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Sample records for global molecular screening

  1. Molecular HIV screening.

    Science.gov (United States)

    Bourlet, Thomas; Memmi, Meriam; Saoudin, Henia; Pozzetto, Bruno

    2013-09-01

    Nuclear acid testing is more and more used for the diagnosis of infectious diseases. This paper focuses on the use of molecular tools for HIV screening. The term 'screening' will be used under the meaning of first-line HIV molecular techniques performed on a routine basis, which excludes HIV molecular tests designed to confirm or infirm a newly discovered HIV-seropositive patient or other molecular tests performed for the follow-up of HIV-infected patients. The following items are developed successively: i) presentation of the variety of molecular tools used for molecular HIV screening, ii) use of HIV molecular tools for the screening of blood products, iii) use of HIV molecular tools for the screening of organs and tissue from human origin, iv) use of HIV molecular tools in medically assisted procreation and v) use of HIV molecular tools in neonates from HIV-infected mothers.

  2. Molecular screening of antibiotic-resistant determinants among ...

    African Journals Online (AJOL)

    Background: Globally, and particularly in developing countries, the menace of anti-microbial resistance is an accelerating problem. In Nigeria, increase in bacterial resistance has been phenotypically established but due to high cost, few molecular studies have been reported. Objectives: This study screened for presence of ...

  3. Electron screening in molecular fusion reactions

    International Nuclear Information System (INIS)

    Shoppa, T.D.

    1996-01-01

    Recent laboratory experiments have measured fusion cross sections at center-of-mass energies low enough for the effects of atomic and molecular electrons to be important. To extract the cross section for bare nuclei from these data (as required for astrophysical applications), it is necessary to understand these screening effects. We study electron screening effects in the low-energy collisions of Z=1 nuclei with hydrogen molecules. Our model is based on a dynamical evolution of the electron wave functions within the TDHF scheme, while the motion of the nuclei is treated classically. We find that at the currently accessible energies the screening effects depend strongly on the molecular orientation. The screening is found to be larger for molecular targets than for atomic targets, due to the reflection symmetry in the latter. The results agree fairly well with data measured for deuteron collisions on molecular deuterium and tritium targets. (orig.)

  4. Diabetic retinopathy screening: global and local perspective.

    Science.gov (United States)

    Gangwani, R A; Lian, J X; McGhee, S M; Wong, D; Li, K Kw

    2016-10-01

    Diabetes mellitus has become a global epidemic. It causes significant macrovascular complications such as coronary artery disease, peripheral artery disease, and stroke; as well as microvascular complications such as retinopathy, nephropathy, and neuropathy. Diabetic retinopathy is known to be the leading cause of blindness in the working-age population and may be asymptomatic until vision loss occurs. Screening for diabetic retinopathy has been shown to reduce blindness by timely detection and effective laser treatment. Diabetic retinopathy screening is being done worldwide either as a national screening programme or hospital-based project or as a community-based screening programme. In this article, we review different methods of screening including grading used to detect the severity of sight-threatening retinopathy and the newer screening methods. This review also includes the method of systematic screening being carried out in Hong Kong, a system that has helped to identify diabetic retinopathy among all attendees in public primary care clinics using a Hong Kong-wide public patients' database.

  5. Fecal Molecular Markers for Colorectal Cancer Screening

    Directory of Open Access Journals (Sweden)

    Rani Kanthan

    2012-01-01

    Full Text Available Despite multiple screening techniques, including colonoscopy, flexible sigmoidoscopy, radiological imaging, and fecal occult blood testing, colorectal cancer remains a leading cause of death. As these techniques improve, their sensitivity to detect malignant lesions is increasing; however, detection of precursor lesions remains problematic and has generated a lack of general acceptance for their widespread usage. Early detection by an accurate, noninvasive, cost-effective, simple-to-use screening technique is central to decreasing the incidence and mortality of this disease. Recent advances in the development of molecular markers in faecal specimens are encouraging for its use as a screening tool. Genetic mutations and epigenetic alterations that result from the carcinogenetic process can be detected by coprocytobiology in the colonocytes exfoliated from the lesion into the fecal matter. These markers have shown promising sensitivity and specificity in the detection of both malignant and premalignant lesions and are gaining popularity as a noninvasive technique that is representative of the entire colon. In this paper, we summarize the genetic and epigenetic fecal molecular markers that have been identified as potential targets in the screening of colorectal cancer.

  6. Global sensitivity analysis of computer-aided molecular design problem for the development of novel working fluids for power cycles

    DEFF Research Database (Denmark)

    Frutiger, Jerome; Abildskov, Jens; Sin, Gürkan

    2016-01-01

    This study compares two methods for global sensitivity analysis as a new approach for the identification and ranking of target properties in molecular design problems: A modified Morris Screening technique and Monte Carlo based standard regression. The two methodologies are highlighted in a case ...

  7. Local-global classifier fusion for screening chest radiographs

    Science.gov (United States)

    Ding, Meng; Antani, Sameer; Jaeger, Stefan; Xue, Zhiyun; Candemir, Sema; Kohli, Marc; Thoma, George

    2017-03-01

    Tuberculosis (TB) is a severe comorbidity of HIV and chest x-ray (CXR) analysis is a necessary step in screening for the infective disease. Automatic analysis of digital CXR images for detecting pulmonary abnormalities is critical for population screening, especially in medical resource constrained developing regions. In this article, we describe steps that improve previously reported performance of NLM's CXR screening algorithms and help advance the state of the art in the field. We propose a local-global classifier fusion method where two complementary classification systems are combined. The local classifier focuses on subtle and partial presentation of the disease leveraging information in radiology reports that roughly indicates locations of the abnormalities. In addition, the global classifier models the dominant spatial structure in the gestalt image using GIST descriptor for the semantic differentiation. Finally, the two complementary classifiers are combined using linear fusion, where the weight of each decision is calculated by the confidence probabilities from the two classifiers. We evaluated our method on three datasets in terms of the area under the Receiver Operating Characteristic (ROC) curve, sensitivity, specificity and accuracy. The evaluation demonstrates the superiority of our proposed local-global fusion method over any single classifier.

  8. Toxoplasmosis: Seroprevalence in pregnant women, and serological and molecular screening in neonatal umbilical cord blood.

    Science.gov (United States)

    Shieh, Mahshad; Didehdar, Mojtaba; Hajihossein, Reza; Ahmadi, Farzam; Eslamirad, Zahra

    2017-10-01

    Toxoplasmosis is a common zoonotic disease that can also be transmitted from the mother to the embryo, with the risk of congenital infection varying around the world. The aim of this study was to screen pregnant women and their neonates for toxoplasmosis by serologic and molecular methods and assess the impact of risk factors associated with toxoplasmosis on the rate of congenital infection. This study was conducted at a regional maternity hospital in Arak, the capital of the Markazi Province in Iran, during a period of six months. All selected pregnant women (n=261) and the corresponding cord blood samples were serologically screened for toxoplasmosis, with seropositive samples also undergoing molecular testing. Demographic data, as well as information related to the risk factors associated with the transmission of the disease, were collected from mothers and their neonates. The detection of anti-Toxoplasma antibodies and the extraction of DNA from blood samples were conducted using commercial kits. Results showed that the sera of 87 maternal blood samples (33.3%) and 40 cord blood samples (15.3%) were positive for anti-Toxoplasma antibodies (IgG and/or IgM). Molecular screening of the seropositive samples only identified one positive cord blood sample. In other words, the diagnosis of congenital toxoplasmosis was definitive in only one neonate. There was no significant association between the risk of parasite transmission and neonatal seropositivity (p >0.05). Therefore, the results showed that the prevalence of congenital toxoplasmosis in the studied area was consistent with the global rate and suggest that the implementation of newborn screening and follow-up testing could help reduce the disease risk. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Colorectal Cancer in Iran: Molecular Epidemiology and Screening Strategies

    Directory of Open Access Journals (Sweden)

    Roya Dolatkhah

    2015-01-01

    Full Text Available Purpose. The increasing incidence of colorectal cancer (CRC in the past three decades in Iran has made it a major public health burden. This study aimed to report its epidemiologic features, molecular genetic aspects, survival, heredity, and screening pattern in Iran. Methods. A comprehensive literature review was conducted to identify the relevant published articles. We used medical subject headings, including colorectal cancer, molecular genetics, KRAS and BRAF mutations, screening, survival, epidemiologic study, and Iran. Results. Age standardized incidence rate of Iranian CRCs was 11.6 and 10.5 for men and women, respectively. Overall five-year survival rate was 41%, and the proportion of CRC among the younger age group was higher than that of western countries. Depending on ethnicity, geographical region, dietary, and genetic predisposition, mutation genes were considerably diverse and distinct among CRCs across Iran. The high occurrence of CRC in records of relatives of CRC patients showed that family history of CRC was more common among young CRCs. Conclusion. Appropriate screening strategies for CRC which is amenable to early detection through screening, especially in relatives of CRCs, should be considered as the first step in CRC screening programs.

  10. Colorectal Cancer in Iran: Molecular Epidemiology and Screening Strategies

    International Nuclear Information System (INIS)

    Dolatkhah, R.; Somi, M. H.; Dolatkhah, R.; Kermani, I. A.; Dastgiri, S.

    2015-01-01

    The increasing incidence of colorectal cancer (CRC) in the past three decades in Iran has made it a major public health burden. This study aimed to report its epidemiologic features, molecular genetic aspects, survival, heredity, and screening pattern in Iran. Methods. A comprehensive literature review was conducted to identify the relevant published articles. We used medical subject headings, including colorectal cancer, molecular genetics, KRAS and BRAF mutations, screening, survival, epidemiologic study, and Iran. Results. Age standardized incidence rate of Iranian CRCs was 11.6 and 10.5 for men and women, respectively. Overall five-year survival rate was 41%, and the proportion of CRC among the younger age group was higher than that of western countries. Depending on ethnicity, geographical region, dietary, and genetic predisposition, mutation genes were considerably diverse and distinct among CRCs across Iran. The high occurrence of CRC in records of relatives of CRC patients showed that family history of CRC was more common among young CRCs. Conclusion. Appropriate screening strategies for CRC which is amenable to early detection through screening, especially in relatives of CRCs, should be considered as the first step in CRC screening programs.

  11. Molecular marker screening of peanut ( Arachis hypogaea L ...

    African Journals Online (AJOL)

    Molecular marker screening of peanut (Arachis hypogaea L.) germplasm for Meloidogyne arenaria resistance. V Carpentieri-Pipolo, M Gallo-Meagher, DW Dickson, DW Gorbet, M de Lurdes Mendes, SG Hulse de Souza ...

  12. Virtual Screening of Receptor Sites for Molecularly Imprinted Polymers.

    Science.gov (United States)

    Bates, Ferdia; Cela-Pérez, María Concepción; Karim, Kal; Piletsky, Sergey; López-Vilariño, José Manuel

    2016-08-01

    Molecularly Imprinted Polymers (MIPs) are highly advantageous in the field of analytical chemistry. However, interference from secondary molecules can also impede capture of a target by a MIP receptor. This greatly complicates the design process and often requires extensive laboratory screening which is time consuming, costly, and creates substantial waste products. Herein, is presented a new technique for screening of "virtually imprinted receptors" for rebinding of the molecular template as well as secondary structures, correlating the virtual predictions with experimentally acquired data in three case studies. This novel technique is particularly applicable to the evaluation and prediction of MIP receptor specificity and efficiency in complex aqueous systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Global screening for Critical Habitat in the terrestrial realm.

    Science.gov (United States)

    Brauneder, Kerstin M; Montes, Chloe; Blyth, Simon; Bennun, Leon; Butchart, Stuart H M; Hoffmann, Michael; Burgess, Neil D; Cuttelod, Annabelle; Jones, Matt I; Kapos, Val; Pilgrim, John; Tolley, Melissa J; Underwood, Emma C; Weatherdon, Lauren V; Brooks, Sharon E

    2018-01-01

    Critical Habitat has become an increasingly important concept used by the finance sector and businesses to identify areas of high biodiversity value. The International Finance Corporation (IFC) defines Critical Habitat in their highly influential Performance Standard 6 (PS6), requiring projects in Critical Habitat to achieve a net gain of biodiversity. Here we present a global screening layer of Critical Habitat in the terrestrial realm, derived from global spatial datasets covering the distributions of 12 biodiversity features aligned with guidance provided by the IFC. Each biodiversity feature is categorised as 'likely' or 'potential' Critical Habitat based on: 1. Alignment between the biodiversity feature and the IFC Critical Habitat definition; and 2. Suitability of the spatial resolution for indicating a feature's presence on the ground. Following the initial screening process, Critical Habitat must then be assessed in-situ by a qualified assessor. This analysis indicates that a total of 10% and 5% of the global terrestrial environment can be considered as likely and potential Critical Habitat, respectively, while the remaining 85% did not overlap with any of the biodiversity features assessed and was classified as 'unknown'. Likely Critical Habitat was determined principally by the occurrence of Key Biodiversity Areas and Protected Areas. Potential Critical Habitat was predominantly characterised by data representing highly threatened and unique ecosystems such as ever-wet tropical forests and tropical dry forests. The areas we identified as likely or potential Critical Habitat are based on the best available global-scale data for the terrestrial realm that is aligned with IFC's Critical Habitat definition. Our results can help businesses screen potential development sites at the early project stage based on a range of biodiversity features. However, the study also demonstrates several important data gaps and highlights the need to incorporate new and

  14. A methodological overview on molecular preimplantation genetic diagnosis and screening: a genomic future?

    Science.gov (United States)

    Vendrell, Xavier; Bautista-Llácer, Rosa

    2012-12-01

    The genetic diagnosis and screening of preimplantation embryos generated by assisted reproduction technology has been consolidated in the prenatal care framework. The rapid evolution of DNA technologies is tending to molecular approaches. Our intention is to present a detailed methodological view, showing different diagnostic strategies based on molecular techniques that are currently applied in preimplantation genetic diagnosis. The amount of DNA from one single, or a few cells, obtained by embryo biopsy is a limiting factor for the molecular analysis. In this sense, genetic laboratories have developed molecular protocols considering this restrictive condition. Nevertheless, the development of whole-genome amplification methods has allowed preimplantation genetic diagnosis for two or more indications simultaneously, like the selection of histocompatible embryos plus detection of monogenic diseases or aneuploidies. Moreover, molecular techniques have permitted preimplantation genetic screening to progress, by implementing microarray-based comparative genome hybridization. Finally, a future view of the embryo-genetics field based on molecular advances is proposed. The normalization, cost-effectiveness analysis, and new technological tools are the next topics for preimplantation genetic diagnosis and screening. Concomitantly, these additions to assisted reproduction technologies could have a positive effect on the schedules of preimplantation studies.

  15. An Automated Algorithm to Screen Massive Training Samples for a Global Impervious Surface Classification

    Science.gov (United States)

    Tan, Bin; Brown de Colstoun, Eric; Wolfe, Robert E.; Tilton, James C.; Huang, Chengquan; Smith, Sarah E.

    2012-01-01

    An algorithm is developed to automatically screen the outliers from massive training samples for Global Land Survey - Imperviousness Mapping Project (GLS-IMP). GLS-IMP is to produce a global 30 m spatial resolution impervious cover data set for years 2000 and 2010 based on the Landsat Global Land Survey (GLS) data set. This unprecedented high resolution impervious cover data set is not only significant to the urbanization studies but also desired by the global carbon, hydrology, and energy balance researches. A supervised classification method, regression tree, is applied in this project. A set of accurate training samples is the key to the supervised classifications. Here we developed the global scale training samples from 1 m or so resolution fine resolution satellite data (Quickbird and Worldview2), and then aggregate the fine resolution impervious cover map to 30 m resolution. In order to improve the classification accuracy, the training samples should be screened before used to train the regression tree. It is impossible to manually screen 30 m resolution training samples collected globally. For example, in Europe only, there are 174 training sites. The size of the sites ranges from 4.5 km by 4.5 km to 8.1 km by 3.6 km. The amount training samples are over six millions. Therefore, we develop this automated statistic based algorithm to screen the training samples in two levels: site and scene level. At the site level, all the training samples are divided to 10 groups according to the percentage of the impervious surface within a sample pixel. The samples following in each 10% forms one group. For each group, both univariate and multivariate outliers are detected and removed. Then the screen process escalates to the scene level. A similar screen process but with a looser threshold is applied on the scene level considering the possible variance due to the site difference. We do not perform the screen process across the scenes because the scenes might vary due to

  16. Molecular marker screening of tomato, ( solanum lycopersicum L ...

    African Journals Online (AJOL)

    Tomato is one of the crops in which genetic resistance has specially been effective against root-knot nematodes. In this study, molecular screening was done on some tomato germplasm to detect markers for the gene that confers resistance (Mi) with specific primer (Mi23/F//Mi23/R). The cultivars; VFNT, FLA 505-BL 1172, ...

  17. Molecular screening in galactosemia

    Energy Technology Data Exchange (ETDEWEB)

    Elsas, L.J.; Singh, R.; Fernhoff, P.M. [Emory Univ., Atlanta, GA (United States)] [and others

    1994-09-01

    Classical galactosemia (G/G) is caused by the absence of galactose-1-phosphate uridyl transferase (GALT) activity while the Duarte allele produces partial impairment and a specific biochemical phenotype. Cloning and sequencing of the human GALT gene has enabled the identification of prevalent mutations for both Classical and Duarte alleles. The G allele is caused by a Q188R codon mutation in exon 6 in 70% of a Caucasian population while the D allele is caused by an N134D codon mutation in exon 10. Since the Q188R sequence creates a new Hpa II site and the N314D sequence creates a new Sin I site, it is relatively easy to screen for both mutations by multiplex PCR and restriction digest. Here we describe a method for detection of new mutations producing impaired GALT. Patient DNAs are subjected to SSCP (single strand conformational polymorphism) analysis of their 11 GALT exons. Direct sequencing of the exons targeted by SSCP has revealed many codon changes: IVSC 956 (a splice acceptor site loss), S135L, V151A, E203K, A320T, and Y323D. Two of these codon changes, V151A and S135L, have been confirmed as mutations by finding impaired GALT activity in a yeast expression system. We conclude that molecular screening of GALT DNA will clarify the structural biology of GALT and the pathophysiology of galactosemia.

  18. Molecular screening and isolation of Newcastle disease virus from ...

    African Journals Online (AJOL)

    Molecular screening and isolation of Newcastle disease virus from live poultry markets and chickens from commercial poultry farms in Zaria, Kaduna state, Nigeria. ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader).

  19. Recharging of a screened ion on the molecular ion

    International Nuclear Information System (INIS)

    Karbovanets, M.I.; Lazur, V.Yu.; Yudin, G.L.; Gosudarstvennyj Komitet po Ispol'zovaniyu Atomnoj Ehnergii SSSR, Obninsk. Fiziko-Ehnergeticheskij Inst.)

    1987-01-01

    Charge exchange of a screened ion on a molecular ion is studied in the Oppenheimer-Brinkman-Cramers approximation. To calculate ion exchange probabilities and cross sections summed over the final degenerated electron states method of Green functions analogous to that applied earlier in the direct Coulomb excitation theory and atomic ionization is developed

  20. Fast screening of ketamine in biological samples based on molecularly imprinted photonic hydrogels

    International Nuclear Information System (INIS)

    Meng, Liang; Meng, Pinjia; Zhang, Qingqing; Wang, Yanji

    2013-01-01

    Graphical abstract: A novel label-free colorimetric chemosensor: with the increase in the concentration of ketamine, the Bragg diffraction peak of MIPHs gradually shifted to the longer wavelength region. Accompanying the peak shift, the color change of MIPHs was also observed obviously: from green to red. Highlights: ► We developed the label-free colorimetric MIPHs for handy and fast screening of ketamine. ► The obvious color change of MIPHs was observed upon ketamine. ► The MIPHs exhibited good sensing abilities in an aqueous environment. ► The sensing mechanisms of the water-compatible MIPHs were investigated. ► The MIPHs were employed to screening ketamine in real biological samples. -- Abstract: A novel label-free colorimetric chemosensor was developed for handy and fast screening of ketamine with high sensitivity and specificity based on molecularly imprinted photonic hydrogels (MIPHs) that combined the colloidal-crystal with molecular imprinting technique. The unique inverse opal arrays with a thin polymer wall in which the imprinted nanocavities of ketamine moleculars distributed allowed high sensitive, quick responsive, specific detection of the target analyte, and good regenerating ability in an aqueous environment. Due to the hierarchical inverse opal structural characteristics, the specific ketamine molecular recognition process can induce obvious swelling of the MIPHs to be directly transferred into visually perceptible optical signal (change in color) which can be detected by the naked eye through Bragg diffractive shifts of ordered macroporous arrays. In order to enhance the recognition ability in aqueous environments, the MIPHs were designed as water-compatible and synthesized in a water–methanol system. The molecular recognition mechanisms were investigated. The proposed MIPHs were successfully employed to screen trace level ketamine in human urine and saliva samples, exhibiting high sensitivity, rapid response, and specificity in the

  1. Fast screening of ketamine in biological samples based on molecularly imprinted photonic hydrogels

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Liang [Department of Forensic Science, People' s Public Security University of China, Beijing (China); Meng, Pinjia, E-mail: mengpinjia@163.com [Department of Forensic Science, People' s Public Security University of China, Beijing (China); Zhang, Qingqing; Wang, Yanji [Department of Forensic Science, People' s Public Security University of China, Beijing (China)

    2013-04-10

    Graphical abstract: A novel label-free colorimetric chemosensor: with the increase in the concentration of ketamine, the Bragg diffraction peak of MIPHs gradually shifted to the longer wavelength region. Accompanying the peak shift, the color change of MIPHs was also observed obviously: from green to red. Highlights: ► We developed the label-free colorimetric MIPHs for handy and fast screening of ketamine. ► The obvious color change of MIPHs was observed upon ketamine. ► The MIPHs exhibited good sensing abilities in an aqueous environment. ► The sensing mechanisms of the water-compatible MIPHs were investigated. ► The MIPHs were employed to screening ketamine in real biological samples. -- Abstract: A novel label-free colorimetric chemosensor was developed for handy and fast screening of ketamine with high sensitivity and specificity based on molecularly imprinted photonic hydrogels (MIPHs) that combined the colloidal-crystal with molecular imprinting technique. The unique inverse opal arrays with a thin polymer wall in which the imprinted nanocavities of ketamine moleculars distributed allowed high sensitive, quick responsive, specific detection of the target analyte, and good regenerating ability in an aqueous environment. Due to the hierarchical inverse opal structural characteristics, the specific ketamine molecular recognition process can induce obvious swelling of the MIPHs to be directly transferred into visually perceptible optical signal (change in color) which can be detected by the naked eye through Bragg diffractive shifts of ordered macroporous arrays. In order to enhance the recognition ability in aqueous environments, the MIPHs were designed as water-compatible and synthesized in a water–methanol system. The molecular recognition mechanisms were investigated. The proposed MIPHs were successfully employed to screen trace level ketamine in human urine and saliva samples, exhibiting high sensitivity, rapid response, and specificity in the

  2. Molecular genetic approach for screening of hereditary non-polyposis colorectal cancer

    Directory of Open Access Journals (Sweden)

    Metka Ravnik-Glavač

    2005-07-01

    Full Text Available Background: The main goal of knowledge concerning human diseases is to transfer as much as possible useful information into clinical applications. Hereditary non-polyposis colorectal cancer (HNPCC is the most common autosomal dominant inherited predisposition for colorectal cancer, accounting for 1–2% of all bowel cancer. The only way to diagnose HNPCC is by a family history consistent with the disease defined by International Collaborative Group on HNPCC (Amsterdam criteria I and II. The main molecular cause of HNPCC is a constitutional mutation in one of the mismatch repair (MMR genes. Since HNPCC mutations have been detected also in families that did not fulfil the Amsterdam criteria, molecular genetic characteristics of HNPCC cancers have been proposed as valuable first step in HNPCC identification. Microsatellite instability is present in about 90% of cancers of HNPCC patients. However, of all MSI colorectal cancers 80– 90% are sporadic. Several molecular mechanisms have been uncovered that enable distinguishing to some extent between sporadic and HNPCC cancers with MSI including hypermethylation of hMLH1 promoter and frequent mutations in BAX and TGFBR2 in sporadic CRC with MSI-H.Conclusions: The determination of MSI status and careful separation of MSI positive colorectal cancer into sporadic MSIL, sporadic MSI-H, and HNPCC MSI-H followed by mutation detection in MMR genes is important for prevention, screening and management of colorectal cancer. In some studies we and others have already shown that large-scale molecular genetic analysis for HNPCC can be done and is sensitive enough to approve population screening. Population screening includes also colonoscopy which is restricted only to the obligate carriers of the mutation. This enables that the disease is detected in earlier stages which would greatly decrease medical treatment costs and most importantly decrease mortality. In Slovenia we have started population screening based

  3. Cellular and molecular modifier pathways in tauopathies: the big picture from screening invertebrate models.

    Science.gov (United States)

    Hannan, Shabab B; Dräger, Nina M; Rasse, Tobias M; Voigt, Aaron; Jahn, Thomas R

    2016-04-01

    Abnormal tau accumulations were observed and documented in post-mortem brains of patients affected by Alzheimer's disease (AD) long before the identification of mutations in the Microtubule-associated protein tau (MAPT) gene, encoding the tau protein, in a different neurodegenerative disease called Frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). The discovery of mutations in the MAPT gene associated with FTDP-17 highlighted that dysfunctions in tau alone are sufficient to cause neurodegeneration. Invertebrate models have been diligently utilized in investigating tauopathies, contributing to the understanding of cellular and molecular pathways involved in disease etiology. An important discovery came with the demonstration that over-expression of human tau in Drosophila leads to premature mortality and neuronal dysfunction including neurodegeneration, recapitulating some key neuropathological features of the human disease. The simplicity of handling invertebrate models combined with the availability of a diverse range of experimental resources make these models, in particular Drosophila a powerful invertebrate screening tool. Consequently, several large-scale screens have been performed using Drosophila, to identify modifiers of tau toxicity. The screens have revealed not only common cellular and molecular pathways, but in some instances the same modifier has been independently identified in two or more screens suggesting a possible role for these modifiers in regulating tau toxicity. The purpose of this review is to discuss the genetic modifier screens on tauopathies performed in Drosophila and C. elegans models, and to highlight the common cellular and molecular pathways that have emerged from these studies. Here, we summarize results of tau toxicity screens providing mechanistic insights into pathological alterations in tauopathies. Key pathways or modifiers that have been identified are associated with a broad range of processes

  4. Is high pressure liquid chromatography an effective screening tool for characterization of molecular defects in hemoglobinopathies?

    Directory of Open Access Journals (Sweden)

    Nikhil Moorchung

    2013-01-01

    Full Text Available Introduction: Hemoglobinopathies constitute entities that are generated by either abnormal hemoglobin or thalassemias. high pressure liquid chromatography (HPLC is one of the best methods for screening and detection of various hemoglobinopathies but it has intrinsic interpretive problems. The study was designed to evaluate the different mutations seen in cases of hemoglobinopathies and compare the same with screening tests. Materials and Methods: 68 patients of hemoglobinopathies were screened by HPLC. Mutation studies in the beta globin gene was performed using the polymerase chain reaction (PCR-based allele-specific Amplification Refractory Mutation System (ARMS. Molecular analysis for the sickle cell mutation was done by standard methods. Results: The IVS 1/5 mutation was the commonest mutation seen and it was seen in 26 (38.23% of the cases. This was followed by the IVS 1/1, codon 41/42, codon 8/9, del 22 mutation, codon 15 mutation and the -619 bp deletion. No mutation was seen in eight cases. There was a 100% concordance between the sickle cell trait as diagnosed by HPLC and genetic testing. Discussion and Conclusion: Our study underlies the importance of molecular testing in all cases of hemoglobinopathies. Although HPLC is a useful screening tool, molecular testing is very useful in accurately diagnosing the mutations. Molecular testing is especially applicable in cases with an abnormal hemoglobin (HbD, HbE and HbS because there may be a concomitant inheritance of a beta thalassemia mutation. Molecular testing is the gold standard when it comes to the diagnosis of hemoglobinopathies.

  5. Oral Administration and Detection of a Near-Infrared Molecular Imaging Agent in an Orthotopic Mouse Model for Breast Cancer Screening.

    Science.gov (United States)

    Bhatnagar, Sumit; Verma, Kirti Dhingra; Hu, Yongjun; Khera, Eshita; Priluck, Aaron; Smith, David E; Thurber, Greg M

    2018-05-07

    Molecular imaging is advantageous for screening diseases such as breast cancer by providing precise spatial information on disease-associated biomarkers, something neither blood tests nor anatomical imaging can achieve. However, the high cost and risks of ionizing radiation for several molecular imaging modalities have prevented a feasible and scalable approach for screening. Clinical studies have demonstrated the ability to detect breast tumors using nonspecific probes such as indocyanine green, but the lack of molecular information and required intravenous contrast agent does not provide a significant benefit over current noninvasive imaging techniques. Here we demonstrate that negatively charged sulfate groups, commonly used to improve solubility of near-infrared fluorophores, enable sufficient oral absorption and targeting of fluorescent molecular imaging agents for completely noninvasive detection of diseased tissue such as breast cancer. These functional groups improve the pharmacokinetic properties of affinity ligands to achieve targeting efficiencies compatible with clinical imaging devices using safe, nonionizing radiation (near-infrared light). Together, this enables development of a "disease screening pill" capable of oral absorption and systemic availability, target binding, background clearance, and imaging at clinically relevant depths for breast cancer screening. This approach should be adaptable to other molecular targets and diseases for use as a new class of screening agents.

  6. Multi-Targeted Molecular Effects of Hibiscus sabdariffa Polyphenols: An Opportunity for a Global Approach to Obesity.

    Science.gov (United States)

    Herranz-López, María; Olivares-Vicente, Mariló; Encinar, José Antonio; Barrajón-Catalán, Enrique; Segura-Carretero, Antonio; Joven, Jorge; Micol, Vicente

    2017-08-20

    Improper diet can alter gene expression by breaking the energy balance equation and changing metabolic and oxidative stress biomarkers, which can result in the development of obesity-related metabolic disorders. The pleiotropic effects of dietary plant polyphenols are capable of counteracting by modulating different key molecular targets at the cell, as well as through epigenetic modifications. Hibiscus sabdariffa (HS)-derived polyphenols are known to ameliorate various obesity-related conditions. Recent evidence leads to propose the complex nature of the underlying mechanism of action. This multi-targeted mechanism includes the regulation of energy metabolism, oxidative stress and inflammatory pathways, transcription factors, hormones and peptides, digestive enzymes, as well as epigenetic modifications. This article reviews the accumulated evidence on the multiple anti-obesity effects of HS polyphenols in cell and animal models, as well as in humans, and its putative molecular targets. In silico studies reveal the capacity of several HS polyphenols to act as putative ligands for different digestive and metabolic enzymes, which may also deserve further attention. Therefore, a global approach including integrated and networked omics techniques, virtual screening and epigenetic analysis is necessary to fully understand the molecular mechanisms of HS polyphenols and metabolites involved, as well as their possible implications in the design of safe and effective polyphenolic formulations for obesity.

  7. Multi-Targeted Molecular Effects of Hibiscus sabdariffa Polyphenols: An Opportunity for a Global Approach to Obesity

    Science.gov (United States)

    Herranz-López, María; Olivares-Vicente, Mariló; Barrajón-Catalán, Enrique; Segura-Carretero, Antonio; Joven, Jorge; Micol, Vicente

    2017-01-01

    Improper diet can alter gene expression by breaking the energy balance equation and changing metabolic and oxidative stress biomarkers, which can result in the development of obesity-related metabolic disorders. The pleiotropic effects of dietary plant polyphenols are capable of counteracting by modulating different key molecular targets at the cell, as well as through epigenetic modifications. Hibiscus sabdariffa (HS)-derived polyphenols are known to ameliorate various obesity-related conditions. Recent evidence leads to propose the complex nature of the underlying mechanism of action. This multi-targeted mechanism includes the regulation of energy metabolism, oxidative stress and inflammatory pathways, transcription factors, hormones and peptides, digestive enzymes, as well as epigenetic modifications. This article reviews the accumulated evidence on the multiple anti-obesity effects of HS polyphenols in cell and animal models, as well as in humans, and its putative molecular targets. In silico studies reveal the capacity of several HS polyphenols to act as putative ligands for different digestive and metabolic enzymes, which may also deserve further attention. Therefore, a global approach including integrated and networked omics techniques, virtual screening and epigenetic analysis is necessary to fully understand the molecular mechanisms of HS polyphenols and metabolites involved, as well as their possible implications in the design of safe and effective polyphenolic formulations for obesity. PMID:28825642

  8. Impact of transition from microscopy to molecular screening for detection of intestinal protozoa in Dutch patients.

    Science.gov (United States)

    Svraka-Latifovic, S; Bouter, S; Naus, H; Bakker, L J; Timmerman, C P; Dorigo-Zetsma, J W

    2014-11-01

    Detection of intestinal protozoa by PCR methods has been described as being sensitive and specific, and as improving the diagnostic yield. Here we present the outcome of the transition from microscopy to molecular screening for detection of a select group of intestinal protozoa in faeces in our laboratory. Introduction of molecular screening for intestinal protozoa resulted in higher sensitivity, reduced hands-on-time, reduced time-to-results, leading to improved diagnostic efficiency. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

  9. Extending the Global Dialogue about Media, Technology, Screen Time, and Young Children

    Science.gov (United States)

    Ernest, James M.; Causey, Cora; Newton, Allison B.; Sharkins, Kimberly; Summerlin, Jennifer; Albaiz, Najla

    2014-01-01

    Questions about the potential benefits and dangers of media and technology use abound, with competing theories regarding its effects among young children. This article explores global perspectives on children's exposure to media, technology, and screen time (MeTS) in the schools, homes, and communities of an increasingly technology-driven world.…

  10. Screening of Potential Lead Molecule as Novel MurE Inhibitor: Virtual Screening, Molecular Dynamics and In Vitro Studies.

