MMP7. CEA and CA72-4 remain the best markers for gastric cancer diagnostics. We suggest a mathematical model for the assessment of risk of gastric cancer. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  20. Networking in autism: leveraging genetic, biomarker and model system findings in the search for new treatments.

    Science.gov (United States)

    Veenstra-VanderWeele, Jeremy; Blakely, Randy D

    2012-01-01

    Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder affecting approximately 1% of children. ASD is defined by core symptoms in two domains: negative symptoms of impairment in social and communication function, and positive symptoms of restricted and repetitive behaviors. Available treatments are inadequate for treating both core symptoms and associated conditions. Twin studies indicate that ASD susceptibility has a large heritable component. Genetic studies have identified promising leads, with converging insights emerging from single-gene disorders that bear ASD features, with particular interest in mammalian target of rapamycin (mTOR)-linked synaptic plasticity mechanisms. Mouse models of these disorders are revealing not only opportunities to model behavioral perturbations across species, but also evidence of postnatal rescue of brain and behavioral phenotypes. An intense search for ASD biomarkers has consistently pointed to elevated platelet serotonin (5-HT) levels and a surge in brain growth in the first 2 years of life. Following a review of the diversity of ASD phenotypes and its genetic origins and biomarkers, we discuss opportunities for translation of these findings into novel ASD treatments, focusing on mTor- and 5-HT-signaling pathways, and their possible intersection. Paralleling the progress made in understanding the root causes of rare genetic syndromes that affect cognitive development, we anticipate progress in models systems using bona fide ASD-associated molecular changes that have the potential to accelerate the development of ASD diagnostics and therapeutics.

  1. The imbalance in expression of angiogenic and anti-angiogenic factors as candidate predictive biomarker in preeclampsia

    Directory of Open Access Journals (Sweden)

    Pooneh Nikuei

    2015-07-01

    Full Text Available Preeclampsia is an important pregnancy disorder with serious maternal and fetal complications which its etiology has not been completely understood yet. Early diagnosis and management of disease could reduce its potential side effects. The vascular endothelial growth factor (VEGF family including VEGF-A is the most potent endothelial growth factor which induces angiogenesis and endothelial cell proliferation and has basic role in vasculogenesis. VEGF and its tyrosine kinase receptors (Flt1 and KDR are major factors for fetal and placental angiogenic development. Finding mechanisms involved in expression of angiogenic factors may lead to new prognostic and therapeutic points in management of preeclampsia. Recent researches, has shown capability of some anti-angiogenic factors as potential candidate to be used as early predictors for preeclampsia. Soluble fms-like tyrosin kinase-1 (sFlt1 is a truncated splice variant of the membrane-bound VEGF receptor Flt1, that is produced by the placenta and it can bind to angiogenic growth factors and neutraliz, their effects. It is also observed that the ratio of sFlt1 to placental growth factor is valuable as prognostic marker. In this review, VEGF family member’s role in angiogenesis is evaluated as biomarkers to be used for prediction of preeclampsia.

  2. Non-invasive detection of candidate pregnancy protein biomarkers in the feces of captive polar bears (Ursus maritimus).

    Science.gov (United States)

    Curry, E; Stoops, M A; Roth, T L

    2012-07-15

    Currently, there is no method of accurately and non-invasively diagnosing pregnancy in polar bears. Specific proteins may exhibit altered profiles in the feces of pregnant bears, but predicting appropriate candidate proteins to investigate is speculative at best. The objective of this study was to identify potential pregnancy biomarker proteins based on their increased abundance in the feces of pregnant polar bears compared to pseudopregnant females (controls) using two-dimensional in-gel electrophoresis (2D-DIGE) and mass spectrometry (MS). Three 2D-DIGE gels were performed to evaluate fecal protein profiles from controls (n=3) and pregnant polar bears (n=3). There were 2224.67±52.39 (mean±SEM) spots resolved per gel. Of these, only five proteins were elevated in the pregnant group (P99.9% confidence interval. The 11 spots represented seven distinct proteins, five of which were significantly more abundant in the pregnant group: IgGFc-binding protein, filamin-C, carboxypeptidase B, transthyretin, and immunoglobulin heavy chain variable region. To our knowledge, this was the first study that employed 2D-DIGE to identify differentially expressed proteins in fecal samples to characterize a physiological condition other than those related to gastrointestinal disorders. These promising results provided a strong foundation for ensuing efforts to develop a non-invasive pregnancy assay for use in both captive and wild polar bears. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Spectroscopy of Luminous z > 7 Galaxy Candidates and Sources of Contamination in z > 7 Galaxy Searches

    Science.gov (United States)

    Capak, P.; Mobasher, B.; Scoville, N. Z.; McCracken, H.; Ilbert, O.; Salvato, M.; Menéndez-Delmestre, K.; Aussel, H.; Carilli, C.; Civano, F.; Elvis, M.; Giavalisco, M.; Jullo, E.; Kartaltepe, J.; Leauthaud, A.; Koekemoer, A. M.; Kneib, J.-P.; LeFloch, E.; Sanders, D. B.; Schinnerer, E.; Shioya, Y.; Shopbell, P.; Tanaguchi, Y.; Thompson, D.; Willott, C. J.

    2011-04-01

    We present three bright z +-dropout candidates selected from deep near-infrared (NIR) imaging of the COSMOS 2 deg2 field. All three objects match the 0.8-8 μm colors of other published z > 7 candidates but are 3 mag brighter, facilitating further study. Deep spectroscopy of two of the candidates covering 0.64-1.02 μm with Keck-DEIMOS and all three covering 0.94-1.10 μm and 1.52-1.80 μm with Keck-NIRSPEC detects weak spectral features tentatively identified as Lyα at z = 6.95 and z = 7.69 in two of the objects. The third object is placed at z ~ 1.6 based on a 24 μm and weak optical detection. A comparison with the spectral energy distributions of known z 1 μm properties of all three objects can be matched to optically detected sources with photometric redshifts at z ~ 1.8, so the non-detection in the i + and z + bands is the primary factor which favors a z > 7 solution. If any of these objects are at z ~ 7, the bright end of the luminosity function is significantly higher at z > 7 than suggested by previous studies, but consistent within the statistical uncertainty and the dark matter halo distribution. If these objects are at low redshift, the Lyman break selection must be contaminated by a previously unknown population of low-redshift objects with very strong breaks in their broadband spectral energy distributions and blue NIR colors. The implications of this result on luminosity function evolution at high redshift are discussed. We show that the primary limitation of z > 7 galaxy searches with broad filters is the depth of the available optical data. Based on observations with the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration and made possible by the generous financial support of the W. M. Keck Foundation; the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory, California

  4. Search and characterization of T-type planetary mass candidates in the σ Orionis cluster

    Science.gov (United States)

    Peña Ramírez, K.; Zapatero Osorio, M. R.; Béjar, V. J. S.; Rebolo, R.; Bihain, G.

    2011-08-01

    Context. The proper characterization of the least massive population of the young σ Orionis star cluster is required to understand the form of the cluster mass function and its impact on our comprehension of the substellar formation processes. S Ori 70 (T5.5 ± 1) and 73, two T-type cluster member candidates, are likely to have masses between 3 and 7 MJup if their age is 3 Myr. It awaits confirmation whether S Ori 73 has a methane atmosphere. Aims: We aim to: i) confirm the presence of methane absorption in S Ori 73 by performing methane imaging; ii) study S Ori 70 and 73 cluster membership via photometric colors and accurate proper motion analysis; and iii) perform a new search to identify additional T-type σ Orionis member candidates. Methods: We obtained HAWK-I (VLT) J, H, and CH4off photometry of an area of 119.15 arcmin2 in σ Orionis down to Jcomp = 21.7 and Hcomp = 21 mag. S Ori 70 and 73 are contained in the explored area. Near-infrared data were complemented with optical photometry using images acquired with OSIRIS (GTC) and VISTA as part of the VISTA Orion survey. Color-magnitude and color-color diagrams were constructed to characterize S Ori 70 and 73 photometrically, and to identify new objects with methane absorption and masses below 7 MJup. We derived proper motions by comparing of the new HAWK-I and VISTA images with published near-infrared data taken 3.4 - 7.9 yr ago. Results.S Ori 73 has a red H - CH4off color indicating methane absorption in the H-band and a spectral type of T4 ± 1. S Ori 70 displays a redder methane color than S Ori 73 in agreement with its latter spectral classification. Our proper motion measurements (μα cos δ = 26.7 ± 6.1, μδ = 21.3 ± 6.1 mas yr-1 for S Ori 70, and μα cos δ = 46.7 ± 4.9, μδ = -6.3 ± 4.7 mas yr-1 for S Ori 73) are larger than the motion of σ Orionis, rendering S Ori 70 and 73 cluster membership uncertain. From our survey, we identified one new photometric candidate with J = 21.69 ± 0.12 mag

  5. Searching for an oscillating massive scalar field as a dark matter candidate using atomic hyperfine frequency comparisons

    OpenAIRE

    Hees, A.; Guéna, J.; Abgrall, M.; Bize, S.; Wolf, P.

    2016-01-01

    We use six years of accurate hyperfine frequency comparison data of the dual rubidium and caesium cold atom fountain FO2 at LNE-SYRTE to search for a massive scalar dark matter candidate. Such a scalar field can induce harmonic variations of the fine structure constant, of the mass of fermions and of the quantum chromodynamic mass scale, which will directly impact the rubidium/caesium hyperfine transition frequency ratio. We find no signal consistent with a scalar dark matter candidate but pr...

  6. Searching for native tree species and respective potential biomarkers for future assessment of pollution effects on the highly diverse Atlantic Forest in SE-Brazil

    International Nuclear Information System (INIS)

    Domingos, Marisa; Bulbovas, Patricia; Camargo, Carla Z.S.; Aguiar-Silva, Cristiane; Brandão, Solange E.; Dafré-Martinelli, Marcelle; Dias, Ana Paula L.; Engela, Marcela R.G.S.; Gagliano, Janayne; Moura, Barbara B.; Alves, Edenise S.; Rinaldi, Mirian C.S.; Gomes, Eduardo P.C.; Furlan, Claudia M.; Figueiredo, Ana Maria G.

    2015-01-01

    This study summarizes the first effort to search for bioindicator tree species and respective potential biomarkers for future assessment of potential mixed pollution effects on the highly diverse Atlantic Forest in SE-Brazil. Leaves of the three most abundant species inventoried in a phytosociological survey (Croton floribundus, Piptadenia gonoacantha and Astronium graveolens) were collected in four forest remnants during winter and summer (2012). Their potential bioindicator attributes were highlighted using a screening of morphological, chemical and biochemical markers. The leaf surface structure and/or epicuticular wax composition pointed the accumulator properties of C. floribundus and P. gonoacantha. C. floribundus is a candidate for assessing potential accumulation of Cu, Cd, Mn, Ni, S and Zn. P. gonoacantha is a candidate to monitor polycyclic aromatic hydrocarbons. Increased levels of secondary metabolites and decreased antioxidant capacity in leaves of A. graveolens may support its value as a bioindicator for oxidative pollutants by visible dark stipplings. - Highlights: • We searched for tree species from Atlantic Forest for future air pollution monitoring in Brazil. • Croton floribundus, Astronium graveolens and Piptadenia gonoacantha were possible bioindicators. • P. gonoachanta was a potential bioindicator of polycyclic aromatic hydrocarbons. • C. floribundus was a potential bioindicator of heavy metals and sulfur. • A. graveolens may be used for monitoring oxidative pollutants, due to its biochemical leaf traits. - Inherent characteristics of the most abundant native tree species were potential biomarkers for assessing pollution effects on the highly diverse Atlantic Forest in SE-Brazil

  7. Heritability and clinical determinants of serum indoxyl sulfate and p-cresyl sulfate, candidate biomarkers of the human microbiome enterotype.

    Directory of Open Access Journals (Sweden)

    Liesbeth Viaene

    Full Text Available BACKGROUND: Indoxyl sulfate and p-cresyl sulfate are unique microbial co-metabolites. Both co-metabolites have been involved in the pathogenesis of accelerated cardiovascular disease and renal disease progression. Available evidence suggests that indoxyl sulfate and p-cresyl sulfate may be considered candidate biomarkers of the human enterotype and may help to explain the link between diet and cardiovascular disease burden. OBJECTIVE AND DESIGN: Information on clinical determinants and heritability of indoxyl sulfate and p-cresyl sulfate serum is non-existing. To clarify this issue, the authors determined serum levels of indoxyl sulfate and p-cresyl sulfate in 773 individuals, recruited in the frame of the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO study. RESULTS: Serum levels of indoxyl sulfate and p-cresyl sulfate amounted to 3.1 (2.4-4.3 and 13.0 (7.4-21.5 μM, respectively. Regression analysis identified renal function, age and sex as independent determinants of both co-metabolites. Both serum indoxyl sulfate (h2 = 0.17 and p-cresyl sulfate (h2 = 0.18 concentrations showed moderate but significant heritability after adjustment for covariables, with significant genetic and environmental correlations for both co-metabolites. LIMITATIONS: Family studies cannot provide conclusive evidence for a genetic contribution, as confounding by shared environmental effects can never be excluded. CONCLUSIONS: The heritability of indoxyl sulfate and p-cresyl sulfate is moderate. Besides genetic host factors and environmental factors, also renal function, sex and age influence the serum levels of these co-metabolites.

  8. Multiple reaction monitoring assay based on conventional liquid chromatography and electrospray ionization for simultaneous monitoring of multiple cerebrospinal fluid biomarker candidates for Alzheimer's disease.

    Science.gov (United States)

    Choi, Yong Seok; Lee, Kelvin H

    2016-03-01

    Alzheimer's disease (AD) is the most common type of dementia, but early and accurate diagnosis remains challenging. Previously, a panel of cerebrospinal fluid (CSF) biomarker candidates distinguishing AD and non-AD CSF accurately (>90 %) was reported. Furthermore, a multiple reaction monitoring (MRM) assay based on nano liquid chromatography tandem mass spectrometry (nLC-MS/MS) was developed to help validate putative AD CSF biomarker candidates including proteins from the panel. Despite the good performance of the MRM assay, wide acceptance may be challenging because of limited availability of nLC-MS/MS systems in laboratories. Thus, here, a new MRM assay based on conventional LC-MS/MS is presented. This method monitors 16 peptides representing 16 (of 23) biomarker candidates that belonged to the previous AD CSF panel. A 30-times more concentrated sample than the sample used for the previous study was loaded onto a high capacity trap column, and all 16 MRM transitions showed good linearity (average R(2) = 0.966), intra-day reproducibility (average coefficient of variance (CV) = 4.78 %), and inter-day reproducibility (average CV = 9.85 %). The present method has several advantages such as a shorter analysis time, no possibility of target variability, and no need for an internal standard.

  9. Gene expression analysis of 4 biomarker candidates in Eisenia fetida exposed to an environmental metallic trace elements gradient: A microcosm study

    Energy Technology Data Exchange (ETDEWEB)

    Brulle, Franck; Lemiere, Sebastien [Univ Lille Nord de France, F-59000 Lille (France); LGCgE, Equipe Ecologie Numerique et Ecotoxicologie, Lille 1, F-59650 Villeneuve d' Ascq (France); Waterlot, Christophe; Douay, Francis [Univ Lille Nord de France, F-59000 Lille (France); LGCgE, Equipe Sols et Environnement, Groupe ISA, 48 boulevard Vauban, F-59046 Lille Cedex (France); Vandenbulcke, Franck, E-mail: franck.vandenbulcke@univ-lille1.fr [Univ Lille Nord de France, F-59000 Lille (France); LGCgE, Equipe Ecologie Numerique et Ecotoxicologie, Lille 1, F-59650 Villeneuve d' Ascq (France)

    2011-11-15

    Past activities of 2 smelters (Metaleurop Nord and Nyrstar) led to the accumulation of high amounts of Metal Trace Elements (TEs) in top soils of the Noyelles-Godault/Auby area, Northern France. Earthworms were exposed to polluted soils collected in this area to study and better understand the physiological changes, the mechanisms of acclimation, and detoxification resulting from TE exposure. Previously we have cloned and transcriptionally characterized potential biomarkers from immune cells of the ecotoxicologically important earthworm species Eisenia fetida exposed in vivo to TE-spiked standard soils. In the present study, analysis of expression kinetics of four candidate indicator genes (Cadmium-metallothionein, coactosin like protein, phytochelatin synthase and lysenin) was performed in E. fetida after microcosm exposures to natural soils exhibiting an environmental cadmium (Cd) gradient in a kinetic manner. TE body burdens were also measured. This microcosm study provided insights into: (1) the ability of the 4 tested genes to serve as expression biomarkers, (2) detoxification processes through the expression analysis of selected genes, and (3) influence of land uses on the response of potential biomarkers (gene expression or TE uptake). - Highlights: {yields} Expression biomarkers in animals exposed to Cadmium-contaminated field soils. {yields} Expression kinetics to test the ability of genes to serve as expression biomarkers. {yields} Study of detoxification processes through the expression analysis of selected genes.

  10. Bio-markers and the search for extinct life on Mars

    Science.gov (United States)

    Schwartz, D. E.; Mancinelli, R. L.

    1989-01-01

    In order to predict what biomarkers could be used on Mars, several biomarkers, or key signatures, of extinct life on earth are identified. Some of these biomarkers which may be applicable to Mars include reduced carbon and nitrogen compounds, CO3(2-), SO4(2-), NO3(-), Mg, Mn, Fe, and the isotopic ratios of C, N, and S. It is suggested that a fully equipped Mars rover might be able to perform analyses to measure most of these biomarkers while on the Martian surface.

  11. A SYSTEMATIC SEARCH FOR MOLECULAR OUTFLOWS TOWARD CANDIDATE LOW-LUMINOSITY PROTOSTARS AND VERY LOW LUMINOSITY OBJECTS

    Energy Technology Data Exchange (ETDEWEB)

    Schwarz, Kamber R.; Shirley, Yancy L. [Steward Observatory, 933 N. Cherry Ave., Tucson, AZ 85721 (United States); Dunham, Michael M. [Department of Astronomy, Yale University, P.O. Box 208101, New Haven, CT 06520 (United States)

    2012-10-01

    We present a systematic single-dish search for molecular outflows toward a sample of nine candidate low-luminosity protostars and 30 candidate very low luminosity objects (VeLLOs; L{sub int} {<=} 0.1 L{sub Sun }). The sources are identified using data from the Spitzer Space Telescope cataloged by Dunham et al. toward nearby (D < 400 pc) star-forming regions. Each object was observed in {sup 12}CO and {sup 13}CO J = 2 {yields} 1 simultaneously using the sideband separating ALMA Band-6 prototype receiver on the Heinrich Hertz Telescope at 30'' resolution. Using five-point grid maps, we identify five new potential outflow candidates and make on-the-fly maps of the regions surrounding sources in the dense cores B59, L1148, L1228, and L1165. Of these new outflow candidates, only the map of B59 shows a candidate blue outflow lobe associated with a source in our survey. We also present larger and more sensitive maps of the previously detected L673-7 and the L1251-A-IRS4 outflows and analyze their properties in comparison to other outflows from VeLLOs. The accretion luminosities derived from the outflow properties of the VeLLOs with detected CO outflows are higher than the observed internal luminosity of the protostars, indicating that these sources likely had higher accretion rates in the past. The known L1251-A-IRS3 outflow is detected but not re-mapped. We do not detect clear, unconfused signatures of red and blue molecular wings toward the other 31 sources in the survey indicating that large-scale, distinct outflows are rare toward this sample of candidate protostars. Several potential outflows are confused with the kinematic structure in the surrounding core and cloud. Interferometric imaging is needed to disentangle large-scale molecular cloud kinematics from these potentially weak protostellar outflows.

  12. A SYSTEMATIC SEARCH FOR MOLECULAR OUTFLOWS TOWARD CANDIDATE LOW-LUMINOSITY PROTOSTARS AND VERY LOW LUMINOSITY OBJECTS

    International Nuclear Information System (INIS)

    Schwarz, Kamber R.; Shirley, Yancy L.; Dunham, Michael M.

    2012-01-01

    We present a systematic single-dish search for molecular outflows toward a sample of nine candidate low-luminosity protostars and 30 candidate very low luminosity objects (VeLLOs; L int ≤ 0.1 L ☉ ). The sources are identified using data from the Spitzer Space Telescope cataloged by Dunham et al. toward nearby (D 12 CO and 13 CO J = 2 → 1 simultaneously using the sideband separating ALMA Band-6 prototype receiver on the Heinrich Hertz Telescope at 30'' resolution. Using five-point grid maps, we identify five new potential outflow candidates and make on-the-fly maps of the regions surrounding sources in the dense cores B59, L1148, L1228, and L1165. Of these new outflow candidates, only the map of B59 shows a candidate blue outflow lobe associated with a source in our survey. We also present larger and more sensitive maps of the previously detected L673-7 and the L1251-A-IRS4 outflows and analyze their properties in comparison to other outflows from VeLLOs. The accretion luminosities derived from the outflow properties of the VeLLOs with detected CO outflows are higher than the observed internal luminosity of the protostars, indicating that these sources likely had higher accretion rates in the past. The known L1251-A-IRS3 outflow is detected but not re-mapped. We do not detect clear, unconfused signatures of red and blue molecular wings toward the other 31 sources in the survey indicating that large-scale, distinct outflows are rare toward this sample of candidate protostars. Several potential outflows are confused with the kinematic structure in the surrounding core and cloud. Interferometric imaging is needed to disentangle large-scale molecular cloud kinematics from these potentially weak protostellar outflows.

  13. Searching for an Oscillating Massive Scalar Field as a Dark Matter Candidate Using Atomic Hyperfine Frequency Comparisons.

    Science.gov (United States)

    Hees, A; Guéna, J; Abgrall, M; Bize, S; Wolf, P

    2016-08-05

    We use 6 yrs of accurate hyperfine frequency comparison data of the dual rubidium and caesium cold atom fountain FO2 at LNE-SYRTE to search for a massive scalar dark matter candidate. Such a scalar field can induce harmonic variations of the fine structure constant, of the mass of fermions, and of the quantum chromodynamic mass scale, which will directly impact the rubidium/caesium hyperfine transition frequency ratio. We find no signal consistent with a scalar dark matter candidate but provide improved constraints on the coupling of the putative scalar field to standard matter. Our limits are complementary to previous results that were only sensitive to the fine structure constant and improve them by more than an order of magnitude when only a coupling to electromagnetism is assumed.

  14. Improving the quality of biomarker candidates in untargeted metabolomics via peak table-based alignment of comprehensive two-dimensional gas chromatography-mass spectrometry data

    Science.gov (United States)

    Bean, Heather D.; Hill, Jane E.; Dimandja, Jean-Marie D.

    2015-01-01

    The potential of high-resolution analytical technologies like GC×GC/TOF MS in untargeted metabolomics and biomarker discovery has been limited by the development of fully automated software that can efficiently align and extract information from multiple chromatographic data sets. In this work we report the first investigation on a peak-by-peak basis of the chromatographic factors that impact GC×GC data alignment. A representative set of 16 compounds of different chromatographic characteristics were followed through the alignment of 63 GC×GC chromatograms. We found that varying the mass spectral match parameter had a significant influence on the alignment for poorly- resolved peaks, especially those at the extremes of the detector linear range, and no influence on well- chromatographed peaks. Therefore, optimized chromatography is required for proper GC×GC data alignment. Based on these observations, a workflow is presented for the conservative selection of biomarker candidates from untargeted metabolomics analyses. PMID:25857541

  15. WIMP dark matter candidates and searches-current status and future prospects.

    Science.gov (United States)

    Roszkowski, Leszek; Sessolo, Enrico Maria; Trojanowski, Sebastian

    2018-06-01

    We review several current aspects of dark matter theory and experiment. We overview the present experimental status, which includes current bounds and recent claims and hints of a possible signal in a wide range of experiments: direct detection in underground laboratories, gamma-ray, cosmic ray, x-ray, neutrino telescopes, and the LHC. We briefly review several possible particle candidates for a weakly interactive massive particle (WIMP) and dark matter that have recently been considered in the literature. We pay particular attention to the lightest neutralino of supersymmetry as it remains the best motivated candidate for dark matter and also shows excellent detection prospects. Finally we briefly review some alternative scenarios that can considerably alter properties and prospects for the detection of dark matter obtained within the standard thermal WIMP paradigm.

  16. A search for lithium in Pleiades brown dwarf candidates using the Keck hires echelle

    Science.gov (United States)

    Marcy, Geoffrey W.; Basri, Gibor; Graham, James R.

    1994-01-01

    We report Keck Observatory high-resolution echelle spectra of lithium at 670.8 nm in two of the lowest luminosity brown dwarf candidates in the Pleiades. These objects have estimated masses of 0.055 to 0.059 solar mass from their location on a color-magnitude diagram relative to theoretical isochrones. Stellar interior models predict that Li has not burned in them. However, we find no evidence of the Li line, at limits 100 to 1000 times below the initial abundance. This indicates that Li has in fact been depleted, presumably by nuclear processing as occurs in Pleiades stars. Interior models suggest that such large Li depletion occurs only for objects with M greater than 0.09 solar mass at the age of the Pleiades. Thus, it is unlikely that the candidates are brown dwarfs. The brown dwarf candidates present a conflict: either they have masses greater than suggested from their placement on the H-R diagram, or they do have the very low suggested masses but are nonetheless capable of destroying Li, in only 70 Myr. Until this dilemma is resolved, the photometric identification of brown dwarfs will remain difficult. Resolution may reside in higher T(sub eff) derived from optical and IR colors or in lower T(sub eff) in the interior models.

  17. Search for neutrino generated air shower candidates with energy ≥ 1019 eV and Zenith angle θ

    Science.gov (United States)

    Knurenko, Stanislav; Petrov, Igor; Sabourov, Artem

    2017-06-01

    The description of the methodology and results of searching for air showers generated by neutral particles such as high energy gamma quanta and astroneutrinos are presented. For this purpose, we conducted a comprehensive analysis of the data: the electron, the muon and the EAS Cerenkov light, and their response time in scintillation and Cherenkov detectors. Air showers with energy more than 5·1018 eV and zenith angle θ ≥ 55∘ are selected and analyzed. Search results indicate a lack of air shower events formed by gamma-rays or high-energy neutrinos, but it does not mean that such air showers do not exist in nature; for example, experiments that recorded showers having a marked low muon content, i.e., "Muonless", are likely to be candidates for showers produced by neutral primary particles.

  18. Search for Gamma-Ray Emission from DES Dwarf Spheroidal Galaxy Candidates with Fermi-LAT Data

    Energy Technology Data Exchange (ETDEWEB)

    Drlica-Wagner, A.; et al.

    2015-08-04

    Due to their proximity, high dark-matter (DM) content, and apparent absence of non-thermal processes, Milky Way dwarf spheroidal satellite galaxies (dSphs) are excellent targets for the indirect detection of DM. Recently, eight new dSph candidates were discovered using the first year of data from the Dark Energy Survey (DES). We searched for gamma-ray emission coincident with the positions of these new objects in six years of Fermi Large Area Telescope data. We found no significant excesses of gamma-ray emission. Under the assumption that the DES candidates are dSphs with DM halo properties similar to the known dSphs, we computed individual and combined limits on the velocity-averaged DM annihilation cross section for these new targets. If the estimated DM content of these dSph candidates is confirmed, they will constrain the annihilation cross section to lie below the thermal relic cross section for DM particles with masses $\\lesssim 20\\,\\mathrm{GeV}$ annihilating via the $b\\bar{b}$ or τ(+)τ(-) channels.

  19. [Search for potential gastric cancer biomarkers using low molecular weight blood plasma proteome profiling by mass spectrometry].

    Science.gov (United States)

    Shevchenko, V E; Arnotskaia, N E; Ogorodnikova, E V; Davydov, M M; Ibraev, M A; Turkin, I N; Davydov, M I

    2014-01-01

    Gastric cancer, one of the most widespread malignant tumors, still lacks reliable serum/plasma biomarkers of its early detection. In this study we have developed, unified, and tested a new methodology for search of gastric cancer biomarkers based on profiling of low molecular weight proteome (LMWP) (1-17 kDa). This approach included three main components: sample pre-fractionation, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), data analysis by a bioinformatics software package. Applicability and perspectives of the developed approach for detection of potential gastric cancer markers during LMWP analysis have been demonstrated using 69 plasma samples from patients with gastric cancer (stages I-IV) and 238 control samples. The study revealed peptides/polypeptides, which may be potentially used for detection of this pathology.

  20. Analysis of the ectoenzymes ADA, ALP, ENPP1, and ENPP3, in the contents of ovarian endometriomas as candidate biomarkers of endometriosis.

    Science.gov (United States)

    Trapero, Carla; Jover, Lluis; Fernández-Montolí, Maria Eulàlia; García-Tejedor, Amparo; Vidal, August; Gómez de Aranda, Inmaculada; Ponce, Jordi; Matias-Guiu, Xavier; Martín-Satué, Mireia

    2018-02-01

    The diagnosis of endometriosis, a prevalent chronic disease with a strong inflammatory component, is usually delayed due to the lack of noninvasive diagnostic tests. Purinergic signaling, a key cell pathway, is altered in many inflammatory disorders. The aim of the present work was to evaluate the levels of adenosine deaminase (ADA), alkaline phosphatase (ALP), ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and ENPP3, elements of purinergic signaling, as biomarker candidates for endometriosis. A case-control comparative study was conducted to determine ADA, ALP, ENPP1 and ENPP3 levels in echo-guided aspirated fluids of endometriomas (case group) and simple ovarian cysts (control group) using the ELISA technique. Adenosine deaminase, ALP, ENPP1, and ENPP3 were present and quantifiable in the contents of endometriomas and simple cysts. There were significant differences in ADA and ENPP1 levels in endometriomas in comparison with simple cysts (2787 U/L and 103.9 ng/mL more in endometriomas, for ADA and ENPP1, respectively). Comparisons of ALP and ENPP3 levels between the two groups did not reveal significant differences. The ectoenzymes ADA and ENPP1 are biomarker candidates for endometriosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Label-Free LC-MS/MS Proteomic Analysis of Cerebrospinal Fluid Identifies Protein/Pathway Alterations and Candidate Biomarkers for Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Collins, Mahlon A; An, Jiyan; Hood, Brian L; Conrads, Thomas P; Bowser, Robert P

    2015-11-06

    Analysis of the cerebrospinal fluid (CSF) proteome has proven valuable to the study of neurodegenerative disorders. To identify new protein/pathway alterations and candidate biomarkers for amyotrophic lateral sclerosis (ALS), we performed comparative proteomic profiling of CSF from sporadic ALS (sALS), healthy control (HC), and other neurological disease (OND) subjects using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 1712 CSF proteins were detected and relatively quantified by spectral counting. Levels of several proteins with diverse biological functions were significantly altered in sALS samples. Enrichment analysis was used to link these alterations to biological pathways, which were predominantly related to inflammation, neuronal activity, and extracellular matrix regulation. We then used our CSF proteomic profiles to create a support vector machines classifier capable of discriminating training set ALS from non-ALS (HC and OND) samples. Four classifier proteins, WD repeat-containing protein 63, amyloid-like protein 1, SPARC-like protein 1, and cell adhesion molecule 3, were identified by feature selection and externally validated. The resultant classifier distinguished ALS from non-ALS samples with 83% sensitivity and 100% specificity in an independent test set. Collectively, our results illustrate the utility of CSF proteomic profiling for identifying ALS protein/pathway alterations and candidate disease biomarkers.

  2. Fluid biomarkers in multiple system atrophy

    DEFF Research Database (Denmark)

    Laurens, Brice; Constantinescu, Radu; Freeman, Roy

    2015-01-01

    Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target...... engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood...... and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results...

  3. Search for new candidates for the neutrino-oriented mass determination by electron-capture

    CERN Multimedia

    Herfurth, F; Boehm, C; Blaum, K; Beck, D

    2008-01-01

    This proposal is part of an extended program dedicated to the neutrino-mass determination in the electron-capture sector, which aims at ultra-precise mass measurements by Penning traps in combination with cryogenic micro-calorimetry for atomic de-excitation measurements. Here, precise mass measurements with ISOLTRAP are proposed for the orbital electron-capture nuclides $^{194}$Hg and $^{202}$Pb, as well as their daughters, with the goal to determine accurately their Q-values. These values are expected to be the smallest ones among a great variety of known electron-capture precursors. Therefore, these nuclides are strong candidates for an improved electron-neutrino mass determination. We ask for 8 shifts of on-line beam at ISOLDE for mass measurements of $^{194}$Hg, $^{194}$ Au, $^{202}$Pb, and $^{202}$Tl at ISOLTRAP.

  4. Planetary nebulae search in the outskirts of M33: looking for the farthest candidates

    Science.gov (United States)

    Galera Rosillo, Rebeca; Corradi, Romano L. M.; Mampaso Recio, Antonio

    2015-08-01

    The nearby disc galaxy M33 is one of the best laboratories for testing chemical evolution models in galaxies and for understanding disc formation mechanisms. In this galaxy, planetary nebulae (PNe) were previously extensively studied only within a galactocentric radius of 8 kpc.In the framework of a broad study of the population of PNe in Local Group disc galaxies, we present the results of a deep narrow-band imaging of the outer regions of M33, performed using the Wide Field Camera at the 2.5 m Isaac Newton Telescope (INT).The INT images were obtained in the narrow-band filters selecting the [OIII] 5007 Å and Hα 6563 Å lines, plus broad-band filters SDSS g and i. A photometric catalog of around 150000 sources covering a total area of 5 square degrees, and extending out to 2 deg (30 kpc at the adopted distance of 840 kpc) from the centre of the galaxy is presented.PNe candidates are selected in the [OIII]-g vs Hα-r colour-colour diagram as bright emitters in the narrowband filters. A number of candidates with similar colours to those of known PNe, and with an apparent [OIII] magnitude > 21 have been selected for future follow-up. Three of these have been already spectroscopically confirmed at the William Herschel Telescope (WHT).Our survey will improve the knowledge of the PNe population in the outskirts of M33, constraining the properties of its metal-poor halo and of the extended disc substructures that have been proposed to be related to a relatively recent interaction with M31.

  5. Host Response to Environmental Hazards: Using Literature, Bioinformatics, and Computation to Derive Candidate Biomarkers of Toxic Industrial Chemical Exposure

    Science.gov (United States)

    2015-10-01

    military threat chemicals with adverse health effects and clinical outcomes to improve diagnostic potential after exposure to toxic industrial...end organ injury following chemical exposures in the field. Markers of end-organ injury and toxicity and other health effects markers, particularly...Biomarkers of Toxic Industrial Chemical Exposure Major Jonathan D. Stallings *1 , Danielle L. Ippolito 1 , Anders Wallqvist 2 , B. Claire McDyre 3 , and

  6. Search for specific biomarkers of IFNβ bioactivity in patients with multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Sunny Malhotra

    Full Text Available Myxovirus A (MxA, a protein encoded by the MX1 gene with antiviral activity, has proven to be a sensitive measure of IFNβ bioactivity in multiple sclerosis (MS. However, the use of MxA as a biomarker of IFNβ bioactivity has been criticized for the lack of evidence of its role on disease pathogenesis and the clinical response to IFNβ. Here, we aimed to identify specific biomarkers of IFNβ bioactivity in order to compare their gene expression induction by type I IFNs with the MxA, and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB to IFNβ at 12 and/or 24 months of treatment and patients who remained NAB negative. Nine genes followed patterns in gene expression over time similar to the MX1, which was considered the gold standard gene, and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments in PBMC from healthy controls revealed specific induction of selected biomarkers by IFNβ but not IFNγ, and several markers, in particular USP18 and HERC5, were shown to be significantly induced at lower IFNβ concentrations and more selective than the MX1 as biomarkers of IFNβ bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p = 0.0004. We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFNβ bioactivity, and to further explore their implication in MS pathogenesis.

  7. Developmental origins of metabolic disorders: The need for biomarker candidates and therapeutic targets from adequate preclinical models

    Directory of Open Access Journals (Sweden)

    Antonio Gonzalez-Bulnes

    2016-03-01

    Full Text Available The investigation on obesity and associated disorders have changed from an scenario in which genome drove the phenotype to a dynamic setup in which prenatal and early-postnatal conditions are determinant. However, research in human beings is difficult due to confounding factors (lifestyle and socioeconomic heterogeneity plus ethical issues. Hence, there is currently an intensive effort for developing adequate preclinical models, aiming for an adequate combination of basic studies in rodent models and specific preclinical studies in large animals. The results of these research strategies may increase the identification and development of contrasted biomarkers and therapeutic targets.

  8. Comprehensive Quantitative Profiling of Tau and Phosphorylated Tau Peptides in Cerebrospinal Fluid by Mass Spectrometry Provides New Biomarker Candidates.

    Science.gov (United States)

    Russell, Claire L; Mitra, Vikram; Hansson, Karl; Blennow, Kaj; Gobom, Johan; Zetterberg, Henrik; Hiltunen, Mikko; Ward, Malcolm; Pike, Ian

    2017-01-01

    Aberrant tau phosphorylation is a hallmark in Alzheimer's disease (AD), believed to promote formation of paired helical filaments, the main constituent of neurofibrillary tangles in the brain. While cerebrospinal fluid (CSF) levels of total tau and tau phosphorylated at threonine residue 181 (pThr181) are established core biomarkers for AD, the value of alternative phosphorylation sites, which may have more direct relevance to pathology, for early diagnosis is not yet known, largely due to their low levels in CSF and lack of standardized detection methods. To overcome sensitivity limitations for analysis of phosphorylated tau in CSF, we have applied an innovative mass spectrometry (MS) workflow, TMTcalibratortrademark, to enrich and enhance the detection of phosphoproteome components of AD brain tissue in CSF, and enable the quantitation of these analytes. We aimed to identify which tau species present in the AD brain are also detectable in CSF and which, if any, are differentially regulated with disease. Over 75% coverage of full-length (2N4R) tau was detected in the CSF with 47 phosphopeptides covering 31 different phosphorylation sites. Of these, 11 phosphopeptides were upregulated by at least 40%, along with an overall increase in tau levels in the CSF of AD patients relative to controls. Use of the TMTcalibratortrademark workflow dramatically improved our ability to detect tau-derived peptides that are directly related to human AD pathology. Further validation of regulated tau peptides as early biomarkers of AD is warranted and is currently being undertaken.

  9. Tubulin Beta-3 Chain as a New Candidate Protein Biomarker of Human Skin Aging: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Sylvia G. Lehmann

    2017-01-01

    Full Text Available Skin aging is a complex process, and a lot of efforts have been made to identify new and specific targets that could help to diagnose, prevent, and treat skin aging. Several studies concerning skin aging have analyzed the changes in gene expression, and very few investigations have been performed at the protein level. Moreover, none of these proteomic studies has used a global quantitative labeled proteomic offgel approach that allows a more accurate description of aging phenotype. We applied such an approach on human primary keratinocytes obtained from sun-nonexposed skin biopsies of young and elderly women. A total of 517 unique proteins were identified, and 58 proteins were significantly differentially expressed with 40 that were downregulated and 18 upregulated with aging. Gene ontology and pathway analysis performed on these 58 putative biomarkers of skin aging evidenced that these dysregulated proteins were mostly involved in metabolism and cellular processes such as cell cycle and signaling pathways. Change of expression of tubulin beta-3 chain was confirmed by western blot on samples originated from several donors. Thus, this study suggested the tubulin beta-3 chain has a promising biomarker in skin aging.

  10. Comparing human pancreatic cell secretomes by in vitro aptamer selection identifies cyclophilin B as a candidate pancreatic cancer biomarker.

    Science.gov (United States)

    Ray, Partha; Rialon-Guevara, Kristy L; Veras, Emanuela; Sullenger, Bruce A; White, Rebekah R

    2012-05-01

    Most cases of pancreatic cancer are not diagnosed until they are no longer curable with surgery. Therefore, it is critical to develop a sensitive, preferably noninvasive, method for detecting the disease at an earlier stage. In order to identify biomarkers for pancreatic cancer, we devised an in vitro positive/negative selection strategy to identify RNA ligands (aptamers) that could detect structural differences between the secretomes of pancreatic cancer and non-cancerous cells. Using this molecular recognition approach, we identified an aptamer (M9-5) that differentially bound conditioned media from cancerous and non-cancerous human pancreatic cell lines. This aptamer further discriminated between the sera of pancreatic cancer patients and healthy volunteers with high sensitivity and specificity. We utilized biochemical purification methods and mass-spectrometric analysis to identify the M9-5 target as cyclophilin B (CypB). This molecular recognition-based strategy simultaneously identified CypB as a serum biomarker and generated a new reagent to recognize it in body fluids. Moreover, this approach should be generalizable to other diseases and complementary to traditional approaches that focus on differences in expression level between samples. Finally, we suggest that the aptamer we identified has the potential to serve as a tool for the early detection of pancreatic cancer.

  11. Improving the quality of biomarker candidates in untargeted metabolomics via peak table-based alignment of comprehensive two-dimensional gas chromatography-mass spectrometry data.

    Science.gov (United States)

    Bean, Heather D; Hill, Jane E; Dimandja, Jean-Marie D

    2015-05-15

    The potential of high-resolution analytical technologies like GC×GC/TOF MS in untargeted metabolomics and biomarker discovery has been limited by the development of fully automated software that can efficiently align and extract information from multiple chromatographic data sets. In this work we report the first investigation on a peak-by-peak basis of the chromatographic factors that impact GC×GC data alignment. A representative set of 16 compounds of different chromatographic characteristics were followed through the alignment of 63 GC×GC chromatograms. We found that varying the mass spectral match parameter had a significant influence on the alignment for poorly-resolved peaks, especially those at the extremes of the detector linear range, and no influence on well-chromatographed peaks. Therefore, optimized chromatography is required for proper GC×GC data alignment. Based on these observations, a workflow is presented for the conservative selection of biomarker candidates from untargeted metabolomics analyses. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Global DNA methylation in earthworms: A candidate biomarker of epigenetic risks related to the presence of metals/metalloids in terrestrial environments

    Energy Technology Data Exchange (ETDEWEB)

    Maldonado Santoyo, Maria; Rodriguez Flores, Crescencio; Lopez Torres, Adolfo; Wrobel, Kazimierz [Department of Chemistry, University of Guanajuato, L de Retana No 5, 36000 Guanajuato (Mexico); Wrobel, Katarzyna, E-mail: katarzyn@quijote.ugto.mx [Department of Chemistry, University of Guanajuato, L de Retana No 5, 36000 Guanajuato (Mexico)

    2011-10-15

    In this work, possible relationships between global DNA methylation and metal/metalloid concentrations in earthworms have been explored. Direct correlation was observed between soil and tissue As, Se, Sb, Zn, Cu, Mn, Ag, Co, Hg, Pb (p < 0.05). Speciation results obtained for As and Hg hint at the capability of earthworms for conversion of inorganic element forms present in soil to methylated species. Inverse correlation was observed between the percentage of methylated DNA cytosines and total tissue As, As + Hg, As + Hg + Se + Sb ({beta} = -0.8456, p = 0.071; {beta} = -0.9406, p = 0.017; {beta} = -0.9526, p = 0.012 respectively), as well as inorganic As + Hg ({beta} = -0.8807, p = 0.049). It was concluded that earthworms would be particularly helpful as bioindicators of elements undergoing in vivo methylation and might also be used to assess the related risk of epigenetic changes in DNA methylation. - Graphical abstract: Display Omitted Highlights: > Several metals and metalloids contribute to epigenetic gene regulation. > As, Hg, Se, Sb inversely correlated with global DNA methylation in earthworms. > Biomethylation of the above elements in worms suggested. > Elements biomethylation apparently competes with DNA methylation. > DNA methylation a biomarker of epigenetic risks related to soil metals/metalloids. - Biomethylation of As, Hg in earthworms versus DNA methylation - a candidate biomarker of epigenetic risks related to the presence of metals/metalloids in soil.

  13. Evaluation of the biomarker candidate MFAP4 for non-invasive assessment of hepatic fibrosis in hepatitis C patients

    DEFF Research Database (Denmark)

    Bracht, Thilo; Mölleken, Christian; Ahrens, Maike

    2016-01-01

    in a retrospective study including n = 542 hepatitis C patients. We applied a univariate logistic regression model based on MFAP4 serum levels and furthermore derived a multivariate model including also age and gender. Youden-optimal cutoffs for binary classification were determined for both models without......). CONCLUSIONS: We confirmed the applicability of MFAP4 as a novel serum biomarker for assessment of hepatic fibrosis and identification of high-risk patients with severe fibrosis stages in hepatitis C. The combination of MFAP4 with existing tests might lead to a more accurate non-invasive diagnosis of hepatic...... fibrosis and allow a cost-effective disease management in the era of new direct acting antivirals....

  14. A systems biology strategy reveals biological pathways and plasma biomarker candidates for potentially toxic statin-induced changes in muscle.

    Directory of Open Access Journals (Sweden)

    Reijo Laaksonen

    Full Text Available BACKGROUND: Aggressive lipid lowering with high doses of statins increases the risk of statin-induced myopathy. However, the cellular mechanisms leading to muscle damage are not known and sensitive biomarkers are needed to identify patients at risk of developing statin-induced serious side effects. METHODOLOGY: We performed bioinformatics analysis of whole genome expression profiling of muscle specimens and UPLC/MS based lipidomics analyses of plasma samples obtained in an earlier randomized trial from patients either on high dose simvastatin (80 mg, atorvastatin (40 mg, or placebo. PRINCIPAL FINDINGS: High dose simvastatin treatment resulted in 111 differentially expressed genes (1.5-fold change and p-value<0.05, while expression of only one and five genes was altered in the placebo and atorvastatin groups, respectively. The Gene Set Enrichment Analysis identified several affected pathways (23 gene lists with False Discovery Rate q-value<0.1 in muscle following high dose simvastatin, including eicosanoid synthesis and Phospholipase C pathways. Using lipidomic analysis we identified previously uncharacterized drug-specific changes in the plasma lipid profile despite similar statin-induced changes in plasma LDL-cholesterol. We also found that the plasma lipidomic changes following simvastatin treatment correlate with the muscle expression of the arachidonate 5-lipoxygenase-activating protein. CONCLUSIONS: High dose simvastatin affects multiple metabolic and signaling pathways in skeletal muscle, including the pro-inflammatory pathways. Thus, our results demonstrate that clinically used high statin dosages may lead to unexpected metabolic effects in non-hepatic tissues. The lipidomic profiles may serve as highly sensitive biomarkers of statin-induced metabolic alterations in muscle and may thus allow us to identify patients who should be treated with a lower dose to prevent a possible toxicity.

  15. Alpha-fetoprotein-L3 and Golgi protein 73 may serve as candidate biomarkers for diagnosing alpha-fetoprotein-negative hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang ZG

    2015-12-01

    Full Text Available Zhiguo Zhang,1 Yanying Zhang,2 Yeying Wang,1 Lingling Xu,3 Wanju Xu3 1Department of Clinical Laboratory, Zhangqiu Maternity and Child Care Hospital, Zhangqiu, 2Department of Clinical Laboratory, Zaozhuang City Wangkai Infection Hospital, Zaozhuang, 3Department of Clinical Laboratory, Qianfoshan Hospital, Jinan, People’s Republic of China Abstract: Currently, there is no reliable biomarker for use in diagnosing alpha-fetoprotein (AFP-negative hepatocellular carcinoma (HCC. Such a biomarker would aid in making an early diagnosis of AFP-negative HCC, ensuring the timely initiation of treatment. This study examined AFP-L3 and Golgi protein 73 (GP73 as candidate biomarkers for AFP-negative HCC. The affinity adsorption method and enzyme-linked immunoassays were separately used to determine serum levels of AFP-L3 and GP73 in 50 patients with AFP-negative HCC, 30 non-HCC patients, and 50 healthy subjects. Fifty percent of patients with AFP-negative HCC tested positive for AFP-L3, while 3.33% of non-HCC patients and 2.00% of healthy subjects were AFP-L3 positive. Patients with AFP-negative HCC had significantly higher serum levels of AFP-L3 compared to non-HCC patients and healthy individuals; however, there was no significant difference in the AFP-L3 levels of non-HCC patients and healthy subjects. Sixty-six percent of patients with AFP-negative HCC tested positive for GP73, while 10% of non-HCC patients and 0% of healthy subjects were GP73-positive. Patients with AFP-negative HCC had significantly higher serum levels of GP73 compared to non-HCC patients and healthy subjects, but there was no significant difference between the GP73 levels of non-HCC patients and healthy individuals. Moreover, 20 patients with AFP-negative HCC were both AFP-L3- and GP73-positive, while no non-HCC patients or healthy subjects tested positive for both markers. Either AFP-L3 or GP73 may be used as a biomarker for diagnosing AFP-negative HCC, while their combined use

  16. Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers.

    Science.gov (United States)

    Novakova, Lenka; Axelsson, Markus; Malmeström, Clas; Imberg, Henrik; Elias, Olle; Zetterberg, Henrik; Nerman, Olle; Lycke, Jan

    2018-01-01

    Neurodegeneration occurs during the early stages of multiple sclerosis. It is an essential, devastating part of the pathophysiology. Tools for measuring the degree of neurodegeneration could improve diagnostics and patient characterization. This study aimed to determine the diagnostic value of biomarkers of degeneration in patients with recent clinical onset of suspected multiple sclerosis, and to evaluate these biomarkers for characterizing disease course. This cross-sectional study included 271 patients with clinical features of suspected multiple sclerosis onset and was the baseline of a prospective study. After diagnostic investigations, the patients were classified into the following disease groups: patients with clinically isolated syndrome (n = 4) or early relapsing remitting multiple sclerosis (early RRMS; n = 93); patients with relapsing remitting multiple sclerosis with disease durations ≥2 years (established RRMS; n = 39); patients without multiple sclerosis, but showing symptoms (symptomatic controls; n = 89); and patients diagnosed with other diseases (n = 46). In addition, we included healthy controls (n = 51) and patients with progressive multiple sclerosis (n = 23). We analyzed six biomarkers of neurodegeneration: cerebrospinal fluid neurofilament light chain levels; cerebral spinal fluid glial fibrillary acidic protein; cerebral spinal fluid tau; retinal nerve fiber layer thickness; macula volume; and the brain parenchymal fraction. Except for increased cerebral spinal fluid neurofilament light chain levels, median 670 ng/L (IQR 400-2110), we could not find signs of early degeneration in the early disease group with recent clinical onset. However, the intrathecal immunoglobin G production and cerebral spinal fluid neurofilament light chain levels showed diagnostic value. Moreover, elevated levels of cerebral spinal fluid glial fibrillary acidic protein, thin retinal nerve fiber layers, and low brain parenchymal fractions were associated with

  17. Search for elemental and mineral biomarkers using inelastic neutron scattering spectroscopy (INSS)

    Science.gov (United States)

    Wielopolski, Lucian; Hoover, Richard B.; Mitra, Sudeep

    2004-02-01

    Life on Earth is characterized by a select group of low Z elements: C, H, N, O, P, K, S, Na, Cl. The presence of these elements and their ratios can provide indications of possible biogenicity and thus they may constitute valuable biomarkers that may help determine the best locations to seek more definitive evidence of life. We discuss the possible applications and significance of the inelastic neutron scattering induced gamma spectroscopy (INSGS) for future Astrobiology Missions to Mars or other solar System bodies. The general requirements and capabilities of the proposed approach are presented.

  18. Neopterin: A candidate biomarker for the early assessment of toxicity of aluminum among bauxite dust exposed mine workers

    Science.gov (United States)

    Pingle, Shubhangi K.; Thakkar, Lucky R.; Jawade, Aruna A.; Tumane, Rajani G.; Jain, Ruchika K.; Soni, Pravin N.

    2015-01-01

    Introduction: Bauxite ore is a major source of aluminum (Al) which contains approximately 35–60% Al by weight. Occupational and environmental bauxite dust exposure may cause toxicity by interaction with human biological systems resulting in oxidative stress (OS) and cell death. A neopterin derivative as an antioxidant is able to modulate cytotoxicity by the induction of OS. Materials and Methods: A total of 273 subjects were selected for blood collection from three different major Al producing bauxite mines and were categorized into three groups as experimental (Exp) (n = 150), experimental controls (ExC) (n = 73) and control (Con) (n = 50). Whole blood and serum samples were used for measurement of Al, neopterin, urea and creatinine values. Statistical analysis was performed using R-2.15.1 programming language. Results and Discussion: The result showed that age, body mass index and the behavioral habits, that is, smoking, tobacco and alcohol consumption have possible effects on neopterin level. Serum neopterin levels were found to be significantly higher (P bauxite dust (even at low levels of Al) changes biochemical profile leading to high levels of serum neopterin. Levels of serum neopterin in workers exposed to bauxite dust were probably examined for the 1st time in India. The outcome of this study suggested that serum neopterin may be used as potential biomarker for early detection of health risks associated with bauxite dust exposed population. PMID:26500413

  19. An integrated workflow for multiplex CSF proteomics and peptidomics-identification of candidate cerebrospinal fluid biomarkers of Alzheimer's disease.

    Science.gov (United States)

    Hölttä, Mikko; Minthon, Lennart; Hansson, Oskar; Holmén-Larsson, Jessica; Pike, Ian; Ward, Malcolm; Kuhn, Karsten; Rüetschi, Ulla; Zetterberg, Henrik; Blennow, Kaj; Gobom, Johan

    2015-02-06

    Many disease processes in the brain are reflected in the protein composition of the cerebrospinal fluid (CSF). In addition to proteins, CSF also contains a large number of endogenous peptides whose potential as disease biomarkers largely remains to be explored. We have developed a novel workflow in which multiplex isobaric labeling is used for simultaneous quantification of endogenous CSF peptides and proteins by liquid chromatography coupled with mass spectrometry. After the labeling of CSF samples, endogenous peptides are separated from proteins by ultrafiltration. The proteins retained on the filters are trypsinized, and the tryptic peptides are collected separately. We evaluated this technique in a comparative pilot study of CSF peptide and protein profiles in eight patients with Alzheimer's disease (AD) and eight nondemented controls. We identified several differences between the AD and control group among endogenous peptides derived from proteins known to be associated with AD, including neurosecretory protein VGF (ratios AD/controls 0.45-0.81), integral membrane protein 2B (ratios AD/controls 0.72-0.84), and metallothionein-3 (ratios AD/controls 0.51-0.61). Analysis of tryptic peptides identified several proteins that were altered in the AD group, some of which have previously been reported as changed in AD, for example, VGF (ratio AD/controls 0.70).

  20. Search for Chemical Biomarkers on Mars Using the Sample Analysis at Mars Instrument Suite on the Mars Science Laboratory

    Science.gov (United States)

    Glavin, D. P.; Conrad, P.; Dworkin, J. P.; Eigenbrode, J.; Mahaffy, P. R.

    2011-01-01

    One key goal for the future exploration of Mars is the search for chemical biomarkers including complex organic compounds important in life on Earth. The Sample Analysis at Mars (SAM) instrument suite on the Mars Science Laboratory (MSL) will provide the most sensitive measurements of the organic composition of rocks and regolith samples ever carried out in situ on Mars. SAM consists of a gas chromatograph (GC), quadrupole mass spectrometer (QMS), and tunable laser spectrometer to measure volatiles in the atmosphere and released from rock powders heated up to 1000 C. The measurement of organics in solid samples will be accomplished by three experiments: (1) pyrolysis QMS to identify alkane fragments and simple aromatic compounds; pyrolysis GCMS to separate and identify complex mixtures of larger hydrocarbons; and (3) chemical derivatization and GCMS extract less volatile compounds including amino and carboxylic acids that are not detectable by the other two experiments.

  1. Search for high confidence AGN candidates and its counterparts in the Fermi-LAT unassociated sample using machine learning

    Energy Technology Data Exchange (ETDEWEB)

    Einecke, Sabrina [Technical University Dortmund (Germany); Doert, Marlene [Ruhr-University Bochum (Germany)

    2016-07-01

    The third Fermi-LAT source catalog (3FGL) is the deepest all-sky survey in gamma-rays and comprises 3033 point sources. While for 2023 sources plausible associations have been found, 1010 remain unassociated. A search for active galactic nuclei (AGN) will help to reduce the number of unassociated sources, and will increase our knowledge of the population of gamma-ray emitting AGN. Several machine learning approaches applied to Fermi data have shown the capability of this method. The extension to multiwavelength data improves these studies, and at the same time offers the possibility to determine the most likely corresponding counterpart. As the 95% confidence region of the localization by the Fermi measurement is in the order of several arcminutes, generally multiple point sources at different wavelengths are located within this region and the association is ambiguous. To figure out the most likely counterpart, the associated sample is used to train machine learning classifiers as e.g. the random forest. Therefore, all possible combinations of the Fermi measurement and the measurements at a second wavelength are considered for a particular source. In this talk, the statistical model to obtain high confidence AGN counterpart candidates is described as well as the validation of the model to estimate the performance.