    Science.gov (United States)

    Zaveri, Kunal; Kiranmayi, Patnala

    2017-01-01

    The prevalence of multi-drug resistance S. aureus is one of the most challenging tasks for the treatment of nosocomial infections. Proteins and enzymes of peptidoglycan biosynthesis pathway are one among the well-studied targets, but many of the enzymes are unexplored as targets. MurE is one such enzyme featured to be a promising target. As MurE plays an important role in ligating the L-lys to stem peptide at third position that is crucial for peptidoglycan synthesis. To screen the potential MurE inhibitor by in silico approach and evaluate the best potential lead molecule by in vitro methods. In the current study, we have employed structure based virtual screening targeting the active site of MurE, followed by Molecular dynamics and in vitro studies. Virtual screening resulted in successful screening of potential lead molecule ((2R)-2-[[1-[(2R)- 2-(benzyloxycarbonylamino) propanoyl] piperidine-4-carbonyl]amino]-5-guanidino-pentan). The molecular dynamics of the MurE and Lead molecule complex emphasizes that lead molecule has shown stable interactions with active site residues Asp 406 and with Glu 460. In vitro studies demonstrate that the lead molecule shows antibacterial activity close to standard antibiotic Vancomycin and higher than that of Ampicillin, Streptomycin and Rifampicin. The MIC of lead molecule at 50μg/mL was observed to be 3.75 μg/mL, MBC being bactericidal with value of 6.25 μg/mL, cytotoxicity showing 34.44% and IC50 of 40.06μg/mL. These results suggest ((2R)-2-[[1-[(2R)-2-(benzyloxycarbonylamino) propanoyl] piperidine-4-carbonyl]amino]-5-guanidino-pentan) as a promising lead molecule for developing a MurE inhibitor against treatment of S. aureus infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. The Effects of Using Touch-Screen Devices on Students' Molecular Visualization and Representational Competence Skills

    Science.gov (United States)

    McCollum, Brett M.; Regier, Lisa; Leong, Jaque; Simpson, Sarah; Sterner, Shayne

    2014-01-01

    The impact of touch-screen technology on spatial cognitive skills as related to molecular geometries was assessed through 102 one-on-one interviews with undergraduate students. Participants were provided with either printed 2D ball-and-stick images of molecules or manipulable projections of 3D molecular structures on an iPad. Following a brief…

  12. Molecular profiles of screen detected vs. symptomatic breast cancer and their impact on survival: results from a clinical series

    International Nuclear Information System (INIS)

    Crispo, Anna; Esposito, Emanuela; Amore, Alfonso; Di Bonito, Maurizio; Botti, Gerardo; Montella, Maurizio; Barba, Maddalena; D’Aiuto, Giuseppe; De Laurentiis, Michelino; Grimaldi, Maria; Rinaldo, Massimo; Caolo, Giuseppina; D’Aiuto, Massimiliano; Capasso, Immacolata

    2013-01-01

    Stage shift is widely considered a major determinant of the survival benefit conferred by breast cancer screening. However, factors and mechanisms underlying such a prognostic advantage need further clarification. We sought to compare the molecular characteristics of screen detected vs. symptomatic breast cancers and assess whether differences in tumour biology might translate into survival benefit. In a clinical series of 448 women with operable breast cancer, the Kaplan-Meier method and the log-rank test were used to estimate the likelihood of cancer recurrence and death. The Cox proportional hazard model was used for the multivariate analyses including mode of detection, age at diagnosis, tumour size, and lymph node status. These same models were applied to subgroups defined by molecular subtypes. Screen detected breast cancers tended to show more favourable clinicopathological features and survival outcomes compared to symptomatic cancers. The luminal A subtype was more common in women with mammography detected tumours than in symptomatic patients (68.5 vs. 59.0%, p=0.04). Data analysis across categories of molecular subtypes revealed significantly longer disease free and overall survival for screen detected cancers with a luminal A subtype only (p=0.01 and 0.02, respectively). For women with a luminal A subtype, the independent prognostic role of mode of detection on recurrence was confirmed in Cox proportional hazard models (p=0.03). An independent role of modality of detection on survival was also suggested (p=0.05). Molecular subtypes did not substantially explain the differences in survival outcomes between screened and symptomatic patients. However, our results suggest that molecular profiles might play a role in interpreting such differences at least partially. Further studies are warranted to reinterpret the efficacy of screening programmes in the light of tumour biology

  13. Global Molecular Epidemiology of IMP-Producing Enterobacteriaceae.

    Science.gov (United States)

    Matsumura, Yasufumi; Peirano, Gisele; Motyl, Mary R; Adams, Mark D; Chen, Liang; Kreiswirth, Barry; DeVinney, Rebekah; Pitout, Johann D D

    2017-04-01

    International data on the molecular epidemiology of Enterobacteriaceae with IMP carbapenemases are lacking. We performed short-read (Illumina) whole-genome sequencing on a global collection of 38 IMP-producing clinical Enterobacteriaceae (2008 to 2014). IMP-producing Enterobacteriaceae (7 varieties within 11 class 1 integrons) were mainly present in the South Pacific and Asia. Specific bla IMP -containing integrons (In809 with bla IMP-4 , In722 with bla IMP-6 , and In687 with bla IMP-14 ) were circulating among different bacteria in countries such as Australia, Japan, and Thailand. In1312 with bla IMP-1 was present in Klebsiella pneumoniae from Japan and Citrobacter freundii from Brazil. Klebsiella pneumoniae ( n = 22) was the most common species; clonal complex 14 (CC14) from Philippines and Japan was the most common clone and contained In1310 with bla IMP-26 and In1321 with bla IMP-6 The Enterobacter cloacae complex ( n = 9) consisted of Enterobacter hormaechei and E. cloacae cluster III. CC78 (from Taiwan) containing In73 with bla IMP-8 was the most common clone among the E. cloacae complex. This study highlights the importance of surveillance programs using the latest molecular techniques for providing insight into the characteristics and global distribution of Enterobacteriaceae with bla IMP genes. Copyright © 2017 American Society for Microbiology.

  14. Pharmacophore-based virtual screening, molecular docking, molecular dynamics simulation, and biological evaluation for the discovery of novel BRD4 inhibitors.

    Science.gov (United States)

    Yan, Guoyi; Hou, Manzhou; Luo, Jiang; Pu, Chunlan; Hou, Xueyan; Lan, Suke; Li, Rui

    2018-02-01

    Bromodomain is a recognition module in the signal transduction of acetylated histone. BRD4, one of the bromodomain members, is emerging as an attractive therapeutic target for several types of cancer. Therefore, in this study, an attempt has been made to screen compounds from an integrated database containing 5.5 million compounds for BRD4 inhibitors using pharmacophore-based virtual screening, molecular docking, and molecular dynamics simulations. As a result, two molecules of twelve hits were found to be active in bioactivity tests. Among the molecules, compound 5 exhibited potent anticancer activity, and the IC 50 values against human cancer cell lines MV4-11, A375, and HeLa were 4.2, 7.1, and 11.6 μm, respectively. After that, colony formation assay, cell cycle, apoptosis analysis, wound-healing migration assay, and Western blotting were carried out to learn the bioactivity of compound 5. © 2017 John Wiley & Sons A/S.

  15. Identification of critical chemical features for Aurora kinase-B inhibitors using Hip-Hop, virtual screening and molecular docking

    Science.gov (United States)

    Sakkiah, Sugunadevi; Thangapandian, Sundarapandian; John, Shalini; Lee, Keun Woo

    2011-01-01

    This study was performed to find the selective chemical features for Aurora kinase-B inhibitors using the potent methods like Hip-Hop, virtual screening, homology modeling, molecular dynamics and docking. The best hypothesis, Hypo1 was validated toward a wide range of test set containing the selective inhibitors of Aurora kinase-B. Homology modeling and molecular dynamics studies were carried out to perform the molecular docking studies. The best hypothesis Hypo1 was used as a 3D query to screen the chemical databases. The screened molecules from the databases were sorted based on ADME and drug like properties. The selective hit compounds were docked and the hydrogen bond interactions with the critical amino acids present in Aurora kinase-B were compared with the chemical features present in the Hypo1. Finally, we suggest that the chemical features present in the Hypo1 are vital for a molecule to inhibit the Aurora kinase-B activity.

  16. Association of Screening and Treatment With Breast Cancer Mortality by Molecular Subtype in US Women, 2000-2012.

    Science.gov (United States)

    Plevritis, Sylvia K; Munoz, Diego; Kurian, Allison W; Stout, Natasha K; Alagoz, Oguzhan; Near, Aimee M; Lee, Sandra J; van den Broek, Jeroen J; Huang, Xuelin; Schechter, Clyde B; Sprague, Brian L; Song, Juhee; de Koning, Harry J; Trentham-Dietz, Amy; van Ravesteyn, Nicolien T; Gangnon, Ronald; Chandler, Young; Li, Yisheng; Xu, Cong; Ergun, Mehmet Ali; Huang, Hui; Berry, Donald A; Mandelblatt, Jeanne S

    2018-01-09

    Given recent advances in screening mammography and adjuvant therapy (treatment), quantifying their separate and combined effects on US breast cancer mortality reductions by molecular subtype could guide future decisions to reduce disease burden. To evaluate the contributions associated with screening and treatment to breast cancer mortality reductions by molecular subtype based on estrogen-receptor (ER) and human epidermal growth factor receptor 2 (ERBB2, formerly HER2 or HER2/neu). Six Cancer Intervention and Surveillance Network (CISNET) models simulated US breast cancer mortality from 2000 to 2012 using national data on plain-film and digital mammography patterns and performance, dissemination and efficacy of ER/ERBB2-specific treatment, and competing mortality. Multiple US birth cohorts were simulated. Screening mammography and treatment. The models compared age-adjusted, overall, and ER/ERBB2-specific breast cancer mortality rates from 2000 to 2012 for women aged 30 to 79 years relative to the estimated mortality rate in the absence of screening and treatment (baseline rate); mortality reductions were apportioned to screening and treatment. In 2000, the estimated reduction in overall breast cancer mortality rate was 37% (model range, 27%-42%) relative to the estimated baseline rate in 2000 of 64 deaths (model range, 56-73) per 100 000 women: 44% (model range, 35%-60%) of this reduction was associated with screening and 56% (model range, 40%-65%) with treatment. In 2012, the estimated reduction in overall breast cancer mortality rate was 49% (model range, 39%-58%) relative to the estimated baseline rate in 2012 of 63 deaths (model range, 54-73) per 100 000 women: 37% (model range, 26%-51%) of this reduction was associated with screening and 63% (model range, 49%-74%) with treatment. Of the 63% associated with treatment, 31% (model range, 22%-37%) was associated with chemotherapy, 27% (model range, 18%-36%) with hormone therapy, and 4% (model range, 1

  17. FieldChopper, a new tool for automatic model generation and virtual screening based on molecular fields.

    Science.gov (United States)

    Kalliokoski, Tuomo; Ronkko, Toni; Poso, Antti

    2008-06-01

    Algorithms were developed for ligand-based virtual screening of molecular databases. FieldChopper (FC) is based on the discretization of the electrostatic and van der Waals field into three classes. A model is built from a set of superimposed active molecules. The similarity of the compounds in the database to the model is then calculated using matrices that define scores for comparing field values of different categories. The method was validated using 12 publicly available data sets by comparing the method to the electrostatic similarity comparison program EON. The results suggest that FC is competitive with more complex descriptors and could be used as a molecular sieve in virtual screening experiments when multiple active ligands are known.

  18. In vivo quantification of fluorescent molecular markers in real-time by ratio Imaging for diagnostic screening and image-guided surgery

    NARCIS (Netherlands)

    Bogaards, A.; Sterenborg, H. J. C. M.; Trachtenberg, J.; Wilson, B. C.; Lilge, L.

    2007-01-01

    Future applications of "molecular diagnostic screening" and "molecular image-guided surgery" will demand images of molecular markers with high resolution and high throughput (similar to >= 30 frames/second). MRI, SPECT, PET, optical fluorescence tomography, hyper-spectral fluorescence imaging, and

  19. Use of Subjective Global Assessment, Patient-Generated Subjective Global Assessment and Nutritional Risk Screening 2002 to evaluate the nutritional status of non-critically ill patients on parenteral nutrition.

    Science.gov (United States)

    Badia-Tahull, M B; Cobo-Sacristán, S; Leiva-Badosa, E; Miquel-Zurita, M E; Méndez-Cabalerio, N; Jódar-Masanés, R; Llop-Talaverón, J

    2014-02-01

    To evaluate the nutritional status of non-critically ill digestive surgery patients at the moment of parenteral nutrition initiation using three different nutritional test tools and to study their correlation. To study the association between the tests and the clinical and laboratory parameters used in the follow-up of PN treatment. Prospective study over 4 months. Anthropometric and clinical variables were recorded. Results of Subjective Global Assessment; Patient-Generated Subjective Global Assessment; and Nutritional Risk Screening 2002 were compared applying kappa test. Relationship between the clinical and laboratory parameters with Subjective Global Assessment was studied by multinominal regression and with the other two tests by multiple linear regression models. Age and sex were included as adjustment variables. Malnutrition in 45 studied patients varied from 51% to 57%. Subjective Global Assessment correlated well with Patient-Generated Subjective Global Assessment and Nutritional Risk Screening 2002 (κ = 0531 p = 0.000). The test with the greatest correlation with the clinical and analytical variables was the Nutritional Risk Screening 2002. Worse nutritional state in this test was associated with worse results in albumin (B = -0.087; CI = -0.169/-0.005], prealbumin (B = -0.005; CI = [-0.011/-0.001]), C-reactive protein (B = 0.006;CI = [0.001/ 0.011]) and leukocytes (B = 0.134; CI = [0.031/0.237]) at the en of parenteral nutrition treatment. Half of the digestive surgery patients were at malnutritional risk at the moment of initiating parenteral nutrition. Nutritional Risk Screening 2002 was the test with best association with the parameters used in the clinical follow-up of parenteral nutrition treated patients. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  20. Revealing molecular mechanisms by integrating high-dimensional functional screens with protein interaction data.

    Directory of Open Access Journals (Sweden)

    Angela Simeone

    2014-09-01

    Full Text Available Functional genomics screens using multi-parametric assays are powerful approaches for identifying genes involved in particular cellular processes. However, they suffer from problems like noise, and often provide little insight into molecular mechanisms. A bottleneck for addressing these issues is the lack of computational methods for the systematic integration of multi-parametric phenotypic datasets with molecular interactions. Here, we present Integrative Multi Profile Analysis of Cellular Traits (IMPACT. The main goal of IMPACT is to identify the most consistent phenotypic profile among interacting genes. This approach utilizes two types of external information: sets of related genes (IMPACT-sets and network information (IMPACT-modules. Based on the notion that interacting genes are more likely to be involved in similar functions than non-interacting genes, this data is used as a prior to inform the filtering of phenotypic profiles that are similar among interacting genes. IMPACT-sets selects the most frequent profile among a set of related genes. IMPACT-modules identifies sub-networks containing genes with similar phenotype profiles. The statistical significance of these selections is subsequently quantified via permutations of the data. IMPACT (1 handles multiple profiles per gene, (2 rescues genes with weak phenotypes and (3 accounts for multiple biases e.g. caused by the network topology. Application to a genome-wide RNAi screen on endocytosis showed that IMPACT improved the recovery of known endocytosis-related genes, decreased off-target effects, and detected consistent phenotypes. Those findings were confirmed by rescreening 468 genes. Additionally we validated an unexpected influence of the IGF-receptor on EGF-endocytosis. IMPACT facilitates the selection of high-quality phenotypic profiles using different types of independent information, thereby supporting the molecular interpretation of functional screens.

  1. Pharmacophore modeling, virtual screening and molecular docking of ATPase inhibitors of HSP70.

    Science.gov (United States)

    Sangeetha, K; Sasikala, R P; Meena, K S

    2017-10-01

    Heat shock protein 70 is an effective anticancer target as it influences many signaling pathways. Hence the study investigated the important pharmacophore feature required for ATPase inhibitors of HSP70 by generating a ligand based pharmacophore model followed by virtual based screening and subsequent validation by molecular docking in Discovery studio V4.0. The most extrapolative pharmacophore model (hypotheses 8) consisted of four hydrogen bond acceptors. Further validation by external test set prediction identified 200 hits from Mini Maybridge, Drug Diverse, SCPDB compounds and Phytochemicals. Consequently, the screened compounds were refined by rule of five, ADMET and molecular docking to retain the best competitive hits. Finally Phytochemical compounds Muricatetrocin B, Diacetylphiladelphicalactone C, Eleutheroside B and 5-(3-{[1-(benzylsulfonyl)piperidin-4-yl]amino}phenyl)- 4-bromo-3-(carboxymethoxy)thiophene-2-carboxylic acid were obtained as leads to inhibit the ATPase activity of HSP70 in our findings and thus can be proposed for further in vitro and in vivo evaluation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Successful application of virtual screening and molecular dynamics simulations against antimalarial molecular targets

    Directory of Open Access Journals (Sweden)

    Renata Rachide Nunes

    Full Text Available The main challenge in the control of malaria has been the emergence of drug-resistant parasites. The presence of drug-resistant Plasmodium sp. has raised the need for new antimalarial drugs. Molecular modelling techniques have been used as tools to develop new drugs. In this study, we employed virtual screening of a pyrazol derivative (Tx001 against four malaria targets: plasmepsin-IV, plasmepsin-II, falcipain-II, and PfATP6. The receiver operating characteristic curves and area under the curve (AUC were established for each molecular target. The AUC values obtained for plasmepsin-IV, plasmepsin-II, and falcipain-II were 0.64, 0.92, and 0.94, respectively. All docking simulations were carried out using AutoDock Vina software. The ligand Tx001 exhibited a better interaction with PfATP6 than with the reference compound (-12.2 versus -6.8 Kcal/mol. The Tx001-PfATP6 complex was submitted to molecular dynamics simulations in vacuum implemented on an NAMD program. The ligand Tx001 docked at the same binding site as thapsigargin, which is a natural inhibitor of PfATP6. Compound TX001 was evaluated in vitro with a P. falciparum strain (W2 and a human cell line (WI-26VA4. Tx001 was discovered to be active against P. falciparum (IC50 = 8.2 µM and inactive against WI-26VA4 (IC50 > 200 µM. Further ligand optimisation cycles generated new prospects for docking and biological assays.

  3. Integration of Molecular Pathology, Epidemiology, and Social Science for Global Precision Medicine

    Science.gov (United States)

    Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L.; Nishihara, Reiko; Tan, Andy S.; Kawachi, Ichiro; Ogino, Shuji

    2015-01-01

    Summary The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations, and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial, and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors, and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference, and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology, and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors, and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging, and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science. PMID:26636627

  4. Integration of molecular pathology, epidemiology and social science for global precision medicine.

    Science.gov (United States)

    Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L; Nishihara, Reiko; Tan, Andy S; Kawachi, Ichiro; Ogino, Shuji

    2016-01-01

    The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science.

  5. Design of efficient molecular organic light-emitting diodes by a high-throughput virtual screening and experimental approach

    Science.gov (United States)

    Gómez-Bombarelli, Rafael; Aguilera-Iparraguirre, Jorge; Hirzel, Timothy D.; Duvenaud, David; MacLaurin, Dougal; Blood-Forsythe, Martin A.; Chae, Hyun Sik; Einzinger, Markus; Ha, Dong-Gwang; Wu, Tony; Markopoulos, Georgios; Jeon, Soonok; Kang, Hosuk; Miyazaki, Hiroshi; Numata, Masaki; Kim, Sunghan; Huang, Wenliang; Hong, Seong Ik; Baldo, Marc; Adams, Ryan P.; Aspuru-Guzik, Alán

    2016-10-01

    Virtual screening is becoming a ground-breaking tool for molecular discovery due to the exponential growth of available computer time and constant improvement of simulation and machine learning techniques. We report an integrated organic functional material design process that incorporates theoretical insight, quantum chemistry, cheminformatics, machine learning, industrial expertise, organic synthesis, molecular characterization, device fabrication and optoelectronic testing. After exploring a search space of 1.6 million molecules and screening over 400,000 of them using time-dependent density functional theory, we identified thousands of promising novel organic light-emitting diode molecules across the visible spectrum. Our team collaboratively selected the best candidates from this set. The experimentally determined external quantum efficiencies for these synthesized candidates were as large as 22%.

  6. An effective HIV-1 integrase inhibitor screening platform: Rationality validation of drug screening, conformational mobility and molecular recognition analysis for PFV integrase complex with viral DNA.

    Science.gov (United States)

    Du, Wenyi; Zuo, Ke; Sun, Xin; Liu, Wei; Yan, Xiao; Liang, Li; Wan, Hua; Chen, Fengzheng; Hu, Jianping

    2017-11-01

    As an important target for the development of novel anti-AIDS drugs, HIV-1 integrase (IN) has been widely concerned. However, the lack of a complete accurate crystal structure of HIV-1 IN greatly blocks the discovery of novel inhibitors. In this work, an effective HIV-1 IN inhibitor screening platform, namely PFV IN, was filtered from all species of INs. Next, the 40.8% similarity with HIV-1 IN, as well as the high efficiency of virtual screening and the good agreement between calculated binding free energies and experimental ones all proved PFV IN is a promising screening platform for HIV-1 IN inhibitors. Then, the molecular recognition mechanism of PFV IN by its substrate viral DNA and six naphthyridine derivatives (NRDs) inhibitors was investigated through molecular docking, molecular dynamics simulations and water-mediated interactions analyses. The functional partition of NRDs IN inhibitors could be divided into hydrophobic and hydrophilic ones, and the Mg 2+ ions, water molecules and conserved DDE motif residues all interacted with the hydrophilic partition, while the bases in viral DNA and residues like Tyr212, Pro214 interacted with the hydrophobic one. Finally, the free energy landscape (FEL) and cluster analyses were performed to explore the molecular motion of PFV IN-DNA system. It is found that the association with NRDs inhibitors would obviously decrease the motion amplitude of PFV IN-DNA, which may be one of the most potential mechanisms of IN inhibitors. This work will provide a theoretical basis for the inhibitor design based on the structure of HIV-1 IN. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular Studies

    Directory of Open Access Journals (Sweden)

    Serena Catarzi

    2013-01-01

    Full Text Available Medium-chain acyl-CoA dehydrogenase deficiency (MCADD is a disorder of fatty acid oxidation characterized by hypoglycemic crisis under fasting or during stress conditions, leading to lethargy, seizures, brain damage, or even death. Biochemical acylcarnitines data obtained through newborn screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS were confirmed by molecular analysis of the medium-chain acyl-CoA dehydrogenase (ACADM gene. Out of 324.000 newborns screened, we identified 14 MCADD patients, in whom, by molecular analysis, we found a new nonsense c.823G>T (p.Gly275* and two new missense mutations: c.253G>C (p.Gly85Arg and c.356T>A (p.Val119Asp. Bioinformatics predictions based on both phylogenetic conservation and functional/structural software were used to characterize the new identified variants. Our findings confirm the rising incidence of MCADD whose existence is increasingly recognized due to the efficacy of an expanded newborn screening panel by LC-MS/MS making possible early specific therapies that can prevent possible crises in at-risk infants. We noticed that the “common” p.Lys329Glu mutation only accounted for 32% of the defective alleles, while, in clinically diagnosed patients, this mutation accounted for 90% of defective alleles. Unclassified variants (UVs or VUSs are especially critical when considering screening programs. The functional and pathogenic characterization of genetic variants presented here is required to predict their medical consequences in newborns.

  8. Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular Studies

    Science.gov (United States)

    Catarzi, Serena; Caciotti, Anna; Thusberg, Janita; Tonin, Rodolfo; Malvagia, Sabrina; la Marca, Giancarlo; Pasquini, Elisabetta; Cavicchi, Catia; Ferri, Lorenzo; Donati, Maria A.; Baronio, Federico; Guerrini, Renzo; Mooney, Sean D.; Morrone, Amelia

    2013-01-01

    Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder of fatty acid oxidation characterized by hypoglycemic crisis under fasting or during stress conditions, leading to lethargy, seizures, brain damage, or even death. Biochemical acylcarnitines data obtained through newborn screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were confirmed by molecular analysis of the medium-chain acyl-CoA dehydrogenase (ACADM) gene. Out of 324.000 newborns screened, we identified 14 MCADD patients, in whom, by molecular analysis, we found a new nonsense c.823G>T (p.Gly275∗) and two new missense mutations: c.253G>C (p.Gly85Arg) and c.356T>A (p.Val119Asp). Bioinformatics predictions based on both phylogenetic conservation and functional/structural software were used to characterize the new identified variants. Our findings confirm the rising incidence of MCADD whose existence is increasingly recognized due to the efficacy of an expanded newborn screening panel by LC-MS/MS making possible early specific therapies that can prevent possible crises in at-risk infants. We noticed that the “common” p.Lys329Glu mutation only accounted for 32% of the defective alleles, while, in clinically diagnosed patients, this mutation accounted for 90% of defective alleles. Unclassified variants (UVs or VUSs) are especially critical when considering screening programs. The functional and pathogenic characterization of genetic variants presented here is required to predict their medical consequences in newborns. PMID:24294134

  9. AMMOS: Automated Molecular Mechanics Optimization tool for in silico Screening

    Directory of Open Access Journals (Sweden)

    Pajeva Ilza

    2008-10-01

    Full Text Available Abstract Background Virtual or in silico ligand screening combined with other computational methods is one of the most promising methods to search for new lead compounds, thereby greatly assisting the drug discovery process. Despite considerable progresses made in virtual screening methodologies, available computer programs do not easily address problems such as: structural optimization of compounds in a screening library, receptor flexibility/induced-fit, and accurate prediction of protein-ligand interactions. It has been shown that structural optimization of chemical compounds and that post-docking optimization in multi-step structure-based virtual screening approaches help to further improve the overall efficiency of the methods. To address some of these points, we developed the program AMMOS for refining both, the 3D structures of the small molecules present in chemical libraries and the predicted receptor-ligand complexes through allowing partial to full atom flexibility through molecular mechanics optimization. Results The program AMMOS carries out an automatic procedure that allows for the structural refinement of compound collections and energy minimization of protein-ligand complexes using the open source program AMMP. The performance of our package was evaluated by comparing the structures of small chemical entities minimized by AMMOS with those minimized with the Tripos and MMFF94s force fields. Next, AMMOS was used for full flexible minimization of protein-ligands complexes obtained from a mutli-step virtual screening. Enrichment studies of the selected pre-docked complexes containing 60% of the initially added inhibitors were carried out with or without final AMMOS minimization on two protein targets having different binding pocket properties. AMMOS was able to improve the enrichment after the pre-docking stage with 40 to 60% of the initially added active compounds found in the top 3% to 5% of the entire compound collection

  10. Identification and characterization of tebuconazole transformation products in soil by combining suspect screening and molecular typology

    International Nuclear Information System (INIS)

    Storck, Veronika; Lucini, Luigi; Mamy, Laure; Ferrari, Federico; Papadopoulou, Evangelia S.; Nikolaki, Sofia; Karas, Panagiotis A.; Servien, Remi; Karpouzas, Dimitrios G.; Trevisan, Marco; Benoit, Pierre; Martin-Laurent, Fabrice

    2016-01-01

    Pesticides generate transformation products (TPs) when they are released into the environment. These TPs may be of ecotoxicological importance. Past studies have demonstrated how difficult it is to predict the occurrence of pesticide TPs and their environmental risk. The monitoring approaches mostly used in current regulatory frameworks target only known ecotoxicologically relevant TPs. Here, we present a novel combined approach which identifies and categorizes known and unknown pesticide TPs in soil by combining suspect screening time-of-flight mass spectrometry with in silico molecular typology. We used an empirical and theoretical pesticide TP library for compound identification by both non-target and target time-of-flight (tandem) mass spectrometry, followed by structural proposition through a molecular structure correlation program. In silico molecular typology was then used to group TPs according to common molecular descriptors and to indirectly elucidate their environmental parameters by analogy to known pesticide compounds with similar molecular descriptors. This approach was evaluated via the identification of TPs of the triazole fungicide tebuconazole occurring in soil during a field dissipation study. Overall, 22 empirical and 12 yet unknown TPs were detected, and categorized into three groups with defined environmental properties. This approach combining suspect screening time-of-flight mass spectrometry with molecular typology could be extended to other organic pollutants and used to rationalize the choice of TPs to be investigated towards a more comprehensive environmental risk assessment scheme. - Highlights: • Combined method to detect and categorize pesticide transformation products in soil. • Detection by QTOF-MS of new tebuconazole transformation products without standards. • Estimation by in silico molecular typology of their environmental parameters. • Method to rationally choose relevant transformation products to be studied. • The

  11. Design of a multi-purpose fragment screening library using molecular complexity and orthogonal diversity metrics

    Science.gov (United States)

    Lau, Wan F.; Withka, Jane M.; Hepworth, David; Magee, Thomas V.; Du, Yuhua J.; Bakken, Gregory A.; Miller, Michael D.; Hendsch, Zachary S.; Thanabal, Venkataraman; Kolodziej, Steve A.; Xing, Li; Hu, Qiyue; Narasimhan, Lakshmi S.; Love, Robert; Charlton, Maura E.; Hughes, Samantha; van Hoorn, Willem P.; Mills, James E.

    2011-07-01

    Fragment Based Drug Discovery (FBDD) continues to advance as an efficient and alternative screening paradigm for the identification and optimization of novel chemical matter. To enable FBDD across a wide range of pharmaceutical targets, a fragment screening library is required to be chemically diverse and synthetically expandable to enable critical decision making for chemical follow-up and assessing new target druggability. In this manuscript, the Pfizer fragment library design strategy which utilized multiple and orthogonal metrics to incorporate structure, pharmacophore and pharmacological space diversity is described. Appropriate measures of molecular complexity were also employed to maximize the probability of detection of fragment hits using a variety of biophysical and biochemical screening methods. In addition, structural integrity, purity, solubility, fragment and analog availability as well as cost were important considerations in the selection process. Preliminary analysis of primary screening results for 13 targets using NMR Saturation Transfer Difference (STD) indicates the identification of uM-mM hits and the uniqueness of hits at weak binding affinities for these targets.

  12. The global security perspective on the effects of executive cognitive function on complex behavioral screening intervention and HIV/AIDS.

    Science.gov (United States)

    Kim, Suk-Hee

    2010-11-01

    The purpose of this quantitative study is to understand the global security perspective on the effects of executive cognitive function (ECF) on Complex Behavioral Screening Intervention and HIV/AIDS. The HIV/AIDS pandemic is as much a social, political, economic, and cultural problem as a biomedical one. HIV/AIDS is associated centrally with the collapse not just of communities and families but potentially of states, with some of the largest public health interventions ever and enormous questions about governance, a huge population of orphans, and deep questions about intergenerational relations and cultural transmission. This study also is to develop a screening instrument that improves quality of life for individuals with executive cognitive impairments and behavior problems in our communities and the global society.

  13. A Similarity Search Using Molecular Topological Graphs

    Directory of Open Access Journals (Sweden)

    Yoshifumi Fukunishi

    2009-01-01

    Full Text Available A molecular similarity measure has been developed using molecular topological graphs and atomic partial charges. Two kinds of topological graphs were used. One is the ordinary adjacency matrix and the other is a matrix which represents the minimum path length between two atoms of the molecule. The ordinary adjacency matrix is suitable to compare the local structures of molecules such as functional groups, and the other matrix is suitable to compare the global structures of molecules. The combination of these two matrices gave a similarity measure. This method was applied to in silico drug screening, and the results showed that it was effective as a similarity measure.

  14. Molecular-Simulation-Driven Fragment Screening for the Discovery of New CXCL12 Inhibitors.

    Science.gov (United States)

    Martinez-Rosell, Gerard; Harvey, Matt J; De Fabritiis, Gianni

    2018-03-26

    Fragment-based drug discovery (FBDD) has become a mainstream approach in drug design because it allows the reduction of the chemical space and screening libraries while identifying fragments with high protein-ligand efficiency interactions that can later be grown into drug-like leads. In this work, we leverage high-throughput molecular dynamics (MD) simulations to screen a library of 129 fragments for a total of 5.85 ms against the CXCL12 monomer, a chemokine involved in inflammation and diseases such as cancer. Our in silico binding assay was able to recover binding poses, affinities, and kinetics for the selected library and was able to predict 8 mM-affinity fragments with ligand efficiencies higher than 0.3. All of the fragment hits present a similar chemical structure, with a hydrophobic core and a positively charged group, and bind to either sY7 or H1S68 pockets, where they share pharmacophoric properties with experimentally resolved natural binders. This work presents a large-scale screening assay using an exclusive combination of thousands of short MD adaptive simulations analyzed with a Markov state model (MSM) framework.

  15. Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico.

    Science.gov (United States)

    Jhong, Chien-Hung; Riyaphan, Jirawat; Lin, Shih-Hung; Chia, Yi-Chen; Weng, Ching-Feng

    2015-01-01

    The alpha-glucosidase inhibitor is a common oral anti-diabetic drug used for controlling carbohydrates normally converted into simple sugars and absorbed by the intestines. However, some adverse clinical effects have been observed. The present study seeks an alternative drug that can regulate the hyperglycemia by down-regulating alpha-glucosidase and alpha-amylase activity by molecular docking approach to screen the hyperglycemia antagonist against alpha-glucosidase and alpha-amylase activities from the 47 natural compounds. The docking data showed that Curcumin, 16-hydroxy-cleroda-3,13-dine-16,15-olide (16-H), Docosanol, Tetracosanol, Antroquinonol, Berberine, Catechin, Quercetin, Actinodaphnine, and Rutin from 47 natural compounds had binding ability towards alpha-amylase and alpha-glucosidase as well. Curcumin had a better biding ability of alpha-amylase than the other natural compounds. Analyzed alpha-glucosidase activity reveals natural compound inhibitors (below 0.5 mM) are Curcumin, Actinodaphnine, 16-H, Quercetin, Berberine, and Catechin when compared to the commercial drug Acarbose (3 mM). A natural compound with alpha-amylase inhibitors (below 0.5 mM) includes Curcumin, Berberine, Docosanol, 16-H, Actinodaphnine/Tetracosanol, Catechin, and Quercetin when compared to Acarbose (1 mM). When taken together, the implication is that molecular docking is a fast and effective way to screen alpha-glucosidase and alpha-amylase inhibitors as lead compounds of natural sources isolated from medicinal plants. © 2015 International Union of Biochemistry and Molecular Biology.

  16. Raman spectroscopy-based screening of hepatitis C and associated molecular changes

    Science.gov (United States)

    Bilal, Maria; Bilal, M.; Saleem, M.; Khan, Saranjam; Ullah, Rahat; Fatima, Kiran; Ahmed, M.; Hayat, Abbas; Shahzada, Shaista; Ullah Khan, Ehsan

    2017-09-01

    This study presents the optical screening of hepatitis C and its associated molecular changes in human blood sera using a partial least-squares regression model based on their Raman spectra. In total, 152 samples were tested through enzyme-linked immunosorbent assay for confirmation. This model utilizes minor spectral variations in the Raman spectra of the positive and control groups. Regression coefficients of this model were analyzed with reference to the variations in concentration of associated molecules in these two groups. It was found that trehalose, chitin, ammonia, and cytokines are positively correlated while lipids, beta structures of proteins, and carbohydrate-binding proteins are negatively correlated with hepatitis C. The regression vector yielded by this model is utilized to predict hepatitis C in unknown samples. This model has been evaluated by a cross-validation method, which yielded a correlation coefficient of 0.91. Moreover, 30 unknown samples were screened for hepatitis C infection using this model to test its performance. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve from these predictions were found to be 93.3%, 100%, 96.7%, and 1, respectively.

  17. Environmental screening tools for assessment of infrastructure plans based on biodiversity preservation and global warming (PEIT, Spain)

    International Nuclear Information System (INIS)

    Garcia-Montero, Luis G.; Lopez, Elena; Monzon, Andres; Otero Pastor, Isabel

    2010-01-01

    Most Strategic Environmental Assessment (SEA) research has been concerned with SEA as a procedure, and there have been relatively few developments and tests of analytical methodologies. The first stage of the SEA is the 'screening', which is the process whereby a decision is taken on whether or not SEA is required for a particular programme or plan. The effectiveness of screening and SEA procedures will depend on how well the assessment fits into the planning from the early stages of the decision-making process. However, it is difficult to prepare the environmental screening for an infrastructure plan involving a whole country. To be useful, such methodologies must be fast and simple. We have developed two screening tools which would make it possible to estimate promptly the overall impact an infrastructure plan might have on biodiversity and global warming for a whole country, in order to generate planning alternatives, and to determine whether or not SEA is required for a particular infrastructure plan.

  18. Globally homochiral assembly of two-dimensional molecular networks triggered by co-absorbers.

    Science.gov (United States)

    Chen, Ting; Yang, Wen-Hong; Wang, Dong; Wan, Li-Jun

    2013-01-01

    Understanding the chirality induction and amplification processes, and the construction of globally homochiral surfaces, represent essential challenges in surface chirality studies. Here we report the induction of global homochirality in two-dimensional enantiomorphous networks of achiral molecules via co-assembly with chiral co-absorbers. The scanning tunnelling microscopy investigations and molecular mechanics simulations demonstrate that the point chirality of the co-absorbers transfers to organizational chirality of the assembly units via enantioselective supramolecular interactions, and is then hierarchically amplified to the global homochirality of two-dimensional networks. The global homochirality of the network assembly shows nonlinear dependence on the enantiomeric excess of chiral co-absorber in the solution phase, demonstrating, for the first time, the validation of the 'majority rules' for the homochirality control of achiral molecules at the liquid/solid interface. Such an induction and nonlinear chirality amplification effect promises a new approach towards two-dimensional homochirality control and may reveal important insights into asymmetric heterogeneous catalysis, chiral separation and chiral crystallization.

  19. The high throughput biomedicine unit at the institute for molecular medicine Finland: high throughput screening meets precision medicine.

    Science.gov (United States)

    Pietiainen, Vilja; Saarela, Jani; von Schantz, Carina; Turunen, Laura; Ostling, Paivi; Wennerberg, Krister

    2014-05-01

    The High Throughput Biomedicine (HTB) unit at the Institute for Molecular Medicine Finland FIMM was established in 2010 to serve as a national and international academic screening unit providing access to state of the art instrumentation for chemical and RNAi-based high throughput screening. The initial focus of the unit was multiwell plate based chemical screening and high content microarray-based siRNA screening. However, over the first four years of operation, the unit has moved to a more flexible service platform where both chemical and siRNA screening is performed at different scales primarily in multiwell plate-based assays with a wide range of readout possibilities with a focus on ultraminiaturization to allow for affordable screening for the academic users. In addition to high throughput screening, the equipment of the unit is also used to support miniaturized, multiplexed and high throughput applications for other types of research such as genomics, sequencing and biobanking operations. Importantly, with the translational research goals at FIMM, an increasing part of the operations at the HTB unit is being focused on high throughput systems biological platforms for functional profiling of patient cells in personalized and precision medicine projects.

  20. UCLA's Molecular Screening Shared Resource: enhancing small molecule discovery with functional genomics and new technology.

    Science.gov (United States)

    Damoiseaux, Robert

    2014-05-01

    The Molecular Screening Shared Resource (MSSR) offers a comprehensive range of leading-edge high throughput screening (HTS) services including drug discovery, chemical and functional genomics, and novel methods for nano and environmental toxicology. The MSSR is an open access environment with investigators from UCLA as well as from the entire globe. Industrial clients are equally welcome as are non-profit entities. The MSSR is a fee-for-service entity and does not retain intellectual property. In conjunction with the Center for Environmental Implications of Nanotechnology, the MSSR is unique in its dedicated and ongoing efforts towards high throughput toxicity testing of nanomaterials. In addition, the MSSR engages in technology development eliminating bottlenecks from the HTS workflow and enabling novel assays and readouts currently not available.

  1. IVSPlat 1.0: an integrated virtual screening platform with a molecular graphical interface.

    Science.gov (United States)

    Sun, Yin Xue; Huang, Yan Xin; Li, Feng Li; Wang, Hong Yan; Fan, Cong; Bao, Yong Li; Sun, Lu Guo; Ma, Zhi Qiang; Kong, Jun; Li, Yu Xin

    2012-01-05

    The virtual screening (VS) of lead compounds using molecular docking and pharmacophore detection is now an important tool in drug discovery. VS tasks typically require a combination of several software tools and a molecular graphics system. Thus, the integration of all the requisite tools in a single operating environment could reduce the complexity of running VS experiments. However, only a few freely available integrated software platforms have been developed. A free open-source platform, IVSPlat 1.0, was developed in this study for the management and automation of VS tasks. We integrated several VS-related programs into a molecular graphics system to provide a comprehensive platform for the solution of VS tasks based on molecular docking, pharmacophore detection, and a combination of both methods. This tool can be used to visualize intermediate and final results of the VS execution, while also providing a clustering tool for the analysis of VS results. A case study was conducted to demonstrate the applicability of this platform. IVSPlat 1.0 provides a plug-in-based solution for the management, automation, and visualization of VS tasks. IVSPlat 1.0 is an open framework that allows the integration of extra software to extend its functionality and modified versions can be freely distributed. The open source code and documentation are available at http://kyc.nenu.edu.cn/IVSPlat/.

  2. Genarris: Random generation of molecular crystal structures and fast screening with a Harris approximation

    Science.gov (United States)

    Li, Xiayue; Curtis, Farren S.; Rose, Timothy; Schober, Christoph; Vazquez-Mayagoitia, Alvaro; Reuter, Karsten; Oberhofer, Harald; Marom, Noa

    2018-06-01

    We present Genarris, a Python package that performs configuration space screening for molecular crystals of rigid molecules by random sampling with physical constraints. For fast energy evaluations, Genarris employs a Harris approximation, whereby the total density of a molecular crystal is constructed via superposition of single molecule densities. Dispersion-inclusive density functional theory is then used for the Harris density without performing a self-consistency cycle. Genarris uses machine learning for clustering, based on a relative coordinate descriptor developed specifically for molecular crystals, which is shown to be robust in identifying packing motif similarity. In addition to random structure generation, Genarris offers three workflows based on different sequences of successive clustering and selection steps: the "Rigorous" workflow is an exhaustive exploration of the potential energy landscape, the "Energy" workflow produces a set of low energy structures, and the "Diverse" workflow produces a maximally diverse set of structures. The latter is recommended for generating initial populations for genetic algorithms. Here, the implementation of Genarris is reported and its application is demonstrated for three test cases.

  3. Molecular dynamics simulations and in silico peptide ligand screening of the Elk-1 ETS domain

    Directory of Open Access Journals (Sweden)

    Hussain Abrar

    2011-11-01

    Full Text Available Abstract Background The Elk-1 transcription factor is a member of a group of proteins called ternary complex factors, which serve as a paradigm for gene regulation in response to extracellular signals. Its deregulation has been linked to multiple human diseases including the development of tumours. The work herein aims to inform the design of potential peptidomimetic compounds that can inhibit the formation of the Elk-1 dimer, which is key to Elk-1 stability. We have conducted molecular dynamics simulations of the Elk-1 ETS domain followed by virtual screening. Results We show the ETS dimerisation site undergoes conformational reorganisation at the α1β1 loop. Through exhaustive screening of di- and tri-peptide libraries against a collection of ETS domain conformations representing the dynamics of the loop, we identified a series of potential binders for the Elk-1 dimer interface. The di-peptides showed no particular preference toward the binding site; however, the tri-peptides made specific interactions with residues: Glu17, Gln18 and Arg49 that are pivotal to the dimer interface. Conclusions We have shown molecular dynamics simulations can be combined with virtual peptide screening to obtain an exhaustive docking protocol that incorporates dynamic fluctuations in a receptor. Based on our findings, we suggest experimental binding studies to be performed on the 12 SILE ranked tri-peptides as possible compounds for the design of inhibitors of Elk-1 dimerisation. It would also be reasonable to consider the score-ranked tri-peptides as a comparative test to establish whether peptide size is a determinant factor of binding to the ETS domain.

  4. Search for β2 adrenergic receptor ligands by virtual screening via grid computing and investigation of binding modes by docking and molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Qifeng Bai

    Full Text Available We designed a program called MolGridCal that can be used to screen small molecule database in grid computing on basis of JPPF grid environment. Based on MolGridCal program, we proposed an integrated strategy for virtual screening and binding mode investigation by combining molecular docking, molecular dynamics (MD simulations and free energy calculations. To test the effectiveness of MolGridCal, we screened potential ligands for β2 adrenergic receptor (β2AR from a database containing 50,000 small molecules. MolGridCal can not only send tasks to the grid server automatically, but also can distribute tasks using the screensaver function. As for the results of virtual screening, the known agonist BI-167107 of β2AR is ranked among the top 2% of the screened candidates, indicating MolGridCal program can give reasonable results. To further study the binding mode and refine the results of MolGridCal, more accurate docking and scoring methods are used to estimate the binding affinity for the top three molecules (agonist BI-167107, neutral antagonist alprenolol and inverse agonist ICI 118,551. The results indicate agonist BI-167107 has the best binding affinity. MD simulation and free energy calculation are employed to investigate the dynamic interaction mechanism between the ligands and β2AR. The results show that the agonist BI-167107 also has the lowest binding free energy. This study can provide a new way to perform virtual screening effectively through integrating molecular docking based on grid computing, MD simulations and free energy calculations. The source codes of MolGridCal are freely available at http://molgridcal.codeplex.com.

  5. Determination of liquid's molecular interference function based on X-ray diffraction and dual-energy CT in security screening

    International Nuclear Information System (INIS)

    Zhang, Li; YangDai, Tianyi

    2016-01-01

    A method for deriving the molecular interference function (MIF) of an unknown liquid for security screening is presented. Based on the effective atomic number reconstructed from dual-energy computed tomography (CT), equivalent molecular formula of the liquid is estimated. After a series of optimizations, the MIF and a new effective atomic number are finally obtained from the X-ray diffraction (XRD) profile. The proposed method generates more accurate results with less sensitivity to the noise and data deficiency of the XRD profile. - Highlights: • EDXRD combined with dual-energy CT has been utilized for deriving the molecular interference function of an unknown liquid. • The liquid's equivalent molecular formula is estimated based on the effective atomic number reconstructed from dual-energy CT. • The proposed method provides two ways to estimate the molecular interference function: the simplified way and accurate way. • A new effective atomic number of the liquid could be obtained.

  6. Which part of a short, global risk assessment, the Risk Instrument for Screening in the Community, predicts adverse healthcare outcomes?

    LENUS (Irish Health Repository)

    O’Caoimh, Rónán

    2015-01-01

    The Risk Instrument for Screening in the Community (RISC) is a short, global risk assessment to identify community-dwelling older adults’ one-year risk of institutionalisation, hospitalisation, and death. We investigated the contribution that the three components of the RISC (\

  7. Validation of periodontitis screening model using sociodemographic, systemic, and molecular information in a Korean population.

    Science.gov (United States)

    Kim, Hyun-Duck; Sukhbaatar, Munkhzaya; Shin, Myungseop; Ahn, Yoo-Been; Yoo, Wook-Sung

    2014-12-01

    This study aims to evaluate and validate a periodontitis screening model that includes sociodemographic, metabolic syndrome (MetS), and molecular information, including gingival crevicular fluid (GCF), matrix metalloproteinase (MMP), and blood cytokines. The authors selected 506 participants from the Shiwha-Banwol cohort: 322 participants from the 2005 cohort for deriving the screening model and 184 participants from the 2007 cohort for its validation. Periodontitis was assessed by dentists using the community periodontal index. Interleukin (IL)-6, IL-8, and tumor necrosis factor-α in blood and MMP-8, -9, and -13 in GCF were assayed using enzyme-linked immunosorbent assay. MetS was assessed by physicians using physical examination and blood laboratory data. Information about age, sex, income, smoking, and drinking was obtained by interview. Logistic regression analysis was applied to finalize the best-fitting model and validate the model using sensitivity, specificity, and c-statistics. The derived model for periodontitis screening had a sensitivity of 0.73, specificity of 0.85, and c-statistic of 0.86 (P validated model were 0.64, 0.91, and 0.83 (P <0.001), respectively. The model that included age, sex, income, smoking, drinking, and blood and GCF biomarkers could be useful in screening for periodontitis. A future prospective study is indicated for evaluating this model's ability to predict the occurrence of periodontitis.

  8. The influence of the negative-positive ratio and screening database size on the performance of machine learning-based virtual screening.

    Science.gov (United States)

    Kurczab, Rafał; Bojarski, Andrzej J

    2017-01-01

    The machine learning-based virtual screening of molecular databases is a commonly used approach to identify hits. However, many aspects associated with training predictive models can influence the final performance and, consequently, the number of hits found. Thus, we performed a systematic study of the simultaneous influence of the proportion of negatives to positives in the testing set, the size of screening databases and the type of molecular representations on the effectiveness of classification. The results obtained for eight protein targets, five machine learning algorithms (SMO, Naïve Bayes, Ibk, J48 and Random Forest), two types of molecular fingerprints (MACCS and CDK FP) and eight screening databases with different numbers of molecules confirmed our previous findings that increases in the ratio of negative to positive training instances greatly influenced most of the investigated parameters of the ML methods in simulated virtual screening experiments. However, the performance of screening was shown to also be highly dependent on the molecular library dimension. Generally, with the increasing size of the screened database, the optimal training ratio also increased, and this ratio can be rationalized using the proposed cost-effectiveness threshold approach. To increase the performance of machine learning-based virtual screening, the training set should be constructed in a way that considers the size of the screening database.

  9. Virtual Ligand Screening Using PL-PatchSurfer2, a Molecular Surface-Based Protein-Ligand Docking Method.

    Science.gov (United States)

    Shin, Woong-Hee; Kihara, Daisuke

    2018-01-01

    Virtual screening is a computational technique for predicting a potent binding compound for a receptor protein from a ligand library. It has been a widely used in the drug discovery field to reduce the efforts of medicinal chemists to find hit compounds by experiments.Here, we introduce our novel structure-based virtual screening program, PL-PatchSurfer, which uses molecular surface representation with the three-dimensional Zernike descriptors, which is an effective mathematical representation for identifying physicochemical complementarities between local surfaces of a target protein and a ligand. The advantage of the surface-patch description is its tolerance on a receptor and compound structure variation. PL-PatchSurfer2 achieves higher accuracy on apo form and computationally modeled receptor structures than conventional structure-based virtual screening programs. Thus, PL-PatchSurfer2 opens up an opportunity for targets that do not have their crystal structures. The program is provided as a stand-alone program at http://kiharalab.org/plps2 . We also provide files for two ligand libraries, ChEMBL and ZINC Drug-like.

  10. Molecular screening of Chinese medicinal plants for progestogenic ...

    Indian Academy of Sciences (India)

    2014-05-01

    May 1, 2014 ... 2010). The risks of coronary heart diseases, breast cancer and pul- ... screened for phytoestrogen, but research and literature on the screening of ..... 2002 Risks and benefits of estrogen plus progestin in healthy postmeno-.

  11. Preconception carrier screening and prenatal diagnosis in thalassemia and hemoglobinopathies: challenges and future perspectives.

    Science.gov (United States)

    Traeger-Synodinos, Joanne; Harteveld, Cornelis L

    2017-03-01

    Hemoglobinopathies constitute the most common severe monogenic disorders worldwide, with an increasing global burden each year. The benefit of applying programmes for preconception carrier screening, with the option of prenatal diagnosis, to minimize the incidence of new cases is recognized in many countries. Areas covered: The challenges associated with identifying carrier couples using hematology-based screening, along with DNA diagnosis and prenatal diagnosis were addressed, based on a literature search and the authors expertise. Expert commentary: The hemoglobinopathies are extremely heterogeneous at the haematological, molecular and clinical level, requiring appropriately equipped and staffed laboratories with experience to support comprehensive screening and diagnosis. However complete services with adequate infrastructure to address the associated technical challenges do not exist widely, especially in low-income countries that, coincidentally, are often those with the highest frequency of hemoglobinopathies in their population. Additionally, overcoming limited public awareness, education and absence of systematic dissemination of information also constitutes a challenge. This article aims to highlight these challenges and to evaluate potential future developments that may address at least some of them, focusing mainly on the technical challenges related to molecular diagnostics.

  12. Extensive Evaluation of the Conductor-like Screening Model for Real Solvents Method in Predicting Liquid-Liquid Equilibria in Ternary Systems of Ionic Liquids with Molecular Compounds.

    Science.gov (United States)

    Paduszyński, Kamil

    2018-04-12

    A conductor-like screening model for real solvents (COSMO-RS) is nowadays one of the most popular and commonly applied tools for the estimation of thermodynamic properties of complex fluids. The goal of this work is to provide a comprehensive review and analysis of the performance of this approach in calculating liquid-liquid equilibrium (LLE) phase diagrams in ternary systems composed of ionic liquid and two molecular compounds belonging to diverse families of chemicals (alkanes, aromatics, S/N-compounds, alcohols, ketones, ethers, carboxylic acid, esters, and water). The predictions are presented for extensive experimental database, including 930 LLE data sets and more than 9000 data points (LLE tie lines) reported for 779 unique ternary mixtures. An impact of the type of molecular binary subsystem on the accuracy of predictions is demonstrated and discussed on the basis of representative examples. The model's capability of capturing qualitative trends in the LLE distribution ratio and selectivity is also checked for a number of structural effects. Comparative analysis of two levels of quantum chemical theory (BP-TZVP-COSMO vs BP-TZVPD-FINE) for the input molecular data for COSMO-RS is presented. Finally, some general recommendations for the applicability of the model are indicated based on the analysis of the global performance as well as on the results obtained for systems relevant from the point of view of important separation problems.

  13. Molecular marker screening of tomato, (solanum lycopersicum L ...

    African Journals Online (AJOL)

    user

    2011-02-28

    Suscept. check). TGRC, V. Williamson and young seedlings can be screened very early for the presence or absence of a particular trait (Luc et al., 1999;. Hussey and Janssen, 2002). Standard bioassays used for the screening of ...

  14. International Cancer Screening Network

    Science.gov (United States)

    The International Cancer Screening Network promotes evidence-based cancer screening implementation and evaluation with cooperation from multilateral organizations around the globe. Learn more about how ICSN aims to reduce the global burden of cancer by supporting research and international collaboration.

  15. The colorectal cancer mortality-to-incidence ratio as an indicator of global cancer screening and care.

    Science.gov (United States)

    Sunkara, Vasu; Hébert, James R

    2015-05-15

    Disparities in cancer screening, incidence, treatment, and survival are worsening globally. The mortality-to-incidence ratio (MIR) has been used previously to evaluate such disparities. The MIR for colorectal cancer is calculated for all Organisation for Economic Cooperation and Development (OECD) countries using the 2012 GLOBOCAN incidence and mortality statistics. Health system rankings were obtained from the World Health Organization. Two linear regression models were fit with the MIR as the dependent variable and health system ranking as the independent variable; one included all countries and one model had the "divergents" removed. The regression model for all countries explained 24% of the total variance in the MIR. Nine countries were found to have regression-calculated MIRs that differed from the actual MIR by >20%. Countries with lower-than-expected MIRs were found to have strong national health systems characterized by formal colorectal cancer screening programs. Conversely, countries with higher-than-expected MIRs lack screening programs. When these divergent points were removed from the data set, the recalculated regression model explained 60% of the total variance in the MIR. The MIR proved useful for identifying disparities in cancer screening and treatment internationally. It has potential as an indicator of the long-term success of cancer surveillance programs and may be extended to other cancer types for these purposes. © 2015 American Cancer Society.

  16. In-bead screening

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to screening of one-bead-one-compound (OBOC) combinatorial libraries which is useful for the discovery of compounds displaying molecular interactions with a biological or a physicochemical system, such as substrates and inhibitors of enzymes and the like. The invention...... provides a method for screening a library of compounds for their interaction with a physico- chemical or biological system and a corresponding kit for performing the method of screening a one-bead-one-compound library of compounds....

  17. The Q* Index: A Useful Global Measure of Dementia Screening Test Accuracy

    Directory of Open Access Journals (Sweden)

    A.J. Larner

    2015-06-01

    Full Text Available Background/Aims: Single, global or unitary, indicators of test diagnostic performance have intuitive appeal for clinicians. The Q* index, the point in receiver operating characteristic (ROC curve space closest to the ideal top left-hand corner and where test sensitivity and specificity are equal, is one such measure. Methods: Datasets from four pragmatic accuracy studies which examined the Mini-Mental State Examination, Addenbrooke's Cognitive Examination-Revised, Montreal Cognitive Assessment, Test Your Memory test, and Mini-Addenbrooke's Cognitive Examination were examined to calculate and compare the Q* index, the maximal correct classification accuracy, and the maximal Youden index, as well as the sensitivity and specificity at these cutoffs. Results: Tests ranked similarly for the Q* index and the area under the ROC curve (AUC ROC. The Q* index cutoff was more sensitive (and less specific than the maximal correct classification accuracy cutoff, and less sensitive (and more specific than the maximal Youden index cutoff. Conclusion: The Q* index may be a useful global parameter summarising the test accuracy of cognitive screening instruments, facilitating comparison between tests, and defining a possible test cutoff value. As the point of equal sensitivity and specificity, its use may be more intuitive and appealing for clinicians than AUC ROC.

  18. Virtual screening for potential inhibitors of Mcl-1 conformations sampled by normal modes, molecular dynamics, and nuclear magnetic resonance

    Directory of Open Access Journals (Sweden)

    Glantz-Gashai Y

    2017-06-01

    Full Text Available Yitav Glantz-Gashai,* Tomer Meirson,* Eli Reuveni, Abraham O Samson Faculty of Medicine in the Galilee, Bar Ilan University, Safed, Israel *These authors contributed equally to this work Abstract: Myeloid cell leukemia-1 (Mcl-1 is often overexpressed in human cancer and is an important target for developing antineoplastic drugs. In this study, a data set containing 2.3 million lead-like molecules and a data set of all the US Food and Drug Administration (FDA-approved drugs are virtually screened for potential Mcl-1 ligands using Protein Data Bank (PDB ID 2MHS. The potential Mcl-1 ligands are evaluated and computationally docked on to three conformation ensembles generated by normal mode analysis (NMA, molecular dynamics (MD, and nuclear magnetic resonance (NMR, respectively. The evaluated potential Mcl-1 ligands are then compared with their clinical use. Remarkably, half of the top 30 potential drugs are used clinically to treat cancer, thus partially validating our virtual screen. The partial validation also favors the idea that the other half of the top 30 potential drugs could be used in the treatment of cancer. The normal mode-, MD-, and NMR-based conformation greatly expand the conformational sampling used herein for in silico identification of potential Mcl-1 inhibitors. Keywords: virtual screening, Mcl-1, molecular dynamics, NMR, normal modes

  19. Southern-by-Sequencing: A Robust Screening Approach for Molecular Characterization of Genetically Modified Crops

    Directory of Open Access Journals (Sweden)

    Gina M. Zastrow-Hayes

    2015-03-01

    Full Text Available Molecular characterization of events is an integral part of the advancement process during genetically modified (GM crop product development. Assessment of these events is traditionally accomplished by polymerase chain reaction (PCR and Southern blot analyses. Southern blot analysis can be time-consuming and comparatively expensive and does not provide sequence-level detail. We have developed a sequence-based application, Southern-by-Sequencing (SbS, utilizing sequence capture coupled with next-generation sequencing (NGS technology to replace Southern blot analysis for event selection in a high-throughput molecular characterization environment. SbS is accomplished by hybridizing indexed and pooled whole-genome DNA libraries from GM plants to biotinylated probes designed to target the sequence of transformation plasmids used to generate events within the pool. This sequence capture process enriches the sequence data obtained for targeted regions of interest (transformation plasmid DNA. Taking advantage of the DNA adjacent to the targeted bases (referred to as next-to-target sequence that accompanies the targeted transformation plasmid sequence, the data analysis detects plasmid-to-genome and plasmid-to-plasmid junctions introduced during insertion into the plant genome. Analysis of these junction sequences provides sequence-level information as to the following: the number of insertion loci including detection of unlinked, independently segregating, small DNA fragments; copy number; rearrangements, truncations, or deletions of the intended insertion DNA; and the presence of transformation plasmid backbone sequences. This molecular evidence from SbS analysis is used to characterize and select GM plants meeting optimal molecular characterization criteria. SbS technology has proven to be a robust event screening tool for use in a high-throughput molecular characterization environment.

  20. Octopus: a platform for the virtual high-throughput screening of a pool of compounds against a set of molecular targets.

    Science.gov (United States)

    Maia, Eduardo Habib Bechelane; Campos, Vinícius Alves; Dos Reis Santos, Bianca; Costa, Marina Santos; Lima, Iann Gabriel; Greco, Sandro J; Ribeiro, Rosy I M A; Munayer, Felipe M; da Silva, Alisson Marques; Taranto, Alex Gutterres

    2017-01-01

    Octopus is an automated workflow management tool that is scalable for virtual high-throughput screening (vHTS). It integrates MOPAC2016, MGLTools, PyMOL, and AutoDock Vina. In contrast to other platforms, Octopus can perform docking simulations of an unlimited number of compounds into a set of molecular targets. After generating the ligands in a drawing package in the Protein Data Bank (PDB) format, Octopus can carry out geometry refinement using the semi-empirical method PM7 implemented in MOPAC2016. Docking simulations can be performed using AutoDock Vina and can utilize the Our Own Molecular Targets (OOMT) databank. Finally, the proposed software compiles the best binding energies into a standard table. Here, we describe two successful case studies that were verified by biological assay. In the first case study, the vHTS process was carried out for 22 (phenylamino)urea derivatives. The vHTS process identified a metalloprotease with the PDB code 1GKC as a molecular target for derivative LE&007. In a biological assay, compound LE&007 was found to inhibit 80% of the activity of this enzyme. In the second case study, compound Tx001 was submitted to the Octopus routine, and the results suggested that Plasmodium falciparum ATP6 (PfATP6) as a molecular target for this compound. Following an antimalarial assay, Tx001 was found to have an inhibitory concentration (IC 50 ) of 8.2 μM against PfATP6. These successful examples illustrate the utility of this software for finding appropriate molecular targets for compounds. Hits can then be identified and optimized as new antineoplastic and antimalarial drugs. Finally, Octopus has a friendly Linux-based user interface, and is available at www.drugdiscovery.com.br . Graphical Abstract Octopus: A platform for inverse virtual screening (IVS) to search new molecular targets for drugs.

  1. Combined Ligand/Structure-Based Virtual Screening and Molecular Dynamics Simulations of Steroidal Androgen Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Yuwei Wang

    2017-01-01

    Full Text Available The antiandrogens, such as bicalutamide, targeting the androgen receptor (AR, are the main endocrine therapies for prostate cancer (PCa. But as drug resistance to antiandrogens emerges in advanced PCa, there presents a high medical need for exploitation of novel AR antagonists. In this work, the relationships between the molecular structures and antiandrogenic activities of a series of 7α-substituted dihydrotestosterone derivatives were investigated. The proposed MLR model obtained high predictive ability. The thoroughly validated QSAR model was used to virtually screen new dihydrotestosterones derivatives taken from PubChem, resulting in the finding of novel compounds CID_70128824, CID_70127147, and CID_70126881, whose in silico bioactivities are much higher than the published best one, even higher than bicalutamide. In addition, molecular docking, molecular dynamics (MD simulations, and MM/GBSA have been employed to analyze and compare the binding modes between the novel compounds and AR. Through the analysis of the binding free energy and residue energy decomposition, we concluded that the newly discovered chemicals can in silico bind to AR with similar position and mechanism to the reported active compound and the van der Waals interaction is the main driving force during the binding process.

  2. Spherical harmonics coefficients for ligand-based virtual screening of cyclooxygenase inhibitors.

    Science.gov (United States)

    Wang, Quan; Birod, Kerstin; Angioni, Carlo; Grösch, Sabine; Geppert, Tim; Schneider, Petra; Rupp, Matthias; Schneider, Gisbert

    2011-01-01

    Molecular descriptors are essential for many applications in computational chemistry, such as ligand-based similarity searching. Spherical harmonics have previously been suggested as comprehensive descriptors of molecular structure and properties. We investigate a spherical harmonics descriptor for shape-based virtual screening. We introduce and validate a partially rotation-invariant three-dimensional molecular shape descriptor based on the norm of spherical harmonics expansion coefficients. Using this molecular representation, we parameterize molecular surfaces, i.e., isosurfaces of spatial molecular property distributions. We validate the shape descriptor in a comprehensive retrospective virtual screening experiment. In a prospective study, we virtually screen a large compound library for cyclooxygenase inhibitors, using a self-organizing map as a pre-filter and the shape descriptor for candidate prioritization. 12 compounds were tested in vitro for direct enzyme inhibition and in a whole blood assay. Active compounds containing a triazole scaffold were identified as direct cyclooxygenase-1 inhibitors. This outcome corroborates the usefulness of spherical harmonics for representation of molecular shape in virtual screening of large compound collections. The combination of pharmacophore and shape-based filtering of screening candidates proved to be a straightforward approach to finding novel bioactive chemotypes with minimal experimental effort.

  3. [Screen potential CYP450 2E1 inhibitors from Chinese herbal medicine based on support vector regression and molecular docking method].

    Science.gov (United States)

    Chen, Xi; Lu, Fang; Jiang, Lu-di; Cai, Yi-Lian; Li, Gong-Yu; Zhang, Yan-Ling

    2016-07-01

    Inhibition of cytochrome P450 (CYP450) enzymes is the most common reasons for drug interactions, so the study on early prediction of CYPs inhibitors can help to decrease the incidence of adverse reactions caused by drug interactions.CYP450 2E1(CYP2E1), as a key role in drug metabolism process, has broad spectrum of drug metabolism substrate. In this study, 32 CYP2E1 inhibitors were collected for the construction of support vector regression (SVR) model. The test set data were used to verify CYP2E1 quantitative models and obtain the optimal prediction model of CYP2E1 inhibitor. Meanwhile, one molecular docking program, CDOCKER, was utilized to analyze the interaction pattern between positive compounds and active pocket to establish the optimal screening model of CYP2E1 inhibitors.SVR model and molecular docking prediction model were combined to screen traditional Chinese medicine database (TCMD), which could improve the calculation efficiency and prediction accuracy. 6 376 traditional Chinese medicine (TCM) compounds predicted by SVR model were obtained, and in further verification by using molecular docking model, 247 TCM compounds with potential inhibitory activities against CYP2E1 were finally retained. Some of them have been verified by experiments. The results demonstrated that this study could provide guidance for the virtual screening of CYP450 inhibitors and the prediction of CYPs-mediated DDIs, and also provide references for clinical rational drug use. Copyright© by the Chinese Pharmaceutical Association.

  4. Screening of broad spectrum natural pesticides against conserved target arginine kinase in cotton pests by molecular modeling.

    Science.gov (United States)

    Sakthivel, Seethalakshmi; Habeeb, S K M; Raman, Chandrasekar

    2018-03-12

    Cotton is an economically important crop and its production is challenged by the diversity of pests and related insecticide resistance. Identification of the conserved target across the cotton pest will help to design broad spectrum insecticide. In this study, we have identified conserved sequences by Expressed Sequence Tag profiling from three cotton pests namely Aphis gossypii, Helicoverpa armigera, and Spodoptera exigua. One target protein arginine kinase having a key role in insect physiology and energy metabolism was studied further using homology modeling, virtual screening, molecular docking, and molecular dynamics simulation to identify potential biopesticide compounds from the Zinc natural database. We have identified four compounds having excellent inhibitor potential against the identified broad spectrum target which are highly specific to invertebrates.

  5. Molecular Basis for Saccharomyces cerevisiae Biofilm Development

    DEFF Research Database (Denmark)

    Andersen, Kaj Scherz

    In this study, I sought to identify genes regulating the global molecular program for development of sessile multicellular communities, also known as biofilm, of the eukaryotic microorganism, Saccharomyces cerevisiae (yeast). Yeast biofilm has a clinical interest, as biofilms can cause chronic...... infections in humans. Biofilm is also interesting from an evolutionary standpoint, as an example of primitive multicellularity. By using a genome-wide screen of yeast deletion mutants, I show that 71 genes are essential for biofilm formation. Two-thirds of these genes are required for transcription of FLO11......, but only a small subset is previously described as regulators of FLO11. These results reveal that the regulation of biofilm formation and FLO11 is even more complex than what has previously been described. I find that the molecular program for biofilm formation shares many essential components with two...

  6. Fragment screening by SPR and advanced application to GPCRs.

    Science.gov (United States)

    Shepherd, Claire A; Hopkins, Andrew L; Navratilova, Iva

    2014-01-01

    Surface plasmon resonance (SPR) is one of the primary biophysical methods for the screening of low molecular weight 'fragment' libraries, due to its low protein consumption and 'label-free' methodology. SPR biosensor interaction analysis is employed to both screen and confirm the binding of compounds in fragment screening experiments, as it provides accurate information on the affinity and kinetics of molecular interactions. The most advanced application of the use of SPR for fragment screening is against membrane protein drug targets, such G-protein coupled receptors (GPCRs). Biophysical GPCR assays using SPR have been validated with pharmacological measurements approximate to cell-based methods, yet provide the advantage of biophysical methods in their ability to measure the weak affinities of low molecular weight fragments. A number of SPR fragment screens against GPCRs have now been disclosed in the literature. SPR fragment screening is proving versatile to screen both thermostabilised GPCRs and solubilised wild type receptors. In this chapter, we discuss the state-of-the-art in GPCR fragment screening by SPR and the technical considerations in performing such experiments. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Molecular galactose-galectin association in neuroblastoma cells: An unconventional tool for qualitative/quantitative screening.

    Science.gov (United States)

    Pastorino, Fabio; Ponzoni, Mirco; Simone, Giuseppina

    2017-05-01

    Galectin decorates the cell membrane and forms an extracellular molecular association with galactoside units. Here, galactoside probes have been used to study galectin expression in neuroblastoma cells. The hypothesis behind this investigation has been that the molecular mechanisms by which glycans modulate neural metastatic cells involve a protein-carbohydrate association, galectin-galactose. Preliminary screening to validate the hypothesis has been performed with galactose moieties anchored to beads. The molecular association has been studied by FACS. In vitro experiments reveal the molecular binding preferences of the metastatic neuroblastoma cells. Ex vivo, the galactose probes discriminate healthy tissues. The unconventional assay in microfluidics used in this study displayed results analogous to the above (GI-LI-N cell capture efficiency overcomes IMR-32). At the point of equilibrium of shear and binding forces, the capture yield inside the chamber was measured to 60 ± 4.4% in GI-LI-N versus 40 ± 2.1% in IMR-32. Staining of the fished cells and subsequent conjugation with red beads bearing the galactose also have evidenced that microfluidics can be used to study and quantify the molecular association of galectin-galactose. Most importantly, a crucial insight for obtaining single-cell qualitative/quantitative glycome analysis has been achieved. Finally, the specificity of the assay performed in microfluidics is demonstrated by comparing GI-LI-N fishing efficiency in galactose and fucose environments. The residual adhesion to fucose confirmed the existence of receptors for this glycan and that its eventual unspecific binding (i.e. due to electrostatic interactions) is insignificant compared with the molecular binding. Identification and understanding of this mechanism of discrimination can be relevant for diagnostic monitoring and for producing probes tailored to interfere with galectin activities associated with the malignant phenotype. Besides, the given

  8. Health system barriers and enablers to early access to breast cancer screening, detection, and diagnosis: a global analysis applied to the MENA region.

    Science.gov (United States)

    Bowser, D; Marqusee, H; El Koussa, M; Atun, R

    2017-11-01

    To identify barriers and enablers that impact access to early screening, detection, and diagnosis of breast cancer both globally and more specifically in the Middle East and North Africa (MENA) region (with a specific focus on Egypt, Jordan, Oman, Saudi Arabia, United Arab Emirates [UAE], and Kuwait) with a specific focus on the health system. A systematic review of literature. We conducted a systematic reviewing using the PRISMA methodology. We searched PubMed, Global Index Medicus, and EMBASE for studies on 'breast cancer', 'breast neoplasm,' or 'screening, early detection, and early diagnosis' as well as key words related to the following barriers: religion, culture, health literacy, lack of knowledge/awareness/understanding, attitudes, fatalism/fear, shame/embarrassment, and physician gender from January 1, 2000 until September 1, 2016. Two independent reviewers screened both titles and abstracts. The application of inclusion and exclusion criteria yielded a final list of articles. A conceptual framework was used to guide the thematic analysis and examine health system barriers and enablers to breast cancer screening at the broader macro health system level, at the health provider level, and the individual level. The analysis was conducted globally and in the MENA region. A total of 11,936 references were identified through the initial search strategy, of which 55 were included in the final thematic analysis. The results found the following barriers and enablers to access to breast cancer screening at the health system level, the health provider level, and the individual level: health system structures such as health insurance and care coordination systems, costs, time concerns, provider characteristics including gender of the provider, quality of care issues, medical concerns, and fear. In addition, the following seven barriers and enablers were identified at the health system or provider level as significantly impacting screening for breast cancer: (1) access

  9. Reference evapotranspiration forecasting based on local meteorological and global climate information screened by partial mutual information

    Science.gov (United States)

    Fang, Wei; Huang, Shengzhi; Huang, Qiang; Huang, Guohe; Meng, Erhao; Luan, Jinkai

    2018-06-01

    In this study, reference evapotranspiration (ET0) forecasting models are developed for the least economically developed regions subject to meteorological data scarcity. Firstly, the partial mutual information (PMI) capable of capturing the linear and nonlinear dependence is investigated regarding its utility to identify relevant predictors and exclude those that are redundant through the comparison with partial linear correlation. An efficient input selection technique is crucial for decreasing model data requirements. Then, the interconnection between global climate indices and regional ET0 is identified. Relevant climatic indices are introduced as additional predictors to comprise information regarding ET0, which ought to be provided by meteorological data unavailable. The case study in the Jing River and Beiluo River basins, China, reveals that PMI outperforms the partial linear correlation in excluding the redundant information, favouring the yield of smaller predictor sets. The teleconnection analysis identifies the correlation between Nino 1 + 2 and regional ET0, indicating influences of ENSO events on the evapotranspiration process in the study area. Furthermore, introducing Nino 1 + 2 as predictors helps to yield more accurate ET0 forecasts. A model performance comparison also shows that non-linear stochastic models (SVR or RF with input selection through PMI) do not always outperform linear models (MLR with inputs screen by linear correlation). However, the former can offer quite comparable performance depending on smaller predictor sets. Therefore, efforts such as screening model inputs through PMI and incorporating global climatic indices interconnected with ET0 can benefit the development of ET0 forecasting models suitable for data-scarce regions.

  10. Integrated and global pseudotargeted metabolomics strategy applied to screening for quality control markers of Citrus TCMs.

    Science.gov (United States)

    Shu, Yisong; Liu, Zhenli; Zhao, Siyu; Song, Zhiqian; He, Dan; Wang, Menglei; Zeng, Honglian; Lu, Cheng; Lu, Aiping; Liu, Yuanyan

    2017-08-01

    Traditional Chinese medicine (TCM) exerts its therapeutic effect in a holistic fashion with the synergistic function of multiple characteristic constituents. The holism philosophy of TCM is coincident with global and systematic theories of metabolomics. The proposed pseudotargeted metabolomics methodologies were employed for the establishment of reliable quality control markers for use in the screening strategy of TCMs. Pseudotargeted metabolomics integrates the advantages of both targeted and untargeted methods. In the present study, targeted metabolomics equipped with the gold standard RRLC-QqQ-MS method was employed for in vivo quantitative plasma pharmacochemistry study of characteristic prototypic constituents. Meanwhile, untargeted metabolomics using UHPLC-QE Orbitrap HRMS with better specificity and selectivity was employed for identification of untargeted metabolites in the complex plasma matrix. In all, 32 prototypic metabolites were quantitatively determined, and 66 biotransformed metabolites were convincingly identified after being orally administered with standard extracts of four labeled Citrus TCMs. The global absorption and metabolism process of complex TCMs was depicted in a systematic manner.