  2. Search for high-energy neutrinos from gravitational wave event GW151226 and candidate LVT151012 with ANTARES and IceCube

    NARCIS (Netherlands)

    Albert, A.; Andre, M.; Anghinolfi, M.; Anton, G.; Ardid, M.; Aubert, J. -J.; Avgitas, T.; Baret, B.; Barrios-Marti, J.; Basa, S.; Bertin, V.; Biagi, S.; Bormuth, R.; Bourret, S.; Bouwhuis, M. C.; Bruijn, R.; Brunner, J.; Busto, J.; Capone, A.; Caramete, L.; Carr, J.; Celli, S.; Chiarusi, T.; Circella, M.; Coelho, J. A. B.; Coleiro, A.; Coniglione, R.; Costantini, H.; Coyle, P.; Creusot, A.; Deschamps, A.; De Bonis, G.; Distefano, C.; Di Palma, I.; Donzaud, C.; Dornic, D.; Drouhin, D.; Eberl, T.; El Bojaddaini, I.; Elsaesser, D.; Enzenhofer, A.; Felis, I.; Fusco, L. A.; Galata, S.; Gay, P.; Giordano, V.; Glotin, H.; Gregoire, T.; Ruiz, R. Gracia; Graf, K.; Hallmann, S.; van Haren, H.; Heijboer, A. J.; Hello, Y.; Hernandez-Rey, J. J.; Hoessl, J.; Hofestaedt, J.; Hugon, C.; Illuminati, G.; James, C. W.; de Jong, M.; Jongen, M.; Kadler, M.; Kalekin, O.; Katz, U.; Kiessling, D.; Kouchner, A.; Kreter, M.; Kreykenbohm, I.; Kulikovskiy, V.; Lachaud, C.; Lahmann, R.; Lefevre, D.; Leonora, E.; Lotze, M.; Loucatos, S.; Marcelin, M.; Margiotta, A.; Marinelli, A.; Martinez-Mora, J. A.; Mathieu, A.; Mele, R.; Melis, K.; Michael, T.; Migliozzi, P.; Moussa, A.; Nezri, E.; Pavalas, G. E.; Pellegrino, C.; Perrina, C.; Piattelli, P.; Popa, V.; Pradier, T.; Quinn, L.; Racca, C.; Riccobene, G.; Sanchez-Losa, A.; Saldana, M.; Salvadori, I.; Samtleben, D. F. E.; Sanguineti, M.; Sapienza, P.; Schussler, F.; Sieger, C.; Spurio, M.; Stolarczyk, Th.; Taiuti, M.; Tayalati, Y.; Trovato, A.; Turpin, D.; Tonnis, C.; Vallage, B.; Vallee, C.; Van Elewyck, V.; Versari, F.; Vivolo, D.; Vizzoca, A.; Wilms, J.; Zornoza, J. D.; Zuniga, J.; Aartsen, M. G.; Ackermann, M.; Adams, J.; Aguilar, J. A.; Ahlers, M.; Ahrens, M.; Al Samarai, I.; Altmann, D.; Andeen, K.; Anderson, T.; Ansseau, I.; Anton, G.; Archinger, M.; Arguelles, C.; Auffenberg, J.; Axani, S.; Bagherpour, H.; Bai, X.; Barwick, S. W.; Baum, V.; Bay, R.; Beatty, J. J.; Tjus, J. Becker; Becker, K. -H.; BenZvi, S.; Berley, D.; Bernardini, E.; Besson, D. Z.; Binder, G.; Bindig, D.; Blaufuss, E.; Blot, S.; Bohm, C.; Borner, M.; Bos, F.; Bose, D.; Boser, S.; Botner, O.; Bradascio, F.; Braun, J.; Brayeur, L.; Bretz, H. -P.; Bron, S.; Burgman, A.; Carver, T.; Casier, M.; Cheung, E.; Chirkin, D.; Christov, A.; Clark, K.; Classen, L.; Coenders, S.; Collin, G. H.; Conrad, J. M.; Cowen, D. F.; Cross, R.; Day, M.; de Andre, J. P. A. M.; De Clercq, C.; Rosendo, E. del Pino; Dembinski, H.; De Ridder, S.; Desiati, P.; de Vries, K. D.; de Wasseige, G.; de With, M.; DeYoung, T.; Diaz-Velez, J. C.; di Lorenzo, V.; Dujmovic, H.; Dumm, J. P.; Dunkman, M.; Eberhardt, B.; Ehrhardt, T.; Eichmann, B.; Eller, P.; Euler, S.; Evenson, P. A.; Fahey, S.; Fazely, A. R.; Feintzeig, J.; Felde, J.; Filimonov, K.; Finley, C.; Flis, S.; Fosig, C. -C.; Franckowiak, A.; Friedman, E.; Fuchs, T.; Gaisser, T. K.; Gallagher, J.; Gerhardt, L.; Ghorbani, K.; Giang, W.; Gladstone, L.; Glauch, T.; Gluesenkamp, T.; Goldschmidt, A.; Gonzalez, J. G.; Grant, D.; Griffith, Z.; Haack, C.; Hallgren, A.; Halzen, F.; Hansen, E.; Hansmann, T.; Hanson, K.; Hebecker, D.; Heereman, D.; Helbing, K.; Hellauer, R.; Hickford, S.; Hignight, J.; Hill, G. C.; Hoffman, K. D.; Hoffmann, R.; Hoshina, K.; Huang, F.; Huber, M.; Hultqvist, K.; In, S.; Ishihara, A.; Jacobi, E.; Japaridze, G. S.; Jeong, M.; Jero, K.; Jones, B. J. P.; Kang, W.; Kappes, A.; Karg, T.; Karle, A.; Katz, U.; Kauer, M.; Keivani, A.; Kelley, J. L.; Kheirandish, A.; Kim, J.; Kim, M.; Kintscher, T.; Kiryluk, J.; Kittler, T.; Klein, S. R.; Kohnen, G.; Koirala, R.; Kolanoski, H.; Konietz, R.; Kopke, L.; Kopper, C.; Kopper, S.; Koskinen, D. J.; Kowalski, M.; Krings, K.; Kroll, M.; Kruckl, G.; Kruger, C.; Kunnen, J.; Kunwar, S.; Kurahashi, N.; Kuwabara, T.; Kyriacou, A.; Labare, M.; Lanfranchi, J. L.; Larson, M. J.; Lauber, F.; Lennarz, D.; Lesiak-Bzdak, M.; Leuermann, M.; Lu, L.; Lunemann, J.; Madsen, J.; Maggi, G.; Mahn, K. B. M.; Mancina, S.; Maruyama, R.; Mase, K.; Maunu, R.; McNally, F.; Meagher, K.; Medici, M.; Meier, M.; Menne, T.; Merino, G.; Meures, T.; Miarecki, S.; Micallef, J.; Momente, G.; Montaruli, T.; Moulai, M.; Nahnhauer, R.; Naumann, U.; Neer, G.; Niederhausen, H.; Nowicki, S. C.; Nygren, D. R.; Pollmann, A. Obertacke; Olivas, A.; O'Murchadha, A.; Palczewski, T.; Pandya, H.; Pankova, D. V.; Peiffer, P.; Penek, O.; Pepper, J. A.; de los Heros, C. Perez; Pieloth, D.; Pinat, E.; Price, P. B.; Przybylski, G. T.; Quinnan, M.; Raab, C.; Raedel, L.; Rameez, M.; Rawlins, K.; Reimann, R.; Relethford, B.; Relich, M.; Resconi, E.; Rhode, W.; Richman, M.; Riedel, B.; Robertson, S.; Rongen, M.; Rott, C.; Ruhe, T.; Ryckbosch, D.; Rysewyk, D.; Sabbatini, L.; Herrera, S. E. Sanchez; Sandrock, A.; Sandroos, J.; Sarkar, S.; Satalecka, K.; Schlunder, P.; Schmidt, T.; Schoenen, S.; Schoeneberg, S.; Schumacher, L.; Seckel, D.; Seunarine, S.; Soldin, D.; Song, M.; Spiczak, G. M.; Spiering, C.; Stachurska, J.; Stanev, T.; Stasik, A.; Stettner, J.; Steuer, A.; Stezelberger, T.; Stokstad, R. G.; Stossl, A.; Strom, R.; Strotjohann, N. L.; Sullivan, G. W.; Sutherland, M.; Taavola, H.; Taboada, I.; Tatar, J.; Tenholt, F.; Ter-Antonyan, S.; Terliuk, A.; Tesic, G.; Tilav, S.; Toale, P. A.; Tobin, M. N.; Toscano, S.; Tosi, D.; Tselengidou, M.; Tung, C. F.; Turcati, A.; Unger, E.; Usner, M.; Vandenbroucke, J.; van Eijndhoven, N.; Vanheule, S.; van Rossem, M.; van Santen, J.; Vehring, M.; Voge, M.; Vogel, E.; Vraeghe, M.; Walck, C.; Wallace, A.; Wallraff, M.; Wandkowsky, N.; Waza, A.; Weaver, Ch.; Weiss, M. J.; Wendt, C.; Westerhoff, S.; Whelan, B. J.; Wickmann, S.; Wiebe, K.; Wiebusch, C. H.; Wille, L.; Williams, D. R.; Wills, L.; Wolf, M.; Wood, T. R.; Woolsey, E.; Woschnagg, K.; Xu, D. L.; Xu, X. W.; Xu, Y.; Yanez, J. P.; Yodh, G.; Yoshida, S.; Zoll, M.; Abbott, B. P.; Abbott, R.; Abbott, T. D.; Abernathy, M. R.; Acernese, F.; Ackley, K.; Adams, C.; Adams, T.; Addesso, P.; Adhikari, R. X.; Adya, V. B.; Affeldt, C.; Agathos, M.; Agatsuma, K.; Aggarwal, N.; Aguiar, O. D.; Aiello, L.; Ain, A.; Ajith, P.; Allen, B.; Allocca, A.; Altin, P. A.; Ananyeva, A.; Anderson, S. B.; Anderson, W. G.; Appert, S.; Arai, K.; Araya, M. C.; Areeda, J. S.; Arnaud, N.; Arun, K. G.; Ascenzi, S.; Ashton, G.; Ast, M.; Aston, S. M.; Astone, P.; Aufmuth, P.; Aulbert, C.; Avila-Alvarez, A.; Babak, S.; Bacon, P.; Bader, M. K. M.; Baker, P. T.; Baldaccini, F.; Ballardin, G.; Ballmer, S. W.; Barayoga, J. C.; Barclay, S. E.; Barish, B. C.; Barker, D.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; D. Barta,; Bartlett, J.; Bartos, I.; Bassiri, R.; Basti, A.; Batch, J. C.; Baune, C.; Bavigadda, V.; Bazzan, M.; Beer, C.; Bejger, M.; Belahcene, I.; Belgin, M.; Bell, A. S.; Berger, B. K.; Bergmann, G.; Berry, C. P. L.; Bersanetti, D.; Bertolini, A.; Betzwieser, J.; Bhagwat, S.; Bhandare, R.; Bilenko, I. A.; Billingsley, G.; Billman, C. R.; Birch, J.; Birney, R.; Birnholtz, O.; Biscans, S.; Bisht, A.; Bitossi, M.; Biwer, C.; Bizouard, M. A.; Blackburn, J. K.; Blackman, J.; Blair, C. D.; Blair, D. G.; Blair, R. M.; Bloemen, S.; Bock, O.; Boer, M.; Bogaert, G.; Bohe, A.; Bondu, F.; Bonnand, R.; Boom, B. A.; Bork, R.; Boschi, V.; Bose, S.; Bouffanais, Y.; Bozzi, A.; Bradaschia, C.; Brady, P. R.; Braginsky, V. B.; Branchesi, M.; Brau, J. E.; Briant, T.; Brillet, A.; Brinkmann, M.; Brisson, V.; Brockill, P.; Broida, J. E.; Brooks, A. F.; Brown, D. A.; Brown, D. D.; Brown, N. M.; Brunett, S.; Buchanan, C. C.; Buikema, A.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Buskulic, D.; Buy, C.; Byer, R. L.; Cabero, M.; Cadonati, L.; Cagnoli, G.; Cahillane, C.; Bustillo, J. Calderon; Callister, T. A.; Calloni, E.; Camp, J. B.; Canepa, M.; Cannon, K. C.; Cao, H.; Cao, J.; Capano, C. D.; Capocasa, E.; Carbognani, F.; Caride, S.; Diaz, J. Casanueva; Casentini, C.; Caudill, S.; Cavaglia, M.; Cavalier, F.; Cavalieri, R.; Cella, G.; Cepeda, C. B.; Baiardi, L. Cerboni; Cerretani, G.; Cesarini, E.; Chamberlin, S. J.; Chan, M.; Chao, S.; Charlton, P.; Chassande-Mottin, E.; Cheeseboro, B. D.; Chen, H. Y.; Chen, Y.; Cheng, H. -P.; Chincarini, A.; Chiummo, A.; Chmiel, T.; Cho, H. S.; Cho, M.; Chow, J. H.; Christensen, N.; Chu, Q.; Chua, A. J. K.; Chua, S.; Chung, S.; Ciani, G.; Clara, F.; Clark, J. A.; Cleva, F.; Cocchieri, C.; Coccia, E.; Cohadon, P. -F.; Colla, A.; Collette, C. G.; Cominsky, L.; Constancio, M., Jr.; Conti, L.; Cooper, S. J.; Corbitt, T. R.; Cornish, N.; Corsi, A.; Cortese, S.; Costa, C. A.; Coughlin, M. W.; Coughlin, S. B.; Coulon, J. -P.; Countryman, S. T.; Couvares, P.; Covas, P. B.; Cowan, E. E.; Coward, D. M.; Cowart, M. J.; Coyne, D. C.; Coyne, R.; Creighton, J. D. E.; Creighton, T. D.; Cripe, J.; Crowder, S. G.; Cullen, T. J.; Cumming, A.; Cunningham, L.; Cuoco, E.; Dal Canton, T.; Danilishin, S. L.; D'Antonio, S.; Danzmann, K.; Dasgupta, A.; Costa, C. F. Da Silva; Dattilo, V.; Dave, I.; Davier, M.; Davies, G. S.; Davis, D.; Daw, E. J.; Day, B.; Day, R.; De, S.; DeBra, D.; G. Debreczeni,; Degallaix, J.; De Laurentis, M.; Deleglise, S.; Del Pozzo, W.; Denker, T.; Dent, T.; Dergachev, V.; De Rosa, R.; DeRosa, R. T.; DeSalvo, R.; Devine, R. C.; Dhurandhar, S.; Diaz, M. C.; Di Fiore, L.; Di Giovanni, M.; Di Girolamo, T.; Di Lieto, A.; Di Pace, S.; Di Palma, I.; Di Virgilio, A.; Doctor, Z.; Dolique, V.; Donovan, F.; Dooley, K. L.; Doravari, S.; Dorrington, I.; Douglas, R.; Alvarez, M. Dovale; Downes, T. P.; Drago, M.; Drever, R. W. P.; Driggers, J. C.; Du, Z.; Ducrot, M.; Dwyer, S. E.; Edo, T. B.; Edwards, M. C.; Effler, A.; Eggenstein, H. -B.; Ehrens, P.; Eichholz, J.; Eikenberry, S. S.; Eisenstein, R. A.; Essick, R. C.; Etienne, Z.; Etzel, T.; Evans, M.; Evans, T. M.; Everett, R.; Factourovich, M.; Fafone, V.; Fair, H.; Fairhurst, S.; Fan, X.; Farinon, S.; Farr, B.; Farr, W. M.; Fauchon-Jones, E. J.; Favata, M.; Fays, M.; Fehrmann, H.; Fejer, M. M.; Galiana, A. Fernandez; Ferrante, I.; Ferreira, E. C.; Ferrini, F.; Fidecaro, F.; Fiori, I.; Fiorucci, D.; Fisher, R. P.; Flaminio, R.; Fletcher, M.; Fong, H.; Forsyth, S. S.; Fournier, J. -D.; Frasca, S.; Frasconi, F.; Z. Frei,; Freise, A.; Frey, R.; Frey, V.; Fries, E. M.; Fritschel, P.; Frolov, V. V.; Fulda, P.; Fyffe, M.; Gabbard, H.; Gadre, B. U.; Gaebel, S. M.; Gair, J. R.; Gammaitoni, L.; Gaonkar, S. G.; Garufi, F.; Gaur, G.; Gayathri, V.; Gehrels, N.; Gemme, G.; Genin, E.; Gennai, A.; George, J.; L. Gergely,; Germain, V.; Ghonge, S.; Ghosh, Abhirup; Ghosh, Archisman; Ghosh, S.; Giaime, J. A.; Giardina, K. D.; Giazotto, A.; Gill, K.; Glaefke, A.; Goetz, E.; Goetz, R.; L. Gondan,; Gonzalez, G.; Castro, J. M. Gonzalez; Gopakumar, A.; Gorodetsky, M. L.; Gossan, S. E.; Gosselin, M.; Gouaty, R.; Grado, A.; Graef, C.; Granata, M.; Grant, A.; Gras, S.; Gray, C.; Greco, G.; Green, A. C.; Groot, P.; Grote, H.; Grunewald, S.; Guidi, G. M.; Guo, X.; Gupta, A.; Gupta, M. K.; Gushwa, K. E.; Gustafson, E. K.; Gustafson, R.; Hacker, J. J.; Hall, B. R.; Hall, E. D.; Hammond, G.; Haney, M.; Hanke, M. M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hanson, J.; Hardwick, T.; Harms, J.; Harry, G. M.; Harry, I. W.; Hart, M. J.; Hartman, M. T.; Haster, C. -J.; Haughian, K.; Healy, J.; Heidmann, A.; Heintze, M. C.; Heitmann, H.; Hello, P.; Hemming, G.; Hendry, M.; Heng, I. S.; Hennig, J.; Henry, J.; Heptonstall, A. W.; Heurs, M.; Hild, S.; Hoak, D.; Hofman, D.; Holt, K.; Holz, D. E.; Hopkins, P.; Hough, J.; Houston, E. A.; Howell, E. J.; Hu, Y. M.; Huerta, E. A.; Huet, D.; Hughey, B.; Husa, S.; Huttner, S. H.; Huynh-Dinh, T.; Indik, N.; Ingram, D. R.; Inta, R.; Isa, H. N.; Isac, J. -M.; Isi, M.; Isogai, T.; Iyer, B. R.; Izumi, K.; Jacqmin, T.; Jani, K.; Jaranowski, P.; Jawahar, S.; Jimenez-Forteza, F.; Johnson, W. W.; Jones, D. I.; Jones, R.; Jonker, R. J. G.; Ju, L.; Junker, J.; Kalaghatgi, C. V.; Kalogera, V.; Kandhasamy, S.; Kang, G.; Kanner, J. B.; Karki, S.; Karvinen, K. S.; Kasprzack, M.; Katsavounidis, E.; Katzman, W.; Kaufer, S.; Kaur, T.; Kawabe, K.; Kefelian, F.; Keitel, D.; Kelley, D. B.; Kennedy, R.; Key, J. S.; Khalili, F. Y.; Khan, I.; Khan, S.; Khan, Z.; Khazanov, E. A.; Kijbunchoo, N.; Kim, Chunglee; Kim, J. C.; Kim, Whansun; Kim, W.; Kim, Y. -M.; Kimbrell, S. J.; King, E. J.; King, P. J.; Kirchhoff, R.; Kissel, J. S.; Klein, B.; Kleybolte, L.; Klimenko, S.; Koch, P.; Koehlenbeck, S. M.; Koley, S.; Kondrashov, V.; Kontos, A.; Korobko, M.; Korth, W. Z.; Kowalska, I.; Kozak, D. B.; Kraemer, C.; Kringel, V.; Krolak, A.; Kuehn, G.; Kumar, P.; Kumar, R.; Kuo, L.; Kutynia, A.; Lackey, B. D.; Landry, M.; Lang, R. N.; Lange, J.; Lantz, B.; Lanza, R. K.; Lartaux-Vollard, A.; Lasky, P. D.; Laxen, M.; Lazzarini, A.; Lazzaro, C.; Leaci, P.; Leavey, S.; Lebigot, E. O.; Lee, C. H.; Lee, H. K.; Lee, H. M.; Lee, K.; Lehmann, J.; Lenon, A.; Leonardi, M.; Leong, J. R.; Leroy, N.; Letendre, N.; Levin, Y.; Li, T. G. F.; Libson, A.; Littenberg, T. B.; Liu, J.; Lockerbie, N. A.; Lombardi, A. L.; London, L. T.; Lord, J. E.; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lough, J. D.; Lovelace, G.; Lueck, H.; Lundgren, A. P.; Lynch, R.; Ma, Y.; Macfoy, S.; Machenschalk, B.; MacInnis, M.; Macleod, D. M.; Magana-Sandoval, F.; Majorana, E.; Maksimovic, I.; Malvezzi, V.; Man, N.; Mandic, V.; Mangano, V.; Mansell, G. L.; Manske, M.; Mantovani, M.; Marchesoni, F.; Marion, F.; Marka, S.; Marka, Z.; Markosyan, A. S.; Maros, E.; Martelli, F.; Martellini, L.; Martin, I. W.; Martynov, D. V.; Mason, K.; Masserot, A.; Massinger, T. J.; Masso-Reid, M.; Mastrogiovanni, S.; Matichard, F.; Matone, L.; Mavalvala, N.; Mazumder, N.; McCarthy, R.; McClelland, D. E.; McCormick, S.; McGrath, C.; McGuire, S. C.; McIntyre, G.; McIver, J.; McManus, D. J.; Mcrae, T.; McWilliams, S. T.; Meacher, D.; Meadors, G. D.; Meidam, J.; Melatos, A.; Mendell, G.; Mendoza-Gandara, D.; Mercer, R. A.; Merilh, E. L.; Merzougui, M.; Meshkov, S.; Messenger, C.; Messick, C.; Metzdorff, R.; Meyers, P. M.; Mezzani, F.; Miao, H.; Michel, C.; Middleton, H.; Mikhailov, E. E.; Milano, L.; Miller, A. L.; Miller, A.; Miller, B. B.; Miller, J.; Millhouse, M.; Minenkov, Y.; Ming, J.; Mirshekari, S.; Mishra, C.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Moggi, A.; Mohan, M.; Mohapatra, S. R. P.; Montani, M.; Moore, B. C.; Moore, C. J.; Moraru, D.; Moreno, G.; Morriss, S. R.; Mours, B.; Mow-Lowry, C. M.; Mueller, G.; Muir, A. W.; Mukherjee, Arunava; Mukherjee, D.; Mukherjee, S.; Mukund, N.; Mullavey, A.; Munch, J.; Muniz, E. A. M.; Murray, P. G.; Mytidis, A.; Napier, K.; Nardecchia, I.; Naticchioni, L.; Nelemans, G.; Nelson, T. J. N.; Neri, M.; Nery, M.; Neunzert, A.; Newport, J. M.; Newton, G.; Nguyen, T. T.; Nielsen, A. B.; Nissanke, S.; Nitz, A.; Noack, A.; Nocera, F.; Nolting, D.; Normandin, M. E. N.; Nuttall, L. K.; Oberling, J.; Ochsner, E.; Oelker, E.; Ogin, G. H.; Oh, J. J.; Oh, S. H.; Ohme, F.; Oliver, M.; Oppermann, P.; Oram, Richard J.; O'Reilly, B.; O'Shaughnessy, R.; Ottaway, D. J.; Overmier, H.; Owen, B. J.; Pace, A. E.; Page, J.; Pai, A.; Pai, S. A.; Palamos, J. R.; Palashov, O.; Palomba, C.; Pal-Singh, A.; Pan, H.; Pankow, C.; Pannarale, F.; Pant, B. C.; Paoletti, F.; Paoli, A.; Papa, M. A.; Paris, H. R.; Parker, W.; Pascucci, D.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Patricelli, B.; Pearlstone, B. L.; Pedraza, M.; Pedurand, R.; Pekowsky, L.; Pele, A.; Penn, S.; Perez, C. J.; Perreca, A.; Perri, L. M.; Pfeiffer, H. P.; Phelps, M.; Piccinni, O. J.; Pichot, M.; Piergiovanni, F.; Pierro, V.; Pillant, G.; Pinard, L.; Pinto, I. M.; Pitkin, M.; Poe, M.; Poggiani, R.; Popolizio, P.; Post, A.; Powell, J.; Prasad, J.; Pratt, J. W. W.; Predoi, V.; Prestegard, T.; Prijatelj, M.; Principe, M.; Privitera, S.; Prodi, G. A.; Prokhorov, L. G.; Puncken, O.; Punturo, M.; Puppo, P.; Puerrer, M.; Qi, H.; Qin, J.; Qiu, S.; Quetschke, V.; Quintero, E. A.; Quitzow-James, R.; Raab, F. J.; Rabeling, D. S.; Radkins, H.; P. Raffai,; Raja, S.; Rajan, C.; Rakhmanov, M.; Rapagnani, P.; Raymond, V.; Razzano, M.; Re, V.; Read, J.; Regimbau, T.; Rei, L.; Reid, S.; Reitze, D. H.; Rew, H.; Reyes, S. D.; Rhoades, E.; Ricci, F.; Riles, K.; Rizzo, M.; Robertson, N. A.; Robie, R.; Robinet, F.; Rocchi, A.; Rolland, L.; Rollins, J. G.; Roma, V. J.; Romano, R.; Romie, J. H.; Rosinska, D.; Rowan, S.; Ruediger, A.; Ruggi, P.; Ryan, K.; Sachdev, S.; Sadecki, T.; Sadeghian, L.; Sakellariadou, M.; Salconi, L.; Saleem, M.; Salemi, F.; Samajdar, A.; Sammut, L.; Sampson, L. M.; Sanchez, E. J.; Sandberg, V.; Sanders, J. R.; Sassolas, B.; Sathyaprakash, B. S.; Saulson, P. R.; Sauter, O.; Savage, R. L.; Sawadsky, A.; Schale, P.; Scheuer, J.; Schmidt, E.; Schmidt, J.; Schmidt, P.; Schnabel, R.; Schofield, R. M. S.; Schoenbeck, A.; Schreiber, E.; Schuette, D.; Schutz, B. F.; Schwalbe, S. G.; Scott, J.; Scott, S. M.; Sellers, D.; Sengupta, A. S.; Sentenac, D.; Sequino, V.; Sergeev, A.; Setyawati, Y.; Shaddock, D. A.; Shaffer, T. J.; Shahriar, M. S.; Shapiro, B.; Shawhan, P.; Sheperd, A.; Shoemaker, D. H.; Shoemaker, D. M.; Siellez, K.; Siemens, X.; Sieniawska, M.; Sigg, D.; Silva, A. D.; Singer, A.; Singer, L. P.; Singh, A.; Singh, R.; Singhal, A.; Sintes, A. M.; Slagmolen, B. J. J.; Smith, B.; Smith, R. J. E.; Smith, R. J. E.; Son, E. J.; Sorazu, B.; Sorrentino, F.; Souradeep, T.; Spencer, A. P.; Srivastava, A. K.; Staley, A.; Steinke, M.; Steinlechner, J.; Steinlechner, S.; Steinmeyer, D.; Stephens, B. C.; Stevenson, S. P.; Stone, R.; Strain, K. A.; Straniero, N.; Stratta, G.; Strigin, S. E.; Sturani, R.; Stuver, A. L.; Summerscales, T. Z.; Sun, L.; Sunil, S.; Sutton, P. J.; Swinkels, B. L.; Szczepanczyk, M. J.; Tacca, M.; Talukder, D.; Tanner, D. B.; M. Tapai,; Taracchini, A.; Taylor, R.; Theeg, T.; Thomas, E. G.; Thomas, M.; Thomas, P.; Thorne, K. A.; Thrane, E.; Tippens, T.; Tiwari, S.; Tiwari, V.; Tokmakov, K. V.; Toland, K.; Tomlinson, C.; Tonelli, M.; Tornasi, Z.; Torrie, C. I.; Toyra, D.; Travasso, F.; Traylor, G.; Trifiro, D.; Trinastic, J.; Tringali, M. C.; Trozzo, L.; Tse, M.; Tso, R.; Turconi, M.; Tuyenbayev, D.; Ugolini, D.; Unnikrishnan, C. S.; Urban, A. L.; Usman, S. A.; Vahlbruch, H.; Vajente, G.; Valdes, G.; van Bakel, N.; van Beuzekom, M.; van den Brand, J. F. J.; Van Den Broeck, C.; Vander-Hyde, D. C.; van der Schaaf, L.; van Heijningen, J. V.; van Veggel, A. A.; Vardaro, M.; Varma, V.; Vass, S.; M. Vasuth,; Vecchio, A.; Vedovato, G.; Veitch, J.; Veitch, P. J.; Venkateswara, K.; Venugopalan, G.; Verkindt, D.; Vetrano, F.; Vicere, A.; Viets, A. D.; Vinciguerra, S.; Vine, D. J.; Vinet, J. -Y.; Vitale, S.; Vo, T.; Vocca, H.; Vorvick, C.; Voss, D. V.; Vousden, W. D.; Vyatchanin, S. P.; Wade, A. R.; Wade, L. E.; Wade, M.; Walker, M.; Wallace, L.; Walsh, S.; Wang, G.; Wang, H.; Wang, M.; Wang, Y.; Ward, R. L.; Warner, J.; Was, M.; Watchi, J.; Weaver, B.; Wei, L. -W.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Wen, L.; Wessels, P.; Westphal, T.; Wette, K.; Whelan, J. T.; Whiting, B. F.; Whittle, C.; Williams, D.; Williams, R. D.; Williamson, A. R.; Willis, J. L.; Willke, B.; Wimmer, M. H.; Winkler, W.; Wipf, C. C.; Wittel, H.; Woan, G.; Woehler, J.; Worden, J.; Wright, J. L.; Wu, D. S.; Wu, G.; Yam, W.; Yamamoto, H.; Yancey, C. C.; Yap, M. J.; Yu, Hang; Yu, Haocun; Yvert, M.; Zadrozny, A.; Zangrando, L.; Zanolin, M.; Zendri, J. -P.; Zevin, M.; Zhang, L.; Zhang, M.; Zhang, T.; Zhang, Y.; Zhao, C.; Zhou, M.; Zhou, Z.; Zhu, S. J.; Zhu, X. J.; Zucker, M. E.; Zweizig, J.

    2017-01-01

    The Advanced LIGO observatories detected gravitational waves from two binary black hole mergers during their first observation run (O1). We present a high-energy neutrino follow-up search for the second gravitational wave event, GW151226, as well as for gravitational wave candidate LVT151012. We

  3. GC-MS Based Plasma Metabolomics for Identification of Candidate Biomarkers for Hepatocellular Carcinoma in Egyptian Cohort.

    Directory of Open Access Journals (Sweden)

    Mohammad R Nezami Ranjbar

    Full Text Available This study evaluates changes in metabolite levels in hepatocellular carcinoma (HCC cases vs. patients with liver cirrhosis by analysis of human blood plasma using gas chromatography coupled with mass spectrometry (GC-MS. Untargeted metabolomic analysis of plasma samples from participants recruited in Egypt was performed using two GC-MS platforms: a GC coupled to single quadruple mass spectrometer (GC-qMS and a GC coupled to a time-of-flight mass spectrometer (GC-TOFMS. Analytes that showed statistically significant changes in ion intensities were selected using ANOVA models. These analytes and other candidates selected from related studies were further evaluated by targeted analysis in plasma samples from the same participants as in the untargeted metabolomic analysis. The targeted analysis was performed using the GC-qMS in selected ion monitoring (SIM mode. The method confirmed significant changes in the levels of glutamic acid, citric acid, lactic acid, valine, isoleucine, leucine, alpha tocopherol, cholesterol, and sorbose in HCC cases vs. patients with liver cirrhosis. Specifically, our findings indicate up-regulation of metabolites involved in branched-chain amino acid (BCAA metabolism. Although BCAAs are increasingly used as a treatment for cancer cachexia, others have shown that BCAA supplementation caused significant enhancement of tumor growth via activation of mTOR/AKT pathway, which is consistent with our results that BCAAs are up-regulated in HCC.

  4. A tuberculosis biomarker database: the key to novel TB diagnostics

    Directory of Open Access Journals (Sweden)

    Seda Yerlikaya

    2017-03-01

    Full Text Available New diagnostic innovations for tuberculosis (TB, including point-of-care solutions, are critical to reach the goals of the End TB Strategy. However, despite decades of research, numerous reports on new biomarker candidates, and significant investment, no well-performing, simple and rapid TB diagnostic test is yet available on the market, and the search for accurate, non-DNA biomarkers remains a priority. To help overcome this ‘biomarker pipeline problem’, FIND and partners are working on the development of a well-curated and user-friendly TB biomarker database. The web-based database will enable the dynamic tracking of evidence surrounding biomarker candidates in relation to target product profiles (TPPs for needed TB diagnostics. It will be able to accommodate raw datasets and facilitate the verification of promising biomarker candidates and the identification of novel biomarker combinations. As such, the database will simplify data and knowledge sharing, empower collaboration, help in the coordination of efforts and allocation of resources, streamline the verification and validation of biomarker candidates, and ultimately lead to an accelerated translation into clinically useful tools.

  5. Systemic sclerosis biomarkers discovered using mass-spectrometry-based proteomics: a systematic review.

    Science.gov (United States)

    Bălănescu, Paul; Lădaru, Anca; Bălănescu, Eugenia; Băicuş, Cristian; Dan, Gheorghe Andrei

    2014-08-01

    Systemic sclerosis (SSc) is an autoimmune disease with incompletely known physiopathology. There is a great challenge to predict its course and therapeutic response using biomarkers. To critically review proteomic biomarkers discovered from biological specimens from systemic sclerosis patients using mass spectrometry technologies. Medline and Embase databases were searched in February 2014. Out of the 199 records retrieved, a total of 20 records were included, identifying 116 candidate proteomic biomarkers. Research in SSc proteomic biomarkers should focus on biomarker validation, as there are valuable mass-spectrometry proteomics studies in the literature.

  6. Searching for biomarkers of developmental toxicity with microarrays: normal eye morphogenesis in rodent embryos

    International Nuclear Information System (INIS)

    Nemeth, Kimberly A.; Singh, Amar V.; Knudsen, Thomas B.

    2005-01-01

    Gene expression arrays reveal the potential linkage of altered gene expression with specific adverse effects leading to disease phenotypes. But how closely do microarray data reflect early physiological or pharmacological measures that predict toxic event(s)? To explore this issue, we have undertaken experiments in early mouse embryos exposed to various teratogens during neurulation stages with the aim of correlating large-scale changes in gene expression across the critical period during exposure. This study reports some of the large-scale changes in gene expression that can be detected in the optic rudiment of the developing mouse and rat embryo across the window of development during which the eye is exceedingly sensitive to teratogen-induced micro-/anophthalmia. Microarray analysis was performed on RNA from the headfold or ocular region at the optic vesicle and optic cup stages when the ocular primordium is enriched for Pax-6, a master control gene for eye morphogenesis. Statistical selection of differentially regulated genes and various clustering techniques identified groups of genes in upward or downward trajectories in the normal optic primordium during early eye development in mouse and rat species. We identified 165 genes with significant differential expression during eye development, and a smaller subset of 58 genes that showed a tight correlation between mouse-rat development. Significantly over-represented functional categories included fatty acid metabolism (up-regulated) and glycolysis (down-regulated). From studies such as these that benchmark large-scale gene expression during normal embryonic development, we may be able to identify the panel of biomarkers that best correlate with species differences and the risks for developmental toxicity

  7. Using MALDI-IMS and MRM to stablish a pipeline for discovery and validation of tumor neovasculature biomarker candidates. — EDRN Public Portal

    Science.gov (United States)

    In an effort to circumvent the limitations associated with biomarker discovery workflows involving cell lines and cell cultures, histology-directed MALDI protein profiling and imaging mass spectrometry will be used for identification of vascular endothelial biomarkers suitable for early prostate cancer detection by CEUS targeted molecular imaging

  8. Search for Breast Cancer Biomarkers in Fractionated Serum Samples by Protein Profiling With SELDI-TOF MS

    NARCIS (Netherlands)

    Opstal - van Winden, A.W.J.; Beijnen, J.H.; de Loof, A.; van Heerde, W.L.; Vermeulen, R.; Peeters, P.H.M.; van Gils, C.H.

    2012-01-01

    BackgroundMany high-abundant acute phase reactants have been previously detected as potential breast cancer biomar-kers. However, they are unlikely to be specific for breast cancer. Cancer-specific biomarkers are thought to be among the lower abundant proteins.MethodsWe aimed to detect lower

  9. MicroRNA Profiling in the Medial and Lateral Habenula of Rats Exposed to the Learned Helplessness Paradigm: Candidate Biomarkers for Susceptibility and Resilience to Inescapable Shock.

    Science.gov (United States)

    Svenningsen, Katrine; Venø, Morten T; Henningsen, Kim; Mallien, Anne S; Jensen, Line; Christensen, Trine; Kjems, Jørgen; Vollmayr, Barbara; Wiborg, Ove

    2016-01-01

    Depression is a highly heterogeneous disorder presumably caused by a combination of several factors ultimately causing the pathological condition. The genetic liability model of depression is likely to be of polygenic heterogeneity. miRNAs can regulate multiple genes simultaneously and therefore are candidates that align with this model. The habenula has been linked to depression in both clinical and animal studies, shifting interest towards this region as a neural substrate in depression. The goal of the present study was to search for alterations in miRNA expression levels in the medial and lateral habenula of rats exposed to the learned helplessness (LH) rat model of depression. Ten miRNAs showed significant alterations associating with their response to the LH paradigm. Of these, six and four miRNAs were significantly regulated in the MHb and LHb, respectively. In the MHb we identified miR-490, miR-291a-3p, MiR-467a, miR-216a, miR-18b, and miR-302a. In the LHb miR-543, miR-367, miR-467c, and miR-760-5p were significantly regulated. A target gene analysis showed that several of the target genes are involved in MAPK signaling, neutrophin signaling, and ErbB signaling, indicating that neurotransmission is affected in the habenula as a consequence of exposure to the LH paradigm.

  10. Critical Assessment of Analytical Techniques in the Search for Biomarkers on Mars: A Mummified Microbial Mat from Antarctica as a Best-Case Scenario.

    Science.gov (United States)

    Blanco, Yolanda; Gallardo-Carreño, Ignacio; Ruiz-Bermejo, Marta; Puente-Sánchez, Fernando; Cavalcante-Silva, Erika; Quesada, Antonio; Prieto-Ballesteros, Olga; Parro, Víctor

    2017-10-01

    The search for biomarkers of present or past life is one of the major challenges for in situ planetary exploration. Multiple constraints limit the performance and sensitivity of remote in situ instrumentation. In addition, the structure, chemical, and mineralogical composition of the sample may complicate the analysis and interpretation of the results. The aim of this work is to highlight the main constraints, performance, and complementarity of several techniques that have already been implemented or are planned to be implemented on Mars for detection of organic and molecular biomarkers on a best-case sample scenario. We analyzed a 1000-year-old desiccated and mummified microbial mat from Antarctica by Raman and IR (infrared) spectroscopies (near- and mid-IR), thermogravimetry (TG), differential thermal analysis, mass spectrometry (MS), and immunological detection with a life detector chip. In spite of the high organic content (ca. 20% wt/wt) of the sample, the Raman spectra only showed the characteristic spectral peaks of the remaining beta-carotene biomarker and faint peaks of phyllosilicates over a strong fluorescence background. IR spectra complemented the mineralogical information from Raman spectra and showed the main molecular vibrations of the humic acid functional groups. The TG-MS system showed the release of several volatile compounds attributed to biopolymers. An antibody microarray for detecting cyanobacteria (CYANOCHIP) detected biomarkers from Chroococcales, Nostocales, and Oscillatoriales orders. The results highlight limitations of each technique and suggest the necessity of complementary approaches in the search for biomarkers because some analytical techniques might be impaired by sample composition, presentation, or processing. Key Words: Planetary exploration-Life detection-Microbial mat-Life detector chip-Thermogravimetry-Raman spectroscopy-NIR-DRIFTS. Astrobiology 17, 984-996.

  11. Critical Assessment of Analytical Techniques in the Search for Biomarkers on Mars: A Mummified Microbial Mat from Antarctica as a Best-Case Scenario

    Science.gov (United States)

    Blanco, Yolanda; Gallardo-Carreño, Ignacio; Ruiz-Bermejo, Marta; Puente-Sánchez, Fernando; Cavalcante-Silva, Erika; Quesada, Antonio; Prieto-Ballesteros, Olga; Parro, Víctor

    2017-10-01

    The search for biomarkers of present or past life is one of the major challenges for in situ planetary exploration. Multiple constraints limit the performance and sensitivity of remote in situ instrumentation. In addition, the structure, chemical, and mineralogical composition of the sample may complicate the analysis and interpretation of the results. The aim of this work is to highlight the main constraints, performance, and complementarity of several techniques that have already been implemented or are planned to be implemented on Mars for detection of organic and molecular biomarkers on a best-case sample scenario. We analyzed a 1000-year-old desiccated and mummified microbial mat from Antarctica by Raman and IR (infrared) spectroscopies (near- and mid-IR), thermogravimetry (TG), differential thermal analysis, mass spectrometry (MS), and immunological detection with a life detector chip. In spite of the high organic content (ca. 20% wt/wt) of the sample, the Raman spectra only showed the characteristic spectral peaks of the remaining beta-carotene biomarker and faint peaks of phyllosilicates over a strong fluorescence background. IR spectra complemented the mineralogical information from Raman spectra and showed the main molecular vibrations of the humic acid functional groups. The TG-MS system showed the release of several volatile compounds attributed to biopolymers. An antibody microarray for detecting cyanobacteria (CYANOCHIP) detected biomarkers from Chroococcales, Nostocales, and Oscillatoriales orders. The results highlight limitations of each technique and suggest the necessity of complementary approaches in the search for biomarkers because some analytical techniques might be impaired by sample composition, presentation, or processing.

  12. Dopaminergic, Serotonergic, and Oxytonergic Candidate Genes Associated with Infant Attachment Security and Disorganization? In Search of Main and Interaction Effects

    Science.gov (United States)

    Luijk, Maartje P. C. M.; Roisman, Glenn I.; Haltigan, John D.; Tiemeier, Henning; Booth-LaForce, Cathryn; van IJzendoorn, Marinus H.; Belsky, Jay; Uitterlinden, Andre G.; Jaddoe, Vincent W. V.; Hofman, Albert; Verhulst, Frank C.; Tharner, Anne; Bakermans-Kranenburg, Marian J.

    2011-01-01

    Background and methods: In two birth cohort studies with genetic, sensitive parenting, and attachment data of more than 1,000 infants in total, we tested main and interaction effects of candidate genes involved in the dopamine, serotonin, and oxytocin systems ("DRD4", "DRD2", "COMT", "5-HTT", "OXTR") on attachment security and disorganization.…

  13. Diagnostic Potential of Novel Salivary Host Biomarkers as Candidates for the Immunological Diagnosis of Tuberculosis Disease and Monitoring of Tuberculosis Treatment Response.

    Science.gov (United States)

    Jacobs, Ruschca; Maasdorp, Elizna; Malherbe, Stephanus; Loxton, Andre G; Stanley, Kim; van der Spuy, Gian; Walzl, Gerhard; Chegou, Novel N

    2016-01-01

    There is an urgent need for new tools for the early diagnosis of TB disease and monitoring of the response to treatment, especially in resource-constrained settings. We investigated the usefulness of host markers detected in saliva as candidate biomarkers for the immunological diagnosis of TB disease and monitoring of treatment response. We prospectively collected saliva samples from 51 individuals that presented with signs and symptoms suggestive of TB disease at a health centre in Cape Town, South Africa, prior to the establishment of a clinical diagnosis. Patients were later classified as having TB disease or other respiratory disease (ORD), using a combination of clinical, radiological and laboratory findings. We evaluated the concentrations of 69 host markers in saliva samples using a multiplex cytokine platform, and assessed the diagnostic potentials of these markers by receiver operator characteristics (ROC) curve analysis, and general discriminant analysis. Out of the 51 study participants, 18 (35.4%) were diagnosed with TB disease and 12 (23.5%) were HIV infected. Only two of the 69 host markers that were evaluated (IL-16 and IL-23) diagnosed TB disease individually with area under the ROC curve ≥0.70. A five-marker biosignature comprising of IL-1β, IL-23, ECM-1, HCC1 and fibrinogen diagnosed TB disease with a sensitivity of 88.9% (95% CI,76.7-99.9%) and specificity of 89.7% (95% CI, 60.4-96.6%) after leave-one-out cross validation, regardless of HIV infection status. Eight-marker biosignatures performed with a sensitivity of 100% (95% CI, 83.2-100%) and specificity of 95% (95% CI, 68.1-99.9%) in the absence of HIV infection. Furthermore, the concentrations of 11 of the markers changed during treatment, indicating that they may be useful in monitoring of TB treatment response. We have identified novel salivary biosignatures which may be useful in the diagnosis of TB disease and monitoring of the response to TB treatment. Our findings require further

  14. Searching for new biomarkers in ovarian cancer patients: Rationale and design of a retrospective study under the Mermaid III project

    Directory of Open Access Journals (Sweden)

    Julie L. Hentze

    2017-12-01

    A thorough investigation of biomarkers in ovarian cancer, including large numbers of different markers, has never been done before. Besides from improving diagnosis and treatment, other outcomes could be markers for screening, knowledge of the molecular aspects of cancer and the discovery of new drugs. Moreover, biomarkers are a prerequisite for the development of precision medicine. This study will attack the ovarian cancer problem from several angles, thereby increasing the chance of successfully contributing to saving lives.

  15. Potential Peripheral Biomarkers for the Diagnosis of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Seema Patel

    2011-01-01

    Full Text Available Advances in the discovery of a peripheral biomarker for the diagnosis of Alzheimer's would provide a way to better detect the onset of this debilitating disease in a manner that is both noninvasive and universally available. This paper examines the current approaches that are being used to discover potential biomarker candidates available in the periphery. The search for a peripheral biomarker that could be utilized diagnostically has resulted in an extensive amount of studies that employ several biological approaches, including the assessment of tissues, genomics, proteomics, epigenetics, and metabolomics. Although a definitive biomarker has yet to be confirmed, advances in the understanding of the mechanisms of the disease and major susceptibility factors have been uncovered and reveal promising possibilities for the future discovery of a useful biomarker.

  16. Children's exposure to environmental pollutants and biomarkers of genetic damage. II. Results of a comprehensive literature search and meta-analysis

    DEFF Research Database (Denmark)

    Neri, Monica; Ugolini, Donatella; Bonassi, Stefano

    2005-01-01

    The present review is based on findings from 178 publications retrieved through an extensive search of the MedLine/PubMed database for a 25 years time period (1980-2004) and 10 manually identified papers. Among the cytogenetic biomarkers that are frequently used in field studies, chromosome...... pollutants, soil and drinking water contaminants, mostly increased CA and, to a lesser extent, MN levels in children. The effect of exposure to airborne urban pollutants was consistently reported by field studies measuring DNA, albumin and hemoglobin adducts. Prenatal (in utero) and postnatal exposure...

  17. A SEARCH FOR L/T TRANSITION DWARFS WITH Pan-STARRS1 AND WISE: DISCOVERY OF SEVEN NEARBY OBJECTS INCLUDING TWO CANDIDATE SPECTROSCOPIC VARIABLES

    International Nuclear Information System (INIS)

    Best, William M. J.; Liu, Michael C.; Magnier, Eugene A.; Aller, Kimberly M.; Burgett, W. S.; Chambers, K. C.; Hodapp, K. W.; Kaiser, N.; Kudritzki, R.-P.; Morgan, J. S.; Tonry, J. L.; Wainscoat, R. J.; Deacon, Niall R.; Dupuy, Trent J.; Redstone, Joshua; Price, P. A.

    2013-01-01

    We present initial results from a wide-field (30,000 deg 2 ) search for L/T transition brown dwarfs within 25 pc using the Pan-STARRS1 and Wide-field Infrared Survey Explorer (WISE) surveys. Previous large-area searches have been incomplete for L/T transition dwarfs, because these objects are faint in optical bands and have near-infrared (near-IR) colors that are difficult to distinguish from background stars. To overcome these obstacles, we have cross-matched the Pan-STARRS1 (optical) and WISE (mid-IR) catalogs to produce a unique multi-wavelength database for finding ultracool dwarfs. As part of our initial discoveries, we have identified seven brown dwarfs in the L/T transition within 9-15 pc of the Sun. The L9.5 dwarf PSO J140.2308+45.6487 and the T1.5 dwarf PSO J307.6784+07.8263 (both independently discovered by Mace et al.) show possible spectroscopic variability at the Y and J bands. Two more objects in our sample show evidence of photometric J-band variability, and two others are candidate unresolved binaries based on their spectra. We expect our full search to yield a well-defined, volume-limited sample of L/T transition dwarfs that will include many new targets for study of this complex regime. PSO J307.6784+07.8263 in particular may be an excellent candidate for in-depth study of variability, given its brightness (J = 14.2 mag) and proximity (11 pc)

  18. A SEARCH FOR L/T TRANSITION DWARFS WITH Pan-STARRS1 AND WISE: DISCOVERY OF SEVEN NEARBY OBJECTS INCLUDING TWO CANDIDATE SPECTROSCOPIC VARIABLES

    Energy Technology Data Exchange (ETDEWEB)

    Best, William M. J.; Liu, Michael C.; Magnier, Eugene A.; Aller, Kimberly M.; Burgett, W. S.; Chambers, K. C.; Hodapp, K. W.; Kaiser, N.; Kudritzki, R.-P.; Morgan, J. S.; Tonry, J. L.; Wainscoat, R. J. [Institute for Astronomy, University of Hawaii at Manoa, Honolulu, HI 96822 (United States); Deacon, Niall R. [Max Planck Institute for Astronomy, Koenigstuhl 17, D-69117 Heidelberg (Germany); Dupuy, Trent J. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Redstone, Joshua [Facebook, 335 Madison Ave, New York, NY 10017-4677 (United States); Price, P. A., E-mail: wbest@ifa.hawaii.edu [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States)

    2013-11-10

    We present initial results from a wide-field (30,000 deg{sup 2}) search for L/T transition brown dwarfs within 25 pc using the Pan-STARRS1 and Wide-field Infrared Survey Explorer (WISE) surveys. Previous large-area searches have been incomplete for L/T transition dwarfs, because these objects are faint in optical bands and have near-infrared (near-IR) colors that are difficult to distinguish from background stars. To overcome these obstacles, we have cross-matched the Pan-STARRS1 (optical) and WISE (mid-IR) catalogs to produce a unique multi-wavelength database for finding ultracool dwarfs. As part of our initial discoveries, we have identified seven brown dwarfs in the L/T transition within 9-15 pc of the Sun. The L9.5 dwarf PSO J140.2308+45.6487 and the T1.5 dwarf PSO J307.6784+07.8263 (both independently discovered by Mace et al.) show possible spectroscopic variability at the Y and J bands. Two more objects in our sample show evidence of photometric J-band variability, and two others are candidate unresolved binaries based on their spectra. We expect our full search to yield a well-defined, volume-limited sample of L/T transition dwarfs that will include many new targets for study of this complex regime. PSO J307.6784+07.8263 in particular may be an excellent candidate for in-depth study of variability, given its brightness (J = 14.2 mag) and proximity (11 pc)

  19. MARVELS-1b: A SHORT-PERIOD, BROWN DWARF DESERT CANDIDATE FROM THE SDSS-III MARVELS PLANET SEARCH

    International Nuclear Information System (INIS)

    Lee, Brian L.; Ge Jian; Fleming, Scott W.; Mahadevan, Suvrath; Sivarani, Thirupathi; Stassun, Keivan G.; Gary, Bruce; Pepper, Joshua; Gaudi, B. Scott; Eastman, Jason D.; Siverd, Robert J.; Barnes, Rory; Laws, Chris; Wisniewski, John P.; Wright, Jason; Ghezzi, Luan; Ogando, Ricardo L. C.; Maia, Marcio A. G.; Da Costa, Luiz Nicolaci; Porto de Mello, G. F.

    2011-01-01

    We present a new short-period brown dwarf (BD) candidate around the star TYC 1240-00945-1. This candidate was discovered in the first year of the Multi-object APO Radial Velocity Exoplanets Large-area Survey (MARVELS), which is part of the Sloan Digital Sky Survey (SDSS) III, and we designate the BD as MARVELS-1b. MARVELS uses the technique of dispersed fixed-delay interferometery to simultaneously obtain radial velocity (RV) measurements for 60 objects per field using a single, custom-built instrument that is fiber fed from the SDSS 2.5 m telescope. From our 20 RV measurements spread over a ∼370 day time baseline, we derive a Keplerian orbital fit with semi-amplitude K = 2.533 ± 0.025 km s -1 , period P = 5.8953 ± 0.0004 days, and eccentricity consistent with circular. Independent follow-up RV data confirm the orbit. Adopting a mass of 1.37 ± 0.11 M sun for the slightly evolved F9 host star, we infer that the companion has a minimum mass of 28.0 ± 1.5 M Jup , a semimajor axis 0.071 ± 0.002 AU assuming an edge-on orbit, and is probably tidally synchronized. We find no evidence for coherent intrinsic variability of the host star at the period of the companion at levels greater than a few millimagnitudes. The companion has an a priori transit probability of ∼14%. Although we find no evidence for transits, we cannot definitively rule them out for companion radii ∼ Jup .

  20. Searching for non-genetic molecular and imaging PTSD risk and resilience markers: Systematic review of literature and design of the German Armed Forces PTSD biomarker study.

    Science.gov (United States)

    Schmidt, Ulrike; Willmund, Gerd-Dieter; Holsboer, Florian; Wotjak, Carsten T; Gallinat, Jürgen; Kowalski, Jens T; Zimmermann, Peter

    2015-01-01

    Biomarkers allowing the identification of individuals with an above average vulnerability or resilience for posttraumatic stress disorder (PTSD) would especially serve populations at high risk for trauma exposure like firefighters, police officers and combat soldiers. Aiming to identify the most promising putative PTSD vulnerability markers, we conducted the first systematic review on potential imaging and non-genetic molecular markers for PTSD risk and resilience. Following the PRISMA guidelines, we systematically screened the PubMed database for prospective longitudinal clinical studies and twin studies reporting on pre-trauma and post-trauma PTSD risk and resilience biomarkers. Using 25 different combinations of search terms, we retrieved 8151 articles of which we finally included and evaluated 9 imaging and 27 molecular studies. In addition, we briefly illustrate the design of the ongoing prospective German Armed Forces (Bundeswehr) PTSD biomarker study (Bw-BioPTSD) which not only aims to validate these previous findings but also to identify novel and clinically applicable molecular, psychological and imaging risk, resilience and disease markers for deployment-related psychopathology in a cohort of German soldiers who served in Afghanistan. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Searching for a new ionomer for 3D printable ionic polymer-metal composites: Aquivion as a candidate

    Science.gov (United States)

    Trabia, Sarah; Olsen, Zakai; Kim, Kwang J.

    2017-11-01

    The work presented in this paper introduces Aquivion as a potential candidate for additive manufacturing of ionomeric polymers for the application of IPMCs. First, Aquivion was characterized and compared with Nafion to show that it has the similar qualities, with the major difference being the ionic conductivity. Ionic polymer-metal composites (IPMCs) were fabricated using off-the-shelf membranes of Nafion and Aquivion. The actuation tests showed improved performance for an IPMC with Aquivion as the base compared to an IPMC with a Nafion base. With these results in mind, additive manufacturing of unique shapes using Aquivion filament was studied. A 3D printer was modified to work with Aquivion filament and the polymer was printed into various shapes. Using the printed membranes, IPMCs were fabricated using an electroless plating process. Nafion-based and printed Aquivion-based IPMCs were tested for their performance in back relaxation, frequency driven actuation, blocking force, and mechano-electric sensing. The printed Aquivion-based IPMCs performed comparably to Nafion-based IPMC in back relaxation and showed significantly improved performance in frequency driven actuation, blocking force generation, and mechano-electric sensing.

  2. Progress and roadblocks in the search for brain-based biomarkers of autism and attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Uddin, L Q; Dajani, D R; Voorhies, W; Bednarz, H; Kana, R K

    2017-08-22

    Children with neurodevelopmental disorders benefit most from early interventions and treatments. The development and validation of brain-based biomarkers to aid in objective diagnosis can facilitate this important clinical aim. The objective of this review is to provide an overview of current progress in the use of neuroimaging to identify brain-based biomarkers for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), two prevalent neurodevelopmental disorders. We summarize empirical work that has laid the foundation for using neuroimaging to objectively quantify brain structure and function in ways that are beginning to be used in biomarker development, noting limitations of the data currently available. The most successful machine learning methods that have been developed and applied to date are discussed. Overall, there is increasing evidence that specific features (for example, functional connectivity, gray matter volume) of brain regions comprising the salience and default mode networks can be used to discriminate ASD from typical development. Brain regions contributing to successful discrimination of ADHD from typical development appear to be more widespread, however there is initial evidence that features derived from frontal and cerebellar regions are most informative for classification. The identification of brain-based biomarkers for ASD and ADHD could potentially assist in objective diagnosis, monitoring of treatment response and prediction of outcomes for children with these neurodevelopmental disorders. At present, however, the field has yet to identify reliable and reproducible biomarkers for these disorders, and must address issues related to clinical heterogeneity, methodological standardization and cross-site validation before further progress can be achieved.

  3. Molecular biomarkers in idiopathic pulmonary fibrosis

    Science.gov (United States)

    Ley, Brett; Brown, Kevin K.

    2014-01-01

    Molecular biomarkers are highly desired in idiopathic pulmonary fibrosis (IPF), where they hold the potential to elucidate underlying disease mechanisms, accelerated drug development, and advance clinical management. Currently, there are no molecular biomarkers in widespread clinical use for IPF, and the search for potential markers remains in its infancy. Proposed core mechanisms in the pathogenesis of IPF for which candidate markers have been offered include alveolar epithelial cell dysfunction, immune dysregulation, and fibrogenesis. Useful markers reflect important pathological pathways, are practically and accurately measured, have undergone extensive validation, and are an improvement upon the current approach for their intended use. The successful development of useful molecular biomarkers is a central challenge for the future of translational research in IPF and will require collaborative efforts among those parties invested in advancing the care of patients with IPF. PMID:25260757

  4. A COMPREHENSIVE SEARCH FOR STELLAR BOWSHOCK NEBULAE IN THE MILKY WAY: A CATALOG OF 709 MID-INFRARED SELECTED CANDIDATES

    Energy Technology Data Exchange (ETDEWEB)

    Kobulnicky, Henry A.; Chick, William T.; Schurhammer, Danielle P.; Andrews, Julian E.; Munari, Stephan A.; Olivier, Grace M.; Sorber, Rebecca L.; Wernke, Heather N.; Dale, Daniel A. [Dept. of Physics and Astronomy, University of Wyoming, Laramie, WY 82070 (United States); Povich, Matthew S.; Dixon, Don M. [Department of Physics and Astronomy, California State Polytechnic University, 3801 West Temple Avenue, Pomona, CA 91768 (United States)

    2016-12-01

    We identify 709 arc-shaped mid-infrared nebula in 24 μ m Spitzer Space Telescope or 22 μ m Wide Field Infrared Explorer surveys of the Galactic Plane as probable dusty interstellar bowshocks powered by early-type stars. About 20% are visible at 8 μ m or at shorter mid-infrared wavelengths. The vast majority (660) have no previous identification in the literature. These extended infrared sources are strongly concentrated near the Galactic mid-plane, with an angular scale height of ∼0.°6. All host a symmetrically placed star implicated as the source of a stellar wind sweeping up interstellar material. These are candidate “runaway” stars potentially having high velocities in the reference frame of the local medium. Among the 286 objects with measured proper motions, we find an unambiguous excess with velocity vectors aligned with the infrared morphology—kinematic evidence that many of these are “runaway” stars with large peculiar motions responsible for the bowshock signature. We discuss a population of “in situ” bowshocks (∼103 objects) that face giant H ii regions where the relative motions between the star and ISM may be caused by bulk outflows from an overpressured bubble. We also identify ∼58 objects that face 8 μ m bright-rimmed clouds and apparently constitute a sub-class of in situ bowshocks where the stellar wind interacts with a photoevaporative flow (PEF) from an eroding molecular cloud interface (i.e., “PEF bowshocks”). Orientations of the arcuate nebulae exhibit a correlation over small angular scales, indicating that external influences such as H ii regions are responsible for producing some bowshock nebulae. However, the vast majority of the nebulae in this sample appear to be isolated (499 objects) from obvious external influences.

  5. Search for the glueball candidates $f_{0}$(1500) and $f_{J}$(1710) in $\\gamma\\gamma$ collisions in ALEPH Detector

    CERN Document Server

    Barate, R.; Ghez, Philippe; Goy, C.; Lees, J.P.; Merle, E.; Minard, M.N.; Pietrzyk, B.; Alemany, R.; Bravo, S.; Casado, M.P.; Chmeissani, M.; Crespo, J.M.; Fernandez, E.; Fernandez-Bosman, M.; Garrido, L.; Grauges, E.; Juste, A.; Martinez, M.; Merino, G.; Miquel, R.; Mir, L.M.; Pacheco, A.; Riu, I.; Ruiz, H.; Colaleo, A.; Creanza, D.; De Palma, M.; Iaselli, G.; Maggi, G.; Maggi, M.; Nuzzo, S.; Ranieri, A.; Raso, G.; Ruggieri, F.; Selvaggi, G.; Silvestris, L.; Tempesta, P.; Tricomi, A.; Zito, G.; Huang, X.; Lin, J.; Ouyang, Q.; Wang, T.; Xie, Y.; Xu, R.; Xue, S.; Zhang, J.; Zhang, L.; Zhao, W.; Abbaneo, D.; Boix, G.; Buchmuller, O.; Cattaneo, M.; Cerutti, F.; Ciulli, V.; Dissertori, G.; Drevermann, H.; Forty, R.W.; Frank, M.; Greening, T.C.; Halley, A.W.; Hansen, J.B.; Harvey, John; Janot, P.; Jost, B.; Lehraus, I.; Leroy, O.; Mato, P.; Minten, A.; Moutoussi, A.; Ranjard, F.; Rolandi, Gigi; Schlatter, D.; Schmitt, M.; Schneider, O.; Spagnolo, P.; Tejessy, W.; Teubert, F.; Tournefier, E.; Wright, A.E.; Ajaltouni, Z.; Badaud, F.; Chazelle, G.; Deschamps, O.; Falvard, A.; Ferdi, C.; Gay, P.; Guicheney, C.; Henrard, P.; Jousset, J.; Michel, B.; Monteil, S.; Montret, J.C.; Pallin, D.; Perret, P.; Podlyski, F.; Hansen, J.D.; Hansen, J.R.; Hansen, P.H.; Nilsson, B.S.; Rensch, B.; Waananen, A.; Daskalakis, G.; Kyriakis, A.; Markou, C.; Simopoulou, E.; Siotis, I.; Vayaki, A.; Blondel, A.; Bonneaud, G.; Brient, J.C.; Rouge, A.; Rumpf, M.; Swynghedauw, M.; Verderi, M.; Videau, H.; Focardi, E.; Parrini, G.; Zachariadou, K.; Corden, M.; Georgiopoulos, C.; Antonelli, A.; Bencivenni, G.; Bologna, G.; Bossi, F.; Campana, P.; Capon, G.; Chiarella, V.; Laurelli, P.; Mannocchi, G.; Murtas, F.; Murtas, G.P.; Passalacqua, L.; Pepe-Altarelli, M.; Curtis, L.; Lynch, J.G.; Negus, P.; O'Shea, V.; Raine, C.; Teixeira-Dias, P.; Thompson, A.S.; Cavanaugh, R.; Dhamotharan, S.; Geweniger, C.; Hanke, P.; Hansper, G.; Hepp, V.; Kluge, E.E.; Putzer, A.; Sommer, J.; Tittel, K.; Werner, S.; Wunsch, M.; Beuselinck, R.; Binnie, D.M.; Cameron, W.; Dornan, P.J.; Girone, M.; Goodsir, S.; Martin, E.B.; Marinelli, N.; Sciaba, A.; Sedgbeer, J.K.; Thomson, Evelyn J.; Williams, M.D.; Ghete, V.M.; Girtler, P.; Kneringer, E.; Kuhn, D.; Rudolph, G.; Bowdery, C.K.; Buck, P.G.; Finch, A.J.; Foster, F.; Hughes, G.; Jones, R.W.L.; Robertson, N.A.; Williams, M.I.; Giehl, I.; Jakobs, K.; Kleinknecht, K.; Quast, G.; Renk, B.; Rohne, E.; Sander, H.G.; Wachsmuth, H.; Zeitnitz, C.; Aubert, J.J.; Bonissent, A.; Carr, J.; Coyle, P.; Payre, P.; Rousseau, D.; Aleppo, M.; Antonelli, M.; Ragusa, F.; Buescher, Volker; Dietl, H.; Ganis, G.; Huttmann, K.; Lutjens, G.; Mannert, C.; Manner, W.; Moser, H.G.; Schael, S.; Settles, R.; Seywerd, H.; Stenzel, H.; Wiedenmann, W.; Wolf, G.; Azzurri, P.; Boucrot, J.; Callot, O.; Chen, S.; Cordier, A.; Davier, M.; Duflot, L.; Grivaz, J.F.; Heusse, P.; Jacholkowska, A.; Le Diberder, F.; Lefrancois, J.; Lutz, A.M.; Schune, M.H.; Veillet, J.J.; Videau, I.; Zerwas, D.; Bagliesi, Giuseppe; Boccali, T.; Bozzi, C.; Calderini, G.; Dell'Orso, R.; Ferrante, I.; Foa, L.; Giassi, A.; Gregorio, A.; Ligabue, F.; Marrocchesi, P.S.; Messineo, A.; Palla, F.; Rizzo, G.; Sanguinetti, G.; Sguazzoni, G.; Tenchini, R.; Venturi, A.; Verdini, P.G.; Blair, G.A.; Cowan, G.; Green, M.G.; Medcalf, T.; Strong, J.A.; Botterill, D.R.; Clifft, R.W.; Edgecock, T.R.; Norton, P.R.; Thompson, J.C.; Tomalin, I.R.; Bloch-Devaux, Brigitte; Colas, P.; Emery, S.; Kozanecki, W.; Lancon, E.; Lemaire, M.C.; Locci, E.; Perez, P.; Rander, J.; Renardy, J.F.; Roussarie, A.; Schuller, J.P.; Schwindling, J.; Trabelsi, A.; Vallage, B.; Black, S.N.; Dann, J.H.; Johnson, R.P.; Kim, H.Y.; Konstantinidis, N.; Litke, A.M.; McNeil, M.A.; Taylor, G.; Booth, C.N.; Cartwright, S.; Combley, F.; Lehto, M.; Thompson, L.F.; Affholderbach, K.; Boehrer, Armin; Brandt, S.; Grupen, C.; Hess, J.; Misiejuk, A.; Prange, G.; Sieler, U.; Giannini, G.; Gobbo, B.; Rothberg, J.; Wasserbaech, S.; Armstrong, S.R.; Elmer, P.; Ferguson, D.P.S.; Gao, Y.; Gonzalez, S.; Hayes, O.J.; Hu, H.; Jin, S.; Kile, J.; McNamara, P.A., III; Nielsen, J.; Orejudos, W.; Pan, Y.B.; Saadi, Y.; Scott, I.J.; Walsh, J.; von Wimmersperg-Toeller, J.H.; Wu, Sau Lan; Wu, X.; Zobernig, G.

    2000-01-01

    Data taken with the ALEPH detector at LEP1 have been used to search for gamma gamma production of the glueball candidates f0(1500) and fJ(1710) via their decay to pi+pi-. No signal is observed and upper limits to the product of gamma gamma width and pi+pi- branching ratio of the f0(1500) and the fJ(1710) have been measured to be Gamma_(gamma gamma -> f0(1500)). BR(f0(1500)->pi+pi-) fJ(1710)). BR(fJ(1710)->pi+pi-) < 0.55 keV at 95\\-onfidence level.

  6. Search for the glueball candidates f/sub 0/(1500) and f/sub J/(1710) in gamma gamma collisions

    CERN Document Server

    Shan, Jin

    2001-01-01

    Summary form only given. Data taken with the ALEPH detector at LEP1 have been used to search for gamma gamma production of the glueball candidates f/sub 0/(1500) and f/sub J/(1710) via their decay to pi /sup +/ pi /sup -//sub ./ No signal is observed and upper limits to the product of gamma gamma width and pi /sup +/ pi /sup b/ranching ratio of the f/sub 0/(1500) and the f/sub J/(1710) have been measured to be Gamma ( gamma gamma to f/sub 0/(1500)) BR(f/sub 0/(1500) to pi /sup +/ pi /sup -/) < 0 31keV and Gamma ( gamma gamma to f/sub J /(1710)) BR(f/sub J/(1710) to pi /sup +/ pi /sup -/) < 0 55keV at 95% confidence level.