  11. Telehealth solutions to enable global collaboration in rheumatic heart disease screening.

    Science.gov (United States)

    Lopes, Eduardo Lv; Beaton, Andrea Z; Nascimento, Bruno R; Tompsett, Alison; Dos Santos, Julia Pa; Perlman, Lindsay; Diamantino, Adriana C; Oliveira, Kaciane Kb; Oliveira, Cassio M; Nunes, Maria do Carmo P; Bonisson, Leonardo; Ribeiro, Antônio Lp; Sable, Craig

    2018-02-01

    Background The global burden of rheumatic heart disease is nearly 33 million people. Telemedicine, using cloud-server technology, provides an ideal solution for sharing images performed by non-physicians with cardiologists who are experts in rheumatic heart disease. Objective We describe our experience in using telemedicine to support a large rheumatic heart disease outreach screening programme in the Brazilian state of Minas Gerais. Methods The Programa de Rastreamento da Valvopatia Reumática (PROVAR) is a prospective cross-sectional study aimed at gathering epidemiological data on the burden of rheumatic heart disease in Minas Gerais and testing of a non-expert, telemedicine-supported model of outreach rheumatic heart disease screening. The primary goal is to enable expert support of remote rheumatic heart disease outreach through cloud-based sharing of echocardiographic images between Minas Gerais and Washington. Secondary goals include (a) developing and sharing online training modules for non-physicians in echocardiography performance and interpretation and (b) utilising a secure web-based system to share clinical and research data. Results PROVAR included 4615 studies that were performed by non-experts at 21 schools and shared via cloud-telemedicine technology. Latent rheumatic heart disease was found in 251 subjects (4.2% of subjects: 3.7% borderline and 0.5% definite disease). Of the studies, 50% were preformed on full functional echocardiography machines and transmitted via Digital Imaging and Communications in Medicine (DICOM) and 50% were performed on handheld echocardiography machines and transferred via a secure Dropbox connection. The average time between study performance date and interpretation was 10 days. There was 100% success in initial image transfer. Less than 1% of studies performed by non-experts could not be interpreted. Discussion A sustainable, low-cost telehealth model, using task-shifting with non-medical personal in low and middle

  12. Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations

    DEFF Research Database (Denmark)

    Ferré, Marc; Bonneau, Dominique; Milea, Dan

    2009-01-01

    We report the results of molecular screening in 980 patients carried out as part of their work-up for suspected hereditary optic neuropathies. All the patients were investigated for Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA), by searching for the ten...... and OPA3 mutations in cases of suspected hereditary optic neuropathy, even in absence of a family history of the disease....... novel OPA1 mutations reported here. The statistical analysis of this large set of mutations has led us to propose a diagnostic strategy that should help with the molecular work-up of optic neuropathies. Our results highlight the importance of investigating LHON-causing mtDNA mutations as well as OPA1...

  13. Quantum probability ranking principle for ligand-based virtual screening

    Science.gov (United States)

    Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

    2017-04-01

    Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

  14. Quantum probability ranking principle for ligand-based virtual screening.

    Science.gov (United States)

    Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

    2017-04-01

    Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

  15. Screening of photosynthetic pigments for herbicidal activity with a new computational molecular approach.

    Science.gov (United States)

    Krishnaraj, R Navanietha; Chandran, Saravanan; Pal, Parimal; Berchmans, Sheela

    2013-12-01

    There is an immense interest among the researchers to identify new herbicides which are effective against the herbs without affecting the environment. In this work, photosynthetic pigments are used as the ligands to predict their herbicidal activity. The enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase is a good target for the herbicides. Homology modeling of the target enzyme is done using Modeler 9.11 and the model is validated. Docking studies were performed with AutoDock Vina algorithm to predict the binding of the natural pigments such as β-carotene, chlorophyll a, chlorophyll b, phycoerythrin and phycocyanin to the target. β-carotene, phycoerythrin and phycocyanin have higher binding energies indicating the herbicidal activity of the pigments. This work reports a procedure to screen herbicides with computational molecular approach. These pigments will serve as potential bioherbicides in the future.

  16. Improving molecular tools for global surveillance of measles virus⋆

    Science.gov (United States)

    Bankamp, Bettina; Byrd-Leotis, Lauren A.; Lopareva, Elena N.; Woo, Gibson K.S.; Liu, Chunyu; Jee, Youngmee; Ahmed, Hinda; Lim, Wilina W.; Ramamurty, Nalini; Mulders, Mick N.; Featherstone, David; Bellini, William J.; Rota, Paul A.

    2017-01-01

    Background The genetic characterization of wild-type measles viruses plays an important role in the description of viral transmission pathways and the verification of measles elimination. The 450 nucleotides that encode the carboxyl-terminus of the nucleoprotein (N-450) are routinely sequenced for genotype analysis. Objectives The objectives of this study were to develop improved primers and controls for RT-PCR reactions used for genotyping of measles samples and to develop a method to provide a convenient, safe, and inexpensive means to distribute measles RNA for RT-PCR assays and practice panels. Study design A newly designed, genetically defined synthetic RNA and RNA isolated from cells infected with currently circulating genotypes were used to compare the sensitivity of primer pairs in RT-PCR and nested PCR. FTA® cards loaded with lysates of measles infected cells were tested for their ability to preserve viral RNA and destroy virus infectivity. Results A new primer pair, MeV216/MeV214, was able to amplify N-450 from viruses representing 10 currently circulating genotypes and a genotype A vaccine strain and demonstrated 100-fold increased sensitivity compared to the previously used primer set. A nested PCR assay further increased the sensitivity of detection from patient samples. A synthetic positive control RNA was developed that produced PCR products that are distinguishable by size from PCR products amplified from clinical samples. FTA® cards completely inactivated measles virus and stabilized RNA for at least six months. Conclusions These improved molecular tools will advance molecular characterization of circulating measles viruses globally and provide enhanced quality control measures. PMID:23806666

  17. Improving molecular tools for global surveillance of measles virus.

    Science.gov (United States)

    Bankamp, Bettina; Byrd-Leotis, Lauren A; Lopareva, Elena N; Woo, Gibson K S; Liu, Chunyu; Jee, Youngmee; Ahmed, Hinda; Lim, Wilina W; Ramamurty, Nalini; Mulders, Mick N; Featherstone, David; Bellini, William J; Rota, Paul A

    2013-09-01

    The genetic characterization of wild-type measles viruses plays an important role in the description of viral transmission pathways and the verification of measles elimination. The 450 nucleotides that encode the carboxyl-terminus of the nucleoprotein (N-450) are routinely sequenced for genotype analysis. The objectives of this study were to develop improved primers and controls for RT-PCR reactions used for genotyping of measles samples and to develop a method to provide a convenient, safe, and inexpensive means to distribute measles RNA for RT-PCR assays and practice panels. A newly designed, genetically defined synthetic RNA and RNA isolated from cells infected with currently circulating genotypes were used to compare the sensitivity of primer pairs in RT-PCR and nested PCR. FTA® cards loaded with lysates of measles infected cells were tested for their ability to preserve viral RNA and destroy virus infectivity. A new primer pair, MeV216/MeV214, was able to amplify N-450 from viruses representing 10 currently circulating genotypes and a genotype A vaccine strain and demonstrated 100-fold increased sensitivity compared to the previously used primer set. A nested PCR assay further increased the sensitivity of detection from patient samples. A synthetic positive control RNA was developed that produced PCR products that are distinguishable by size from PCR products amplified from clinical samples. FTA® cards completely inactivated measles virus and stabilized RNA for at least six months. These improved molecular tools will advance molecular characterization of circulating measles viruses globally and provide enhanced quality control measures. Published by Elsevier B.V.

  18. Molecular screening of antibiotic-resistant determinants among multidrug-resistant clinical isolates of Proteus mirabilis from SouthWest Nigeria.

    Science.gov (United States)

    Alabi, Olumuyiwa Samuel; Mendonça, Nuno; Adeleke, Olufemi Ezekiel; da Silva, Gabriela Jorge

    2017-06-01

    Globally, and particularly in developing countries, the menace of anti-microbial resistance is an accelerating problem. In Nigeria, increase in bacterial resistance has been phenotypically established but due to high cost, few molecular studies have been reported. This study screened for presence of transferable resistance genes and mobile genetic elements (MGEs) such as integron among multi-drug resistant (MDR) P. mirabilis . A total of 108 P. mirabilis strains collected from five tertiary hospitals in SouthWest Nigeria were subjected to antibiotic susceptibility study using disc-diffusion method. Transferable resistance genes and MGEs were amplified using Polymerase chain reaction (PCR) analysis and amplicons sequenced. Varied resistance was observed against all the antibiotics tested. About 56% of the isolates were MDR including those from 0-12 years old children. PCR analysis revealed the presence of aac(6')-Ib (33.3%), plasmid mediated quinolone resistance (PMQR) genes [qnrA (36.7%), acc(6')-Ib-cr (5%)], TEM (48.3%), CTX-M (6.7%) and integrons class 1 (58.3%) and class 2 (26.7%). Sequencing analysis revealed bla TEM-1 , bla CTX-M-15 associated with IS Ecp1 and eight different arrays of gene cassettes: aadA1, aadA1-qacH, aadB-aadA2, aadA5, dfrA7, dfrA15, dfrA17, dfrA17-aadA5 . Transferable resistance genes in association with MGEs are present in Nigerian P. mirabilis thus their potential in disseminating resistance.

  19. Zebrafish embryos as a screen for DNA methylation modifications after compound exposure

    Energy Technology Data Exchange (ETDEWEB)

    Bouwmeester, Manon C.; Ruiter, Sander; Lommelaars, Tobias; Sippel, Josefine; Hodemaekers, Hennie M. [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Brandhof, Evert-Jan van den [Center for Environmental Quality, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Pennings, Jeroen L.A. [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Kamstra, Jorke H. [Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Jelinek, Jaroslav [Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA (United States); Issa, Jean-Pierre J. [Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA (United States); Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX (United States); Legler, Juliette [Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Ven, Leo T.M. van der, E-mail: leo.van.der.ven@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands)

    2016-01-15

    Modified epigenetic programming early in life is proposed to underlie the development of an adverse adult phenotype, known as the Developmental Origins of Health and Disease (DOHaD) concept. Several environmental contaminants have been implicated as modifying factors of the developing epigenome. This underlines the need to investigate this newly recognized toxicological risk and systematically screen for the epigenome modifying potential of compounds. In this study, we examined the applicability of the zebrafish embryo as a screening model for DNA methylation modifications. Embryos were exposed from 0 to 72 h post fertilization (hpf) to bisphenol-A (BPA), diethylstilbestrol, 17α-ethynylestradiol, nickel, cadmium, tributyltin, arsenite, perfluoroctanoic acid, valproic acid, flusilazole, 5-azacytidine (5AC) in subtoxic concentrations. Both global and site-specific methylation was examined. Global methylation was only affected by 5AC. Genome wide locus-specific analysis was performed for BPA exposed embryos using Digital Restriction Enzyme Analysis of Methylation (DREAM), which showed minimal wide scale effects on the genome, whereas potential informative markers were not confirmed by pyrosequencing. Site-specific methylation was examined in the promoter regions of three selected genes vasa, vtg1 and cyp19a2, of which vasa (ddx4) was the most responsive. This analysis distinguished estrogenic compounds from metals by direction and sensitivity of the effect compared to embryotoxicity. In conclusion, the zebrafish embryo is a potential screening tool to examine DNA methylation modifications after xenobiotic exposure. The next step is to examine the adult phenotype of exposed embryos and to analyze molecular mechanisms that potentially link epigenetic effects and altered phenotypes, to support the DOHaD hypothesis. - Highlights: • Compound induced effects on DNA methylation in zebrafish embryos • Global methylation not an informative biomarker • Minimal genome

  20. Zebrafish embryos as a screen for DNA methylation modifications after compound exposure

    International Nuclear Information System (INIS)

    Bouwmeester, Manon C.; Ruiter, Sander; Lommelaars, Tobias; Sippel, Josefine; Hodemaekers, Hennie M.; Brandhof, Evert-Jan van den; Pennings, Jeroen L.A.; Kamstra, Jorke H.; Jelinek, Jaroslav; Issa, Jean-Pierre J.; Legler, Juliette; Ven, Leo T.M. van der

    2016-01-01

    Modified epigenetic programming early in life is proposed to underlie the development of an adverse adult phenotype, known as the Developmental Origins of Health and Disease (DOHaD) concept. Several environmental contaminants have been implicated as modifying factors of the developing epigenome. This underlines the need to investigate this newly recognized toxicological risk and systematically screen for the epigenome modifying potential of compounds. In this study, we examined the applicability of the zebrafish embryo as a screening model for DNA methylation modifications. Embryos were exposed from 0 to 72 h post fertilization (hpf) to bisphenol-A (BPA), diethylstilbestrol, 17α-ethynylestradiol, nickel, cadmium, tributyltin, arsenite, perfluoroctanoic acid, valproic acid, flusilazole, 5-azacytidine (5AC) in subtoxic concentrations. Both global and site-specific methylation was examined. Global methylation was only affected by 5AC. Genome wide locus-specific analysis was performed for BPA exposed embryos using Digital Restriction Enzyme Analysis of Methylation (DREAM), which showed minimal wide scale effects on the genome, whereas potential informative markers were not confirmed by pyrosequencing. Site-specific methylation was examined in the promoter regions of three selected genes vasa, vtg1 and cyp19a2, of which vasa (ddx4) was the most responsive. This analysis distinguished estrogenic compounds from metals by direction and sensitivity of the effect compared to embryotoxicity. In conclusion, the zebrafish embryo is a potential screening tool to examine DNA methylation modifications after xenobiotic exposure. The next step is to examine the adult phenotype of exposed embryos and to analyze molecular mechanisms that potentially link epigenetic effects and altered phenotypes, to support the DOHaD hypothesis. - Highlights: • Compound induced effects on DNA methylation in zebrafish embryos • Global methylation not an informative biomarker • Minimal genome

  1. Alternative global goodness metrics and sensitivity analysis: heuristics to check the robustness of conclusions from studies comparing virtual screening methods.

    Science.gov (United States)

    Sheridan, Robert P

    2008-02-01

    We introduce two ways of testing the robustness of conclusions from studies comparing virtual screening methods: alternative "global goodness" metrics and sensitivity analysis. While the robustness tests cannot eliminate all biases in virtual screening comparisons, they are useful as a "reality check" for any given study. To illustrate this, we apply them to a set of enrichments published in McGaughey et al. (J. Chem. Inf. Model. 2007, 47, 1504-1519) where 11 target protein/ligand combinations are tested on 2D and 3D similarity methods, plus docking. The major conclusions in that paper, for instance, that ligand-based methods are better than docking methods, hold up. However, some minor conclusions, such as Glide being the best docking method, do not.

  2. Bayesian screening for active compounds in high-dimensional chemical spaces combining property descriptors and molecular fingerprints.

    Science.gov (United States)

    Vogt, Martin; Bajorath, Jürgen

    2008-01-01

    Bayesian classifiers are increasingly being used to distinguish active from inactive compounds and search large databases for novel active molecules. We introduce an approach to directly combine the contributions of property descriptors and molecular fingerprints in the search for active compounds that is based on a Bayesian framework. Conventionally, property descriptors and fingerprints are used as alternative features for virtual screening methods. Following the approach introduced here, probability distributions of descriptor values and fingerprint bit settings are calculated for active and database molecules and the divergence between the resulting combined distributions is determined as a measure of biological activity. In test calculations on a large number of compound activity classes, this methodology was found to consistently perform better than similarity searching using fingerprints and multiple reference compounds or Bayesian screening calculations using probability distributions calculated only from property descriptors. These findings demonstrate that there is considerable synergy between different types of property descriptors and fingerprints in recognizing diverse structure-activity relationships, at least in the context of Bayesian modeling.

  3. Reconstruction and validation of RefRec: a global model for the yeast molecular interaction network.

    Directory of Open Access Journals (Sweden)

    Tommi Aho

    2010-05-01

    Full Text Available Molecular interaction networks establish all cell biological processes. The networks are under intensive research that is facilitated by new high-throughput measurement techniques for the detection, quantification, and characterization of molecules and their physical interactions. For the common model organism yeast Saccharomyces cerevisiae, public databases store a significant part of the accumulated information and, on the way to better understanding of the cellular processes, there is a need to integrate this information into a consistent reconstruction of the molecular interaction network. This work presents and validates RefRec, the most comprehensive molecular interaction network reconstruction currently available for yeast. The reconstruction integrates protein synthesis pathways, a metabolic network, and a protein-protein interaction network from major biological databases. The core of the reconstruction is based on a reference object approach in which genes, transcripts, and proteins are identified using their primary sequences. This enables their unambiguous identification and non-redundant integration. The obtained total number of different molecular species and their connecting interactions is approximately 67,000. In order to demonstrate the capacity of RefRec for functional predictions, it was used for simulating the gene knockout damage propagation in the molecular interaction network in approximately 590,000 experimentally validated mutant strains. Based on the simulation results, a statistical classifier was subsequently able to correctly predict the viability of most of the strains. The results also showed that the usage of different types of molecular species in the reconstruction is important for accurate phenotype prediction. In general, the findings demonstrate the benefits of global reconstructions of molecular interaction networks. With all the molecular species and their physical interactions explicitly modeled, our

  4. Current Cervical Carcinoma Screening Guidelines

    Directory of Open Access Journals (Sweden)

    Megan J. Schlichte

    2015-05-01

    Full Text Available A formidable threat to the health of women, cervical carcinoma can be prevented in many cases with adequate screening. The current guidelines for cervical carcinoma screening were created as joint recommendations of the American Cancer Society (ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP and the American Society for Clinical Pathology (ASCP in 2012, and later accepted and promoted by the American Congress of Obstetricians and Gynecologists (ACOG. The 2012 recommendations underscore the utility of molecular testing as an adjunct to cytology screening for certain women and provide guidance to clinicians based on different risk-benefit considerations for different ages. This manuscript will review screening techniques and current recommendations for cervical cancer screening and human papilloma virus (HPV testing, as well as possible future screening strategies.

  5. Liver diseases: A major, neglected global public health problem requiring urgent actions and large-scale screening.

    Science.gov (United States)

    Marcellin, Patrick; Kutala, Blaise K

    2018-02-01

    CLDs represent an important, and certainly underestimated, global public health problem. CLDs are highly prevalent and silent, related to different, sometimes associated causes. The distribution of the causes of these diseases is slowly changing, and within the next decade, the proportion of virus-induced CLDs will certainly decrease significantly while the proportion of NASH will increase. There is an urgent need for effective global actions including education, prevention and early diagnosis to manage and treat CLDs, thus preventing cirrhosis-related morbidity and mortality. Our role is to increase the awareness of the public, healthcare professionals and public health authorities to encourage active policies for early management that will decrease the short- and long-term public health burden of these diseases. Because necroinflammation is the key mechanism in the progression of CLDs, it should be detected early. Thus, large-scale screening for CLDs is needed. ALT levels are an easy and inexpensive marker of liver necroinflammation and could be the first-line tool in this process. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Rational approach to identify newer caspase-1 inhibitors using pharmacophore based virtual screening, docking and molecular dynamic simulation studies.

    Science.gov (United States)

    Patel, Shivani; Modi, Palmi; Chhabria, Mahesh

    2018-05-01

    Caspase-1 is a key endoprotease responsible for the post-translational processing of pro-inflammatory cytokines IL-1β, 18 & 33. Excessive secretion of IL-1β leads to numerous inflammatory and autoimmune diseases. Thus caspase-1 inhibition would be considered as an important therapeutic strategy for development of newer anti-inflammatory agents. Here we have employed an integrated virtual screening by combining pharmacophore mapping and docking to identify small molecules as caspase-1 inhibitors. The ligand based 3D pharmacophore model was generated having the essential structural features of (HBA, HY & RA) using a data set of 27 compounds. A validated pharmacophore hypothesis (Hypo 1) was used to screen ZINC and Minimaybridge chemical databases. The retrieved virtual hits were filtered by ADMET properties and molecular docking analysis. Subsequently, the cross-docking study was also carried out using crystal structure of caspase-1, 3, 7 and 8 to identify the key residual interaction for specific caspase-1 inhibition. Finally, the best mapped and top scored (ZINC00885612, ZINC72003647, BTB04175 and BTB04410) molecules were subjected to molecular dynamics simulation for accessing the dynamic structure of protein after ligand binding. This study identifies the most promising hits, which can be leads for the development of novel caspase-1 inhibitors as anti-inflammatory agents. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Molecular architectures based on π-conjugated block copolymers for global quantum computation

    International Nuclear Information System (INIS)

    Mujica Martinez, C A; Arce, J C; Reina, J H; Thorwart, M

    2009-01-01

    We propose a molecular setup for the physical implementation of a barrier global quantum computation scheme based on the electron-doped π-conjugated copolymer architecture of nine blocks PPP-PDA-PPP-PA-(CCH-acene)-PA-PPP-PDA-PPP (where each block is an oligomer). The physical carriers of information are electrons coupled through the Coulomb interaction, and the building block of the computing architecture is composed by three adjacent qubit systems in a quasi-linear arrangement, each of them allowing qubit storage, but with the central qubit exhibiting a third accessible state of electronic energy far away from that of the qubits' transition energy. The third state is reached from one of the computational states by means of an on-resonance coherent laser field, and acts as a barrier mechanism for the direct control of qubit entanglement. Initial estimations of the spontaneous emission decay rates associated to the energy level structure allow us to compute a damping rate of order 10 -7 s, which suggest a not so strong coupling to the environment. Our results offer an all-optical, scalable, proposal for global quantum computing based on semiconducting π-conjugated polymers.

  8. Molecular architectures based on pi-conjugated block copolymers for global quantum computation

    Energy Technology Data Exchange (ETDEWEB)

    Mujica Martinez, C A; Arce, J C [Universidad del Valle, Departamento de QuImica, A. A. 25360, Cali (Colombia); Reina, J H [Universidad del Valle, Departamento de Fisica, A. A. 25360, Cali (Colombia); Thorwart, M, E-mail: camujica@univalle.edu.c, E-mail: j.reina-estupinan@physics.ox.ac.u, E-mail: jularce@univalle.edu.c [Institut fuer Theoretische Physik IV, Heinrich-Heine-Universitaet Duesseldorf, 40225 Duesseldorf (Germany)

    2009-05-01

    We propose a molecular setup for the physical implementation of a barrier global quantum computation scheme based on the electron-doped pi-conjugated copolymer architecture of nine blocks PPP-PDA-PPP-PA-(CCH-acene)-PA-PPP-PDA-PPP (where each block is an oligomer). The physical carriers of information are electrons coupled through the Coulomb interaction, and the building block of the computing architecture is composed by three adjacent qubit systems in a quasi-linear arrangement, each of them allowing qubit storage, but with the central qubit exhibiting a third accessible state of electronic energy far away from that of the qubits' transition energy. The third state is reached from one of the computational states by means of an on-resonance coherent laser field, and acts as a barrier mechanism for the direct control of qubit entanglement. Initial estimations of the spontaneous emission decay rates associated to the energy level structure allow us to compute a damping rate of order 10{sup -7} s, which suggest a not so strong coupling to the environment. Our results offer an all-optical, scalable, proposal for global quantum computing based on semiconducting pi-conjugated polymers.

  9. Comprehensive Molecular Screening in Chinese Usher Syndrome Patients.

    Science.gov (United States)

    Sun, Tengyang; Xu, Ke; Ren, Yanfan; Xie, Yue; Zhang, Xiaohui; Tian, Lu; Li, Yang

    2018-03-01

    Usher syndrome (USH) refers to a group of autosomal recessive disorders causing deafness and blindness. The objectives of this study were to determine the mutation spectrum in a cohort of Chinese patients with USH and to describe the clinical features of the patients with mutations. A total of 119 probands who were clinically diagnosed with USH were recruited for genetic analysis. All probands underwent ophthalmic examinations. A combination of molecular screening methods, including targeted next-generation sequencing, Sanger-DNA sequencing, and multiplex ligation probe amplification assay, was used to detect mutations. We found biallelic mutations in 92 probands (77.3%), monoallelic mutations in 5 patients (4.2%), and 1 hemizygous mutation in 1 patient (0.8%), resulting in an overall mutation detection rate of 78.2%. Overall, 132 distinct disease-causing mutations involving seven USH (ABHD12, CDH23, GPR98, MYO7A, PCDH15, USH1C, and USH2A) genes; 5 other retinal degeneration genes (CHM, CNGA1, EYS, PDE6B, and TULP1); and 1 nonsyndromic hearing loss gene (MYO15A) were identified, and 78 were novel. Mutations of MYOA7 were responsible for 60% of USH1 families, followed by PCDH15 (20%) and USH1C (10%). Mutations of USH2A accounted for 67.7% of USH2 families, and mutation c.8559-2A>G was the most frequent one, accounting for 19.1% of the identified USH2A alleles. Our results confirm that the mutation spectrum for each USH gene in Chinese patients differs from those of other populations. The formation of the mutation profile for the Chinese population will enable a precise genetic diagnosis for USH patients in the future.

  10. Chemical Risk Assessment Screening Tool of a Global Chemical Company

    Directory of Open Access Journals (Sweden)

    Evelyn Tjoe-Nij

    2018-03-01

    Full Text Available Background: This paper describes a simple-to-use and reliable screening tool called Critical Task Exposure Screening (CTES, developed by a chemical company. The tool assesses if the exposure to a chemical for a task is likely to be within acceptable levels. Methods: CTES is a Microsoft Excel tool, where the inhalation risk score is calculated by relating the exposure estimate to the corresponding occupational exposure limit (OEL or occupational exposure band (OEB. The inhalation exposure is estimated for tasks by preassigned ART1.5 activity classes and modifying factors. Results: CTES requires few inputs. The toxicological data, including OELs, OEBs, and vapor pressure are read from a database. Once the substance is selected, the user specifies its concentration and then chooses the task description and its duration. CTES has three outputs that may trigger follow-up: (1 inhalation risk score; (2 identification of the skin hazard with the skin warnings for local and systemic adverse effects; and (3 status for carcinogenic, mutagenic, or reprotoxic effects. Conclusion: The tool provides an effective way to rapidly screen low-concern tasks, and quickly identifies certain tasks involving substances that will need further review with, nevertheless, the appropriate conservatism. This tool shows that the higher-tier ART1.5 inhalation exposure assessment model can be included effectively in a screening tool. After 2 years of worldwide extensive use within the company, CTES is well perceived by the users, including the shop floor management, and it fulfills its target of screening tool. Keywords: occupational exposure, risk assessment, risk management

  11. Molecular structures enumeration and virtual screening in the chemical space with RetroPath2.0.

    Science.gov (United States)

    Koch, Mathilde; Duigou, Thomas; Carbonell, Pablo; Faulon, Jean-Loup

    2017-12-19

    Network generation tools coupled with chemical reaction rules have been mainly developed for synthesis planning and more recently for metabolic engineering. Using the same core algorithm, these tools apply a set of rules to a source set of compounds, stopping when a sink set of compounds has been produced. When using the appropriate sink, source and rules, this core algorithm can be used for a variety of applications beyond those it has been developed for. Here, we showcase the use of the open source workflow RetroPath2.0. First, we mathematically prove that we can generate all structural isomers of a molecule using a reduced set of reaction rules. We then use this enumeration strategy to screen the chemical space around a set of monomers and predict their glass transition temperatures, as well as around aminoglycosides to search structures maximizing antibacterial activity. We also perform a screening around aminoglycosides with enzymatic reaction rules to ensure biosynthetic accessibility. We finally use our workflow on an E. coli model to complete E. coli metabolome, with novel molecules generated using promiscuous enzymatic reaction rules. These novel molecules are searched on the MS spectra of an E. coli cell lysate interfacing our workflow with OpenMS through the KNIME Analytics Platform. We provide an easy to use and modify, modular, and open-source workflow. We demonstrate its versatility through a variety of use cases including molecular structure enumeration, virtual screening in the chemical space, and metabolome completion. Because it is open source and freely available on MyExperiment.org, workflow community contributions should likely expand further the features of the tool, even beyond the use cases presented in the paper.

  12. Preimplantation genetic screening.

    Science.gov (United States)

    Harper, Joyce C

    2018-03-01

    Preimplantation genetic diagnosis was first successfully performed in 1989 as an alternative to prenatal diagnosis for couples at risk of transmitting a genetic or chromosomal abnormality, such as cystic fibrosis, to their child. From embryos generated in vitro, biopsied cells are genetically tested. From the mid-1990s, this technology has been employed as an embryo selection tool for patients undergoing in vitro fertilisation, screening as many chromosomes as possible, in the hope that selecting chromosomally normal embryos will lead to higher implantation and decreased miscarriage rates. This procedure, preimplantation genetic screening, was initially performed using fluorescent in situ hybridisation, but 11 randomised controlled trials of screening using this technique showed no improvement in in vitro fertilisation delivery rates. Progress in genetic testing has led to the introduction of array comparative genomic hybridisation, quantitative polymerase chain reaction, and next generation sequencing for preimplantation genetic screening, and three small randomised controlled trials of preimplantation genetic screening using these new techniques indicate a modest benefit. Other trials are still in progress but, regardless of their results, preimplantation genetic screening is now being offered globally. In the near future, it is likely that sequencing will be used to screen the full genetic code of the embryo.

  13. Quantitative genome-wide genetic interaction screens reveal global epistatic relationships of protein complexes in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Mohan Babu

    2014-02-01

    Full Text Available Large-scale proteomic analyses in Escherichia coli have documented the composition and physical relationships of multiprotein complexes, but not their functional organization into biological pathways and processes. Conversely, genetic interaction (GI screens can provide insights into the biological role(s of individual gene and higher order associations. Combining the information from both approaches should elucidate how complexes and pathways intersect functionally at a systems level. However, such integrative analysis has been hindered due to the lack of relevant GI data. Here we present a systematic, unbiased, and quantitative synthetic genetic array screen in E. coli describing the genetic dependencies and functional cross-talk among over 600,000 digenic mutant combinations. Combining this epistasis information with putative functional modules derived from previous proteomic data and genomic context-based methods revealed unexpected associations, including new components required for the biogenesis of iron-sulphur and ribosome integrity, and the interplay between molecular chaperones and proteases. We find that functionally-linked genes co-conserved among γ-proteobacteria are far more likely to have correlated GI profiles than genes with divergent patterns of evolution. Overall, examining bacterial GIs in the context of protein complexes provides avenues for a deeper mechanistic understanding of core microbial systems.

  14. Digital diffraction analysis enables low-cost molecular diagnostics on a smartphone.

    Science.gov (United States)

    Im, Hyungsoon; Castro, Cesar M; Shao, Huilin; Liong, Monty; Song, Jun; Pathania, Divya; Fexon, Lioubov; Min, Changwook; Avila-Wallace, Maria; Zurkiya, Omar; Rho, Junsung; Magaoay, Brady; Tambouret, Rosemary H; Pivovarov, Misha; Weissleder, Ralph; Lee, Hakho

    2015-05-05

    The widespread distribution of smartphones, with their integrated sensors and communication capabilities, makes them an ideal platform for point-of-care (POC) diagnosis, especially in resource-limited settings. Molecular diagnostics, however, have been difficult to implement in smartphones. We herein report a diffraction-based approach that enables molecular and cellular diagnostics. The D3 (digital diffraction diagnosis) system uses microbeads to generate unique diffraction patterns which can be acquired by smartphones and processed by a remote server. We applied the D3 platform to screen for precancerous or cancerous cells in cervical specimens and to detect human papillomavirus (HPV) DNA. The D3 assay generated readouts within 45 min and showed excellent agreement with gold-standard pathology or HPV testing, respectively. This approach could have favorable global health applications where medical access is limited or when pathology bottlenecks challenge prompt diagnostic readouts.

  15. Chemical Risk Assessment Screening Tool of a Global Chemical Company

    OpenAIRE

    Evelyn Tjoe-Nij; Christophe Rochin; Nathalie Berne; Alessandro Sassi; Antoine Leplay

    2018-01-01

    Background: This paper describes a simple-to-use and reliable screening tool called Critical Task Exposure Screening (CTES), developed by a chemical company. The tool assesses if the exposure to a chemical for a task is likely to be within acceptable levels. Methods: CTES is a Microsoft Excel tool, where the inhalation risk score is calculated by relating the exposure estimate to the corresponding occupational exposure limit (OEL) or occupational exposure band (OEB). The inhalation exposure i...

  16. Screening of recombinant inbred lines for salinity tolerance in bread ...

    African Journals Online (AJOL)

    Jane

    2011-10-05

    Oct 5, 2011 ... 2Department of Molecular Physiology, Agricultural Biotechnology Research Institute of Iran ... indexes for screening bread wheat genotypes for salinity tolerance. ... published on screening methods in salinity tolerance in.

  17. Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking

    DEFF Research Database (Denmark)

    Wang, Mingxun; Carver, Jeremy J.; Pevzner, Pavel

    2016-01-01

    are well-suited to high-throughput characterization of NP, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social Molecular Networking (GNPS; http://gnps.ucsd.edu), an open-access knowledge base for community-wide organization...... and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS, crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations...

  18. Fragment-based screening in tandem with phenotypic screening provides novel antiparasitic hits.

    Science.gov (United States)

    Blaazer, Antoni R; Orrling, Kristina M; Shanmugham, Anitha; Jansen, Chimed; Maes, Louis; Edink, Ewald; Sterk, Geert Jan; Siderius, Marco; England, Paul; Bailey, David; de Esch, Iwan J P; Leurs, Rob

    2015-01-01

    Methods to discover biologically active small molecules include target-based and phenotypic screening approaches. One of the main difficulties in drug discovery is elucidating and exploiting the relationship between drug activity at the protein target and disease modification, a phenotypic endpoint. Fragment-based drug discovery is a target-based approach that typically involves the screening of a relatively small number of fragment-like (molecular weight <300) molecules that efficiently cover chemical space. Here, we report a fragment screening on TbrPDEB1, an essential cyclic nucleotide phosphodiesterase (PDE) from Trypanosoma brucei, and human PDE4D, an off-target, in a workflow in which fragment hits and a series of close analogs are subsequently screened for antiparasitic activity in a phenotypic panel. The phenotypic panel contained T. brucei, Trypanosoma cruzi, Leishmania infantum, and Plasmodium falciparum, the causative agents of human African trypanosomiasis (sleeping sickness), Chagas disease, leishmaniasis, and malaria, respectively, as well as MRC-5 human lung cells. This hybrid screening workflow has resulted in the discovery of various benzhydryl ethers with antiprotozoal activity and low toxicity, representing interesting starting points for further antiparasitic optimization. © 2014 Society for Laboratory Automation and Screening.

  19. It takes a global village

    NARCIS (Netherlands)

    Damhof, Loes; DeWitt, Janine; Wolfensberger, Marca

    2014-01-01

    Connected through a screen, two classes that are an ocean apart take the same course and do the same assignments. Our course “ The Global Village” is a globally networked learning environment (Starke-Meyerring and Wilson, 2008) where students from two different universities work and learn together

  20. Formation of giant molecular clouds in global spiral structures: the role of orbital dynamics and cloud-cloud collisions

    International Nuclear Information System (INIS)

    Roberts, W.W. Jr.; Stewart, G.R.