  7. A New Serum Biomarker for Lung Cancer - Transthyretin

    Directory of Open Access Journals (Sweden)

    Liyun LIU

    2009-04-01

    Full Text Available Background and objective Lung cancer is the leading cause of cancer death worldwide and very few specific biomarkers could be used in clinical diagnosis at present. The aim of this study is to find novel potential serum biomarkers for lung cancer using Surface Enhanced Laser Desorption/Ionization (SELDI technique. Methods Serumsample of 227 cases including 146 lung cancer, 13 pneumonia, 28 tuberculous pleurisy and 40 normal individuals were analyzed by CM10 chips. The candidate biomarkers were identified by ESI/MS-MS and database searching, and further confirmed by immunoprecipitation. The same sets of serum sample from all groups were re-measured by ELISA assay. Results Three protein peaks with the molecular weight 13.78 kDa, 13.90 kDa and 14.07 kDa were found significantlydecreased in lung cancer serum compared to the other groups and were all automatically selected as specific biomarkers by Biomarker Wizard software. The candidate biomarkers obtained from 1-D SDS gel bands by matching the molecular weight with peaks on CM10 chips were identified by Mass spectrometry as the native transthyretin (nativeTTR, cysTTR and glutTTR, and the identity was further validated by immunoprecipitation using commercial TTR antibodies. Downregulated of TTR was found in both ELISA and SELDI analysis. Conclusion TTRs acted as the potentially useful biomarkers for lung cancer by SELDI technique.

  8. Further Search for the Two-Photon Production of the Glueball Candidate {ital f}{sub {ital J}}(2220)

    Energy Technology Data Exchange (ETDEWEB)

    Alam, M.S.; Athar, S.B.; Ling, Z.; Mahmood, A.H.; Timm, S.; Wappler, F. [State University of New York at Albany, Albany, New York 12222 (United States); Anastassov, A.; Duboscq, J.E.; Gan, K.K.; Hart, T.; Honscheid, K.; Kagan, H.; Kass, R.; Lee, J.; Schwarthoff, H.; Spencer, M.B.; Wolf, A.; Zoeller, M.M. [Ohio State University, Columbus, Ohio 43210 (United States); Richichi, S.J.; Severini, H.; Skubic, P.; Undrus, A. [University of Oklahoma, Norman, Oklahoma 73019 (United States); Bishai, M.; Fast, J.; Hinson, J.W.; Menon, N.; Miller, D.H.; Shibata, E.I.; Shipsey, I.P. [Purdue University, West Lafayette, Indiana 47907 (United States); Glenn, S.; Kwon, Y.; Lyon, A.L.; Roberts, S.; Thorndike, E.H. [University of Rochester, Rochester, New York 14627 (United States); Jessop, C.P.; Lingel, K.; Marsiske, H.; Perl, M.L.; Savinov, V.; Ugolini, D.; Zhou, X. [Stanford Linear Accelerator Center, Stanford University, Stanford, California 94309 (United States); Coan, T.E.; Fadeyev, V.; Korolkov, I.; Maravin, Y.; Narsky, I.; Shelkov, V.; Staeck, J.; Stroynowski, R.; Volobouev, I.; Ye, J. [Southern Methodist University, Dallas, Texas 75275 (United States); Artuso, M.; Dambasuren, E.; Efimov, A.; Kopp, S.; Moneti, G.C.; Mountain, R.; Schuh, S.; Skwarnicki, T.; Stone, S.; Titov, A.; Viehhauser, G.; Wang, J.C. [Syracuse University, Syracuse, New York 13244 (United States); Bartelt, J.; Csorna, S.E.; McLean, K.W.; Marka, S. [Vanderbilt University, Nashville, Tennessee 37235 (United States); Godang, R.; Kinoshita, K.; Lai, I.C.; Pomianowski, P.; Schrenk, S. [Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061 (United States); Bonvicini, G.; Cinabro, D.; Greene, R.; Perera, L.P.; Zhou, G.J. [Wayne State University, Detroit, Michigan 48202 (United States); Chadhha, M.; Chan, S.; Eigen, G.; Miller, J.S.; Schmidtler, M.; Urheim, J.; Weinstein, A.J.; Wuerthwein, F. [California Institute of Technology, Pasadena, California 91125 (United States)

    1998-10-01

    The CLEO II detector at the e{sup +}e{sup {minus}} storage ring CESR has been used to search for two-photon production of the f{sub J}(2220) decaying into {pi}{sup +}{pi}{sup {minus}} . No evidence for a signal is found in 4.77 fb{sup {minus}1} of data and a 95{percent} C.L. upper limit on [{Gamma}{sub {gamma}{gamma}}B{sub {pi}{sup +}{pi}{sup {minus}}}]{sub f{sub J}( 2220)} of 2.5thinspthinspeV is set. If this result is combined with the BES Collaboration{close_quote}s measurement of f{sub J}(2220){r_arrow}{pi}{sup +}{pi}{sup {minus}} in radiative J/{psi} decay and the recent CLEO result for [{Gamma}{sub {gamma}{gamma}}B{sub K{sup 0}{sub S}K{sup 0}{sub S}}]{sub f{sub J} (2220)} , a 95{percent} C.L. lower limit on the stickiness of 102 is obtained. This result for the stickiness provides further support for a substantial neutral parton content in the f{sub J}(2220) . {copyright} {ital 1998} {ital The American Physical Society }

  9. Novel CTL epitopes identified through a Y. pestis proteome-wide analysis in the search for vaccine candidates against plague.

    Science.gov (United States)

    Zvi, Anat; Rotem, Shahar; Zauberman, Ayelet; Elia, Uri; Aftalion, Moshe; Bar-Haim, Erez; Mamroud, Emanuelle; Cohen, Ofer

    2017-10-20

    The causative agent of Plague, Yersinia pestis, is a highly virulent pathogen and a potential bioweapon. Depending on the route of infection, two prevalent occurrences of the disease are known, bubonic and pneumonic. The latter has a high fatality rate. In the absence of a licensed vaccine, intense efforts to develop a safe and efficacious vaccine have been conducted, and humoral-driven subunit vaccines containing the F1 and LcrV antigens are currently under clinical trials. It is well known that a cellular immune response might have an essential additive value to immunity and protection against Y. pestis infection. Nevertheless, very few documented epitopes eliciting a protective T-cell response have been reported. Here, we present a combined high throughput computational and experimental effort towards identification of CD8 T-cell epitopes. All 4067 proteins of Y. pestis were analyzed with state-of-the-art recently developed prediction algorithms aimed at mapping potential MHC class I binders. A compilation of the results obtained from several prediction methods revealed a total of 238,000 peptide candidates, which necessitated downstream filtering criteria. Our previously established and proven approach for enrichment of true positive CTL epitopes, which relies on mapping clusters rich in tandem or overlapping predicted MHC binders ("hotspots"), was applied, as well as considerations of predicted binding affinity. A total of 1532 peptides were tested for their ability to elicit a specific T-cell response by following the production of IFNγ from splenocytes isolated from vaccinated mice. Altogether, the screen resulted in 178 positive responders (11.8%), all novel Y. pestis CTL epitopes. These epitopes span 113 Y. pestis proteins. Substantial enrichment of membrane-associated proteins was detected for epitopes selected from hotspots of predicted MHC binders. These results considerably expand the repertoire of known CTL epitopes in Y. pestis and pave the way to

  10. LABORATORY BIOMARKERS FOR ANKYLOSING SPONDYLITIS

    Directory of Open Access Journals (Sweden)

    E. N. Aleksandrova

    2017-01-01

    Full Text Available Ankylosing spondylitis (AS is a chronic inflammatory disease from a group of spondyloarthritis (SpA, which is characterized by lesions of the sacroiliac joints and spine with the common involvement of entheses and peripheral joints in the pathological process. Advances in modern laboratory medicine have contributed to a substantial expansion of the range of pathogenetic, diagnostic, and prognostic biomarkers of AS. As of now, there are key pathogenetic biomarkers of AS (therapeutic targets, which include tumor necrosis factor-α (TNF-α, interleukin 17 (IL-17, and IL-23. Among the laboratory diagnostic and prognostic biomarkers, HLA-B27 and C-reactive protein are of the greatest value in clinical practice; the former for the early diagnosis of the disease and the latter for the assessment of disease activity, the risk of radiographic progression and the efficiency of therapy. Anti-CD74 antibodies are a new biomarker that has high sensitivity and specificity values in diagnosing axial SpA at an early stage. A number of laboratory biomarkers, including calprotectin, matrix metalloproteinase-3 (MMP-3, vascular endothelial growth factor, Dickkopf-1 (Dkk-1, and C-terminal telopeptide of type II collagen (CTX II do not well reflect disease activity, but may predict progressive structural changes in the spine and sacroiliac joints in AS. Blood calprotectin level monitoring allows the effective prediction of a response to therapy with TNF inhibitors and anti-IL-17А monoclonal antibodies. The prospects for the laboratory diagnosis of AS are associated with the clinical validation of candidate biomarkers during large-scale prospective cohort studies and with a search for new proteomic, transcriptomic and genomic markers, by using innovative molecular and cellular technologies.

  11. Data for iTRAQ profiling of micro-vesicular plasma specimens: In search of potential prognostic circulatory biomarkers for Lacunar infarction

    Directory of Open Access Journals (Sweden)

    Arnab Datta

    2015-09-01

    Full Text Available To discover potential prognostic biomarkers of Lacunar infarction (LACI, here we present quantitative proteomics data of plasma microvesicle-enriched fraction derived by comparative isobaric profiling of three groups of prospectively followed-up LACI patients (LACI – no adverse outcome, LACI –recurrent vascular event and LACI – cognitive decline and a demographically matched control group. We confidently (unused prot score >3, FDR=1.1% identified 183 proteins, 43 out of which were significantly regulated (p-value<0.05 in at least one of the three LACI groups in comparison to control group. Bioinformatics analysis and data mining revealed upregulation of brain-specific proteins including myelin basic protein, proteins of coagulation cascade (e.g., fibrinogen alpha chain, fibrinogen beta chain and focal adhesion (e.g., integrin alpha-IIb, talin-1, and filamin-A while albumin was downregulated in both groups of patients with adverse outcome. The data of this study are also in line with our previously published article entitled “Discovery of prognostic biomarker candidates of Lacunar infarction by quantitative proteomics of microvesicles enriched plasma” by Datta et al. (2014. The raw data had been deposited to the ProteomeXchange consortium with identifier PXD000748.

  12. Serotonin Metabolites in the Cerebrospinal Fluid in the Sudden Infant Death Syndrome: In Search of a Biomarker of Risk

    Science.gov (United States)

    Rognum, Ingvar J.; Tran, Hoa; Haas, Elisabeth A.; Hyland, Keith; Paterson, David S.; Haynes, Robin L.; Broadbelt, Kevin G.; Harty, Brian J.; Mena, Othon; Krous, Henry F.; Kinney, Hannah C.

    2015-01-01

    Clinical biomarkers are urgently needed in the sudden infant death syndrome (SIDS) to identify living infants at risk because it because it occurs without occurs without clinical warning. Previously, we reported multiple serotonergic (5-HT) abnormalities in nuclei of the medulla oblongata that help mediate protective responses to homeostatic stressors. Here we test the hypothesis that 5-HT-related measures are abnormal in the cerebrospinal fluid (CSF) of SIDS infants compared to autopsy controls, as a first step towards their assessment as diagnostic biomarkers of medullary pathology. Levels of CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), the degradative products of 5-HT and dopamine, respectively, were measured by high performance liquid chromatography in 57 SIDS and 29 non-SIDS autopsy cases. Tryptophan (Trp) and tyrosine (Tyr), the substrates of 5-HT and dopamine, respectively, were also measured. There were no significant differences in 5-HIAA, Trp, HVA, or Tyr levels between the SIDS and non-SIDS groups. These data preclude use of 5-HIAA, HVA, Trp or Tyr measurements as CSF biomarkers of 5-HT medullary pathology in infants at risk. They provide, however, important information about monoaminergic measurements in human CSF at autopsy and their developmental profile in infancy that is applicable to multiple pediatric disorders beyond SIDS. PMID:24423636

  13. Mining biomarker information in biomedical literature

    Directory of Open Access Journals (Sweden)

    Younesi Erfan

    2012-12-01

    Full Text Available Abstract Background For selection and evaluation of potential biomarkers, inclusion of already published information is of utmost importance. In spite of significant advancements in text- and data-mining techniques, the vast knowledge space of biomarkers in biomedical text has remained unexplored. Existing named entity recognition approaches are not sufficiently selective for the retrieval of biomarker information from the literature. The purpose of this study was to identify textual features that enhance the effectiveness of biomarker information retrieval for different indication areas and diverse end user perspectives. Methods A biomarker terminology was created and further organized into six concept classes. Performance of this terminology was optimized towards balanced selectivity and specificity. The information retrieval performance using the biomarker terminology was evaluated based on various combinations of the terminology's six classes. Further validation of these results was performed on two independent corpora representing two different neurodegenerative diseases. Results The current state of the biomarker terminology contains 119 entity classes supported by 1890 different synonyms. The result of information retrieval shows improved retrieval rate of informative abstracts, which is achieved by including clinical management terms and evidence of gene/protein alterations (e.g. gene/protein expression status or certain polymorphisms in combination with disease and gene name recognition. When additional filtering through other classes (e.g. diagnostic or prognostic methods is applied, the typical high number of unspecific search results is significantly reduced. The evaluation results suggest that this approach enables the automated identification of biomarker information in the literature. A demo version of the search engine SCAIView, including the biomarker retrieval, is made available to the public through http

  14. Biomarkers of systemic lupus erythematosus identified using mass spectrometry-based proteomics: a systematic review.

    Science.gov (United States)

    Nicolaou, Orthodoxia; Kousios, Andreas; Hadjisavvas, Andreas; Lauwerys, Bernard; Sokratous, Kleitos; Kyriacou, Kyriacos

    2017-05-01

    Advances in mass spectrometry technologies have created new opportunities for discovering novel protein biomarkers in systemic lupus erythematosus (SLE). We performed a systematic review of published reports on proteomic biomarkers identified in SLE patients using mass spectrometry-based proteomics and highlight their potential disease association and clinical utility. Two electronic databases, MEDLINE and EMBASE, were systematically searched up to July 2015. The methodological quality of studies included in the review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Twenty-five studies were included in the review, identifying 241 SLE candidate proteomic biomarkers related to various aspects of the disease including disease diagnosis and activity or pinpointing specific organ involvement. Furthermore, 13 of the 25 studies validated their results for a selected number of biomarkers in an independent cohort, resulting in the validation of 28 candidate biomarkers. It is noteworthy that 11 candidate biomarkers were identified in more than one study. A significant number of potential proteomic biomarkers that are related to a number of aspects of SLE have been identified using mass spectrometry proteomic approaches. However, further studies are required to assess the utility of these biomarkers in routine clinical practice. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  15. Fine mapping and candidate gene search of quantitative trait loci for growth and obesity using mouse intersubspecific subcongenic intercrosses and exome sequencing.

    Directory of Open Access Journals (Sweden)

    Akira Ishikawa

    Full Text Available Although growth and body composition traits are quantitative traits of medical and agricultural importance, the genetic and molecular basis of those traits remains elusive. Our previous genome-wide quantitative trait locus (QTL analyses in an intersubspecific backcross population between C57BL/6JJcl (B6 and wild Mus musculus castaneus mice revealed a major growth QTL (named Pbwg1 on a proximal region of mouse chromosome 2. Using the B6.Cg-Pbwg1 intersubspecific congenic strain created, we revealed 12 closely linked QTLs for body weight and body composition traits on an approximately 44.1-Mb wild-derived congenic region. In this study, we narrowed down genomic regions harboring three (Pbwg1.12, Pbwg1.3 and Pbwg1.5 of the 12 linked QTLs and searched for possible candidate genes for the QTLs. By phenotypic analyses of F2 intercross populations between B6 and each of four B6.Cg-Pbwg1 subcongenic strains with overlapping and non-overlapping introgressed regions, we physically defined Pbwg1.12 affecting body weight to a 3.8-Mb interval (61.5-65.3 Mb on chromosome 2. We fine-mapped Pbwg1.3 for body length to an 8.0-Mb interval (57.3-65.3 and Pbwg1.5 for abdominal white fat weight to a 2.1-Mb interval (59.4-61.5. The wild-derived allele at Pbwg1.12 and Pbwg1.3 uniquely increased body weight and length despite the fact that the wild mouse has a smaller body size than that of B6, whereas it decreased fat weight at Pbwg1.5. Exome sequencing and candidate gene prioritization suggested that Gcg and Grb14 are putative candidate genes for Pbwg1.12 and that Ly75 and Itgb6 are putative candidate genes for Pbwg1.5. These genes had nonsynonymous SNPs, but the SNPs were predicted to be not harmful to protein functions. These results provide information helpful to identify wild-derived quantitative trait genes causing enhanced growth and resistance to obesity.

  16. Validation of New Cancer Biomarkers

    DEFF Research Database (Denmark)

    Duffy, Michael J; Sturgeon, Catherine M; Söletormos, Georg

    2015-01-01

    BACKGROUND: Biomarkers are playing increasingly important roles in the detection and management of patients with cancer. Despite an enormous number of publications on cancer biomarkers, few of these biomarkers are in widespread clinical use. CONTENT: In this review, we discuss the key steps...... in advancing a newly discovered cancer candidate biomarker from pilot studies to clinical application. Four main steps are necessary for a biomarker to reach the clinic: analytical validation of the biomarker assay, clinical validation of the biomarker test, demonstration of clinical value from performance...... of the biomarker test, and regulatory approval. In addition to these 4 steps, all biomarker studies should be reported in a detailed and transparent manner, using previously published checklists and guidelines. Finally, all biomarker studies relating to demonstration of clinical value should be registered before...

  17. Hypermethylated 14-3-3-σ and ESR1 gene promoters in serum as candidate biomarkers for the diagnosis and treatment efficacy of breast cancer metastasis

    International Nuclear Information System (INIS)

    Zurita, Mercedes; Lara, Pedro C; Moral, Rosario del; Torres, Blanca; Linares-Fernández, José Luis; Arrabal, Sandra Ríos; Martínez-Galán, Joaquina; Oliver, Francisco Javier; Ruiz de Almodóvar, José Mariano

    2010-01-01

    Numerous hypermethylated genes have been reported in breast cancer, and the silencing of these genes plays an important role in carcinogenesis, tumor progression and diagnosis. These hypermethylated promoters are very rarely found in normal breast. It has been suggested that aberrant hypermethylation may be useful as a biomarker, with implications for breast cancer etiology, diagnosis, and management. The relationship between primary neoplasm and metastasis remains largely unknown. There has been no comprehensive comparative study on the clinical usefulness of tumor-associated methylated DNA biomarkers in primary breast carcinoma and metastatic breast carcinoma. The objective of the present study was to investigate the association between clinical extension of breast cancer and methylation status of Estrogen Receptor1 (ESR1) and Stratifin (14-3-3-σ) gene promoters in disease-free and metastatic breast cancer patients. We studied two cohorts of patients: 77 patients treated for breast cancer with no signs of disease, and 34 patients with metastatic breast cancer. DNA was obtained from serum samples, and promoter methylation status was determined by using DNA bisulfite modification and quantitative methylation-specific PCR. Serum levels of methylated gene promoter 14-3-3-σ significantly differed between Control and Metastatic Breast Cancer groups (P < 0.001), and between Disease-Free and Metastatic Breast Cancer groups (P < 0.001). The ratio of the 14-3-3-σ level before the first chemotherapy cycle to the level just before administration of the second chemotherapy cycle was defined as the Biomarker Response Ratio [BRR]. We calculated BRR values for the 'continuous decline' and 'rise-and-fall' groups. Subsequent ROC analysis showed a sensitivity of 75% (95% CI: 47.6 - 86.7) and a specificity of 66.7% (95% CI: 41.0 - 86.7) to discriminate between the groups for a cut-off level of BRR = 2.39. The area under the ROC curve (Z = 0.804 ± 0

  18. Search for dark matter particle candidates production in association with a Z boson in pp collisions at center-of-mass energy of 13 TeV with the ATLAS detector

    CERN Document Server

    Basalaev, Artem; The ATLAS collaboration

    2017-01-01

    A search for dark matter particle candidates produced in association with a Z boson in proton-proton collisions at the total center-of-mass energy of 13 TeV is presented. The search uses 36.1 inverse femtobarn of data collected by the ATLAS experiment at the Large Hadron Collider in 2015 and 2016. Events with large missing transverse momentum and consistent with the decay of a Z boson into oppositely charged electron or muon pairs were selected in the analysis. Background estimates and corresponding systematic uncertainties are shown. Exclusion limits on the dark matter candidate and mediator masses are reported.

  19. Search for dark matter particle candidates produced in association with a Z boson in pp collisions at a center-of-mass energy of 13 TeV with the ATLAS detector

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00399337; The ATLAS collaboration

    2017-01-01

    A search for dark matter particle candidates produced in association with a Z boson in proton-proton collisions at the total center-of-mass energy of 13 TeV is presented. The search uses 36.1 inverse femtobarn of data collected by the ATLAS experiment at the Large Hadron Collider in 2015 and 2016. Events with large missing transverse momentum and consistent with the decay of a Z boson into oppositely charged electron or muon pairs were selected in the analysis. Background estimates and corresponding systematic uncertainties are shown. Exclusion limits on the dark matter candidate and mediator masses are reported.

  20. A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients.

    Directory of Open Access Journals (Sweden)

    Anne-Li Lind

    Full Text Available The objective of this study was to develop and apply a novel multiplex panel of solid-phase proximity ligation assays (SP-PLA requiring only 20 μL of samples, as a tool for discovering protein biomarkers for neurological disease and treatment thereof in cerebrospinal fluid (CSF. We applied the SP-PLA to samples from two sets of patients with poorly understood nervous system pathologies amyotrophic lateral sclerosis (ALS and neuropathic pain, where patients were treated with spinal cord stimulation (SCS. Forty-seven inflammatory and neurotrophic proteins were measured in samples from 20 ALS patients and 15 neuropathic pain patients, and compared to normal concentrations in CSF from control individuals. Nineteen of the 47 proteins were detectable in more than 95% of the 72 controls. None of the 21 proteins detectable in CSF from neuropathic pain patients were significantly altered by SCS. The levels of the three proteins, follistatin, interleukin-1 alpha, and kallikrein-5 were all significantly reduced in the ALS group compared to age-matched controls. These results demonstrate the utility of purpose designed multiplex SP-PLA panels in CSF biomarker research for understanding neuropathological and neurotherapeutic mechanisms. The protein changes found in the CSF of ALS patients may be of diagnostic interest.

  1. iTRAQ-Based Proteomics Analysis of Serum Proteins in Wistar Rats Treated with Sodium Fluoride: Insight into the Potential Mechanism and Candidate Biomarkers of Fluorosis

    Directory of Open Access Journals (Sweden)

    Yan Wei

    2016-09-01

    Full Text Available Fluorosis induced by exposure to high level fluoride is quite widespread in the world. The manifestations of fluorosis include dental mottling, bone damage, and impaired malfunction of soft tissues. However, the molecular mechanism of fluorosis has not been clarified until now. To explore the underlying mechanisms of fluorosis and screen out serum biomarkers, we carried out a quantitative proteomics study to identify differentially expressed serum proteins in Wistar rats treated with sodium fluoride (NaF by using a proteomics approach of isobaric tagging for relative and absolute quantitation (iTRAQ. We fed Wistar rats drinking water that had 50, 150, and 250 mg/L of dissolved NaF for 24 weeks. For the experimental duration, each rat was given an examination of the lower incisors to check for the condition of dental fluorosis (DF. By the end of the treatment, fluoride ion concentration in serum and lower incisors were detected. The results showed that NaF treatment can induce rat fluorosis. By iTRAQ analysis, a total of 37 differentially expressed serum proteins were identified between NaF-treated and control rats. These proteins were further analyzed by bioinformatics, out of which two proteins were validated by enzyme-linked immunoadsorbent assays (ELISA. The major proteins were involved in complement and coagulation cascade, inflammatory response, complement activation, defense response, and wound response, suggesting that inflammation and immune reactions may play a key role in fluorosis pathogenesis. These proteins may contribute to the understanding of the mechanism of fluoride toxicity, and may serve as potential biomarkers for fluorosis.

  2. Proteomic Analysis of Plasma from California Sea Lions (Zalophus californianus Reveals Apolipoprotein E as a Candidate Biomarker of Chronic Domoic Acid Toxicosis.

    Directory of Open Access Journals (Sweden)

    Benjamin A Neely

    Full Text Available Domoic acid toxicosis (DAT in California sea lions (Zalophus californianus is caused by exposure to the marine biotoxin domoic acid and has been linked to massive stranding events and mortality. Diagnosis is based on clinical signs in addition to the presence of domoic acid in body fluids. Chronic DAT further is characterized by reoccurring seizures progressing to status epilepticus. Diagnosis of chronic DAT is often slow and problematic, and minimally invasive tests for DAT have been the focus of numerous recent biomarker studies. The goal of this study was to retrospectively profile plasma proteins in a population of sea lions with chronic DAT and those without DAT using two dimensional gel electrophoresis to discover whether individual, multiple, or combinations of protein and clinical data could be utilized to identify sea lions with DAT. Using a training set of 32 sea lion sera, 20 proteins and their isoforms were identified that were significantly different between the two groups (p<0.05. Interestingly, 11 apolipoprotein E (ApoE charge forms were decreased in DAT samples, indicating that ApoE charge form distributions may be important in the progression of DAT. In order to develop a classifier of chronic DAT, an independent blinded test set of 20 sea lions, seven with chronic DAT, was used to validate models utilizing ApoE charge forms and eosinophil counts. The resulting support vector machine had high sensitivity (85.7% with 92.3% negative predictive value and high specificity (92.3% with 85.7% positive predictive value. These results suggest that ApoE and eosinophil counts along with machine learning can perform as a robust and accurate tool to diagnose chronic DAT. Although this analysis is specifically focused on blood biomarkers and routine clinical data, the results demonstrate promise for future studies combining additional variables in multidimensional space to create robust classifiers.

  3. Searching for biomarkers of CDKL5 disorder: early-onset visual impairment in CDKL5 mutant mice.

    Science.gov (United States)

    Mazziotti, Raffaele; Lupori, Leonardo; Sagona, Giulia; Gennaro, Mariangela; Della Sala, Grazia; Putignano, Elena; Pizzorusso, Tommaso

    2017-06-15

    CDKL5 disorder is a neurodevelopmental disorder still without a cure. Murine models of CDKL5 disorder have been recently generated raising the possibility of preclinical testing of treatments. However, unbiased, quantitative biomarkers of high translational value to monitor brain function are still missing. Moreover, the analysis of treatment is hindered by the challenge of repeatedly and non-invasively testing neuronal function. We analyzed the development of visual responses in a mouse model of CDKL5 disorder to introduce visually evoked responses as a quantitative method to assess cortical circuit function. Cortical visual responses were assessed in CDKL5 null male mice, heterozygous females, and their respective control wild-type littermates by repeated transcranial optical imaging from P27 until P32. No difference between wild-type and mutant mice was present at P25-P26 whereas defective responses appeared from P27-P28 both in heterozygous and homozygous CDKL5 mutant mice. These results were confirmed by visually evoked potentials (VEPs) recorded from the visual cortex of a different cohort. The previously imaged mice were also analyzed at P60-80 using VEPs, revealing a persistent reduction of response amplitude, reduced visual acuity and defective contrast function. The level of adult impairment was significantly correlated with the reduction in visual responses observed during development. Support vector machine showed that multi-dimensional visual assessment can be used to automatically classify mutant and wt mice with high reliability. Thus, monitoring visual responses represents a promising biomarker for preclinical and clinical studies on CDKL5 disorder. © The Author 2017. Published by Oxford University Press.

  4. Selection of candidate radiation bio-markers in the serum of rats exposed to gamma-rays by GC/TOFMS-based metabolomics

    International Nuclear Information System (INIS)

    Liu, H.; Wang, Z.; Zhang, X.; Qiao, Y.; Wu, S.; Dong, F.; Chen, Y.

    2013-01-01

    In the study, gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) techniques coupled with principal components analysis (PCA) were used to investigate metabolite perturbations in the serum of the rats exposed to 0.75, 3 or 8 Gy gamma rays. Male standard deviation rats were gamma-irradiated at doses of 0.75, 3 and 8 Gy (1.9 Gy min -1 ) or sham-irradiated. Serum samples were collected over the first 24 h under the exposure to irradiation in order to analyse the samples by GC/TOFMS. And multivariate data were analysed by PCA. The composition of metabolites in serum yielded distinct metabolomic phenotypes for 0.75, 3 and 8 Gy at 24 h after irradiation. Nine serum metabolites were significantly altered as a result of radiation exposure. Up-regulated metabolites included inositol, serine, lysine, glycine, threonine and glycerol; down regulated metabolites included isocitrate, gluconic acid and stearic acid. The nine metabolites were significantly altered after ionising radiation for they may be the potential bio-markers for the diagnosis of radiation injury. All rights reserved. (authors)

  5. Metabolomics reveals dose effects of low-dose chronic exposure to uranium in rats: identification of candidate biomarkers in urine samples.

    Science.gov (United States)

    Grison, Stéphane; Favé, Gaëlle; Maillot, Matthieu; Manens, Line; Delissen, Olivia; Blanchardon, Éric; Dublineau, Isabelle; Aigueperse, Jocelyne; Bohand, Sandra; Martin, Jean-Charles; Souidi, Maâmar

    2016-01-01

    Data are sparse about the potential health risks of chronic low-dose contamination of humans by uranium (natural or anthropogenic) in drinking water. Previous studies report some molecular imbalances but no clinical signs due to uranium intake. In a proof-of-principle study, we reported that metabolomics is an appropriate method for addressing this chronic low-dose exposure in a rat model (uranium dose: 40 mg L -1 ; duration: 9 months, n = 10). In the present study, our aim was to investigate the dose-effect pattern and identify additional potential biomarkers in urine samples. Compared to our previous protocol, we doubled the number of rats per group (n = 20), added additional sampling time points (3 and 6 months) and included several lower doses of natural uranium (doses used: 40, 1.5, 0.15 and 0.015 mg L -1 ). LC-MS metabolomics was performed on urine samples and statistical analyses were made with SIMCA-P+ and R packages. The data confirmed our previous results and showed that discrimination was both dose and time related. Uranium exposure was revealed in rats contaminated for 9 months at a dose as low as 0.15 mg L -1 . Eleven features, including the confidently identified N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide and 4-hydroxyphenylacetylglycine, discriminated control from contaminated rats with a specificity and a sensitivity ranging from 83 to 96 %, when combined into a composite score. These findings show promise for the elucidation of underlying radiotoxicologic mechanisms and the design of a diagnostic test to assess exposure in urine, in a dose range experimentally estimated to be above a threshold between 0.015 and 0.15 mg L -1 .

  6. Spatiotemporal proteomic analyses during pancreas cancer progression identifies serine/threonine stress kinase 4 (STK4) as a novel candidate biomarker for early stage disease.

    Science.gov (United States)

    Mirus, Justin E; Zhang, Yuzheng; Hollingsworth, Michael A; Solan, Joell L; Lampe, Paul D; Hingorani, Sunil R

    2014-12-01

    Pancreas cancer, or pancreatic ductal adenocarcinoma, is the deadliest of solid tumors, with a five-year survival rate of pancreas cancer. Mouse models that accurately recapitulate the human condition allow disease tracking from inception to invasion and can therefore be useful for studying early disease stages in which surgical resection is possible. Using a highly faithful mouse model of pancreas cancer in conjunction with a high-density antibody microarray containing ∼2500 antibodies, we interrogated the pancreatic tissue proteome at preinvasive and invasive stages of disease. The goal was to discover early stage tissue markers of pancreas cancer and follow them through histologically defined stages of disease using cohorts of mice lacking overt clinical signs and symptoms and those with end-stage metastatic disease, respectively. A panel of seven up-regulated proteins distinguishing pancreas cancer from normal pancreas was validated, and their levels were assessed in tissues collected at preinvasive, early invasive, and moribund stages of disease. Six of the seven markers also differentiated pancreas cancer from an experimental model of chronic pancreatitis. The levels of serine/threonine stress kinase 4 (STK4) increased between preinvasive and invasive stages, suggesting its potential as a tissue biomarker, and perhaps its involvement in progression from precursor pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma. Immunohistochemistry of STK4 at different stages of disease revealed a dynamic expression pattern further implicating it in early tumorigenic events. Immunohistochemistry of a panel of human pancreas cancers confirmed that STK4 levels were increased in tumor epithelia relative to normal tissue. Overall, this integrated approach yielded several tissue markers that could serve as signatures of disease stage, including early (resectable), and therefore clinically meaningful, stages. © 2014 by The American Society for

  7. Technological challenges in Magnetic Resonance Imaging: enhancing sensitivity, moving to quantitative imaging and searching for disease biomarkers

    Science.gov (United States)

    Retico, A.

    2018-02-01

    Diagnostic imaging based on the Nuclear Magnetic Resonance phenomenon has increasingly spread in the recent few decades, mainly owing to its exquisite capability in depicting a contrast between soft tissues, to its generally non-invasive nature, and to the priceless advantage of using non-ionizing radiation. Magnetic Resonance (MR)-based acquisition techniques allow gathering information on the structure (through Magnetic Resonance Imaging— MRI), the metabolic composition (through Magnetic Resonance Spectroscopy—MRS), and the functioning (through functional MRI —fMRI) of the human body. MR investigations are the methods of choice for studying the brain in vivo, including anatomy, structural wiring and functional connectivity, in healthy and pathological conditions. Alongside the efforts of the clinical research community in extending the acquisition protocols to allow the exploration of a large variety of pathologies affecting diverse body regions, some relevant technological improvements are on the way to maximize the impact of MR in medical diagnostic. The development of MR scanners operating at ultra-high magnetic field (UHF) strength (>= 7 tesla), is pushing forward the spatial resolution of MRI and the spectral resolution of MRS, and it is increasing the specificity of fMRI to grey matter signal. UHF MR systems are currently in use for research purposes only; nevertheless, UHF technological advances are positively affecting MR investigations at clinical field strengths. To overcome the current major limitation of MRI, which is mostly based on contrast between tissues rather than on absolute measurements of physical quantities, a new acquisition modality is under development, which is referred as Magnetic Resonance Fingerprinting technique. Finally, as neuroimaging data acquired worldwide are reaching the typical size of Big Data, dedicated technical solutions are required to mine large amount of information and to identify specific biomarkers of

  8. Pleural effusion adenosine deaminase: a candidate biomarker to discriminate between Gram-negative and Gram-positive bacterial infections of the pleural space

    Directory of Open Access Journals (Sweden)

    Ruolin Li

    2016-05-01

    Full Text Available OBJECTIVES: Delay in the treatment of pleural infection may contribute to its high mortality. In this retrospective study, we aimed to evaluate the diagnostic accuracy of pleural adenosine deaminase in discrimination between Gram-negative and Gram-positive bacterial infections of the pleural space prior to selecting antibiotics. METHODS: A total of 76 patients were enrolled and grouped into subgroups according to Gram staining: 1 patients with Gram-negative bacterial infections, aged 53.2±18.6 years old, of whom 44.7% had empyemas and 2 patients with Gram-positive bacterial infections, aged 53.5±21.5 years old, of whom 63.1% had empyemas. The pleural effusion was sampled by thoracocentesis and then sent for adenosine deaminase testing, biochemical testing and microbiological culture. The Mann-Whitney U test was used to examine the differences in adenosine deaminase levels between the groups. Correlations between adenosine deaminase and specified variables were also quantified using Spearman’s correlation coefficient. Moreover, receiver operator characteristic analysis was performed to evaluate the diagnostic accuracy of pleural effusion adenosine deaminase. RESULTS: Mean pleural adenosine deaminase levels differed significantly between Gram-negative and Gram-positive bacterial infections of the pleural space (191.8±32.1 U/L vs 81.0±16.9 U/L, p<0.01. The area under the receiver operator characteristic curve was 0.689 (95% confidence interval: 0.570, 0.792, p<0.01 at the cutoff value of 86 U/L. Additionally, pleural adenosine deaminase had a sensitivity of 63.2% (46.0-78.2%; a specificity of 73.7% (56.9-86.6%; positive and negative likelihood ratios of 2.18 and 0.50, respectively; and positive and negative predictive values of 70.6% and 66.7%, respectively. CONCLUSIONS: Pleural effusion adenosine deaminase is a helpful alternative biomarker for early and quick discrimination of Gram-negative from Gram-positive bacterial infections of the

  9. Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity.

    Science.gov (United States)

    Malik, Zulezwan Ab; Cobley, James N; Morton, James P; Close, Graeme L; Edwards, Ben J; Koch, Lauren G; Britton, Steven L; Burniston, Jatin G

    2013-12-01

    earlier transcriptome profiling work and show LC-MS is a viable means of profiling the abundance of almost all major metabolic enzymes of skeletal muscle in a highly parallel manner. Moreover, our approach is relatively more time efficient than techniques relying on orthogonal separations, and we demonstrate LC-MS profiling of the HCR/LCR selection model was able to highlight biomarkers that also exhibit differences in trained and untrained human muscle.

  10. Investigating the emerging role of comparative proteomics in the search for new biomarkers of metal contamination under varying abiotic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Vellinger, Céline, E-mail: celine.vellinger@gmail.com [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France); Sohm, Bénédicte, E-mail: benedicte.sohm@univ-lorraine.fr [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France); Parant, Marc, E-mail: marc.parant@univ-lorraine.fr [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France); Immel, Françoise, E-mail: Francoise.Immel@u-bourgogne.fr [Biogéosciences, CNRS UMR 6282, Université de Bourgogne – Dijon (France); Usseglio-Polatera, Philippe, E-mail: philippe.usseglio-polatera@univ-lorraine.fr [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France)

    2016-08-15

    mixture previously observed on G. pulex mortality at 10 °C. - Highlights: • We tested comparative proteomics for identifying new biomarkers of chemical exposure. • Both metal interactions and temperature confounding effects were taken into account. • 129 spots have been highlighted as potential Protein Expression Signatures at 10 °C. • Proteomics has high potential but a long way still to go to efficient multi-marker. • Recommendations and precautions for future studies have been presented.

  11. Investigating the emerging role of comparative proteomics in the search for new biomarkers of metal contamination under varying abiotic conditions

    International Nuclear Information System (INIS)

    Vellinger, Céline; Sohm, Bénédicte; Parant, Marc; Immel, Françoise; Usseglio-Polatera, Philippe

    2016-01-01

    mixture previously observed on G. pulex mortality at 10 °C. - Highlights: • We tested comparative proteomics for identifying new biomarkers of chemical exposure. • Both metal interactions and temperature confounding effects were taken into account. • 129 spots have been highlighted as potential Protein Expression Signatures at 10 °C. • Proteomics has high potential but a long way still to go to efficient multi-marker. • Recommendations and precautions for future studies have been presented.

  12. Optimization of ultra-high pressure liquid chromatography - tandem mass spectrometry determination in plasma and red blood cells of four sphingolipids and their evaluation as biomarker candidates of Gaucher's disease.

    Science.gov (United States)

    Chipeaux, Caroline; de Person, Marine; Burguet, Nathalie; Billette de Villemeur, Thierry; Rose, Christian; Belmatoug, Nadia; Héron, Sylvie; Le Van Kim, Caroline; Franco, Mélanie; Moussa, Fathi

    2017-11-24

    While important advances have been recently achieved in the optimization of lipid classes' separation, information on the specific determination of medium polarity lipids such as sphingolipids (SLs) in highly complex matrices remains fragmentary. In human, disorders of SL metabolism known as sphingolipidoses are a heterogeneous group of inherited disorders affecting primarily the central nervous. Early diagnosis of these conditions is of importance notably when a corrective therapy is available. The diagnosis is generally based on the determination of specific SLs in plasma and red blood cells (RBCs). For instance, glucosylceramide (GL1), glucosylsphingosine (Lyso-GL1), sphingosine (Sph), and sphingosine-1-phosphate (S1P) are proposed as relevant biomarkers for Gaucher disease (GD). Our main objective was to evaluate these biomarker candidates in a cohort of GD patients. However, most of current methods of GL1, Lyso-GL1, Sph, and S1P determination in plasma of GD patients require at least two liquid chromatographic runs. On the other hand, except for GL1 nothing is known concerning the RBC sphingolipid content. Yet, several reversed phase LC-MS methods of SLs separation and/or determination in various media with different sample preparation approaches have been proposed since 2010. Here we focused on stationary phase selection and mobile phase composition as well as on the sample preparation step to optimize and validate an UHPLC-MS/MS method for the simultaneous quantification of the four sphingolipids in both plasma and RBCs. A comparison between seven stationary phases including two RP18, two polar embedded RP18, and three HILIC phases shows that under our conditions polar embedded RP18 phases are the most appropriate for the separation of the four SLs, in terms of efficiency, peak symmetry, and separation time. In the same way, a comparison between a single step extraction with methanol and a liquid-liquid extraction with a mixture of methanol/methyl tert

  13. Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity

    Directory of Open Access Journals (Sweden)

    Zulezwan A. Malik

    2013-12-01

    .54-fold (p = 0.0064 more abundant in HCR than LCR soleus. This discovery was verified using selective reaction monitoring (SRM of the y5 ion (551.21 m/z of the doubly-charged peptide SLGVGFATR (454.19 m/z of residues 23–31 of FABPH. SRM was conducted on technical replicates of each biological sample and exhibited a coefficient of variation of 20%. The abundance of FABPH measured by SRM was 2.84-fold greater (p = 0.0095 in HCR muscle. In addition, SRM of FABPH was performed in vastus lateralis samples of young and elderly humans with different habitual activity levels (collected during a previous study finding FABPH abundance was 2.23-fold greater (p = 0.0396 in endurance-trained individuals regardless of differences in age. In summary, our findings in HCR/LCR rats provide protein-level confirmation for earlier transcriptome profiling work and show LC-MS is a viable means of profiling the abundance of almost all major metabolic enzymes of skeletal muscle in a highly parallel manner. Moreover, our approach is relatively more time efficient than techniques relying on orthogonal separations, and we demonstrate LC-MS profiling of the HCR/LCR selection model was able to highlight biomarkers that also exhibit differences in trained and untrained human muscle.

  14. Search for a dark matter candidate produced in association with a single top quark in pp collisions at √[s]=1.96  TeV.

    Science.gov (United States)

    Aaltonen, T; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Anzá, F; Apollinari, G; Appel, J A; Arisawa, T; Artikov, A; Asaadi, J; Ashmanskas, W; Auerbach, B; Aurisano, A; Azfar, F; Badgett, W; Bae, T; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Barria, P; Bartos, P; Bauce, M; Bedeschi, F; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Bhatti, A; Bisello, D; Bizjak, I; Bland, K R; Blumenfeld, B; Bocci, A; Bodek, A; Bortoletto, D; Boudreau, J; Boveia, A; Brigliadori, L; Bromberg, C; Brucken, E; Budagov, J; Budd, H S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Calamba, A; Calancha, C; Camarda, S; Campanelli, M; Campbell, M; Canelli, F; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chung, W H; Chung, Y S; Ciocci, M A; Clark, A; Clarke, C; Compostella, G; Convery, M E; Conway, J; Corbo, M; Cordelli, M; Cox, C A; Cox, D J; Crescioli, F; Cuevas, J; Culbertson, R; Dagenhart, D; d'Ascenzo, N; Datta, M; de Barbaro, P; Dell'Orso, M; Demortier, L; Deninno, M; Devoto, F; d'Errico, M; Di Canto, A; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Dorigo, M; Dorigo, T; Ebina, K; Elagin, A; Eppig, A; Erbacher, R; Errede, S; Ershaidat, N; Eusebi, R; Farrington, S; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Forrest, R; Frank, M J; Franklin, M; Freeman, J C; Fuks, B; Funakoshi, Y; Furic, I; Gallinaro, M; Garcia, J E; Garfinkel, A F; Garosi, P; Gerberich, H; Gerchtein, E; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Ginsburg, C M; Giokaris, N; Giromini, P; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldin, D; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Grinstein, S; Grosso-Pilcher, C; Group, R C; Guimaraes da Costa, J; Hahn, S R; Halkiadakis, E; Hamaguchi, A; Han, J Y; Happacher, F; Hara, K; Hare, D; Hare, M; Harr, R F; Hatakeyama, K; Hays, C; Heck, M; Heinrich, J; Herndon, M; Hewamanage, S; Hocker, A; Hopkins, W; Horn, D; Hou, S; Hughes, R E; Hurwitz, M; Husemann, U; Hussain, N; Hussein, M; Huston, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Junk, T R; Kamon, T; Karchin, P E; Kasmi, A; Kato, Y; Ketchum, W; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kim, Y J; Kimura, N; Kirby, M; Klimenko, S; Knoepfel, K; Kondo, K; Kong, D J; Konigsberg, J; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Kruse, M; Krutelyov, V; Kuhr, T; Kurata, M; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; LeCompte, T; Lee, E; Lee, H S; Lee, J S; Lee, S W; Leo, S; Leone, S; Lewis, J D; Limosani, A; Lin, C-J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, H; Liu, Q; Liu, T; Lockwitz, S; Loginov, A; Lucchesi, D; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lys, J; Lysak, R; Madrak, R; Maeshima, K; Maestro, P; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Martínez, M; Mastrandrea, P; Matera, K; Mattson, M E; Mazzacane, A; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Mesropian, C; Miao, T; Mietlicki, D; Mitra, A; Miyake, H; Moed, S; Moggi, N; Mondragon, M N; Moon, C S; Moore, R; Morello, M J; Morlock, J; Movilla Fernandez, P; Mukherjee, A; Muller, Th; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Naganoma, J; Nakano, I; Napier, A; Nett, J; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Noh, S Y; Norniella, O; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Ortolan, L; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Paramonov, A A; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pilot, J; Pitts, K; Plager, C; Pondrom, L; Poprocki, S; Potamianos, K; Prokoshin, F; Pranko, A; Ptohos, F; Punzi, G; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Renton, P; Rescigno, M; Riddick, T; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Ruffini, F; Ruiz, A; Russ, J; Rusu, V; Safonov, A; Sakumoto, W K; Sakurai, Y; Santi, L; Sato, K; Saveliev, V; Savoy-Navarro, A; Schlabach, P; Schmidt, A; Schmidt, E E; Schwarz, T; Scodellaro, L; Scribano, A; Scuri, F; Seidel, S; Seiya, Y; Semenov, A; Sforza, F; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shochet, M; Shreyber-Tecker, I; Simonenko, A; Sinervo, P; Sliwa, K; Smith, J R; Snider, F D; Soha, A; Sorin, V; Song, H; Squillacioti, P; Stancari, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Strycker, G L; Sudo, Y; Sukhanov, A; Suslov, I; Takemasa, K; Takeuchi, Y; Tang, J; Tecchio, M; Teng, P K; Thom, J; Thome, J; Thompson, G A; Thomson, E; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Trovato, M; Ukegawa, F; Uozumi, S; Varganov, A; Vázquez, F; Velev, G; Vellidis, C; Vidal, M; Vila, I; Vilar, R; Vizán, J; Vogel, M; Volpi, G; Wagner, P; Wagner, R L; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Wester, W C; Whiteson, D; Wicklund, A B; Wicklund, E; Wilbur, S; Wick, F; Williams, H H; Wilson, J S; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, H; Wright, T; Wu, X; Wu, Z; Yamamoto, K; Yamato, D; Yang, T; Yang, U K; Yang, Y C; Yao, W-M; Yeh, G P; Yi, K; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanetti, A; Zeng, Y; Zhou, C; Zucchelli, S

    2012-05-18

    We report a new search for dark matter in a data sample of an integrated luminosity of 7.7  fb-1 of Tevatron pp[over ¯] collisions at √[s]=1.96  TeV, collected by the CDF II detector. We search for production of a dark-matter candidate, D, in association with a single top quark. We consider the hadronic decay mode of the top quark exclusively, yielding a final state of three jets with missing transverse energy. The data are consistent with the standard model; we thus set 95% confidence level upper limits on the cross section of the process pp[over ¯]→t+D as a function of the mass of the dark-matter candidate. The limits are approximately 0.5 pb for a dark-matter particle with mass in the range of 0-150  GeV/c2.

  15. Search for an invisibly decaying Higgs boson or dark matter candidates produced in association with a Z boson in pp collisions at s=13 TeV with the ATLAS detector

    Directory of Open Access Journals (Sweden)

    M. Aaboud

    2018-01-01

    Full Text Available A search for an invisibly decaying Higgs boson or dark matter candidates produced in association with a leptonically decaying Z boson in proton–proton collisions at s=13 TeV is presented. This search uses 36.1 fb−1 of data collected by the ATLAS experiment at the Large Hadron Collider. No significant deviation from the expectation of the Standard Model backgrounds is observed. Assuming the Standard Model ZH production cross-section, an observed (expected upper limit of 67% (39% at the 95% confidence level is set on the branching ratio of invisible decays of the Higgs boson with mass mH=125 GeV. The corresponding limits on the production cross-section of the ZH process with the invisible Higgs boson decays are also presented. Furthermore, exclusion limits on the dark matter candidate and mediator masses are reported in the framework of simplified dark matter models.

  16. Search for an invisibly decaying Higgs boson or dark matter candidates produced in association with a Z boson in pp collisions at √{ s } = 13 TeV with the ATLAS detector

    Science.gov (United States)