    1987-01-01

    The different roles played by orbital dynamics and dissipative cloud-cloud collisions in the formation of giant molecular clouds (GMCs) in a global spiral structure are investigated. The interstellar medium (ISM) is simulated by a system of particles, representing clouds, which orbit in a spiral-perturbed, galactic gravitational field. The overall magnitude and width of the global cloud density distribution in spiral arms is very similar in the collisional and collisionless simulations. The results suggest that the assumed number density and size distribution of clouds and the details of individual cloud-cloud collisions have relatively little effect on these features. Dissipative cloud-cloud collisions play an important steadying role for the cloud system's global spiral structure. Dissipative cloud-cloud collisions also damp the relative velocity dispersion of clouds in massive associations and thereby aid in the effective assembling of GMC-like complexes

  1. A focus group study of consumer attitudes toward genetic testing and newborn screening for deafness.

    Science.gov (United States)

    Burton, Sarah K; Withrow, Kara; Arnos, Kathleen S; Kalfoglou, Andrea L; Pandya, Arti

    2006-12-01

    Progress in identifying genes for deafness together with implementation of universal audiologic screening of newborns has provided the opportunity for more widespread use of molecular tests to detect genetic forms of hearing loss. Efforts to assess consumer attitudes toward these advances have lagged behind. Consumer focus groups were held to explore attitudes toward genetic advances and technologies for hearing loss, views about newborn hearing screening, and reactions to the idea of adding molecular screening for hearing loss at birth. Focus group discussions were recorded, transcribed and analyzed. Five focus groups with 44 participants including hearing parents of deaf children, deaf parents and young deaf adults were held. Focus group participants supported the use of genetic tests to identify the etiology of hearing loss but were concerned that genetic information might influence reproductive decisions. Molecular newborn screening was advocated by some; however, others expressed concern about its effectiveness. Documenting the attitudes of parents and other consumers toward genetic technologies establishes the framework for discussions on the appropriateness of molecular newborn screening for hearing loss and informs specialists about potential areas of public education necessary prior to the implementation of such screening.

  2. Molecular screening of antibiotic-resistant determinants among ...

    African Journals Online (AJOL)

    In Nigeria, increase in bacterial resistance has been phenotypically established but due to high cost, few molecular studies ... ocomial opportunistic infections such as urinary tract .... Twelve (20%) of these MDR isolates were from children.

  3. Identification of Potent Chloride Intracellular Channel Protein 1 Inhibitors from Traditional Chinese Medicine through Structure-Based Virtual Screening and Molecular Dynamics Analysis

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2017-01-01

    Full Text Available Chloride intracellular channel 1 (CLIC1 is involved in the development of most aggressive human tumors, including gastric, colon, lung, liver, and glioblastoma cancers. It has become an attractive new therapeutic target for several types of cancer. In this work, we aim to identify natural products as potent CLIC1 inhibitors from Traditional Chinese Medicine (TCM database using structure-based virtual screening and molecular dynamics (MD simulation. First, structure-based docking was employed to screen the refined TCM database and the top 500 TCM compounds were obtained and reranked by X-Score. Then, 30 potent hits were achieved from the top 500 TCM compounds using cluster and ligand-protein interaction analysis. Finally, MD simulation was employed to validate the stability of interactions between each hit and CLIC1 protein from docking simulation, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA analysis was used to refine the virtual hits. Six TCM compounds with top MM-GBSA scores and ideal-binding models were confirmed as the final hits. Our study provides information about the interaction between TCM compounds and CLIC1 protein, which may be helpful for further experimental investigations. In addition, the top 6 natural products structural scaffolds could serve as building blocks in designing drug-like molecules for CLIC1 inhibition.

  4. [The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies--will a global change start in Israel?].

    Science.gov (United States)

    Bronshtein, Moshe; Solt, Ido; Blumenfeld, Zeev

    2014-06-01

    Despite more than three decades of universal popularity of fetal sonography as an integral part of pregnancy evaluation, there is still no unequivocal agreement regarding the optimal dating of fetal sonographic screening and the type of ultrasound (transvaginal vs abdominal). TransvaginaL systematic sonography at 14-17 weeks for fetal organ screening. The evaluation of over 72.000 early (14-17 weeks) and late (18-24 weeks) fetal ultrasonographic systematic organ screenings revealed that 96% of the malformations are detectable in the early screening with an incidence of 1:50 gestations. Only 4% of the fetal anomalies are diagnosed later in pregnancy. Over 99% of the fetal cardiac anomalies are detectable in the early screening and most of them appear in low risk gestations. Therefore, we suggest a new platform of fetal sonographic evaluation and follow-up: The extensive systematic fetal organ screening should be performed by an expert sonographer who has been trained in the detection of fetal malformations, at 14-17 weeks gestation. This examination should also include fetal cardiac echography Three additional ultrasound examinations are suggested during pregnancy: the first, performed by the patient's obstetrician at 6-7 weeks for the exclusion of ectopic pregnancy, confirmation of fetal viability, dating, assessment of chorionicity in multiple gestations, and visualization of maternal adnexae. The other two, at 22-26 and 32-34 weeks, require less training and should be performed by an obstetrician who has been qualified in the sonographic detection of fetal anomalies. The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies may dictate a global change.

  5. Development of novel HER2 inhibitors against gastric cancer derived from flavonoid source of Syzygium alternifolium through molecular dynamics and pharmacophore-based screening

    Directory of Open Access Journals (Sweden)

    Babu TMC

    2016-11-01

    Full Text Available Tirumalasetty Muni Chandra Babu,1 Aluru Rammohan,2 Vijaya Bhaskar Baki,1 Savita Devi,3 Duvvuru Gunasekar,2 Wudayagiri Rajendra1 1Bioinformatics Center, Division of Molecular Biology, Department of Zoology, 2Natural Products Division, Department of Chemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh, 3Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, India Abstract: Continuous usage of synthetic chemotherapeutic drugs causes adverse effects, which prompted for the development of alternative therapeutics for gastric cancer from natural source. This study was carried out with a specific aim to screen gastroprotective compounds from the fruits of Syzygium alternifolium (Myrtaceae. Three flavonoids, namely, 1 5-hydroxy-7,4'-dimethoxy-6,8-di-C-methylflavone, 2 kaempferol-3-O-β-D-glucopyranoside, and 3 kaempferol-3-O-α-L-rhamnopyranoside were isolated from the above medicinal plant by employing silica gel column chromatography and are characterized by NMR techniques. Antigastric cancer activity of these flavonoids was examined on AGS cell lines followed by cell cycle progression assay. In addition, pharmacophore-based screening and molecular dynamics of protein–ligand complex were carried out to identify potent scaffolds. The results showed that compounds 2 and 3 exhibited significant cytotoxic effect, whereas compound 1 showed moderate effect on AGS cells by inhibiting G2/M phase of cell cycle. Molecular docking analysis revealed that compound 2 has higher binding energies on human growth factor receptor-2 (HER2. The constructed pharmacophore models reveal that the compounds have more number of H-bond Acc/Don features which contribute to the inhibition of HER2 activity. By selecting these features, 34 hits were retrieved using the query compound 2. Molecular dynamic simulations (MDS of protein–ligand complexes demonstrated conspicuous

  6. High-throughput molecular binding analysis on open-microfluidic platform

    OpenAIRE

    Pan, Yuchen

    2016-01-01

    Biomolecular binding interactions underpin life sciences tools that are essential to fields as diverse as molecular biology and clinical chemistry. Merging needs in life science research entail fast, robust and quantitative binding reaction characterization, such as antibody selection, gene regulation screening and drug screening. Identification, characterization, and optimization of these diverse molecular binding reactions demands the availability of powerful, quantitative analytical tools....

  7. Breast cancer screening controversies: who, when, why, and how?

    Science.gov (United States)

    Chetlen, Alison; Mack, Julie; Chan, Tiffany

    2016-01-01

    Mammographic screening is effective in reducing mortality from breast cancer. The issue is not whether mammography is effective, but whether the false positive rate and false negative rates can be reduced. This review will discuss controversies including the reduction in breast cancer mortality, overdiagnosis, the ideal screening candidate, and the optimal imaging modality for breast cancer screening. The article will compare and contrast screening mammography, tomosynthesis, whole-breast screening ultrasound, magnetic resonance imaging, and molecular breast imaging. Though supplemental imaging modalities are being utilized to improve breast cancer diagnosis, mammography still remains the gold standard for breast cancer screening. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Complex polarimetric and spectral techniques in diagnostics of blood plasma of patients with ovarian cancer as a preliminary stage molecular genetic screening

    Science.gov (United States)

    Grzegorzewski, B.; Peresunko, O. P.; Yermolenko, S. B.

    2018-01-01

    This work is devoted to the substantiation and selection of patients with ovarian cancer (OC) for the purpose of conducting expensive molecular genetic studies on genotyping. As diagnostic methods have been used ultraviolet spectrometry samples of blood plasma in the liquid state, infrared spectroscopy middle range (2,5 - 25 microns) dry residue of plasma polarization and laser diagnostic technique of thin histological sections of biological tissues. Obtained results showed that the use of spectrophotometry in the range of 1000-3000 cm-1 allowed to establish quantitative parameters of the plasma absorption rate of blood of patients in the third group in different ranges, which would allow in the future to conduct an express analysis of the patient's condition (procedure screening) for further molecular-genetic typing on BRCA I and II.

  9. Virtual screening of natural inhibitors to the predicted HBx protein structure of Hepatitis B Virus using molecular docking for identification of potential lead molecules for liver cancer

    Science.gov (United States)

    Pathak, Rajesh Kumar; Baunthiyal, Mamta; Taj, Gohar; Kumar, Anil

    2014-01-01

    The HBx protein in Hepatitis B Virus (HBV) is a potential target for anti-liver cancer molecules. Therefore, it is of interest to screen known natural compounds against the HBx protein using molecular docking. However, the structure of HBx is not yet known. Therefore, the predicted structure of HBx using threading in LOMET was used for docking against plant derived natural compounds (curcumin, oleanolic acid, resveratrol, bilobetin, luteoline, ellagic acid, betulinic acid and rutin) by Molegro Virtual Docker. The screening identified rutin with binding energy of -161.65 Kcal/mol. Thus, twenty derivatives of rutin were further designed and screened against HBx. These in silico experiments identified compounds rutin01 (-163.16 Kcal/mol) and rutin08 (- 165.76 Kcal/mol) for further consideration and downstream validation. PMID:25187683

  10. Molecular biodiversity of Red Sea demosponges

    International Nuclear Information System (INIS)

    Erpenbeck, Dirk; Voigt, Oliver; Al-Aidaroos, Ali M.; Berumen, Michael L.; Büttner, Gabriele; Catania, Daniela; Guirguis, Adel Naguib; Paulay, Gustav; Schätzle, Simone

    2016-01-01

    Sponges are important constituents of coral reef ecosystems, including those around the Arabian Peninsula. Despite their importance, our knowledge on demosponge diversity in this area is insufficient to recognize, for example, faunal changes caused by anthropogenic disturbances. We here report the first assessment of demosponge molecular biodiversity from Arabia, with focus on the Saudi Arabian Red Sea, based on mitochondrial and nuclear ribosomal molecular markers gathered in the framework of the Sponge Barcoding Project. We use a rapid molecular screening approach on Arabian demosponge collections and analyze results in comparison against published material in terms of biodiversity. We use a variable region of 28S rDNA, applied for the first time in the assessment of demosponge molecular diversity. Our data constitutes a solid foundation for a future more comprehensive understanding of sponge biodiversity of the Red Sea and adjacent waters. - Highlights: •First assessment of demosponge molecular biodiversity from Arabia •Rapid molecular screening approach on Arabian demosponge collections •Assessment of 28S 'C-Region' for demosponge barcoding •Data for a future comprehensive understanding of sponge biodiversity of the Red Sea

  11. [Strategy for molecular testing in pulmonary carcinoma].

    Science.gov (United States)

    Penault-Llorca, Frédérique; Tixier, Lucie; Perrot, Loïc; Cayre, Anne

    2016-01-01

    Nowadays, the analysis of theranostic molecular markers is central in the management of lung cancer. As those tumors are diagnosed in two third of the cases at an advanced stage, molecular screening is frequently performed on "small samples". The screening strategy starts by an accurate histopathological characterization, including on biopsies or cytological specimens. WHO 2015 provided a new classification for small biopsy and cytology, defining categories such as non-small cell carcinoma (NSCC), favor adenocarcinoma (TTF1 positive), or favor squamous cell carcinoma (p40 positive). Only the NSCC tumors, non-squamous, are eligible to molecular testing. A strategy aiming at tissue sparing for the small biopsies has to be organized. Tests corresponding to available drugs are prioritized. Blank slides will be prepared for immunohistochemistry and in situ hybridization based tests such as ALK. DNA will then be extracted for the other tests, EGFR mutation screening first associated or not to KRAS. Then, the emerging biomarkers (HER2, ROS1, RET, BRAF…) as well as potentially other markers in case of clinical trials, can been tested. The spread of next generation sequencing technologies, with a very sensitive all-in-one approach will allow the identification of minority clones. Eventually, the development of liquid biopsies will provide the opportunity to monitor the apparition of resistance clones during treatment. This non-invasive approach allows patients with a contraindication to perform biopsy or with non-relevant biopsies to access to molecular screening. Copyright © 2016. Published by Elsevier Masson SAS.

  12. Molecular science solving global problems

    International Nuclear Information System (INIS)

    Dunning, T.H. Jr.; Stults, B.R.

    1995-01-01

    From the late 1940s to the late 1980s, the Department of Energy (DOE) had a critical role in the Cold War. Many sites were built to contribute to the nation's nuclear weapons effort. However, not enough attention was paid to how the waste generated at these facilities should be handled. As a result, a number of sites fouled the soil around them or dumped low-level radioactive waste into nearby rivers. A DOE laboratory is under construction with a charter to help. Called the Environmental Molecular Sciences Laboratory (EMSL), this national user facility will be located at DOE's Pacific Northwest Laboratory (PNL) in Richland, WA. This laboratory has been funded by DOE and Congress to play a major role as the nation confronts the enormous challenge of reducing environmental and human risks from hundreds of government and industrial waste sites in an economically viable manner. The original proposal for the EMSL took a number of twists and turns on its way to its present form, but one thing remained constant: the belief that safe, permanent, cost-effective solutions to many of the country's environmental problems could be achieved only by multidisciplinary teams working to understand and control molecular processes. The processes of most concern are those that govern the transport and transformation of contaminants, the treatment and storage of high-level mixed wastes, and the risks those contaminants ultimately pose to workers and the public

  13. Comparative analysis of pharmacophore screening tools.

    NARCIS (Netherlands)

    Sanders, M.P.A.; Barbosa, A.J.; Zarzycka, B.; Nicolaes, G.A.; Klomp, J.P.G.; Vlieg, J. de; Rio, A. Del

    2012-01-01

    The pharmacophore concept is of central importance in computer-aided drug design (CADD) mainly because of its successful application in medicinal chemistry and, in particular, high-throughput virtual screening (HTVS). The simplicity of the pharmacophore definition enables the complexity of molecular

  14. A Comparison of the Nutritional Risk Screening 2002 Tool With the Subjective Global Assessment Tool to Detect Nutritional Status in Chinese Patients Undergoing Surgery With Gastrointestinal Cancer.

    Science.gov (United States)

    Chi, Juntao; Yin, Shaohua; Zhu, Yongjian; Gao, Fengli; Song, Xinna; Song, Zhenlan; Lv, Junying; Li, Miaomiao

    The objectives of this study were to describe the nutritional status of Chinese patients with gastrointestinal cancer undergoing surgery and to compare the ease of use, diversity, and concordance of the Nutritional Risk Screening 2002 with the Subjective Global Assessment in the same patients. A total of 280 gastrointestinal cancer patients admitted for elective surgery were evaluated by the Nutritional Risk Screening 2002 (NRS 2002) and Subjective Global Assessment (SGA) tools within 48 hours of admission from April to October 2012. Related opinions about ease of using the tools were obtained from 10 nurses. The prevalence of patients at nutritional risk with the SGA and NRS 2002 was 33.9% and 53.2% on admission. In the total group, ≤70 age group, and >70 age group, respectively, consistency was observed in 214 (76.4%), 175 (91.1%), and 39 (44.3%); and kappa values were 0.54 (p 70 age group (p nutritional status of patients with gastrointestinal cancer undergoing surgery, but it appeared to detect more patients at nutritional risk in the >70 age group.

  15. Molecular imaging: current status and emerging strategies

    International Nuclear Information System (INIS)

    Pysz, M.A.; Gambhir, S.S.; Willmann, J.K.

    2010-01-01

    In vivo molecular imaging has a great potential to impact medicine by detecting diseases in early stages (screening), identifying extent of disease, selecting disease- and patient-specific treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current clinical molecular imaging approaches primarily use positron-emission tomography (PET) or single photon-emission computed tomography (SPECT)-based techniques. In ongoing preclinical research, novel molecular targets of different diseases are identified and, sophisticated and multifunctional contrast agents for imaging these molecular targets are developed along with new technologies and instrumentation for multi-modality molecular imaging. Contrast-enhanced molecular ultrasound (US) with molecularly-targeted contrast microbubbles is explored as a clinically translatable molecular imaging strategy for screening, diagnosing, and monitoring diseases at the molecular level. Optical imaging with fluorescent molecular probes and US imaging with molecularly-targeted microbubbles are attractive strategies as they provide real-time imaging, are relatively inexpensive, produce images with high spatial resolution, and do not involve exposure to ionizing irradiation. Raman spectroscopy/microscopy has emerged as a molecular optical imaging strategy for ultrasensitive detection of multiple biomolecules/biochemicals with both in vivo and ex vivo versatility. Photoacoustic imaging is a hybrid of optical and US techniques involving optically-excitable molecularly-targeted contrast agents and quantitative detection of resulting oscillatory contrast agent movement with US. Current preclinical findings and advances in instrumentation, such as endoscopes and microcatheters, suggest that these molecular imaging methods have numerous potential clinical applications and will be translated into clinical use in the near future.

  16. Efficient Management of High-Throughput Screening Libraries with SAVANAH

    DEFF Research Database (Denmark)

    List, Markus; Elnegaard, Marlene Pedersen; Schmidt, Steffen

    2017-01-01

    ) sample information from the library to experimental results from the assay plates. All results can be exported to the R statistical environment or piped into HiTSeekR (http://hitseekr.compbio.sdu.dk) for comprehensive follow-up analyses. In summary, SAVANAH supports the HTS community in managing...... for such screens are molecular libraries, that is, microtiter plates with solubilized reagents such as siRNAs, shRNAs, miRNA inhibitors or mimics, and sgRNAs, or small compounds, that is, drugs. These reagents are typically condensed to provide enough material for covering several screens. Library plates thus need...... to be serially diluted before they can be used as assay plates. This process, however, leads to an explosion in the number of plates and samples to be tracked. Here, we present SAVANAH, the first tool to effectively manage molecular screening libraries across dilution series. It conveniently links (connects...

  17. Global cost-effectiveness of GDM screening and management

    DEFF Research Database (Denmark)

    Weile, Louise K K; Kahn, James G; Marseille, Elliot

    2015-01-01

    a systematic search and abstraction of cost-effectiveness and cost-utility studies from 2002 to 2014. We standardized all findings to 2014 US dollars. We found that cost-effectiveness ratios varied widely. Most variation was found to be due to differences in geographic setting, diagnostic criteria...... and intervention approaches, and outcomes (e.g., inclusion or exclusion of long-term type 2 diabetes risk and associated costs). We concluded that incorporation of long-term benefits of GDM screening and treatment has huge impact on cost-effectiveness estimates. Based on the large methodological heterogeneity...

  18. COSMO-RS-based extractant screening for phenol extraction as model system

    NARCIS (Netherlands)

    Burghoff, B.; Goetheer, E.L.V.; Haan, A.B. de

    2008-01-01

    The focus of this investigation is the development of a fast and reliable extractant screening approach. Phenol extraction is selected as the model process. A quantum chemical conductor-like screening model for real solvents (COSMO-RS) is combined with molecular design considerations. For this

  19. Molecular modeling

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2009-01-01

    Full Text Available The use of computational chemistry in the development of novel pharmaceuticals is becoming an increasingly important tool. In the past, drugs were simply screened for effectiveness. The recent advances in computing power and the exponential growth of the knowledge of protein structures have made it possible for organic compounds to be tailored to decrease the harmful side effects and increase the potency. This article provides a detailed description of the techniques employed in molecular modeling. Molecular modeling is a rapidly developing discipline, and has been supported by the dramatic improvements in computer hardware and software in recent years.

  20. [Screening of anti-aging active ingredients and mechanism analysis based on molecular docking technology].

    Science.gov (United States)

    Du, Ran-Feng; Zhang, Xiao-Hua; Ye, Xiao-Tong; Yu, Wen-Kang; Wang, Yun

    2016-07-01

    Dampness evil is the source of all diseases, which is easy to cause disease and promote aging, while aging could also promote the occurence and development of diseases. In this paper, the relationship between the dampness evil and aging would be discussed, to find the anti-aging active ingredients in traditional Chinese medicine (TCM), and analyze the anti-aging mechanism of dampness eliminating drug. Molecular docking technology was used, with aging-related mammalian target of rapamycin as the docking receptors, and chemical components of Fuling, Sangzhi, Mugua, Yiyiren and Houpo as the docking molecules, to preliminarily screen the anti-aging active ingredients in dampness eliminating drug. Through the comparison with active drugs already on the market (temsirolimus and everolimus), 12 kinds of potential anti-aging active ingredients were found, but their drug gability still needs further study. The docking results showed that various components in the dampness eliminating drug can play anti-aging activities by acting on mammalian target of rapamycin. This result provides a new thought and direction for the method of delaying aging by eliminating dampness. Copyright© by the Chinese Pharmaceutical Association.

  1. Discovery of Novel Inhibitors for Nek6 Protein through Homology Model Assisted Structure Based Virtual Screening and Molecular Docking Approaches

    Directory of Open Access Journals (Sweden)

    P. Srinivasan

    2014-01-01

    Full Text Available Nek6 is a member of the NIMA (never in mitosis, gene A-related serine/threonine kinase family that plays an important role in the initiation of mitotic cell cycle progression. This work is an attempt to emphasize the structural and functional relationship of Nek6 protein based on homology modeling and binding pocket analysis. The three-dimensional structure of Nek6 was constructed by molecular modeling studies and the best model was further assessed by PROCHECK, ProSA, and ERRAT plot in order to analyze the quality and consistency of generated model. The overall quality of computed model showed 87.4% amino acid residues under the favored region. A 3 ns molecular dynamics simulation confirmed that the structure was reliable and stable. Two lead compounds (Binding database ID: 15666, 18602 were retrieved through structure-based virtual screening and induced fit docking approaches as novel Nek6 inhibitors. Hence, we concluded that the potential compounds may act as new leads for Nek6 inhibitors designing.

  2. Screening a library of household substances for inhibitors of phosphatases: An introduction to high-throughput screening.

    Science.gov (United States)

    Taylor, Ann T S

    2005-01-01

    Library screening methods are commonly used in industry and research. This article describes an experiment that screens a library of household substances for properties that would make a good "drug," including enzyme inhibition, neutral pH, and nondenaturing to proteins, using wheat germ acid phosphatase as the target protein. An adaptation of the experiment appropriate for lower level biochemistry or outreach is also described. This work was supported by Wabash College through the Haines Fund for the Study of Biochemistry and the National Science Foundation through Grant DUE 0126242. Copyright © 2005 International Union of Biochemistry and Molecular Biology, Inc.

  3. A non-biological method for screening active components against influenza virus from traditional Chinese medicine by coupling a LC column with oseltamivir molecularly imprinted polymers.

    Directory of Open Access Journals (Sweden)

    Ya-Jun Yang

    Full Text Available To develop a non-biological method for screening active components against influenza virus from traditional Chinese medicine (TCM extraction, a liquid chromatography (LC column prepared with oseltamivir molecularly imprinted polymer (OSMIP was employed with LC-mass spectrometry (LC-MS. From chloroform extracts of compound TCM liquid preparation, we observed an affinitive component m/z 249, which was identified to be matrine following analysis of phytochemical literatures, OSMIP-LC column on-line of control compounds and MS/MS off-line. The results showed that matrine had similar bioactivities with OS against avian influenza virus H9N2 in vitro for both alleviating cytopathic effect and hemagglutination inhibition and that the stereostructures of these two compounds are similar while their two-dimensional structures were different. In addition, our results suggested that the bioactivities of those affinitive compounds were correlated with their chromatographic behaviors, in which less difference of the chromatographic behaviors might have more similar bioactivities. This indicates that matrine is a potential candidate drug to prevent or cure influenza for human or animal. In conclusion, the present study showed that molecularly imprinted polymers can be used as a non-biological method for screening active components against influenza virus from TCM.

  4. Cellular and molecular screening of connective tissue dysplasia in adolescent athletes (pilot study

    Directory of Open Access Journals (Sweden)

    M. V. Dvornichenko

    2017-01-01

    Full Text Available The purpose of the study is to evaluate the cellular and molecular parameters of bone remodeling in the blood as potential markers of undifferentiated forms of connective tissue dysplasiaMaterials and methods. The structural and functional status of cellular elements of in vitro culturing of mononuclear leukocytes of peripheral blood in adolescent athletes connected with phenotypic manifestations of undifferentiated connective tissue dysplasia (UCTD were investigated. 25 pupils of sport schools from 10–14 years old (main disciplines: figure skating, gymnastics, athletics were examined with the help of express analysis. The average age of the examined adolescents was (12,0 ± 1,7 years. Clinical examination of adolescents allowed ranking the UCTD signs on a scale of 4–11,5 points.Results. A comparison of questionnaire survey results and an evaluation of bone remodeling distant markers allowed the revelation of 2 groups in the distribution of adolescent athletes: those with minimal signs of UCTD (scores lesser than 7 points – 10 pupils, and those with expressed UCTD phenotype (scores are equal or more than 7 points –15 pupils. Significant statistical decrease in the content of collagen type I degradation products (CrossLaps (by 80% and ionized calcium (by 5% has been determined in the peripheral blood of adolescent athletes with expressed UCTD phenotype. In conditions of short-term 72-h cultivation of mononuclear leukocytes in the presence of a 3D matrix imitating the properties of the mineral substance of the regenerating bone tissue, morphofunctional features of cellular reaction in adolescent athletes with clinical manifestations of UCTD, as well the heterogeneity of the cell population associated with the appearance of cells with an osteoblast-like phenotype in the blood have been revealed. The results of investigation propose the use of distant cellular and molecular parameters of bone remodeling to screen the mechanisms and dynamics

  5. New molecular data shed light on the global phylogeny and species limits of the Rhipicephalus sanguineus complex.

    Science.gov (United States)

    Hekimoğlu, Olcay; Sağlam, İsmail K; Özer, Nurdan; Estrada-Peña, Agustin

    2016-07-01

    The Rhipicephalus sanguineus complex is a group of closely related tick species distributed all around the world. In this study, using mitochondrial 16S ribosomal DNA, new specimens of R sanguineus sensu lato from Turkey and Rhipicephalus camicasi from Kenya, were evaluated together with available sequences of this complex in GenBank. Our objectives were to delimit the complex, re-evaluate its global phylogeny and develop a reconstruction of its biogeographic history. Given Turkey's geographical location and its neighboring status within Africa, Asia and Europe, molecular information of R. sanguineus s.l. species from this region could have important implications both on a regional and global scale. Phylogenetic trees obtained with three methods (Bayesian, Maximum Likelihood and Maximum Parsimony) were highly similar and consensus trees gave the same branching patterns and similar node support values. A total of four different clades with up to 9 Operational Taxonomic Units formed strong monophyletic groups. Biogeographic reconstructions demonstrated the importance of populations in Middle East (Turkey) in the spread of the group from Europe to Africa and Asia. Data supported previous conclusions on the existence of two species of R. sanguineus s.l. in South America and the strong molecular similarity between R. camicasi and the so-called tropical lineage of R. sanguineus s.l. These results point to the need of a re-evaluation of most specimens designated as R. sanguineus s.l. in East Europe, Middle East, Africa and Asia after an adequate re-description of this taxon. Copyright © 2016 Elsevier GmbH. All rights reserved.

  6. Triagem auditiva neonatal: das alterações auditivas à análise molecular Newborn hearing screening: from audiological alterations to molecular analyses

    Directory of Open Access Journals (Sweden)

    Jaqueline Medeiros de Mello

    2011-10-01

    Full Text Available OBJETIVO: verificar a prevalência da deficiência auditiva em um programa de triagem auditiva neonatal e investigar mutações do gene GJB2 naqueles com suspeita de deficiência auditiva. MÉTODO: foi realizado estudo longitudinal com 908 RN a termo, pós-termo e pré-termo que foram submetidos à realização da triagem auditiva por meio do teste de Emissão Otoacústica Evocada por Estímulo Transiente (EOA-T e reflexo cócleo-palpebral (RCP. Para os recém-nascidos, em que houve falha na triagem auditiva em uma ou ambas as orelhas, eram encaminhados para uma segunda avaliação. No reteste, quando o teste de EOA-T resultasse em não passa em uma ou ambas as orelhas, a criança era encaminhada para avaliação e conduta otorrinolaringológica. Após realização do Potencial Evocado Auditivo de Tronco Encefálico (PEATE a equipe de avaliadores decidia se deveria encaminhar a criança para investigação da mutação. Quando havia suspeita de deficiência auditiva era colhido 3 mL de sangue venoso periférico para a pesquisa de mutação do gene da conexina 26. RESULTADOS: foi constatado a presença de deficiência auditiva condutiva em 2 recém-nascidos (0,22% e neurossensorial em 1 (0,11%. Na criança com deficiência auditiva neurossensorial foi detectada a presença da mutação 35delG. CONCLUSÃO: a avaliação audiológica em conjunto com exames moleculares das principais mutações do gene GJB2 em recém-nascidos com suspeita da deficiência auditiva contribuiu para a rapidez do diagnóstico audiológico, visando uma intervenção precoce, aconselhamento genético e prognóstico educacional da criança.PURPOSE: to assess the prevalence of hearing loss in a newborn hearing screening program and investigate mutations in the GJB2 gene in those with suspected hearing loss. METHOD: we performed longitudinal study of 908 term infants, post-term and preterm infants who underwent hearing screening by the test Emission Transient Evoked

  7. Developmental screening in South Africa: comparing the national ...

    African Journals Online (AJOL)

    parent completed screening tool, instead of a clinician administered .... velopment on the following areas, global/ cognitive, ex- ... needed for other services such as occupational therapy, ..... fy Developmental-Behavioral Problems in Their Chil-.

  8. Pharmacist-led screening in sexually transmitted infections: current perspectives

    Directory of Open Access Journals (Sweden)

    Wood H

    2018-06-01

    Full Text Available Helen Wood, Sajni Gudka School of Allied Health, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, WA, Australia Introduction: Sexually transmitted infection (STI screening is a crucial initiative that aims to reduce the increasing global prevalence of many common STIs such as chlamydia, gonorrhea, and herpes simplex virus (HSV. Many STIs are either asymptomatic or show mild symptoms that are often attributed to other infections; hence, screening is the only way to identify – and by extension, treat – them. In this way, the spread of STIs can be reduced, and the health implications of an untreated STI are minimized. Community pharmacies could provide an avenue to convenient, confidential STI screening by using noninvasive or minimally invasive sample collection techniques that are used by the consumer or pharmacist. We identified the most common STIs found globally and investigated the current and potential role of pharmacists in provision of STI screening interventions.Discussion: There is sufficient evidence for pharmacy-based chlamydia screening, with many consumers and pharmacists finding it an acceptable and highly valued service. Some evidence was found for pharmacy-based gonorrhea, hepatitis B virus (HBV, and human immunodeficiency virus (HIV screening. Appropriate sample collection for gonorrhea screening needs to be further examined in a pharmacy setting. HBV screening presented an increased risk of personal injury to pharmacists through the collection of whole blood specimens, which could be reduced through consumer self-sampling. Pharmacist-collected specimens for HIV is less risky as an oral swab can be used, nullifying the risk of transmission; but pre- and post-screen consultations can be time-intensive; hence, pharmacists would require remuneration to provide an ongoing HIV screening service. Not enough evidence was found for syphilis screening through community pharmacies; more studies are

  9. Vision-Augmented Molecular Dynamics Simulation of Nanoindentation

    Directory of Open Access Journals (Sweden)

    Rajab Al-Sayegh

    2015-01-01

    Full Text Available We present a user-friendly vision-augmented technique to carry out atomic simulation using hand gestures. The system is novel in its concept as it enables the user to directly manipulate the atomic structures on the screen, in 3D space using hand gestures, allowing the exploration and visualisation of molecular interactions at different relative conformations. The hand gestures are used to pick and place atoms on the screen allowing thereby the ease of carrying out molecular dynamics simulation in a more efficient way. The end result is that users with limited expertise in developing molecular structures can now do so easily and intuitively by the use of body gestures to interact with the simulator to study the system in question. The proposed system was tested by simulating the crystal anisotropy of crystalline silicon during nanoindentation. A long-range (Screened bond order Tersoff potential energy function was used during the simulation which revealed the value of hardness and elastic modulus being similar to what has been found previously from the experiments. We anticipate that our proposed system will open up new horizons to the current methods on how an MD simulation is designed and executed.

  10. Quantitative Structure-Activity Relationship Modeling Coupled with Molecular Docking Analysis in Screening of Angiotensin I-Converting Enzyme Inhibitory Peptides from Qula Casein Hydrolysates Obtained by Two-Enzyme Combination Hydrolysis.

    Science.gov (United States)

    Lin, Kai; Zhang, Lanwei; Han, Xue; Meng, Zhaoxu; Zhang, Jianming; Wu, Yifan; Cheng, Dayou

    2018-03-28

    In this study, Qula casein derived from yak milk casein was hydrolyzed using a two-enzyme combination approach, and high angiotensin I-converting enzyme (ACE) inhibitory activity peptides were screened by quantitative structure-activity relationship (QSAR) modeling integrated with molecular docking analysis. Hydrolysates (casein presents an excellent source to produce ACE inhibitory peptides.

  11. AMMOS: A Software Platform to Assist in silico Screening

    Directory of Open Access Journals (Sweden)

    Lagorce D.

    2009-12-01

    Full Text Available Three software packages based on the common platform of AMMOS (Automated Molecular Mechanics Optimization tool for in silico Screening for assisting virtual ligand screening purposes have been recently developed. DG-AMMOS allows generation of 3D conformations of small molecules using distance geometry and molecular mechanics optimization. AMMOS_SmallMol is a package for structural refinement of compound collections that can be used prior to docking experiments. AMMOS_ProtLig is a package for energy minimization of protein-ligand complexes. It performs an automatic procedure for molecular mechanics minimization at different levels of flexibility - from rigid to fully flexible structures of both the ligand and the receptor. The packages have been tested on small molecules with a high structural diversity and proteins binding sites of completely different geometries and physicochemical properties. The platform is developed as an open source software and can be used in a broad range of in silico drug design studies.

  12. Molecular Modelling

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2009-12-01

    Full Text Available

    The use of computational chemistry in the development of novel pharmaceuticals is becoming an increasingly important
    tool. In the past, drugs were simply screened for effectiveness. The recent advances in computing power and
    the exponential growth of the knowledge of protein structures have made it possible for organic compounds to tailored to
    decrease harmful side effects and increase the potency. This article provides a detailed description of the techniques
    employed in molecular modeling. Molecular modelling is a rapidly developing discipline, and has been supported from
    the dramatic improvements in computer hardware and software in recent years.

  13. Variable expression of molecular markers in juvenile nasopharyngeal angiofibroma.

    Science.gov (United States)

    Mishra, A; Pandey, A; Mishra, S C

    2017-09-01

    Molecular categorisation may explain the wide variation in the clinical characteristics of juvenile nasopharyngeal angiofibroma. Variations in molecular markers in juvenile nasopharyngeal angiofibroma in an Indian population were investigated and compared with global reports. Variable molecular marker expression was demonstrated at the regional and global levels. A wide variation in molecular characteristics is evident. Molecular data have been reported for only 11 countries, indicating a clear geographical bias. Only 58 markers have been studied, and most are yet to be validated. Research into the molecular epidemiology of juvenile nasopharyngeal angiofibroma is still in its infancy. Although the molecular variation is not well understood, data obtained so far have prompted important research questions. Hence, multicentre collaborative molecular studies are needed to establish the aetiopathogenesis and establish molecular surrogates for clinical characteristics.

  14. Achieving public and global health competencies: A teaching case study of Botswana's cervical cancer screening program.

    Science.gov (United States)

    Okatch, Harriet; Sowicz, Timothy Joseph; Teng, Helen; Ramogola-Masire, Doreen; Buttenheim, Alison M

    2018-02-09

    To design and implement a case study on the cervical cancer screening program in Botswana to teach public and global health competencies to undergraduate nursing students. The case study was developed following a review of the literature on the epidemiology and health policies of cervical cancer in Botswana, and an interview with an obstetrician/gynecologist engaged in both clinical practice and research in Botswana. The case study has been implemented over seven semesters to students enrolled in the Nursing in the Community course at the University of Pennsylvania. Approximately 75-100 students are enrolled each semester. Student's perceptions of epidemiologic skills gained and group functioning. Students responded to an open-ended question about lessons learned and offered suggestions to improve the learning experience. Faculty assessment of student deliverables demonstrated that students achieved the learning objectives and mastered necessary competencies. More than 70% (n = 69) of the students indicated that they acquired relevant skills at greater than a satisfactory level. Generally, students had great experiences working in groups measured across five dimensions: engagement/contribution, creativity/resilience, on task/works independently, social interaction/communication, and preparedness. However, isolated cases of poor group functioning were reported for engagement/contribution, and creativity/resilience. The case study, which has been revised with respect to length, content and group processes, has been valuable in educating undergraduate nursing students in a more engaging way that mimics real life public health nursing scenarios. Students achieved both public and global health competencies through participation in the case study. © 2018 Wiley Periodicals, Inc.

  15. Molecular screening of compounds to the predicted Protein-Protein Interaction site of Rb1-E7 with p53- E6 in HPV

    Science.gov (United States)

    Shaikh, Faraz; Sanehi, Parvish; Rawal, Rakesh

    2012-01-01

    Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. Human Papillomaviruses (HPVs) which are heterogeneous groups of small double stranded DNA viruses are considered as the primary cause of cervical cancer, involved in 90% of all Cervical Cancers. Two early HPV genes, E6 and E7, are known to play crucial role in tumor formation. E6 binds with p53 and prevents its translocation and thereby inhibit the ability of p53 to activate or repress target genes. E7 binds to hypophosphorylated Rb and thereby induces cells to enter into premature S-phase by disrupting Rb-E2F complexes. The strategy of the research work was to target the site of interaction of Rb1 -E7 & p53-E6. A total of 88 compounds were selected for molecular screening, based on comprehensive literature survey for natural compounds with anti-cancer activity. Molecular docking analysis was carried out with Molegro Virtual Docker, to screen the 88 chosen compounds and rank them according to their binding affinity towards the site of interaction of the viral oncoproteins and human tumor suppressor proteins. The docking result revealed that Nicandrenone a member of Withanolides family of chemical compounds as the most likely molecule that can be used as a candidate drug against HPV induced cervical cancer. Abbreviations HPV - Human Papiloma Virus, HTSP - Human Tumor Suppressor Proteins, VOP - Viral oncoproteins. PMID:22829740

  16. A new focus for the International Cancer Screening Network

    Science.gov (United States)

    The ICSN is thinking about how to take advantage of the nearly three decades of work in cancer screening program research and implementation and reach out more actively to low- and middle-income countries considering screening. For that purpose, ICSN is migrating from its historical place under NCI Division of Cancer Control and Population Sciences to assume its new role within the Center for Global Health.

  17. Molecular Dynamics Pinpoint the Global Fluorine Effect in Balanoid Binding to PKCε and PKA.

    Science.gov (United States)

    Hardianto, Ari; Liu, Fei; Ranganathan, Shoba

    2018-02-26

    (-)-Balanol is an adenosine triphosphate mimic that inhibits protein kinase C (PKC) isozymes and cAMP-dependent protein kinase (PKA) with limited selectivity. While PKA is known as a tumor promoter, PKC isozymes can be tumor promoters or suppressors. In particular, PKCε is frequently involved in tumorigenesis and a potential target for anticancer drugs. We recently reported that stereospecific fluorination of balanol yielded a balanoid with enhanced selectivity for PKCε over other PKC isozymes and PKA, although the global fluorine effect behind the selectivity enhancement is not fully understood. Interestingly, in contrast to PKA, PKCε is more sensitive to this fluorine effect. Here we investigate the global fluorine effect on the different binding responses of PKCε and PKA to balanoids using molecular dynamics (MD) simulations. For the first time to the best of our knowledge, we found that a structurally equivalent residue in each kinase, Thr184 in PKA and Ala549 in PKCε, is essential for the different binding responses. Furthermore, the study revealed that the invariant Lys, Lys73 in PKA and Lys437 in PKCε, already known to have a crucial role in the catalytic activity of kinases, serves as the main anchor for balanol binding. Overall, while Thr184 in PKA attenuates the effect of fluorination, Ala549 permits remote response of PKCε to fluorine substitution, with implications for rational design of future balanol-based PKCε inhibitors.

  18. The Diabetic Retinopathy Screening Workflow

    Science.gov (United States)

    Bolster, Nigel M.; Giardini, Mario E.; Bastawrous, Andrew

    2015-01-01

    Complications of diabetes mellitus, namely diabetic retinopathy and diabetic maculopathy, are the leading cause of blindness in working aged people. Sufferers can avoid blindness if identified early via retinal imaging. Systematic screening of the diabetic population has been shown to greatly reduce the prevalence and incidence of blindness within the population. Many national screening programs have digital fundus photography as their basis. In the past 5 years several techniques and adapters have been developed that allow digital fundus photography to be performed using smartphones. We review recent progress in smartphone-based fundus imaging and discuss its potential for integration into national systematic diabetic retinopathy screening programs. Some systems have produced promising initial results with respect to their agreement with reference standards. However further multisite trialling of such systems’ use within implementable screening workflows is required if an evidence base strong enough to affect policy change is to be established. If this were to occur national diabetic retinopathy screening would, for the first time, become possible in low- and middle-income settings where cost and availability of trained eye care personnel are currently key barriers to implementation. As diabetes prevalence and incidence is increasing sharply in these settings, the impact on global blindness could be profound. PMID:26596630

  19. Screening for nutritional rickets in a community.

    Science.gov (United States)

    Pettifor, John M

    2016-11-01

    Concern has been expressed about the rising incidence of nutritional rickets with its associated long-term sequelae in children globally. In order to address the condition worldwide, it is imperative that accurate figures of its incidence are available particularly in at-risk communities. In order to obtain these figures, various screening tools and diagnostic criteria have been used with no standardization of methodologies, resulting in varying prevalences which may under- or over-estimate the prevalence depending of the techniques used. This review discusses the advantages and disadvantages of various screening tests used to diagnose rickets in communities. Clinical signs characteristic of rachitic deformities have been used extensively, but are likely to over-estimate the prevalence and are dependent on the clinical skills of the observer. Biochemical tests such as alkaline phosphatase and 25-hydroxyvitamin D have also been proposed. There is no consensus on the usefulness of alkaline phosphatase as a screening tool, while there is general agreement that the measurement of vitamin D status is unhelpful in screening for rickets. Finally, the confirmation of the presence of active rickets in suspected infants and children is dependent on radiographic findings, although these may be less helpful in adolescents whose growth plates might be closed or nearly so. In order to obtain uniformity in screening for rickets globally, the is a need for consensus among public health specialists, paediatric endocrinologists and those interested in paediatric bone disease as to the best methods to be employed to determine the prevalence of rickets, particularly in communities with limited resources. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach

    Science.gov (United States)

    2016-03-01

    proportion of smokers , former 146 smokers and never smokers was not different between cases and controls. 147 Detection of DNA Methylation 148 We...highest risk smokers for an expensive screening modality such as CT scanning. Hypothesis: DNA methylation testing is more specific in selecting those...with non -cancerous nodules, and have completed the writing of a manuscript containing these results. The abstract of that manuscript is as follows

  1. Genetic and epigenetic markers in colorectal cancer screening: recent advances.

    Science.gov (United States)

    Singh, Manish Pratap; Rai, Sandhya; Suyal, Shradha; Singh, Sunil Kumar; Singh, Nand Kumar; Agarwal, Akash; Srivastava, Sameer

    2017-07-01

    Colorectal cancer (CRC) is a heterogenous disease which develops from benign intraepithelial lesions known as adenomas to malignant carcinomas. Acquired alterations in Wnt signaling, TGFβ, MAPK pathway genes and clonal propagation of altered cells are responsible for this transformation. Detection of adenomas or early stage cancer in asymptomatic patients and better prognostic and predictive markers is important for improving the clinical management of CRC. Area covered: In this review, the authors have evaluated the potential of genetic and epigenetic alterations as markers for early detection, prognosis and therapeutic predictive potential in the context of CRC. We have discussed molecular heterogeneity present in CRC and its correlation to prognosis and response to therapy. Expert commentary: Molecular marker based CRC screening methods still fail to gain trust of clinicians. Invasive screening methods, molecular heterogeneity, chemoresistance and low quality test samples are some key challenges which need to be addressed in the present context. New sequencing technologies and integrated omics data analysis of individual or population cohort results in GWAS. MPE studies following a GWAS could be future line of research to establish accurate correlations between CRC and its risk factors. This strategy would identify most reliable biomarkers for CRC screening and management.

  2. Screening for novel laccase-producing microbes.

    Science.gov (United States)

    Kiiskinen, L-L; Rättö, M; Kruus, K

    2004-01-01

    To discover novel laccases potential for industrial applications. Fungi were cultivated on solid media containing indicator compounds that enabled the detection of laccases as specific colour reactions. The indicators used were Remazol Brilliant Blue R (RBBR), Poly R-478, guaiacol and tannic acid. The screening work resulted in isolation of 26 positive fungal strains. Liquid cultivations of positive strains confirmed that four efficient laccase producers were found in the screening. Biochemical characteristics of the four novel laccases were typical for fungal laccases in terms of molecular weight, pH optima and pI. The laccases showed good thermal stability at 60 degrees C. Plate-test screening based on polymeric dye compounds, guaiacol and tannic acid is an efficient way to discover novel laccase producers. The results indicated that screening for laccase activity can be performed with guaiacol and RBBR or Poly R-478. Laccases have many potential industrial applications including textile dye decolourization, delignification of pulp and effluent detoxification. It is essential to find novel, efficient enzymes to further develop these applications. This study showed that relatively simple plate test screening method can be used for discovery of novel laccases. Copyright 2004 The Society for Applied Microbiology

  3. Performance of machine learning methods for ligand-based virtual screening.

    Science.gov (United States)

    Plewczynski, Dariusz; Spieser, Stéphane A H; Koch, Uwe

    2009-05-01

    Computational screening of compound databases has become increasingly popular in pharmaceutical research. This review focuses on the evaluation of ligand-based virtual screening using active compounds as templates in the context of drug discovery. Ligand-based screening techniques are based on comparative molecular similarity analysis of compounds with known and unknown activity. We provide an overview of publications that have evaluated different machine learning methods, such as support vector machines, decision trees, ensemble methods such as boosting, bagging and random forests, clustering methods, neuronal networks, naïve Bayesian, data fusion methods and others.

  4. iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan.

    Science.gov (United States)

    Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian

    2011-06-01

    The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

  5. iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan

    Science.gov (United States)

    Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian

    2011-06-01

    The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

  6. Noninvasive molecular screening for oral precancer in Fanconi anemia patients

    NARCIS (Netherlands)

    Smetsers, Stephanie E.; Velleuer, Eunike; Dietrich, Ralf; Wu, Thijs; Brink, Arjen; Buijze, Marijke; Deeg, Dorly J H; Soulier, Jean; Leemans, C. René; Braakhuis, Boudewijn J M; Brakenhoff, Ruud H.

    2015-01-01

    LOH at chromosome arms 3p, 9p, 11q, and 17p are wellestablished oncogenetic aberrations in oral precancerous lesions and promising biomarkers to monitor the development of oral cancer. Noninvasive LOH screening of brushed oral cells is a preferable method for precancer detection in patients at

  7. Recombinant Kinase Production and Fragment Screening by NMR Spectroscopy.

    Science.gov (United States)

    Han, Byeonggu; Ahn, Hee-Chul

    2016-01-01

    During the past decade fragment-based drug discovery (FBDD) has rapidly evolved and several drugs or drug candidates developed by FBDD approach are clinically in use or in clinical trials. For example, vemurafenib, a V600E mutated BRAF inhibitor, was developed by utilizing FBDD approach and approved by FDA in 2011. In FBDD, screening of fragments is the starting step for identification of hits and lead generation. Fragment screening usually relies on biophysical techniques by which the protein-bound small molecules can be detected. NMR spectroscopy has been extensively used to study the molecular interaction between the protein and the ligand, and has many advantages in fragment screening over other biophysical techniques. This chapter describes the practical aspects of fragment screening by saturation transfer difference NMR.

  8. Photocatalytic water splitting: Materials design and high-throughput screening of molecular compositions

    Science.gov (United States)

    Khnayzer, Rony S.

    , photons of low energy are converted into higher energy light using a process termed photon upconversion. Using this technique, low energy photons supplied by the sun can be converted into light of appropriate energy to trigger electronic transitions in high energy absorbing photoactive materials without any chemical modification of the latter. We have shown, that this technology is capable of upconverting visible sunlight to sensitize wide-bandgap semiconductors such as WO3, subsequently extending the photoaction of these materials to cover a larger portion of the solar spectrum. Besides the engineering of different compositions that serve as either sensitizers or catalysts in these solar energy conversion schemes, we have designed an apparatus for parallel high-throughput screening of these photocatalytic compositions. This combinatorial approach to solar fuels photocatalysis has already led to unprecedented fundamental understanding of the generation of hydrogen gas from pure water. The activity of a series of new Ru(II) sensitizers along with Co(II) molecular WRCs were optimized under visible light excitation utilizing different experimental conditions. The multi-step mechanism of activity of selected compositions was further elucidated by pump-probe transient absorption spectroscopy.

  9. Molecular docking.

    Science.gov (United States)

    Morris, Garrett M; Lim-Wilby, Marguerita

    2008-01-01

    Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. The goal of ligand-protein docking is to predict the predominant binding mode(s) of a ligand with a protein of known three-dimensional structure. Successful docking methods search high-dimensional spaces effectively and use a scoring function that correctly ranks candidate dockings. Docking can be used to perform virtual screening on large libraries of compounds, rank the results, and propose structural hypotheses of how the ligands inhibit the target, which is invaluable in lead optimization. The setting up of the input structures for the docking is just as important as the docking itself, and analyzing the results of stochastic search methods can sometimes be unclear. This chapter discusses the background and theory of molecular docking software, and covers the usage of some of the most-cited docking software.

  10. Dynamic screening in solar and stellar nuclear reactions

    Energy Technology Data Exchange (ETDEWEB)

    Daeppen, W. [Department of Physics and Astronomy, University of Southern California, Los Angeles, CA (United States); Mussack, K. [Los Alamos National Laboratory, XTD-2, Los Alamos, NM (United States)

    2012-02-15

    In the hot, dense plasma of solar and stellar interiors, Coulomb potentials are screened, resulting in increased nuclear reaction rates. Although Salpeter's approximation for static screening is widely accepted and used in stellar modeling, the question of screening in nuclear reactions was revisited in the 1990s. In particular the issue of dynamic effects was raised by Shaviv and Shaviv, who applied the techniques of molecular dynamics to the conditions in the Sun's core in order to numerically determine the effect of screening. By directly calculating the motion of ions and electrons due to Coulomb interactions, the simulations are used to compute the effect of screening without the mean-field assumption inherent in Salpeter's approximation. In the last few years, the USC group has first reproduced Shaviv and Shaviv's numerical analysis of the screening energy, showing an effect of dynamic screening. When the consequence for the reaction-rate was computed, a rather surprising resulted, which is contrary to that from static screening theory. Our calculations showed that dynamic screening does not significantly change the reaction rate from that of the bare Coulomb potential. If this can be independently confirmed, then the effects of dynamic screening are highly relevant and should be included in stellar nuclear reaction rates (copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  11. Screening for Prediabetes Using Machine Learning Models

    Directory of Open Access Journals (Sweden)

    Soo Beom Choi

    2014-01-01

    Full Text Available The global prevalence of diabetes is rapidly increasing. Studies support the necessity of screening and interventions for prediabetes, which could result in serious complications and diabetes. This study aimed at developing an intelligence-based screening model for prediabetes. Data from the Korean National Health and Nutrition Examination Survey (KNHANES were used, excluding subjects with diabetes. The KNHANES 2010 data (n=4685 were used for training and internal validation, while data from KNHANES 2011 (n=4566 were used for external validation. We developed two models to screen for prediabetes using an artificial neural network (ANN and support vector machine (SVM and performed a systematic evaluation of the models using internal and external validation. We compared the performance of our models with that of a screening score model based on logistic regression analysis for prediabetes that had been developed previously. The SVM model showed the areas under the curve of 0.731 in the external datasets, which is higher than those of the ANN model (0.729 and the screening score model (0.712, respectively. The prescreening methods developed in this study performed better than the screening score model that had been developed previously and may be more effective method for prediabetes screening.

  12. Strongyloidiasis--an insight into its global prevalence and management.

    Directory of Open Access Journals (Sweden)

    Santhosh Puthiyakunnon

    2014-08-01

    Full Text Available Strongyloides stercoralis, an intestinal parasitic nematode, infects more than 100 million people worldwide. Strongyloides are unique in their ability to exist as a free-living and autoinfective cycle. Strongyloidiasis can occur without any symptoms or as a potentially fatal hyperinfection or disseminated infection. The most common risk factors for these complications are immunosuppression caused by corticosteroids and infection with human T-lymphotropic virus or human immunodeficiency virus. Even though the diagnosis of strongyloidiasis is improved by advanced instrumentation techniques in isolated and complicated cases of hyperinfection or dissemination, efficient guidelines for screening the population in epidemiological surveys are lacking.In this review, we have discussed various conventional methods for the diagnosis and management of this disease, with an emphasis on recently developed molecular and serological methods that could be implemented to establish guidelines for precise diagnosis of infection in patients and screening in epidemiological surveys. A comprehensive analysis of various cases reported worldwide from different endemic and nonendemic foci of the disease for the last 40 years was evaluated in an effort to delineate the global prevalence of this disease. We also updated the current knowledge of the various clinical spectrum of this parasitic disease, with an emphasis on newer molecular diagnostic methods, treatment, and management of cases in immunosuppressed patients.Strongyloidiasis is considered a neglected tropical disease and is probably an underdiagnosed parasitic disease due to its low parasitic load and uncertain clinical symptoms. Increased infectivity rates in many developed countries and nonendemic regions nearing those in the most prevalent endemic regions of this parasite and the increasing transmission potential to immigrants, travelers, and immunosuppressed populations are indications for initiating an

  13. SUPER-screening

    Energy Technology Data Exchange (ETDEWEB)

    Brax, Philippe, E-mail: Philippe.Brax@cea.fr [Institut de Physique Theorique, CEA, IPhT, CNRS, URA 2306, F-91191Gif/Yvette Cedex (France); Davis, Anne-Christine, E-mail: A.C.Davis@damtp.cam.ac.uk [DAMTP, Centre for Mathematical Sciences, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA (United Kingdom); Sakstein, Jeremy, E-mail: J.A.Sakstein@damtp.cam.ac.uk [DAMTP, Centre for Mathematical Sciences, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA (United Kingdom)

    2013-02-26

    We present a framework for embedding scalar–tensor models of screened modified gravity such as chameleons, symmetrons and environmental dilatons into global supersymmetry. This achieved by secluding the dark sector from both the observable and supersymmetry breaking sectors. We examine the resulting supersymmetric features in a model-independent manner and find that, when the theory follows from an underlying supergravity, the mediation of supersymmetry breaking to the dark sector induces a soft mass for the scalar of order the gravitino mass. This is enough to forbid the construction of supersymmetric symmetrons and ensures that when other screening mechanisms operate, no object in the Universe is unscreened thereby precluding any observable signatures. In view of a possible origin of modified gravity within fundamental physics, we find that only no-scale models can circumvent these features. We also present a novel mechanism where the coupling of the scalar to two other scalars charged under U(1) can dynamically generate a small cosmological constant at late times in the form of a Fayet–Iliopoulos term.

  14. THE GLOBAL EVOLUTION OF GIANT MOLECULAR CLOUDS. II. THE ROLE OF ACCRETION

    International Nuclear Information System (INIS)

    Goldbaum, Nathan J.; Krumholz, Mark R.; Matzner, Christopher D.; McKee, Christopher F.

    2011-01-01

    We present virial models for the global evolution of giant molecular clouds (GMCs). Focusing on the presence of an accretion flow and accounting for the amount of mass, momentum, and energy supplied by accretion and star formation feedback, we are able to follow the growth, evolution, and dispersal of individual GMCs. Our model clouds reproduce the scaling relations observed in both galactic and extragalactic clouds. We find that accretion and star formation contribute roughly equal amounts of turbulent kinetic energy over the lifetime of the cloud. Clouds attain virial equilibrium and grow in such a way as to maintain roughly constant surface densities, with typical surface densities of order 50-200 M sun pc -2 , in good agreement with observations of GMCs in the Milky Way and nearby external galaxies. We find that as clouds grow, their velocity dispersion and radius must also increase, implying that the linewidth-size relation constitutes an age sequence. Lastly, we compare our models to observations of GMCs and associated young star clusters in the Large Magellanic Cloud and find good agreement between our model clouds and the observed relationship between H II regions, young star clusters, and GMCs.

  15. Data mining a small molecule drug screening representative subset from NIH PubChem.

    Science.gov (United States)

    Xie, Xiang-Qun; Chen, Jian-Zhong

    2008-03-01

    PubChem is a scientific showcase of the NIH Roadmap Initiatives. It is a compound repository created to facilitate information exchange and data sharing among the NIH Roadmap-funded Molecular Library Screening Center Network (MLSCN) and the scientific community. However, PubChem has more than 10 million records of compound information. It will be challenging to conduct a drug screening of the whole database of millions of compounds. Thus, the purpose of the present study was to develop a data mining cheminformatics approach in order to construct a representative and structure-diverse sublibrary from the large PubChem database. In this study, a new chemical diverse representative subset, rePubChem, was selected by whole-molecule chemistry-space matrix calculation using the cell-based partition algorithm. The representative subset was generated and was then subjected to evaluations by compound property analyses based on 1D and 2D molecular descriptors. The new subset was also examined and assessed for self-similarity analysis based on 2D molecular fingerprints in comparing with the source compound library. The new subset has a much smaller library size (540K compounds) with minimum similarity and redundancy without loss of the structural diversity and basic molecular properties of its parent library (5.3 million compounds). The new representative subset library generated could be a valuable structure-diverse compound resource for in silico virtual screening and in vitro HTS drug screening. In addition, the established subset generation method of using the combined cell-based chemistry-space partition metrics with pairwised 2D fingerprint-based similarity search approaches will also be important to a broad scientific community interested in acquiring structurally diverse compounds for efficient drug screening, building representative virtual combinatorial chemistry libraries for syntheses, and data mining large compound databases like the PubChem library in general.

  16. Current and future molecular diagnostics in colorectal cancer and colorectal adenoma.

    Science.gov (United States)

    Tsang, Andy Hin-Fung; Cheng, Ka-Ho; Wong, Apple Siu-Ping; Ng, Simon Siu-Man; Ma, Brigette Buig-Yue; Chan, Charles Ming-Lok; Tsui, Nancy Bo-Yin; Chan, Lawrence Wing-Chi; Yung, Benjamin Yat-Ming; Wong, Sze-Chuen Cesar

    2014-04-14

    Colorectal cancer (CRC) is one of the most prevalent cancers in developed countries. On the other hand, CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy. Since CRC develops slowly from precancerous lesions, early detection can reduce both the incidence and mortality of the disease. Fecal occult blood test is a widely used non-invasive screening tool for CRC. Although fecal occult blood test is simple and cost-effective in screening CRC, there is room for improvement in terms of the accuracy of the test. Genetic dysregulations have been found to play an important role in CRC development. With better understanding of the molecular basis of CRC, there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC. In this review, the molecular basis of CRC development, the characteristics and applications of different non-invasive molecular biomarkers, as well as the technologies available for the detection were discussed. This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state, colorectal adenoma.

  17. A new screening method for selection of desired recombinant ...

    African Journals Online (AJOL)

    A new screening method for selection of desired recombinant plasmids in molecular cloning. ... African Journal of Biotechnology ... Regarding the facts of this study, after digestion process, the products directly were subjected to ligation. Due to ...

  18. Contributions to advances in blend pellet products (BPP) research on molecular structure and molecular nutrition interaction by advanced synchrotron and globar molecular (Micro)spectroscopy.

    Science.gov (United States)

    Guevara-Oquendo, Víctor H; Zhang, Huihua; Yu, Peiqiang

    2018-04-13

    To date, advanced synchrotron-based and globar-sourced techniques are almost unknown to food and feed scientists. There has been little application of these advanced techniques to study blend pellet products at a molecular level. This article aims to provide recent research on advanced synchrotron and globar vibrational molecular spectroscopy contributions to advances in blend pellet products research on molecular structure and molecular nutrition interaction. How processing induced molecular structure changes in relation to nutrient availability and utilization of the blend pellet products. The study reviews Utilization of co-product components for blend pellet product in North America; Utilization and benefits of inclusion of pulse screenings; Utilization of additives in blend pellet products; Application of pellet processing in blend pellet products; Conventional evaluation techniques and methods for blend pellet products. The study focus on recent applications of cutting-edge vibrational molecular spectroscopy for molecular structure and molecular structure association with nutrient utilization in blend pellet products. The information described in this article gives better insight on how advanced molecular (micro)spectroscopy contributions to advances in blend pellet products research on molecular structure and molecular nutrition interaction.

  19. Clinical and molecular profile of newborns with confirmed or suspicious congenital adrenal hyperplasia detected after a public screening program implementation.

    Science.gov (United States)

    Kopacek, Cristiane; Prado, Mayara J; da Silva, Claudia M D; de Castro, Simone M; Beltrão, Luciana A; Vargas, Paula R; Grandi, Tarciana; Rossetti, Maria L R; Spritzer, Poli Mara

    2018-04-30

    To describe the results obtained in a neonatal screening program after its implementation and to assess the clinical and molecular profiles of confirmed and suspicious congenital adrenal hyperplasia cases. A cross-sectional study was conducted. Newborns with suspected disease due to high 17-hydroxyprogesterone levels and adjusted for birth weight were selected. Classical congenital adrenal hyperplasia (salt-wasting and simple virilizing forms) was diagnosed by an increase in 17-hydroxyprogesterone levels as confirmed in the retest, clinical evaluation, and genotype determined by SNaPshot and multiplex ligation-dependent probe amplification. After 24 months, 15 classic congenital adrenal hyperplasia cases were diagnosed in a total of 217,965 newborns, with an estimated incidence of 1:14,531. From 132 patients, seven non-classical and 14 heterozygous patients were screened for CYP21A2 mutations, and 96 patients presented false positives with wild type CYP21A2. On retest, increased 17-hydroxyprogesterone levels were found in classical congenital adrenal hyperplasia patients and showed significant correlation with genotype-related classical genital adrenal hyperplasia. The most frequent mutations were IVS2-13A/C>G followed by gene deletion or rearrangement events in the classical form. In non-classical and heterozygous diseases, p.Val282Leu was the most common mutation. The results underscore the effectiveness of congenital adrenal hyperplasia neonatal screening in the public health system and indicate that the adopted strategy was appropriate. The second sample collection along with genotyping of suspected cases helped to properly diagnose both severe and milder cases and delineate them from false positive patients. Copyright © 2018. Published by Elsevier Editora Ltda.

  20. High throughput screening of starch structures using carbohydrate microarrays

    DEFF Research Database (Denmark)

    Tanackovic, Vanja; Rydahl, Maja Gro; Pedersen, Henriette Lodberg

    2016-01-01

    In this study we introduce the starch-recognising carbohydrate binding module family 20 (CBM20) from Aspergillus niger for screening biological variations in starch molecular structure using high throughput carbohydrate microarray technology. Defined linear, branched and phosphorylated...

  1. Earthworm-Derived Pore-Forming Toxin Lysenin and Screening of Its Inhibitors

    Directory of Open Access Journals (Sweden)

    Neelanun Sukumwang

    2013-08-01

    Full Text Available Lysenin is a pore-forming toxin from the coelomic fluid of earthworm Eisenia foetida. This protein specifically binds to sphingomyelin and induces erythrocyte lysis. Lysenin consists of 297 amino acids with a molecular weight of 41 kDa. We screened for cellular signal transduction inhibitors of low molecular weight from microorganisms and plants. The purpose of the screening was to study the mechanism of diseases using the obtained inhibitors and to develop new chemotherapeutic agents acting in the new mechanism. Therefore, our aim was to screen for inhibitors of Lysenin-induced hemolysis from plant extracts and microbial culture filtrates. As a result, we isolated all-E-lutein from an extract of Dalbergia latifolia leaves. All-E-lutein is likely to inhibit the process of Lysenin-membrane binding and/or oligomer formation rather than pore formation. Additionally, we isolated tyrosylproline anhydride from the culture filtrate of Streptomyces as an inhibitor of Lysenin-induced hemolysis.

  2. In-vitro antimicrobial screening and molecular docking studies of synthesized 2-chloro-N-(4-phenylthiazol-2-ylacetamide derivatives

    Directory of Open Access Journals (Sweden)

    Rahmat Ali

    2015-01-01

    Full Text Available Introduction: Glucosamine-6-phosphate (GlcN6P synthase biosynthetic pathway has been identified as potential targets for the development of new antimicrobial agents. Aim: A series of 2-chloro-N-(42-phenylthiazol-25-ylacetamide derivatives (3a-r was synthesized and evaluated their antimicrobial activity. Materials and Methods: The 2-chloro-N-(Para substituted phenylthiazol-25-yl acetamide (2a-c were synthesized by stirring intermediates (1a-c with 2-chloroacetylchloride in dichloromethane in the presence of K2CO3. The intermediate (2a-c were further reacted with different secondary amine such as pyrrolidine, N-methyl piperazine, N-ethyl piperazine, thiomorpholine, morpholine, piperidine etc in ethanol in presence of TEA Triethylamine (TEA to get desired compounds (3a-r. Compounds were characterized by a spectroscopic technique such as Fourier transform infraredFTIR, 1 H-NMR, 13 C-NMR, and mass spectrometry. The synthesized thiazole derivatives (3a-r were screened for anti-bacterial and anti-fungal activity against Escherichia coli, Staphylococcus aureus NCTC 6571, Pseudomonas aeruginosa NCTC 10662, CandidaC. albicans (MTCC-183, AspergillusA. niger (MTCC 281 NCTC 10418 and AspergillusA. flavus (MTCC 277. Result and Conclusion: The results of anti-bacterial screening revealed that among all the screened compounds, eight compounds viz. 3b, 3c, 3d, 3e, 3i, 3j, 3k, and 3p showed moderate to good anti-bacterial and antifungal activity having minimum inhibitory concentration (MIC between 6.25- and 25 µg/ml. While compound 3d showed the most promising antibacterial activity against E. coli and S. aureus, while the compound 3j showed promising antifungal activity with MIC value 6.25 µg/ml against C. albicans, A. niger and A. flavus. In addition, all these eight potential molecules were also examined for possible binding on enzyme GlcN6Pglucosamine-6-phosphate synthase by molecular docking studies on (PDB ID 1JXA.

  3. Evaluation of conducting a screening assessment of nutritional status of hospitalized patients. Presentation of main goals and objectives of the global health project "NutritionDay".

    Science.gov (United States)

    Jeznach-Steinhagen, Anna; Ostrowska, Joanna; Czerwonogrodzka-Senczyna, Aneta

    2016-01-01

    European Society for Clinical Nutrition and Metabolism (ESPEN) commenced in 2004 a global health project named "NutritionDay" aiming to promote awareness of proper nutritional status of hospitalized patients and to draw attention to the need for early detection of malnutrition among patients. Under the Polish law--pursunat to the regulation of the Minister of Health dated September 15, 2011 (amendment as of 27.12.2013)--a nutritional status of each patient should be assessed at the time of a hospital admission. of this study was to analyze the fulfilment of the mandatory questionnaire assessment of nutritional status at selected wards of one of Warsaw's clinical hospitals. The study included an analysis of medical records of patients hospitalized within 6 months (n = 26375). The correct fulfilment of screening questionnaire assessing nutritional status (NRS 2002 survey) and the information about patients' body weight as well as the results assessment of nutritional status were subject to the analysis. NRS 2002 questionnaire was present in only 67,14% medical records of patients, however 49.24% of them were unfilled. The obtained results confirming low degree of NRS 2002 questionnaires' fulfilment in one of the Warsaw clinical hospitals draws attention to the need for education of hospital personnel in the field of significance of screening of nutritional assessment and its regulations. The "NutritionDay" project is an interesting form to attract attention of the aforementioned problem and its global extent additionally encourage medical units to participate in the project.

  4. Rapid and selective screening of melamine in bovine milk using molecularly imprinted matrix solid-phase dispersion coupled with liquid chromatography-ultraviolet detection.

    Science.gov (United States)

    Yan, Hongyuan; Cheng, Xiaoling; Sun, Ning; Cai, Tianyu; Wu, Ruijun; Han, Kun

    2012-11-01

    A simple, convenient and high selective molecularly imprinted matrix solid-phase dispersion (MI-MSPD) using water-compatible cyromazine-imprinted polymer as adsorbent was proposed for the rapid screening of melamine from bovine milk coupled with liquid chromatography-ultraviolet detection. The molecularly imprinted polymers (MIPs) synthesized by cyromazine as dummy template and reformative methanol-water system as reaction medium showed higher affinity and selectivity to melamine, and so they were applied as the specific dispersant of MSPD to extraction of melamine and simultaneously eliminate the effect of template leakage on quantitative analysis. Under the optimized conditions, good linearity was obtained in a range of 0.24-60.0μgg(-1) with the correlation coefficient of 0.9994. The recoveries of melamine at three spiked levels were ranged from 86.0 to 96.2% with the relative standard deviation (RSD)≤4.0%. This proposed MI-MSPD method combined the advantages of MSPD and MIPs, and could be used as an alternative tool for analyzing the residues of melamine in complex milk samples. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. DG-AMMOS: a new tool to generate 3d conformation of small molecules using distance geometry and automated molecular mechanics optimization for in silico screening.

    Science.gov (United States)

    Lagorce, David; Pencheva, Tania; Villoutreix, Bruno O; Miteva, Maria A

    2009-11-13

    Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats. Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine. DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.

  6. On eliminating synchronous communication in molecular simulations to improve scalability

    Science.gov (United States)

    Straatsma, T. P.; Chavarría-Miranda, Daniel G.

    2013-12-01

    Molecular dynamics simulation, as a complementary tool to experimentation, has become an important methodology for the understanding and design of molecular systems as it provides access to properties that are difficult, impossible or prohibitively expensive to obtain experimentally. Many of the available software packages have been parallelized to take advantage of modern massively concurrent processing resources. The challenge in achieving parallel efficiency is commonly attributed to the fact that molecular dynamics algorithms are communication intensive. This paper illustrates how an appropriately chosen data distribution and asynchronous one-sided communication approach can be used to effectively deal with the data movement within the Global Arrays/ARMCI programming model framework. A new put_notify capability is presented here, allowing the implementation of the molecular dynamics algorithm without any explicit global or local synchronization or global data reduction operations. In addition, this push-data model is shown to very effectively allow hiding data communication behind computation. Rather than data movement or explicit global reductions, the implicit synchronization of the algorithm becomes the primary challenge for scalability. Without any explicit synchronous operations, the scalability of molecular simulations is shown to depend only on the ability to evenly balance computational load.

  7. Development of novel vaccines using DNA shuffling and screening strategies.

    Science.gov (United States)

    Locher, Christopher P; Soong, Nay Wei; Whalen, Robert G; Punnonen, Juha

    2004-02-01

    DNA shuffling and screening technologies recombine and evolve genes in vitro to rapidly obtain molecules with improved biological activity and fitness. In this way, genes from related strains are bred like plants or livestock and their successive progeny are selected. These technologies have also been called molecular breeding-directed molecular evolution. Recent developments in bioinformatics-assisted computer programs have facilitated the design, synthesis and analysis of DNA shuffled libraries of chimeric molecules. New applications in vaccine development are among the key features of DNA shuffling and screening technologies because genes from several strains or antigenic variants of pathogens can be recombined to create novel molecules capable of inducing immune responses that protect against infections by multiple strains of pathogens. In addition, molecules such as co-stimulatory molecules and cytokines have been evolved to have improved T-cell proliferation and cytokine production compared with the wild-type human molecules. These molecules can be used to immunomodulate vaccine responsiveness and have multiple applications in infectious diseases, cancer, allergy and autoimmunity. Moreover, DNA shuffling and screening technologies can facilitate process development of vaccine manufacturing through increased expression of recombinant polypeptides and viruses. Therefore, DNA shuffling and screening technologies can overcome some of the challenges that vaccine development currently faces.

  8. Rapid screening of operational freshwater availability using global models

    NARCIS (Netherlands)

    Straatsma, M.W.; Vermeulen, P.; Kuijper, Marijn; Bonte, Matthijs; Niele, Frank; Bierkens, M.F.P.