    Aaboud, M.; Aad, G.; Abbott, B.; Abdinov, O.; Abeloos, B.; Abidi, S. H.; Abouzeid, O. S.; Abraham, N. L.; Abramowicz, H.; Abreu, H.; Abreu, R.; Abulaiti, Y.; Acharya, B. S.; Adachi, S.; Adamczyk, L.; Adelman, J.; Adersberger, M.; Adye, T.; Affolder, A. A.; Afik, Y.; Agatonovic-Jovin, T.; Agheorghiesei, C.; Aguilar-Saavedra, J. A.; Ahlen, S. P.; Ahmadov, F.; Aielli, G.; Akatsuka, S.; Akerstedt, H.; Åkesson, T. P. A.; Akilli, E.; Akimov, A. V.; Alberghi, G. L.; Albert, J.; Albicocco, P.; Alconada Verzini, M. J.; Alderweireldt, S. C.; Aleksa, M.; Aleksandrov, I. N.; Alexa, C.; Alexander, G.; Alexopoulos, T.; Alhroob, M.; Ali, B.; Aliev, M.; Alimonti, G.; Alison, J.; Alkire, S. P.; Allbrooke, B. M. M.; Allen, B. W.; Allport, P. P.; Aloisio, A.; Alonso, A.; Alonso, F.; Alpigiani, C.; Alshehri, A. A.; Alstaty, M. I.; Alvarez Gonzalez, B.; Álvarez Piqueras, D.; Alviggi, M. G.; Amadio, B. T.; Amaral Coutinho, Y.; Amelung, C.; Amidei, D.; Amor Dos Santos, S. P.; Amoroso, S.; Amundsen, G.; Anastopoulos, C.; Ancu, L. S.; Andari, N.; Andeen, T.; Anders, C. F.; Anders, J. K.; Anderson, K. J.; Andreazza, A.; Andrei, V.; Angelidakis, S.; Angelozzi, I.; Angerami, A.; Anisenkov, A. V.; Anjos, N.; Annovi, A.; Antel, C.; Antonelli, M.; Antonov, A.; Antrim, D. J.; Anulli, F.; Aoki, M.; Aperio Bella, L.; Arabidze, G.; Arai, Y.; Araque, J. P.; Araujo Ferraz, V.; Arce, A. T. H.; Ardell, R. E.; Arduh, F. A.; Arguin, J.-F.; Argyropoulos, S.; Arik, M.; Armbruster, A. J.; Armitage, L. J.; Arnaez, O.; Arnold, H.; Arratia, M.; Arslan, O.; Artamonov, A.; Artoni, G.; Artz, S.; Asai, S.; Asbah, N.; Ashkenazi, A.; Asquith, L.; Assamagan, K.; Astalos, R.; Atkinson, M.; Atlay, N. B.; Augsten, K.; Avolio, G.; Axen, B.; Ayoub, M. K.; Azuelos, G.; Baas, A. E.; Baca, M. J.; Bachacou, H.; Bachas, K.; Backes, M.; Bagnaia, P.; Bahmani, M.; Bahrasemani, H.; Baines, J. T.; Bajic, M.; Baker, O. K.; Bakker, P. J.; Baldin, E. M.; Balek, P.; Balli, F.; Balunas, W. K.; Banas, E.; Bandyopadhyay, A.; Banerjee, Sw.; Bannoura, A. A. E.; Barak, L.; Barberio, E. L.; Barberis, D.; Barbero, M.; Barillari, T.; Barisits, M.-S.; Barkeloo, J. T.; Barklow, T.; Barlow, N.; Barnes, S. L.; Barnett, B. M.; Barnett, R. M.; Barnovska-Blenessy, Z.; Baroncelli, A.; Barone, G.; Barr, A. J.; Barranco Navarro, L.; Barreiro, F.; Barreiro Guimarães da Costa, J.; Bartoldus, R.; Barton, A. E.; Bartos, P.; Basalaev, A.; Bassalat, A.; Bates, R. L.; Batista, S. J.; Batley, J. R.; Battaglia, M.; Bauce, M.; Bauer, F.; Bawa, H. S.; Beacham, J. B.; Beattie, M. D.; Beau, T.; Beauchemin, P. H.; Bechtle, P.; Beck, H. P.; Beck, H. C.; Becker, K.; Becker, M.; Becot, C.; Beddall, A. J.; Beddall, A.; Bednyakov, V. A.; Bedognetti, M.; Bee, C. P.; Beermann, T. A.; Begalli, M.; Begel, M.; Behr, J. K.; Bell, A. S.; Bella, G.; Bellagamba, L.; Bellerive, A.; Bellomo, M.; Belotskiy, K.; Beltramello, O.; Belyaev, N. L.; Benary, O.; Benchekroun, D.; Bender, M.; Benekos, N.; Benhammou, Y.; Benhar Noccioli, E.; Benitez, J.; Benjamin, D. P.; Benoit, M.; Bensinger, J. R.; Bentvelsen, S.; Beresford, L.; Beretta, M.; Berge, D.; Bergeaas Kuutmann, E.; Berger, N.; Beringer, J.; Berlendis, S.; Bernard, N. R.; Bernardi, G.; Bernius, C.; Bernlochner, F. U.; Berry, T.; Berta, P.; Bertella, C.; Bertoli, G.; Bertram, I. A.; Bertsche, C.; Besjes, G. J.; Bessidskaia Bylund, O.; Bessner, M.; Besson, N.; Bethani, A.; Bethke, S.; Betti, A.; Bevan, A. J.; Beyer, J.; Bianchi, R. M.; Biebel, O.; Biedermann, D.; Bielski, R.; Bierwagen, K.; Biesuz, N. V.; Biglietti, M.; Billoud, T. R. V.; Bilokon, H.; Bindi, M.; Bingul, A.; Bini, C.; Biondi, S.; Bisanz, T.; Bittrich, C.; Bjergaard, D. M.; Black, J. E.; Black, K. M.; Blair, R. E.; Blazek, T.; Bloch, I.; Blocker, C.; Blue, A.; Blumenschein, U.; Blunier, S.; Bobbink, G. J.; Bobrovnikov, V. S.; Bocchetta, S. S.; Bocci, A.; Bock, C.; Boehler, M.; Boerner, D.; Bogavac, D.; Bogdanchikov, A. G.; Bohm, C.; Boisvert, V.; Bokan, P.; Bold, T.; Boldyrev, A. S.; Bolz, A. E.; Bomben, M.; Bona, M.; Boonekamp, M.; Borisov, A.; Borissov, G.; Bortfeldt, J.; Bortoletto, D.; Bortolotto, V.; Boscherini, D.; Bosman, M.; Bossio Sola, J. D.; Boudreau, J.; Bouhova-Thacker, E. V.; Boumediene, D.; Bourdarios, C.; Boutle, S. K.; Boveia, A.; Boyd, J.; Boyko, I. R.; Bozson, A. J.; Bracinik, J.; Brandt, A.; Brandt, G.; Brandt, O.; Braren, F.; Bratzler, U.; Brau, B.; Brau, J. E.; Breaden Madden, W. D.; Brendlinger, K.; Brennan, A. J.; Brenner, L.; Brenner, R.; Bressler, S.; Briglin, D. L.; Bristow, T. M.; Britton, D.; Britzger, D.; Brochu, F. M.; Brock, I.; Brock, R.; Brooijmans, G.; Brooks, T.; Brooks, W. K.; Brosamer, J.; Brost, E.; Broughton, J. H.; Bruckman de Renstrom, P. A.; Bruncko, D.; Bruni, A.; Bruni, G.; Bruni, L. S.; Bruno, S.; Brunt, Bh; Bruschi, M.; Bruscino, N.; Bryant, P.; Bryngemark, L.; Buanes, T.; Buat, Q.; Buchholz, P.; Buckley, A. G.; Budagov, I. A.; Buehrer, F.; Bugge, M. K.; Bulekov, O.; Bullock, D.; Burch, T. J.; Burdin, S.; Burgard, C. D.; Burger, A. M.; Burghgrave, B.; Burka, K.; Burke, S.; Burmeister, I.; Burr, J. T. P.; Büscher, D.; Büscher, V.; Bussey, P.; Butler, J. M.; Buttar, C. M.; Butterworth, J. M.; Butti, P.; Buttinger, W.; Buzatu, A.; Buzykaev, A. R.; Cabrera Urbán, S.; Caforio, D.; Cai, H.; Cairo, V. M.; Cakir, O.; Calace, N.; Calafiura, P.; Calandri, A.; Calderini, G.; Calfayan, P.; Callea, G.; Caloba, L. P.; Calvente Lopez, S.; Calvet, D.; Calvet, S.; Calvet, T. P.; Camacho Toro, R.; Camarda, S.; Camarri, P.; Cameron, D.; Caminal Armadans, R.; Camincher, C.; Campana, S.; Campanelli, M.; Camplani, A.; Campoverde, A.; Canale, V.; Cano Bret, M.; Cantero, J.; Cao, T.; Capeans Garrido, M. D. M.; Caprini, I.; Caprini, M.; Capua, M.; Carbone, R. M.; Cardarelli, R.; Cardillo, F.; Carli, I.; Carli, T.; Carlino, G.; Carlson, B. T.; Carminati, L.; Carney, R. M. D.; Caron, S.; Carquin, E.; Carrá, S.; Carrillo-Montoya, G. D.; Casadei, D.; Casado, M. P.; Casha, A. F.; Casolino, M.; Casper, D. W.; Castelijn, R.; Castillo Gimenez, V.; Castro, N. F.; Catinaccio, A.; Catmore, J. R.; Cattai, A.; Caudron, J.; Cavaliere, V.; Cavallaro, E.; Cavalli, D.; Cavalli-Sforza, M.; Cavasinni, V.; Celebi, E.; Ceradini, F.; Cerda Alberich, L.; Cerqueira, A. S.; Cerri, A.; Cerrito, L.; Cerutti, F.; Cervelli, A.; Cetin, S. A.; Chafaq, A.; Chakraborty, D.; Chan, S. K.; Chan, W. S.; Chan, Y. L.; Chang, P.; Chapman, J. D.; Charlton, D. G.; Chau, C. C.; Chavez Barajas, C. A.; Che, S.; Cheatham, S.; Chegwidden, A.; Chekanov, S.; Chekulaev, S. V.; Chelkov, G. A.; Chelstowska, M. A.; Chen, C.; Chen, C.; Chen, H.; Chen, J.; Chen, S.; Chen, S.; Chen, X.; Chen, Y.; Cheng, H. C.; Cheng, H. J.; Cheplakov, A.; Cheremushkina, E.; Cherkaoui El Moursli, R.; Cheu, E.; Cheung, K.; Chevalier, L.; Chiarella, V.; Chiarelli, G.; Chiodini, G.; Chisholm, A. S.; Chitan, A.; Chiu, Y. H.; Chizhov, M. V.; Choi, K.; Chomont, A. R.; Chouridou, S.; Chow, Y. S.; Christodoulou, V.; Chu, M. C.; Chudoba, J.; Chuinard, A. J.; Chwastowski, J. J.; Chytka, L.; Ciftci, A. K.; Cinca, D.; Cindro, V.; Cioara, I. A.; Ciocio, A.; Cirotto, F.; Citron, Z. H.; Citterio, M.; Ciubancan, M.; Clark, A.; Clark, B. L.; Clark, M. R.; Clark, P. J.; Clarke, R. N.; Clement, C.; Coadou, Y.; Cobal, M.; Coccaro, A.; Cochran, J.; Colasurdo, L.; Cole, B.; Colijn, A. P.; Collot, J.; Colombo, T.; Conde Muiño, P.; Coniavitis, E.; Connell, S. H.; Connelly, I. A.; Constantinescu, S.; Conti, G.; Conventi, F.; Cooke, M.; Cooper-Sarkar, A. M.; Cormier, F.; Cormier, K. J. R.; Corradi, M.; Corriveau, F.; Cortes-Gonzalez, A.; Costa, G.; Costa, M. J.; Costanzo, D.; Cottin, G.; Cowan, G.; Cox, B. E.; Cranmer, K.; Crawley, S. J.; Creager, R. A.; Cree, G.; Crépé-Renaudin, S.; Crescioli, F.; Cribbs, W. A.; Cristinziani, M.; Croft, V.; Crosetti, G.; Cueto, A.; Cuhadar Donszelmann, T.; Cukierman, A. R.; Cummings, J.; Curatolo, M.; Cúth, J.; Czekierda, S.; Czodrowski, P.; D'Amen, G.; D'Auria, S.; D'Eramo, L.; D'Onofrio, M.; da Cunha Sargedas de Sousa, M. J.; da Via, C.; Dabrowski, W.; Dado, T.; Dai, T.; Dale, O.; Dallaire, F.; Dallapiccola, C.; Dam, M.; Dandoy, J. R.; Daneri, M. F.; Dang, N. P.; Daniells, A. C.; Dann, N. S.; Danninger, M.; Dano Hoffmann, M.; Dao, V.; Darbo, G.; Darmora, S.; Dassoulas, J.; Dattagupta, A.; Daubney, T.; Davey, W.; David, C.; Davidek, T.; Davis, D. R.; Davison, P.; Dawe, E.; Dawson, I.; de, K.; de Asmundis, R.; de Benedetti, A.; de Castro, S.; de Cecco, S.; de Groot, N.; de Jong, P.; de la Torre, H.; de Lorenzi, F.; de Maria, A.; de Pedis, D.; de Salvo, A.; de Sanctis, U.; de Santo, A.; de Vasconcelos Corga, K.; de Vivie de Regie, J. B.; Debbe, R.; Debenedetti, C.; Dedovich, D. V.; Dehghanian, N.; Deigaard, I.; Del Gaudio, M.; Del Peso, J.; Delgove, D.; Deliot, F.; Delitzsch, C. M.; Dell'Acqua, A.; Dell'Asta, L.; Dell'Orso, M.; Della Pietra, M.; Della Volpe, D.; Delmastro, M.; Delporte, C.; Delsart, P. A.; Demarco, D. A.; Demers, S.; Demichev, M.; Demilly, A.; Denisov, S. P.; Denysiuk, D.; Derendarz, D.; Derkaoui, J. E.; Derue, F.; Dervan, P.; Desch, K.; Deterre, C.; Dette, K.; Devesa, M. R.; Deviveiros, P. O.; Dewhurst, A.; Dhaliwal, S.; di Bello, F. A.; di Ciaccio, A.; di Ciaccio, L.; di Clemente, W. K.; di Donato, C.; di Girolamo, A.; di Girolamo, B.; di Micco, B.; di Nardo, R.; di Petrillo, K. F.; di Simone, A.; di Sipio, R.; di Valentino, D.; Diaconu, C.; Diamond, M.; Dias, F. A.; Diaz, M. A.; Diehl, E. B.; Dietrich, J.; Díez Cornell, S.; Dimitrievska, A.; Dingfelder, J.; Dita, P.; Dita, S.; Dittus, F.; Djama, F.; Djobava, T.; Djuvsland, J. I.; Do Vale, M. A. B.; Dobos, D.; Dobre, M.; Dodsworth, D.; Doglioni, C.; Dolejsi, J.; Dolezal, Z.; Donadelli, M.; Donati, S.; Dondero, P.; Donini, J.; Dopke, J.; Doria, A.; Dova, M. T.; Doyle, A. T.; Drechsler, E.; Dris, M.; Du, Y.; Duarte-Campderros, J.; Dubinin, F.; Dubreuil, A.; Duchovni, E.; Duckeck, G.; Ducourthial, A.; Ducu, O. A.; Duda, D.; Dudarev, A.; Dudder, A. Chr.; Duffield, E. M.; Duflot, L.; Dührssen, M.; Dulsen, C.; Dumancic, M.; Dumitriu, A. E.; Duncan, A. K.; Dunford, M.; Duperrin, A.; Duran Yildiz, H.; Düren, M.; Durglishvili, A.; Duschinger, D.; Dutta, B.; Duvnjak, D.; Dyndal, M.; Dziedzic, B. S.; Eckardt, C.; Ecker, K. M.; Edgar, R. C.; Eifert, T.; Eigen, G.; Einsweiler, K.; Ekelof, T.; El Kacimi, M.; El Kosseifi, R.; Ellajosyula, V.; Ellert, M.; Elles, S.; Ellinghaus, F.; Elliot, A. A.; Ellis, N.; Elmsheuser, J.; Elsing, M.; Emeliyanov, D.; Enari, Y.; Ennis, J. S.; Epland, M. B.; Erdmann, J.; Ereditato, A.; Ernst, M.; Errede, S.; Escalier, M.; Escobar, C.; Esposito, B.; Estrada Pastor, O.; Etienvre, A. I.; Etzion, E.; Evans, H.; Ezhilov, A.; Ezzi, M.; Fabbri, F.; Fabbri, L.; Fabiani, V.; Facini, G.; Fakhrutdinov, R. M.; Falciano, S.; Falla, R. J.; Faltova, J.; Fang, Y.; Fanti, M.; Farbin, A.; Farilla, A.; Farina, C.; Farina, E. M.; Farooque, T.; Farrell, S.; Farrington, S. M.; Farthouat, P.; Fassi, F.; Fassnacht, P.; Fassouliotis, D.; Faucci Giannelli, M.; Favareto, A.; Fawcett, W. J.; Fayard, L.; Fedin, O. L.; Fedorko, W.; Feigl, S.; Feligioni, L.; Feng, C.; Feng, E. J.; Fenton, M. J.; Fenyuk, A. B.; Feremenga, L.; Fernandez Martinez, P.; Ferrando, J.; Ferrari, A.; Ferrari, P.; Ferrari, R.; Ferreira de Lima, D. E.; Ferrer, A.; Ferrere, D.; Ferretti, C.; Fiedler, F.; Filipčič, A.; Filipuzzi, M.; Filthaut, F.; Fincke-Keeler, M.; Finelli, K. D.; Fiolhais, M. C. N.; Fiorini, L.; Fischer, A.; Fischer, C.; Fischer, J.; Fisher, W. C.; Flaschel, N.; Fleck, I.; Fleischmann, P.; Fletcher, R. R. M.; Flick, T.; Flierl, B. M.; Flores Castillo, L. R.; Flowerdew, M. J.; Forcolin, G. T.; Formica, A.; Förster, F. A.; Forti, A.; Foster, A. G.; Fournier, D.; Fox, H.; Fracchia, S.; Francavilla, P.; Franchini, M.; Franchino, S.; Francis, D.; Franconi, L.; Franklin, M.; Frate, M.; Fraternali, M.; Freeborn, D.; Fressard-Batraneanu, S. M.; Freund, B.; Froidevaux, D.; Frost, J. A.; Fukunaga, C.; Fusayasu, T.; Fuster, J.; Gabizon, O.; Gabrielli, A.; Gabrielli, A.; Gach, G. P.; Gadatsch, S.; Gadomski, S.; Gagliardi, G.; Gagnon, L. G.; Galea, C.; Galhardo, B.; Gallas, E. J.; Gallop, B. J.; Gallus, P.; Galster, G.; Gan, K. K.; Ganguly, S.; Gao, Y.; Gao, Y. S.; Garay Walls, F. M.; García, C.; García Navarro, J. E.; García Pascual, J. A.; Garcia-Sciveres, M.; Gardner, R. W.; Garelli, N.; Garonne, V.; Gascon Bravo, A.; Gasnikova, K.; Gatti, C.; Gaudiello, A.; Gaudio, G.; Gavrilenko, I. L.; Gay, C.; Gaycken, G.; Gazis, E. N.; Gee, C. N. P.; Geisen, J.; Geisen, M.; Geisler, M. P.; Gellerstedt, K.; Gemme, C.; Genest, M. H.; Geng, C.; Gentile, S.; Gentsos, C.; George, S.; Gerbaudo, D.; Geßner, G.; Ghasemi, S.; Ghneimat, M.; Giacobbe, B.; Giagu, S.; Giangiacomi, N.; Giannetti, P.; Gibson, S. M.; Gignac, M.; Gilchriese, M.; Gillberg, D.; Gilles, G.; Gingrich, D. M.; Giordani, M. P.; Giorgi, F. M.; Giraud, P. F.; Giromini, P.; Giugliarelli, G.; Giugni, D.; Giuli, F.; Giuliani, C.; Giulini, M.; Gjelsten, B. K.; Gkaitatzis, S.; Gkialas, I.; Gkougkousis, E. L.; Gkountoumis, P.; Gladilin, L. K.; Glasman, C.; Glatzer, J.; Glaysher, P. C. F.; Glazov, A.; Goblirsch-Kolb, M.; Godlewski, J.; Goldfarb, S.; Golling, T.; Golubkov, D.; Gomes, A.; Gonçalo, R.; Goncalves Gama, R.; Goncalves Pinto Firmino da Costa, J.; Gonella, G.; Gonella, L.; Gongadze, A.; Gonski, J. L.; González de La Hoz, S.; Gonzalez-Sevilla, S.; Goossens, L.; Gorbounov, P. A.; Gordon, H. A.; Gorelov, I.; Gorini, B.; Gorini, E.; Gorišek, A.; Goshaw, A. T.; Gössling, C.; Gostkin, M. I.; Gottardo, C. A.; Goudet, C. R.; Goujdami, D.; Goussiou, A. G.; Govender, N.; Gozani, E.; Grabowska-Bold, I.; Gradin, P. O. J.; Gramling, J.; Gramstad, E.; Grancagnolo, S.; Gratchev, V.; Gravila, P. M.; Gray, C.; Gray, H. M.; Greenwood, Z. D.; Grefe, C.; Gregersen, K.; Gregor, I. M.; Grenier, P.; Grevtsov, K.; Griffiths, J.; Grillo, A. A.; Grimm, K.; Grinstein, S.; Gris, Ph.; Grivaz, J.-F.; Groh, S.; Gross, E.; Grosse-Knetter, J.; Grossi, G. C.; Grout, Z. J.; Grummer, A.; Guan, L.; Guan, W.; Guenther, J.; Guescini, F.; Guest, D.; Gueta, O.; Gui, B.; Guido, E.; Guillemin, T.; Guindon, S.; Gul, U.; Gumpert, C.; Guo, J.; Guo, W.; Guo, Y.; Gupta, R.; Gurbuz, S.; Gustavino, G.; Gutelman, B. J.; Gutierrez, P.; Gutierrez Ortiz, N. G.; Gutschow, C.; Guyot, C.; Guzik, M. P.; Gwenlan, C.; Gwilliam, C. B.; Haas, A.; Haber, C.; Hadavand, H. K.; Haddad, N.; Hadef, A.; Hageböck, S.; Hagihara, M.; Hakobyan, H.; Haleem, M.; Haley, J.; Halladjian, G.; Hallewell, G. D.; Hamacher, K.; Hamal, P.; Hamano, K.; Hamilton, A.; Hamity, G. N.; Hamnett, P. G.; Han, L.; Han, S.; Hanagaki, K.; Hanawa, K.; Hance, M.; Handl, D. M.; Haney, B.; Hanke, P.; Hansen, J. B.; Hansen, J. D.; Hansen, M. C.; Hansen, P. H.; Hara, K.; Hard, A. S.; Harenberg, T.; Hariri, F.; Harkusha, S.; Harrison, P. F.; Hartmann, N. M.; Hasegawa, Y.; Hasib, A.; Hassani, S.; Haug, S.; Hauser, R.; Hauswald, L.; Havener, L. B.; Havranek, M.; Hawkes, C. M.; Hawkings, R. J.; Hayakawa, D.; Hayden, D.; Hays, C. P.; Hays, J. M.; Hayward, H. S.; Haywood, S. J.; Head, S. J.; Heck, T.; Hedberg, V.; Heelan, L.; Heer, S.; Heidegger, K. K.; Heim, S.; Heim, T.; Heinemann, B.; Heinrich, J. J.; Heinrich, L.; Heinz, C.; Hejbal, J.; Helary, L.; Held, A.; Hellman, S.; Helsens, C.; Henderson, R. C. W.; Heng, Y.; Henkelmann, S.; Henriques Correia, A. M.; Henrot-Versille, S.; Herbert, G. H.; Herde, H.; Herget, V.; Hernández Jiménez, Y.; Herr, H.; Herten, G.; Hertenberger, R.; Hervas, L.; Herwig, T. C.; Hesketh, G. G.; Hessey, N. P.; Hetherly, J. W.; Higashino, S.; Higón-Rodriguez, E.; Hildebrand, K.; Hill, E.; Hill, J. C.; Hiller, K. H.; Hillier, S. J.; Hils, M.; Hinchliffe, I.; Hirose, M.; Hirschbuehl, D.; Hiti, B.; Hladik, O.; Hlaluku, D. R.; Hoad, X.; Hobbs, J.; Hod, N.; Hodgkinson, M. C.; Hodgson, P.; Hoecker, A.; Hoeferkamp, M. R.; Hoenig, F.; Hohn, D.; Holmes, T. R.; Homann, M.; Honda, S.; Honda, T.; Hong, T. M.; Hooberman, B. H.; Hopkins, W. H.; Horii, Y.; Horton, A. J.; Hostachy, J.-Y.; Hostiuc, A.; Hou, S.; Hoummada, A.; Howarth, J.; Hoya, J.; Hrabovsky, M.; Hrdinka, J.; Hristova, I.; Hrivnac, J.; Hryn'ova, T.; Hrynevich, A.; Hsu, P. J.; Hsu, S.-C.; Hu, Q.; Hu, S.; Huang, Y.; Hubacek, Z.; Hubaut, F.; Huegging, F.; Huffman, T. B.; Hughes, E. W.; Huhtinen, M.; Hunter, R. F. H.; Huo, P.; Huseynov, N.; Huston, J.; Huth, J.; Hyneman, R.; Iacobucci, G.; Iakovidis, G.; Ibragimov, I.; Iconomidou-Fayard, L.; Idrissi, Z.; Iengo, P.; Igonkina, O.; Iizawa, T.; Ikegami, Y.; Ikeno, M.; Ilchenko, Y.; Iliadis, D.; Ilic, N.; Iltzsche, F.; Introzzi, G.; Ioannou, P.; Iodice, M.; Iordanidou, K.; Ippolito, V.; Isacson, M. F.; Ishijima, N.; Ishino, M.; Ishitsuka, M.; Issever, C.; Istin, S.; Ito, F.; Iturbe Ponce, J. M.; Iuppa, R.; Iwasaki, H.; Izen, J. M.; Izzo, V.; Jabbar, S.; Jackson, P.; Jacobs, R. M.; Jain, V.; Jakobi, K. B.; Jakobs, K.; Jakobsen, S.; Jakoubek, T.; Jamin, D. O.; Jana, D. K.; Jansky, R.; Janssen, J.; Janus, M.; Janus, P. A.; Jarlskog, G.; Javadov, N.; Javůrek, T.; Javurkova, M.; Jeanneau, F.; Jeanty, L.; Jejelava, J.; Jelinskas, A.; Jenni, P.; Jeske, C.; Jézéquel, S.; Ji, H.; Jia, J.; Jiang, H.; Jiang, Y.; Jiang, Z.; Jiggins, S.; Jimenez Pena, J.; Jin, S.; Jinaru, A.; Jinnouchi, O.; Jivan, H.; Johansson, P.; Johns, K. A.; Johnson, C. A.; Johnson, W. J.; Jon-And, K.; Jones, R. W. L.; Jones, S. D.; Jones, S.; Jones, T. J.; Jongmanns, J.; Jorge, P. M.; Jovicevic, J.; Ju, X.; Juste Rozas, A.; Köhler, M. K.; Kaczmarska, A.; Kado, M.; Kagan, H.; Kagan, M.; Kahn, S. J.; Kaji, T.; Kajomovitz, E.; Kalderon, C. W.; Kaluza, A.; Kama, S.; Kamenshchikov, A.; Kanaya, N.; Kanjir, L.; Kantserov, V. A.; Kanzaki, J.; Kaplan, B.; Kaplan, L. S.; Kar, D.; Karakostas, K.; Karastathis, N.; Kareem, M. J.; Karentzos, E.; Karpov, S. N.; Karpova, Z. M.; Karthik, K.; Kartvelishvili, V.; Karyukhin, A. N.; Kasahara, K.; Kashif, L.; Kass, R. D.; Kastanas, A.; Kataoka, Y.; Kato, C.; Katre, A.; Katzy, J.; Kawade, K.; Kawagoe, K.; Kawamoto, T.; Kawamura, G.; Kay, E. F.; Kazanin, V. F.; Keeler, R.; Kehoe, R.; Keller, J. S.; Kellermann, E.; Kempster, J. J.; Kendrick, J.; Keoshkerian, H.; Kepka, O.; Kerševan, B. P.; Kersten, S.; Keyes, R. A.; Khader, M.; Khalil-Zada, F.; Khanov, A.; Kharlamov, A. G.; Kharlamova, T.; Khodinov, A.; Khoo, T. J.; Khovanskiy, V.; Khramov, E.; Khubua, J.; Kido, S.; Kilby, C. R.; Kim, H. Y.; Kim, S. H.; Kim, Y. K.; Kimura, N.; Kind, O. M.; King, B. T.; Kirchmeier, D.; Kirk, J.; Kiryunin, A. E.; Kishimoto, T.; Kisielewska, D.; Kitali, V.; Kivernyk, O.; Kladiva, E.; Klapdor-Kleingrothaus, T.; Klein, M. H.; Klein, M.; Klein, U.; Kleinknecht, K.; Klimek, P.; Klimentov, A.; Klingenberg, R.; Klingl, T.; Klioutchnikova, T.; Klitzner, F. F.; Kluge, E.-E.; Kluit, P.; Kluth, S.; Kneringer, E.; Knoops, E. B. F. G.; Knue, A.; Kobayashi, A.; Kobayashi, D.; Kobayashi, T.; Kobel, M.; Kocian, M.; Kodys, P.; Koffas, T.; Koffeman, E.; Köhler, N. M.; Koi, T.; Kolb, M.; Koletsou, I.; Kondo, T.; Kondrashova, N.; Köneke, K.; König, A. C.; Kono, T.; Konoplich, R.; Konstantinidis, N.; Konya, B.; Kopeliansky, R.; Koperny, S.; Kopp, A. K.; Korcyl, K.; Kordas, K.; Korn, A.; Korol, A. A.; Korolkov, I.; Korolkova, E. V.; Kortner, O.; Kortner, S.; Kosek, T.; Kostyukhin, V. V.; Kotwal, A.; Koulouris, A.; Kourkoumeli-Charalampidi, A.; Kourkoumelis, C.; Kourlitis, E.; Kouskoura, V.; Kowalewska, A. B.; Kowalewski, R.; Kowalski, T. Z.; Kozakai, C.; Kozanecki, W.; Kozhin, A. S.; Kramarenko, V. A.; Kramberger, G.; Krasnopevtsev, D.; Krasny, M. W.; Krasznahorkay, A.; Krauss, D.; Kremer, J. A.; Kretzschmar, J.; Kreutzfeldt, K.; Krieger, P.; Krizka, K.; Kroeninger, K.; Kroha, H.; Kroll, J.; Kroll, J.; Kroseberg, J.; Krstic, J.; Kruchonak, U.; Krüger, H.; Krumnack, N.; Kruse, M. C.; Kubota, T.; Kucuk, H.; Kuday, S.; Kuechler, J. T.; Kuehn, S.; Kugel, A.; Kuger, F.; Kuhl, T.; Kukhtin, V.; Kukla, R.; Kulchitsky, Y.; Kuleshov, S.; Kulinich, Y. P.; Kuna, M.; Kunigo, T.; Kupco, A.; Kupfer, T.; Kuprash, O.; Kurashige, H.; Kurchaninov, L. L.; Kurochkin, Y. A.; Kurth, M. G.; Kuwertz, E. S.; Kuze, M.; Kvita, J.; Kwan, T.; Kyriazopoulos, D.; La Rosa, A.; La Rosa Navarro, J. L.; La Rotonda, L.; La Ruffa, F.; Lacasta, C.; Lacava, F.; Lacey, J.; Lack, D. P. J.; Lacker, H.; Lacour, D.; Ladygin, E.; Lafaye, R.; Laforge, B.; Lagouri, T.; Lai, S.; Lammers, S.; Lampl, W.; Lançon, E.; Landgraf, U.; Landon, M. P. J.; Lanfermann, M. C.; Lang, V. S.; Lange, J. C.; Langenberg, R. J.; Lankford, A. J.; Lanni, F.; Lantzsch, K.; Lanza, A.; Lapertosa, A.; Laplace, S.; Laporte, J. F.; Lari, T.; Lasagni Manghi, F.; Lassnig, M.; Lau, T. S.; Laurelli, P.; Lavrijsen, W.; Law, A. T.; Laycock, P.; Lazovich, T.; Lazzaroni, M.; Le, B.; Le Dortz, O.; Le Guirriec, E.; Le Quilleuc, E. P.; Leblanc, M.; Lecompte, T.; Ledroit-Guillon, F.; Lee, C. A.; Lee, G. R.; Lee, S. C.; Lee, L.; Lefebvre, B.; Lefebvre, G.; Lefebvre, M.; Legger, F.; Leggett, C.; Lehmann Miotto, G.; Lei, X.; Leight, W. A.; Leite, M. A. L.; Leitner, R.; Lellouch, D.; Lemmer, B.; Leney, K. J. C.; Lenz, T.; Lenzi, B.; Leone, R.; Leone, S.; Leonidopoulos, C.; Lerner, G.; Leroy, C.; Les, R.; Lesage, A. A. J.; Lester, C. G.; Levchenko, M.; Levêque, J.; Levin, D.; Levinson, L. J.; Levy, M.; Lewis, D.; Li, B.; Li, Changqiao; Li, H.; Li, L.; Li, Q.; Li, Q.; Li, S.; Li, X.; Li, Y.; Liang, Z.; Liberti, B.; Liblong, A.; Lie, K.; Liebal, J.; Liebig, W.; Limosani, A.; Lin, K.; Lin, S. C.; Lin, T. H.; Linck, R. A.; Lindquist, B. E.; Lionti, A. E.; Lipeles, E.; Lipniacka, A.; Lisovyi, M.; Liss, T. M.; Lister, A.; Litke, A. M.; Liu, B.; Liu, H.; Liu, H.; Liu, J. K. K.; Liu, J.; Liu, J. B.; Liu, K.; Liu, L.; Liu, M.; Liu, Y. L.; Liu, Y.; Livan, M.; Lleres, A.; Llorente Merino, J.; Lloyd, S. L.; Lo, C. Y.; Lo Sterzo, F.; Lobodzinska, E. M.; Loch, P.; Loebinger, F. K.; Loesle, A.; Loew, K. M.; Lohse, T.; Lohwasser, K.; Lokajicek, M.; Long, B. A.; Long, J. D.; Long, R. E.; Longo, L.; Looper, K. A.; Lopez, J. A.; Lopez Paz, I.; Lopez Solis, A.; Lorenz, J.; Lorenzo Martinez, N.; Losada, M.; Lösel, P. J.; Lou, X.; Lounis, A.; Love, J.; Love, P. A.; Lu, H.; Lu, N.; Lu, Y. J.; Lubatti, H. J.; Luci, C.; Lucotte, A.; Luedtke, C.; Luehring, F.; Lukas, W.; Luminari, L.; Lundberg, O.; Lund-Jensen, B.; Lutz, M. S.; Luzi, P. M.; Lynn, D.; Lysak, R.; Lytken, E.; Lyu, F.; Lyubushkin, V.; Ma, H.; Ma, L. L.; Ma, Y.; Maccarrone, G.; Macchiolo, A.; MacDonald, C. M.; Maček, B.; Machado Miguens, J.; Madaffari, D.; Madar, R.; Mader, W. F.; Madsen, A.; Madysa, N.; Maeda, J.; Maeland, S.; Maeno, T.; Maevskiy, A. S.; Magerl, V.; Maiani, C.; Maidantchik, C.; Maier, T.; Maio, A.; Majersky, O.; Majewski, S.; Makida, Y.; Makovec, N.; Malaescu, B.; Malecki, Pa.; Maleev, V. P.; Malek, F.; Mallik, U.; Malon, D.; Malone, C.; Maltezos, S.; Malyukov, S.; Mamuzic, J.; Mancini, G.; Mandić, I.; Maneira, J.; Manhaes de Andrade Filho, L.; Manjarres Ramos, J.; Mankinen, K. H.; Mann, A.; Manousos, A.; Mansoulie, B.; Mansour, J. D.; Mantifel, R.; Mantoani, M.; Manzoni, S.; Mapelli, L.; Marceca, G.; March, L.; Marchese, L.; Marchiori, G.; Marcisovsky, M.; Marin Tobon, C. A.; Marjanovic, M.; Marley, D. E.; Marroquim, F.; Marsden, S. P.; Marshall, Z.; Martensson, M. U. F.; Marti-Garcia, S.; Martin, C. B.; Martin, T. A.; Martin, V. J.; Martin Dit Latour, B.; Martinez, M.; Martinez Outschoorn, V. I.; Martin-Haugh, S.; Martoiu, V. S.; Martyniuk, A. C.; Marzin, A.; Masetti, L.; Mashimo, T.; Mashinistov, R.; Masik, J.; Maslennikov, A. L.; Mason, L. H.; Massa, L.; Mastrandrea, P.; Mastroberardino, A.; Masubuchi, T.; Mättig, P.; Maurer, J.; Maxfield, S. J.; Maximov, D. A.; Mazini, R.; Maznas, I.; Mazza, S. M.; Mc Fadden, N. C.; Mc Goldrick, G.; Mc Kee, S. P.; McCarn, A.; McCarthy, R. L.; McCarthy, T. G.; McClymont, L. I.; McDonald, E. F.; McFayden, J. A.; McHedlidze, G.; McLean, K. D.; McMahon, S. J.; McNamara, P. C.; McNicol, C. J.; McPherson, R. A.; Meehan, S.; Megy, T. J.; Mehlhase, S.; Mehta, A.; Meideck, T.; Meier, K.; Meirose, B.; Melini, D.; Mellado Garcia, B. R.; Mellenthin, J. D.; Melo, M.; Meloni, F.; Melzer, A.; Menary, S. B.; Meng, L.; Meng, X. T.; Mengarelli, A.; Menke, S.; Meoni, E.; Mergelmeyer, S.; Merlassino, C.; Mermod, P.; Merola, L.; Meroni, C.; Merritt, F. S.; Messina, A.; Metcalfe, J.; Mete, A. S.; Meyer, C.; Meyer, J.-P.; Meyer, J.; Meyer Zu Theenhausen, H.; Miano, F.; Middleton, R. P.; Miglioranzi, S.; Mijović, L.; Mikenberg, G.; Mikestikova, M.; Mikuž, M.; Milesi, M.; Milic, A.; Millar, D. A.; Miller, D. W.; Mills, C.; Milov, A.; Milstead, D. A.; Minaenko, A. A.; Minami, Y.; Minashvili, I. A.; Mincer, A. I.; Mindur, B.; Mineev, M.; Minegishi, Y.; Ming, Y.; Mir, L. M.; Mirto, A.; Mistry, K. P.; Mitani, T.; Mitrevski, J.; Mitsou, V. A.; Miucci, A.; Miyagawa, P. S.; Mizukami, A.; Mjörnmark, J. U.; Mkrtchyan, T.; Mlynarikova, M.; Moa, T.; Mochizuki, K.; Mogg, P.; Mohapatra, S.; Molander, S.; Moles-Valls, R.; Mondragon, M. C.; Mönig, K.; Monk, J.; Monnier, E.; Montalbano, A.; Montejo Berlingen, J.; Monticelli, F.; Monzani, S.; Moore, R. W.; Morange, N.; Moreno, D.; Moreno Llácer, M.; Morettini, P.; Morgenstern, S.; Mori, D.; Mori, T.; Morii, M.; Morinaga, M.; Morisbak, V.; Morley, A. K.; Mornacchi, G.; Morris, J. D.; Morvaj, L.; Moschovakos, P.; Mosidze, M.; Moss, H. J.; Moss, J.; Motohashi, K.; Mount, R.; Mountricha, E.; Moyse, E. J. W.; Muanza, S.; Mueller, F.; Mueller, J.; Mueller, R. S. P.; Muenstermann, D.; Mullen, P.; Mullier, G. A.; Munoz Sanchez, F. J.; Murray, W. J.; Musheghyan, H.; Muškinja, M.; Myagkov, A. G.; Myska, M.; Nachman, B. P.; Nackenhorst, O.; Nagai, K.; Nagai, R.; Nagano, K.; Nagasaka, Y.; Nagata, K.; Nagel, M.; Nagy, E.; Nairz, A. M.; Nakahama, Y.; Nakamura, K.; Nakamura, T.; Nakano, I.; Naranjo Garcia, R. F.; Narayan, R.; Narrias Villar, D. I.; Naryshkin, I.; Naumann, T.; Navarro, G.; Nayyar, R.; Neal, H. A.; Nechaeva, P. Yu.; Neep, T. J.; Negri, A.; Negrini, M.; Nektarijevic, S.; Nellist, C.; Nelson, A.; Nelson, M. E.; Nemecek, S.; Nemethy, P.; Nessi, M.; Neubauer, M. S.; Neumann, M.; Newman, P. R.; Ng, T. Y.; Nguyen Manh, T.; Nickerson, R. B.; Nicolaidou, R.; Nielsen, J.; Nikiforou, N.; Nikolaenko, V.; Nikolic-Audit, I.; Nikolopoulos, K.; Nilsson, P.; Ninomiya, Y.; Nisati, A.; Nishu, N.; Nisius, R.; Nitsche, I.; Nitta, T.; Nobe, T.; Noguchi, Y.; Nomachi, M.; Nomidis, I.; Nomura, M. A.; Nooney, T.; Nordberg, M.; Norjoharuddeen, N.; Novgorodova, O.; Nozaki, M.; Nozka, L.; Ntekas, K.; Nurse, E.; Nuti, F.; O'Connor, K.; O'Neil, D. C.; O'Rourke, A. A.; O'Shea, V.; Oakham, F. G.; Oberlack, H.; Obermann, T.; Ocariz, J.; Ochi, A.; Ochoa, I.; Ochoa-Ricoux, J. P.; Oda, S.; Odaka, S.; Oh, A.; Oh, S. H.; Ohm, C. C.; Ohman, H.; Oide, H.; Okawa, H.; Okumura, Y.; Okuyama, T.; Olariu, A.; Oleiro Seabra, L. F.; Olivares Pino, S. A.; Oliveira Damazio, D.; Olsson, M. J. R.; Olszewski, A.; Olszowska, J.; Onofre, A.; Onogi, K.; Onyisi, P. U. E.; Oppen, H.; Oreglia, M. J.; Oren, Y.; Orestano, D.; Orlando, N.; Orr, R. S.; Osculati, B.; Ospanov, R.; Otero Y Garzon, G.; Otono, H.; Ouchrif, M.; Ould-Saada, F.; Ouraou, A.; Oussoren, K. P.; Ouyang, Q.; Owen, M.; Owen, R. E.; Ozcan, V. E.; Ozturk, N.; Pachal, K.; Pacheco Pages, A.; Pacheco Rodriguez, L.; Padilla Aranda, C.; Pagan Griso, S.; Paganini, M.; Paige, F.; Palacino, G.; Palazzo, S.; Palestini, S.; Palka, M.; Pallin, D.; Panagiotopoulou, E. St.; Panagoulias, I.; Pandini, C. E.; Panduro Vazquez, J. G.; Pani, P.; Panitkin, S.; Pantea, D.; Paolozzi, L.; Papadopoulou, Th. D.; Papageorgiou, K.; Paramonov, A.; Paredes Hernandez, D.; Parker, A. J.; Parker, M. A.; Parker, K. A.; Parodi, F.; Parsons, J. A.; Parzefall, U.; Pascuzzi, V. R.; Pasner, J. M.; Pasqualucci, E.; Passaggio, S.; Pastore, Fr.; Pataraia, S.; Pater, J. R.; Pauly, T.; Pearson, B.; Pedraza Lopez, S.; Pedro, R.; Peleganchuk, S. V.; Penc, O.; Peng, C.; Peng, H.; Penwell, J.; Peralva, B. S.; Perego, M. M.; Perepelitsa, D. V.; Peri, F.; Perini, L.; Pernegger, H.; Perrella, S.; Peschke, R.; Peshekhonov, V. D.; Peters, K.; Peters, R. F. Y.; Petersen, B. A.; Petersen, T. C.; Petit, E.; Petridis, A.; Petridou, C.; Petroff, P.; Petrolo, E.; Petrov, M.; Petrucci, F.; Pettersson, N. E.; Peyaud, A.; Pezoa, R.; Phillips, F. H.; Phillips, P. W.; Piacquadio, G.; Pianori, E.; Picazio, A.; Pickering, M. A.; Piegaia, R.; Pilcher, J. E.; Pilkington, A. D.; Pinamonti, M.; Pinfold, J. L.; Pirumov, H.; Pitt, M.; Plazak, L.; Pleier, M.-A.; Pleskot, V.; Plotnikova, E.; Pluth, D.; Podberezko, P.; Poettgen, R.; Poggi, R.; Poggioli, L.; Pogrebnyak, I.; Pohl, D.; Pokharel, I.; Polesello, G.; Poley, A.; Policicchio, A.; Polifka, R.; Polini, A.; Pollard, C. S.; Polychronakos, V.; Pommès, K.; Ponomarenko, D.; Pontecorvo, L.; Popeneciu, G. A.; Portillo Quintero, D. M.; Pospisil, S.; Potamianos, K.; Potrap, I. N.; Potter, C. J.; Potti, H.; Poulsen, T.; Poveda, J.; Pozo Astigarraga, M. E.; Pralavorio, P.; Pranko, A.; Prell, S.; Price, D.; Primavera, M.; Prince, S.; Proklova, N.; Prokofiev, K.; Prokoshin, F.; Protopopescu, S.; Proudfoot, J.; Przybycien, M.; Puri, A.; Puzo, P.; Qian, J.; Qin, G.; Qin, Y.; Quadt, A.; Queitsch-Maitland, M.; Quilty, D.; Raddum, S.; Radeka, V.; Radescu, V.; Radhakrishnan, S. K.; Radloff, P.; Rados, P.; Ragusa, F.; Rahal, G.; Raine, J. A.; Rajagopalan, S.; Rangel-Smith, C.; Rashid, T.; Raspopov, S.; Ratti, M. G.; Rauch, D. M.; Rauscher, F.; Rave, S.; Ravinovich, I.; Rawling, J. H.; Raymond, M.; Read, A. L.; Readioff, N. P.; Reale, M.; Rebuzzi, D. M.; Redelbach, A.; Redlinger, G.; Reece, R.; Reed, R. G.; Reeves, K.; Rehnisch, L.; Reichert, J.; Reiss, A.; Rembser, C.; Ren, H.; Rescigno, M.; Resconi, S.; Resseguie, E. D.; Rettie, S.; Reynolds, E.; Rezanova, O. L.; Reznicek, P.; Rezvani, R.; Richter, R.; Richter, S.; Richter-Was, E.; Ricken, O.; Ridel, M.; Rieck, P.; Riegel, C. J.; Rieger, J.; Rifki, O.; Rijssenbeek, M.; Rimoldi, A.; Rimoldi, M.; Rinaldi, L.; Ripellino, G.; Ristić, B.; Ritsch, E.; Riu, I.; Rizatdinova, F.; Rizvi, E.; Rizzi, C.; Roberts, R. T.; Robertson, S. H.; Robichaud-Veronneau, A.; Robinson, D.; Robinson, J. E. M.; Robson, A.; Rocco, E.; Roda, C.; Rodina, Y.; Rodriguez Bosca, S.; Rodriguez Perez, A.; Rodriguez Rodriguez, D.; Roe, S.; Rogan, C. S.; Røhne, O.; Roloff, J.; Romaniouk, A.; Romano, M.; Romano Saez, S. M.; Romero Adam, E.; Rompotis, N.; Ronzani, M.; Roos, L.; Rosati, S.; Rosbach, K.; Rose, P.; Rosien, N.-A.; Rossi, E.; Rossi, L. P.; Rosten, J. H. N.; Rosten, R.; Rotaru, M.; Rothberg, J.; Rousseau, D.; Rozanov, A.; Rozen, Y.; Ruan, X.; Rubbo, F.; Ruettinger, E. M.; Rühr, F.; Ruiz-Martinez, A.; Rurikova, Z.; Rusakovich, N. A.; Russell, H. L.; Rutherfoord, J. P.; Ruthmann, N.; Ryabov, Y. F.; Rybar, M.; Rybkin, G.; Ryu, S.; Ryzhov, A.; Rzehorz, G. F.; Saavedra, A. F.; Sabato, G.; Sacerdoti, S.; Sadrozinski, H. F.-W.; Sadykov, R.; Safai Tehrani, F.; Saha, P.; Sahinsoy, M.; Saimpert, M.; Saito, M.; Saito, T.; Sakamoto, H.; Sakurai, Y.; Salamanna, G.; Salazar Loyola, J. E.; Salek, D.; Sales de Bruin, P. H.; Salihagic, D.; Salnikov, A.; Salt, J.; Salvatore, D.; Salvatore, F.; Salvucci, A.; Salzburger, A.; Sammel, D.; Sampsonidis, D.; Sampsonidou, D.; Sánchez, J.; Sanchez Martinez, V.; Sanchez Pineda, A.; Sandaker, H.; Sandbach, R. L.; Sander, C. O.; Sandhoff, M.; Sandoval, C.; Sankey, D. P. C.; Sannino, M.; Sano, Y.; Sansoni, A.; Santoni, C.; Santos, H.; Santoyo Castillo, I.; Sapronov, A.; Saraiva, J. G.; Sarrazin, B.; Sasaki, O.; Sato, K.; Sauvan, E.; Savage, G.; Savard, P.; Savic, N.; Sawyer, C.; Sawyer, L.; Saxon, J.; Sbarra, C.; Sbrizzi, A.; Scanlon, T.; Scannicchio, D. A.; Schaarschmidt, J.; Schacht, P.; Schachtner, B. M.; Schaefer, D.; Schaefer, L.; Schaefer, R.; Schaeffer, J.; Schaepe, S.; Schaetzel, S.; Schäfer, U.; Schaffer, A. C.; Schaile, D.; Schamberger, R. D.; Schegelsky, V. A.; Scheirich, D.; Schernau, M.; Schiavi, C.; Schier, S.; Schildgen, L. K.; Schillo, C.; Schioppa, M.; Schlenker, S.; Schmidt-Sommerfeld, K. R.; Schmieden, K.; Schmitt, C.; Schmitt, S.; Schmitz, S.; Schnoor, U.; Schoeffel, L.; Schoening, A.; Schoenrock, B. D.; Schopf, E.; Schott, M.; Schouwenberg, J. F. P.; Schovancova, J.; Schramm, S.; Schuh, N.; Schulte, A.; Schultens, M. J.; Schultz-Coulon, H.-C.; Schulz, H.; Schumacher, M.; Schumm, B. A.; Schune, Ph.; Schwartzman, A.; Schwarz, T. A.; Schweiger, H.; Schwemling, Ph.; Schwienhorst, R.; Schwindling, J.; Sciandra, A.; Sciolla, G.; Scornajenghi, M.; Scuri, F.; Scutti, F.; Searcy, J.; Seema, P.; Seidel, S. C.; Seiden, A.; Seixas, J. M.; Sekhniaidze, G.; Sekhon, K.; Sekula, S. J.; Semprini-Cesari, N.; Senkin, S.; Serfon, C.; Serin, L.; Serkin, L.; Sessa, M.; Seuster, R.; Severini, H.; Sfiligoj, T.; Sforza, F.; Sfyrla, A.; Shabalina, E.; Shaikh, N. W.; Shan, L. Y.; Shang, R.; Shank, J. T.; Shapiro, M.; Shatalov, P. B.; Shaw, K.; Shaw, S. M.; Shcherbakova, A.; Shehu, C. Y.; Shen, Y.; Sherafati, N.; Sherwood, P.; Shi, L.; Shimizu, S.; Shimmin, C. O.; Shimojima, M.; Shipsey, I. P. J.; Shirabe, S.; Shiyakova, M.; Shlomi, J.; Shmeleva, A.; Shoaleh Saadi, D.; Shochet, M. J.; Shojaii, S.; Shope, D. R.; Shrestha, S.; Shulga, E.; Shupe, M. A.; Sicho, P.; Sickles, A. M.; Sidebo, P. E.; Sideras Haddad, E.; Sidiropoulou, O.; Sidoti, A.; Siegert, F.; Sijacki, Dj.; Silva, J.; Silverstein, S. B.; Simak, V.; Simic, L.; Simion, S.; Simioni, E.; Simmons, B.; Simon, M.; Sinervo, P.; Sinev, N. B.; Sioli, M.; Siragusa, G.; Siral, I.; Sivoklokov, S. Yu.; Sjölin, J.; Skinner, M. B.; Skubic, P.; Slater, M.; Slavicek, T.; Slawinska, M.; Sliwa, K.; Slovak, R.; Smakhtin, V.; Smart, B. H.; Smiesko, J.; Smirnov, N.; Smirnov, S. Yu.; Smirnov, Y.; Smirnova, L. N.; Smirnova, O.; Smith, J. W.; Smith, M. N. K.; Smith, R. W.; Smizanska, M.; Smolek, K.; Snesarev, A. A.; Snyder, I. M.; Snyder, S.; Sobie, R.; Socher, F.; Soffer, A.; Søgaard, A.; Soh, D. A.; Sokhrannyi, G.; Solans Sanchez, C. A.; Solar, M.; Soldatov, E. Yu.; Soldevila, U.; Solodkov, A. A.; Soloshenko, A.; Solovyanov, O. V.; Solovyev, V.; Sommer, P.; Son, H.; Sopczak, A.; Sosa, D.; Sotiropoulou, C. L.; Sottocornola, S.; Soualah, R.; Soukharev, A. M.; South, D.; Sowden, B. C.; Spagnolo, S.; Spalla, M.; Spangenberg, M.; Spanò, F.; Sperlich, D.; Spettel, F.; Spieker, T. M.; Spighi, R.; Spigo, G.; Spiller, L. A.; Spousta, M.; St. Denis, R. D.; Stabile, A.; Stamen, R.; Stamm, S.; Stanecka, E.; Stanek, R. W.; Stanescu, C.; Stanitzki, M. M.; Stapf, B. S.; Stapnes, S.; Starchenko, E. A.; Stark, G. H.; Stark, J.; Stark, S. H.; Staroba, P.; Starovoitov, P.; Stärz, S.; Staszewski, R.; Stegler, M.; Steinberg, P.; Stelzer, B.; Stelzer, H. J.; Stelzer-Chilton, O.; Stenzel, H.; Stevenson, T. J.; Stewart, G. A.; Stockton, M. C.; Stoebe, M.; Stoicea, G.; Stolte, P.; Stonjek, S.; Stradling, A. R.; Straessner, A.; Stramaglia, M. E.; Strandberg, J.; Strandberg, S.; Strauss, M.; Strizenec, P.; Ströhmer, R.; Strom, D. M.; Stroynowski, R.; Strubig, A.; Stucci, S. A.; Stugu, B.; Styles, N. A.; Su, D.; Su, J.; Suchek, S.; Sugaya, Y.; Suk, M.; Sulin, V. V.; Sultan, Dms; Sultansoy, S.; Sumida, T.; Sun, S.; Sun, X.; Suruliz, K.; Suster, C. J. E.; Sutton, M. R.; Suzuki, S.; Svatos, M.; Swiatlowski, M.; Swift, S. P.; Sykora, I.; Sykora, T.; Ta, D.; Tackmann, K.; Taenzer, J.; Taffard, A.; Tafirout, R.; Tahirovic, E.; Taiblum, N.; Takai, H.; Takashima, R.; Takasugi, E. H.; Takeda, K.; Takeshita, T.; Takubo, Y.; Talby, M.; Talyshev, A. A.; Tanaka, J.; Tanaka, M.; Tanaka, R.; Tanaka, S.; Tanioka, R.; Tannenwald, B. B.; Tapia Araya, S.; Tapprogge, S.; Tarem, S.; Tartarelli, G. F.; Tas, P.; Tasevsky, M.; Tashiro, T.; Tassi, E.; Tavares Delgado, A.; Tayalati, Y.; Taylor, A. C.; Taylor, A. J.; Taylor, G. N.; Taylor, P. T. E.; Taylor, W.; Teixeira-Dias, P.; Temple, D.; Ten Kate, H.; Teng, P. K.; Teoh, J. J.; Tepel, F.; Terada, S.; Terashi, K.; Terron, J.; Terzo, S.; Testa, M.; Teuscher, R. J.; Thais, S. J.; Theveneaux-Pelzer, T.; Thiele, F.; Thomas, J. P.; Thomas-Wilsker, J.; Thompson, P. D.; Thompson, A. S.; Thomsen, L. A.; Thomson, E.; Tian, Y.; Tibbetts, M. J.; Ticse Torres, R. E.; Tikhomirov, V. O.; Tikhonov, Yu. A.; Timoshenko, S.; Tipton, P.; Tisserant, S.; Todome, K.; Todorova-Nova, S.; Todt, S.; Tojo, J.; Tokár, S.; Tokushuku, K.; Tolley, E.; Tomlinson, L.; Tomoto, M.; Tompkins, L.; Toms, K.; Tong, B.; Tornambe, P.; Torrence, E.; Torres, H.; Torró Pastor, E.; Toth, J.; Touchard, F.; Tovey, D. R.; Treado, C. J.; Trefzger, T.; Tresoldi, F.; Tricoli, A.; Trigger, I. M.; Trincaz-Duvoid, S.; Tripiana, M. F.; Trischuk, W.; Trocmé, B.; Trofymov, A.; Troncon, C.; Trottier-McDonald, M.; Trovatelli, M.; Truong, L.; Trzebinski, M.; Trzupek, A.; Tsang, K. W.; Tseng, J. C.-L.; Tsiareshka, P. V.; Tsirintanis, N.; Tsiskaridze, S.; Tsiskaridze, V.; Tskhadadze, E. G.; Tsukerman, I. I.; Tsulaia, V.; Tsuno, S.; Tsybychev, D.; Tu, Y.; Tudorache, A.; Tudorache, V.; Tulbure, T. T.; Tuna, A. N.; Turchikhin, S.; Turgeman, D.; Turk Cakir, I.; Turra, R.; Tuts, P. M.; Ucchielli, G.; Ueda, I.; Ughetto, M.; Ukegawa, F.; Unal, G.; Undrus, A.; Unel, G.; Ungaro, F. C.; Unno, Y.; Uno, K.; Unverdorben, C.; Urban, J.; Urquijo, P.; Urrejola, P.; Usai, G.; Usui, J.; Vacavant, L.; Vacek, V.; Vachon, B.; Vadla, K. O. H.; Vaidya, A.; Valderanis, C.; Valdes Santurio, E.; Valente, M.; Valentinetti, S.; Valero, A.; Valéry, L.; Valkar, S.; Vallier, A.; Valls Ferrer, J. A.; van den Wollenberg, W.; van der Graaf, H.; van Gemmeren, P.; van Nieuwkoop, J.; van Vulpen, I.; van Woerden, M. C.; Vanadia, M.; Vandelli, W.; Vaniachine, A.; Vankov, P.; Vardanyan, G.; Vari, R.; Varnes, E. W.; Varni, C.; Varol, T.; Varouchas, D.; Vartapetian, A.; Varvell, K. E.; Vasquez, J. G.; Vasquez, G. A.; Vazeille, F.; Vazquez Furelos, D.; Vazquez Schroeder, T.; Veatch, J.; Veeraraghavan, V.; Veloce, L. M.; Veloso, F.; Veneziano, S.; Ventura, A.; Venturi, M.; Venturi, N.; Venturini, A.; Vercesi, V.; Verducci, M.; Verkerke, W.; Vermeulen, A. T.; Vermeulen, J. C.; Vetterli, M. C.; Viaux Maira, N.; Viazlo, O.; Vichou, I.; Vickey, T.; Vickey Boeriu, O. E.; Viehhauser, G. H. A.; Viel, S.; Vigani, L.; Villa, M.; Villaplana Perez, M.; Vilucchi, E.; Vincter, M. G.; Vinogradov, V. B.; Vishwakarma, A.; Vittori, C.; Vivarelli, I.; Vlachos, S.; Vogel, M.; Vokac, P.; Volpi, G.; von der Schmitt, H.; von Toerne, E.; Vorobel, V.; Vorobev, K.; Vos, M.; Voss, R.; Vossebeld, J. H.; Vranjes, N.; Vranjes Milosavljevic, M.; Vrba, V.; Vreeswijk, M.; Vuillermet, R.; Vukotic, I.; Wagner, P.; Wagner, W.; Wagner-Kuhr, J.; Wahlberg, H.; Wahrmund, S.; Walder, J.; Walker, R.; Walkowiak, W.; Wallangen, V.; Wang, C.; Wang, C.; Wang, F.; Wang, H.; Wang, H.; Wang, J.; Wang, J.; Wang, Q.; Wang, R.-J.; Wang, R.; Wang, S. M.; Wang, T.; Wang, W.; Wang, W.; Wang, Z.; Wanotayaroj, C.; Warburton, A.; Ward, C. P.; Wardrope, D. R.; Washbrook, A.; Watkins, P. M.; Watson, A. T.; Watson, M. F.; Watts, G.; Watts, S.; Waugh, B. M.; Webb, A. F.; Webb, S.; Weber, M. S.; Weber, S. M.; Weber, S. W.; Weber, S. A.; Webster, J. S.; Weidberg, A. R.; Weinert, B.; Weingarten, J.; Weirich, M.; Weiser, C.; Weits, H.; Wells, P. S.; Wenaus, T.; Wengler, T.; Wenig, S.; Wermes, N.; Werner, M. D.; Werner, P.; Wessels, M.; Weston, T. D.; Whalen, K.; Whallon, N. L.; Wharton, A. M.; White, A. S.; White, A.; White, M. J.; White, R.; Whiteson, D.; Whitmore, B. W.; Wickens, F. J.; Wiedenmann, W.; Wielers, M.; Wiglesworth, C.; Wiik-Fuchs, L. A. M.; Wildauer, A.; Wilk, F.; Wilkens, H. G.; Williams, H. H.; Williams, S.; Willis, C.; Willocq, S.; Wilson, J. A.; Wingerter-Seez, I.; Winkels, E.; Winklmeier, F.; Winston, O. J.; Winter, B. T.; Wittgen, M.; Wobisch, M.; Wolf, A.; Wolf, T. M. H.; Wolff, R.; Wolter, M. W.; Wolters, H.; Wong, V. W. S.; Woods, N. L.; Worm, S. D.; Wosiek, B. K.; Wotschack, J.; Wozniak, K. W.; Wu, M.; Wu, S. L.; Wu, X.; Wu, Y.; Wyatt, T. R.; Wynne, B. M.; Xella, S.; Xi, Z.; Xia, L.; Xu, D.; Xu, L.; Xu, T.; Xu, W.; Yabsley, B.; Yacoob, S.; Yamaguchi, D.; Yamaguchi, Y.; Yamamoto, A.; Yamamoto, S.; Yamanaka, T.; Yamane, F.; Yamatani, M.; Yamazaki, T.; Yamazaki, Y.; Yan, Z.; Yang, H.; Yang, H.; Yang, Y.; Yang, Z.; Yao, W.-M.; Yap, Y. C.; Yasu, Y.; Yatsenko, E.; Yau Wong, K. H.; Ye, J.; Ye, S.; Yeletskikh, I.; Yigitbasi, E.; Yildirim, E.; Yorita, K.; Yoshihara, K.; Young, C.; Young, C. J. S.; Yu, J.; Yu, J.; Yuen, S. P. Y.; Yusuff, I.; Zabinski, B.; Zacharis, G.; Zaidan, R.; Zaitsev, A. M.; Zakharchuk, N.; Zalieckas, J.; Zaman, A.; Zambito, S.; Zanzi, D.; Zeitnitz, C.; Zemaityte, G.; Zemla, A.; Zeng, J. C.; Zeng, Q.; Zenin, O.; Ženiš, T.; Zerwas, D.; Zhang, D.; Zhang, D.; Zhang, F.; Zhang, G.; Zhang, H.; Zhang, J.; Zhang, L.; Zhang, L.; Zhang, M.; Zhang, P.; Zhang, R.; Zhang, R.; Zhang, X.; Zhang, Y.; Zhang, Z.; Zhao, X.; Zhao, Y.; Zhao, Z.; Zhemchugov, A.; Zhou, B.; Zhou, C.; Zhou, L.; Zhou, M.; Zhou, M.; Zhou, N.; Zhou, Y.; Zhu, C. G.; Zhu, H.; Zhu, J.; Zhu, Y.; Zhuang, X.; Zhukov, K.; Zibell, A.; Zieminska, D.; Zimine, N. I.; Zimmermann, C.; Zimmermann, S.; Zinonos, Z.; Zinser, M.; Ziolkowski, M.; Živković, L.; Zobernig, G.; Zoccoli, A.; Zou, R.; Zur Nedden, M.; Zwalinski, L.; Atlas Collaboration

    2018-01-01

    A search for an invisibly decaying Higgs boson or dark matter candidates produced in association with a leptonically decaying Z boson in proton-proton collisions at √{ s } = 13 TeV is presented. This search uses 36.1 fb-1 of data collected by the ATLAS experiment at the Large Hadron Collider. No significant deviation from the expectation of the Standard Model backgrounds is observed. Assuming the Standard Model ZH production cross-section, an observed (expected) upper limit of 67% (39%) at the 95% confidence level is set on the branching ratio of invisible decays of the Higgs boson with mass mH = 125 GeV. The corresponding limits on the production cross-section of the ZH process with the invisible Higgs boson decays are also presented. Furthermore, exclusion limits on the dark matter candidate and mediator masses are reported in the framework of simplified dark matter models.

  17. Methane as a biomarker in the search for extraterrestrial life: Lessons learned from Mars analog hypersaline environments

    Science.gov (United States)

    Bebout, B.; Tazaz, A.; Kelley, C. A.; Poole, J. A.; Davila, A.; Chanton, J.

    2010-12-01

    Methane released from discrete regions on Mars, together with previous reports of methane determined with ground-based telescopes, has revived the possibility of past or even extant life near the surface on Mars, since 90% of the methane on Earth has a biological origin. This intriguing possibility is supported by the abundant evidence of large bodies of liquid water, and therefore of conditions conducive to the origin of life, early in the planet's history. The detection and analysis of methane is at the core of NASA’s strategies to search for life in the solar system, and on extrasolar planets. Because methane is also produced abiotically, it is important to generate criteria to unambiguously assess biogenicity. The stable carbon and hydrogen isotopic signature of methane, as well as its ratio to other low molecular weight hydrocarbons (the methane/(ethane + propane) ratio: C1/(C2 + C3)), has been suggested to be diagnostic for biogenic methane. We report measurements of the concentrations and stable isotopic signature of methane from hypersaline environments. We focus on hypersaline environments because spectrometers orbiting Mars have detected widespread chloride bearing deposits resembling salt flats. Other evaporitic minerals, e.g., sulfates, are also abundant in several regions, including those studied by the Mars Exploration Rovers. The presence of evaporitic minerals, together with the known evolution of the Martian climate, from warmer and wetter to cold and hyper-arid, suggest that evaporitic and hypersaline environments were common in the past. Hypersaline environments examined to date include salt ponds located in Baja California, the San Francisco Bay, and the Atacama Desert. Methane was found in gas produced both in the sediments, and in gypsum- and halite-hosted (endolithic) microbial communities. Maximum methane concentrations were as high as 40% by volume. The methane carbon isotopic (δ13C) composition showed a wide range of values, from about

  18. Identification of a novel biomarker candidate, a 4.8-kDa peptide fragment from a neurosecretory protein VGF precursor, by proteomic analysis of cerebrospinal fluid from children with acute encephalopathy using SELDI-TOF-MS

    Directory of Open Access Journals (Sweden)

    Fujino Osamu

    2011-08-01

    Full Text Available Abstract Background Acute encephalopathy includes rapid deterioration and has a poor prognosis. Early intervention is essential to prevent progression of the disease and subsequent neurologic complications. However, in the acute period, true encephalopathy cannot easily be differentiated from febrile seizures, especially febrile seizures of the complex type. Thus, an early diagnostic marker has been sought in order to enable early intervention. The purpose of this study was to identify a novel marker candidate protein differentially expressed in the cerebrospinal fluid (CSF of children with encephalopathy using proteomic analysis. Methods For detection of biomarkers, CSF samples were obtained from 13 children with acute encephalopathy and 42 children with febrile seizure. Mass spectral data were generated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS technology, which is currently applied in many fields of biological and medical sciences. Diagnosis was made by at least two pediatric neurologists based on the clinical findings and routine examinations. All specimens were collected for diagnostic tests and the remaining portion of the specimens were used for the SELDI-TOF MS investigations. Results In experiment 1, CSF from patients with febrile seizures (n = 28, patients with encephalopathy (n = 8 (including influenza encephalopathy (n = 3, encephalopathy due to rotavirus (n = 1, human herpes virus 6 (n = 1 were used for the SELDI analysis. In experiment 2, SELDI analysis was performed on CSF from a second set of febrile seizure patients (n = 14 and encephalopathy patients (n = 5. We found that the peak with an m/z of 4810 contributed the most to the separation of the two groups. After purification and identification of the 4.8-kDa protein, a 4.8-kDa proteolytic peptide fragment from the neurosecretory protein VGF precursor (VGF4.8 was identified as a novel biomarker for encephalopathy. Conclusions

  19. Novel Plasmodium falciparum malaria vaccines: evidence-based searching for variant surface antigens as candidates for vaccination against pregnancy-associated malaria

    DEFF Research Database (Denmark)

    Staalsoe, Trine; Jensen, Anja T R; Theander, Thor G

    2002-01-01

    Malaria vaccine development has traditionally concentrated on careful molecular, biochemical, and immunological characterisation of candidate antigens. In contrast, evidence of the importance of identified antigens in immunity to human infection and disease has generally been limited to statistic......Malaria vaccine development has traditionally concentrated on careful molecular, biochemical, and immunological characterisation of candidate antigens. In contrast, evidence of the importance of identified antigens in immunity to human infection and disease has generally been limited...... to statistically significant co-variation with protection rather than on demonstration of causal relationships. We have studied the relationship between variant surface antigen-specific antibodies and clinical protection from Plasmodium falciparum malaria in general, and from pregnancy-associated malaria (PAM......) in particular, to provide robust evidence of a causal link between the two in order to allow efficient and evidence-based identification of candidate antigens for malaria vaccine development....

  20. NEAR-INFRARED SURVEY OF THE GOODS-NORTH FIELD: SEARCH FOR LUMINOUS GALAXY CANDIDATES AT z {approx}> 6.5 {sup ,}

    Energy Technology Data Exchange (ETDEWEB)

    Hathi, Nimish P. [Observatories of the Carnegie Institution for Science, Pasadena, CA 91101 (United States); Mobasher, Bahram [Department of Physics and Astronomy, University of California, Riverside, CA 92521 (United States); Capak, Peter [Department of Astronomy, 249-17 Caltech, 1201 East California Boulevard, Pasadena, CA 91125 (United States); Wang, Wei-Hao [Institute of Astronomy and Astrophysics, Academia Sinica, P.O. Box 23-141, Taipei 10617, Taiwan (China); Ferguson, Henry C., E-mail: nhathi@obs.carnegiescience.edu [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States)

    2012-09-20

    We present near-infrared (NIR; J and K{sub s}) survey of the Great Observatories Origins Deep Survey-North (GOODS-N) field. The publicly available imaging data were obtained using the MOIRCS instrument on the 8.2 m Subaru and the WIRCam instrument on the 3.6 m Canada-France-Hawaii Telescope (CFHT). These observations fulfill a serious wavelength gap in the GOODS-N data, i.e., lack of deep NIR observations. We combine the Subaru/MOIRCS and CFHT/WIRCam archival data to generate deep J- and K{sub s}-band images, covering the full GOODS-N field ({approx}169 arcmin{sup 2}) to an AB magnitude limit of {approx}25 mag (3{sigma}). We applied z{sub 850}-band dropout color selection criteria, using the NIR data generated here. We have identified two possible Lyman break galaxy (LBG) candidates at z {approx}> 6.5 with J {approx}< 24.5. The first candidate is a likely LBG at z {approx_equal} 6.5 based on a weak spectral feature tentatively identified as Ly{alpha} line in the deep Keck/DEIMOS spectrum, while the second candidate is a possible LBG at z {approx_equal} 7 based on its photometric redshift. These z{sub 850}-dropout objects, if confirmed, are among the brightest such candidates found so far. At z {approx}> 6.5, their star formation rate is estimated as 100-200 M{sub Sun} yr{sup -1}. If they continue to form stars at this rate, they assemble a stellar mass of {approx}5 Multiplication-Sign 10{sup 10} M{sub Sun} after about 400 million years, becoming the progenitors of massive galaxies observed at z {approx_equal} 5. We study the implication of the z{sub 850}-band dropout candidates discovered here, in constraining the bright end of the luminosity function and understanding the nature of high-redshift galaxies.

  1. Prognostic Biomarkers Used for Localised Prostate Cancer Management: A Systematic Review.

    Science.gov (United States)

    Lamy, Pierre-Jean; Allory, Yves; Gauchez, Anne-Sophie; Asselain, Bernard; Beuzeboc, Philippe; de Cremoux, Patricia; Fontugne, Jacqueline; Georges, Agnès; Hennequin, Christophe; Lehmann-Che, Jacqueline; Massard, Christophe; Millet, Ingrid; Murez, Thibaut; Schlageter, Marie-Hélène; Rouvière, Olivier; Kassab-Chahmi, Diana; Rozet, François; Descotes, Jean-Luc; Rébillard, Xavier

    2017-03-07

    Prostate cancer stratification is based on tumour size, pretreatment PSA level, and Gleason score, but it remains imperfect. Current research focuses on the discovery and validation of novel prognostic biomarkers to improve the identification of patients at risk of aggressive cancer or of tumour relapse. This systematic review by the Intergroupe Coopérateur Francophone de Recherche en Onco-urologie (ICFuro) analysed new evidence on the analytical validity and clinical validity and utility of six prognostic biomarkers (PHI, 4Kscore, MiPS, GPS, Prolaris, Decipher). All available data for the six biomarkers published between January 2002 and April 2015 were systematically searched and reviewed. The main endpoints were aggressive prostate cancer prediction, additional value compared to classical prognostic parameters, and clinical benefit for patients with localised prostate cancer. The preanalytical and analytical validations were heterogeneous for all tests and often not adequate for the molecular signatures. Each biomarker was studied for specific indications (candidates for a first or second biopsy, and potential candidates for active surveillance, radical prostatectomy, or adjuvant treatment) for which the level of evidence (LOE) was variable. PHI and 4Kscore were the biomarkers with the highest LOE for discriminating aggressive and indolent tumours in different indications. Blood biomarkers (PHI and 4Kscore) have the highest LOE for the prediction of more aggressive prostate cancer and could help clinicians to manage patients with localised prostate cancer. The other biomarkers show a potential prognostic value; however, they should be evaluated in additional studies to confirm their clinical validity. We reviewed studies assessing the value of six prognostic biomarkers for prostate cancer. On the basis of the available evidence, some biomarkers could help in discriminating between aggressive and non-aggressive tumours with an additional value compared to the

  2. Biomarkers in Airway Diseases

    Directory of Open Access Journals (Sweden)

    Janice M Leung

    2013-01-01

    Full Text Available The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

  3. The role of double dissociation studies in the search for candidate endophenotypes for the comorbidity of attention deficit hyperactivity disorder and reading disability.

    NARCIS (Netherlands)

    de Jong, C.G.W.; Oosterlaan, J.; Sergeant, J.A.

    2006-01-01

    The neuropsychological underpinnings of Attention Deficit Hyperactivity Disorder (ADHD) and Reading Disability (RD) and their comorbidity may be studied usefully with the double dissociation design. The results of studies using the double dissociation method may be linked to the search for an

  4. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    International Nuclear Information System (INIS)

    Tamura, Akitoshi; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-01-01

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

  5. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Akitoshi, E-mail: akitoshi-tamura@ds-pharma.co.jp; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased

  6. NEAR-INFRARED SURVEY OF THE GOODS-NORTH FIELD: SEARCH FOR LUMINOUS GALAXY CANDIDATES AT z ∼> 6.5 ,

    International Nuclear Information System (INIS)

    Hathi, Nimish P.; Mobasher, Bahram; Capak, Peter; Wang, Wei-Hao; Ferguson, Henry C.