    Freshwater shortage already affects large parts of the world, and is expected to increase rapidly over the coming decades as a result of increased water demands and the impacts of climate change. Global-scale water risk or stress maps are available online, but these lack quantitative information on

  9. Multidisciplinary molecular diagnostics: the 9th European meeting on molecular diagnostics.

    Science.gov (United States)

    Loonen, Anne J M; Schuurman, Rob; van den Brule, Adriaan J C

    2016-01-01

    This report presents a summary of the 9th European Meeting on Molecular Diagnostics held in Noordwijk, The Netherlands, 14-16 October 2015. This 3-day conference covered many relevant topics in the field of molecular diagnostics in humans, including infectious disease, oncology, outbreak management, population-based cancer screening, standardization and quality control, chronic diseases and pharmacogenetics. Beyond these different areas, shared values are new technologies and novel technical and clinical applications. Approximately 450 participants, the majority coming from European countries, attended the meeting. Besides high quality scientific presentations, more than 35 diagnostic companies presented their latest innovations, altogether in an informal and inspiring scientific ambience.

  10. Molecular similarity measures.

    Science.gov (United States)

    Maggiora, Gerald M; Shanmugasundaram, Veerabahu

    2011-01-01

    Molecular similarity is a pervasive concept in chemistry. It is essential to many aspects of chemical reasoning and analysis and is perhaps the fundamental assumption underlying medicinal chemistry. Dissimilarity, the complement of similarity, also plays a major role in a growing number of applications of molecular diversity in combinatorial chemistry, high-throughput screening, and related fields. How molecular information is represented, called the representation problem, is important to the type of molecular similarity analysis (MSA) that can be carried out in any given situation. In this work, four types of mathematical structure are used to represent molecular information: sets, graphs, vectors, and functions. Molecular similarity is a pairwise relationship that induces structure into sets of molecules, giving rise to the concept of chemical space. Although all three concepts - molecular similarity, molecular representation, and chemical space - are treated in this chapter, the emphasis is on molecular similarity measures. Similarity measures, also called similarity coefficients or indices, are functions that map pairs of compatible molecular representations that are of the same mathematical form into real numbers usually, but not always, lying on the unit interval. This chapter presents a somewhat pedagogical discussion of many types of molecular similarity measures, their strengths and limitations, and their relationship to one another. An expanded account of the material on chemical spaces presented in the first edition of this book is also provided. It includes a discussion of the topography of activity landscapes and the role that activity cliffs in these landscapes play in structure-activity studies.

  11. Exploring the Potential of a Global Emerging Contaminant Early Warning Network through the Use of Retrospective Suspect Screening with High-Resolution Mass Spectrometry.

    Science.gov (United States)

    Alygizakis, Nikiforos A; Samanipour, Saer; Hollender, Juliane; Ibáñez, María; Kaserzon, Sarit; Kokkali, Varvara; van Leerdam, Jan A; Mueller, Jochen F; Pijnappels, Martijn; Reid, Malcolm J; Schymanski, Emma L; Slobodnik, Jaroslav; Thomaidis, Nikolaos S; Thomas, Kevin V

    2018-04-13

    A key challenge in the environmental and exposure sciences is to establish experimental evidence of the role of chemical exposure in human and environmental systems. High resolution and accurate tandem mass spectrometry (HRMS) is increasingly being used for the analysis of environmental samples. One lauded benefit of HRMS is the possibility to retrospectively process data for (previously omitted) compounds that has led to the archiving of HRMS data. Archived HRMS data affords the possibility of exploiting historical data to rapidly and effectively establish the temporal and spatial occurrence of newly identified contaminants through retrospective suspect screening. We propose to establish a global emerging contaminant early warning network to rapidly assess the spatial and temporal distribution of contaminants of emerging concern in environmental samples through performing retrospective analysis on HRMS data. The effectiveness of such a network is demonstrated through a pilot study, where eight reference laboratories with available archived HRMS data retrospectively screened data acquired from aqueous environmental samples collected in 14 countries on 3 different continents. The widespread spatial occurrence of several surfactants (e.g., polyethylene glycols ( PEGs ) and C12AEO-PEGs ), transformation products of selected drugs (e.g., gabapentin-lactam, metoprolol-acid, carbamazepine-10-hydroxy, omeprazole-4-hydroxy-sulfide, and 2-benzothiazole-sulfonic-acid), and industrial chemicals (3-nitrobenzenesulfonate and bisphenol-S) was revealed. Obtaining identifications of increased reliability through retrospective suspect screening is challenging, and recommendations for dealing with issues such as broad chromatographic peaks, data acquisition, and sensitivity are provided.

  12. Screening and characterization a RAPD marker of tobacco brown ...

    African Journals Online (AJOL)

    RAPD) methods were used to analyze F2 individuals of 82-3041 × Yunyan 84 to screen and characterize the molecular marker linked to brown-spot resistant gene. A total of 800 arbitrary decamer oligonucleotide primers were used for RAPD ...

  13. Identifying the Molecular Origin of Global Warming

    Science.gov (United States)

    Bera, Partha P.; Francisco, Joseph S.; Lee, Timothy J.

    2009-01-01

    We have investigated the physical characteristics of greenhouse gases (GHGs) to assess which properties are most important in determining the efficiency of a GHG. Chlorofluorcarbons (CFCs), hydrofluorocarbons (HFCs), perfluorocarbons (PFCs), nitrogen fluorides, and various other known atmospheric trace molecules have been included in this study. Compounds containing the halogens F or Cl have in common very polar X-F or X-Cl bonds, particularly the X-F bonds. It is shown that as more F atoms bond to the same central atom, the bond dipoles become larger as a result of the central atom becoming more positive. This leads to a linear increase in the total or integrated XF bond dipole derivatives for the molecule, which leads to a non-linear (quadratic) increase in infrared (IR) intensity. Moreover, virtually all of the X-F bond stretches occur in the atmospheric IR window as opposed to X-H stretches, which do not occur in the atmospheric window. It is concluded that molecules possessing several F atoms will always have a large radiative forcing parameter in the calculation of their global warming potential. Some of the implications for global warming and climate change are discussed.

  14. Epidemiology, aetiology, diagnosis and screening of lung cancer

    International Nuclear Information System (INIS)

    Berzinec, P.

    2006-01-01

    Lung cancer is the leading cause of cancer death globally. Smoking causes about 90 % of all lung cancer cases. Passive, i.e. involuntary smoking has been confirmed to enhance the risk of lung cancer in exposed people. Individual susceptibility is one of important factors in lung cancer formation. New knowledge in epidemiology and aetiology of lung cancer gives new possibilities in diagnostic and screening of this disease. Results of large randomised trials aimed at new technologies in lung cancer screening will be available in a few years. (author)

  15. Under the (legal radar screen: global health initiatives and international human rights obligations

    Directory of Open Access Journals (Sweden)

    Hammonds Rachel

    2012-11-01

    Full Text Available Abstract Background Given that many low income countries are heavily reliant on external assistance to fund their health sectors the acceptance of obligations of international assistance and cooperation with regard to the right to health (global health obligations is insufficiently understood and studied by international health and human rights scholars. Over the past decade Global Health Initiatives, like the Global Fund to fight AIDS, Tuberculosis and Malaria (Global Fund have adopted novel approaches to engaging with stakeholders in high and low income countries. This article explores how this experience impacted on acceptance of the international obligation to (help fulfil the right to health beyond borders. Methods The authors conducted an extensive review of international human rights law literature, transnational legal process literature, global public health literature and grey literature pertaining to Global Health Initiatives. To complement this desk work and deepen their understanding of how and why different legal norms evolve the authors conducted 19 in-depth key informant interviews with actors engaged with three stakeholders; the European Union, the United States and Belgium. The authors then analysed the interviews through a transnational legal process lens. Results Through according value to the process of examining how and why different legal norms evolve transnational legal process offers us a tool for engaging with the dynamism of developments in global health suggesting that operationalising global health obligations could advance the right to health for all. Conclusions In many low-income countries the health sector is heavily dependent on external assistance to fulfil the right to health of people thus it is vital that policies and tools for delivering reliable, long-term assistance are developed so that the right to health for all becomes more than a dream. Our research suggests that the Global Fund experience offers

  16. Under the (legal) radar screen: global health initiatives and international human rights obligations

    Science.gov (United States)

    2012-01-01

    Background Given that many low income countries are heavily reliant on external assistance to fund their health sectors the acceptance of obligations of international assistance and cooperation with regard to the right to health (global health obligations) is insufficiently understood and studied by international health and human rights scholars. Over the past decade Global Health Initiatives, like the Global Fund to fight AIDS, Tuberculosis and Malaria (Global Fund) have adopted novel approaches to engaging with stakeholders in high and low income countries. This article explores how this experience impacted on acceptance of the international obligation to (help) fulfil the right to health beyond borders. Methods The authors conducted an extensive review of international human rights law literature, transnational legal process literature, global public health literature and grey literature pertaining to Global Health Initiatives. To complement this desk work and deepen their understanding of how and why different legal norms evolve the authors conducted 19 in-depth key informant interviews with actors engaged with three stakeholders; the European Union, the United States and Belgium. The authors then analysed the interviews through a transnational legal process lens. Results Through according value to the process of examining how and why different legal norms evolve transnational legal process offers us a tool for engaging with the dynamism of developments in global health suggesting that operationalising global health obligations could advance the right to health for all. Conclusions In many low-income countries the health sector is heavily dependent on external assistance to fulfil the right to health of people thus it is vital that policies and tools for delivering reliable, long-term assistance are developed so that the right to health for all becomes more than a dream. Our research suggests that the Global Fund experience offers lessons to build on. PMID

  17. Under the (legal) radar screen: global health initiatives and international human rights obligations.

    Science.gov (United States)

    Hammonds, Rachel; Ooms, Gorik; Vandenhole, Wouter

    2012-11-15

    Given that many low income countries are heavily reliant on external assistance to fund their health sectors the acceptance of obligations of international assistance and cooperation with regard to the right to health (global health obligations) is insufficiently understood and studied by international health and human rights scholars. Over the past decade Global Health Initiatives, like the Global Fund to fight AIDS, Tuberculosis and Malaria (Global Fund) have adopted novel approaches to engaging with stakeholders in high and low income countries. This article explores how this experience impacted on acceptance of the international obligation to (help) fulfil the right to health beyond borders. The authors conducted an extensive review of international human rights law literature, transnational legal process literature, global public health literature and grey literature pertaining to Global Health Initiatives. To complement this desk work and deepen their understanding of how and why different legal norms evolve the authors conducted 19 in-depth key informant interviews with actors engaged with three stakeholders; the European Union, the United States and Belgium. The authors then analysed the interviews through a transnational legal process lens. Through according value to the process of examining how and why different legal norms evolve transnational legal process offers us a tool for engaging with the dynamism of developments in global health suggesting that operationalising global health obligations could advance the right to health for all. In many low-income countries the health sector is heavily dependent on external assistance to fulfil the right to health of people thus it is vital that policies and tools for delivering reliable, long-term assistance are developed so that the right to health for all becomes more than a dream. Our research suggests that the Global Fund experience offers lessons to build on.

  18. [Human papillomavirus testing in cervical cancer screening at a public health service of Santiago, Chile].

    Science.gov (United States)

    Terrazas, Solana; Ibáñez, Carolina; Lagos, Marcela; Poggi, Helena; Brañes, Jorge; Barriga, María Isabel; Cartagena, Jaime; Núñez, Felipe; González, Francisca; Cook, Paz; Van De Wyngard, Vanessa; Ferreccio, Catterina

    2015-01-01

    Molecular techniques for human papillomavirus (HPV) detection have a good performance as screening tests and could be included in cervical cancer early detection programs. We conducted a population-based trial comparing HPV detection and Papanicolaou as primary screening tests, in a public health service in Santiago, Chile. To describe the experience of implementing this new molecular test and present the main results of the study. Women aged 25 to 64 enrolled in three public health centers were invited to participate. In all women, samples were collected for Papanicolaou and HPV DNA testing, and naked-eye visual inspection of the cervix with acetic acid was performed. Women with any positive screening test were referred to the local area hospital for diagnostic confirmation with colposcopy and biopsy of suspicious lesions. Screening results were obtained for 8265 women, of whom 931 (11.3%) were positive to any test. The prevalence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was 1.1%; nine women had invasive cervical cancer. Sensitivities for the detection of CIN2+ were 22.1% (95% confidence interval (CI) 16.4-29.2) for Papanicolaou and 92.7% (95% CI 84.4-96.8) for HPV testing; specificities were 98.9% (95% CI 98.7-99.0) and 92.0% (95% CI 91.4-92.6) respectively. This experience showed that the implementation of a molecular test for cervical cancer screening is not a major challenge in Chile: it was well accepted by both the health team and the participants, and it may improve the effectiveness of the screening program.

  19. Exploiting PubChem for Virtual Screening.

    Science.gov (United States)

    Xie, Xiang-Qun

    2010-12-01

    IMPORTANCE OF THE FIELD: PubChem is a public molecular information repository, a scientific showcase of the NIH Roadmap Initiative. The PubChem database holds over 27 million records of unique chemical structures of compounds (CID) derived from nearly 70 million substance depositions (SID), and contains more than 449,000 bioassay records with over thousands of in vitro biochemical and cell-based screening bioassays established, with targeting more than 7000 proteins and genes linking to over 1.8 million of substances. AREAS COVERED IN THIS REVIEW: This review builds on recent PubChem-related computational chemistry research reported by other authors while providing readers with an overview of the PubChem database, focusing on its increasing role in cheminformatics, virtual screening and toxicity prediction modeling. WHAT THE READER WILL GAIN: These publicly available datasets in PubChem provide great opportunities for scientists to perform cheminformatics and virtual screening research for computer-aided drug design. However, the high volume and complexity of the datasets, in particular the bioassay-associated false positives/negatives and highly imbalanced datasets in PubChem, also creates major challenges. Several approaches regarding the modeling of PubChem datasets and development of virtual screening models for bioactivity and toxicity predictions are also reviewed. TAKE HOME MESSAGE: Novel data-mining cheminformatics tools and virtual screening algorithms are being developed and used to retrieve, annotate and analyze the large-scale and highly complex PubChem biological screening data for drug design.

  20. Usage of Capillary Electrophoresis for screening common Hemoglobinopathies

    Directory of Open Access Journals (Sweden)

    2016-06-01

    Full Text Available Hemoglobinopathies are most common inherited disorders in the world approximately 7 percent of the worldwide population and 5-6 percent of population of Iran are carriers. For control of this inherited hemoglobin disorders need to accurate screening by more advanced and more accurate methods. This study explains features of current Iran hemoglobin disorders, nominates the accessible methods for screening them and introduces the capillary zone electrophoresis as a rapid & more accurate method. The required data were extracted of various articles and then for good explanation, current Iran hemoglobinopathies properties were showed in the tables and electropherograms of important hemoglobin disorders in Iran population were provided for help to interpretation results of blood tests by capillary zone electrophoresis method. Hemoglobin disorders are including thalassemias & hemoglobin variants Disruption in the production and malfunction of globin chains cause types of hemoglobin disorders. We cannot introduce one of clinical laboratory tests as critical and basic method for screening and distinguishing types of inherited hemoglobin disorders as alone. For distinguishing the types of them must be prepared enough information and data of the hemoglobin disorders and for more accurate analysis must be used simultaneously different methods as Gel electrophoresis, High performance liquid chromatography, Isoelectric focusing, Capillary zone electrophoresis or molecular tests. The capillary electrophoresis is an accurate and rapid method for screening types of the hemoglobin disorders. Other side this method cannot analyze all of them, so must be used biochemical, biophysical and molecular methods for confirmation the results. This review showed we can use the capillary electrophoresis and HPLC as two complementary methods for hemoglobinopathies screening. We can analyze by the methods more hemoglobin disorders and decrease more laboratory errors. Moreover

  1. DG-AMMOS: A New tool to generate 3D conformation of small molecules using Distance Geometry and Automated Molecular Mechanics Optimization for in silico Screening

    Directory of Open Access Journals (Sweden)

    Villoutreix Bruno O

    2009-11-01

    Full Text Available Abstract Background Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats. Results Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine. Conclusion DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.

  2. Homology modeling, molecular dynamics, and virtual screening of NorA efflux pump inhibitors of Staphylococcus aureus.

    Science.gov (United States)

    Bhaskar, Baki Vijaya; Babu, Tirumalasetty Muni Chandra; Reddy, Netala Vasudeva; Rajendra, Wudayagiri

    2016-01-01

    Emerging drug resistance in clinical isolates of Staphylococcus aureus might be implicated to the overexpression of NorA efflux pump which is capable of extruding numerous structurally diverse compounds. However, NorA efflux pump is considered as a potential drug target for the development of efflux pump inhibitors. In the present study, NorA model was constructed based on the crystal structure of glycerol-3-phosphate transporter (PDBID: 1PW4). Molecular dynamics (MD) simulation was performed using NAMD2.7 for NorA which is embedded in the hydrated lipid bilayer. Structural design of NorA unveils amino (N)- and carboxyl (C)-terminal domains which are connected by long cytoplasmic loop. N and C domains are composed of six transmembrane α-helices (TM) which exhibits pseudo-twofold symmetry and possess voluminous substrate binding cavity between TM helices. Molecular docking of reserpine, totarol, ferruginol, salvin, thioxanthene, phenothiazine, omeprazole, verapamil, nalidixic acid, ciprofloxacin, levofloxacin, and acridine to NorA found that all the molecules were bound at the large hydrophobic cleft and indicated significant interactions with the key residues. In addition, structure-based virtual screening was employed which indicates that 14 potent novel lead molecules such as CID58685302, CID58685367, CID5799283, CID5578487, CID60028372, ZINC12196383, ZINC72140751, ZINC72137843, ZINC39227983, ZINC43742707, ZINC12196375, ZINC66166948, ZINC39228014, and ZINC14616160 have highest binding affinity for NorA. These lead molecules displayed considerable pharmacological properties as evidenced by Lipinski rule of five and prophecy of toxicity risk assessment. Thus, the present study will be helpful in designing and synthesis of a novel class of NorA efflux pump inhibitors that restore the susceptibilities of drug compounds.

  3. Molecular Phylogenetic Screening of Withania somnifera Relative From Indonesia Based on Internal Transcribed Spacer Region

    Directory of Open Access Journals (Sweden)

    Topik Hidayat

    2016-04-01

    Full Text Available Withania somnifera (family Solanaceae, known commonly as Ashwaganda, is one of the important medicinal plants, and recent studies reported that Withanone, one of the chemical components in this plant, has ability to kill cancer cell. Because of endemic state of this plant to South Asia, exploring plant species under the same family which grow well in Indonesia has been of interest. The purpose of this study was to screen the Indonesian plant which has strong phylogenetic relationship with Ashwaganda. Thus, phylogenetic analysis using DNA sequences of internal transcribed spacer (ITS region was conducted. Thus, 19 species of Solanaceae and two species of Convolvulaceae as outgroup were examined. Five ITS regions of Ashwaganda retrieved from GenBank were included in the phylogenetic analysis. Parsimony analysis showed that Indonesia Solanaceae comprises seven groups which is consistent with the global Solanaceae relationship as previously reported. Furthermore, our study revealed that two species, Physalis angulata and Physalis peruviana, are relative to W. somnifera. Morphologically, they share characters of flower and fruit. This result indicated that these two species are potential to have similar chemical properties as Ashwaganda, thus we can have new variants of Withanone originated from Indonesia with similar effect.

  4. Molecular Testing for Gastrointestinal Cancer

    Directory of Open Access Journals (Sweden)

    Hye Seung Lee

    2017-03-01

    Full Text Available With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC and colorectal cancer (CRC. Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4. A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2 and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.

  5. Evaluation of a two-question screening tool in the detection of ...

    African Journals Online (AJOL)

    South African Family Practice ... Introduction: Intimate partner violence has been recognised globally as a human rights violation. ... understanding of the screening questions, which utilise Eurocentric definitions of intimate partner violence.

  6. Parenting style, the home environment, and screen time of 5-year-old children; the 'be active, eat right' study

    NARCIS (Netherlands)

    L. Veldhuis (Lydian); A. van Grieken (Amy); C.M. Renders (Carry); R.A. Hirasing (Remy); H. Raat (Hein)

    2014-01-01

    textabstractIntroduction: The global increase in childhood overweight and obesity has been ascribed partly to increases in children's screen time. Parents have a large influence on their children's screen time. Studies investigating parenting and early childhood screen time are limited. In this

  7. Parenting Style, the Home Environment, and Screen Time of 5-Year-Old Children; The 'Be Active, Eat Right' Study

    NARCIS (Netherlands)

    Veldhuis, L.; van Grieken, A.; Renders, C.M.; Hira Sing, R.A.; Raat, H.

    2014-01-01

    Introduction: The global increase in childhood overweight and obesity has been ascribed partly to increases in children's screen time. Parents have a large influence on their children's screen time. Studies investigating parenting and early childhood screen time are limited. In this study, we

  8. Tiered High-Throughput Screening Approach to Identify ...

    Science.gov (United States)

    High-throughput screening (HTS) for potential thyroid–disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge on perturbed thyroid hormone (TH) homeostasis. Screening for MIEs specific to TH-disrupting pathways is limited in the US EPA ToxCast screening assay portfolio. To fill one critical screening gap, the Amplex UltraRed-thyroperoxidase (AUR-TPO) assay was developed to identify chemicals that inhibit TPO, as decreased TPO activity reduces TH synthesis. The ToxCast Phase I and II chemical libraries, comprised of 1,074 unique chemicals, were initially screened using a single, high concentration to identify potential TPO inhibitors. Chemicals positive in the single concentration screen were retested in concentration-response. Due to high false positive rates typically observed with loss-of-signal assays such as AUR-TPO, we also employed two additional assays in parallel to identify possible sources of nonspecific assay signal loss, enabling stratification of roughly 300 putative TPO inhibitors based upon selective AUR-TPO activity. A cell-free luciferase inhibition assay was used to identify nonspecific enzyme inhibition among the putative TPO inhibitors, and a cytotoxicity assay using a human cell line was used to estimate the cellular tolerance limit. Additionally, the TPO inhibition activities of 150 chemicals were compared between the AUR-TPO and an orthogonal peroxidase oxidation assay using

  9. Evolutionary ARMS Race: Antimalarial Resistance Molecular Surveillance.

    Science.gov (United States)

    Prosser, Christiane; Meyer, Wieland; Ellis, John; Lee, Rogan

    2018-04-01

    Molecular surveillance of antimalarial drug resistance markers has become an important part of resistance detection and containment. In the current climate of multidrug resistance, including resistance to the global front-line drug artemisinin, there is a consensus to upscale molecular surveillance. The most salient limitation to current surveillance efforts is that skill and infrastructure requirements preclude many regions. This includes sub-Saharan Africa, where Plasmodium falciparum is responsible for most of the global malaria disease burden. New molecular and data technologies have emerged with an emphasis on accessibility. These may allow surveillance to be conducted in broad settings where it is most needed, including at the primary healthcare level in endemic countries, and extending to the village health worker. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Virtual screening of electron acceptor materials for organic photovoltaic applications

    International Nuclear Information System (INIS)

    D Halls, Mathew; Giesen, David J; Goldberg, Alexander; Djurovich, Peter J; Sommer, Jonathan; McAnally, Eric; Thompson, Mark E

    2013-01-01

    Virtual screening involves the generation of structure libraries, automated analysis to predict properties related to application performance and subsequent screening to identify lead systems and estimate critical structure–property limits across a targeted chemical design space. This approach holds great promise for informing experimental discovery and development efforts for next-generation materials, such as organic semiconductors. In this work, the virtual screening approach is illustrated for nitrogen-substituted pentacene molecules to identify systems for development as electron acceptor materials for use in organic photovoltaic (OPV) devices. A structure library of tetra-azapentacenes (TAPs) was generated by substituting four nitrogens for CH at 12 sites on the pentacene molecular framework. Molecular properties (e.g. E LUMO , E g and μ) were computed for each candidate structure using hybrid DFT at the B3LYP/6-311G** level of theory. The resulting TAPs library was then analyzed with respect to intrinsic properties associated with OPV acceptor performance. Marcus reorganization energies for charge transport for the most favorable TAP candidates were then calculated to further determine suitability as OPV electron acceptors. The synthesis, characterization and OPV device testing of TAP materials is underway, guided by these results. (paper)

  11. High-throughput screening with micro-x-ray fluorescence

    International Nuclear Information System (INIS)

    Havrilla, George J.; Miller, Thomasin C.

    2005-01-01

    Micro-x-ray fluorescence (MXRF) is a useful characterization tool for high-throughput screening of combinatorial libraries. Due to the increasing threat of use of chemical warfare (CW) agents both in military actions and against civilians by terrorist extremists, there is a strong push to improve existing methods and develop means for the detection of a broad spectrum of CW agents in a minimal amount of time to increase national security. This paper describes a combinatorial high-throughput screening technique for CW receptor discovery to aid in sensor development. MXRF can screen materials for elemental composition at the mesoscale level (tens to hundreds of micrometers). The key aspect of this work is the use of commercial MXRF instrumentation coupled with the inherent heteroatom elements within the target molecules of the combinatorial reaction to provide rapid and specific identification of lead species. The method is demonstrated by screening an 11-mer oligopeptide library for selective binding of the degradation products of the nerve agent VX. The identified oligopeptides can be used as selective molecular receptors for sensor development. The MXRF screening method is nondestructive, requires minimal sample preparation or special tags for analysis, and the screening time depends on the desired sensitivity

  12. Omics approaches on fresh-cut lettuce reveal global molecular responses to sodium hypochlorite and peracetic acid treatment.

    Science.gov (United States)

    Daddiego, Loretta; Bianco, Linda; Capodicasa, Cristina; Carbone, Fabrizio; Dalmastri, Claudia; Daroda, Lorenza; Del Fiore, Antonella; De Rossi, Patrizia; Di Carli, Mariasole; Donini, Marcello; Lopez, Loredana; Mengoni, Alessio; Paganin, Patrizia; Perrotta, Gaetano; Bevivino, Annamaria

    2018-01-01

    Lettuce is a leafy vegetable that is extensively commercialized as a ready-to-eat product because of its widespread use in human nutrition as salad. It is well known that washing treatments can severely affect the quality and shelf-life of ready-to-eat vegetables. The study presented here evaluated the effect of two washing procedures on fresh-cut lettuce during storage. An omics approach was applied to reveal global changes at molecular level induced by peracetic acid washing in comparison with sodium hypochlorite treatment. Microbiological analyses were also performed to quantify total bacterial abundance and composition. The study revealed wide metabolic alterations induced by the two sanitizers. In particular, transcriptomic and proteomic analyses pointed out a number of transcripts and proteins differentially accumulated in response to peracetic acid washing, mainly occurring on the first day of storage. In parallel, different microbiota composition and significant reduction in total bacterial load following washing were also observed. The results provide useful information for the fresh-cut industry to select an appropriate washing procedure preserving fresh-like attributes as much as possible during storage of the end product. Molecular evidence indicated peracetic acid to be a valid alternative to sodium hypochlorite as sanitizer solution. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  13. A desirability-based multi objective approach for the virtual screening discovery of broad-spectrum anti-gastric cancer agents.

    Directory of Open Access Journals (Sweden)

    Yunierkis Perez-Castillo

    Full Text Available Gastric cancer is the third leading cause of cancer-related mortality worldwide and despite advances in prevention, diagnosis and therapy, it is still regarded as a global health concern. The efficacy of the therapies for gastric cancer is limited by a poor response to currently available therapeutic regimens. One of the reasons that may explain these poor clinical outcomes is the highly heterogeneous nature of this disease. In this sense, it is essential to discover new molecular agents capable of targeting various gastric cancer subtypes simultaneously. Here, we present a multi-objective approach for the ligand-based virtual screening discovery of chemical compounds simultaneously active against the gastric cancer cell lines AGS, NCI-N87 and SNU-1. The proposed approach relays in a novel methodology based on the development of ensemble models for the bioactivity prediction against each individual gastric cancer cell line. The methodology includes the aggregation of one ensemble per cell line using a desirability-based algorithm into virtual screening protocols. Our research leads to the proposal of a multi-targeted virtual screening protocol able to achieve high enrichment of known chemicals with anti-gastric cancer activity. Specifically, our results indicate that, using the proposed protocol, it is possible to retrieve almost 20 more times multi-targeted compounds in the first 1% of the ranked list than what is expected from a uniform distribution of the active ones in the virtual screening database. More importantly, the proposed protocol attains an outstanding initial enrichment of known multi-targeted anti-gastric cancer agents.

  14. Globalisation and global trade influence molecular viral population genetics of Torque Teno Sus Viruses 1 and 2 in pigs.

    Science.gov (United States)

    Cortey, Martí; Pileri, Emanuela; Segalés, Joaquim; Kekarainen, Tuija

    2012-04-23

    Globalisation, in terms of the rapid and free movement of people, animals and food, has created a new paradigm, increasing the range and rate of distribution of many pathogens. In the present study, Torque teno sus viruses (TTSuVs) have been used as a model to evaluate the effects of global trade on viral heterogeneity, and how the movement of live pigs can affect the distribution and composition of virus populations. Seventeen countries from different parts of the world have been screened for TTSuV1 and TTSuvV2. High levels of genetic diversity have been found as well as two new TTSuV subtypes. A small fraction of this diversity (50%) was best explained by the exchange of live pigs among countries, pointing to the direct relationship between the movement of hosts and the diversity of their accompanying viruses. Taking TTSuVs as sentinels, this study revealed that the distribution and diversity of comensal microflora in live animals subjected to global trade is shaped by the commercial movements among countries. In the case of TTSuVs, it appears that commercial movements of animals are eroding the genetic composition of the virus populations that may have been present in pig herds since their domestication. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Utility of molecular tests in cytopathology

    Directory of Open Access Journals (Sweden)

    Arthur David Somoza

    2014-01-01

    Full Text Available With the popularity of interventional radiology, diagnostic material obtained can be limited requiring critical decisions on making the best use of it. Molecular testing using nanogram amounts of tissue can add useful diagnostic information by improving sensitivity and/or specificity of the diagnosis. This review examines the use of molecular tests in cervical cytology, "indeterminate" thyroid cytology specimens, pancreatic cyst fluid, urinary tract and pulmonary adenocarcinoma cytologic material. Molecular human papillomavirus (HPV testing combined with cervical cytology increases sensitivity of detection of high grade lesions. In cytologically negative cases, the HPV negative predictive value endorses longer screening intervals. With the high prevalence of benign thyroid nodules, cytology plays a vital role in screening. However, 10-40% of the specimens obtained are cytologically indeterminate. Molecular analysis of these specimens can predict the malignant risk in these cases. Increased detection of pancreatic cysts has necessitated accurate pre-operative diagnosis delineating non-mucinous from mucinous cysts, which have a potential for progression to adenocarcinoma. Multimodal diagnosis of pancreatic cysts and molecular analysis help to clarify neoplastic risk; and in cases of limited fluid, may be the only available diagnostic information. Urothelial carcinoma (UC of the bladder, a common cancer with frequent recurrences, requires lifelong surveillance. The UroVysion ™ test kit can increase the sensitivity of detection of UC especially in cases of residual/recurrent carcinoma after therapy. Subsets of lung adenocarcinomas are now commonly targeted by therapies based on molecular mutation results of epidermal growth factor receptor, KRAS or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase re-arrangements. The move toward standardization of reporting of cytology specimens commencing with cervical smears and more

  16. Democratizing molecular diagnostics for the developing world.

    Science.gov (United States)

    Abou Tayoun, Ahmad N; Burchard, Paul R; Malik, Imran; Scherer, Axel; Tsongalis, Gregory J

    2014-01-01

    Infectious diseases that are largely treatable continue to pose a tremendous burden on the developing world despite the availability of highly potent drugs. The high mortality and morbidity rates of these diseases are largely due to a lack of affordable diagnostics that are accessible to resource-limited areas and that can deliver high-quality results. In fact, modified molecular diagnostics for infectious diseases were rated as the top biotechnology to improve health in developing countries. In this review, we describe the characteristics of accessible molecular diagnostic tools and discuss the challenges associated with implementing such tools at low infrastructure sites. We highlight our experience as part of the "Grand Challenge" project supported by the Gates Foundation for addressing global health inequities and describe issues and solutions associated with developing adequate technologies or molecular assays needed for broad access in the developing world. We believe that sharing this knowledge will facilitate the development of new molecular technologies that are extremely valuable for improving global health.

  17. Comparison of LAMP and PCR for molecular mass screening of sand flies for Leishmania martiniquensis infection.

    Science.gov (United States)

    Tiwananthagorn, Saruda; Kato, Hirotomo; Yeewa, Ranchana; Muengpan, Amontip; Polseela, Raxsina; Leelayoova, Saovanee

    2017-02-01

    Leishmaniasis caused by Leishmania martiniquensis infection has been reported in human and domestic animals of Martinique Island, Germany, Switzerland, USA, Myanmar and Thailand. The peculiar clinical features of disseminated cutaneous and visceral forms co-existence render the urgent need of specific diagnostic tool to identify the natural sand fly vectors for effective prevention and control strategies. Loop-mediated isothermal amplification (LAMP) of 18S rRNA gene as well as polymerase chain reaction (PCR) of minicircle kinetoplast DNA gene (PCR-mkDNA) have never been applied to detect L. martiniquensis and L. siamensis in sand fly vectors. The present study was aimed to validate malachite green-LAMP (MG-LAMP) and PCR-mkDNA techniques to detect L. martiniquensis in sand fly vectors, compared with the conventional PCR of internal transcribed spacer 1 (PCR-ITS1). We compared the validity of LAMP of 18S rRNA gene and PCR-mkDNA, to PCR-ITS1 in simulation model of L. martiniquensis infection in Sergentomyia gemmea sand flies. Attributable to the sensitivity and specificity, PCR-mkDNA was consecutively applied to detect L. martiniquensis in 380 female sand fly individuals captured in the newly identified affected region of Lamphun Province, Thailand. Results showed that PCR-mkDNA could detect at least one promastigote per sand fly, which was 10-time superior to LAMP and PCR-ITS1. In addition, PCR-mkDNA was more specific, able to differentiate L. martiniquensis from other viscerotropic Leishmania species, such as L. siamensis, L. (L.) donovani, and L. (L.) infantum. Consecutively, mass screening of L. martiniquensis in 380 female sand fly individuals by PCR-mkDNA was implemented in a new affected area of Thailand where a patient with leishmaniasis/HIV co-infection resides; however Leishmania DNA was undetected. In conclusion, PCR-mkDNA is a promising tool for molecular mass screening of L. martiniquensis infection in outbreak areas where several species of Leishmania

  18. Comparison of LAMP and PCR for molecular mass screening of sand flies for Leishmania martiniquensis infection

    Science.gov (United States)

    Tiwananthagorn, Saruda; Kato, Hirotomo; Yeewa, Ranchana; Muengpan, Amontip; Polseela, Raxsina; Leelayoova, Saovanee

    2017-01-01

    BACKGROUND Leishmaniasis caused by Leishmania martiniquensis infection has been reported in human and domestic animals of Martinique Island, Germany, Switzerland, USA, Myanmar and Thailand. The peculiar clinical features of disseminated cutaneous and visceral forms co-existence render the urgent need of specific diagnostic tool to identify the natural sand fly vectors for effective prevention and control strategies. Loop-mediated isothermal amplification (LAMP) of 18S rRNA gene as well as polymerase chain reaction (PCR) of minicircle kinetoplast DNA gene (PCR-mkDNA) have never been applied to detect L. martiniquensis and L. siamensis in sand fly vectors. OBJECTIVE The present study was aimed to validate malachite green-LAMP (MG-LAMP) and PCR-mkDNA techniques to detect L. martiniquensis in sand fly vectors, compared with the conventional PCR of internal transcribed spacer 1 (PCR-ITS1). METHODS We compared the validity of LAMP of 18S rRNA gene and PCR-mkDNA, to PCR-ITS1 in simulation model of L. martiniquensis infection in Sergentomyia gemmea sand flies. Attributable to the sensitivity and specificity, PCR-mkDNA was consecutively applied to detect L. martiniquensis in 380 female sand fly individuals captured in the newly identified affected region of Lamphun Province, Thailand. FINDINGS AND MAIN CONCLUSIONS Results showed that PCR-mkDNA could detect at least one promastigote per sand fly, which was 10-time superior to LAMP and PCR-ITS1. In addition, PCR-mkDNA was more specific, able to differentiate L. martiniquensis from other viscerotropic Leishmania species, such as L. siamensis, L. (L.) donovani, and L. (L.) infantum. Consecutively, mass screening of L. martiniquensis in 380 female sand fly individuals by PCR-mkDNA was implemented in a new affected area of Thailand where a patient with leishmaniasis/HIV co-infection resides; however Leishmania DNA was undetected. In conclusion, PCR-mkDNA is a promising tool for molecular mass screening of L. martiniquensis

  19. High-throughput strategy for molecular identification of Vel- blood donors employing nucleic acids extracted from plasma pools used for viral nucleic acid test screening.