    2012-01-01

    We present near-infrared (NIR; J and K s ) survey of the Great Observatories Origins Deep Survey-North (GOODS-N) field. The publicly available imaging data were obtained using the MOIRCS instrument on the 8.2 m Subaru and the WIRCam instrument on the 3.6 m Canada-France-Hawaii Telescope (CFHT). These observations fulfill a serious wavelength gap in the GOODS-N data, i.e., lack of deep NIR observations. We combine the Subaru/MOIRCS and CFHT/WIRCam archival data to generate deep J- and K s -band images, covering the full GOODS-N field (∼169 arcmin 2 ) to an AB magnitude limit of ∼25 mag (3σ). We applied z 850 -band dropout color selection criteria, using the NIR data generated here. We have identified two possible Lyman break galaxy (LBG) candidates at z ∼> 6.5 with J ∼ 850 -dropout objects, if confirmed, are among the brightest such candidates found so far. At z ∼> 6.5, their star formation rate is estimated as 100-200 M ☉ yr –1 . If they continue to form stars at this rate, they assemble a stellar mass of ∼5 × 10 10 M ☉ after about 400 million years, becoming the progenitors of massive galaxies observed at z ≅ 5. We study the implication of the z 850 -band dropout candidates discovered here, in constraining the bright end of the luminosity function and understanding the nature of high-redshift galaxies.

  7. Biomarkers of Pediatric Brain Tumors

    Directory of Open Access Journals (Sweden)

    Mark D Russell

    2013-03-01

    Full Text Available Background and Need for Novel Biomarkers: Brain tumors are the leading cause of death by solid tumors in children. Although improvements have been made in their radiological detection and treatment, our capacity to promptly diagnose pediatric brain tumors in their early stages remains limited. This contrasts several other cancers where serum biomarkers such as CA 19-9 and CA 125 facilitate early diagnosis and treatment. Aim: The aim of this article is to review the latest literature and highlight biomarkers which may be of clinical use in the common types of primary pediatric brain tumor. Methods: A PubMed search was performed to identify studies reporting biomarkers in the bodily fluids of pediatric patients with brain tumors. Details regarding the sample type (serum, cerebrospinal fluid or urine, biomarkers analyzed, methodology, tumor type and statistical significance were recorded. Results: A total of 12 manuscripts reporting 19 biomarkers in 367 patients vs. 397 controls were identified in the literature. Of the 19 biomarkers identified, 12 were isolated from cerebrospinal fluid, 2 from serum, 3 from urine, and 2 from multiple bodily fluids. All but one study reported statistically significant differences in biomarker expression between patient and control groups.Conclusions: This review identifies a panel of novel biomarkers for pediatric brain tumors. It provides a platform for the further studies necessary to validate these biomarkers and, in addition, highlights several techniques through which new biomarkers can be discovered.

  8. Probiotic and technological properties of Lactobacillus spp. strains from the human stomach in the search for potential candidates against gastric microbial dysbiosis.

    Science.gov (United States)

    Delgado, Susana; Leite, Analy M O; Ruas-Madiedo, Patricia; Mayo, Baltasar

    2014-01-01

    This work characterizes a set of lactobacilli strains isolated from the stomach of healthy humans that might serve as probiotic cultures. Ten different strains were recognized by rep-PCR and PFGE fingerprinting among 19 isolates from gastric biopsies and stomach juice samples. These strains belonged to five species, Lactobacillus gasseri (3), Lactobacillus reuteri (2), Lactobacillus vaginalis (2), Lactobacillus fermentum (2) and Lactobacillus casei (1). All ten strains were subjected to a series of in vitro tests to assess their functional and technological properties, including acid resistance, bile tolerance, adhesion to epithelial gastric cells, production of antimicrobial compounds, inhibition of Helicobacter pylori, antioxidative activity, antibiotic resistance, carbohydrate fermentation, glycosidic activities, and ability to grow in milk. As expected, given their origin, all strains showed good resistance to low pH (3.0), with small reductions in counts after 90 min exposition to this pH. Species- and strain-specific differences were detected in terms of the production of antimicrobials, antagonistic effects toward H. pylori, antioxidative activity and adhesion to gastric epithelial cells. None of the strains showed atypical resistance to a series of 16 antibiotics of clinical and veterinary importance. Two L. reuteri strains were deemed as the most appropriate candidates to be used as potential probiotics against microbial gastric disorders; these showed good survival under gastrointestinal conditions reproduced in vitro, along with strong anti-Helicobacter and antioxidative activities. The two L. reuteri strains further displayed appropriated technological traits for their inclusion as adjunct functional cultures in fermented dairy products.

  9. Multiple Sclerosis Cerebrospinal Fluid Biomarkers

    Directory of Open Access Journals (Sweden)

    Gavin Giovannoni

    2006-01-01

    Full Text Available Cerebrospinal fluid (CSF is the body fluid closest to the pathology of multiple sclerosis (MS. For many candidate biomarkers CSF is the only fluid that can be investigated. Several factors need to be standardized when sampling CSF for biomarker research: time/volume of CSF collection, sample processing/storage, and the temporal relationship of sampling to clinical or MRI markers of disease activity. Assays used for biomarker detection must be validated so as to optimize the power of the studies. A formal method for establishing whether or not a particular biomarker can be used as a surrogate end-point needs to be adopted. This process is similar to that used in clinical trials, where the reporting of studies has to be done in a standardized way with sufficient detail to permit a critical review of the study and to enable others to reproduce the study design. A commitment must be made to report negative studies so as to prevent publication bias. Pre-defined consensus criteria need to be developed for MS-related prognostic biomarkers. Currently no candidate biomarker is suitable as a surrogate end-point. Bulk biomarkers of the neurodegenerative process such as glial fibrillary acidic protein (GFAP and neurofilaments (NF have advantages over intermittent inflammatory markers.

  10. Probiotic and technological properties of Lactobacillus spp. strains from the human stomach in the search for potential candidates against gastric microbial dysbiosis

    Directory of Open Access Journals (Sweden)

    Susana eDelgado

    2015-01-01

    Full Text Available This work characterizes a set of lactobacilli strains isolated from the stomach of healthy humans that might serve as probiotic cultures. Ten different strains were recognized by rep-PCR and PFGE fingerprinting among 19 isolates from gastric biopsies and stomach juice samples. These strains belonged to five species, Lactobacillus gasseri (3, Lactobacillus reuteri (2, Lactobacillus vaginalis (2, Lactobacillus fermentum (2 and Lactobacillus casei (1. All ten strains were subjected to a series of in vitro tests to assess their functional and technological properties, including acid resistance, bile tolerance, adhesion to epithelial gastric cells, production of antimicrobial compounds, inhibition of Helicobacter pylori, antioxidative activity, antibiotic resistance, carbohydrate fermentation, glycosidic activities, and ability to grow in milk. As expected, given their origin, all strains showed good resistance to low pH (3.0, with small reductions in counts after 90 min exposition to this pH. Species- and strain-specific differences were detected in terms of the production of antimicrobials, antagonistic effects towards H. pylori, antioxidative activity and adhesion to gastric epithelial cells. None of the strains showed atypical resistance to a series of 16 antibiotics of clinical and veterinary importance. Two L. reuteri strains were deemed as the most appropriate candidates to be used as potential probiotics against microbial gastric disorders; these showed good survival under gastrointestinal conditions reproduced in vitro, along with strong anti-Helicobacter and antioxidative activities. The two L. reuteri strains further displayed appropriated technological traits for their inclusion as adjunct functional cultures in fermented dairy products.

  11. Search for the associated production of a Higgs boson and a top quark pair in multilepton (2 leptons, no hadronically-decaying $\\tau$ lepton candidates and 4 leptons) final states with the ATLAS detector.

    CERN Document Server

    Dumitriu, Ana Elena; The ATLAS collaboration

    2017-01-01

    The Yukawa coupling of the Higgs boson to the top quark is a key parameter of the Standard Model. It can be constrained using the associated production process $pp\\rightarrow t\\bar{t}H+X$. \\\\ A search for this process using final states with multiple leptons, primarily targeting the decays $H\\rightarrow WW^*$ and $H\\rightarrow \\tau \\tau$, has been performed using the data set recorded by the ATLAS detector in 2015 and 2016 at a center of mass energy $\\sqrt{s}$= 13 TeV. The analysis presented here includes two of the four final states distinguished by the number and flavor of leptons: two same-charge light leptons ( e or $\\mu$ ) and no hadronically-decaying $\\tau$ lepton candidates ($2l0\\tau_{had}$) and four light leptons ($4l$), the remaining channels not covered being two same-charge light leptons and one hadronically-decaying $\\tau$ lepton candidate ($2l1\\tau_{had}$) and three light leptons ($3l$). The different background sources are also presented for each channel considered. The latest best-fit value for...

  12. Development of a label-free LC-MS/MS strategy to approach the identification of candidate protein biomarkers of disease recurrence in prostate cancer patients in a clinical trial of combined hormone and radiation therapy.

    LENUS (Irish Health Repository)

    Morrissey, Brian

    2013-06-01

    Combined hormone and radiation therapy (CHRT) is one of the principle curative regimes for localised prostate cancer (PCa). Following treatment, many patients subsequently experience disease recurrence however; current diagnostics tests fail to predict the onset of disease recurrence. Biomarkers that address this issue would be of significant advantage.

  13. REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker.

    Directory of Open Access Journals (Sweden)

    Laura Lehtinen

    Full Text Available Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer.

  14. Mass Spectrometry-based Assay for High Throughput and High Sensitivity Biomarker Verification

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Xuejiang; Tang, Keqi

    2017-06-14

    Searching for disease specific biomarkers has become a major undertaking in the biomedical research field as the effective diagnosis, prognosis and treatment of many complex human diseases are largely determined by the availability and the quality of the biomarkers. A successful biomarker as an indicator to a specific biological or pathological process is usually selected from a large group of candidates by a strict verification and validation process. To be clinically useful, the validated biomarkers must be detectable and quantifiable by the selected testing techniques in their related tissues or body fluids. Due to its easy accessibility, protein biomarkers would ideally be identified in blood plasma or serum. However, most disease related protein biomarkers in blood exist at very low concentrations (<1ng/mL) and are “masked” by many none significant species at orders of magnitude higher concentrations. The extreme requirements of measurement sensitivity, dynamic range and specificity make the method development extremely challenging. The current clinical protein biomarker measurement primarily relies on antibody based immunoassays, such as ELISA. Although the technique is sensitive and highly specific, the development of high quality protein antibody is both expensive and time consuming. The limited capability of assay multiplexing also makes the measurement an extremely low throughput one rendering it impractical when hundreds to thousands potential biomarkers need to be quantitatively measured across multiple samples. Mass spectrometry (MS)-based assays have recently shown to be a viable alternative for high throughput and quantitative candidate protein biomarker verification. Among them, the triple quadrupole MS based assay is the most promising one. When it is coupled with liquid chromatography (LC) separation and electrospray ionization (ESI) source, a triple quadrupole mass spectrometer operating in a special selected reaction monitoring (SRM) mode

  15. Pharmacogenomic Biomarkers

    Directory of Open Access Journals (Sweden)

    Sandra C. Kirkwood

    2002-01-01

    Full Text Available Pharmacogenomic biomarkers hold great promise for the future of medicine and have been touted as a means to personalize prescriptions. Genetic biomarkers for disease susceptibility including both Mendelian and complex disease promise to result in improved understanding of the pathophysiology of disease, identification of new potential therapeutic targets, and improved molecular classification of disease. However essential to fulfilling the promise of individualized therapeutic intervention is the identification of drug activity biomarkers that stratify individuals based on likely response to a particular therapeutic, both positive response, efficacy, and negative response, development of side effect or toxicity. Prior to the widespread clinical application of a genetic biomarker multiple scientific studies must be completed to identify the genetic variants and delineate their functional significance in the pathophysiology of a carefully defined phenotype. The applicability of the genetic biomarker in the human population must then be verified through both retrospective studies utilizing stored or clinical trial samples, and through clinical trials prospectively stratifying patients based on the biomarker. The risk conferred by the polymorphism and the applicability in the general population must be clearly understood. Thus, the development and widespread application of a pharmacogenomic biomarker is an involved process and for most disease states we are just at the beginning of the journey towards individualized therapy and improved clinical outcome.

  16. Classification of genes and putative biomarker identification using distribution metrics on expression profiles.

    Directory of Open Access Journals (Sweden)

    Hung-Chung Huang

    Full Text Available BACKGROUND: Identification of genes with switch-like properties will facilitate discovery of regulatory mechanisms that underlie these properties, and will provide knowledge for the appropriate application of Boolean networks in gene regulatory models. As switch-like behavior is likely associated with tissue-specific expression, these gene products are expected to be plausible candidates as tissue-specific biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: In a systematic classification of genes and search for biomarkers, gene expression profiles (GEPs of more than 16,000 genes from 2,145 mouse array samples were analyzed. Four distribution metrics (mean, standard deviation, kurtosis and skewness were used to classify GEPs into four categories: predominantly-off, predominantly-on, graded (rheostatic, and switch-like genes. The arrays under study were also grouped and examined by tissue type. For example, arrays were categorized as 'brain group' and 'non-brain group'; the Kolmogorov-Smirnov distance and Pearson correlation coefficient were then used to compare GEPs between brain and non-brain for each gene. We were thus able to identify tissue-specific biomarker candidate genes. CONCLUSIONS/SIGNIFICANCE: The methodology employed here may be used to facilitate disease-specific biomarker discovery.

  17. Biomarkers of delirium as a clue to diagnosis and pathogenesis of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Wijnia, J W; Oudman, E

    2013-12-01

    Wernicke's encephalopathy (WE) and Korsakoff's syndrome are considered to be different stages of the same disorder due to thiamine deficiency, which is called Wernicke-Korsakoff syndrome (WKS). The earliest biochemical change is the decrease of α-ketoglutarate-dehydrogenase activity in astrocytes. According to autopsy-based series, mental status changes are present in 82% of WE cases. The objective of the present review is to identify possible underlying mechanisms relating the occurrence of delirium to WKS. Studies involving delirium in WKS, however, are rare. Therefore, first, a search was done for candidate biomarkers of delirium irrespective of the clinical setting. Secondly, the results were focused on identification of these biomarkers in reports on WKS. In various settings, 10 biochemical and/or genetic biomarkers showed strong associations with the occurrence of delirium. For WKS three of these candidate biomarkers were identified, namely brain tissue cell counts of CD68 positive cells as a marker of microglial activation, high cerebrospinal fluid lactate levels, and MHPG, a metabolite of norepinephrine. Based on current literature, markers of microglial activation may present an interesting patho-etiological relationship between thiamine deficiency and delirium in WKS. In WKS cases, changes in astroglia and microglial proliferation were reported. The possible loss-of-function mechanisms following thiamine deficiency in WKS are proposed to come from microglial activation, resulting in a delirium in the initial phase of WKS. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

  18. Proteomic Biomarkers for Spontaneous Preterm Birth

    DEFF Research Database (Denmark)

    Kacerovsky, Marian; Lenco, Juraj; Musilova, Ivana

    2014-01-01

    This review aimed to identify, synthesize, and analyze the findings of studies on proteomic biomarkers for spontaneous preterm birth (PTB). Three electronic databases (Medline, Embase, and Scopus) were searched for studies in any language reporting the use of proteomic biomarkers for PTB published...

  19. Time Course of Metabolic Capacities in Paralarvae of the Common Octopus, Octopus vulgaris, in the First Stages of Life. Searching Biomarkers of Nutritional Imbalance

    Directory of Open Access Journals (Sweden)

    Amalia E. Morales

    2017-06-01

    Full Text Available The culture of the common octopus (Octopus vulgaris is promising since the species has a relatively short lifecycle, rapid growth, and high food conversion ratios. However, recent attempts at successful paralarvae culture have failed due to slow growth and high mortality rates. Establishing an optimal nutritional regime for the paralarvae seems to be the impeding step in successful culture methods. Gaining a thorough knowledge of food regulation and assimilation is essential for paralarvae survival and longevity under culture conditions. The aim of this study, then, was to elucidate the characteristic metabolic organization of octopus paralarvae throughout an ontogenic period of 12 days post-hatching, as well as assess the effect of diet enrichment with live prey containing abundant marine phospholipids. Our results showed that throughout the ontogenic period studied, an increase in anaerobic metabolism took place largely due to an increased dependence of paralarvae on exogenous food. Our studies showed that this activity was supported by octopine dehydrogenase activity, with a less significant contribution of lactate dehydrogenase activity. Regarding aerobic metabolism, the use of amino acids was maintained for the duration of the experiment. Our studies also showed a significant increase in the rate of oxidation of fatty acids from 6 days after-hatching. A low, although sustained, capacity for de novo synthesis of glucose from amino acids and glycerol was also observed. Regardless of the composition of the food, glycerol kinase activity significantly increased a few days prior to a massive mortality event. This could be related to a metabolic imbalance in the redox state responsible for the high mortality. Thus, glycerol kinase might be used as an effective nutritional and welfare biomarker. The studies in this report also revealed the important finding that feeding larvae with phospholipid-enriched Artemia improved animal viability and

  20. Gene Expression Profiling of Human Vaginal Cells In Vitro Discriminates Compounds with Pro-Inflammatory and Mucosa-Altering Properties: Novel Biomarkers for Preclinical Testing of HIV Microbicide Candidates.

    Directory of Open Access Journals (Sweden)

    Irina A Zalenskaya

    Full Text Available Inflammation and immune activation of the cervicovaginal mucosa are considered factors that increase susceptibility to HIV infection. Therefore, it is essential to screen candidate anti-HIV microbicides for potential mucosal immunomodulatory/inflammatory effects prior to further clinical development. The goal of this study was to develop an in vitro method for preclinical evaluation of the inflammatory potential of new candidate microbicides using a microarray gene expression profiling strategy.To this end, we compared transcriptomes of human vaginal cells (Vk2/E6E7 treated with well-characterized pro-inflammatory (PIC and non-inflammatory (NIC compounds. PICs included compounds with different mechanisms of action. Gene expression was analyzed using Affymetrix U133 Plus 2 arrays. Data processing was performed using GeneSpring 11.5 (Agilent Technologies, Santa Clara, CA.Microarraray comparative analysis allowed us to generate a panel of 20 genes that were consistently deregulated by PICs compared to NICs, thus distinguishing between these two groups. Functional analysis mapped 14 of these genes to immune and inflammatory responses. This was confirmed by the fact that PICs induced NFkB pathway activation in Vk2 cells. By testing microbicide candidates previously characterized in clinical trials we demonstrated that the selected PIC-associated genes properly identified compounds with mucosa-altering effects. The discriminatory power of these genes was further demonstrated after culturing vaginal cells with vaginal bacteria. Prevotella bivia, prevalent bacteria in the disturbed microbiota of bacterial vaginosis, induced strong upregulation of seven selected PIC-associated genes, while a commensal Lactobacillus gasseri associated to vaginal health did not cause any changes.In vitro evaluation of the immunoinflammatory potential of microbicides using the PIC-associated genes defined in this study could help in the initial screening of candidates prior

  1. Biomarkers of PTSD: military applications and considerations

    Directory of Open Access Journals (Sweden)

    Amy Lehrner

    2014-08-01

    Full Text Available Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. Objective: This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Method: Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Results: Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Conclusions: Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

  2. Biomarkers of PTSD: military applications and considerations.

    Science.gov (United States)

    Lehrner, Amy; Yehuda, Rachel

    2014-01-01

    Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

  3. Towards Improved Biomarker Research

    DEFF Research Database (Denmark)

    Kjeldahl, Karin

    This thesis takes a look at the data analytical challenges associated with the search for biomarkers in large-scale biological data such as transcriptomics, proteomics and metabolomics data. These studies aim to identify genes, proteins or metabolites which can be associated with e.g. a diet...... with very specific competencies. In order to optimize the basis of a sound and fruitful data analysis, suggestions are givenwhich focus on (1) collection of good data, (2) preparation of data for the data analysis and (3) a sound data analysis. If these steps are optimized, PLS is a also a very goodmethod...

  4. Status of gluonium searches

    International Nuclear Information System (INIS)

    Heusch, C.A.; California Univ., Santa Cruz, CA

    1991-01-01

    Quantum chromodynamics predicts the existence of quarkless mesons. The search for these hadrons has been ingenious and persevering. A review is presented of the current status of research that considers all model-dependent theoretical prejudice when searching for specific states. Early hints for candidate states have been investigated in the light of recent data, mostly from the Mark III Collaboration, in radiative charmonium decay. No 'smoking-gun' candidate stands out. (R.P.) 25 refs., 20 figs., 2 tabs

  5. Large Neighborhood Search

    DEFF Research Database (Denmark)

    Pisinger, David; Røpke, Stefan

    2010-01-01

    Heuristics based on large neighborhood search have recently shown outstanding results in solving various transportation and scheduling problems. Large neighborhood search methods explore a complex neighborhood by use of heuristics. Using large neighborhoods makes it possible to find better...... candidate solutions in each iteration and hence traverse a more promising search path. Starting from the large neighborhood search method,we give an overview of very large scale neighborhood search methods and discuss recent variants and extensions like variable depth search and adaptive large neighborhood...

  6. Biomarkers in DILI: one more step forward

    Directory of Open Access Journals (Sweden)

    Mercedes Robles-Díaz

    2016-08-01

    Full Text Available Despite being relatively rare, drug-induced liver injury (DILI is a serious condition, both for the individual patient due to the risk of acute liver failure, and for the drug development industry and regulatory agencies due to associations with drug development attritions, black box warnings and postmarketing withdrawals. A major limitation in DILI diagnosis and prediction is the current lack of specific biomarkers. Despite refined usage of traditional liver biomarkers in DILI, reliable disease outcome predictions are still difficult to make. These limitations have driven the growing interest in developing new more sensitive and specific DILI biomarkers, which can improve early DILI prediction, diagnosis and course of action. Several promising DILI biomarker candidates have been discovered to date, including mechanistic-based biomarker candidates such as glutamate dehydrogenase, high-mobility group box 1 protein and keratin-18, which can also provide information on the injury mechanism of different causative agents. Furthermore, microRNAs have received much attention lately as potential non-invasive DILI biomarker candidates, in particular miR-122. Advances in omics technologies offer a new approach for biomarker exploration studies. The ability to screen a large number of molecules (for example metabolites, proteins or DNA simultaneously enables the identification of ‘toxicity signatures’, which may be used to enhance preclinical safety assessments and disease diagnostics. Omics-based studies can also provide information on the underlying mechanisms of distinct forms of DILI that may further facilitate the identification of early diagnostic biomarkers and safer implementation of personalized medicine. In this review we summarize recent advances in the area of DILI biomarker studies.

  7. Quantitative measurement of a candidate serum biomarker peptide derived from α2-HS-glycoprotein, and a preliminary trial of multidimensional peptide analysis in females with pregnancy-induced hypertension.

    Science.gov (United States)

    Hamamura, Kensuke; Yanagida, Mitsuaki; Ishikawa, Hitoshi; Banzai, Michio; Yoshitake, Hiroshi; Nonaka, Daisuke; Tanaka, Kenji; Sakuraba, Mayumi; Miyakuni, Yasuka; Takamori, Kenji; Nojima, Michio; Yoshida, Koyo; Fujiwara, Hiroshi; Takeda, Satoru; Araki, Yoshihiko

    2018-03-01

    Purpose We previously attempted to develop quantitative enzyme-linked immunosorbent assay (ELISA) systems for the PDA039/044/071 peptides, potential serum disease biomarkers (DBMs) of pregnancy-induced hypertension (PIH), primarily identified by a peptidomic approach (BLOTCHIP®-mass spectrometry (MS)). However, our methodology did not extend to PDA071 (cysteinyl α2-HS-glycoprotein 341-367 ), due to difficulty to produce a specific antibody against the peptide. The aim of the present study was to establish an alternative PDA071 quantitation system using liquid chromatography-multiple reaction monitoring (LC-MRM)/MS, to explore the potential utility of PDA071 as a DBM for PIH. Methods We tested heat/acid denaturation methods in efforts to purify serum PDA071 and developed an LC-MRM/MS method allowing for specific quantitation thereof. We measured serum PDA071 concentrations, and these results were validated including by three-dimensional (3D) plotting against PDA039 (kininogen-1 439-456 )/044 (kininogen-1 438-456 ) concentrations, followed by discriminant analysis. Results PDA071 was successfully extracted from serum using a heat denaturation method. Optimum conditions for quantitation via LC-MRM/MS were developed; the assayed serum PDA071 correlated well with the BLOTCHIP® assay values. Although the PDA071 alone did not significantly differ between patients and controls, 3D plotting of PDA039/044/071 peptide concentrations and construction of a Jackknife classification matrix were satisfactory in terms of PIH diagnostic precision. Conclusions Combination analysis using both PDA071 and PDA039/044 concentrations allowed PIH diagnostic accuracy to be attained, and our method will be valuable in future pathophysiological studies of hypertensive disorders of pregnancy.

  8. Biomarkers for hepatocellular carcinoma: diagnostic and therapeutic utility

    Directory of Open Access Journals (Sweden)

    Ferrín G

    2015-04-01

    Full Text Available Gustavo Ferrín,1,2 Patricia Aguilar-Melero,1 Manuel Rodríguez-Perálvarez,1,2 José Luis Montero-Álvarez,1,2 Manuel de la Mata1,2 1Liver Unit, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC, Hospital Universitario Reina Sofía, Córdoba, Spain; 2Centro de Investigación Biomédica en Red (CIBER, Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain Abstract: Because of the high prevalence and associated-mortality of hepatocellular carcinoma (HCC, early diagnosis of the disease is vital for patient survival. In this regard, tumor size is one of the two main prognostic factors for surgical resection, which constitutes the only curative treatment for HCC along with liver transplantation. However, techniques for HCC surveillance and diagnosis that are currently used in clinical practice have certain limitations that may be inherent to the tumor development. Thus, it is important to continue efforts in the search for biomarkers that increase diagnostic accuracy for HCC. In this review, we focus on different biological sources of candidate biomarkers for HCC diagnosis. Although those biomarkers identified from biological samples obtained by noninvasive methods have greater diagnostic value, we have also considered those obtained from liver tissue because of their potential therapeutic value. To date, sorafenib is the only US Food and Drug Administration-approved antineoplastic for HCC. However, this therapeutic agent shows very low tumor response rates and frequently causes acquired resistance in HCC patients. We discuss the use of HCC biomarkers as therapeutic targets themselves, or as targets to increase sensitivity to sorafenib treatment. Keywords: diagnosis, sorafenib, therapy

  9. Lung Cancer Serum Biomarker Discovery Using Label Free LC-MS/MS

    Science.gov (United States)

    Zeng, Xuemei; Hood, Brian L.; Zhao, Ting; Conrads, Thomas P.; Sun, Mai; Gopalakrishnan, Vanathi; Grover, Himanshu; Day, Roger S.; Weissfeld, Joel L.; Wilson, David O.; Siegfried, Jill M.; Bigbee, William L.

    2011-01-01

    Introduction Lung cancer remains the leading cause of cancer-related death with poor survival due to the late stage at which lung cancer is typically diagnosed. Given the clinical burden from lung cancer, and the relatively favorable survival associated with early stage lung cancer, biomarkers for early detection of lung cancer are of important potential clinical benefit. Methods We performed a global lung cancer serum biomarker discovery study using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in a set of pooled non-small cell lung cancer (NSCLC) case sera and matched controls. Immunoaffinity subtraction was used to deplete the top most abundant serum proteins; the remaining serum proteins were subjected to trypsin digestion and analyzed in triplicate by LC-MS/MS. The tandem mass spectrum data were searched against the human proteome database and the resultant spectral counting data were used to estimate the relative abundance of proteins across the case/control serum pools. The spectral counting derived abundances of some candidate biomarker proteins were confirmed with multiple reaction monitoring MS assays. Results A list of 49 differentially abundant candidate proteins was compiled by applying a negative binomial regression model to the spectral counting data (pbiomarkers with statistically significant differential abundance across the lung cancer case/control pools which, when validated, could improve lung cancer early detection. PMID:21304412

  10. Salivary proteomic and genomic biomarkers for primary Sjogren's syndrome

    NARCIS (Netherlands)

    Hu, Shen; Wang, Jianghua; Leong, Sonya; Xie, Yongming; Yu, Tianwei; Zhou, Hui; Henry, Sharon; Vissink, Arjan; Pijpe, Justin; Kallenberg, Cees; Elashoff, David; Loo, Joseph A.; Wong, David T.

    2007-01-01

    Objective. To identify a panel of protein and messenger RNA (mRNA) biomarkers in human whole saliva (WS) that may be used in the detection of primary Sjogren's syndrome (SS). Methods. Mass spectrometry and expression microarray profiling were used to identify candidate protein and mRNA, biomarkers

  11. Salivary proteomic and genomic biomarkers for primary Sjogren's syndrome

    NARCIS (Netherlands)

    Hu, Shen; Wang, Jianghua; Leong, Sonya; Xie, Yongming; Yu, Tianwei; Zhou, Hui; Henry, Sharon; Vissink, Arjan; Pijpe, Justin; Kallenberg, Cees; Elashoff, David; Loo, Joseph A.; Wong, David T.

    Objective. To identify a panel of protein and messenger RNA (mRNA) biomarkers in human whole saliva (WS) that may be used in the detection of primary Sjogren's syndrome (SS). Methods. Mass spectrometry and expression microarray profiling were used to identify candidate protein and mRNA, biomarkers

  12. Lung Cancer Signature Biomarkers: tissue specific semantic similarity based clustering of Digital Differential Display (DDD data

    Directory of Open Access Journals (Sweden)

    Srivastava Mousami

    2012-11-01

    Full Text Available Abstract Background The tissue-specific Unigene Sets derived from more than one million expressed sequence tags (ESTs in the NCBI, GenBank database offers a platform for identifying significantly and differentially expressed tissue-specific genes by in-silico methods. Digital differential display (DDD rapidly creates transcription profiles based on EST comparisons and numerically calculates, as a fraction of the pool of ESTs, the relative sequence abundance of known and novel genes. However, the process of identifying the most likely tissue for a specific disease in which to search for candidate genes from the pool of differentially expressed genes remains difficult. Therefore, we have used ‘Gene Ontology semantic similarity score’ to measure the GO similarity between gene products of lung tissue-specific candidate genes from control (normal and disease (cancer sets. This semantic similarity score matrix based on hierarchical clustering represents in the form of a dendrogram. The dendrogram cluster stability was assessed by multiple bootstrapping. Multiple bootstrapping also computes a p-value for each cluster and corrects the bias of the bootstrap probability. Results Subsequent hierarchical clustering by the multiple bootstrapping method (α = 0.95 identified seven clusters. The comparative, as well as subtractive, approach revealed a set of 38 biomarkers comprising four distinct lung cancer signature biomarker clusters (panel 1–4. Further gene enrichment analysis of the four panels revealed that each panel represents a set of lung cancer linked metastasis diagnostic biomarkers (panel 1, chemotherapy/drug resistance biomarkers (panel 2, hypoxia regulated biomarkers (panel 3 and lung extra cellular matrix biomarkers (panel 4. Conclusions Expression analysis reveals that hypoxia induced lung cancer related biomarkers (panel 3, HIF and its modulating proteins (TGM2, CSNK1A1, CTNNA1, NAMPT/Visfatin, TNFRSF1A, ETS1, SRC-1, FN1, APLP2, DMBT1

  13. CURRENT APPROACHES FOR RESEARCH OF MULTIPLE SCLEROSIS BIOMARKERS

    Directory of Open Access Journals (Sweden)

    Kolyada T.I

    2016-12-01

    severity, progression, pathogenetic type and treatment efficacy are based on transcriptomics, proteomics and metabolomics technologies. Transcriptomics includes genome-wide research of RNA sequences based on the results obtained with comparative genomic hybridization on biochips, massive parallel RNA sequencing, and measuring the amount of mRNA by real-time PCR. This technology is actively used in studies of gene expression profile of peripheral blood mononuclear cells from MS patients aimed at identifying molecular markers of disease status suitable for clinical use. Proteomics is a large-scale expression and protein distribution studies in patients with MS based on the results obtained via microarray and mass spectrometry, liquid and gas chromatography methods. In recent years, a growing number of MS proteomic studies using 2DE-MS method (two-dimensional electrophoresis coupled with mass spectrometry. Metabolomics studies of low-molecular-weight metabolic profiles based on the results obtained by mass spectrometry, liquid and gas chromatography, nuclear magnetic resonance. However, unlike other «-omics»-technologies, in metabolomics microarray-techniques are not used. Conclusion. Search, verification and clinical application of biomarkers for multiple sclerosis are one of the most challenging medical and biological problems. Its solution requires an interdisciplinary approach, organization of large-scale research and engagement of new research methods. In recent years, a significant amount of data received allowed to reveal hundreds of candidate biomarkers. Some of these biomarkers have significant potential for the monitoring of disease activity and assessment of therapy efficiency. However, the verification is required for a widespread clinical application; it implies further large-scale studies in different countries. The development of personalized medicine in Ukraine, the application of its principles to the management of multiple sclerosis patients, along with

  14. First-void urine: A potential biomarker source for triage of high-risk human papillomavirus infected women.

    Science.gov (United States)

    Van Keer, Severien; Pattyn, Jade; Tjalma, Wiebren A A; Van Ostade, Xaveer; Ieven, Margareta; Van Damme, Pierre; Vorsters, Alex

    2017-09-01

    Great interest has been directed towards the use of first-void urine as a liquid biopsy for high-risk human papillomavirus DNA testing. Despite the high correlations established between urinary and cervical infections, human papillomavirus testing is unable to distinguish between productive and transforming high-risk infections that have the tendency to progress to cervical cancer. Thus far, investigations have been primarily confined to the identification of biomarkers for triage of high-risk human papillomavirus-positive women in cervicovaginal specimens and tissue biopsies. This paper reviews urinary biomarkers for cervical cancer and triage of high-risk human papillomavirus infections and elaborates on the opportunities and challenges that have emerged regarding the use of first-void urine as a liquid biopsy for the analysis of both morphological- (conventional cytology and novel immunohistochemical techniques) and molecular-based (HPV16/18 genotyping, host/viral gene methylation, RNA, and proteins) biomarkers. A literature search was performed in PubMed and Web of Science for studies investigating the use of urine as a biomarker source for cervical cancer screening. Five studies were identified reporting on biomarkers that are still in preclinical exploratory or clinical assay development phases and on assessments of non-invasive (urine) samples. Although large-scale validation studies are still needed, we conclude that methylation of both host and viral genes in urine has been proven feasible for use as a molecular cervical cancer triage and screening biomarker in phase two studies. This is especially promising and underscores our hypothesis that human papillomavirus DNA and candidate human and viral biomarkers are washed away with the initial, first-void urine, together with exfoliated cells, debris and impurities that line the urethra opening. Similar to the limitations of self-collected cervicovaginal samples, first-void urine will likely not fulfil the

  15. Transmembrane amyloid-related proteins in CSF as potential biomarkers for Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Inmaculada eLopez-Font

    2015-06-01

    Full Text Available In the continuing search for new cerebrospinal fluid (CSF biomarkers for Alzheimer’s disease (AD, reasonable candidates are the secretase enzymes involved in the processing of the amyloid precursor protein (APP, as well as the large proteolytic cleavage fragments sAPPα and sAPPβ. The enzymatic activities of some of these secretases, such as BACE1 and TACE, have been investigated as potential AD biomarkers, and it has been assumed that these activities present in human CSF result from the soluble truncated forms of the membrane-bound enzymes. However, we and others recently identified soluble forms of BACE1 and APP in CSF containing the intracellular domains, as well as the multi-pass transmembrane presenilin-1 (PS1 and other subunits of γ-secretase. We also review recent findings that suggest that most of these soluble transmembrane proteins could display self-association properties based on hydrophobic and/or ionic interactions leading to the formation of heteromeric complexes. The oligomerization state of these potential new biomarkers needs to be taken into consideration for assessing their real potential as CSF biomarkers for AD by adequate molecular tools.

  16. Multiple Protein Biomarker Assessment for Recombinant Bovine Somatotropin (rbST) Abuse in Cattle

    NARCIS (Netherlands)

    Ludwig, S.K.J.; Smits, N.G.E.; Veer, van der G.; Bremer, M.G.E.G.; Nielen, M.W.F.

    2012-01-01

    Biomarker profiling, as a rapid screening approach for detection of hormone abuse, requires well selected candidate biomarkers and a thorough in vivo biomarker evaluation as previously done for detection of growth hormone doping in athletes. The bovine equivalent of growth hormone, called

  17. Comparison of proteomic biomarker panels in urine and serum for ovarian cancer diagnosis

    DEFF Research Database (Denmark)

    Petri, Anette Lykke; Simonsen, Anja Hviid; Høgdall, Estrid

    2010-01-01

    The purposes of this study were to confirm previously found candidate epithelial ovarian cancer biomarkers in urine and to compare a paired serum biomarker panel and a urine biomarker panel from the same study cohort with regard to the receiver operating characteristic curve (ROC) area under the ...

  18. Emerging biomarkers for cancer immunotherapy in melanoma.

    Science.gov (United States)

    Axelrod, Margaret L; Johnson, Douglas B; Balko, Justin M

    2017-09-14

    The treatment and prognosis of metastatic melanoma has changed substantially since the advent of novel immune checkpoint inhibitors (ICI), agents that enhance the anti-tumor immune response. Despite the success of these agents, clinically actionable biomarkers to aid patient and regimen selection are lacking. Herein, we summarize and review the evidence for candidate biomarkers of response to ICIs in melanoma. Many of these candidates can be examined as parts of a known molecular pathway of immune response, while others are clinical in nature. Due to the ability of ICIs to illicit dramatic and durable responses, well-validated biomarkers that can be effectively implemented in the clinic will require strong negative predictive values that do not limit patients with who may benefit from ICI therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Use of biomarkers in ALS drug development and clinical trials.

    Science.gov (United States)

    Bakkar, Nadine; Boehringer, Ashley; Bowser, Robert

    2015-05-14

    The past decade has seen a dramatic increase in the discovery of candidate biomarkers for ALS. These biomarkers typically can either differentiate ALS from control subjects or predict disease course (slow versus fast progression). At the same time, late-stage clinical trials for ALS have failed to generate improved drug treatments for ALS patients. Incorporation of biomarkers into the ALS drug development pipeline and the use of biologic and/or imaging biomarkers in early- and late-stage ALS clinical trials have been absent and only recently pursued in early-phase clinical trials. Further clinical research studies are needed to validate biomarkers for disease progression and develop biomarkers that can help determine that a drug has reached its target within the central nervous system. In this review we summarize recent progress in biomarkers across ALS model systems and patient population, and highlight continued research directions for biomarkers that stratify the patient population to enrich for patients that may best respond to a drug candidate, monitor disease progression and track drug responses in clinical trials. It is crucial that we further develop and validate ALS biomarkers and incorporate these biomarkers into the ALS drug development process. This article is part of a Special Issue entitled ALS complex pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Citizen Candidates Under Uncertainty

    OpenAIRE

    Eguia, Jon X.

    2005-01-01

    In this paper we make two contributions to the growing literature on "citizen-candidate" models of representative democracy. First, we add uncertainty about the total vote count. We show that in a society with a large electorate, where the outcome of the election is uncertain and where winning candidates receive a large reward from holding office, there will be a two-candidate equilibrium and no equilibria with a single candidate. Second, we introduce a new concept of equilibrium, which we te...

  1. Chronic Obstructive Pulmonary Disease Biomarkers

    Directory of Open Access Journals (Sweden)

    Tatsiana Beiko

    2016-04-01

    Full Text Available Despite significant decreases in morbidity and mortality of cardiovascular diseases (CVD and cancers, morbidity and cost associated with chronic obstructive pulmonary disease (COPD continue to be increasing. Failure to improve disease outcomes has been related to the paucity of interventions improving survival. Insidious onset and slow progression halter research successes in developing disease-modifying therapies. In part, the difficulty in finding new therapies is because of the extreme heterogeneity within recognized COPD phenotypes. Novel biomarkers are necessary to help understand the natural history and pathogenesis of the different COPD subtypes. A more accurate phenotyping and the ability to assess the therapeutic response to new interventions and pharmaceutical agents may improve the statistical power of longitudinal clinical studies. In this study, we will review known candidate biomarkers for COPD, proposed pathways of pathogenesis, and future directions in the field.

  2. Alternative dark matter candidates. Axions

    International Nuclear Information System (INIS)

    Ringwald, Andreas

    2017-01-01

    The axion is arguably one of the best motivated candidates for dark matter. For a decay constant >or similar 10 9 GeV, axions are dominantly produced non-thermally in the early universe and hence are ''cold'', their velocity dispersion being small enough to fit to large scale structure. Moreover, such a large decay constant ensures the stability at cosmological time scales and its behaviour as a collisionless fluid at cosmological length scales. Here, we review the state of the art of axion dark matter predictions and of experimental efforts to search for axion dark matter in laboratory experiments.

  3. Alternative dark matter candidates. Axions

    Energy Technology Data Exchange (ETDEWEB)

    Ringwald, Andreas

    2017-01-15

    The axion is arguably one of the best motivated candidates for dark matter. For a decay constant >or similar 10{sup 9} GeV, axions are dominantly produced non-thermally in the early universe and hence are ''cold'', their velocity dispersion being small enough to fit to large scale structure. Moreover, such a large decay constant ensures the stability at cosmological time scales and its behaviour as a collisionless fluid at cosmological length scales. Here, we review the state of the art of axion dark matter predictions and of experimental efforts to search for axion dark matter in laboratory experiments.

  4. Early biomarkers of joint damage in rheumatoid and psoriatic arthritis.

    LENUS (Irish Health Repository)

    Mc Ardle, Angela

    2015-01-01

    Joint destruction, as evidenced by radiographic findings, is a significant problem for patients suffering from rheumatoid arthritis and psoriatic arthritis. Inherently irreversible and frequently progressive, the process of joint damage begins at and even before the clinical onset of disease. However, rheumatoid and psoriatic arthropathies are heterogeneous in nature and not all patients progress to joint damage. It is therefore important to identify patients susceptible to joint destruction in order to initiate more aggressive treatment as soon as possible and thereby potentially prevent irreversible joint damage. At the same time, the high cost and potential side effects associated with aggressive treatment mean it is also important not to over treat patients and especially those who, even if left untreated, would not progress to joint destruction. It is therefore clear that a protein biomarker signature that could predict joint damage at an early stage would support more informed clinical decisions on the most appropriate treatment regimens for individual patients. Although many candidate biomarkers for rheumatoid and psoriatic arthritis have been reported in the literature, relatively few have reached clinical use and as a consequence the number of prognostic biomarkers used in rheumatology has remained relatively static for several years. It has become evident that a significant challenge in the transition of biomarker candidates to clinical diagnostic assays lies in the development of suitably robust biomarker assays, especially multiplexed assays, and their clinical validation in appropriate patient sample cohorts. Recent developments in mass spectrometry-based targeted quantitative protein measurements have transformed our ability to rapidly develop multiplexed protein biomarker assays. These advances are likely to have a significant impact on the validation of biomarkers in the future. In this review, we have comprehensively compiled a list of candidate

  5. The Wide and Complex Field of NAFLD Biomarker Research: Trends

    OpenAIRE

    Wichro, Erika; Macheiner, Tanja; Schmid, Jasmin; Kavsek, Barbara; Sargsyan, Karine

    2014-01-01

    Background. Nonalcoholic fatty liver disease is now acknowledged as a complex public health issue linked to sedentary lifestyle, obesity, and related disorders like type 2 diabetes and metabolic syndrome. Aims. We aimed to retrieve its trends out of the huge amount of published data. Therefore, we conducted an extensive literature search to identify possible biomarker and/or biomarker combinations by retrospectively assessing and evaluating common and novel biomarkers to predict progression a...

  6. Imaging biomarkers as surrogate endpoints for drug development

    International Nuclear Information System (INIS)

    Richter, Wolf S.

    2006-01-01

    The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates - thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of ''personalised medicine''. A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may - if properly validated - serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's ''critical path initiative''. (orig.)

  7. Brain oscillations as biomarkers in neuropsychiatric disorders: following an interactive panel discussion and synopsis.

    Science.gov (United States)

    Yener, Görsev G; Başar, Erol

    2013-01-01

    This survey covers the potential use of neurophysiological changes as a biomarker in four neuropsychiatric diseases (attention deficit hyperactivity disorder (ADHD), Alzheimer's disease (AD), bipolar disorder (BD), and schizophrenia (SZ)). Great developments have been made in the search of biomarkers in these disorders, especially in AD. Nevertheless, there is a tremendous need to develop an efficient, low-cost, potentially portable, non-invasive biomarker in the diagnosis, course, or treatment of the above-mentioned disorders. Electrophysiological methods would provide a tool that would reflect functional brain dynamic changes within milliseconds and also may be used as an ensemble of biomarkers that is greatly needed in the evaluation of cognitive changes seen in these disorders. The strategies for measuring cognitive changes include spontaneous electroencephalography (EEG), sensory evoked oscillation (SEO), and event-related oscillations (ERO). Further selective connectivity deficit in sensory or cognitive networks is reflected by coherence measurements. Possible candidate biomarkers discussed in an interactive panel can be summarized as follows: for ADHD: (a) elevation of delta and theta, (b) diminished alpha and beta responses in spontaneous EEG; for SZ: (a) decrease of ERO gamma responses, (b) decreased ERO in all other frequency ranges, (c) invariant ERO gamma response in relation to working memory demand; for euthymic BD: (a) decreased event-related gamma coherence, (b) decreased alpha in ERO and in spontaneous EEG; for manic BD: (a) lower alpha and higher beta in ERO, (b) decreased event-related gamma coherence, (c) lower alpha and beta in ERO after valproate; and for AD: (a) decreased alpha and beta, and increased theta and delta in spontaneous EEG, (b) hyperexcitability of motor cortices as shown by transcortical magnetic stimulation, (c) hyperexcitability of visual sensory cortex as indicated by increased SEO theta responses, (d) lower delta ERO, (e

  8. Identification and validation of candidate epigenetic biomarkers in lung adenocarcinoma

    DEFF Research Database (Denmark)

    Daugaard, Iben; Dominguez, Diana; Kjeldsen, Tina E

    2016-01-01

    -adjacent normal lung tissue from four lung adenocarcinoma (LAC) patients using DNA methylation microarrays and identified 74 differentially methylated regions (DMRs). Eighteen DMRs were selected for validation in a cohort comprising primary tumors from 52 LAC patients and tumor-adjacent normal lung tissue from 32...... patients by methylation-sensitive high resolution melting (MS-HRM) analysis. Significant increases in methylation were confirmed for 15 DMRs associated with the genes and genomic regions: OSR1, SIM1, GHSR, OTX2, LOC648987, HIST1H3E, HIST1H3G/HIST1H2BI, HIST1H2AJ/HIST1H2BM, HOXD10, HOXD3, HOXB3/HOXB4, HOXA3...

  9. Search for black holes

    International Nuclear Information System (INIS)

    Cherepashchuk, Anatolii M

    2003-01-01

    Methods and results of searching for stellar mass black holes in binary systems and for supermassive black holes in galactic nuclei of different types are described. As of now (June 2002), a total of 100 black hole candidates are known. All the necessary conditions Einstein's General Relativity imposes on the observational properties of black holes are satisfied for candidate objects available, thus further assuring the existence of black holes in the Universe. Prospects for obtaining sufficient criteria for reliably distinguishing candidate black holes from real black holes are discussed. (reviews of topical problems)

  10. Biomarkers of problem drinking in homeless patients

    DEFF Research Database (Denmark)

    Hesse, Morten; Thiesen, Henrik

    2010-01-01

    Objective. In the search for optimal biomarkers of excessive drinking, a central limitation has been the lack of sensitivity of measures. Many patients have apparently normal values of liver markers despite a considerable alcohol intake. This study aimed to test a novel combined indicator...

  11. Biomarkers in T cell therapy clinical trials

    Directory of Open Access Journals (Sweden)

    Kalos Michael

    2011-08-01

    Full Text Available Abstract T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials.

  12. Combination of biomarkers

    DEFF Research Database (Denmark)

    Thurfjell, Lennart; Lötjönen, Jyrki; Lundqvist, Roger

    2012-01-01

    The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury.......The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury....

  13. Search Help

    Science.gov (United States)

    Guidance and search help resource listing examples of common queries that can be used in the Google Search Appliance search request, including examples of special characters, or query term seperators that Google Search Appliance recognizes.

  14. Identification of peroxiredoxin-1 as a novel biomarker of abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Martinez-Pinna, Roxana; Ramos-Mozo, Priscila; Madrigal-Matute, Julio

    2011-01-01

    In the search of novel biomarkers of abdominal aortic aneurysm (AAA) progression, proteins released by intraluminal thrombus (ILT) were analyzed by a differential proteomic approach.......In the search of novel biomarkers of abdominal aortic aneurysm (AAA) progression, proteins released by intraluminal thrombus (ILT) were analyzed by a differential proteomic approach....

  15. The Wide and Complex Field of NAFLD Biomarker Research: Trends.

    Science.gov (United States)

    Wichro, Erika; Macheiner, Tanja; Schmid, Jasmin; Kavsek, Barbara; Sargsyan, Karine

    2014-01-01

    Background. Nonalcoholic fatty liver disease is now acknowledged as a complex public health issue linked to sedentary lifestyle, obesity, and related disorders like type 2 diabetes and metabolic syndrome. Aims. We aimed to retrieve its trends out of the huge amount of published data. Therefore, we conducted an extensive literature search to identify possible biomarker and/or biomarker combinations by retrospectively assessing and evaluating common and novel biomarkers to predict progression and prognosis of obesity related liver diseases. Methodology. We analyzed finally 62 articles accounting for 157 cohorts and 45,288 subjects. Results. Despite the various approaches, most cohorts were considerably small and rarely comparable. Also, we found that the same standard parameters were measured rather than novel biomarkers. Diagnostics approaches appeared incomparable. Conclusions. Further collaborative investigations on harmonizing ways of data acquisition and identifying such biomarkers for clinical use are necessary to yield sufficient significant results of potential biomarkers.

  16. Biology and Biomarkers for Wound Healing

    Science.gov (United States)

    Lindley, Linsey E.; Stojadinovic, Olivera; Pastar, Irena; Tomic-Canic, Marjana

    2016-01-01

    Background As the population grows older, the incidence and prevalence of conditions which lead to a predisposition for poor wound healing also increases. Ultimately, this increase in non-healing wounds has led to significant morbidity and mortality with subsequent huge economic ramifications. Therefore, understanding specific molecular mechanisms underlying aberrant wound healing is of great importance. It has, and will continue to be the leading pathway to the discovery of therapeutic targets as well as diagnostic molecular biomarkers. Biomarkers may help identify and stratify subsets of non-healing patients for whom biomarker-guided approaches may aid in healing. Methods A series of literature searches were performed using Medline, PubMed, Cochrane Library, and Internet searches. Results Currently, biomarkers are being identified using biomaterials sourced locally, from human wounds and/or systemically using systematic high-throughput “omics” modalities (genomic, proteomic, lipidomic, metabolomic analysis). In this review we highlight the current status of clinically applicable biomarkers and propose multiple steps in validation and implementation spectrum including those measured in tissue specimens e.g. β-catenin and c-myc, wound fluid e.g. MMP’s and interleukins, swabs e.g. wound microbiota and serum e.g. procalcitonin and MMP’s. Conclusions Identification of numerous potential biomarkers utilizing different avenues of sample collection and molecular approaches is currently underway. A focus on simplicity, and consistent implementation of these biomarkers as well as an emphasis on efficacious follow-up therapeutics is necessary for transition of this technology to clinically feasible point-of-care applications. PMID:27556760

  17. Biomarker discovery in biological specimens (plasma, hair, liver and kidney) of diabetic mice based upon metabolite profiling using ultra-performance liquid chromatography with electrospray ionization time-of-flight mass spectrometry.

    Science.gov (United States)

    Tsutsui, Haruhito; Maeda, Toshio; Min, Jun Zhe; Inagaki, Shinsuke; Higashi, Tatsuya; Kagawa, Yoshiyuki; Toyo'oka, Toshimasa

    2011-05-12

    The number of diabetic patients has recently been increasing worldwide. Diabetes is a multifactorial disorder based on environmental factors and genetic background. In many cases, diabetes is asymptomatic for a long period and the patient is not aware of the disease. Therefore, the potential biomarker(s), leading to the early detection and/or prevention of diabetes mellitus, are strongly required. However, the diagnosis of the prediabetic state in humans is a very difficult issue, because the lifestyle is variable in each person. Although the development of a diagnosis method in humans is the goal of our research, the extraction and structural identification of biomarker candidates in several biological specimens (i.e., plasma, hair, liver and kidney) of ddY strain mice, which undergo naturally occurring diabetes along with aging, were carried out based upon a metabolite profiling study. The low-molecular-mass compounds including metabolites in the biological specimens of diabetic mice (ddY-H) and normal mice (ddY-L) were globally separated by ultra-performance liquid chromatography (UPLC) using different reversed-phase columns (i.e., T3-C18 and HS-F5) and detected by electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS). The biomarker candidates related to diabetes mellitus were extracted from a multivariate statistical analysis, such as an orthogonal partial least-squares-discriminant analysis (OPLS-DA), followed by a database search, such as ChemSpider, KEGG and HMDB. Many metabolites and unknown compounds in each biological specimen were detected as the biomarker candidates related to diabetic mellitus. Among them, the elucidation of the chemical structures of several possible metabolites, including more than two biological specimens, was carried out along with the comparison of the tandem MS/MS analyses using authentic compounds. One metabolite was clearly identified as N-acetyl-L-leucine based upon the MS/MS spectra and the retention time on

  18. Gamma-ray astronomy from the ground and the space: first analyses of the HESS-II hybrid array and search for blazar candidates among the unidentified Fermi-LAT sources

    International Nuclear Information System (INIS)

    Lefaucheur, Julien

    2015-01-01

    This manuscript is about high energy gamma-ray astronomy (between 30 GeV and 300 GeV) with the Fermi-LAT satellite and very high energy gamma-ray astronomy (above ∼100 GeV) via the H.E.S.S. experiment. The second phase of the H.E.S.S. experiment began in July 2012 with the inauguration of a fifth 28 m-diameter telescope added to the initial array composed of four 12 m-diameter imaging atmospheric Cherenkov telescopes. In the first part of this thesis, we present the development of an analysis in hybrid mode based on a multivariate method dedicated to detect and study sources with different spectral shapes and the first analysis results on real data. The second part is dedicated to the research of blazar candidates among the Fermi-LAT unidentified sources of the 2FGL catalog. A first development is based on a multivariate approach using discriminant parameters built with the 2FGL catalog parameters. A second development is done with the use of the WISE satellite catalog and a non-parametric technic in order to find the blazar-like infrared counterparts of the unidentified sources of the 2FGL catalog. (author)

  19. Allergic asthma biomarkers using systems approaches

    Directory of Open Access Journals (Sweden)

    Gaurab eSircar

    2014-01-01

    Full Text Available Asthma is characterized by lung inflammation caused by complex interaction between the immune system and environmental factors such as allergens and inorganic pollutants. Recent research in this field is focused on discovering new biomarkers associated with asthma pathogenesis. This review illustrates updated research associating biomarkers of allergic asthma and their potential use in systems biology of the disease. We focus on biomolecules with altered expression, which may serve as inflammatory, diagnostic and therapeutic biomarkers of asthma discovered in human or experimental asthma model using genomic, proteomic and epigenomic approaches for gene and protein expression profiling. These include high-throughput technologies such as state of the art microarray and proteomics Mass Spectrometry (MS platforms. Emerging concepts of molecular interactions and pathways may provide new insights in searching potential clinical biomarkers. We summarized certain pathways with significant linkage to asthma pathophysiology by analyzing the compiled biomarkers. Systems approaches with this data can identify the regulating networks, which will eventually identify the key biomarkers to be used for diagnostics and drug discovery.

  20. Target biomarker profile for the clinical management of paracetamol overdose

    Science.gov (United States)

    Vliegenthart, A D Bastiaan; Antoine, Daniel J; Dear, James W

    2015-01-01

    Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. PMID:26076366

  1. Biomarkers in the clinical development of asthma therapies.

    Science.gov (United States)

    Staton, Tracy L; Choy, David F; Arron, Joseph R

    2016-01-01

    Here we review how biomarkers have been used in the design, execution and interpretation of recent clinical studies of therapeutic candidates targeting cytokine-mediated inflammatory pathways in asthma. This review focuses on type 2 inflammation, as there are multiple therapeutics and/or clinical studies that can be compared within that specific pathway. Comparative analyses of data from these clinical studies illustrate the utility of biomarkers to quantify pharmacodynamic effects, clarify mechanism of action and stratify patients, which may facilitate the interpretation of outcomes in the development of molecularly targeted therapies. These case examples provide a basis for biomarker considerations in the design of future studies in the asthma setting.

  2. In search of ancient biomarkers: Using femtosecond - Laser Desorption Post Ionization - Mass Spectrometry (fs-LDPI-MS) to map organic compounds within ca. 2.7 Ga samples from the Abitibi greenstone belt, Ontario, Canada

    Science.gov (United States)

    Pasterski, M. J.; Barry, G.; Hanley, L.; Kenig, F. P. H.

    2016-12-01

    One of the major challenges within the field of organic geochemistry is to determine whether an observed biomarker signature was emplaced during sedimentation (indigenous), after sedimentation via the post-depositional migration of fluids (non-indigenous), or during sampling, storage, or analysis (contaminant). Current geochemical techniques (e.g. gas chromatography-mass spectrometry, GC-MS and GCxGC-MS) can effectively determine the composition and structure of the organic constituents of a sample. However, because of the multiple preparatory steps necessary prior to GC-MS analysis (sample crushing, solvent extraction, organic fraction separation) it is impossible to precisely determine the spatial relationship between the host sample and the organic molecules within. We used an MS imaging method developed by Prof. Luke Hanley at the University of Illinois at Chicago, femtosecond-laser desorption post ionization-MS (fs-LDPI-MS), to map the organics within previously characterized ca.2.7 billion year old (Ga) metasediments from the Abitibi greenstone belt near Timmins, ON, Canada. We then compared the MS images to petrographic observations that displayed the distribution of mineral species with well constrained mineralization ages as well as fluid inclusions within the samples. Fluid inclusions are formed during mineralization and have the ability to remain intact over long timescales (up to billions of years), protecting the fluids inside from the introduction of non-indigenous and contaminant biomarkers. Although migrating post-depositional fluids can remineralize sediments, fluid inclusions associated with secondary additions are focused along grain boundaries and microfractures (secondary inclusions), thus, inclusions which are located within grain boundaries can be considered primary and the age of their formation can be determined relative to the host rock. Preliminary results indicate that previously observed biomarkers may be linked to a series of

  3. Is telomere length a biomarker for aging: cross-sectional evidence from the west of Scotland?

    Science.gov (United States)

    Der, Geoff; Batty, G David; Benzeval, Michaela; Deary, Ian J; Green, Michael J; McGlynn, Liane; McIntyre, Alan; Robertson, Tony; Shiels, Paul G

    2012-01-01

    The search for biomarkers of aging (BoAs) has been largely unsuccessful to-date and there is widespread skepticism about the prospects of finding any that satisfy the criteria developed by the American Federation of Aging Research. This may be because the criteria are too strict or because a composite measure might be more appropriate. Telomere length has attracted a great deal of attention as a candidate BoA. We investigate whether it meets the criteria to be considered as a single biomarker of aging, and whether it makes a useful contribution to a composite measure. Using data from a large population based study, we show that telomere length is associated with age, with several measures of physical and cognitive functioning that are related to normal aging, and with three measures of overall health. In the majority of cases, telomere length adds predictive power to that of age, although it was not nearly as good a predictor overall. We used principal components analysis to form two composites from the measures of functioning, one including telomere length and the other not including it. These composite BoAs were better predictors of the health outcomes than chronological age. There was little difference between the two composites. Telomere length does not satisfy the strict criteria for a BoA, but does add predictive power to that of chronological age. Equivocal results from previous studies might be due to lack of power or the choice of measures examined together with a focus on single biomarkers. Composite biomarkers of aging have the potential to outperform age and should be considered for future research in this area.

  4. Is telomere length a biomarker for aging: cross-sectional evidence from the west of Scotland?

    Directory of Open Access Journals (Sweden)

    Geoff Der

    Full Text Available BACKGROUND: The search for biomarkers of aging (BoAs has been largely unsuccessful to-date and there is widespread skepticism about the prospects of finding any that satisfy the criteria developed by the American Federation of Aging Research. This may be because the criteria are too strict or because a composite measure might be more appropriate. Telomere length has attracted a great deal of attention as a candidate BoA. We investigate whether it meets the criteria to be considered as a single biomarker of aging, and whether it makes a useful contribution to a composite measure. METHODOLOGY/PRINCIPAL FINDINGS: Using data from a large population based study, we show that telomere length is associated with age, with several measures of physical and cognitive functioning that are related to normal aging, and with three measures of overall health. In the majority of cases, telomere length adds predictive power to that of age, although it was not nearly as good a predictor overall. We used principal components analysis to form two composites from the measures of functioning, one including telomere length and the other not including it. These composite BoAs were better predictors of the health outcomes than chronological age. There was little difference between the two composites. CONCLUSIONS: Telomere length does not satisfy the strict criteria for a BoA, but does add predictive power to that of chronological age. Equivocal results from previous studies might be due to lack of power or the choice of measures examined together with a focus on single biomarkers. Composite biomarkers of aging have the potential to outperform age and should be considered for future research in this area.

  5. Exosomal microRNAs as potential circulating biomarkers in gastrointestinal tract cancers: a systematic review protocol

    Directory of Open Access Journals (Sweden)

    Elmira Gheytanchi

    2017-11-01

    Full Text Available Abstract Background Metastasis is the most frequent type of recurrence in gastrointestinal (GI cancers, and there is an emerging potential for new diagnostic and therapeutic approaches, especially in the cases of metastatic GI carcinomas. The expression profiles of circulating exosomal microRNAs are of particular interest as novel non-invasive diagnostic and prognostic biomarkers for improved detection of GI cancers in body fluids, especially in the serum of patients with recurrent cancers. The aim of this study is to systematically review primary studies and identify the miRNA profiles of serum exosomes of GI cancers. Methods and design This systematic review will be reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA guidance. Relevant studies will be identified through a comprehensive search of the following main electronic databases: PubMed, Web of Science, Embase, Scopus, and Google Scholar, with no language restrictions (up to July 2017. Full copies of articles will be identified by a defined search strategy and will be considered for inclusion against pre-defined criteria. The quality assessment of the included studies will be performed by the Newcastle-Ottawa Scale (NOS. Data will be analyzed using Stata software V.12. Publication bias will be assessed by funnel plots, Beggs’ and Eggers’ tests. The levels of evidence for primary outcomes will be evaluated using the GRADE criteria. Discussion The analysis of circulating exosomal miRNA profiles provides attractive screening and non-invasive diagnostic tools for the majority of solid tumors including GI cancers. There is limited information regarding the relationship between serum exosomal miRNA profiles and the pathological condition of patients with different GI cancers. Since there is no specific biomarker for GI cancers, we aim to suggest a number of circulating exosomal miRNA candidates as potential multifaceted GI cancer biomarkers

  6. Cardiac biomarkers in Neonatology

    OpenAIRE

    Vijlbrief, D.C.