    Science.gov (United States)

    Dezan, Marcia R; Dinardo, Carla L; Bosi, Silvia R A; Vega, Sileni; Salles, Nanci A; Mendrone-Júnior, Alfredo; Levi, José E

    2016-06-01

    Serologic methods to determine the Vel- phenotype require the use of rare human antisera and do not allow for many samples to be tested simultaneously, which limits their application as a tool to search for rare donors. This study developed a low-cost molecular screening strategy using real-time polymerase chain reaction (PCR) and DNA, extracted from plasma pools for viral nucleic acid test (NAT) screening, to identify Vel- and Vel+(W) donors. A total of 4680 blood donors from the Brazilian southeast region were genotyped through real-time PCR targeting the 17-nucleotide (c.64_80del) deletion in the SMIM1 gene, which determines the Vel- phenotype, by using remaining nucleic acid from plasma pools of six donors, routinely discarded after the release of viral NAT results. Twenty pools tested reactive and individual testing of samples from reactive pools identified 19 heterozygous donors with the SMIM1*64_80del deletion (0.40%) and one homozygous donor (0.02%). Fourteen of the 19 donors were confirmed as Vel- or Vel+(W) using anti-Vel human antiserum. The DNA pool genotyping strategy using real-time PCR designed to detect the deletion in the SMIM1 gene proved effective and accurate in identifying donors with the Vel- and Vel+(W) phenotypes. The fact that remaining nucleic acid from routine viral NAT screening was used makes this technique economically attractive and definitely superior to the serologic techniques available to search for this rare phenotype. © 2016 AABB.

  20. Advances in Predictive Toxicology for Discovery Safety through High Content Screening.

    Science.gov (United States)

    Persson, Mikael; Hornberg, Jorrit J

    2016-12-19

    High content screening enables parallel acquisition of multiple molecular and cellular readouts. In particular the predictive toxicology field has progressed from the advances in high content screening, as more refined end points that report on cellular health can be studied in combination, at the single cell level, and in relatively high throughput. Here, we discuss how high content screening has become an essential tool for Discovery Safety, the discipline that integrates safety and toxicology in the drug discovery process to identify and mitigate safety concerns with the aim to design drug candidates with a superior safety profile. In addition to customized mechanistic assays to evaluate target safety, routine screening assays can be applied to identify risk factors for frequently occurring organ toxicities. We discuss the current state of high content screening assays for hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, and genotoxicity, including recent developments and current advances.

  1. Molecular techniques for MRSA typing: current issues and perspectives

    Directory of Open Access Journals (Sweden)

    P. A. Trindade

    Full Text Available Staphylococcus aureus has long been recognised as an important pathogen in human disease. Serious staphylococcal infections can frequently occur in inpatients and may lead to dire consequences, especially as to therapy with antimicrobial agents. The increase in the frequency of Methicillin-Resistant Staphylococcus aureus (MRSA as the causal agent of nosocomial infection and the possibility of emergence of resistance to vancomycin demands a quick and trustworthy characterization of isolates and identification of clonal spread within hospitals. Enough information must be generated to permit the implementation of appropriate measures for control of infection, so that outbreaks can be contained. Molecular typing techniques reviewed in this manuscript include: plasmid profile analysis, analysis of chromosomal DNA after enzymatic restriction, Southern blotting, pulsed field gel electrophoresis (PFGE, techniques involving polymerase chain reaction and multilocus sequence typing (MLST. Repetitive DNA Sequence PCR (rep-PCR may be used for screening due to its practicality, low cost and reproducibility. Because of its high discriminatory power Pulsed-Field Gel Electrophoresis (PFGE still remains the gold standard for MRSA typing. New techniques with higher reproducibility and discriminatory power, such as Multi-Locus Sequence Typing (MLST, are appearing. These are mostly useful for global epidemiology studies. Molecular typing techniques are invaluable tools for the assessment of putative MRSA outbreaks and so should be extensively used for this purpose.

  2. Molecular techniques for MRSA typing: current issues and perspectives

    Directory of Open Access Journals (Sweden)

    Trindade P. A.

    2003-01-01

    Full Text Available Staphylococcus aureus has long been recognised as an important pathogen in human disease. Serious staphylococcal infections can frequently occur in inpatients and may lead to dire consequences, especially as to therapy with antimicrobial agents. The increase in the frequency of Methicillin-Resistant Staphylococcus aureus (MRSA as the causal agent of nosocomial infection and the possibility of emergence of resistance to vancomycin demands a quick and trustworthy characterization of isolates and identification of clonal spread within hospitals. Enough information must be generated to permit the implementation of appropriate measures for control of infection, so that outbreaks can be contained. Molecular typing techniques reviewed in this manuscript include: plasmid profile analysis, analysis of chromosomal DNA after enzymatic restriction, Southern blotting, pulsed field gel electrophoresis (PFGE, techniques involving polymerase chain reaction and multilocus sequence typing (MLST. Repetitive DNA Sequence PCR (rep-PCR may be used for screening due to its practicality, low cost and reproducibility. Because of its high discriminatory power Pulsed-Field Gel Electrophoresis (PFGE still remains the gold standard for MRSA typing. New techniques with higher reproducibility and discriminatory power, such as Multi-Locus Sequence Typing (MLST, are appearing. These are mostly useful for global epidemiology studies. Molecular typing techniques are invaluable tools for the assessment of putative MRSA outbreaks and so should be extensively used for this purpose.

  3. Library fingerprints: a novel approach to the screening of virtual libraries.

    Science.gov (United States)

    Klon, Anthony E; Diller, David J

    2007-01-01

    We propose a novel method to prioritize libraries for combinatorial synthesis and high-throughput screening that assesses the viability of a particular library on the basis of the aggregate physical-chemical properties of the compounds using a naïve Bayesian classifier. This approach prioritizes collections of related compounds according to the aggregate values of their physical-chemical parameters in contrast to single-compound screening. The method is also shown to be useful in screening existing noncombinatorial libraries when the compounds in these libraries have been previously clustered according to their molecular graphs. We show that the method used here is comparable or superior to the single-compound virtual screening of combinatorial libraries and noncombinatorial libraries and is superior to the pairwise Tanimoto similarity searching of a collection of combinatorial libraries.

  4. Global patterns of amphibian phylogenetic diversity

    DEFF Research Database (Denmark)

    Fritz, Susanne; Rahbek, Carsten

    2012-01-01

    Aim  Phylogenetic diversity can provide insight into how evolutionary processes may have shaped contemporary patterns of species richness. Here, we aim to test for the influence of phylogenetic history on global patterns of amphibian species richness, and to identify areas where macroevolutionary...... processes such as diversification and dispersal have left strong signatures on contemporary species richness. Location  Global; equal-area grid cells of approximately 10,000 km2. Methods  We generated an amphibian global supertree (6111 species) and repeated analyses with the largest available molecular...... phylogeny (2792 species). We combined each tree with global species distributions to map four indices of phylogenetic diversity. To investigate congruence between global spatial patterns of amphibian species richness and phylogenetic diversity, we selected Faith’s phylogenetic diversity (PD) index...

  5. Simultaneous measurements of global vibrational spectra and dephasing times of molecular vibrational modes by broadband time-resolved coherent anti-Stokes Raman scattering spectrography

    International Nuclear Information System (INIS)

    Yin Jun; Yu Ling-Yao; Liu Xing; Wan Hui; Lin Zi-Yang; Niu Han-Ben

    2011-01-01

    In broadband coherent anti-Stokes Raman scattering (CARS) spectroscopy with supercontinuum (SC), the simultaneously detectable spectral coverage is limited by the spectral continuity and the simultaneity of various spectral components of SC in an enough bandwidth. By numerical simulations, the optimal experimental conditions for improving the SC are obtained. The broadband time-resolved CARS spectrography based on the SC with required temporal and spectral distributions is realised. The global molecular vibrational spectrum with well suppressed nonresonant background noise can be obtained in a single measurement. At the same time, the measurements of dephasing times of various molecular vibrational modes can be conveniently achieved from intensities of a sequence of time-resolved CARS signals. It will be more helpful to provide a complete picture of molecular vibrations, and to exhibit a potential to understand not only both the solvent dynamics and the solute-solvent interactions, but also the mechanisms of chemical reactions in the fields of biology, chemistry and material science. (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

  6. In Silico Screening Hepatitis B Virus DNA Polymerase Inhibitors from Medicinal Plants

    Directory of Open Access Journals (Sweden)

    Mokhtar Nosrati

    2017-08-01

    Full Text Available Abstract Background: Hepatitis B virus infection (HBV is a significant global health problem and is a major cause of morbidity and mortality worldwide. Therefore, currently, introducing novel anti Hepatitis B drugs is taken into consideration. This study was planned to in silico screening novel Hepatitis B virus DNA polymerase inhibitors from two medicinal plants Terminalis chebula and Caesalpinia sappan. Materials and Methods: This is a descriptive-analytic study. In the study, three-dimensional structure of the Hepatitis B virus DNA polymerase was predicted using homology modeling method. A set of phytochemicals from mentioned plants were retrieved from Pubchem database in SDF format. In silico screening was carried out using molecular docking between mentioned phytochemicals and modeled polymerase by iGemdock 2.1 software. Results: Results of the study confirmed that all evaluated ligands have appropriate interactions to the polymerase with least toxicity and without genotoxicity potential. Results also showed that most interactions occur in reverse transcriptase domain which located in 354-694 area in the amino acid sequence of tested polymerase. Analysis of energy and amino acids involved in ligand-polymerase interaction revealed that Terchebin, Chebulinic Acid and Terflavin A have more effective interaction with the polymerase in compared to other ligands. Conclusion: Based on the results it can be concluded that evaluated compounds could be good candidates for in vitro and in vivo research in order to develop novel anti- Hepatitis B drugs.

  7. Usage of capillary electrophoresis for common hemoglobinopathies screening

    Directory of Open Access Journals (Sweden)

    Alireza Ebrahimi

    2016-06-01

    Full Text Available Hemoglobinopathies are most common inherited disorders in the world; approximately 7 percent of the worldwide population and 5-6 percent of population of Iran are carriers. The hemoglobin disorders inherit as autosomal recessive and are very common in the Mediterranean area and much of the Asia and Africa. The control of this inherited disorders need to genetic counseling and accurate screening by more advanced and more accurate methods. This study explains features of current Iran hemoglobin disorders, nominates the accessible methods for screening them and introduces the capillary zone electrophoresis as a rapid and more accurate method. The required data were extracted of various articles and then for good explanation, current Iran hemoglobinopathies properties were showed in the tables and electropherograms of important hemoglobin disorders in Iran population were provided for help to interpretation results of blood tests by capillary zone electrophoresis method. Hemoglobin disorders are including thalassemias and hemoglobin variants; Disruption in the production and malfunction of globin chains cause types of hemoglobin disorders. We cannot introduce one of clinical laboratory tests as critical and basic method for screening and distinguishing types of inherited hemoglobin disorders as alone. For distinguishing the types of them must be prepared enough information and data of the hemoglobin disorders and for more accurate analysis must be used simultaneously different methods as gel electrophoresis, high performance liquid chromatography, isoelectric focusing, capillary zone electrophoresis or molecular tests. The capillary electrophoresis is an accurate and rapid method for screening types of the hemoglobin disorders. Other side this method cannot analyze all of them, so must be used biochemical, biophysical and molecular methods for confirmation the results. This review showed we can use the capillary electrophoresis and HPLC as two

  8. LASSO-ligand activity by surface similarity order: a new tool for ligand based virtual screening.

    Science.gov (United States)

    Reid, Darryl; Sadjad, Bashir S; Zsoldos, Zsolt; Simon, Aniko

    2008-01-01

    Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more successful. eHiTS LASSO uses a new interacting surface point types (ISPT) molecular descriptor that is generated from the 3D structure of the ligand, but unlike most 3D descriptors it is conformation independent. Combined with a neural network machine learning technique, LASSO screens molecular databases at an ultra fast speed of 1 million structures in under 1 min on a standard PC. The results obtained from eHiTS LASSO trained on relatively small training sets of just 2, 4 or 8 actives are presented using the diverse directory of useful decoys (DUD) dataset. It is shown that over a wide range of receptor families, eHiTS LASSO is consistently able to enrich screened databases and provides scaffold hopping ability.

  9. LASSO—ligand activity by surface similarity order: a new tool for ligand based virtual screening

    Science.gov (United States)

    Reid, Darryl; Sadjad, Bashir S.; Zsoldos, Zsolt; Simon, Aniko

    2008-06-01

    Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more successful. eHiTS LASSO uses a new interacting surface point types (ISPT) molecular descriptor that is generated from the 3D structure of the ligand, but unlike most 3D descriptors it is conformation independent. Combined with a neural network machine learning technique, LASSO screens molecular databases at an ultra fast speed of 1 million structures in under 1 min on a standard PC. The results obtained from eHiTS LASSO trained on relatively small training sets of just 2, 4 or 8 actives are presented using the diverse directory of useful decoys (DUD) dataset. It is shown that over a wide range of receptor families, eHiTS LASSO is consistently able to enrich screened databases and provides scaffold hopping ability.

  10. Fast Molecular Cloud Destruction Requires Fast Cloud Formation

    Energy Technology Data Exchange (ETDEWEB)

    Mac Low, Mordecai-Mark [American Museum of Natural History, 79th Street at Central Park West, New York, NY 10024 (United States); Burkert, Andreas [Universitäts Sternwarte München, Ludwigs-Maximilian-Universität, D-81679 München (Germany); Ibáñez-Mejía, Juan C., E-mail: mordecai@amnh.org, E-mail: burkert@usm.lmu.de, E-mail: ibanez@ph1.uni-koeln.de [Max-Planck-Institut für Extraterrestrische Physik, D-85748 Garching bei München (Germany)

    2017-09-20

    A large fraction of the gas in the Galaxy is cold, dense, and molecular. If all this gas collapsed under the influence of gravity and formed stars in a local free-fall time, the star formation rate in the Galaxy would exceed that observed by more than an order of magnitude. Other star-forming galaxies behave similarly. Yet, observations and simulations both suggest that the molecular gas is indeed gravitationally collapsing, albeit hierarchically. Prompt stellar feedback offers a potential solution to the low observed star formation rate if it quickly disrupts star-forming clouds during gravitational collapse. However, this requires that molecular clouds must be short-lived objects, raising the question of how so much gas can be observed in the molecular phase. This can occur only if molecular clouds form as quickly as they are destroyed, maintaining a global equilibrium fraction of dense gas. We therefore examine cloud formation timescales. We first demonstrate that supernova and superbubble sweeping cannot produce dense gas at the rate required to match the cloud destruction rate. On the other hand, Toomre gravitational instability can reach the required production rate. We thus argue that, although dense, star-forming gas may last only around a single global free-fall time; the dense gas in star-forming galaxies can globally exist in a state of dynamic equilibrium between formation by gravitational instability and disruption by stellar feedback. At redshift z ≳ 2, the Toomre instability timescale decreases, resulting in a prediction of higher molecular gas fractions at early times, in agreement with the observations.

  11. Rectal swab screening assays of public health importance in molecular diagnostics: Sample adequacy control.

    Science.gov (United States)

    Glisovic, Sanja; Eintracht, Shaun; Longtin, Yves; Oughton, Matthew; Brukner, Ivan

    Rectal swabs are routinely used by public health authorities to screen for multi-drug resistant enteric bacteria including vancomycin-resistant enterococci (VRE) and carbapenem-resistant enterobacteriaceae (CRE). Screening sensitivity can be influenced by the quality of the swabbing, whether performed by the patient (self-swabbing) or a healthcare practitioner. One common exclusion criterion for rectal swabs is absence of "visible soiling" from fecal matter. In our institution, this criterion excludes almost 10% of rectal swabs received in the microbiology laboratory. Furthermore, over 30% of patients in whom rectal swabs are cancelled will not be re-screened within the next 48h, resulting in delays in removing infection prevention measures. We describe two quantitative polymerase chain reaction (qPCR)-based assays, human RNAse P and eubacterial 16S rDNA, which might serve as suitable controls for sampling adequacy. However, lower amounts of amplifiable human DNA make the 16s rDNA assay a better candidate for sample adequacy control. Copyright © 2017. Published by Elsevier Ltd.

  12. A screen-printed carbon electrode modified with gold nanoparticles, poly(3,4-ethylenedioxythiophene), poly(styrene sulfonate) and a molecular imprint for voltammetric determination of nitrofurantoin.

    Science.gov (United States)

    Dechtrirat, Decha; Yingyuad, Peerada; Prajongtat, Pongthep; Chuenchom, Laemthong; Sriprachuabwong, Chakrit; Tuantranont, Adisorn; Tang, I-Ming

    2018-04-23

    A molecularly imprinted polymer (MIP) and a nanocomposite prepared from gold nanoparticles (AuNP) and poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonate) (PEDOT:PSS) were deposited on a screen-printed carbon electrode (SPCE). The nanocomposite was prepared by one-pot simultaneous in-situ formation of AuNPs and PEDOT:PSS and was then inkjet-coated onto the SPCE. The MIP film was subsequently placed on the modified SPCE by co-electrodeposition of o-phenylenediamine and resorcinol in the presence of the antibiotic nitrofurantoin (NFT). Using differential pulse voltammetry (DPV), response at the potential of ~ 0.1 V (vs. Ag/AgCl) is linear in 1 nM to 1000 nM NFT concentration range, with a remarkably low detection limit (at S/N = 3) of 0.1 nM. This is two orders of magnitude lower than that of the control MIP sensor without the nanocomposite interlayer, thus showing the beneficial effect of AuNP-PEDOT:PSS. The electrode is highly reproducible (relative standard deviation 3.1% for n = 6) and selective over structurally related molecules. It can be re-used for at least ten times and was found to be stable for at least 45 days. It was successfully applied to the determination of NFT in (spiked) feed matrices and gave good recoveries. Graphical abstract Schematic representation of a voltammetric sensor for the determination of nitrofurantoin. The sensor is based on a screen-printed carbon electrode (SPCE) modified with an inkjet-printed gold nanoparticles-poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) nanocomposite and a molecularly imprinted polymer.

  13. [Towards a molecular psychiatry].

    Science.gov (United States)

    de la Fuente, J R

    1988-06-01

    Recent research data from psychopharmacology, brain imaging and molecular genetics support the notion of a new psychiatric frontier: that of molecular psychiatry. Identification of different subtypes of neurotransmitter receptors and their changes in density and sensitivity in response to endogenous ligands and/or psychotropic drugs may account for the clinical expression of various behavioral phenomena, including some psychiatric disorders. Brain imaging, in particular positron-emission tomographic evaluations, are likely to change psychiatric nosology. New diagnostic elements derived from these scanners will allow to associate psychotic states to neuroreceptor changes. Molecular genetics has shown that bipolar affective disorder can be caused by a single gene. A strong linkage seems to exist between a gene locus on chromosome 11 and bipolar illness. An amyloid gene located on chromosome 21 has also been shown to be strongly related to familial Alzheimer's disease. While genetic heterogeneity limits the screening value of these findings, the powerful techniques of molecular biology have entered the field of psychiatry. Ethical issues regarding DNA immortality, gene cloning and gene therapy will strengthen this relationship.

  14. Clinical and molecular characterization of Chilean patients with Léri-Weill dyschondrosteosis.

    Science.gov (United States)

    Rodríguez, Fernando Adrián; Unanue, Nancy; Hernandez, María Isabel; Basaure, Javiera; Heath, Karen Elise; Cassorla, Fernando

    2013-01-01

    Léri-Weill dyschondrosteosis (LWD) is a mesomelic dysplasia with disproportionate short stature associated with short stature homeobox-containing gene (SHOX) haploinsufficiency. The objective of this study was to improve the diagnosis of patients with suspected LWD through molecular analysis. Twelve patients from 11 families with a clinical diagnosis of LWD were analyzed with multiplex ligation-dependent probe amplification to detect deletions and duplications of SHOX and its enhancer regions. High resolution melting and sequencing was employed to screen for mutations in SHOX coding exons. The molecular-based screening strategy applied in these patients allowed detection of five SHOX deletions and two previously unreported SHOX missense mutations. Molecular studies confirmed the clinical diagnosis of LWD in seven out of 12 patients, which provided support for therapeutic decisions and improved genetic counseling in their families.

  15. Structure-based virtual screening of molecular libraries as cdk2 inhibitors

    International Nuclear Information System (INIS)

    Riaz, U.; Khaleeq, M.

    2011-01-01

    CDK2 inhibitor is an important target in multiple processes associated with tumor growth and development, including proliferation, neovascularization, and metastasis. In this study, hit identification was performed by virtual screening of commercial and in-house compound libraries. Docking studies for the hits were performed, and scoring functions were used to evaluate the docking results and to rank ligand-binding affinities. Subsequently, hit optimization for potent and selective candidate CDK2 inhibitors was performed through focused library design and docking analyses. Consequently, we report that a novel compound with an IC50 value of 89 nM, representing 2-Amino-4,6-di-(4',6'-dibromophenyl)pyrimidine 1, is highly selective for CDK2 inhibitors. The docking structure of compound 1 with CDK2 inhibitor disclosed that the NH moiety and pyrimidine ring appeared to fit tightly into the hydrophobic pocket of CDK2 inhibitor. Additionally, the pyrimidine NH forms a hydrogen bond with the carboxyl group of Asp348. These results confirm the successful application of virtual screening studies in the lead discovery process, and suggest that our novel compound can be an effective CDK2 inhibitor candidate for further lead optimization. (author)

  16. Molecular biodiversity of Red Sea demosponges

    KAUST Repository

    Erpenbeck, Dirk

    2016-01-07

    Sponges are important constituents of coral reef ecosystems, including those around the Arabian Peninsula. Despite their importance, our knowledge on demosponge diversity in this area is insufficient to recognize, for example, faunal changes caused by anthropogenic disturbances. We here report the first assessment of demosponge molecular biodiversity from Arabia, with focus on the Saudi Arabian Red Sea, based on mitochondrial and nuclear ribosomal molecular markers gathered in the framework of the Sponge Barcoding Project. We use a rapid molecular screening approach on Arabian demosponge collections and analyze results in comparison against published material in terms of biodiversity. We use a variable region of 28S rDNA, applied for the first time in the assessment of demosponge molecular diversity. Our data constitutes a solid foundation for a future more comprehensive understanding of sponge biodiversity of the Red Sea and adjacent waters.

  17. Molecular biodiversity of Red Sea demosponges

    KAUST Repository

    Erpenbeck, Dirk; Voigt, Oliver; Al-Aidaroos, Ali M.; Berumen, Michael L.; Bü ttner, Gabriele; Catania, Daniela; Guirguis, Adel Naguib; Paulay, Gustav; Schä tzle, Simone; Wö rheide, Gert

    2016-01-01

    Sponges are important constituents of coral reef ecosystems, including those around the Arabian Peninsula. Despite their importance, our knowledge on demosponge diversity in this area is insufficient to recognize, for example, faunal changes caused by anthropogenic disturbances. We here report the first assessment of demosponge molecular biodiversity from Arabia, with focus on the Saudi Arabian Red Sea, based on mitochondrial and nuclear ribosomal molecular markers gathered in the framework of the Sponge Barcoding Project. We use a rapid molecular screening approach on Arabian demosponge collections and analyze results in comparison against published material in terms of biodiversity. We use a variable region of 28S rDNA, applied for the first time in the assessment of demosponge molecular diversity. Our data constitutes a solid foundation for a future more comprehensive understanding of sponge biodiversity of the Red Sea and adjacent waters.

  18. Evaluation of nutritional screening tools for patients scheduled for cardiac surgery.

    Science.gov (United States)

    Lomivorotov, Vladimir V; Efremov, Sergey M; Boboshko, Vladimir A; Nikolaev, Dmitry A; Vedernikov, Pavel E; Lomivorotov, Vladimir N; Karaskov, Alexander M

    2013-02-01

    The aim of this study was to assess the prognostic value of different nutritional screening tools in patients undergoing cardiopulmonary bypass with regard to an adverse clinical course. This prospective cohort study analyzed 894 adult patients who underwent cardiopulmonary bypass. Patients were screened using four nutritional screening tools: Nutritional Risk Screening 2002 (NRS-2002), the Malnutrition Universal Screening Tool (MUST), the Mini-Nutritional Assessment (MNA), and the Short Nutritional Assessment Questionnaire (SNAQ). Nutritional status was assessed using the Subjective Global Assessment. In-hospital mortality, postoperative complications, length of stay in the intensive care unit, and length of hospitalization were analyzed. The sensitivities of the SNAQ, MUST, and NRS-2002 to detect the malnutrition confirmed by the Subjective Global Assessment were 91.5%, 97.9%, and 38.3%, respectively, and the MNA showed a sensitivity of 81.8% for the elderly. Malnutrition detected by the SNAQ, MUST, and NRS-2002 was associated with postoperative complications (odds ratios [ORs] 1.75, 1.98, and 1.82, respectively) and a stay in the intensive care unit longer than 2 d (ORs 1.46, 1.56, and 2.8). Malnutrition as detected by the SNAQ and MUST was also associated with prolonged hospitalization (ORs 1.49 and 1.59). According to multivariate logistic regression analysis, postoperative complications were independently predicted by the European System for Cardiac Operative Risk Evaluation (OR 1.1, P nutritional therapy would improve the outcome in malnourished patients needs to be studied. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Introducing Thermal Wave Transport Analysis (TWTA): A Thermal Technique for Dopamine Detection by Screen-Printed Electrodes Functionalized with Molecularly Imprinted Polymer (MIP) Particles.

    Science.gov (United States)

    Peeters, Marloes M; van Grinsven, Bart; Foster, Christopher W; Cleij, Thomas J; Banks, Craig E

    2016-04-26

    A novel procedure is developed for producing bulk modified Molecularly Imprinted Polymer (MIP) screen-printed electrodes (SPEs), which involves the direct mixing of the polymer particles within the screen-printed ink. This allowed reduction of the sample preparation time from 45 min to 1 min, and resulted in higher reproducibility of the electrodes. The samples are measured with a novel detection method, namely, thermal wave transport analysis (TWTA), relying on the analysis of thermal waves through a functional interface. As a first proof-of-principle, MIPs for dopamine are developed and successfully incorporated within a bulk modified MIP SPE. The detection limits of dopamine within buffer solutions for the MIP SPEs are determined via three independent techniques. With cyclic voltammetry this was determined to be 4.7 × 10(-6) M, whereas by using the heat-transfer method (HTM) 0.35 × 10(-6) M was obtained, and with the novel TWTA concept 0.26 × 10(-6) M is possible. This TWTA technique is measured simultaneously with HTM and has the benefits of reducing measurement time to less than 5 min and increasing effect size by nearly a factor of two. The two thermal methods are able to enhance dopamine detection by one order of magnitude compared to the electrochemical method. In previous research, it was not possible to measure neurotransmitters in complex samples with HTM, but with the improved signal-to-noise of TWTA for the first time, spiked dopamine concentrations were determined in a relevant food sample. In summary, novel concepts are presented for both the sensor functionalization side by employing screen-printing technology, and on the sensing side, the novel TWTA thermal technique is reported. The developed bio-sensing platform is cost-effective and suitable for mass-production due to the nature of screen-printing technology, which makes it very interesting for neurotransmitter detection in clinical diagnostic applications.

  20. [Molecular genetic diagnostics and screening of hereditary hemochromatosis].

    Science.gov (United States)

    Zlocha, J; Kovács, L; Pozgayová, S; Kupcová, V; Durínová, S

    2006-06-01

    identified through biochemical testing for iron overload using serum transferrin saturation and genetic testing for C282Y homozygosity. DNA analysis is recommended in patients whose transferrin saturation is 45% or more on a repeated test. General population screening has been waived in preference to targeting high-risk groups such as first-degree relatives of affected individuals and those with secondary iron overload, especially patients with chronic liver disorders and chronic anemia. This screening strategy is likely to continue until uncertainties regarding the natural history of the disease, age-related penetrance, and management of asymptomatic individuals are clarified.

  1. Application of support vector machine to three-dimensional shape-based virtual screening using comprehensive three-dimensional molecular shape overlay with known inhibitors.

    Science.gov (United States)

    Sato, Tomohiro; Yuki, Hitomi; Takaya, Daisuke; Sasaki, Shunta; Tanaka, Akiko; Honma, Teruki

    2012-04-23

    In this study, machine learning using support vector machine was combined with three-dimensional (3D) molecular shape overlay, to improve the screening efficiency. Since the 3D molecular shape overlay does not use fingerprints or descriptors to compare two compounds, unlike 2D similarity methods, the application of machine learning to a 3D shape-based method has not been extensively investigated. The 3D similarity profile of a compound is defined as the array of 3D shape similarities with multiple known active compounds of the target protein and is used as the explanatory variable of support vector machine. As the measures of 3D shape similarity for our new prediction models, the prediction performances of the 3D shape similarity metrics implemented in ROCS, such as ShapeTanimoto and ScaledColor, were validated, using the known inhibitors of 15 target proteins derived from the ChEMBL database. The learning models based on the 3D similarity profiles stably outperformed the original ROCS when more than 10 known inhibitors were available as the queries. The results demonstrated the advantages of combining machine learning with the 3D similarity profile to process the 3D shape information of plural active compounds.

  2. Interventions Promoting Breast Cancer Screening Among Turkish Women With Global Implications: A Systematic Review.

    Science.gov (United States)

    Secginli, Selda; Nahcivan, Nursen O; Gunes, Gussun; Fernandez, Ritin

    2017-08-01

    Breast cancer is a major health concern and remains the most common malignancy in women worldwide and in Turkey. Mammography, clinical breast examination (CBE), and breast self-examination (BSE) are recommended methods to detect early breast cancer in women. Many strategies have been developed to increase the rates of mammography, CBE, and BSE among Turkish women. Despite the benefits of breast cancer screening, these modalities are still underutilized by the majority of Turkish women. To systematically review the scientific evidence on the effectiveness of various strategies aimed at improving screening behaviors for breast cancer in Turkish women. A systematic review of the literature published between 2000 and 2015 was conducted, searching 10 databases of Ovid MEDLINE, PubMed, Cochrane CENTRAL Register of Controlled Trials, CINAHL, PsycINFO, Web of Knowledge, Scopus, Google Scholar, ULAKBIM Turkish Medical Database, and Council of Higher Education Thesis Center. Twenty-three studies were included in the final review. The majority of the studies investigated the effects of multiple strategies to improve BSE. Group education comprised educational sessions, printed and audiovisual materials, which significantly improved BSE, CBE, and mammography screening rates at 3 months, 6 months, and 12 months after the intervention. One-to-one education demonstrated no significant difference in BSE rates at 6-month and 12-month follow-up. However, one-to-one education demonstrated significant differences in CBE and mammography rates at the 3-month follow-up. The use of group education comprising a multicomponent intervention demonstrated an increase in breast-screening behaviors among Turkish women. Further research investigating the duration of educational interventions is needed in order to suggest a "dose response." © 2017 Sigma Theta Tau International.

  3. Tiered High-Throughput Screening Approach to Identify Thyroperoxidase Inhibitors within the ToxCast Phase I and II Chemical Libraries

    Science.gov (United States)

    High-throughput screening (HTS) for potential thyroid–disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge on perturbed thyroid hormone (TH) homeostasis. Screening for MIEs specific to TH-disrupting pathways is limi...

  4. Antiprotozoan lead discovery by aligning dry and wet screening: prediction, synthesis, and biological assay of novel quinoxalinones.

    Science.gov (United States)

    Martins Alho, Miriam A; Marrero-Ponce, Yovani; Barigye, Stephen J; Meneses-Marcel, Alfredo; Machado Tugores, Yanetsy; Montero-Torres, Alina; Gómez-Barrio, Alicia; Nogal, Juan J; García-Sánchez, Rory N; Vega, María Celeste; Rolón, Miriam; Martínez-Fernández, Antonio R; Escario, José A; Pérez-Giménez, Facundo; Garcia-Domenech, Ramón; Rivera, Norma; Mondragón, Ricardo; Mondragón, Mónica; Ibarra-Velarde, Froylán; Lopez-Arencibia, Atteneri; Martín-Navarro, Carmen; Lorenzo-Morales, Jacob; Cabrera-Serra, Maria Gabriela; Piñero, Jose; Tytgat, Jan; Chicharro, Roberto; Arán, Vicente J

    2014-03-01

    Protozoan parasites have been one of the most significant public health problems for centuries and several human infections caused by them have massive global impact. Most of the current drugs used to treat these illnesses have been used for decades and have many limitations such as the emergence of drug resistance, severe side-effects, low-to-medium drug efficacy, administration routes, cost, etc. These drugs have been largely neglected as models for drug development because they are majorly used in countries with limited resources and as a consequence with scarce marketing possibilities. Nowadays, there is a pressing need to identify and develop new drug-based antiprotozoan therapies. In an effort to overcome this problem, the main purpose of this study is to develop a QSARs-based ensemble classifier for antiprotozoan drug-like entities from a heterogeneous compounds collection. Here, we use some of the TOMOCOMD-CARDD molecular descriptors and linear discriminant analysis (LDA) to derive individual linear classification functions in order to discriminate between antiprotozoan and non-antiprotozoan compounds as a way to enable the computational screening of virtual combinatorial datasets and/or drugs already approved. Firstly, we construct a wide-spectrum benchmark database comprising of 680 organic chemicals with great structural variability (254 of them antiprotozoan agents and 426 to drugs having other clinical uses). This series of compounds was processed by a k-means cluster analysis in order to design training and predicting sets. In total, seven discriminant functions were obtained, by using the whole set of atom-based linear indices. All the LDA-based QSAR models show accuracies above 85% in the training set and values of Matthews correlation coefficients (C) vary from 0.70 to 0.86. The external validation set shows rather-good global classifications of around 80% (92.05% for best equation). Later, we developed a multi-agent QSAR classification system, in

  5. Fragment-based screening by protein crystallography: successes and pitfalls.

    Science.gov (United States)

    Chilingaryan, Zorik; Yin, Zhou; Oakley, Aaron J

    2012-10-08

    Fragment-based drug discovery (FBDD) concerns the screening of low-molecular weight compounds against macromolecular targets of clinical relevance. These compounds act as starting points for the development of drugs. FBDD has evolved and grown in popularity over the past 15 years. In this paper, the rationale and technology behind the use of X-ray crystallography in fragment based screening (FBS) will be described, including fragment library design and use of synchrotron radiation and robotics for high-throughput X-ray data collection. Some recent uses of crystallography in FBS will be described in detail, including interrogation of the drug targets β-secretase, phenylethanolamine N-methyltransferase, phosphodiesterase 4A and Hsp90. These examples provide illustrations of projects where crystallography is straightforward or difficult, and where other screening methods can help overcome the limitations of crystallography necessitated by diffraction quality.

  6. Fragment-Based Screening by Protein Crystallography: Successes and Pitfalls

    Directory of Open Access Journals (Sweden)

    Aaron J. Oakley

    2012-10-01

    Full Text Available Fragment-based drug discovery (FBDD concerns the screening of low-molecular weight compounds against macromolecular targets of clinical relevance. These compounds act as starting points for the development of drugs. FBDD has evolved and grown in popularity over the past 15 years. In this paper, the rationale and technology behind the use of X-ray crystallography in fragment based screening (FBS will be described, including fragment library design and use of synchrotron radiation and robotics for high-throughput X-ray data collection. Some recent uses of crystallography in FBS will be described in detail, including interrogation of the drug targets β-secretase, phenylethanolamine N-methyltransferase, phosphodiesterase 4A and Hsp90. These examples provide illustrations of projects where crystallography is straightforward or difficult, and where other screening methods can help overcome the limitations of crystallography necessitated by diffraction quality.

  7. Global Microbial Identifier

    DEFF Research Database (Denmark)

    Wielinga, Peter; Hendriksen, Rene S.; Aarestrup, Frank Møller

    2017-01-01

    ) will likely also enable a much better understanding of the pathogenesis of the infection and the molecular basis of the host response to infection. But the full potential of these advances will only transpire if the data in this area become transferable and thereby comparable, preferably in open-source...... of microorganisms, for the identification of relevant genes and for the comparison of genomes to detect outbreaks and emerging pathogens. To harness the full potential of WGS, a shared global database of genomes linked to relevant metadata and the necessary software tools needs to be generated, hence the global...... microbial identifier (GMI) initiative. This tool will ideally