    2015-01-01

    In this thesis, the role for cardiac biomarkers in neonatology was investigated. Several clinically relevant results were reported. In term and preterm infants, hypoxia and subsequent adaptation play an important role in cardiac biomarker elevation. The elevated natriuretic peptides are indicative of abnormal function; elevated troponins are suggestive for cardiomyocyte damage. This methodology makes these biomarkers of additional value in the treatment of newborn infants, separate or as a co...

  7. Candidates for non-baryonic dark matter

    International Nuclear Information System (INIS)

    Fornengo, Nicolao

    2002-01-01

    This report is a brief review of the efforts to explain the nature of non-baryonic dark matter and of the studies devoted to the search for relic particles. Among the different dark matter candidates, special attention is devoted to relic neutralinos, by giving an overview of the recent calculations of its relic abundance and detection rates in a wide variety of supersymmetric schemes

  8. Candidates for non-baryonic dark matter

    OpenAIRE

    Fornengo, Nicolao

    2002-01-01

    This report is a brief review of the efforts to explain the nature of non-baryonic dark matter and of the studies devoted to the search for relic particles. Among the different dark matter candidates, special attention is devoted to relic neutralinos, by giving an overview of the recent calculations of its relic abundance and detection rates in a wide variety of supersymmetric schemes.

  9. Biomarkers of Therapeutic Response in the IL-23 Pathway in Inflammatory Bowel Disease

    OpenAIRE

    Cayatte, Corinne; Joyce-Shaikh, Barbara; Vega, Felix; Boniface, Katia; Grein, Jeffrey; Murphy, Erin; Blumenschein, Wendy M; Chen, Smiley; Malinao, Maria-Christina; Basham, Beth; Pierce, Robert H; Bowman, Edward P; McKenzie, Brent S; Elson, Charles O; Faubion, William A

    2012-01-01

    OBJECTIVES: Interleukin-23 (IL-23) has emerged as a new therapeutic target for the treatment of inflammatory bowel disease (IBD). As biomarkers of disease state and treatment efficacy are becoming increasingly important in drug development, we sought to identify efficacy biomarkers for anti-IL-23 therapy in Crohn's disease (CD). METHODS: Candidate IL-23 biomarkers, downstream of IL-23 signaling, were identified using shotgun proteomic analysis of feces and colon lavages obtained from a short-...

  10. Proteomic biomarkers for ovarian cancer risk in women with polycystic ovary syndrome: a systematic review and biomarker database integration.

    Science.gov (United States)

    Galazis, Nicolas; Olaleye, Olalekan; Haoula, Zeina; Layfield, Robert; Atiomo, William

    2012-12-01

    To review and identify possible biomarkers for ovarian cancer (OC) in women with polycystic ovary syndrome (PCOS). Systematic literature searches of MEDLINE, EMBASE, and Cochrane using the search terms "proteomics," "proteomic," and "ovarian cancer" or "ovarian carcinoma." Proteomic biomarkers for OC were then integrated with an updated previously published database of all proteomic biomarkers identified to date in patients with PCOS. Academic department of obstetrics and gynecology in the United Kingdom. A total of 180 women identified in the six studies. Tissue samples from women with OC vs. tissue samples from women without OC. Proteomic biomarkers, proteomic technique used, and methodologic quality score. A panel of six biomarkers was overexpressed both in women with OC and in women with PCOS. These biomarkers include calreticulin, fibrinogen-γ, superoxide dismutase, vimentin, malate dehydrogenase, and lamin B2. These biomarkers could help improve our understanding of the links between PCOS and OC and could potentially be used to identify subgroups of women with PCOS at increased risk of OC. More studies are required to further evaluate the role these biomarkers play in women with PCOS and OC. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  11. Investigating the biomarker potential of glycoproteins using comparative glycoprofiling - application to tissue inhibitor of metalloproteinases-1

    DEFF Research Database (Denmark)

    Thaysen-Andersen, Morten; Thøgersen, Ida; Lademann, Ulrik Axel

    2008-01-01

    Cancer-induced alterations of protein glycosylations are well-known phenomena. Hence, the glycoprofile of certain glycoproteins can potentially be used as biomarkers for early diagnosis. However, there are a substantial number of candidates and the techniques for measuring their biomarker potential...

  12. JELLYFISH GALAXY CANDIDATES AT LOW REDSHIFT

    Energy Technology Data Exchange (ETDEWEB)

    Poggianti, B. M.; Fasano, G.; Omizzolo, A.; Gullieuszik, M.; Bettoni, D.; Paccagnella, A. [INAF-Astronomical Observatory of Padova (Italy); Moretti, A.; D’Onofrio, M. [Physics and Astronomy Department, University of Padova (Italy); Jaffé, Y. L. [Department of Astronomy, Universidad de Concepción, Concepción (Chile); Vulcani, B. [Kavli Institute for the Physics and Mathematics of the universe (WPI), The University of Tokyo Institutes for Advanced Study (UTIAS), the University of Tokyo, Kashiwa, 277-8582 (Japan); Fritz, J. [Centro de Radioastronomía y Astrofísica, CRyA, UNAM, Michoacán (Mexico); Couch, W. [Australian Astronomical Observatory, North Ryde, NSW 1670 (Australia)

    2016-03-15

    Galaxies that are being stripped of their gas can sometimes be recognized from their optical appearance. Extreme examples of stripped galaxies are the so-called “jellyfish galaxies” that exhibit tentacles of debris material with a characteristic jellyfish morphology. We have conducted the first systematic search for galaxies that are being stripped of their gas at low-z (z = 0.04−0.07) in different environments, selecting galaxies with varying degrees of morphological evidence for stripping. We have visually inspected B- and V-band images and identified 344 candidates in 71 galaxy clusters of the OMEGAWINGS+WINGS sample and 75 candidates in groups and lower mass structures in the PM2GC sample. We present the atlas of stripping candidates and a first analysis of their environment and their basic properties, such as morphologies, star formation rates and galaxy stellar masses. Candidates are found in all clusters and at all clustercentric radii, and their number does not correlate with the cluster velocity dispersion σ or X-ray luminosity L{sub X}. Interestingly, convincing cases of candidates are also found in groups and lower mass halos (10{sup 11}−10{sup 14}M{sub ⊙}), although the physical mechanism at work needs to be securely identified. All the candidates are disky, have stellar masses ranging from log M/M{sub ⊙} < 9 to > 11.5 and the majority of them form stars at a rate that is on average a factor of 2 higher (2.5σ) compared to non-stripped galaxies of similar mass. The few post-starburst and passive candidates have weak stripping evidence. We conclude that disturbed morphologies suggestive of stripping phenomena are ubiquitous in clusters and could be present even in groups and low mass halos. Further studies will reveal the physics of the gas stripping and clarify the mechanisms at work.

  13. Biomarkers in Autism

    Directory of Open Access Journals (Sweden)

    Robert eHendren

    2014-08-01

    Full Text Available Autism spectrum disorders (ASD are complex, heterogeneous disorders caused by an interaction between genetic vulnerability and environmental factors. In an effort to better target the underlying roots of ASD for diagnosis and treatment, efforts to identify reliable biomarkers in genetics, neuroimaging, gene expression and measures of the body’s metabolism are growing. For this article, we review the published studies of potential biomarkers in autism and conclude that while there is increasing promise of finding biomarkers that can help us target treatment, there are none with enough evidence to support routine clinical use unless medical illness is suspected. Promising biomarkers include those for mitochondrial function, oxidative stress, and immune function. Genetic clusters are also suggesting the potential for useful biomarkers.

  14. SUSY Searches at ATLAS

    CERN Document Server

    Mamuzic, Judita; The ATLAS collaboration

    2017-01-01

    Supersymmetry (SUSY) is considered one of the best motivated extensions of the Standard Model. It postulates a fundamental symmetry between fermions and bosons, and introduces a set of new supersymmetric particles at the electroweak scale. It addresses the hierarchy and naturalness problem, gives a solution to the gauge coupling unification, and offers a cold dark matter candidate. Different aspects of SUSY searches, using strong, electroweak, third generation production, and R-parity violation and long lived particles are being studied at the LHC. An overview of most recent SUSY searches results using the 13 TeV ATLAS RUN2 data will be presented.

  15. Dark matter candidates

    International Nuclear Information System (INIS)

    Turner, M.S.

    1989-01-01

    One of the simplest, yet most profound, questions we can ask about the Universe is, how much stuff is in it, and further what is that stuff composed of? Needless to say, the answer to this question has very important implications for the evolution of the Universe, determining both the ultimate fate and the course of structure formation. Remarkably, at this late date in the history of the Universe we still do not have a definitive answer to this simplest of questions---although we have some very intriguing clues. It is known with certainty that most of the material in the Universe is dark, and we have the strong suspicion that the dominant component of material in the Cosmos is not baryons, but rather is exotic relic elementary particles left over from the earliest, very hot epoch of the Universe. If true, the Dark Matter question is a most fundamental one facing both particle physics and cosmology. The leading particle dark matter candidates are: the axion, the neutralino, and a light neutrino species. All three candidates are accessible to experimental tests, and experiments are now in progress. In addition, there are several dark horse, long shot, candidates, including the superheavy magnetic monopole and soliton stars. 13 refs

  16. Preclinical Validation of Salivary Biomarkers for Primary Sjogren's Syndrome

    NARCIS (Netherlands)

    Hu, Shen; Gao, Kai; Pollard, Rodney; Arellano-Garcia, Martha; Zhou, Hui; Zhang, Lei; Elashoff, David; Kallenberg, Cees G. M.; Vissink, Arjan; Wong, David T.

    2010-01-01

    Objective. Sjogren's syndrome (SS) is a systemic autoimmune disease with a variety of presenting symptoms that may delay its diagnosis. We previously discovered a number of candidate salivary biomarkers for primary SS using both mass spectrometry and expression microarray analysis. In the current

  17. Metabolomics approach for discovering disease biomarkers and understanding metabolic pathway

    Directory of Open Access Journals (Sweden)

    Jeeyoun Jung

    2011-12-01

    Full Text Available Metabolomics, the multi-targeted analysis of endogenous metabolites from biological samples, can be efficiently applied to screen disease biomarkers and investigate pathophysiological processes. Metabolites change rapidly in response to physiological perturbations, making them the closest link to disease phenotypes. This study explored the role of metabolomics in gaining mechanistic insight into disease processes and in searching for novel biomarkers of human diseases

  18. Characterization of potential ionizing radiation biomarkers by a proteomic approach

    Energy Technology Data Exchange (ETDEWEB)

    Guipaud, O; Vereycken-Holler, V; Benderitter, M [Institut de Radioprotection et de Surete Nucleaire, Lab. de Radiopathologie, 92 - Fontenay aux Roses (France); Royer, N; Vinh, J [Ecole Superieure de Physique et de Chimie Industrielles, 75 - Paris (France)

    2006-07-01

    Radio-induced lesions are tissue specific, hardly predictable, and can arise months or years later. The finding of prognostic bio-markers is of fundamental relevance for the settlement of therapeutic or preventive strategies. Using two-dimensional gel electrophoresis and mass spectrometry, a proteomic study was applied to look for differentially expressed proteins, i.e. potential bio-markers candidates, in mouse serums after a local irradiation of the dorsal skin. Our results clearly indicated that serum protein content was dynamically modified after a local skin irradiation. A set of specific proteins were early down- or up-regulated and could turn out to be good candidates as diagnostic or prognostic bio-markers. (author)

  19. Characterization of potential ionizing radiation biomarkers by a proteomic approach

    International Nuclear Information System (INIS)

    Guipaud, O.; Vereycken-Holler, V.; Benderitter, M.; Royer, N.; Vinh, J.

    2006-01-01

    Radio-induced lesions are tissue specific, hardly predictable, and can arise months or years later. The finding of prognostic bio-markers is of fundamental relevance for the settlement of therapeutic or preventive strategies. Using two-dimensional gel electrophoresis and mass spectrometry, a proteomic study was applied to look for differentially expressed proteins, i.e. potential bio-markers candidates, in mouse serums after a local irradiation of the dorsal skin. Our results clearly indicated that serum protein content was dynamically modified after a local skin irradiation. A set of specific proteins were early down- or up-regulated and could turn out to be good candidates as diagnostic or prognostic bio-markers. (author)

  20. Random searching

    International Nuclear Information System (INIS)

    Shlesinger, Michael F

    2009-01-01

    There are a wide variety of searching problems from molecules seeking receptor sites to predators seeking prey. The optimal search strategy can depend on constraints on time, energy, supplies or other variables. We discuss a number of cases and especially remark on the usefulness of Levy walk search patterns when the targets of the search are scarce.

  1. Identification of a novel panel of cerebrospinal fluid biomarkers for Alzheimer's disease

    DEFF Research Database (Denmark)

    Simonsen, A.H.; McGuire, J.; Podust, V.N.

    2008-01-01

    samples from AD patients (n=95) and population-based healthy controls (n=72) were analyzed by SELDI-TOF-MS in order to discover and characterize novel candidate biomarker combinations that differentiate AD patients from normal aging in this explorative study. Thirty candidate biomarkers (ROC AUC>0.7) were...... healthy control individuals with high sensitivity (97%) and specificity (98%). The panel of five markers was tested on a blinded independent data set of 30 AD samples and 28 controls giving 100% sensitivity and 97% specificity. This novel panel of biomarkers could potentially be used to improve...

  2. Search Patterns

    CERN Document Server

    Morville, Peter

    2010-01-01

    What people are saying about Search Patterns "Search Patterns is a delight to read -- very thoughtful and thought provoking. It's the most comprehensive survey of designing effective search experiences I've seen." --Irene Au, Director of User Experience, Google "I love this book! Thanks to Peter and Jeffery, I now know that search (yes, boring old yucky who cares search) is one of the coolest ways around of looking at the world." --Dan Roam, author, The Back of the Napkin (Portfolio Hardcover) "Search Patterns is a playful guide to the practical concerns of search interface design. It cont

  3. The potential biomarkers of drug addiction: proteomic and metabolomics challenges.

    Science.gov (United States)

    Wang, Lv; Wu, Ning; Zhao, Tai-Yun; Li, Jin

    2016-07-28

    Drug addiction places a significant burden on society and individuals. Proteomics and metabolomics approaches pave the road for searching potential biomarkers to assist the diagnosis and treatment. This review summarized putative drug addiction-related biomarkers in proteomics and metabolomics studies and discussed challenges and prospects in future studies. Alterations of several hundred proteins and metabolites were reported when exposure to abused drug, which enriched in energy metabolism, oxidative stress response, protein modification and degradation, synaptic function and neurotrasmission, etc. Hsp70, peroxiredoxin-6 and α- and β-synuclein, as well as n-methylserotonin and purine metabolites, were promising as potential biomarker for drug addiction.

  4. Systems Biology Genetic Approach Identifies Serotonin Pathway as a Possible Target for Obstructive Sleep Apnea: Results from a Literature Search Review

    Directory of Open Access Journals (Sweden)

    Ram Jagannathan

    2017-01-01

    Full Text Available Rationale. Overall validity of existing genetic biomarkers in the diagnosis of obstructive sleep apnea (OSA remains unclear. The objective of this systematic genetic study is to identify “novel” biomarkers for OSA using systems biology approach. Methods. Candidate genes for OSA were extracted from PubMed, MEDLINE, and Embase search engines and DisGeNET database. The gene ontology (GO analyses and candidate genes prioritization were performed using Enrichr tool. Genes pertaining to the top 10 pathways were extracted and used for Ingenuity Pathway Analysis. Results. In total, we have identified 153 genes. The top 10 pathways associated with OSA include (i serotonin receptor interaction, (ii pathways in cancer, (iii AGE-RAGE signaling in diabetes, (iv infectious diseases, (v serotonergic synapse, (vi inflammatory bowel disease, (vii HIF-1 signaling pathway, (viii PI3-AKT signaling pathway, (ix regulation lipolysis in adipocytes, and (x rheumatoid arthritis. After removing the overlapping genes, we have identified 23 candidate genes, out of which >30% of the genes were related to the genes involved in the serotonin pathway. Among these 4 serotonin receptors SLC6A4, HTR2C, HTR2A, and HTR1B were strongly associated with OSA. Conclusions. This preliminary report identifies several potential candidate genes associated with OSA and also describes the possible regulatory mechanisms.

  5. Prognostic biomarkers in osteoarthritis

    Science.gov (United States)

    Attur, Mukundan; Krasnokutsky-Samuels, Svetlana; Samuels, Jonathan; Abramson, Steven B.

    2013-01-01

    Purpose of review Identification of patients at risk for incident disease or disease progression in osteoarthritis remains challenging, as radiography is an insensitive reflection of molecular changes that presage cartilage and bone abnormalities. Thus there is a widely appreciated need for biochemical and imaging biomarkers. We describe recent developments with such biomarkers to identify osteoarthritis patients who are at risk for disease progression. Recent findings The biochemical markers currently under evaluation include anabolic, catabolic, and inflammatory molecules representing diverse biological pathways. A few promising cartilage and bone degradation and synthesis biomarkers are in various stages of development, awaiting further validation in larger populations. A number of studies have shown elevated expression levels of inflammatory biomarkers, both locally (synovial fluid) and systemically (serum and plasma). These chemical biomarkers are under evaluation in combination with imaging biomarkers to predict early onset and the burden of disease. Summary Prognostic biomarkers may be used in clinical knee osteoarthritis to identify subgroups in whom the disease progresses at different rates. This could facilitate our understanding of the pathogenesis and allow us to differentiate phenotypes within a heterogeneous knee osteoarthritis population. Ultimately, such findings may help facilitate the development of disease-modifying osteoarthritis drugs (DMOADs). PMID:23169101

  6. Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Guiot, Julien; Moermans, Catherine; Henket, Monique; Corhay, Jean-Louis; Louis, Renaud

    2017-06-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging. This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality). Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers.

  7. A systematic review of biomarkers in the diagnosis of infective endocarditis.

    Science.gov (United States)

    Snipsøyr, Magnus G; Ludvigsen, Maja; Petersen, Eskild; Wiggers, Henrik; Honoré, Bent

    2016-01-01

    Timely diagnosis of bacterial infective endocarditis (IE) is crucial, as mortality remains high in this severe bacterial infection, currently without any distinct biological markers. Our goal was to evaluate potential diagnostic biomarkers by reviewing current literature. The MEDLINE, Embase and Scopus databases were searched for articles published from 1980 through June 2015 restricted to English, Norwegian, Danish and Swedish. Eighteen studies qualified, providing a review of the most promising candidates for future studies. Several studies are inconclusive, since they are characterized by using improper control groups. Patients with IE have bacteremia, and control groups should therefore be patients with bacteremia without IE. Based on current research, N-terminal-pro-B-type natriuretic peptide (NT-proBNP) alone or in combination with Cystatin C (Cys C), lipopolysaccharide-binding protein (LBP), troponins, aquaporin-9 (AQP9), S100 calcium binding protein A11 (S100A11), E-selectin (CD62E) and VCAM-1 (CD54) and interleukin-6 (IL-6) are potential biomarkers for future studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Mass Spectrometry-Based Biomarker Discovery.

    Science.gov (United States)

    Zhou, Weidong; Petricoin, Emanuel F; Longo, Caterina

    2017-01-01

    The discovery of candidate biomarkers within the entire proteome is one of the most important and challenging goals in proteomic research. Mass spectrometry-based proteomics is a modern and promising technology for semiquantitative and qualitative assessment of proteins, enabling protein sequencing and identification with exquisite accuracy and sensitivity. For mass spectrometry analysis, protein extractions from tissues or body fluids and subsequent protein fractionation represent an important and unavoidable step in the workflow for biomarker discovery. Following extraction of proteins, the protein mixture must be digested, reduced, alkylated, and cleaned up prior to mass spectrometry. The aim of our chapter is to provide comprehensible and practical lab procedures for sample digestion, protein fractionation, and subsequent mass spectrometry analysis.

  9. Biomarkers in Prodromal Parkinson Disease: a Qualitative Review.

    Science.gov (United States)

    Cooper, Christine A; Chahine, Lama M

    2016-11-01

    Over the past several years, the concept of prodromal Parkinson disease (PD) has been increasingly recognized. This term refers to individuals who do not fulfill motor diagnostic criteria for PD, but who have clinical, genetic, or biomarker characteristics suggesting risk of developing PD in the future. Clinical diagnosis of prodromal PD has low specificity, prompting the need for objective biomarkers with higher specificity. In this qualitative review, we discuss objectively defined putative biomarkers for PD and prodromal PD. We searched Pubmed and Embase for articles pertaining to objective biomarkers for PD and their application in prodromal cohorts. Articles were selected based on relevance and methodology. Objective biomarkers of demonstrated utility in prodromal PD include ligand-based imaging and transcranial sonography. Development of serum, cerebrospinal fluid, and tissue-based biomarkers is underway, but their application in prodromal PD has yet to meaningfully occur. Combining objective biomarkers with clinical or genetic prodromal features increases the sensitivity and specificity for identifying prodromal PD. Several objective biomarkers for prodromal PD show promise but require further study, including their application to and validation in prodromal cohorts followed longitudinally. Accurate identification of prodromal PD will likely require a multimodal approach. (JINS, 2016, 22, 956-967).

  10. amphibian_biomarker_data

    Data.gov (United States)

    U.S. Environmental Protection Agency — Amphibian metabolite data used in Snyder, M.N., Henderson, W.M., Glinski, D.G., Purucker, S. T., 2017. Biomarker analysis of american toad (Anaxyrus americanus) and...

  11. Biomarkers in Alzheimer’s Disease Analysis by Mass Spectrometry-Based Proteomics

    Directory of Open Access Journals (Sweden)

    Yahui Liu

    2014-05-01

    Full Text Available Alzheimer’s disease (AD is a common chronic and destructive disease. The early diagnosis of AD is difficult, thus the need for clinically applicable biomarkers development is growing rapidly. There are many methods to biomarker discovery and identification. In this review, we aim to summarize Mass spectrometry (MS-based proteomics studies on AD and discuss thoroughly the methods to identify candidate biomarkers in cerebrospinal fluid (CSF and blood. This review will also discuss the potential research areas on biomarkers.

  12. Utilization of metabonomics to identify serum biomarkers in murine H22 hepatocarcinoma and deduce antitumor mechanism of Rhizoma Paridis saponins.

    Science.gov (United States)

    Qiu, Peiyu; Man, Shuli; Yang, He; Fan, Wei; Yu, Peng; Gao, Wenyuan

    2016-08-25

    Murine H22 hepatocarcinoma model is so popular to be used for the preclinical anticancer candidate's evaluation. However, the metabolic biomarkers of this model were not identified. Meanwhile, Rhizoma Paridis saponins (RPS) as natural products have been found to show strong antitumor activity, while its anti-cancer mechanism is not clear. To search for potential metabolite biomarkers of this model, serum metabonomics approach was applied to detect the variation of metabolite biomarkers and the related metabolism genes and signaling pathway were used to deduce the antitumor mechanisms of RPS. As a result, ten serum metabolites were identified in twenty-four mice including healthy mice, non-treated cancer mice, RPS-treated cancer mice and RPS-treated healthy mice. RPS significantly decreased tumor weight correlates to down-regulating lactate, acetate, N-acetyl amino acid and glutamine signals (p < 0.05), which were marked metabolites screened according to the very important person (VIP), loading plot and receiver operating characteristic curve (ROC) tests. For the analysis of metabolic enzyme related genes, RPS reversed the aerobic glycolysis through activating tumor suppressor p53 and PTEN, and suppressed FASN to inhibit lipogenesis. What's more, RPS repressed Myc and GLS expression and decreased glutamine level. The regulating PI3K/Akt/mTOR and HIF-1α/Myc/Ras networks also participated in these metabolic changes. Taken together, RPS suppressed ATP product made the tumor growth slow, which indicated a good anti-cancer effect and new angle for understanding the mechanism of RPS. In conclusion, this study demonstrated that the utility of (1)H NMR metabolic profiles taken together with tumor weight and viscera index was a promising screening tool for evaluating the antitumor effect of candidates. In addition, RPS was a potent anticancer agent through inhibiting cancer cellular metabolism to suppress proliferation in hepatoma H22 tumor murine, which promoted the

  13. Scrutinizing the Biomarkers for the Neglected Chagas Disease: How Remarkable!

    Science.gov (United States)

    Pinho, Rosa T; Waghabi, Mariana C; Cardillo, Fabíola; Mengel, José; Antas, Paulo R Z

    2016-01-01

    Biomarkers or biosignature profiles have become accessible over time in population-based studies for Chagas disease. Thus, the identification of consistent and reliable indicators of the diagnosis and prognosis of patients with heart failure might facilitate the prioritization of therapeutic management to those with the highest chance of contracting this disease. The purpose of this paper is to review the recent state and the upcoming trends in biomarkers for human Chagas disease. As an emerging concept, we propose a classification of biomarkers based on plasmatic-, phenotype-, antigenic-, genetic-, and management-related candidates. The available data revisited here reveal the lessons learned thus far and the existing challenges that still lie ahead to enable biomarkers to be employed consistently in risk evaluation for this disease. There is a strong need for biomarker validation, particularly for biomarkers that are specific to the clinical forms of Chagas disease. The current failure to achieve the eradication of the transmission of this disease has produced determination to solve this validation issue. Finally, it would be strategic to develop a wide variety of biomarkers and to test them in both preclinical and clinical trials.

  14. Optimized candidal biofilm microtiter assay

    NARCIS (Netherlands)

    Krom, Bastiaan P.; Cohen, Jesse B.; Feser, Gail E. McElhaney; Cihlar, Ronald L.

    Microtiter based candidal biofilm formation is commonly being used. Here we describe the analysis of factors influencing the development of candidal biofilms such as the coating with serum, growth medium and pH. The data reported here show that optimal candidal biofilm formation is obtained when

  15. Particle Dark Matter: Status and Searches

    OpenAIRE

    Sandick, Pearl

    2010-01-01

    A brief overview is given of the phenomenology of particle dark matter and the properties of some of the most widely studied dark matter candidates. Recent developments in direct and indirect dark matter searches are discussed.

  16. Oriented regions grouping based candidate proposal for infrared pedestrian detection

    Science.gov (United States)

    Wang, Jiangtao; Zhang, Jingai; Li, Huaijiang

    2018-04-01

    Effectively and accurately locating the positions of pedestrian candidates in image is a key task for the infrared pedestrian detection system. In this work, a novel similarity measuring metric is designed. Based on the selective search scheme, the developed similarity measuring metric is utilized to yield the possible locations for pedestrian candidate. Besides this, corresponding diversification strategies are also provided according to the characteristics of the infrared thermal imaging system. Experimental results indicate that the presented scheme can achieve more efficient outputs than the traditional selective search methodology for the infrared pedestrian detection task.

  17. Personalized Search

    CERN Document Server

    AUTHOR|(SzGeCERN)749939

    2015-01-01

    As the volume of electronically available information grows, relevant items become harder to find. This work presents an approach to personalizing search results in scientific publication databases. This work focuses on re-ranking search results from existing search engines like Solr or ElasticSearch. This work also includes the development of Obelix, a new recommendation system used to re-rank search results. The project was proposed and performed at CERN, using the scientific publications available on the CERN Document Server (CDS). This work experiments with re-ranking using offline and online evaluation of users and documents in CDS. The experiments conclude that the personalized search result outperform both latest first and word similarity in terms of click position in the search result for global search in CDS.

  18. Serologic and molecular biomarkers for recurrence of hepatocellular carcinoma after liver transplantation

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Burcharth, Jakob Hornstrup Frølunde; Rosenberg, Jacob

    2016-01-01

    INTRODUCTION: Recurrence after liver transplantation (LT) for hepatocellular carcinoma (HCC) is a major cause of mortality. Knowledge on biomarkers may contribute to better surveillance based on the patients' risk of recurrence. Reviewing the literature, we aimed to identify serological...... and molecular biomarkers for recurrence of hepatocellular carcinoma after liver transplantation. METHODS: A literature search was performed in the databases PubMed and Scopus to identify observational studies evaluating serological or molecular biomarkers for recurrence of HCC after LT using adjusted analysis...

  19. Improved multimodal biomarkers for Alzheimer's disease and mild cognitive impairment diagnosis: data from ADNI

    Science.gov (United States)

    Martinez-Torteya, Antonio; Treviño-Alvarado, Víctor; Tamez-Peña, José

    2013-02-01

    The accurate diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) confers many clinical research and patient care benefits. Studies have shown that multimodal biomarkers provide better diagnosis accuracy of AD and MCI than unimodal biomarkers, but their construction has been based on traditional statistical approaches. The objective of this work was the creation of accurate AD and MCI diagnostic multimodal biomarkers using advanced bioinformatics tools. The biomarkers were created by exploring multimodal combinations of features using machine learning techniques. Data was obtained from the ADNI database. The baseline information (e.g. MRI analyses, PET analyses and laboratory essays) from AD, MCI and healthy control (HC) subjects with available diagnosis up to June 2012 was mined for case/controls candidates. The data mining yielded 47 HC, 83 MCI and 43 AD subjects for biomarker creation. Each subject was characterized by at least 980 ADNI features. A genetic algorithm feature selection strategy was used to obtain compact and accurate cross-validated nearest centroid biomarkers. The biomarkers achieved training classification accuracies of 0.983, 0.871 and 0.917 for HC vs. AD, HC vs. MCI and MCI vs. AD respectively. The constructed biomarkers were relatively compact: from 5 to 11 features. Those multimodal biomarkers included several widely accepted univariate biomarkers and novel image and biochemical features. Multimodal biomarkers constructed from previously and non-previously AD associated features showed improved diagnostic performance when compared to those based solely on previously AD associated features.

  20. What is a biomarker? Research investments and lack of clinical integration necessitate a review of biomarker terminology and validation schema.

    Science.gov (United States)

    Ptolemy, Adam S; Rifai, Nader

    2010-01-01

    A continual trend of annual growth can be seen within research devoted to the discovery and validation of disease biomarkers within both the natural and clinical sciences. This expansion of intellectual endeavours was quantified through database searches of (a) research grant awards provided by the various branches of the National Institutes of Health (NIH) and (b) academic publications. A search of awards presented between 1986 and 2009 revealed a total of 28,856 grants awarded by the NIH containing the term "biomarker". The total funds for these awards in 2008 and 2009 alone were over $2.5 billion. During the same respective time frames, searches of "biomarker" and either "discovery", "genomics", "proteomics" or "metabolomics" yielded a total of 4,928 NIH grants whose combined funding exceeded $1.2 billion. The derived trend in NIH awards paralleled the annual expansion in "biomarker" literature. A PubMed search for the term, between 1990 and 2009, revealed a total of 441,510 published articles, with 38,457 published in 2008. These enormous investments and academic outputs however have not translated into the expected integration of new biomarkers for patient care. For example no proteomics derived biomarkers are currently being utilized in routine clinical management. This translational chasm necessitates a review of the previously proposed biomarker definitions and evaluation schema. A subsequent discussion of both the analytical and pre-analytical considerations for such research is also presented within. This required knowledge should aid scientists in their pursuit and validation of new biological markers of disease.

  1. Search for infrared counterparts of gamma-ray bursters

    International Nuclear Information System (INIS)

    Schaefer, B.E.; Cline, T.L.

    1985-01-01

    The result of two searches for infrared counterparts of Gamma-ray Bursters (GRB's) is reported. The first search was made using data from the Infrared Astronomy Satellite and covered 23 positions. The second search was made with the Kitt Peak 1.5 m telescope and covered 3 positions. In neither of these two searches was any infrared candidate detected

  2. Atacama Rover Astrobiology Drilling Studies: Roving to Find Subsurface Preserved Biomarkers

    Science.gov (United States)

    Glass, B.; Davila, A.; Parro, V.; Quinn, R.; Willis, P.; Brinckerhoff, W.; DiRuggiero, J.; Williams, M.; Bergman, D.; Stoker, C.

    2016-05-01

    The ARADS project is a NASA PSTAR that will drill into a Mars analog site in search of biomarkers. Leading to a field test of an integrated rover-drill system with four prototype in-situ instruments for biomarker detection and analysis.

  3. Biomarkers of sepsis

    Science.gov (United States)

    2013-01-01

    Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

  4. Identification of biomarkers for genotyping Aspergilli using non-linear methods for clustering and classification

    DEFF Research Database (Denmark)

    Kouskoumvekaki, Irene; Yang, Zhiyong; Jonsdottir, Svava Osk

    2008-01-01

    Background: In the present investigation, we have used an exhaustive metabolite profiling approach to search for biomarkers in recombinant Aspergillus nidulans (mutants that produce the 6- methyl salicylic acid polyketide molecule) for application in metabolic engineering. Results: More than 450...

  5. Biomarkers for severity of spinal cord injury in the cerebrospinal fluid of rats.

    Directory of Open Access Journals (Sweden)

    Joanna M Lubieniecka

    Full Text Available One of the major challenges in management of spinal cord injury (SCI is that the assessment of injury severity is often imprecise. Identification of reliable, easily quantifiable biomarkers that delineate the severity of the initial injury and that have prognostic value for the degree of functional recovery would significantly aid the clinician in the choice of potential treatments. To find such biomarkers we performed quantitative liquid chromatography-mass spectrometry (LC-MS/MS analyses of cerebrospinal fluid (CSF collected from rats 24 h after either a moderate or severe SCI. We identified a panel of 42 putative biomarkers of SCI, 10 of which represent potential biomarkers of SCI severity. Three of the candidate biomarkers, Ywhaz, Itih4, and Gpx3 were also validated by Western blot in a biological replicate of the injury. The putative biomarkers identified in this study may potentially be a valuable tool in the assessment of the extent of spinal cord damage.

  6. Biomarkers for Severity of Spinal Cord Injury in the Cerebrospinal Fluid of Rats

    Science.gov (United States)

    Lubieniecka, Joanna M.; Streijger, Femke; Lee, Jae H. T.; Stoynov, Nikolay; Liu, Jie; Mottus, Randy; Pfeifer, Tom; Kwon, Brian K.; Coorssen, Jens R.; Foster, Leonard J.; Grigliatti, Thomas A.; Tetzlaff, Wolfram

    2011-01-01

    One of the major challenges in management of spinal cord injury (SCI) is that the assessment of injury severity is often imprecise. Identification of reliable, easily quantifiable biomarkers that delineate the severity of the initial injury and that have prognostic value for the degree of functional recovery would significantly aid the clinician in the choice of potential treatments. To find such biomarkers we performed quantitative liquid chromatography-mass spectrometry (LC-MS/MS) analyses of cerebrospinal fluid (CSF) collected from rats 24 h after either a moderate or severe SCI. We identified a panel of 42 putative biomarkers of SCI, 10 of which represent potential biomarkers of SCI severity. Three of the candidate biomarkers, Ywhaz, Itih4, and Gpx3 were also validated by Western blot in a biological replicate of the injury. The putative biomarkers identified in this study may potentially be a valuable tool in the assessment of the extent of spinal cord damage. PMID:21559420

  7. Mass spectrometry for biomarker development

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Chaochao; Liu, Tao; Baker, Erin Shammel; Rodland, Karin D.; Smith, Richard D.

    2015-06-19

    Biomarkers potentially play a crucial role in early disease diagnosis, prognosis and targeted therapy. In the past decade, mass spectrometry based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g. shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy in the different stages in biomarker development, with a particular emphasis on blood biomarker development.

  8. Biomarkers in the early diagnosis of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    CHEN Sheng-di

    2013-08-01

    Full Text Available Parkinson's disease (PD is a chronic and progressive neurodegenerative disorder. It has become clear that PD can have a preclinical phase, a period during which neurodegeneration has already begun years before the onset of typical motor symptoms. Consequently, if the early neurodegeneration in PD can be timely diagnosed, it will significantly slow down the progression of the disease and improve the quality of life. To date, there is no fully reliable and validated biomarker for the early diagnosis of PD, but some promising biomarker candidates exist.

  9. Biomarkers of the Dementia

    Directory of Open Access Journals (Sweden)

    Mikio Shoji

    2011-01-01

    Full Text Available Recent advances in biomarker studies on dementia are summarized here. CSF Aβ40, Aβ42, total tau, and phosphorylated tau are the most sensitive biomarkers for diagnosis of Alzheimer's disease (AD and prediction of onset of AD from mild cognitive impairment (MCI. Based on this progress, new diagnostic criteria for AD, MCI, and preclinical AD were proposed by National Institute of Aging (NIA and Alzheimer's Association in August 2010. In these new criteria, progress in biomarker identification and amyloid imaging studies in the past 10 years have added critical information. Huge contributions of basic and clinical studies have established clinical evidence supporting these markers. Based on this progress, essential therapy for cure of AD is urgently expected.

  10. Inflammatory biomarkers and cancer

    DEFF Research Database (Denmark)

    Rasmussen, Line Jee Hartmann; Schultz, Martin; Gaardsting, Anne

    2017-01-01

    and previous cancer diagnoses compared to patients who were not diagnosed with cancer. Previous cancer, C-reactive protein (CRP) and suPAR were significantly associated with newly diagnosed cancer during follow-up in multiple logistic regression analyses adjusted for age, sex and CRP. Neither any of the PRRs......In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including...... soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin-3, mannose-binding lectin, ficolin-1, ficolin-2 and ficolin-3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer...

  11. Urine Exosomes: An Emerging Trove of Biomarkers.

    Science.gov (United States)

    Street, J M; Koritzinsky, E H; Glispie, D M; Star, R A; Yuen, P S T

    Exosomes are released by most cells and can be isolated from all biofluids including urine. Exosomes are small vesicles formed as part of the endosomal pathway that contain cellular material surrounded by a lipid bilayer that can be traced to the plasma membrane. Exosomes are potentially a more targeted source of material for biomarker discovery than unfractionated urine, and provide diagnostic and pathophysiological information without an invasive tissue biopsy. Cytoplasmic contents including protein, mRNA, miRNA, and lipids have all been studied within the exosomal fraction. Many prospective urinary exosomal biomarkers have been successfully identified for a variety of kidney or genitourinary tract conditions; detection of systemic conditions may also be possible. Isolation and analysis of exosomes can be achieved by several approaches, although many require specialized equipment or involve lengthy protocols. The need for timely analysis in the clinical setting has driven considerable innovation with several promising options recently emerging. Consensus on exosome isolation, characterization, and normalization procedures would resolve critical clinical translational bottlenecks for existing candidate exosomal biomarkers and provide a template for additional discovery studies. 2017 Published by Elsevier Inc.

  12. Search Advertising

    OpenAIRE

    Cornière (de), Alexandre

    2016-01-01

    Search engines enable advertisers to target consumers based on the query they have entered. In a framework with horizontal product differentiation, imperfect product information and in which consumers incur search costs, I study a game in which advertisers have to choose a price and a set of relevant keywords. The targeting mechanism brings about three kinds of efficiency gains, namely lower search costs, better matching, and more intense product market price-competition. A monopolistic searc...

  13. Biomarkers in the Diagnosis and Prognosis of Alzheimer's Disease.

    Science.gov (United States)

    Schaffer, Cole; Sarad, Nakia; DeCrumpe, Ashton; Goswami, Disha; Herrmann, Sara; Morales, Jose; Patel, Parth; Osborne, Jim

    2015-10-01

    Alzheimer's disease (AD) is a neurodegenerative disease that inhibits cognitive functions and has no cure. This report reviews the current diagnostic standards for AD with an emphasis on early diagnosis using the cerebrospinal fluid (CSF) biomarkers amyloid-beta, t-tau, and p-tau and fluorodeoxyglucose positron emission tomography imaging. Abnormal levels of these CSF biomarkers and decreased cerebral uptake of glucose have recently been used in the early diagnosis of AD in experimental studies. These promising biomarkers can be measured using immunoassays performed in singleplex or multiplex formats. Although presently, there are no Food and Drug Administration-approved in vitro diagnostics (IVDs) for early detection of AD, a multiplex immunoassay measuring a panel of promising AD biomarkers in CSF may be a likely IVD candidate for the clinical AD diagnostic market. Specifically, the INNO-BIA AlzBio3 immunoassay kit, performed using bead arrays on the xMAP Luminex analyzer, allows simultaneous quantification of amyloid-beta, t-tau, and p-tau biomarkers. AD biomarkers can also be screened using enzyme-linked immunosorbent assays that are offered as laboratory-developed tests. © 2014 Society for Laboratory Automation and Screening.

  14. Potential biomarkers for bipolar disorder: Where do we stand?

    Directory of Open Access Journals (Sweden)

    Rajesh Sagar

    2017-01-01

    Full Text Available Bipolar disorder (BD is a severe, recurrent mood disorder, associated with a significant morbidity and mortality, with high rates of suicides and medical comorbidities. There is a high risk of mood disorders among the first-degree relatives of patients with BD. In the current clinical practice, the diagnosis of BD is made by history taking, interview and behavioural observations, thereby lacking an objective, biological validation. This approach may result in underdiagnosis, misdiagnosis and eventually poorer outcomes. Due to the heterogeneity of BD, the possibility of developing a single, specific biomarker is still remote; however, there is a set of promising biomarkers which may serve as predictive, prognostic or treatment markers in the future. The review presents a critical appraisal and update on some of the most promising candidates for biomarkers, namely, neuroimaging markers, peripheral biomarkers and genetic markers, including a brief discussion on cognitive endophenotypes as indicative of genetic risk. The lessons learnt from other fields and specialties in medicine need to be applied to psychiatry to translate the knowledge from 'bench to bedside' by means of clinically useful biomarkers. Overall, the biomarkers may help in pushing the shift towards personalized medicine for psychiatric patients.

  15. THE 3 MU-M SPECTRA OF CANDIDATE CARBON STARS

    NARCIS (Netherlands)

    GROENEWEGEN, MAT; DEJONG, T; GEBALLE, TR

    We have searched for the 3.1 mum absorption feature, a well-known characteristic of optical carbon stars, in a sample of sixteen candidate carbon stars, most of which have very red colors and some of which have no optical counterparts. The sample was selected on the basis of similarity of LRS

  16. Elemental abundances of solar sibling candidates

    International Nuclear Information System (INIS)

    Ramírez, I.; Lambert, D. L.; Endl, M.; Cochran, W. D.; MacQueen, P. J.; Bajkova, A. T.; Bobylev, V. V.; Roederer, I. U.; Wittenmyer, R. A.

    2014-01-01

    Dynamical information along with survey data on metallicity and in some cases age have been used recently by some authors to search for candidates of stars that were born in the cluster where the Sun formed. We have acquired high-resolution, high signal-to-noise ratio spectra for 30 of these objects to determine, using detailed elemental abundance analysis, if they could be true solar siblings. Only two of the candidates are found to have solar chemical composition. Updated modeling of the stars' past orbits in a realistic Galactic potential reveals that one of them, HD 162826, satisfies both chemical and dynamical conditions for being a sibling of the Sun. Measurements of rare-element abundances for this star further confirm its solar composition, with the only possible exception of Sm. Analysis of long-term high-precision radial velocity data rules out the presence of hot Jupiters and confirms that this star is not in a binary system. We find that chemical tagging does not necessarily benefit from studying as many elements as possible but instead from identifying and carefully measuring the abundances of those elements that show large star-to-star scatter at a given metallicity. Future searches employing data products from ongoing massive astrometric and spectroscopic surveys can be optimized by acknowledging this fact.

  17. Faceted Search

    CERN Document Server

    Tunkelang, Daniel

    2009-01-01

    We live in an information age that requires us, more than ever, to represent, access, and use information. Over the last several decades, we have developed a modern science and technology for information retrieval, relentlessly pursuing the vision of a "memex" that Vannevar Bush proposed in his seminal article, "As We May Think." Faceted search plays a key role in this program. Faceted search addresses weaknesses of conventional search approaches and has emerged as a foundation for interactive information retrieval. User studies demonstrate that faceted search provides more

  18. Pharmacology of biosimilar candidate drugs in rheumatology: a literature review.

    Science.gov (United States)

    Araújo, F; Cordeiro, I; Teixeira, F; Gonçalves, J; Fonseca, J E

    2014-01-01

    To review current evidence concerning pharmacology of biosimilar candidates to be used in rheumatology. A PubMed search up to August 2013 was performed using relevant search terms to include all studies assessing pharmacological properties of biosimilar candidates to be used in rheumatology. Data on study characteristics, type of intervention, pharmacokinetics (PK), pharmacodynamics (PD) and bioequivalence ratios was extracted. Of 280 articles screened, 5 fulfilled our inclusion criteria. Two trials, PLANETAS and PLANETRA, compared CT-P13 and infliximab in patients with active ankylosing spondylitis and rheumatoid arthritis, respectively. PK bioequivalence was demonstrated in the phase 1 PLANETAS trial by highly comparable area under the curve (AUC) and maximum drug concentrations (Cmax), whose geometric mean ratios fell between the accepted bioequivalence range of 80-125%. Equivalence in efficacy and safety was demonstrated in the phase 3 PLANETRA trial. Two phase 1 trials comparing etanercept biosimilar candidates TuNEX and HD203 in healthy volunteers showed a high degree of similarity in AUC and Cmax, with respective geometric mean ratios between PK bioequivalence range. The last included trial referred to GP2013, a rituximab biosimilar candidate, which demonstrated PK and PD bioequivalence to reference product in three different dosing regimens in cynomolgus monkeys. Infliximab, etanercept and rituximab biosimilar candidates have demonstrated PK bioequivalence in the trials included in this review. CT-P13 has recently been approved for use in the European market and the remaining biosimilar candidates are currently being tested in patients with rheumatoid arthritis.

  19. Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges.

    Science.gov (United States)

    Kim, Dana; Kim, Young Sam; Shin, Dong Wun; Park, Chang Shin; Kang, Ju Hee

    2016-10-01

    No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.

  20. Search for scalar muons

    International Nuclear Information System (INIS)

    Bartel, W.; Becker, L.; Bowdery, C.; Cords, D.; Felst, R.; Haidt, D.; Knies, G.; Krehbiel, H.; Meinke, R.; Naroska, B.; Olsson, J.; Steffen, P.; Junge, H.; Schmidt, D.; Laurikainen, P.; Dietrich, G.; Hagemann, J.; Heinzelmann, G.; Kado, H.; Kleinwort, C.; Kuhlen, M.; Meier, K.; Petersen, A.; Ramcke, R.; Schneekloth, U.; Weber, G.; Allison, J.; Baines, J.; Ball, A.H.; Barlow, R.J.; Chrin, J.; Duerdoth, I.P.; Greenshaw, T.; Hill, P.; Loebinger, F.K.; Macbeth, A.A.; McCann, H.; Mills, H.E.; Murphy, P.G.; Stephens, K.; Warming, P.; Glasser, R.G.; Sechi-Zorn, B.; Skard, J.A.J.; Wagner, S.R.; Zorn, G.T.; Cartwright, S.L.; Clarke, D.; Marshall, R.; Middleton, R.P.; Whittaker, J.B.; Kawamoto, T.; Kobayashi, T.; Mashimo, T.; Minowa, M.; Takeda, H.; Takeshita, T.; Yamada, S.

    1984-12-01

    The supersymmetric partner of the muon was searched for in a systematic way. No candidate was found and 95% CL limits on its mass were given for different cases. If it is stable, the limit is 20.9 GeV/c 2 . If it decays into a muon and an invisible low mass particle, the limit is 20.3 GeV/c 2 . If it decays into a muon and an unstable neutral particle which decays further into a photon and an invisible massless particles, the limit is 19.2 GeV/c 2 . (orig.)

  1. Biomarkers for anorexia nervosa

    DEFF Research Database (Denmark)

    Sjøgren, Jan Magnus

    2017-01-01

    Biomarkers for anorexia nervosa (AN) which reflect the pathophysiology and relate to the aetiology of the disease, are warranted and could bring us one step closer to targeted treatment of AN. Some leads may be found in the biochemistry which often is found disturbed in AN, although normalization...

  2. Advanced Search

    African Journals Online (AJOL)

    Search tips: Search terms are case-insensitive; Common words are ignored; By default only articles containing all terms in the query are returned (i.e., AND is implied); Combine multiple words with OR to find articles containing either term; e.g., education OR research; Use parentheses to create more complex queries; e.g., ...

  3. Biomarkers of cancer cachexia.

    Science.gov (United States)

    Loumaye, Audrey; Thissen, Jean-Paul

    2017-12-01

    Cachexia is a complex multifactorial syndrome, characterized by loss of skeletal muscle and fat mass, which affects the majority of advanced cancer patients and is associated with poor prognosis. Interestingly, reversing muscle loss in animal models of cancer cachexia leads to prolong survival. Therefore, detecting cachexia and maintaining muscle mass represent a major goal in the care of cancer patients. However, early diagnosis of cancer cachexia is currently limited for several reasons. Indeed, cachexia development is variable according to tumor and host characteristics. In addition, safe, accessible and non-invasive tools to detect skeletal muscle atrophy are desperately lacking in clinical practice. Finally, the precise molecular mechanisms and the key players involved in cancer cachexia remain poorly characterized. The need for an early diagnosis of cancer cachexia supports therefore the quest for a biomarker that might reflect skeletal muscle atrophy process. Current research offers different promising ways to identify such a biomarker. Initially, the quest for a biomarker of cancer cachexia has mostly focused on mediators of muscle atrophy, produced by both tumor and host, in an attempt to define new therapeutic approaches. In another hand, molecules released by the muscle into the circulation during the atrophy process have been also considered as potential biomarkers. More recently, several "omics" studies are emerging to identify new muscular or circulating markers of cancer cachexia. Some genetic markers could also contribute to identify patients more susceptible to develop cachexia. This article reviews our current knowledge regarding potential biomarkers of cancer cachexia. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  4. Biomarkers for the Diagnosis of Cholangiocarcinoma: A Systematic Review.

    Science.gov (United States)

    Tshering, Gyem; Dorji, Palden Wangyel; Chaijaroenkul, Wanna; Na-Bangchang, Kesara

    2018-06-01

    Cholangiocarcinoma (CCA), a malignant tumor of the bile duct, is a major public health problem in many Southeast Asian countries, particularly Thailand. The slow progression makes it difficult for early diagnosis and most patients are detected in advanced stages. This study aimed to review all relevant articles related to the biomarkers for the diagnosis of CCA and point out potential biomarkers. A thorough search was performed in PubMed and ScienceDirect for CCA biomarker articles. Required data were extracted. A total of 46 articles that fulfilled the inclusion and had none of the exclusion criteria were included in the analysis (17, 22, 3, 4, and 1 articles on blood, tissue, bile, both blood and tissue, and urine biomarkers, respectively). Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA), either alone or in combination with other biomarkers, are the most commonly studied biomarkers in the serum. Their sensitivity and specificity ranged from 47.2% to 98.2% and 89.7% to 100%, respectively. However, in the tissue, gene methylations and DNA-related markers were the most studied CCA biomarkers. Their sensitivity and specificity ranged from 58% to 87% and 98% to 100%, respectively. Some articles investigated biomarkers both in blood and tissues, particularly CA19-9 and CEA, with sensitivity and specificity ranging from 33% to 100% and 50% to 97.7%, respectively. Although quite a number of biomarkers with a potential role in the early detection of CCA have been established, it is difficult to single out any particular marker that could be used in the routine clinical settings.

  5. Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China

    Directory of Open Access Journals (Sweden)

    Li Zuguo

    2008-06-01

    Full Text Available Abstract Background The pathogenesis of nasopharyngeal carcinoma (NPC is a complicated process involving genetic predisposition, Epstein-Bar Virus infection, and genetic alterations. Although some oncogenes and tumor suppressor genes have been previously reported in NPC, a complete understanding of the pathogenesis of NPC in the context of global gene expression, transcriptional pathways and biomarker assessment remains to be elucidated. Methods Total RNA from 32 pathologically-confirmed cases of poorly-differentiated NPC was divided into pools inclusive of four consecutive specimens and each pool (T1 to T8 was co-hybridized with pooled RNA from 24 normal non-cancerous nasopharyngeal tissues (NP to a human 8K cDNA array platform. The reliability of microarray data was validated for selected genes by semi-quantitative RT-PCR and immunohistochemistry. Results Stringent statistical filtering parameters identified 435 genes to be up-regulated and 257 genes to be down-regulated in NPC compared to NP. Seven up-regulated genes including CYC1, MIF, LAMB3, TUBB2, UBE2C and TRAP1 had been previously proposed as candidate common cancer biomarkers based on a previous extensive comparison among various cancers and normal tissues which did not, however, include NPC or NP. In addition, nine known oncogenes and tumor suppressor genes, MIF, BIRC5, PTTG1, ATM, FOXO1A, TGFBR2, PRKAR1A, KLF5 and PDCD4 were identified through the microarray literature-based annotation search engine MILANO, suggesting these genes may be specifically involved in the promotion of the malignant conversion of nasopharyngeal epithelium. Finally, we found that these differentially expressed genes were involved in apoptosis, MAPK, VEGF and B cell receptor signaling pathways and other functions associated with cell growth, signal transduction and immune system activation. Conclusion This study identified potential candidate biomarkers, oncogenes/tumor suppressor genes involved in several

  6. 275 Candidates and 149 Validated Planets Orbiting Bright Stars in K2 Campaigns 0–10

    DEFF Research Database (Denmark)

    Mayo, Andrew W.; Vanderburg, Andrew; Latham, David W.

    2018-01-01

    Since 2014, NASA’s K2 mission has observed large portions of the ecliptic plane in search of transiting planets and has detected hundreds of planet candidates. With observations planned until at least early 2018, K2 will continue to identify more planet candidates. We present here 275 planet...... candidates observed during Campaigns 0–10 of the K2 mission that are orbiting stars brighter than 13 mag (in Kepler band) and for which we have obtained high-resolution spectra ( R = 44,000). These candidates are analyzed using the vespa package in order to calculate their false-positive probabilities (FPP......). We find that 149 candidates are validated with an FPP lower than 0.1%, 39 of which were previously only candidates and 56 of which were previously undetected. The processes of data reduction, candidate identification, and statistical validation are described, and the demographics of the candidates...

  7. Guidelines for Biomarker of Food Intake Reviews (BFIRev)

    DEFF Research Database (Denmark)

    Praticò, Giulia; Gao, Qian; Scalbert, Augustin

    2018-01-01

    and that the quality of all suggested biomarkers should be systematically evaluated. In order to cover the literature on BFIs in the most appropriate and consistent manner, there is a need for appropriate guidelines on this topic. These guidelines should build upon guidelines in related areas of science while......Identification of new biomarkers of food and nutrient intake has developed fast over the past two decades and could potentially provide important new tools for compliance monitoring and dietary intake assessment in nutrition and health science. In recent years, metabolomics has played an important...... and on validating these as well as other biomarker candidates, thereby providing better tools for future studies in nutrition and health....

  8. Pentaquark searches with ALICE

    CERN Document Server

    Bobulska, Dana

    2016-01-01

    In this report we present the results of the data analysis for searching for possible invariant mass signals from pentaquarks in the ALICE data. Analysis was based on filtered data from real p-Pb events at psNN=5.02 TeV collected in 2013. The motivation for this project was the recent discovery of pentaquark states by the LHCb collaboration (c ¯ cuud resonance P+ c ) [1]. The search for similar not yet observed pentaquarks is an interesting research topic [2]. In this analysis we searched for a s ¯ suud pentaquark resonance P+ s and its possible decay channel to f meson and proton. The ALICE detector is well suited for the search of certain candidates thanks to its low material budget and strong PID capabilities. Additionally we might expect the production of such particles in ALICE as in heavy-ion and proton-ion collisions the thermal models describes well the particle yields and ratios [3]. Therefore it is reasonable to expect other species of hadrons, including also possible pentaquarks, to be produced w...

  9. The serotonin system in autism spectrum disorder: from biomarker to animal models

    OpenAIRE

    Muller, Christopher L.; Anacker, Allison M.J.; Veenstra-VanderWeele, Jeremy

    2015-01-01

    Elevated whole blood serotonin, or hyperserotonemia, was the first biomarker identified in autism spectrum disorder (ASD) and is present in more than 25% of affected children. The serotonin system is a logical candidate for involvement in ASD due to its pleiotropic role across multiple brain systems both dynamically and across development. Tantalizing clues connect this peripheral biomarker with changes in brain and behavior in ASD, but the contribution of the serotonin system to ASD pathophy...

  10. Protein Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma: Progress and Challenges.

    Science.gov (United States)

    Root, Alex; Allen, Peter; Tempst, Paul; Yu, Kenneth

    2018-03-07

    Approximately 75% of patients with pancreatic ductal adenocarcinoma are diagnosed with advanced cancer, which cannot be safely resected. The most commonly used biomarker CA19-9 has inadequate sensitivity and specificity for early detection, which we define as Stage I/II cancers. Therefore, progress in next-generation biomarkers is greatly needed. Recent reports have validated a number of biomarkers, including combination assays of proteins and DNA mutations; however, the history of translating promising biomarkers to clinical utility suggests that several major hurdles require careful consideration by the medical community. The first set of challenges involves nominating and verifying biomarkers. Candidate biomarkers need to discriminate disease from benign controls with high sensitivity and specificity for an intended use, which we describe as a two-tiered strategy of identifying and screening high-risk patients. Community-wide efforts to share samples, data, and analysis methods have been beneficial and progress meeting this challenge has been achieved. The second set of challenges is assay optimization and validating biomarkers. After initial candidate validation, assays need to be refined into accurate, cost-effective, highly reproducible, and multiplexed targeted panels and then validated in large cohorts. To move the most promising candidates forward, ideally, biomarker panels, head-to-head comparisons, meta-analysis, and assessment in independent data sets might mitigate risk of failure. Much more investment is needed to overcome these challenges. The third challenge is achieving clinical translation. To moonshot an early detection test to the clinic requires a large clinical trial and organizational, regulatory, and entrepreneurial know-how. Additional factors, such as imaging technologies, will likely need to improve concomitant with molecular biomarker development. The magnitude of the clinical translational challenge is uncertain, but interdisciplinary

  11. Protein Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Alex Root

    2018-03-01

    Full Text Available Approximately 75% of patients with pancreatic ductal adenocarcinoma are diagnosed with advanced cancer, which cannot be safely resected. The most commonly used biomarker CA19-9 has inadequate sensitivity and specificity for early detection, which we define as Stage I/II cancers. Therefore, progress in next-generation biomarkers is greatly needed. Recent reports have validated a number of biomarkers, including combination assays of proteins and DNA mutations; however, the history of translating promising biomarkers to clinical utility suggests that several major hurdles require careful consideration by the medical community. The first set of challenges involves nominating and verifying biomarkers. Candidate biomarkers need to discriminate disease from benign controls with high sensitivity and specificity for an intended use, which we describe as a two-tiered strategy of identifying and screening high-risk patients. Community-wide efforts to share samples, data, and analysis methods have been beneficial and progress meeting this challenge has been achieved. The second set of challenges is assay optimization and validating biomarkers. After initial candidate validation, assays need to be refined into accurate, cost-effective, highly reproducible, and multiplexed targeted panels and then validated in large cohorts. To move the most promising candidates forward, ideally, biomarker panels, head-to-head comparisons, meta-analysis, and assessment in independent data sets might mitigate risk of failure. Much more investment is needed to overcome these challenges. The third challenge is achieving clinical translation. To moonshot an early detection test to the clinic requires a large clinical trial and organizational, regulatory, and entrepreneurial know-how. Additional factors, such as imaging technologies, will likely need to improve concomitant with molecular biomarker development. The magnitude of the clinical translational challenge is uncertain, but

  12. Novel biomarkers for sepsis

    DEFF Research Database (Denmark)

    Larsen, Frederik Fruergaard; Petersen, J Asger

    2017-01-01

    BACKGROUND: Sepsis is a prevalent condition among hospitalized patients that carries a high risk of morbidity and mortality. Rapid recognition of sepsis as the cause of deterioration is desirable, so effective treatment can be initiated rapidly. Traditionally, diagnosis was based on presence of two...... or more positive SIRS criteria due to infection. However, recently published sepsis-3 criteria put more emphasis on organ dysfunction caused by infection in the definition of sepsis. Regardless of this, no gold standard for diagnosis exist, and clinicians still rely on a number of traditional and novel...... biomarkers to discriminate between patients with and without infection, as the cause of deterioration. METHOD: Narrative review of current literature. RESULTS: A number of the most promising biomarkers for diagnoses and prognostication of sepsis are presented. CONCLUSION: Procalcitonin, presepsin, CD64, su...

  13. Proteome screening of pleural effusions identifies galectin 1 as a diagnostic biomarker and highlights several prognostic biomarkers for malignant mesothelioma.

    Science.gov (United States)

    Mundt, Filip; Johansson, Henrik J; Forshed, Jenny; Arslan, Sertaç; Metintas, Muzaffer; Dobra, Katalin; Lehtiö, Janne; Hjerpe, Anders

    2014-03-01

    Malignant mesothelioma is an aggressive asbestos-induced cancer, and affected patients have a median survival of approximately one year after diagnosis. It is often difficult to reach a conclusive diagnosis, and ancillary measurements of soluble biomarkers could increase diagnostic accuracy. Unfortunately, few soluble mesothelioma biomarkers are suitable for clinical application. Here we screened the effusion proteomes of mesothelioma and lung adenocarcinoma patients to identify novel soluble mesothelioma biomarkers. We performed quantitative mass-spectrometry-based proteomics using isobaric tags for quantification and used narrow-range immobilized pH gradient/high-resolution isoelectric focusing (pH 4-4.25) prior to analysis by means of nano liquid chromatography coupled to MS/MS. More than 1,300 proteins were identified in pleural effusions from patients with malignant mesothelioma (n = 6), lung adenocarcinoma (n = 6), or benign mesotheliosis (n = 7). Data are available via ProteomeXchange with identifier PXD000531. The identified proteins included a set of known mesothelioma markers and proteins that regulate hallmarks of cancer such as invasion, angiogenesis, and immune evasion, plus several new candidate proteins. Seven candidates (aldo-keto reductase 1B10, apolipoprotein C-I, galectin 1, myosin-VIIb, superoxide dismutase 2, tenascin C, and thrombospondin 1) were validated by enzyme-linked immunosorbent assays in a larger group of patients with mesothelioma (n = 37) or metastatic carcinomas (n = 25) and in effusions from patients with benign, reactive conditions (n = 16). Galectin 1 was identified as overexpressed in effusions from lung adenocarcinoma relative to mesothelioma and was validated as an excellent predictor for metastatic carcinomas against malignant mesothelioma. Galectin 1, aldo-keto reductase 1B10, and apolipoprotein C-I were all identified as potential prognostic biomarkers for malignant mesothelioma. This analysis of the effusion proteome

  14. Autonomous search

    CERN Document Server

    Hamadi, Youssef; Saubion, Frédéric

    2012-01-01

    Autonomous combinatorial search (AS) represents a new field in combinatorial problem solving. Its major standpoint and originality is that it considers that problem solvers must be capable of self-improvement operations. This is the first book dedicated to AS.

  15. Development of a biomarkers database for the National Children's Study

    Energy Technology Data Exchange (ETDEWEB)

    Lobdell, Danelle T [US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Human Studies Division, Epidemiology and Biomarkers Branch, MD 58A, Research Triangle Park, NC 27711 (United States); Mendola, Pauline [US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Human Studies Division, Epidemiology and Biomarkers Branch, MD 58A, Research Triangle Park, NC 27711 (United States)

    2005-08-07

    The National Children's Study (NCS) is a federally-sponsored, longitudinal study of environmental influences on the health and development of children across the United States (www.nationalchildrensstudy.gov). Current plans are to study approximately 100,000 children and their families beginning before birth up to age 21 years. To explore potential biomarkers that could be important measurements in the NCS, we compiled the relevant scientific literature to identify both routine or standardized biological markers as well as new and emerging biological markers. Although the search criteria encouraged examination of factors that influence the breadth of child health and development, attention was primarily focused on exposure, susceptibility, and outcome biomarkers associated with four important child health outcomes: autism and neurobehavioral disorders, injury, cancer, and asthma. The Biomarkers Database was designed to allow users to: (1) search the biomarker records compiled by type of marker (susceptibility, exposure or effect), sampling media (e.g., blood, urine, etc.), and specific marker name; (2) search the citations file; and (3) read the abstract evaluations relative to our search criteria. A searchable, user-friendly database of over 2000 articles was created and is publicly available at: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=85844. PubMed was the primary source of references with some additional searches of Toxline, NTIS, and other reference databases. Our initial focus was on review articles, beginning as early as 1996, supplemented with searches of the recent primary research literature from 2001 to 2003. We anticipate this database will have applicability for the NCS as well as other studies of children's environmental health.

  16. Development of a biomarkers database for the National Children's Study

    International Nuclear Information System (INIS)

    Lobdell, Danelle T.; Mendola, Pauline

    2005-01-01

    The National Children's Study (NCS) is a federally-sponsored, longitudinal study of environmental influences on the health and development of children across the United States (www.nationalchildrensstudy.gov). Current plans are to study approximately 100,000 children and their families beginning before birth up to age 21 years. To explore potential biomarkers that could be important measurements in the NCS, we compiled the relevant scientific literature to identify both routine or standardized biological markers as well as new and emerging biological markers. Although the search criteria encouraged examination of factors that influence the breadth of child health and development, attention was primarily focused on exposure, susceptibility, and outcome biomarkers associated with four important child health outcomes: autism and neurobehavioral disorders, injury, cancer, and asthma. The Biomarkers Database was designed to allow users to: (1) search the biomarker records compiled by type of marker (susceptibility, exposure or effect), sampling media (e.g., blood, urine, etc.), and specific marker name; (2) search the citations file; and (3) read the abstract evaluations relative to our search criteria. A searchable, user-friendly database of over 2000 articles was created and is publicly available at: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=85844. PubMed was the primary source of references with some additional searches of Toxline, NTIS, and other reference databases. Our initial focus was on review articles, beginning as early as 1996, supplemented with searches of the recent primary research literature from 2001 to 2003. We anticipate this database will have applicability for the NCS as well as other studies of children's environmental health

  17. [Biomarkers of Alzheimer disease].

    Science.gov (United States)

    Rachel, Wojciech; Grela, Agatha; Zyss, Tomasz; Zieba, Andrzej; Piekoszewski, Wojciech

    2014-01-01

    Cognitive impairment is one of the most abundant age-related psychiatric disorders. The outcome of cognitive impairment in Alzheimer's disease has both individual (the patients and their families) and socio-economic effects. The prevalence of Alzheimer's disease doubles after the age of 65 years, every 4.5 years. An etiologically heterogenic group of disorders related to aging as well as genetic and environmental interactions probably underlie the impairment in Alzheimer's disease. Those factors cause the degeneration of brain tissue which leads to significant cognitive dysfunction. There are two main hypotheses that are linked to the process of neurodegeneration: (i) amyloid cascade and (ii) the role of secretases and dysfunction of mitochondria. From the therapeutic standpoint it is crucial to get an early diagnosis and start with an adequate treatment. The undeniable progress in the field of biomarker research should lead to a better understanding of the early stages of the disorder. So far, the best recognised and described biomarkers of Alzheimer's disease, which can be detected in both cerebrospinal fluid and blood, are: beta-amyloid, tau-protein and phosphorylated tau-protein (phospho-tau). The article discusses the usefulness of the known biomarkers of Alzheimer's disease in early diagnosis.

  18. The Search for Extraterrestrial Intelligence (SETI)

    Science.gov (United States)

    Tarter, Jill

    The search for evidence of extraterrestrial intelligence is placed in the broader astronomical context of the search for extrasolar planets and biomarkers of primitive life elsewhere in the universe. A decision tree of possible search strategies is presented as well as a brief history of the search for extraterrestrial intelligence (SETI) projects since 1960. The characteristics of 14 SETI projects currently operating on telescopes are discussed and compared using one of many possible figures of merit. Plans for SETI searches in the immediate and more distant future are outlined. Plans for success, the significance of null results, and some opinions on deliberate transmission of signals (as well as listening) are also included. SETI results to date are negative, but in reality, not much searching has yet been done.

  19. Measuring and combining multiple diagnostic and prognostic sepsis biomarkers

    DEFF Research Database (Denmark)

    Kofoed, K.

    This PhD-thesis is based on work performed at Clinical Research Centre and Department of Infectious Diseases at Copenhagen University Hospital, Hvidovre, and includes a review, a method development study, and two clinical studies. The background of the thesis is, that timely and accurate diagnosis...... of sepsis is of great importance for choice of treatment, level of monitoring and prognosis. In this biomarkers could be a significant aid, and thus the search for and application of "new" sepsis biomarkers is of great importance. The thesis reviews the definitions and the epidemiology, and gives...

  20. Resting-State Functional Connectivity-Based Biomarkers and Functional MRI-Based Neurofeedback for Psychiatric Disorders: A Challenge for Developing Theranostic Biomarkers.

    Science.gov (United States)

    Yamada, Takashi; Hashimoto, Ryu-Ichiro; Yahata, Noriaki; Ichikawa, Naho; Yoshihara, Yujiro; Okamoto, Yasumasa; Kato, Nobumasa; Takahashi, Hidehiko; Kawato, Mitsuo

    2017-10-01

    Psychiatric research has been hampered by an explanatory gap between psychiatric symptoms and their neural underpinnings, which has resulted in poor treatment outcomes. This situation has prompted us to shift from symptom-based diagnosis to data-driven diagnosis, aiming to redefine psychiatric disorders as disorders of neural circuitry. Promising candidates for data-driven diagnosis include resting-state functional connectivity MRI (rs-fcMRI)-based biomarkers. Although biomarkers have been developed with the aim of diagnosing patients and predicting the efficacy of therapy, the focus has shifted to the identification of biomarkers that represent therapeutic targets, which would allow for more personalized treatment approaches. This type of biomarker (i.e., "theranostic biomarker") is expected to elucidate the disease mechanism of psychiatric conditions and to offer an individualized neural circuit-based therapeutic target based on the neural cause of a condition. To this end, researchers have developed rs-fcMRI-based biomarkers and investigated a causal relationship between potential biomarkers and disease-specific behavior using functional MRI (fMRI)-based neurofeedback on functional connectivity. In this review, we introduce a recent approach for creating a theranostic biomarker, which consists mainly of 2 parts: (1) developing an rs-fcMRI-based biomarker that can predict diagnosis and/or symptoms with high accuracy, and (2) the introduction of a proof-of-concept study investigating the relationship between normalizing the biomarker and symptom changes using fMRI-based neurofeedback. In parallel with the introduction of recent studies, we review rs-fcMRI-based biomarker and fMRI-based neurofeedback, focusing on the technological improvements and limitations associated with clinical use. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  1. Biomarkers in Diabetic Retinopathy

    Science.gov (United States)

    Jenkins, Alicia J.; Joglekar, Mugdha V.; Hardikar, Anandwardhan A.; Keech, Anthony C.; O'Neal, David N.; Januszewski, Andrzej S.

    2015-01-01

    There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

  2. Biomarkers in Diabetic Retinopathy.

    Science.gov (United States)

    Jenkins, Alicia J; Joglekar, Mugdha V; Hardikar, Anandwardhan A; Keech, Anthony C; O'Neal, David N; Januszewski, Andrzej S

    2015-01-01

    There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

  3. Mass Spectrometry-Based Proteomics in Molecular Diagnostics: Discovery of Cancer Biomarkers Using Tissue Culture

    Science.gov (United States)

    Paul, Debasish; Kumar, Avinash; Gajbhiye, Akshada; Santra, Manas K.; Srikanth, Rapole

    2013-01-01

    Accurate diagnosis and proper monitoring of cancer patients remain a key obstacle for successful cancer treatment and prevention. Therein comes the need for biomarker discovery, which is crucial to the current oncological and other clinical practices having the potential to impact the diagnosis and prognosis. In fact, most of the biomarkers have been discovered utilizing the proteomics-based approaches. Although high-throughput mass spectrometry-based proteomic approaches like SILAC, 2D-DIGE, and iTRAQ are filling up the pitfalls of the conventional techniques, still serum proteomics importunately poses hurdle in overcoming a wide range of protein concentrations, and also the availability of patient tissue samples is a limitation for the biomarker discovery. Thus, researchers have looked for alternatives, and profiling of candidate biomarkers through tissue culture of tumor cell lines comes up as a promising option. It is a rich source of tumor cell-derived proteins, thereby, representing a wide array of potential biomarkers. Interestingly, most of the clinical biomarkers in use today (CA 125, CA 15.3, CA 19.9, and PSA) were discovered through tissue culture-based system and tissue extracts. This paper tries to emphasize the tissue culture-based discovery of candidate biomarkers through various mass spectrometry-based proteomic approaches. PMID:23586059

  4. Mass Spectrometry-Based Proteomics in Molecular Diagnostics: Discovery of Cancer Biomarkers Using Tissue Culture

    Directory of Open Access Journals (Sweden)

    Debasish Paul

    2013-01-01

    Full Text Available Accurate diagnosis and proper monitoring of cancer patients remain a key obstacle for successful cancer treatment and prevention. Therein comes the need for biomarker discovery, which is crucial to the current oncological and other clinical practices having the potential to impact the diagnosis and prognosis. In fact, most of the biomarkers have been discovered utilizing the proteomics-based approaches. Although high-throughput mass spectrometry-based proteomic approaches like SILAC, 2D-DIGE, and iTRAQ are filling up the pitfalls of the conventional techniques, still serum proteomics importunately poses hurdle in overcoming a wide range of protein concentrations, and also the availability of patient tissue samples is a limitation for the biomarker discovery. Thus, researchers have looked for alternatives, and profiling of candidate biomarkers through tissue culture of tumor cell lines comes up as a promising option. It is a rich source of tumor cell-derived proteins, thereby, representing a wide array of potential biomarkers. Interestingly, most of the clinical biomarkers in use today (CA 125, CA 15.3, CA 19.9, and PSA were discovered through tissue culture-based system and tissue extracts. This paper tries to emphasize the tissue culture-based discovery of candidate biomarkers through various mass spectrometry-based proteomic approaches.

  5. Improving the quality of biomarker discovery research: the right samples and enough of them.

    Science.gov (United States)

    Pepe, Margaret S; Li, Christopher I; Feng, Ziding

    2015-06-01

    Biomarker discovery research has yielded few biomarkers that validate for clinical use. A contributing factor may be poor study designs. The goal in discovery research is to identify a subset of potentially useful markers from a large set of candidates assayed on case and control samples. We recommend the PRoBE design for selecting samples. We propose sample size calculations that require specifying: (i) a definition for biomarker performance; (ii) the proportion of useful markers the study should identify (Discovery Power); and (iii) the tolerable number of useless markers amongst those identified (False Leads Expected, FLE). We apply the methodology to a study of 9,000 candidate biomarkers for risk of colon cancer recurrence where a useful biomarker has positive predictive value ≥ 30%. We find that 40 patients with recurrence and 160 without recurrence suffice to filter out 98% of useless markers (2% FLE) while identifying 95% of useful biomarkers (95% Discovery Power). Alternative methods for sample size calculation required more assumptions. Biomarker discovery research should utilize quality biospecimen repositories and include sample sizes that enable markers meeting prespecified performance characteristics for well-defined clinical applications to be identified. The scientific rigor of discovery research should be improved. ©2015 American Association for Cancer Research.

  6. ALS Biomarkers for Therapy Development: State of the Field & Future Directions

    Science.gov (United States)

    Benatar, Michael; Boylan, Kevin; Jeromin, Andreas; Rutkove, Seward B.; Berry, James; Atassi, Nazem; Bruijn, Lucie

    2015-01-01

    Biomarkers have become the focus of intense research in the field of amyotrophic lateral sclerosis (ALS), with the hope that they might aid therapy development efforts. Notwithstanding the discovery of many candidate biomarkers, none have yet emerged as validated tools for drug development. In this review we present a nuanced view of biomarkers based on the perspective of the FDA; highlight the distinction between discovery and validation; describe existing and emerging resources; review leading biological fluid-based, electrophysiological and neuroimaging candidates relevant to therapy development efforts; discuss lessons learned from biomarker initiatives in related neurodegenerative diseases; and outline specific steps that we, as a field, might take in order to hasten the development and validation of biomarkers that will prove useful in enhancing efforts to develop effective treatments for ALS patients. Most important among these perhaps is the proposal to establish a federated ALS Biomarker Consortium (ABC) in which all interested and willing stakeholders may participate with equal opportunity to contribute to the broader mission of biomarker development and validation. PMID:26574709

  7. Biomarkers for Wilms Tumor: a Systematic Review

    Science.gov (United States)

    Cone, Eugene B.; Dalton, Stewart S.; Van Noord, Megan; Tracy, Elizabeth T.; Rice, Henry E.; Routh, Jonathan C.

    2016-01-01

    Purpose Wilms tumor is the most common childhood renal malignancy and the fourth most common childhood cancer. Many biomarkers have been studied but there has been no comprehensive summary. We systematically reviewed the literature on biomarkers in Wilms Tumor with the objective of quantifying the prognostic implication of the presence of individual tumor markers. Methods We searched for English language studies from 1980–2015 performed on children with Wilms Tumor under 18 years old with prognostic data. The protocol was conducted as per PRISMA guidelines. Two reviewers abstracted data in duplicate using a standard evaluation form. We performed descriptive statistics, then calculated relative risks and 95% confidence intervals for markers appearing in multiple level 2 or 3 studies. Results 40 studies were included examining 32 biomarkers in 7381 Wilms patients. Studies had a median of 61 patients with 24 biomarker positive patients per study, and a median follow-up of 68.4 months. Median percent of patients in Stage 1, 2, 3, 4, and 5 were 28.5%, 26.4%, 24.5%, 14.1%, and 1.7%, with 10.2% anaplasia. The strongest negative prognostic association was loss of heterozygosity on 11p15, with a risk of recurrence of 5.00, although loss of heterozygosity on 1p and gain of function on 1q were also strongly linked to increased recurrence (2.93 and 2.86 respectively). Conclusions Several tumor markers are associated with an increased risk of recurrence or a decreased risk of overall survival in Wilms Tumor. These data suggest targets for development of diagnostic tests and potential therapies. PMID:27259655

  8. Many-Objective Distinct Candidates Optimization using Differential Evolution

    DEFF Research Database (Denmark)

    Justesen, Peter; Ursem, Rasmus Kjær

    2010-01-01

    for each objective. The Many-Objective Distinct Candidates Optimization using Differential Evolution (MODCODE) algorithm takes a novel approach by focusing search using a user-defined number of subpopulations each returning a distinct optimal solution within the preferred region of interest. In this paper......, we present the novel MODCODE algorithm incorporating the ROD measure to measure and control candidate distinctiveness. MODCODE is tested against GDE3 on three real world centrifugal pump design problems supplied by Grundfos. Our algorithm outperforms GDE3 on all problems with respect to all...

  9. Biomarkers, Trauma, and Sepsis in Pediatrics: A Review

    Directory of Open Access Journals (Sweden)

    Marianne Frieri

    2016-01-01

    Full Text Available Context: There is a logical connection with biomarkers, trauma, and sepsis. This review paper provides new information and clinical practice implications. Biomarkers are very important especially in pediatrics. Procalcitonin and other biomarkers are helpful in identifying neonatal sepsis, defense mechanisms of the immune system. Pediatric trauma and sepsis is very important both in infants and in children. Stress management both in trauma is based upon the notion that stress causes an immune imbalance in susceptible individuals. Evidence Acquisition: Data sources included studies indexed in PubMed, a meta- analysis, predictive values, research strategies, and quality assessments. A recent paper by one of the authors stated marked increase in serum procalcitonin during the course of a septic process often indicates an exacerbation of the illness, and a decreasing level is a sign of improvement. A review of epidemiologic studies on pediatric soccer patients was also addressed. Keywords for searching included biomarkers, immunity, trauma, and sepsis. Results: Of 50 reviewed articles, 34 eligible articles were selected including biomarkers, predictive values for procalcitonin, identifying children at risk for intra-abdominal injuries, blunt trauma, and epidemiology, a meta-analysis. Of neonatal associated sepsis, the NF-kappa B pathway by inflammatory stimuli in human neutrophils, predictive value of gelsolin for the outcomes of preterm neonates, a meta-analysis interleukin-8 for neonatal sepsis diagnosis. Conclusions: Biomarkers are very important especially in pediatrics. Procalcitonin and other biomarkers are helpful in identifying neonatal sepsis, defense mechanisms, and physiological functions of the immune system. Pediatric trauma and sepsis is very important both in infants and in children. Various topics were covered such as biomarkers, trauma, sepsis, inflammation, innate immunity, role of neutrophils and IL-8, reactive oxygen species

  10. An Update on Genetic and Serotoneric Biomarker Findings in Bulimia Nervosa

    DEFF Research Database (Denmark)

    Sjögren, Magnus

    2017-01-01

    support in understanding the pathophysiology of BN, and potentially in diagnosing, and monitoring of effects of treatment. This review describes genetic and serotonergic biomarkers for BN. Method: A literature search using PUBMED (20 June 2017) was done using the following search terms: 1) “Bulimia...

  11. Predictive Biomarkers for Asthma Therapy.

    Science.gov (United States)

    Medrek, Sarah K; Parulekar, Amit D; Hanania, Nicola A

    2017-09-19

    Asthma is a heterogeneous disease characterized by multiple phenotypes. Treatment of patients with severe disease can be challenging. Predictive biomarkers are measurable characteristics that reflect the underlying pathophysiology of asthma and can identify patients that are likely to respond to a given therapy. This review discusses current knowledge regarding predictive biomarkers in asthma. Recent trials evaluating biologic therapies targeting IgE, IL-5, IL-13, and IL-4 have utilized predictive biomarkers to identify patients who might benefit from treatment. Other work has suggested that using composite biomarkers may offer enhanced predictive capabilities in tailoring asthma therapy. Multiple biomarkers including sputum eosinophil count, blood eosinophil count, fractional concentration of nitric oxide in exhaled breath (FeNO), and serum periostin have been used to identify which patients will respond to targeted asthma medications. Further work is needed to integrate predictive biomarkers into clinical practice.

  12. Search strategies

    Science.gov (United States)

    Oliver, B. M.

    Attention is given to the approaches which would provide the greatest chance of success in attempts related to the discovery of extraterrestrial advanced cultures in the Galaxy, taking into account the principle of least energy expenditure. The energetics of interstellar contact are explored, giving attention to the use of manned spacecraft, automatic probes, and beacons. The least expensive approach to a search for other civilizations involves a listening program which attempts to detect signals emitted by such civilizations. The optimum part of the spectrum for the considered search is found to be in the range from 1 to 2 GHz. Antenna and transmission formulas are discussed along with the employment of matched gates and filters, the probable characteristics of the signals to be detected, the filter-signal mismatch loss, surveys of the radio sky, the conduction of targeted searches.

  13. Ensemble candidate classification for the LOTAAS pulsar survey

    Science.gov (United States)

    Tan, C. M.; Lyon, R. J.; Stappers, B. W.; Cooper, S.; Hessels, J. W. T.; Kondratiev, V. I.; Michilli, D.; Sanidas, S.

    2018-03-01

    One of the biggest challenges arising from modern large-scale pulsar surveys is the number of candidates generated. Here, we implemented several improvements to the machine learning (ML) classifier previously used by the LOFAR Tied-Array All-Sky Survey (LOTAAS) to look for new pulsars via filtering the candidates obtained during periodicity searches. To assist the ML algorithm, we have introduced new features which capture the frequency and time evolution of the signal and improved the signal-to-noise calculation accounting for broad profiles. We enhanced the ML classifier by including a third class characterizing RFI instances, allowing candidates arising from RFI to be isolated, reducing the false positive return rate. We also introduced a new training data set used by the ML algorithm that includes a large sample of pulsars misclassified by the previous classifier. Lastly, we developed an ensemble classifier comprised of five different Decision Trees. Taken together these updates improve the pulsar recall rate by 2.5 per cent, while also improving the ability to identify pulsars with wide pulse profiles, often misclassified by the previous classifier. The new ensemble classifier is also able to reduce the percentage of false positive candidates identified from each LOTAAS pointing from 2.5 per cent (˜500 candidates) to 1.1 per cent (˜220 candidates).

  14. Biomarkers in Prostate Cancer Epidemiology

    Directory of Open Access Journals (Sweden)

    Mudit Verma

    2011-09-01

    Full Text Available Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed.

  15. Biomarker Identification Using Text Mining

    Directory of Open Access Journals (Sweden)

    Hui Li

    2012-01-01

    Full Text Available Identifying molecular biomarkers has become one of the important tasks for scientists to assess the different phenotypic states of cells or organisms correlated to the genotypes of diseases from large-scale biological data. In this paper, we proposed a text-mining-based method to discover biomarkers from PubMed. First, we construct a database based on a dictionary, and then we used a finite state machine to identify the biomarkers. Our method of text mining provides a highly reliable approach to discover the biomarkers in the PubMed database.

  16. Direct search for dark matter

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Jonghee; /Fermilab

    2009-12-01

    Dark matter is hypothetical matter which does not interact with electromagnetic radiation. The existence of dark matter is only inferred from gravitational effects of astrophysical observations to explain the missing mass component of the Universe. Weakly Interacting Massive Particles are currently the most popular candidate to explain the missing mass component. I review the current status of experimental searches of dark matter through direct detection using terrestrial detectors.

  17. Biomarkers of postoperative delirium and cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Ganna eAndrosova

    2015-06-01

    Full Text Available Elderly surgical patients frequently experience postoperative delirium (POD and the subsequent development of postoperative cognitive dysfunction (POCD. Clinical features include deterioration in cognition, disturbance in attention and reduced awareness of the environment and result in higher morbidity, mortality and greater utilization of social financial assistance. The aging Western societies can expect an increase in the incidence of POD and POCD. The underlying pathophysiological mechanisms have been studied on the molecular level albeit with unsatisfying small research efforts given their societal burden. Here, we review the known physiological and immunological changes and genetic risk factors, identify candidates for further studies and integrate the information into a draft network for exploration on a systems level. The pathogenesis of these postoperative cognitive impairments is multifactorial; application of integrated systems biology has the potential to reconstruct the underlying network of molecular mechanisms and help in the identification of prognostic and diagnostic biomarkers.

  18. Chiral Biomarkers in Meteorites

    Science.gov (United States)

    Hoover, Richard B.

    2010-01-01

    The chirality of organic molecules with the asymmetric location of group radicals was discovered in 1848 by Louis Pasteur during his investigations of the rotation of the plane of polarization of light by crystals of sodium ammonium paratartrate. It is well established that the amino acids in proteins are exclusively Levorotary (L-aminos) and the sugars in DNA and RNA are Dextrorotary (D-sugars). This phenomenon of homochirality of biological polymers is a fundamental property of all life known on Earth. Furthermore, abiotic production mechanisms typically yield recemic mixtures (i.e. equal amounts of the two enantiomers). When amino acids were first detected in carbonaceous meteorites, it was concluded that they were racemates. This conclusion was taken as evidence that they were extraterrestrial and produced by abiologically. Subsequent studies by numerous researchers have revealed that many of the amino acids in carbonaceous meteorites exhibit a significant L-excess. The observed chirality is much greater than that produced by any currently known abiotic processes (e.g. Linearly polarized light from neutron stars; Circularly polarized ultraviolet light from faint stars; optically active quartz powders; inclusion polymerization in clay minerals; Vester-Ulbricht hypothesis of parity violations, etc.). This paper compares the measured chirality detected in the amino acids of carbonaceous meteorites with the effect of these diverse abiotic processes. IT is concluded that the levels observed are inconsistent with post-arrival biological contamination or with any of the currently known abiotic production mechanisms. However, they are consistent with ancient biological processes on the meteorite parent body. This paper will consider these chiral biomarkers in view of the detection of possible microfossils found in the Orgueil and Murchison carbonaceous meteorites. Energy dispersive x-ray spectroscopy (EDS) data obtained on these morphological biomarkers will be

  19. Hepcidin- A Burgeoning Biomarker

    Directory of Open Access Journals (Sweden)

    Hemkant Manikrao Deshmukh

    2017-10-01

    Full Text Available The discovery of hepcidin has triggered a virtual ignition of studies on iron metabolism and related disorders. The peptide hormone hepcidin is a key homeostatic regulator of iron metabolism. The synthesis of hepcidin is induced by systemic iron levels and by inflammatory stimuli. Several human diseases are associated with variations in hepcidin concentrations. The evaluation of hepcidin in biological fluids is therefore a promising device in the diagnosis and management of medical situations in which iron metabolism is affected. Thus, it made us to recapitulate role of hepcidin as biomarker.

  20. Inflammasome Proteins As Biomarkers of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Robert W. Keane

    2018-03-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease that affects the brain and spinal cord. The inflammasome is a multiprotein complex that contributes to the innate immune response in animal models of MS as well as in patients with the disease. Important to the care of patients with MS is the need for biomarkers that can predict disease onset, disease exacerbation, as well as response to treatment. In this study, we analyzed serum samples from 32 patients with MS and 120 age-matched controls, and provide receiver operator characteristic (ROC curves with associated confidence intervals following analyses of serum samples from patients with MS, most of which had the relapsing-remitting form of the disease, and from healthy unaffected donors, and determine the sensitivity and specificity of inflammasome proteins as biomarkers of MS. We report that caspase-1 (1.662 ± 0.6024 difference between means, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC (407.5 ± 35.79, and interleukin (IL-18 (78.53 + 17.86 were elevated in the serum of MS patients when compared to controls. Interestingly, the levels of IL-1β (−0.5961 ± 0.265 were lower in the MS cohort. Importantly, the area under the curve (AUC for ASC and caspase-1 were 0.9448 and 0.848, respectively. Taken together, these data suggest that ASC and caspase-1 could be potential candidate biomarkers for MS onset.

  1. Finding diabetic nephropathy biomarkers in the plasma peptidome by high-throughput magnetic bead processing and MALDI-TOF-MS analysis

    DEFF Research Database (Denmark)

    Hansen, Henning G; Overgaard, Julie; Lajer, Maria

    2010-01-01

    Diabetic nephropathy (DN) is the most common cause of end-stage renal disease and improved biomarkers would help identify high-risk individuals. The aim of this study was to discover candidate biomarkers for DN in the plasma peptidome in an in-house cross-sectional cohort (n=122) of type 1 diabet...

  2. Biomarkers in Vasculitis

    Science.gov (United States)

    Monach, Paul A.

    2014-01-01

    Purpose of review Better biomarkers are needed for guiding management of patients with vasculitis. Large cohorts and technological advances had led to an increase in pre-clinical studies of potential biomarkers. Recent findings The most interesting markers described recently include a gene expression signature in CD8+ T cells that predicts tendency to relapse or remain relapse-free in ANCA-associated vasculitis, and a pair of urinary proteins that are elevated in Kawasaki disease but not other febrile illnesses. Both of these studies used “omics” technologies to generate and then test hypotheses. More conventional hypothesis-based studies have indicated that the following circulating proteins have potential to improve upon clinically available tests: pentraxin-3 in giant cell arteritis and Takayasu’s arteritis; von Willebrand factor antigen in childhood central nervous system vasculitis; eotaxin-3 and other markers related to eosinophils or Th2 immune responses in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome); and MMP-3, TIMP-1, and CXCL13 in ANCA-associated vasculitis. Summary New markers testable in blood and urine have the potential to assist with diagnosis, staging, assessment of current disease activity, and prognosis. However, the standards for clinical usefulness, in particular the demonstration of either very high sensitivity or very high specificity, have yet to be met for clinically relevant outcomes. PMID:24257367

  3. Integration of Proteomics, Bioinformatics, and Systems Biology in Traumatic Brain Injury Biomarker Discovery

    Science.gov (United States)

    Guingab-Cagmat, J.D.; Cagmat, E.B.; Hayes, R.L.; Anagli, J.

    2013-01-01

    Traumatic brain injury (TBI) is a major medical crisis without any FDA-approved pharmacological therapies that have been demonstrated to improve functional outcomes. It has been argued that discovery of disease-relevant biomarkers might help to guide successful clinical trials for TBI. Major advances in mass spectrometry (MS) have revolutionized the field of proteomic biomarker discovery and facilitated the identification of several candidate markers that are being further evaluated for their efficacy as TBI biomarkers. However, several hurdles have to be overcome even during the discovery phase which is only the first step in the long process of biomarker development. The high-throughput nature of MS-based proteomic experiments generates a massive amount of mass spectral data presenting great challenges in downstream interpretation. Currently, different bioinformatics platforms are available for functional analysis and data mining of MS-generated proteomic data. These tools provide a way to convert data sets to biologically interpretable results and functional outcomes. A strategy that has promise in advancing biomarker development involves the triad of proteomics, bioinformatics, and systems biology. In this review, a brief overview of how bioinformatics and systems biology tools analyze, transform, and interpret complex MS datasets into biologically relevant results is discussed. In addition, challenges and limitations of proteomics, bioinformatics, and systems biology in TBI biomarker discovery are presented. A brief survey of researches that utilized these three overlapping disciplines in TBI biomarker discovery is also presented. Finally, examples of TBI biomarkers and their applications are discussed. PMID:23750150

  4. Hybrid Projected Gradient-Evolutionary Search Algorithm for Mixed Integer Nonlinear Optimization Problems

    National Research Council Canada - National Science Library

    Homaifar, Abdollah; Esterline, Albert; Kimiaghalam, Bahram

    2005-01-01

    The Hybrid Projected Gradient-Evolutionary Search Algorithm (HPGES) algorithm uses a specially designed evolutionary-based global search strategy to efficiently create candidate solutions in the solution space...

  5. Internet Search Engines

    OpenAIRE

    Fatmaa El Zahraa Mohamed Abdou

    2004-01-01

    A general study about the internet search engines, the study deals main 7 points; the differance between search engines and search directories, components of search engines, the percentage of sites covered by search engines, cataloging of sites, the needed time for sites appearance in search engines, search capabilities, and types of search engines.

  6. Teacher Candidate Selection and Evaluation.

    Science.gov (United States)

    Collins, Mary Lynn; And Others

    Summaries are presented of three papers presented at a summer workshop on Quality Assurance in Teacher Education conducted by the Association of Teacher Educators. The general topic covered by these presentations was teacher candidate selection and evaluation. Papers focused upon the following questions: (1) What entry level criteria should be…

  7. Candidate Prediction Models and Methods

    DEFF Research Database (Denmark)

    Nielsen, Henrik Aalborg; Nielsen, Torben Skov; Madsen, Henrik

    2005-01-01

    This document lists candidate prediction models for Work Package 3 (WP3) of the PSO-project called ``Intelligent wind power prediction systems'' (FU4101). The main focus is on the models transforming numerical weather predictions into predictions of power production. The document also outlines...... the possibilities w.r.t. different numerical weather predictions actually available to the project....

  8. Candidate cave entrances on Mars

    Science.gov (United States)

    Cushing, Glen E.

    2012-01-01

    This paper presents newly discovered candidate cave entrances into Martian near-surface lava tubes, volcano-tectonic fracture systems, and pit craters and describes their characteristics and exploration possibilities. These candidates are all collapse features that occur either intermittently along laterally continuous trench-like depressions or in the floors of sheer-walled atypical pit craters. As viewed from orbit, locations of most candidates are visibly consistent with known terrestrial features such as tube-fed lava flows, volcano-tectonic fractures, and pit craters, each of which forms by mechanisms that can produce caves. Although we cannot determine subsurface extents of the Martian features discussed here, some may continue unimpeded for many kilometers if terrestrial examples are indeed analogous. The features presented here were identified in images acquired by the Mars Odyssey's Thermal Emission Imaging System visible-wavelength camera, and by the Mars Reconnaissance Orbiter's Context Camera. Select candidates have since been targeted by the High-Resolution Imaging Science Experiment. Martian caves are promising potential sites for future human habitation and astrobiology investigations; understanding their characteristics is critical for long-term mission planning and for developing the necessary exploration technologies.

  9. Opportunities and Challenges of Proteomics in Pediatric Patients: Circulating Biomarkers After Hematopoietic Stem Cell Transplantation As a Successful Example

    Science.gov (United States)

    Paczesny, Sophie; Duncan, Christine; Jacobsohn, David; Krance, Robert; Leung, Kathryn; Carpenter, Paul; Bollard, Catherine; Renbarger, Jamie; Cooke, Kenneth

    2015-01-01

    Biomarkers have the potential to improve diagnosis and prognosis, facilitate targeted treatment, and reduce health care costs. Thus, there is great hope that biomarkers will be integrated in all clinical decisions in the near future. A decade ago, the biomarker field was launched with great enthusiasm because mass spectrometry revealed that blood contains a rich library of candidate biomarkers. However, biomarker research has not yet delivered on its promise due to several limitations: (i) improper sample handling and tracking as well as limited sample availability in the pediatric population, (ii) omission of appropriate controls in original study designs, (iii) lability and low abundance of interesting biomarkers in blood, and (iv) the inability to mechanistically tie biomarker presence to disease biology. These limitations as well as successful strategies to overcome them are discussed in this review. Several advances in biomarker discovery and validation have been made in hematopoietic stem cell transplantation, the current most effective tumor immunotherapy, and these could serve as examples for other conditions. This review provides fresh optimism that biomarkers clinically relevant in pediatrics are closer to being realized based on: (i) a uniform protocol for low-volume blood collection and preservation, (ii) inclusion of well-controlled independent cohorts, (iii) novel technologies and instrumentation with low analytical sensitivity, and (iv) integrated animal models for exploring potential biomarkers and targeted therapies. PMID:25196024

  10. MiRNAs of peripheral blood as the biomarker of schizophrenia.

    Science.gov (United States)

    He, Kuanjun; Guo, Chuang; He, Lin; Shi, Yongyong

    2018-01-01

    The diagnosis of schizophrenia is currently based on the symptoms and bodily signs rather than on the pathological and physiological markers of the patient. In the search for new molecular targeted therapy medicines, and recurrence of early-warning indicators have become the major focus of contemporary research, because they improve diagnostic accuracy. Biomarkers reflect the physiological, physical and biochemical status of the body, and so have extensive applicability and practical significance. The ascertainment of schizophrenia biomarkers will help diagnose, stratify of disease, and treat of schizophrenia patients. The detection of biomarkers from blood has become a promising area of schizophrenia research. Recently, a series of studies revealed that, MiRNAs play an important role in the genesis of schizophrenia, and their abnormal expressions have the potential to be used as biomarkers of schizophrenia. This article presents and summarizes the value of peripheral blood miRNAs with abnormal expression as the biomarker of schizophrenia.

  11. Identification of Circular RNAs as a Novel Biomarker for Ovarian Endometriosis

    Directory of Open Access Journals (Sweden)

    Xiao-Xuan Xu

    2018-01-01

    Conclusions: This study provides evidence that circRNAs are differentially expressed between eutopic and normal endometrium, which suggests that circRNAs are candidate factors in the activation of endometriosis. circ_0002198 and circ_0004712 may be potential novel biomarkers for the diagnosis of ovarian endometriosis.

  12. Brain Oscillations in Sport: Toward EEG Biomarkers of Performance

    OpenAIRE

    Cheron, Guy; Petit, Géraldine; Cheron, Julian; Leroy, Axelle; Cebolla, Anita; Cevallos, Carlos; Petieau, Mathieu; Hoellinger, Thomas; Zarka, David; Clarinval, Anne-Marie; Dan, Bernard

    2016-01-01

    Brain dynamics is at the basis of top performance accomplishment in sports. The search for neural biomarkers of performance remains a challenge in movement science and sport psychology. The non-invasive nature of high-density electroencephalography (EEG) recording has made it a most promising avenue for providing quantitative feedback to practitioners and coaches. Here, we review the current relevance of the main types of EEG oscillations in order to trace a perspective for future practical a...

  13. Biomarkers identified by urinary metabonomics for noninvasive diagnosis of nutritional rickets.

    Science.gov (United States)

    Wang, Maoqing; Yang, Xue; Ren, Lihong; Li, Songtao; He, Xuan; Wu, Xiaoyan; Liu, Tingting; Lin, Liqun; Li, Ying; Sun, Changhao

    2014-09-05

    Nutritional rickets is a worldwide public health problem; however, the current diagnostic methods retain shortcomings for accurate diagnosis of nutritional rickets. To identify urinary biomarkers associated with nutritional rickets and establish a noninvasive diagnosis method, urinary metabonomics analysis by ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis were employed to investigate the metabolic alterations associated with nutritional rickets in 200 children with or without nutritional rickets. The pathophysiological changes and pathogenesis of nutritional rickets were illustrated by the identified biomarkers. By urinary metabolic profiling, 31 biomarkers of nutritional rickets were identified and five candidate biomarkers for clinical diagnosis were screened and identified by quantitative analysis and receiver operating curve analysis. Urinary levels of five candidate biomarkers were measured using mass spectrometry or commercial kits. In the validation step, the combination of phosphate and sebacic acid was able to give a noninvasive and accurate diagnostic with high sensitivity (94.0%) and specificity (71.2%). Furthermore, on the basis of the pathway analysis of biomarkers, our urinary metabonomics analysis gives new insight into the pathogenesis and pathophysiology of nutritional rickets.

  14. [Autoantibodies as biomarkers].

    Science.gov (United States)

    Tron, François

    2014-01-01

    Activation and differentiation of autoreactive B-lymphocytes lead to the production of autoantibodies, which are thus the direct consequence of the autoimmune process. They often constitute biomarkers of autoimmune diseases and are measured by tests displaying various diagnosis sensitivity and specificity. Autoantibody titers can be correlated to the disease activity and certain autoantibody populations associated with particular clinical manifestations or tissue lesions. The demonstration that autoantibodies appear years before the onset of autoimmune diseases indicates that their presence in healthy individuals may be a predictive marker of the occurrence of disease. Certain autoantibodies could also be predictive markers of a therapeutic response to biologics and of the occurrence of side effects as well. Thus, autoantibodies are useful tools in the diagnosis and the management of patients with organ specific or non-organ specific autoimmune diseases at different steps of the autoimmune process. Copyright © 2013. Published by Elsevier Masson SAS.

  15. Biomarkers of adverse drug reactions.

    Science.gov (United States)

    Carr, Daniel F; Pirmohamed, Munir

    2018-02-01

    Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue

  16. New biomarkers for sepsis

    Directory of Open Access Journals (Sweden)

    Li-xin XIE

    2013-01-01

    Full Text Available There is a higher sepsis rate in the intensive care unit (ICU patients, which is one of the most important causes for patient death, but the sepsis lacks specific clinical manifestations. Exploring sensitive and specific molecular markers for infection that accurately reflect infection severity and prognosis is very clinically important. In this article, based on our previous study, we introduce some new biomarkers with high sensitivity and specificity for the diagnosis and predicting the prognosis and severity of sepsis. Increase of serum soluble(s triggering receptor expressed on myeloid cells-1 (sTREM-1 suggests a poor prognosis of septic patients, and changes of locus rs2234237 of sTREM-1 may be the one of important mechanisms. Additionally, urine sTREM-1 can provide an early warning of possible secondary acute kidney injury (AKI in sepsis patients. Serum sCD163 level was found to be a more important factor than procalcitonin (PCT and C-reactive protein (CRP in prognosis of sepsis, especially severe sepsis. Moreover, urine sCD163 also shows excellent performance in the diagnosis of sepsis and sepsis-associated AKI. Circulating microRNAs, such as miR-150, miR-297, miR-574-5p, miR -146a , miR-223, miR -15a and miR-16, also play important roles in the evaluation of status of septic patients. In the foreseeable future, newly-emerging technologies, including proteomics, metabonomics and trans-omics, may exert profound effects on the discovery of valuable biomarkers for sepsis.

  17. Visualization of Pulsar Search Data

    Science.gov (United States)

    Foster, R. S.; Wolszczan, A.

    1993-05-01

    The search for periodic signals from rotating neutron stars or pulsars has been a computationally taxing problem to astronomers for more than twenty-five years. Over this time interval, increases in computational capability have allowed ever more sensitive searches, covering a larger parameter space. The volume of input data and the general presence of radio frequency interference typically produce numerous spurious signals. Visualization of the search output and enhanced real-time processing of significant candidate events allow the pulsar searcher to optimally processes and search for new radio pulsars. The pulsar search algorithm and visualization system presented in this paper currently runs on serial RISC based workstations, a traditional vector based super computer, and a massively parallel computer. A description of the serial software algorithm and its modifications for massively parallel computing are describe. The results of four successive searches for millisecond period radio pulsars using the Arecibo telescope at 430 MHz have resulted in the successful detection of new long-period and millisecond period radio pulsars.

  18. USING STELLAR DENSITIES TO EVALUATE TRANSITING EXOPLANETARY CANDIDATES

    International Nuclear Information System (INIS)

    Tingley, B.; Deeg, H. J.; Bonomo, A. S.

    2011-01-01

    One of the persistent complications in searches for transiting exoplanets is the low percentage of the detected candidates that ultimately prove to be planets, which significantly increases the load on the telescopes used for the follow-up observations to confirm or reject candidates. Several attempts have been made at creating techniques that can pare down candidate lists without the need of additional observations. Some of these techniques involve a detailed analysis of light curve characteristics; others estimate the stellar density or some proxy thereof. In this paper, we extend upon this second approach, exploring the use of independently calculated stellar densities to identify the most promising transiting exoplanet candidates. We use a set of CoRoT candidates and the set of known transiting exoplanets to examine the potential of this approach. In particular, we note the possibilities inherent in the high-precision photometry from space missions, which can detect stellar asteroseismic pulsations from which accurate stellar densities can be extracted without additional observations.

  19. Utilization of metabolomics to identify serum biomarkers for hepatocellular carcinoma in patients with liver cirrhosis

    International Nuclear Information System (INIS)

    Ressom, Habtom W.; Xiao, Jun Feng; Tuli, Leepika; Varghese, Rency S.; Zhou Bin; Tsai, Tsung-Heng; Nezami Ranjbar, Mohammad R.; Zhao Yi; Wang Jinlian; Di Poto, Cristina; Cheema, Amrita K.; Tadesse, Mahlet G.; Goldman, Radoslav; Shetty, Kirti

    2012-01-01

    Highlights: ► We analyzed sera from HCC and cirrhotic patients by LC–MS in three experiments. ► Metabolites with significant and consistent changes in HCC vs. cirrhosis were selected. ► Verification of the identities of selected metabolites was performed by MS/MS. ► Quantitation of candidate metabolites was conducted using isotope dilution by SRM. - Abstract: Characterizing the metabolic changes pertaining to hepatocellular carcinoma (HCC) in patients with liver cirrhosis is believed to contribute towards early detection, treatment, and understanding of the molecular mechanisms of HCC. In this study, we compare metabolite levels in sera of 78 HCC cases with 184 cirrhotic controls by using ultra performance liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometry (UPLC–QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from patients with cirrhosis are selected by parametric and non-parametric statistical methods. Putative metabolite identifications for these ions are obtained through mass-based database search. Verification of the identities of selected metabolites is conducted by comparing their MS/MS fragmentation patterns and retention time with those from authentic compounds. Quantitation of these metabolites is performed in a subset of the serum samples (10 HCC and 10 cirrhosis) using isotope dilution by selected reaction monitoring (SRM) on triple quadrupole linear ion trap (QqQLIT) and triple quadrupole (QqQ) mass spectrometers. The results of this analysis confirm that metabolites involved in sphingolipid metabolism and phospholipid catabolism such as sphingosine-1-phosphate (S-1-P) and lysophosphatidylcholine (lysoPC 17:0) are up-regulated in sera of HCC vs. those with liver cirrhosis. Down-regulated metabolites include those involved in bile acid biosynthesis (specifically cholesterol metabolism) such as glycochenodeoxycholic acid 3-sulfate (3-sulfo-GCDCA), glycocholic acid

  20. Utilization of metabolomics to identify serum biomarkers for hepatocellular carcinoma in patients with liver cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Ressom, Habtom W., E-mail: hwr@georgetown.edu [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Xiao, Jun Feng; Tuli, Leepika; Varghese, Rency S.; Zhou Bin; Tsai, Tsung-Heng; Nezami Ranjbar, Mohammad R.; Zhao Yi; Wang Jinlian; Di Poto, Cristina; Cheema, Amrita K. [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Tadesse, Mahlet G. [Department of Mathematics and Statistics, Georgetown University, Washington, DC 20057 (United States); Goldman, Radoslav [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Shetty, Kirti [Department of Surgery, Georgetown University Medical Center, Washington, DC 20057 (United States); Georgetown University Hospital, Washington, DC 20057 (United States)

    2012-09-19

    Highlights: Black-Right-Pointing-Pointer We analyzed sera from HCC and cirrhotic patients by LC-MS in three experiments. Black-Right-Pointing-Pointer Metabolites with significant and consistent changes in HCC vs. cirrhosis were selected. Black-Right-Pointing-Pointer Verification of the identities of selected metabolites was performed by MS/MS. Black-Right-Pointing-Pointer Quantitation of candidate metabolites was conducted using isotope dilution by SRM. - Abstract: Characterizing the metabolic changes pertaining to hepatocellular carcinoma (HCC) in patients with liver cirrhosis is believed to contribute towards early detection, treatment, and understanding of the molecular mechanisms of HCC. In this study, we compare metabolite levels in sera of 78 HCC cases with 184 cirrhotic controls by using ultra performance liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from patients with cirrhosis are selected by parametric and non-parametric statistical methods. Putative metabolite identifications for these ions are obtained through mass-based database search. Verification of the identities of selected metabolites is conducted by comparing their MS/MS fragmentation patterns and retention time with those from authentic compounds. Quantitation of these metabolites is performed in a subset of the serum samples (10 HCC and 10 cirrhosis) using isotope dilution by selected reaction monitoring (SRM) on triple quadrupole linear ion trap (QqQLIT) and triple quadrupole (QqQ) mass spectrometers. The results of this analysis confirm that metabolites involved in sphingolipid metabolism and phospholipid catabolism such as sphingosine-1-phosphate (S-1-P) and lysophosphatidylcholine (lysoPC 17:0) are up-regulated in sera of HCC vs. those with liver cirrhosis. Down-regulated metabolites include those involved in bile acid biosynthesis (specifically

  1. Search for $\

    CERN Document Server

    Agafonova, N.

    2011-01-01

    The OPERA neutrino experiment in the underground Gran Sasso Laboratory (LNGS) was designed to perform the first detection of neutrino oscillations in direct appearance mode in the nu_mu to nu_tau channel, the nu_tau signature being the identification of the tau-lepton created in its charged current interaction. The hybrid apparatus consists of a large mass emulsion film/lead target complemented by electronic detectors. It is placed in the high energy long-baseline CERN to LNGS neutrino beam (CNGS) 730 km away from the neutrino source. The observation of a first nu_tau candidate event was reported in 2010. In this paper, we present the status of the experiment based on the analysis of the data taken during the first two years of operation (2008-2009). The statistical significance of the one event observed so far is then assessed.

  2. Candidate genes for COPD: current evidence and research

    Directory of Open Access Journals (Sweden)

    Kim WJ

    2015-10-01

    Full Text Available Woo Jin Kim,1 Sang Do Lee2 1Department of Internal Medicine and Environmental Health Center, Kangwon National University, Chuncheon, 2Department of Pulmonary and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea Abstract: COPD is a common complex disease characterized by progressive airflow limitation. Several genome-wide association studies (GWASs have discovered genes that are associated with COPD. Recently, candidate genes for COPD identified by GWASs include CHRNA3/5 (cholinergic nicotine receptor alpha 3/5, IREB2 (iron regulatory binding protein 2, HHIP (hedgehog-interacting protein, FAM13A (family with sequence similarity 13, member A, and AGER (advanced glycosylation end product–specific receptor. Their association with COPD susceptibility has been replicated in multiple populations. Since these candidate genes have not been considered in COPD, their pathological roles are still largely unknown. Herein, we review some evidences that they can be effective drug targets or serve as biomarkers for diagnosis or subtyping. However, more study is required to understand the functional roles of these candidate genes. Future research is needed to characterize the effect of genetic variants, validate gene function in humans and model systems, and elucidate the genes’ transcriptional and posttranscriptional regulatory mechanisms. Keywords: chronic obstructive pulmonary disease, genetics, genome-wide association study

  3. Accelerating tuberculosis vaccine trials with diagnostic and prognostic biomarkers.

    Science.gov (United States)

    Kaufmann, Stefan H E; Weiner, January; Maertzdorf, Jeroen

    2017-08-01

    The most recent estimates on tuberculosis (TB) morbidity and mortality reveal that the global disease burden is even higher than previously assumed. Better drugs, diagnostics and vaccines are major requirements to control the ongoing TB pandemic. The high complexity of the infectious process and the underlying pathology, however, challenge elucidation of protective immune mechanisms at the various stages towards active TB disease, which need to be understood for rational design of novel intervention measures. Areas covered: Next to the more classical approaches, host biomarkers increasingly receive attention as promising tools on our way to control the disease. In the area of diagnosis, host biomarkers are recognized as promising new means because the identification of small biosignatures with high discriminatory and even prognostic potential has stimulated the hope that rapid and easy-to-perform diagnosis and prognosis will become possible in the near future. For rational design of new vaccine candidates, correlates of protection are highly desirable. High-throughput systems-vaccinology will boost the identification of such biomarker profiles. Expert commentary: Considering their potential to accelerate development of better diagnostics and vaccines, host biomarkers should be firmly integrated into future TB research.

  4. Current status of fluid biomarkers in mild traumatic brain injury

    Science.gov (United States)

    Kulbe, Jacqueline R.; Geddes, James W.

    2015-01-01

    Mild traumatic brain injury (mTBI) affects millions of people annually and is difficult to diagnose. Mild injury is insensitive to conventional imaging techniques and diagnoses are often made using subjective criteria such as self-reported symptoms. Many people who sustain a mTBI develop persistent post-concussive symptoms. Athletes and military personnel are at great risk for repeat injury which can result in second impact syndrome or chronic traumatic encephalopathy. An objective and quantifiable measure, such as a serum biomarker, is needed to aid in mTBI diagnosis, prognosis, return to play/duty assessments, and would further elucidate mTBI pathophysiology. The majority of TBI biomarker research focuses on severe TBI with few studies specific to mild injury. Most studies use a hypothesis-driven approach, screening biofluids for markers known to be associated with TBI pathophysiology. This approach has yielded limited success in identifying markers that can be used clinically, additional candidate biomarkers are needed. Innovative and unbiased methods such as proteomics, microRNA arrays, urinary screens, autoantibody identification and phage display would complement more traditional approaches to aid in the discovery of novel mTBI biomarkers. PMID:25981889

  5. Biomarkers for Detecting Mitochondrial Disorders

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2018-01-01

    Full Text Available (1 Objectives: Mitochondrial disorders (MIDs are a genetically and phenotypically heterogeneous group of slowly or rapidly progressive disorders with onset from birth to senescence. Because of their variegated clinical presentation, MIDs are difficult to diagnose and are frequently missed in their early and late stages. This is why there is a need to provide biomarkers, which can be easily obtained in the case of suspecting a MID to initiate the further diagnostic work-up. (2 Methods: Literature review. (3 Results: Biomarkers for diagnostic purposes are used to confirm a suspected diagnosis and to facilitate and speed up the diagnostic work-up. For diagnosing MIDs, a number of dry and wet biomarkers have been proposed. Dry biomarkers for MIDs include the history and clinical neurological exam and structural and functional imaging studies of the brain, muscle, or myocardium by ultrasound, computed tomography (CT, magnetic resonance imaging (MRI, MR-spectroscopy (MRS, positron emission tomography (PET, or functional MRI. Wet biomarkers from blood, urine, saliva, or cerebrospinal fluid (CSF for diagnosing MIDs include lactate, creatine-kinase, pyruvate, organic acids, amino acids, carnitines, oxidative stress markers, and circulating cytokines. The role of microRNAs, cutaneous respirometry, biopsy, exercise tests, and small molecule reporters as possible biomarkers is unsolved. (4 Conclusions: The disadvantages of most putative biomarkers for MIDs are that they hardly meet the criteria for being acceptable as a biomarker (missing longitudinal studies, not validated, not easily feasible, not cheap, not ubiquitously available and that not all MIDs manifest in the brain, muscle, or myocardium. There is currently a lack of validated biomarkers for diagnosing MIDs.

  6. MortalityPredictors.org: a manually-curated database of published biomarkers of human all-cause mortality.

    Science.gov (United States)

    Peto, Maximus V; De la Guardia, Carlos; Winslow, Ksenia; Ho, Andrew; Fortney, Kristen; Morgen, Eric

    2017-08-31

    Biomarkers of all-cause mortality are of tremendous clinical and research interest. Because of the long potential duration of prospective human lifespan studies, such biomarkers can play a key role in quantifying human aging and quickly evaluating any potential therapies. Decades of research into mortality biomarkers have resulted in numerous associations documented across hundreds of publications. Here, we present MortalityPredictors.org , a manually-curated, publicly accessible database, housing published, statistically-significant relationships between biomarkers and all-cause mortality in population-based or generally healthy samples. To gather the information for this database, we searched PubMed for appropriate research papers and then manually curated relevant data from each paper. We manually curated 1,576 biomarker associations, involving 471 distinct biomarkers. Biomarkers ranged in type from hematologic (red blood cell distribution width) to molecular (DNA methylation changes) to physical (grip strength). Via the web interface, the resulting data can be easily browsed, searched, and downloaded for further analysis. MortalityPredictors.org provides comprehensive results on published biomarkers of human all-cause mortality that can be used to compare biomarkers, facilitate meta-analysis, assist with the experimental design of aging studies, and serve as a central resource for analysis. We hope that it will facilitate future research into human mortality and aging.

  7. Candidate genes in panic disorder

    DEFF Research Database (Denmark)

    Howe, A. S.; Buttenschön, Henriette N; Bani-Fatemi, A.

    2016-01-01

    The utilization of molecular genetics approaches in examination of panic disorder (PD) has implicated several variants as potential susceptibility factors for panicogenesis. However, the identification of robust PD susceptibility genes has been complicated by phenotypic diversity, underpowered...... association studies and ancestry-specific effects. In the present study, we performed a succinct review of case-control association studies published prior to April 2015. Meta-analyses were performed for candidate gene variants examined in at least three studies using the Cochrane Mantel-Haenszel fixed......-effect model. Secondary analyses were also performed to assess the influences of sex, agoraphobia co-morbidity and ancestry-specific effects on panicogenesis. Meta-analyses were performed on 23 variants in 20 PD candidate genes. Significant associations after correction for multiple testing were observed...

  8. Guidelines for uniform reporting of body fluid biomarker studies in neurologic disorders

    DEFF Research Database (Denmark)

    Gnanapavan, Sharmilee; Hegen, Harald; Khalil, Michael

    2014-01-01

    , there are concerns over the high attrition rate of promising candidate biomarkers at later phases of development. METHODS: BioMS-eu consortium, a collaborative network working toward improving the quality of biomarker research in neurologic disorders, discussed the merits of standardizing the reporting of body fluid...... biomarker research. A checklist of items integrating the results of other published guidances, literature, conferences, regulatory opinion, and personal expertise was created to ultimately form a structured summary guidance incorporating the key features. RESULTS: The summary guidance is comprised of a 10......-point uniform reporting format ranging from introduction, materials and methods, through to results and discussion. Each item is discussed in detail in the guidance report. CONCLUSIONS: To enhance the future development of body fluid biomarkers, it will be important to standardize the reporting...

  9. Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies.

    Science.gov (United States)

    Aerts, Johannes M F G; Kallemeijn, Wouter W; Wegdam, Wouter; Joao Ferraz, Maria; van Breemen, Marielle J; Dekker, Nick; Kramer, Gertjan; Poorthuis, Ben J; Groener, Johanna E M; Cox-Brinkman, Josanne; Rombach, Saskia M; Hollak, Carla E M; Linthorst, Gabor E; Witte, Martin D; Gold, Henrik; van der Marel, Gijs A; Overkleeft, Herman S; Boot, Rolf G

    2011-06-01

    A biomarker is an analyte indicating the presence of a biological process linked to the clinical manifestations and outcome of a particular disease. In the case of lysosomal storage disorders (LSDs), primary and secondary accumulating metabolites or proteins specifically secreted by storage cells are good candidates for biomarkers. Clinical applications of biomarkers are found in improved diagnosis, monitoring disease progression, and assessing therapeutic correction. These are illustrated by reviewing the discovery and use of biomarkers for Gaucher disease and Fabry disease. In addition, recently developed chemical tools allowing specific visualization of enzymatically active lysosomal glucocerebrosidase are described. Such probes, coined inhibodies, offer entirely new possibilities for more sophisticated molecular diagnosis, enzyme replacement therapy monitoring, and fundamental research.

  10. Electroencephalography Is a Good Complement to Currently Established Dementia Biomarkers

    DEFF Research Database (Denmark)

    Ferreira, Daniel; Jelic, Vesna; Cavallin, Lena

    2016-01-01

    , 135 Alzheimer's disease (AD), 15 dementia with Lewy bodies/Parkinson's disease with dementia (DLB/PDD), 32 other dementias]. The EEG data were recorded in a standardized way. Structural imaging data were visually rated using scales of atrophy in the medial temporal, frontal, and posterior cortex......BACKGROUND/AIMS: Dementia biomarkers that are accessible and easily applicable in nonspecialized clinical settings are urgently needed. Quantitative electroencephalography (qEEG) is a good candidate, and the statistical pattern recognition (SPR) method has recently provided promising results. We......EEG to the diagnostic workup substantially increases the detection of AD pathology even in pre-dementia stages and improves differential diagnosis. EEG could serve as a good complement to currently established dementia biomarkers since it is cheap, noninvasive, and extensively applied outside academic centers....

  11. Circulating miRNAs as biomarkers for endocrine disorders.

    Science.gov (United States)

    Butz, H; Kinga, N; Racz, K; Patocs, A

    2016-01-01

    Specific, sensitive and non-invasive biomarkers are always needed in endocrine disorders. miRNAs are short, non-coding RNA molecules with well-known role in gene expression regulation. They are frequently dysregulated in metabolic and endocrine diseases. Recently it has been shown that they are secreted into biofluids by nearly all kind of cell types. As they can be taken up by other cells they may have a role in a new kind of paracrine, cell-to-cell communication. Circulating miRNAs are protected by RNA-binding proteins or microvesicles hence they can be attractive candidates as diagnostic or prognostic biomarkers. In this review, we summarize the characteristics of extracellular miRNA's and our knowledge about their origin and potential roles in endocrine and metabolic diseases. Discussions about the technical challenges occurring during identification and measurement of extracellular miRNAs and future perspectives about their roles are also highlighted.

  12. Acute diagnostic biomarkers for spinal cord injury: review of the literature and preliminary research report.

    Science.gov (United States)

    Yokobori, Shoji; Zhang, Zhiqun; Moghieb, Ahmed; Mondello, Stefania; Gajavelli, Shyam; Dietrich, W Dalton; Bramlett, Helen; Hayes, Ronald L; Wang, Michael; Wang, Kevin K W; Bullock, M Ross

    2015-05-01

    Many efforts have been made to create new diagnostic technologies for use in the diagnosis of central nervous system injury. However, there is still no consensus for the use of biomarkers in clinical acute spinal cord injury (SCI). The aims of this review are (1) to evaluate the current status of neurochemical biomarkers and (2) to discuss their potential acute diagnostic role in SCI by reviewing the literature. PubMed (http://www.ncbi.nlm.nih.gov/pubmed) was searched up to 2012 to identify publications concerning diagnostic biomarkers in SCI. To support more knowledge, we also checked secondary references in the primarily retrieved literature. Neurofilaments, cleaved-Tau, microtubule-associated protein 2, myelin basic protein, neuron-specific enolase, S100β, and glial fibrillary acidic protein were identified as structural protein biomarkers in SCI by this review process. We could not find reports relating ubiquitin C-terminal hydrolase-L1 and α-II spectrin breakdown products, which are widely researched in other central nervous system injuries. Therefore, we present our preliminary data relating to these two biomarkers. Some of biomarkers showed promising results for SCI diagnosis and outcome prediction; however, there were unresolved issues relating to accuracy and their accessibility. Currently, there still are not many reports focused on diagnostic biomarkers in SCI. This fact warranted the need for greater efforts to innovate sensitive and reliable biomarkers for SCI. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Indirect search for dark matter with AMS

    International Nuclear Information System (INIS)

    Goy, Corinne

    2006-01-01

    This document summarises the potential of AMS in the indirect search for Dark Matter. Observations and cosmology indicate that the Universe may include a large amount of Dark Matter of unknown nature. A good candidate is the Ligthest Supersymmetric Particle in R-Parity conserving models. AMS offers a unique opportunity to study Dark Matter indirect signature in three spectra: gamma, antiprotons and positrons

  14. Urinary Biomarkers of Brain Diseases

    Directory of Open Access Journals (Sweden)

    Manxia An

    2015-12-01

    Full Text Available Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.

  15. Biomarkers of latent TB infection

    DEFF Research Database (Denmark)

    Ruhwald, Morten; Ravn, Pernille

    2009-01-01

    For the last 100 years, the tuberculin skin test (TST) has been the only diagnostic tool available for latent TB infection (LTBI) and no biomarker per se is available to diagnose the presence of LTBI. With the introduction of M. tuberculosis-specific IFN-gamma release assays (IGRAs), a new area...... of in vitro immunodiagnostic tests for LTBI based on biomarker readout has become a reality. In this review, we discuss existing evidence on the clinical usefulness of IGRAs and the indefinite number of potential new biomarkers that can be used to improve diagnosis of latent TB infection. We also present...... early data suggesting that the monocyte-derived chemokine inducible protein-10 may be useful as a novel biomarker for the immunodiagnosis of latent TB infection....

  16. Clinical librarian support for rapid review of clinical utility of cancer molecular biomarkers.

    Science.gov (United States)

    Geng, Yimin; Fowler, Clara S; Fulton, Stephanie

    2015-01-01

    The clinical librarian used a restricted literature searching and quality-filtering approach to provide relevant clinical evidence for the use of cancer molecular biomarkers by institutional policy makers and clinicians in the rapid review process. The librarian-provided evidence was compared with the cited references in the institutional molecular biomarker algorithm. The overall incorporation rate of the librarian-provided references into the algorithm was above 80%. This study suggests the usefulness of clinical librarian expertise for clinical practice. The searching and filtering methods for high-level evidence can be adopted by information professionals who are involved in the rapid literature review.

  17. The Knowledge-Integrated Network Biomarkers Discovery for Major Adverse Cardiac Events

    Science.gov (United States)

    Jin, Guangxu; Zhou, Xiaobo; Wang, Honghui; Zhao, Hong; Cui, Kemi; Zhang, Xiang-Sun; Chen, Luonan; Hazen, Stanley L.; Li, King; Wong, Stephen T. C.

    2010-01-01

    The mass spectrometry (MS) technology in clinical proteomics is very promising for discovery of new biomarkers for diseases management. To overcome the obstacles of data noises in MS analysis, we proposed a new approach of knowledge-integrated biomarker discovery using data from Major Adverse Cardiac Events (MACE) patients. We first built up a cardiovascular-related network based on protein information coming from protein annotations in Uniprot, protein–protein interaction (PPI), and signal transduction database. Distinct from the previous machine learning methods in MS data processing, we then used statistical methods to discover biomarkers in cardiovascular-related network. Through the tradeoff between known protein information and data noises in mass spectrometry data, we finally could firmly identify those high-confident biomarkers. Most importantly, aided by protein–protein interaction network, that is, cardiovascular-related network, we proposed a new type of biomarkers, that is, network biomarkers, composed of a set of proteins and the interactions among them. The candidate network biomarkers can classify the two groups of patients more accurately than current single ones without consideration of biological molecular interaction. PMID:18665624

  18. Biomarkers-a potential route for improved diagnosis and management of ongoing renal damage.

    Science.gov (United States)

    Oberbauer, R

    2008-12-01

    Currently, the identification and validation of biomarkers of kidney injury is among the top priorities of many diagnostic biotechnology companies as well as academic research institutes. Specifically, in renal transplantation, validated biomarkers of tissue injury with good discriminatory power between the various renal compartments and the underlying pathophysiology are desired, because sequential allograft biopsies are limited in number and cannot be used as a screening tool. Given the high demands on these markers, it is not surprising that none of those currently under evaluation has been thoroughly validated for a specific entity. Published biomarker candidates for early tubular damage include neutrophil gelatinase-associated lipocalin (NGAL), interleukin (IL)-18, soluble CD30, perforin, and granzyme B. Recently, C4d flow panel reactive antibodies were evaluated as biomarkers for humoral alloimmune responses. Additional biomarkers such as FOXP3 and kidney injury molecule 1 have been studied in the maintenance phase of renal transplantation. Given the complex prerequisites, it is not surprising that no biomarker panel has been sufficiently validated for clinical use. However, in the near future a biomarker for use as an indicator of renal tubule cell injury will be available. Troponin T or transaminase of the kidney may then at least be used to differentiate between functional renal failure (equivalent to a rise in creatinine) and intrinsic kidney injury.

  19. Breath biomarkers in toxicology.

    Science.gov (United States)

    Pleil, Joachim D

    2016-11-01

    Exhaled breath has joined blood and urine as a valuable resource for sampling and analyzing biomarkers in human media for assessing exposure, uptake metabolism, and elimination of toxic chemicals. This article focuses current use of exhaled gas, aerosols, and vapor in human breath, the methods for collection, and ultimately the use of the resulting data. Some advantages of breath are the noninvasive and self-administered nature of collection, the essentially inexhaustible supply, and that breath sampling does not produce potentially infectious waste such as needles, wipes, bandages, and glassware. In contrast to blood and urine, breath samples can be collected on demand in rapid succession and so allow toxicokinetic observations of uptake and elimination in any time frame. Furthermore, new technologies now allow capturing condensed breath vapor directly, or just the aerosol fraction alone, to gain access to inorganic species, lung pH, proteins and protein fragments, cellular DNA, and whole microorganisms from the pulmonary microbiome. Future applications are discussed, especially the use of isotopically labeled probes, non-targeted (discovery) analysis, cellular level toxicity testing, and ultimately assessing "crowd breath" of groups of people and the relation to dose of airborne and other environmental chemicals at the population level.

  20. Novel TIA biomarkers identified by mass spectrometry-based proteomics.

    Science.gov (United States)

    George, Paul M; Mlynash, Michael; Adams, Christopher M; Kuo, Calvin J; Albers, Gregory W; Olivot, Jean-Marc

    2015-12-01

    Transient ischemic attacks remain a clinical diagnosis with significant variability between physicians. Finding reliable biomarkers to identify transient ischemic attacks would improve patient care and optimize treatment. Our aim is to identify novel serum TIA biomarkers through the use of mass spectroscopy-based proteomics. Patients with transient neurologic symptoms were prospectively enrolled. Mass spectrometry-based proteomics, an unbiased method to identify candidate proteins, was used to test the serum of the patients for biomarkers of cerebral ischemia. Three candidate proteins were found, and serum concentrations of these proteins were measured by enzyme-linked immunosorbent assay in a second cohort of prospectively enrolled patients. The Student's t-test was used for comparison. The Benjamini-Hochberg false discovery rate controlling procedure for multiple comparison adjustments determined significance for the proteomic screen. Patients with transient ischemic attacks (n = 20), minor strokes (n = 15), and controls (i.e. migraine, seizure, n = 12) were enrolled in the first cohort. Ceruloplasmin, complement component C8 gamma (C8γ), and platelet basic protein were significantly different between the ischemic group (transient ischemic attack and minor stroke) and the controls (P = 0·0001, P = 0·00027, P = 0·00105, respectively). A second cohort of patients with transient ischemic attack (n = 22), minor stroke (n = 20), and controls' (n = 12) serum was enrolled. Platelet basic protein serum concentrations were increased in the ischemic samples compared with control (for transient ischemic attack alone, P = 0·019, for the ischemic group, P = 0·046). Ceruloplasmin trended towards increased concentrations in the ischemic group (P = 0·127); no significant difference in C8γ (P = 0·44) was found. Utilizing mass spectrometry-based proteomics, platelet basic protein has been identified as a candidate serum

  1. Analysis of biomarker data a practical guide

    CERN Document Server

    Looney, Stephen W

    2015-01-01

    A "how to" guide for applying statistical methods to biomarker data analysis Presenting a solid foundation for the statistical methods that are used to analyze biomarker data, Analysis of Biomarker Data: A Practical Guide features preferred techniques for biomarker validation. The authors provide descriptions of select elementary statistical methods that are traditionally used to analyze biomarker data with a focus on the proper application of each method, including necessary assumptions, software recommendations, and proper interpretation of computer output. In addition, the book discusses

  2. A new approach towards biomarker selection in estimation of human exposure to chiral chemicals: a case study of mephedrone.

    Science.gov (United States)

    Castrignanò, Erika; Mardal, Marie; Rydevik, Axel; Miserez, Bram; Ramsey, John; Shine, Trevor; Pantoș, G Dan; Meyer, Markus R; Kasprzyk-Hordern, Barbara

    2017-11-02

    Wastewater-based epidemiology is an innovative approach to estimate public health status using biomarker analysis in wastewater. A new compound detected in wastewater can be a potential biomarker of an emerging trend in public health. However, it is currently difficult to select new biomarkers mainly due to limited human metabolism data. This manuscript presents a new framework, which enables the identification and selection of new biomarkers of human exposure to drugs with scarce or unknown human metabolism data. Mephedrone was targeted to elucidate the assessment of biomarkers for emerging drugs of abuse using a four-step analytical procedure. This framework consists of: (i) identification of possible metabolic biomarkers present in wastewater using an in-vivo study; (ii) verification of chiral signature of the target compound; (iii) confirmation of human metabolic residues in in-vivo/vitro studies and (iv) verification of stability of biomarkers in wastewater. Mephedrone was selected as a suitable biomarker due to its high stability profile in wastewater. Its enantiomeric profiling was studied for the first time in biological and environmental matrices, showing stereoselective metabolism of mephedrone in humans. Further biomarker candidates were also proposed for future investigation: 4'-carboxy-mephedrone, 4'-carboxy-normephedrone, 1-dihydro-mephedrone, 1-dihydro-normephedrone and 4'-hydroxy-normephedrone.

  3. Biochemical Markers for Osteoarthritis: Is There any Promising Candidate?

    Directory of Open Access Journals (Sweden)

    Elif Aydın

    2016-04-01

    Full Text Available Osteoarthritis (OA is the most common degenerative joint disease. OA affects millions of individuals each year and becoming the most important cause of pain in geriatric population. Progressive destruction of articular cartilage is one of the prominent features of the disease. The diagnosis of OA is generally based on clinical and radiographical findings, which are insufficient to determine early-stage OA and predict disease course. There is a need for biomarkers that help clinicians early diagnose, assess disease activity, predict prognosis and monitor response to therapy. There are a growing number of publications regarding candidate markers in this field. The aim of this paper was to review recent studies on biochemical markers that reflect cartilage, synovial and bone turnover and their clinical use in patients with OA.

  4. Identifying candidate driver genes by integrative ovarian cancer genomics data

    Science.gov (United States)

    Lu, Xinguo; Lu, Jibo

    2017-08-01

    Integrative analysis of molecular mechanics underlying cancer can distinguish interactions that cannot be revealed based on one kind of data for the appropriate diagnosis and treatment of cancer patients. Tumor samples exhibit heterogeneity in omics data, such as somatic mutations, Copy Number Variations CNVs), gene expression profiles and so on. In this paper we combined gene co-expression modules and mutation modulators separately in tumor patients to obtain the candidate driver genes for resistant and sensitive tumor from the heterogeneous data. The final list of modulators identified are well known in biological processes associated with ovarian cancer, such as CCL17, CACTIN, CCL16, CCL22, APOB, KDF1, CCL11, HNF1B, LRG1, MED1 and so on, which can help to facilitate the discovery of biomarkers, molecular diagnostics, and drug discovery.

  5. Meta Search Engines.

    Science.gov (United States)

    Garman, Nancy

    1999-01-01

    Describes common options and features to consider in evaluating which meta search engine will best meet a searcher's needs. Discusses number and names of engines searched; other sources and specialty engines; search queries; other search options; and results options. (AEF)

  6. Characterisation of a candidate dual AGN

    Science.gov (United States)

    Lena, D.; Panizo-Espinar, G.; Jonker, P. G.; Torres, M.; Heida, M.

    2018-05-01

    We present Chandra and optical observations of a candidate dual AGN discovered serendipitously while searching for recoiling black holes via a cross-correlation between the serendipitous XMM source catalog (2XMMi) and SDSS-DR7 galaxies with a separation no larger than ten times the sum of their Petrosian radii. The system has a stellar mass ratio M1/M2 ≈ 0.7. One of the galaxies (Source 1) shows clear evidence for AGN activity in the form of hard X-ray emission and optical emission-line diagnostics typical of AGN ionisation. The nucleus of the other galaxy (Source 2) has a soft X-ray spectrum, bluer colours, and optical emission line ratios dominated by stellar photoionisation with a "composite" signature, which might indicate the presence of a weak AGN. When plotted on a diagram with X-ray luminosity vs [OIII] luminosity both nuclei fall within the locus defined by local Seyfert galaxies. From the optical spectrum we estimate the electron densities finding n1 active nature of Source 1 can be established with confidence, whether the nucleus of Source 2 is active remains a matter of debate. Evidence that a faint AGN might reside in its nucleus is, however, tantalising.

  7. PLANETARY CANDIDATES FROM THE FIRST YEAR OF THE K2 MISSION

    Energy Technology Data Exchange (ETDEWEB)

    Vanderburg, Andrew; Latham, David W.; Bieryla, Allyson; Berlind, Perry; Calkins, Michael L.; Esquerdo, Gilbert A.; Welsh, Sophie; Johnson, John Asher [Harvard–Smithsonian Center for Astrophysics, 60 Garden St., Cambridge, MA 02138 (United States); Buchhave, Lars A., E-mail: avanderburg@cfa.harvard.edu [Centre for Star and Planet Formation, Natural History Museum of Denmark and Niels Bohr Institute, University of Copenhagen, Øster Voldgade 5-7, DK-1350 Copenhagen K (Denmark)

    2016-01-15

    The Kepler Space Telescope is currently searching for planets transiting stars along the ecliptic plane as part of its extended K2 mission. We processed the publicly released data from the first year of K2 observations (Campaigns 0, 1, 2, and 3) and searched for periodic eclipse signals consistent with planetary transits. Out of the 59,174 targets that we searched, we detect 234 planetary candidates around 208 stars. These candidates range in size from gas giants to smaller than the Earth, and range in orbital periods from hours to over a month. We conducted initial reconnaissance spectroscopy of 68 of the brighter candidate host stars, and present high-resolution optical spectra for these stars. We make all of our data products, including light curves, spectra, and vetting diagnostics available to users online.

  8. The current state of serum biomarkers of hepatotoxicity.

    Science.gov (United States)

    Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli

    2008-03-20

    The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTalpha) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in

  9. The current state of serum biomarkers of hepatotoxicity

    International Nuclear Information System (INIS)

    Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli

    2008-01-01

    The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTα) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in early

  10. Search for dark-matter particles

    International Nuclear Information System (INIS)

    Cowsik, R.

    1991-01-01

    Experiments performed over the last two years have been very successful in drastically reducing the number of viable elementary particles that could possibly constitute the dark matter that dominates the large-scale gravitational dynamics of astronomical systems. The candidates that survive are the light neutrinos, the axion, and a supersymmetric particle with carefully chosen parameters called the neutralino. Baryonic dark matter, which might contribute not insignificantly over small scales, is perhaps present in the form of brown dwarfs, and a search for these is under way. In this article, the astrophysical studies which bear on the density and the phase-space structure of the dark-matter particles are reviewed and the implications of the various direct and indirect searches for these particles are discussed and, finally, alternative suggestions for the candidates and directions for further searches are pointed out. (author). 35 refs., 29 figs

  11. Transcriptomic biomarkers of altered erythropoiesis to detect autologous blood transfusion.

    Science.gov (United States)

    Salamin, Olivier; Mignot, Jonathan; Kuuranne, Tiia; Saugy, Martial; Leuenberger, Nicolas

    2018-03-01

    Autologous blood transfusion is a powerful means of improving performance and remains one of the most challenging methods to detect. Recent investigations have identified 3 candidate reticulocytes genes whose expression was significantly influenced by blood transfusion. Using quantitative reverse transcription polymerase chain reaction as an alternative quantitative method, the present study supports that delta-aminolevulinate synthase 2 (ALAS2), carbonic anhydrase (CA1), and solute carrier family 4 member 1 (SLC4A1) genes are down-regulated post-transfusion. The expression of these genes exhibited stronger correlation with immature reticulocyte fraction than with reticulocytes percentage. Moreover, the repression of reticulocytes' gene expression was more pronounced than the diminution of immature reticulocyte fraction and reticulocyte percentage following blood transfusion. It suggests that the 3 candidate genes are reliable predictors of bone marrow's response to blood transfusion and that they represent potential biomarkers for the detection of this method prohibited in sports. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Locality in Generic Instance Search from One Example

    NARCIS (Netherlands)

    Tao, R.; Gavves, E.; Snoek, C.G.M.; Smeulders, A.W.M.

    2014-01-01

    This paper aims for generic instance search from a single example. Where the state-of-the-art relies on global image representation for the search, we proceed by including locality at all steps of the method. As the first novelty, we consider many boxes per database image as candidate targets to

  13. Biomarkers for Response to Neoadjuvant Chemoradiation for Rectal Cancer

    International Nuclear Information System (INIS)

    Kuremsky, Jeffrey G.; Tepper, Joel E.; McLeod, Howard L. Phar

    2009-01-01

    Locally advanced rectal cancer (LARC) is currently treated with neoadjuvant chemoradiation. Although approximately 45% of patients respond to neoadjuvant therapy with T-level downstaging, there is no effective method of predicting which patients will respond. Molecular biomarkers have been investigated for their ability to predict outcome in LARC treated with neoadjuvant chemotherapy and radiation. A literature search using PubMed resulted in the initial assessment of 1,204 articles. Articles addressing the ability of a biomarker to predict outcome for LARC treated with neoadjuvant chemotherapy and radiation were included. Six biomarkers met the criteria for review: p53, epidermal growth factor receptor (EGFR), thymidylate synthase, Ki-67, p21, and bcl-2/bax. On the basis of composite data, p53 is unlikely to have utility as a predictor of response. Epidermal growth factor receptor has shown promise as a predictor when quantitatively evaluated in pretreatment biopsies or when EGFR polymorphisms are evaluated in germline DNA. Thymidylate synthase, when evaluated for polymorphisms in germline DNA, is promising as a predictive biomarker. Ki-67 and bcl-2 are not useful in predicting outcome. p21 needs to be further evaluated to determine its usefulness in predicting outcome. Bax requires more investigation to determine its usefulness. Epidermal growth factor receptor, thymidylate synthase, and p21 should be evaluated in larger prospective clinical trials for their ability to guide preoperative therapy choices in LARC.

  14. Planet Candidate Validation in K2 Crowded Fields

    Science.gov (United States)

    Rampalli, Rayna; Vanderburg, Andrew; Latham, David; Quinn, Samuel

    2018-01-01

    In just three years, the K2 mission has yielded some remarkable outcomes with the discovery of over 100 confirmed planets and 500 reported planet candidates to be validated. One challenge with this mission is the search for planets located in star-crowded regions. Campaign 13 is one such example, located towards the galactic plane in the constellation of Taurus. We subject the potential planetary candidates to a validation process involving spectroscopy to derive certain stellar parameters. Seeing-limited on/off imaging follow-up is also utilized in order to rule out false positives due to nearby eclipsing binaries. Using Markov chain Monte Carlo analysis, the best-fit parameters for each candidate are generated. These will be suitable for finding a candidate’s false positive probability through methods including feeding such parameters into the Validation of Exoplanet Signals using a Probabilistic Algorithm (VESPA). These techniques and results serve as important tools for conducting candidate validation and follow-up observations for space-based missions such as the upcoming TESS mission since TESS’s large camera pixels resemble K2’s star-crowded fields.

  15. Proteome analysis of body fluids for amyotrophic lateral sclerosis biomarker discovery.

    Science.gov (United States)

    Krüger, Thomas; Lautenschläger, Janin; Grosskreutz, Julian; Rhode, Heidrun

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of motor neurons leading to death of the patients, mostly within 2-5 years after disease onset. The pathomechanism of motor neuron degeneration is only partially understood and therapeutic strategies based on mechanistic insights are largely ineffective. The discovery of reliable biomarkers of disease diagnosis and progression is the sine qua non of both the revelation of insights into the ALS pathomechanism and the assessment of treatment efficacies. Proteomic approaches are an important pillar in ALS biomarker discovery. Cerebrospinal fluid is the most promising body fluid for differential proteome analyses, followed by blood (serum, plasma), and even urine and saliva. The present study provides an overview about reported peptide/protein biomarker candidates that showed significantly altered levels in certain body fluids of ALS patients. These findings have to be discussed according to proposed pathomechanisms to identify modifiers of disease progression and to pave the way for the development of potential therapeutic strategies. Furthermore, limitations and advantages of proteomic approaches for ALS biomarker discovery in different body fluids and reliable validation of biomarker candidates have been addressed. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. 11 CFR 100.154 - Candidate debates.

    Science.gov (United States)

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Candidate debates. 100.154 Section 100.154 Federal Elections FEDERAL ELECTION COMMISSION GENERAL SCOPE AND DEFINITIONS (2 U.S.C. 431) Exceptions to Expenditures § 100.154 Candidate debates. Funds used to defray costs incurred in staging candidate debates in...

  17. 11 CFR 100.92 - Candidate debates.

    Science.gov (United States)

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Candidate debates. 100.92 Section 100.92 Federal Elections FEDERAL ELECTION COMMISSION GENERAL SCOPE AND DEFINITIONS (2 U.S.C. 431) Exceptions to Contributions § 100.92 Candidate debates. Funds provided to defray costs incurred in staging candidate debates...

  18. Biomarkers in acute heart failure.

    Science.gov (United States)

    Mallick, Aditi; Januzzi, James L

    2015-06-01

    The care of patients with acutely decompensated heart failure is being reshaped by the availability and understanding of several novel and emerging heart failure biomarkers. The gold standard biomarkers in heart failure are B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, which play an important role in the diagnosis, prognosis, and management of acute decompensated heart failure. Novel biomarkers that are increasingly involved in the processes of myocardial injury, neurohormonal activation, and ventricular remodeling are showing promise in improving diagnosis and prognosis among patients with acute decompensated heart failure. These include midregional proatrial natriuretic peptide, soluble ST2, galectin-3, highly-sensitive troponin, and midregional proadrenomedullin. There has also been an emergence of biomarkers for evaluation of acute decompensated heart failure that assist in the differential diagnosis of dyspnea, such as procalcitonin (for identification of acute pneumonia), as well as markers that predict complications of acute decompensated heart failure, such as renal injury markers. In this article, we will review the pathophysiology and usefulness of established and emerging biomarkers for the clinical diagnosis, prognosis, and management of acute decompensated heart failure. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  19. An integrative multi-platform analysis for discovering biomarkers of osteosarcoma

    International Nuclear Information System (INIS)

    Li, Guodong; Zhang, Wenjuan; Zeng, Huazong; Chen, Lei; Wang, Wenjing; Liu, Jilong; Zhang, Zhiyu; Cai, Zhengdong

    2009-01-01

    SELDI-TOF-MS (Surface Enhanced Laser Desorption/Ionization-Time of Flight-Mass Spectrometry) has become an attractive approach for cancer biomarker discovery due to its ability to resolve low mass proteins and high-throughput capability. However, the analytes from mass spectrometry are described only by their mass-to-charge ratio (m/z) values without further identification and annotation. To discover potential biomarkers for early diagnosis of osteosarcoma, we designed an integrative workflow combining data sets from both SELDI-TOF-MS and gene microarray analysis. After extracting the information for potential biomarkers from SELDI data and microarray analysis, their associations were further inferred by link-test to identify biomarkers that could likely be used for diagnosis. Immuno-blot analysis was then performed to examine whether the expression of the putative biomarkers were indeed altered in serum from patients with osteosarcoma. Six differentially expressed protein peaks with strong statistical significances were detected by SELDI-TOF-MS. Four of the proteins were up-regulated and two of them were down-regulated. Microarray analysis showed that, compared with an osteoblastic cell line, the expression of 653 genes was changed more than 2 folds in three osteosarcoma cell lines. While expression of 310 genes was increased, expression of the other 343 genes was decreased. The two sets of biomarkers candidates were combined by the link-test statistics, indicating that 13 genes were potential biomarkers for early diagnosis of osteosarcoma. Among these genes, cytochrome c1 (CYC-1) was selected for further experimental validation. Link-test on datasets from both SELDI-TOF-MS and microarray high-throughput analysis can accelerate the identification of tumor biomarkers. The result confirmed that CYC-1 may be a promising biomarker for early diagnosis of osteosarcoma

  20. GSNFS: Gene subnetwork biomarker identification of lung cancer expression data.

    Science.gov (United States)

    Doungpan, Narumol; Engchuan, Worrawat; Chan, Jonathan H; Meechai, Asawin

    2016-12-05

    Gene expression has been used to identify disease gene biomarkers, but there are ongoing challenges. Single gene or gene-set biomarkers are inadequate to provide sufficient understanding of complex disease mechanisms and the relationship among those genes. Network-based methods have thus been considered for inferring the interaction within a group of genes to further study the disease mechanism. Recently, the Gene-Network-based Feature Set (GNFS), which is capable of handling case-control and multiclass expression for gene biomarker identification, has been proposed, partly taking into account of network topology. However, its performance relies on a greedy search for building subnetworks and thus requires further improvement. In this work, we establish a new approach named Gene Sub-Network-based Feature Selection (GSNFS) by implementing the GNFS framework with two proposed searching and scoring algorithms, namely gene-set-based (GS) search and parent-node-based (PN) search, to identify subnetworks. An additional dataset is used to validate the results. The two proposed searching algorithms of the GSNFS method for subnetwork expansion are concerned with the degree of connectivity and the scoring scheme for building subnetworks and their topology. For each iteration of expansion, the neighbour genes of a current subnetwork, whose expression data improved the overall subnetwork score, is recruited. While the GS search calculated the subnetwork score using an activity score of a current subnetwork and the gene expression values of its neighbours, the PN search uses the expression value of the corresponding parent of each neighbour gene. Four lung cancer expression datasets were used for subnetwork identification. In addition, using pathway data and protein-protein interaction as network data in order to consider the interaction among significant genes were discussed. Classification was performed to compare the performance of the identified gene subnetworks with three

  1. Urine stability studies for novel biomarkers of acute kidney injury.

    Science.gov (United States)

    Parikh, Chirag R; Butrymowicz, Isabel; Yu, Angela; Chinchilli, Vernon M; Park, Meyeon; Hsu, Chi-Yuan; Reeves, W Brian; Devarajan, Prasad; Kimmel, Paul L; Siew, Edward D; Liu, Kathleen D

    2014-04-01

    The study of novel urinary biomarkers of acute kidney injury has expanded exponentially. Effective interpretation of data and meaningful comparisons between studies require awareness of factors that can adversely affect measurement. We examined how variations in short-term storage and processing might affect the measurement of urine biomarkers. Cross-sectional prospective. Hospitalized patients from 2 sites: Yale New Haven Hospital (n=50) and University of California, San Francisco Medical Center (n=36). We tested the impact of 3 urine processing conditions on these biomarkers: (1) centrifugation and storage at 4°C for 48 hours before freezing at -80°C, (2) centrifugation and storage at 25°C for 48 hours before freezing at -80°C, and (3) uncentrifuged samples immediately frozen at -80°C. Urine concentrations of 5 biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), and cystatin C. We measured urine biomarkers by established enzyme-linked immunosorbent assay methods. Biomarker values were log-transformed, and agreement with a reference standard of immediate centrifugation and storage at -80°C was compared using concordance correlation coefficients (CCCs). Neither storing samples at 4°C for 48 hours nor centrifugation had a significant effect on measured levels, with CCCs higher than 0.9 for all biomarkers tested. For samples stored at 25°C for 48 hours, excellent CCC values (>0.9) also were noted between the test sample and the reference standard for NGAL, cystatin C, L-FABP and KIM-1. However, the CCC for IL-18 between samples stored at 25°C for 48 hours and the reference standard was 0.81 (95% CI, 0.66-0.96). No comparisons to fresh, unfrozen samples; no evaluation of the effect of protease inhibitors. All candidate markers tested using the specified assays showed high stability with both short-term storage at 4°C and without centrifugation

  2. Comparing and combining biomarkers as principle surrogates for time-to-event clinical endpoints.

    Science.gov (United States)

    Gabriel, Erin E; Sachs, Michael C; Gilbert, Peter B

    2015-02-10

    Principal surrogate endpoints are useful as targets for phase I and II trials. In many recent trials, multiple post-randomization biomarkers are measured. However, few statistical methods exist for comparison of or combination of biomarkers as principal surrogates, and none of these methods to our knowledge utilize time-to-event clinical endpoint information. We propose a Weibull model extension of the semi-parametric estimated maximum likelihood method that allows for the inclusion of multiple biomarkers in the same risk model as multivariate candidate principal surrogates. We propose several methods for comparing candidate principal surrogates and evaluating multivariate principal surrogates. These include the time-dependent and surrogate-dependent true and false positive fraction, the time-dependent and the integrated standardized total gain, and the cumulative distribution function of the risk difference. We illustrate the operating characteristics of our proposed methods in simulations and outline how these statistics can be used to evaluate and compare candidate principal surrogates. We use these methods to investigate candidate surrogates in the Diabetes Control and Complications Trial. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Argininosuccinate synthetase as a plasma biomarker of liver injury after acetaminophen overdose in rodents and humans

    Science.gov (United States)

    McGill, Mitchell R.; Cao, Mengde; Svetlov, Archie; Sharpe, Matthew R.; Williams, C. David; Curry, Steven C.; Farhood, Anwar; Jaeschke, Hartmut; Svetlov, Stanislav I.

    2014-01-01

    Context New biomarkers are needed in acetaminophen (APAP) hepatotoxicity. Plasma argininosuccinate synthetase (ASS) is a promising candidate. Objective Characterize ASS in APAP hepatotoxicity. Methods ASS was measured in plasma from rodents and humans with APAP hepatotoxicity. Results In mice, ASS increased before injury, peaked before ALT, and decreased rapidly. Fischer rats had a greater increase in ASS relative to ALT. Patients with abnormal liver test results had very high ASS compared to controls. ASS appeared to increase early in some patients, and declined rapidly in all. Conclusions : ASS may be a useful biomarker of acute cell death in APAP hepatotoxicity. PMID:24597531

  4. [Obesity studies in candidate genes].

    Science.gov (United States)

    Ochoa, María del Carmen; Martí, Amelia; Martínez, J Alfredo

    2004-04-17

    There are more than 430 chromosomic regions with gene variants involved in body weight regulation and obesity development. Polymorphisms in genes related to energy expenditure--uncoupling proteins (UCPs), related to adipogenesis and insulin resistance--hormone-sensitive lipase (HLS), peroxisome proliferator-activated receptor gamma (PPAR gamma), beta adrenergic receptors (ADRB2,3), and alfa tumor necrosis factor (TNF-alpha), and related to food intake--ghrelin (GHRL)--appear to be associated with obesity phenotypes. Obesity risk depends on two factors: a) genetic variants in candidate genes, and b) biographical exposure to environmental risk factors. It is necessary to perform new studies, with appropriate control groups and designs, in order to reach relevant conclusions with regard to gene/environmental (diet, lifestyle) interactions.

  5. Biomarkers in inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Bennike, Tue; Birkelund, Svend; Stensballe, Allan

    2014-01-01

    Unambiguous diagnosis of the two main forms of inflammatory bowel diseases (IBD): Ulcerative colitis (UC) and Crohn's disease (CD), represents a challenge in the early stages of the diseases. The diagnosis may be established several years after the debut of symptoms. Hence, protein biomarkers...... for early and accurate diagnostic could help clinicians improve treatment of the individual patients. Moreover, the biomarkers could aid physicians to predict disease courses and in this way, identify patients in need of intensive treatment. Patients with low risk of disease flares may avoid treatment...... with medications with the concomitant risk of adverse events. In addition, identification of disease and course specific biomarker profiles can be used to identify biological pathways involved in the disease development and treatment. Knowledge of disease mechanisms in general can lead to improved future...

  6. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan

    2016-01-01

    Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... arrest. The biomarkers that characterize the path to an irreversible state of cell cycle arrest due to proliferative exhaustion may also be shared by other forms of senescence-inducing mechanisms. Validation of senescence markers is crucial in circumstances where quiescence or temporary growth arrest may...... be triggered or is thought to be induced. Pre-senescence biomarkers are also important to consider as their presence indicate that induction of aging processes is taking place. The bona fide pathway leading to replicative senescence that has been extensively characterized is a consequence of gradual reduction...

  7. Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma

    DEFF Research Database (Denmark)

    Marchi, Fabio Albuquerque; Martins, David Correa; Barros-Filho, Mateus Camargo

    2017-01-01

    Molecular data generation and their combination in penile carcinomas (PeCa), a significant public health problem in poor and underdeveloped countries, remain virtually unexplored. An integrativemethodology combin ing genome-wide copy number alteration, DNA methylation, miRNA and mRNA expression...

  8. Cystatin C is not a good candidate biomarker for HNF1A-MODY.

    Science.gov (United States)

    Nowak, Natalia; Szopa, Magdalena; Thanabalasingham, Gaya; McDonald, Tim J; Colclough, Kevin; Skupien, Jan; James, Timothy J; Kiec-Wilk, Beata; Kozek, Elzbieta; Mlynarski, Wojciech; Hattersley, Andrew T; Owen, Katharine R; Malecki, Maciej T

    2013-10-01

    Cystatin C is a marker of glomerular filtration rate (GFR). Its level is influenced, among the others, by CRP whose concentration is decreased in HNF1A-MODY. We hypothesized that cystatin C level might be altered in HNF1A-MODY. We aimed to evaluate cystatin C in HNF1A-MODY both as a diagnostic marker and as a method of assessing GFR. We initially examined 51 HNF1A-MODY patients, 56 subjects with type 1 diabetes (T1DM), 39 with type 2 diabetes (T2DM) and 43 non-diabetic individuals (ND) from Poland. Subjects from two UK centres were used as replication panels: including 215 HNF1A-MODY, 203 T2DM, 39 HNF4A-MODY, 170 GCK-MODY, 17 HNF1B-MODY and 58 T1DM patients. The data were analysed with additive models, adjusting for gender, age, BMI and estimated GFR (creatinine). In the Polish subjects, adjusted cystatin C level in HNF1A-MODY was lower compared with T1DM, T2DM and ND (p MODY, while the two GFR estimates were similar or cystatin C-based lower in the other groups. In the UK subjects, there were no differences in cystatin C between HNF1A-MODY and the other diabetic subgroups, except HNF1B-MODY. In UK HNF1A-MODY, cystatin C-based GFR estimate was higher than the creatinine-based one (p MODY. In HNF1A-MODY, the cystatin C-based GFR estimate is higher than the creatinine-based one.

  9. Serum IL-6: a candidate biomarker for intracranial pressure elevation following isolated traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Ward Norman H

    2010-03-01

    Full Text Available Abstract Background Increased intracranial pressure (ICP is a serious, life-threatening, secondary event following traumatic brain injury (TBI. In many cases, ICP rises in a delayed fashion, reaching a maximal level 48-96 hours after the initial insult. While pressure catheters can be implanted to monitor ICP, there is no clinically proven method for determining a patient's risk for developing this pathology. Methods In the present study, we employed antibody array and Luminex-based screening methods to interrogate the levels of inflammatory cytokines in the serum of healthy volunteers and in severe TBI patients (GCS≤8 with or without incidence of elevated intracranial pressure (ICP. De-identified samples and ELISAs were used to confirm the sensitivity and specificity of IL-6 as a prognostic marker of elevated ICP in both isolated TBI patients, and polytrauma patients with TBI. Results Consistent with previous reports, we observed sustained increases in IL-6 levels in TBI patients irrespective of their ICP status. However, the group of patients who subsequently experienced ICP ≥ 25 mm Hg had significantly higher IL-6 levels within the first 17 hours of injury as compared to the patients whose ICP remained ≤20 mm Hg. When blinded samples (n = 22 were assessed, a serum IL-6 cut-off of 128 pg/ml correctly identified 85% of isolated TBI patients who subsequently developed elevated ICP, and values between these cut-off values correctly identified 75% of all patients whose ICP remained ≤20 mm Hg throughout the study period. In contrast, the marker had no prognostic value in predicting elevated ICP in polytrauma patients with TBI. When the levels of serum IL-6 were assessed in patients with orthopedic injury (n = 7 in the absence of TBI, a significant increase was found in these patients compared to healthy volunteers, albeit lower than that observed in TBI patients. Conclusions Our results suggest that serum IL-6 can be used for the differential diagnosis of elevated ICP in isolated TBI.

  10. Candidate hippocampal biomarkers of susceptibility and resilience to stress in a rat model of depression

    DEFF Research Database (Denmark)

    Henningsen, Kim; Palmfeldt, Johan; Christiansen, Sofie Friis

    2012-01-01

    -scale proteomics was used to map hippocampal protein alterations in different stress states. Membrane proteins were successfully captured by two-phase separation and peptide based proteomics. Using iTRAQ labeling coupled with mass spectrometry, more than 2000 proteins were quantified and 73 proteins were found......Susceptibility to stress plays a crucial role in the development of psychiatric disorders such as unipolar depression and post-traumatic stress disorder. In the present study the chronic mild stress rat model of depression was used to reveal stress-susceptible and stress-resilient rats. Large...... to be differentially expressed. Stress susceptibility was associated with increased expression of a sodium-channel protein (SCN9A) currently investigated as a potential antidepressant target. Differential protein profiling also indicated stress susceptibility to be associated with deficits in synaptic vesicle release...

  11. Urinary YKL-40 as a Candidate Biomarker for Febrile Urinary Tract Infection in Young Children.

    Science.gov (United States)

    Kim, Hyun Hee; Chung, Mi Hae; Bin, Joong Hyun; Cho, Kyoung Soon; Lee, Juyoung; Suh, Jin Soon

    2018-01-01

    Given that YKL-40 is a known marker of inflammation, we sought to determine its association with urinary tract infection (UTI) in febrile children. In total, 44 children aged 0 to 24 months with febrile UTI and 35 age- and sex-matched controls with fever from other causes were enrolled in the study. ELISA was performed to determine the level of YKL-40 in urine collected from each child. The ratio of urinary YKL-40 to creatinine (Cr) was higher in the children with a UTI than in the controls (PUTI was 0.88 for the urinary YKL-40/Cr ratio, 0.86 for pyuria, and 0.71 for positive nitrite on urinalysis. We applied a cut-off value of 125.23 pg/mg to urinary YKL-40/Cr for detecting UTI. Eight of nine children in the control group with pyuria had urinary YKL-40/Cr levels lower than 125.23 pg/mg, and the one child in the UTI group without pyuria or positive nitrite had a urinary YKL-40/Cr level greater than 125.23 pg/mg. Determining the levels of urinary YKL-40/Cr may help identify true cases of UTI in febrile young children, especially when they have pyuria but not nitrite, or have neither pyuria nor nitrite in the urine. © The Korean Society for Laboratory Medicine

  12. Construction of an miRNA-Regulated Pathway Network Reveals Candidate Biomarkers for Postmenopausal Osteoporosis

    Directory of Open Access Journals (Sweden)

    Min Shao

    2017-01-01

    Full Text Available We aimed to identify risk pathways for postmenopausal osteoporosis (PMOP via establishing an microRNAs- (miRNA- regulated pathway network (MRPN. Firstly, we identified differential pathways through calculating gene- and pathway-level statistics based on the accumulated normal samples using the individual pathway aberrance score (iPAS. Significant pathways based on differentially expressed genes (DEGs using DAVID were extracted, followed by identifying the common pathways between iPAS and DAVID methods. Next, miRNAs prediction was implemented via calculating TargetScore values with precomputed input (log fold change (FC, TargetScan context score (TSCS, and probabilities of conserved targeting (PCT. An MRPN construction was constructed using the common genes in the common pathways and the predicted miRNAs. Using false discovery rate (FDR < 0.05, 279 differential pathways were identified. Using the criteria of FDR < 0.05 and log⁡FC≥2, 39 DEGs were retrieved, and these DEGs were enriched in 64 significant pathways identified by DAVID. Overall, 27 pathways were the common ones between two methods. Importantly, MAPK signaling pathway and PI3K-Akt signaling pathway were the first and second significantly enriched ones, respectively. These 27 common pathways separated PMOP from controls with the accuracy of 0.912. MAPK signaling pathway and PI3K/Akt signaling pathway might play crucial roles in PMOP.

  13. Biological aspects and candidate biomarkers for rapid-cycling in bipolar disorder: A systematic review.

    Science.gov (United States)

    Buoli, Massimiliano; Serati, Marta; Altamura, A Carlo

    2017-12-01

    Rapid-cycling bipolar disorder represents a frequent severe subtype of illness which has been associated with poor response to pharmacological treatment. Aim of the present article is to provide an updated review of biological markers associated with rapid-cycling bipolar disorder. A research in the main database sources has been conducted to identify relevant papers about the topic. Rapid-cycling bipolar disorder patients seem to have a more frequent family history for bipolar spectrum disorders (d range: 0.44-0.74) as well as an increased susceptibility to DNA damage or mRNA hypo-transcription (d range: 0.78-1.67) than non rapid-cycling ones. A susceptibility to hypothyroidism, which is exacerbated by treatment with lithium, is possible in rapid-cycling bipolar disorder, but further studies are needed to draw definitive conclusions. Rapid-cycling bipolar patients might have more insuline resistance as well as more severe brain changes in frontal areas (d range: 0.82-0.94) than non rapid-cycling ones. Many questions are still open about this topic. The first is whether the rapid-cycling is inheritable or is more generally the manifestation of a severe form of bipolar disorder. The second is whether some endocrine dysfunctions (diabetes and hypothyroidism) predispose to rapid-cycling or rapid-cycling is the consequence of drug treatment or medical comorbidities (e.g. obesity). Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Urinary YKL-40 as a Candidate Biomarker for Febrile Urinary Tract Infection in Young Children

    Science.gov (United States)

    Kim, Hyun Hee; Chung, Mi Hae; Bin, Joong Hyun; Cho, Kyoung Soon; Lee, Juyoung

    2018-01-01

    Background Given that YKL-40 is a known marker of inflammation, we sought to determine its association with urinary tract infection (UTI) in febrile children. Methods In total, 44 children aged 0 to 24 months with febrile UTI and 35 age- and sex-matched controls with fever from other causes were enrolled in the study. ELISA was performed to determine the level of YKL-40 in urine collected from each child. Results The ratio of urinary YKL-40 to creatinine (Cr) was higher in the children with a UTI than in the controls (Purinary YKL-40/Cr ratio, 0.86 for pyuria, and 0.71 for positive nitrite on urinalysis. We applied a cut-off value of 125.23 pg/mg to urinary YKL-40/Cr for detecting UTI. Eight of nine children in the control group with pyuria had urinary YKL-40/Cr levels lower than 125.23 pg/mg, and the one child in the UTI group without pyuria or positive nitrite had a urinary YKL-40/Cr level greater than 125.23 pg/mg. Conclusions Determining the levels of urinary YKL-40/Cr may help identify true cases of UTI in febrile young children, especially when they have pyuria but not nitrite, or have neither pyuria nor nitrite in the urine. PMID:29071817

  15. Validation of biomarkers for the study of environmental carcinogens: a review

    DEFF Research Database (Denmark)

    Gallo, Valentina; Khan, Aneire; Gonzales, Carlos

    2008-01-01

    There is a need for validation of biomarkers. Our aim is to review published work on the validation of selected biomarkers: bulky DNA adducts, N-nitroso compounds, 1-hydroxypyrene, and oxidative damage to DNA. A systematic literature search in PubMed was performed. Information on the variability...... and reliability of the laboratory tests used for biomarkers measurements was collected. For the evaluation of the evidence on validation we referred to the ACCE criteria. Little is known about intraindividual variation of DNA adduct measurements, but measurements have a good repeatability irrespective...... of the technique used for their identification; reproducibility improved after the correction for a laboratory factor. A high-sensitivity method is available for the measurement of 1-hydroxypyrene in urine. There is consensus on validation of biomarkers of oxidative damage DNA based on the comet assay...

  16. The Present and Future of Biomarkers in Prostate Cancer: Proteomics, Genomics, and Immunology Advancements

    Directory of Open Access Journals (Sweden)

    Pierre-Olivier Gaudreau

    2016-01-01

    Full Text Available Prostate cancer (PC is the second most common form of cancer in men worldwide. Biomarkers have emerged as essential tools for treatment and assessment since the variability of disease behavior, the cost and diversity of treatments, and the related impairment of quality of life have given rise to a need for a personalized approach. High-throughput technology platforms in proteomics and genomics have accelerated the development of biomarkers. Furthermore, recent successes of several new agents in PC, including immunotherapy, have stimulated the search for predictors of response and resistance and have improved the understanding of the biological mechanisms at work. This review provides an overview of currently established biomarkers in PC, as well as a selection of the most promising biomarkers within these particular fields of development.

  17. Diagnostic and Prognostic MicroRNA Biomarkers for Prostate Cancer in Cell-free Urine

    DEFF Research Database (Denmark)

    Fredsøe, Jacob Christian; Rasmussen, Anne Karin; Thomsen, Anni Rønfeldt

    2017-01-01

    Background: Widespread use of prostate-specific antigen (PSA) testing for prostate cancer (PC) detection has led to extensive overdiagnosis and overtreatment. Urine-based microRNA (miRNA) biomarkers could be useful in PC diagnosis and prognosis. Objective: To train and validate urine-based micro......RNA (miRNA) biomarkers that may assist in PC diagnosis and prognosis. Design, setting, and participants: We profiled the expression levels of 92 miRNAs via reverse transcriptase–poymerase chain reaction in cell-free urine samples from 29 patients with benign prostatic hyperplasia (BPH) and 215 patients...... could help in primary diagnosis of PC and guide treatment decisions. Further validation studies are warranted. Patient summary: Using two large patient cohorts, we searched for novel prostate cancer biomarkers in urine. We found two new sets of microRNA biomarkers in urine that could accurately predict...

  18. Biomarkers for the detection of prenatal alcohol exposure (PAE)

    DEFF Research Database (Denmark)

    Bjerregaard, Lene Berit Skov; Bager, Heidi; Husby, Steffen

    2017-01-01

    Alcohol exposure during pregnancy can cause adverse effects to the fetus, because it interferes with fetal development, leading to later physical and mental impairment. The most common clinical tool to determine fetal alcohol exposure is maternal self-reporting. However, a more objective and useful...... method is based on the use of biomarkers in biological specimens alone or in combination with maternal self-reporting. This review reports on clinically relevant biomarkers for detection of prenatal alcohol exposure (PAE). A systematic search was performed to ensure a proper overview in existing...... to be applicable for detection of even low levels of alcohol exposure. Meconium is an accessible matrix for determination of FAEEs and EtG, and blood an accessible matrix for determination of PEth....

  19. Biomarkers of Chondrocyte Apoptosis and Autophagy in Osteoarthritis

    Science.gov (United States)

    Musumeci, Giuseppe; Castrogiovanni, Paola; Trovato, Francesca Maria; Weinberg, Annelie Martina; Al-Wasiyah, Mohammad K.; Alqahtani, Mohammed H.; Mobasheri, Ali

    2015-01-01

    Cell death with morphological and molecular features of apoptosis has been detected in osteoarthritic (OA) cartilage, which suggests a key role for chondrocyte death/survival in the pathogenesis of OA. Identification of biomarkers of chondrocyte apoptosis may facilitate the development of novel therapies that may eliminate the cause or, at least, slow down the degenerative processes in OA. The aim of this review was to explore the molecular markers and signals that induce chondrocyte apoptosis in OA. A literature search was conducted in PubMed, Scopus, Web of Science and Google Scholar using the keywords chondrocyte death, apoptosis, osteoarthritis, autophagy and biomarker. Several molecules considered to be markers of chondrocyte apoptosis will be discussed in this brief review. Molecular markers and signalling pathways associated with chondroycte apoptosis may turn out to be therapeutic targets in OA and approaches aimed at neutralizing apoptosis-inducing molecules may at least delay the progression of cartilage degeneration in OA. PMID:26334269

  20. Dark-matter QCD-axion searches

    International Nuclear Information System (INIS)

    Rosenberg, Leslie J

    2010-01-01

    The axion is a hypothetical elementary particle appearing in a simple and elegant extension to the Standard Model of particle physics that cancels otherwise huge CP-violating effects in QCD; this extension has a broken U(1) axial symmetry, where the resulting Goldstone Boson is the axion. A light axion of mass 10 -(6-3) eV (the so-called i nvisible axion ) would couple extraordinarily weakly to normal matter and radiation and would therefore be extremely difficult to detect in the laboratory. However, such an axion would be a compelling dark-matter candidate and is therefore a target of a number of searches. Compared to other dark-matter candidates, the plausible range of axion dark-matter couplings and masses is narrowly constrained. This restricted search space allows for 'definitive' searches, where non-observation would seriously impugn the dark-matter QCD-axion hypothesis. Axion searches employ a wide range of technologies and techniques, from astrophysical observations to laboratory electromagnetic signal detection. For some experiments, sensitivities are have reached likely dark-matter axion couplings and masses. This is a brief and selective overview of axion searches. With only very limited space, I briefly describe just two of the many experiments that are searching for dark-matter axions.

  1. Unraveling the molecular repertoire of tears as a source of biomarkers: beyond ocular diseases.

    Science.gov (United States)

    Pieragostino, Damiana; D'Alessandro, Michele; di Ioia, Maria; Di Ilio, Carmine; Sacchetta, Paolo; Del Boccio, Piero

    2015-02-01

    Proteomics and metabolomics investigations of body fluids present several challenges for biomarker discovery of several diseases. The search for biomarkers is actually conducted in different body fluids, even if the ideal biomarker can be found in an easily accessible biological fluid, because, if validated, the biomarker could be sought in the healthy population. In this regard, tears could be considered an optimum material obtained by noninvasive procedures. In the past years, the scientific community has become more interested in the study of tears for the research of new biomarkers not only for ocular diseases. In this review, we provide a discussion on the current state of biomarkers research in tears and their relevance for clinical practice, and report the main results of clinical proteomics studies on systemic and eye diseases. We summarize the main methods for tear samples analyses and report recent advances in "omics" platforms for tears investigations. Moreover, we want to take stock of the emerging field of metabolomics and lipidomics as a new and integrated approach to study protein-metabolites interplay for biomarkers research, where tears represent a still unexplored and attractive field. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. A homogeneous catalogue of quasar candidates found with slitless spectroscopy

    International Nuclear Information System (INIS)

    Beauchemin, M.; Borra, E.F.; Edwards, G.

    1990-01-01

    This paper gives a list of all quasar candidates obtained from an automated computer search performed on 11 grens plates. The description of the main characteristics of the survey is given along with the latest improvements in the selection techniques. Particular attention has been paid to understanding and quantifying selection effects. This allows the construction of homogeneous samples having well-understood characteristics. The noteworthy aspect of our homogenization process is the correction that we apply to our probability classes in order to take into account the signal-to-noise differences; at a given magnitude, among plates of different limiting magnitudes. (author)

  3. Elementary particles, dark matter candidate and new extended standard model

    Science.gov (United States)

    Hwang, Jaekwang

    2017-01-01

    Elementary particle decays and reactions are discussed in terms of the three-dimensional quantized space model beyond the standard model. Three generations of the leptons and quarks correspond to the lepton charges. Three heavy leptons and three heavy quarks are introduced. And the bastons (new particles) are proposed as the possible candidate of the dark matters. Dark matter force, weak force and strong force are explained consistently. Possible rest masses of the new particles are, tentatively, proposed for the experimental searches. For more details, see the conference paper at https://www.researchgate.net/publication/308723916.

  4. Biomarkers in scleroderma: Current status

    Directory of Open Access Journals (Sweden)

    Latika Gupta

    2017-01-01

    Full Text Available Scleroderma is an autoimmune disease characterized by indolent obliterative vasculopathy and widespread fibrosis. The two main morphological manifestations of the disease overlap and may make it difficult to separate activity from damage. Many patients, especially those with the limited subset of the disease, have an indolent course without clear-cut inflammatory manifestations. There is a felt need for validated biomarkers, which can differentiate activity from damage, and yet be sensitive to change with therapy. Multiplex arrays of biomarkers have ushered an era of targeted or personalized medicine based on phenotypic characteristics in an individual.

  5. Potential biomarkers for the clinical prognosis of severe dengue

    Directory of Open Access Journals (Sweden)

    Mayara Marques Carneiro da Silva

    2013-09-01

    Full Text Available Currently, several assays can confirm acute dengue infection at the point-of-care. However, none of these assays can predict the severity of the disease symptoms. A prognosis test that predicts the likelihood of a dengue patient to develop a severe form of the disease could permit more efficient patient triage and treatment. We hypothesise that mRNA expression of apoptosis and innate immune response-related genes will be differentially regulated during the early stages of dengue and might predict the clinical outcome. Aiming to identify biomarkers for dengue prognosis, we extracted mRNA from the peripheral blood mononuclear cells of mild and severe dengue patients during the febrile stage of the disease to measure the expression levels of selected genes by quantitative polymerase chain reaction. The selected candidate biomarkers were previously identified by our group as differentially expressed in microarray studies. We verified that the mRNA coding for CFD, MAGED1, PSMB9, PRDX4 and FCGR3B were differentially expressed between patients who developed clinical symptoms associated with the mild type of dengue and patients who showed clinical symptoms associated with severe dengue. We suggest that this gene expression panel could putatively serve as biomarkers for the clinical prognosis of dengue haemorrhagic fever.

  6. Electrophysiological biomarkers of epileptogenicity after traumatic brain injury.

    Science.gov (United States)

    Perucca, Piero; Smith, Gregory; Santana-Gomez, Cesar; Bragin, Anatol; Staba, Richard

    2018-06-05

    Post-traumatic epilepsy is the architype of acquired epilepsies, wherein a brain insult initiates an epileptogenic process culminating in an unprovoked seizure after weeks, months or years. Identifying biomarkers of such process is a prerequisite for developing and implementing targeted therapies aimed at preventing the development of epilepsy. Currently, there are no validated electrophysiological biomarkers of post-traumatic epileptogenesis. Experimental EEG studies using the lateral fluid percussion injury model have identified three candidate biomarkers of post-traumatic epileptogenesis: pathological high-frequency oscillations (HFOs, 80-300 Hz); repetitive HFOs and spikes (rHFOSs); and reduction in sleep spindle duration and dominant frequency at the transition from stage III to rapid eye movement sleep. EEG studies in humans have yielded conflicting data; recent evidence suggests that epileptiform abnormalities detected acutely after traumatic brain injury carry a significantly increased risk of subsequent epilepsy. Well-designed studies are required to validate these promising findings, and ultimately establish whether there are post-traumatic electrophysiological features which can guide the development of 'antiepileptogenic' therapies. Copyright © 2017. Published by Elsevier Inc.

  7. Common Subcluster Mining in Microarray Data for Molecular Biomarker Discovery.

    Science.gov (United States)

    Sadhu, Arnab; Bhattacharyya, Balaram

    2017-10-11

    Molecular biomarkers can be potential facilitators for detection of cancer at early stage which is otherwise difficult through conventional biomarkers. Gene expression data from microarray experiments on both normal and diseased cell samples provide enormous scope to explore genetic relations of disease using computational techniques. Varied patterns of expressions of thousands of genes at different cell conditions along with inherent experimental error make the task of isolating disease related genes challenging. In this paper, we present a data mining method, common subcluster mining (CSM), to discover highly perturbed genes under diseased condition from differential expression patterns. The method builds heap through superposing near centroid clusters from gene expression data of normal samples and extracts its core part. It, thus, isolates genes exhibiting the most stable state across normal samples and constitute a reference set for each centroid. It performs the same operation on datasets from corresponding diseased samples and isolates the genes showing drastic changes in their expression patterns. The method thus finds the disease-sensitive genesets when applied to datasets of lung cancer, prostrate cancer, pancreatic cancer, breast cancer, leukemia and pulmonary arterial hypertension. In majority of the cases, few new genes are found over and above some previously reported ones. Genes with distinct deviations in diseased samples are prospective candidates for molecular biomarkers of the respective disease.

  8. Searching for the Next Generation of Teacher Educators: Assessing the Success of Academic Searches

    Science.gov (United States)

    Twombly, Susan B.; Wolf-Wendel, Lisa; Williams, James; Green, Pamela

    2006-01-01

    In light of a documented shortage of candidates for teacher education faculty positions, this article explores the academic labor market for teacher education faculty using job announcements from the Chronicle of Higher Education and a survey of search chairs to examine the qualifications sought. The authors conclude that the demand for teacher…

  9. Synovial tissue heterogeneity in rheumatoid arthritis in relation to disease activity and biomarkers in peripheral blood

    NARCIS (Netherlands)

    van Baarsen, Lisa G. M.; Wijbrandts, Carla A.; Timmer, Trieneke C. G.; van der Pouw Kraan, Tineke C. T. M.; Tak, Paul P.; Verweij, Cornelis L.

    2010-01-01

    OBJECTIVE: To investigate the clinical relevance of synovial tissue subtypes in rheumatoid arthritis (RA) and to search for peripheral blood (PB) markers that may serve as biomarkers for tissue subtypes. METHODS: Gene expression analysis using complementary DNA microarrays was applied on paired

  10. Early diagnostic protein biomarkers for breast cancer: how far have we come?

    NARCIS (Netherlands)

    Opstal - van Winden, A.W.J.; Vermeulen, R.C.H.; Peeters, P.H.M.; Beijnen, J.H.; van Gils, C.H.

    2012-01-01

    Many studies have used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to search for blood-based proteins that are related to the presence of breast cancer. We review the biomarkers

  11. Strategies to design clinical studies to identify predictive biomarkers in cancer research.

    Science.gov (United States)

    Perez-Gracia, Jose Luis; Sanmamed, Miguel F; Bosch, Ana; Patiño-Garcia, Ana; Schalper, Kurt A; Segura, Victor; Bellmunt, Joaquim; Tabernero, Josep; Sweeney, Christopher J; Choueiri, Toni K; Martín, Miguel; Fusco, Juan Pablo; Rodriguez-Ruiz, Maria Esperanza; Calvo, Alfonso; Prior, Celia; Paz-Ares, Luis; Pio, Ruben; Gonzalez-Billalabeitia, Enrique; Gonzalez Hernandez, Alvaro; Páez, David; Piulats, Jose María; Gurpide, Alfonso; Andueza, Mapi; de Velasco, Guillermo; Pazo, Roberto; Grande, Enrique; Nicolas, Pilar; Abad-Santos, Francisco; Garcia-Donas, Jesus; Castellano, Daniel; Pajares, María J; Suarez, Cristina; Colomer, Ramon; Montuenga, Luis M; Melero, Ignacio

    2017-02-01

    The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated. The lack of a proper methodology also determines that many anti-cancer drugs are developed below their potential, due to failure to identify predictive biomarkers. While some drugs will be systematically administered to many patients who will not benefit from them, leading to unnecessary toxicities and costs, others will never reach registration due to our inability to identify the specific patient population in which they are active. Despite these drawbacks, a limited number of outstanding predictive biomarkers have been successfully identified and validated, and have changed the standard practice of oncology. In this manuscript, a multidisciplinary panel reviews how those key biomarkers were identified and, based on those experiences, proposes a methodological framework-the DESIGN guidelines-to standardize the clinical design of biomarker identification studies and to develop future research in this pivotal field. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease—From Brain Starch to Bench and Bedside

    Directory of Open Access Journals (Sweden)

    Matthias Pawlowski

    2017-07-01

    Full Text Available Alzheimer’s disease is the most common cause of dementia. Over the last three decades, research has advanced dramatically and provided a detailed understanding of the molecular events underlying the pathogenesis of Alzheimer’s disease. In parallel, assays for the detection of biomarkers that reflect the typical Alzheimer’s disease-associated pathology have been developed and validated in myriads of clinical studies. Such biomarkers complement clinical diagnosis and improve diagnostic accuracy. The use of biomarkers will become even more important with the advent of disease-modifying therapies. Such therapies will likely be most beneficial when administered early in the disease course. Here, we summarise the development of the core Alzheimer’s disease cerebrospinal fluid biomarkers: amyloid-β and tau. We provide an overview of their role in cellular physiology and Alzheimer’s disease pathology, and embed their development as cerebrospinal fluid biomarkers into the historical context of Alzheimer’s disease research. Finally, we summarise recommendations for their use in clinical practice, and outline perspectives for novel cerebrospinal fluid candidate biomarkers.

  13. Computational identification of candidate nucleotide cyclases in higher plants

    KAUST Repository

    Wong, Aloysius Tze

    2013-09-03

    In higher plants guanylyl cyclases (GCs) and adenylyl cyclases (ACs) cannot be identified using BLAST homology searches based on annotated cyclic nucleotide cyclases (CNCs) of prokaryotes, lower eukaryotes, or animals. The reason is that CNCs are often part of complex multifunctional proteins with different domain organizations and biological functions that are not conserved in higher plants. For this reason, we have developed CNC search strategies based on functionally conserved amino acids in the catalytic center of annotated and/or experimentally confirmed CNCs. Here we detail this method which has led to the identification of >25 novel candidate CNCs in Arabidopsis thaliana, several of which have been experimentally confirmed in vitro and in vivo. We foresee that the application of this method can be used to identify many more members of the growing family of CNCs in higher plants. © Springer Science+Business Media New York 2013.

  14. Aptamer-based multiplexed proteomic technology for biomarker discovery.

    Science.gov (United States)

    Gold, Larry; Ayers, Deborah; Bertino, Jennifer; Bock, Christopher; Bock, Ashley; Brody, Edward N; Carter, Jeff; Dalby, Andrew B; Eaton, Bruce E; Fitzwater, Tim; Flather, Dylan; Forbes, Ashley; Foreman, Trudi; Fowler, Cate; Gawande, Bharat; Goss, Meredith; Gunn, Magda; Gupta, Shashi; Halladay, Dennis; Heil, Jim; Heilig, Joe; Hicke, Brian; Husar, Gregory; Janjic, Nebojsa; Jarvis, Thale; Jennings, Susan; Katilius, Evaldas; Keeney, Tracy R; Kim, Nancy; Koch, Tad H; Kraemer, Stephan; Kroiss, Luke; Le, Ngan; Levine, Daniel; Lindsey, Wes; Lollo, Bridget; Mayfield, Wes; Mehan, Mike; Mehler, Robert; Nelson, Sally K; Nelson, Michele; Nieuwlandt, Dan; Nikrad, Malti; Ochsner, Urs; Ostroff, Rachel M; Otis, Matt; Parker, Thomas; Pietrasiewicz, Steve; Resnicow, Daniel I; Rohloff, John; Sanders, Glenn; Sattin, Sarah; Schneider, Daniel; Singer, Britta; Stanton, Martin; Sterkel, Alana; Stewart, Alex; Stratford, Suzanne; Vaught, Jonathan D; Vrkljan, Mike; Walker, Jeffrey J; Watrobka, Mike; Waugh, Sheela; Weiss, Allison; Wilcox, Sheri K; Wolfson, Alexey; Wolk, Steven K; Zhang, Chi; Zichi, Dom

    2010-12-07

    The interrogation of proteomes ("proteomics") in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology and medicine. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 µL of serum or plasma). Our current assay measures 813 proteins with low limits of detection (1 pM median), 7 logs of overall dynamic range (~100 fM-1 µM), and 5% median coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding signature of DNA aptamer concentrations, which is quantified on a DNA microarray. Our assay takes advantage of the dual nature of aptamers as both folded protein-binding entities with defined shapes and unique nucleotide sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to rapidly discover unique protein signatures characteristic of various disease states. We describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine.

  15. Aptamer-based multiplexed proteomic technology for biomarker discovery.

    Directory of Open Access Journals (Sweden)

    Larry Gold

    2010-12-01

    Full Text Available The interrogation of proteomes ("proteomics" in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology and medicine.We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 µL of serum or plasma. Our current assay measures 813 proteins with low limits of detection (1 pM median, 7 logs of overall dynamic range (~100 fM-1 µM, and 5% median coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomi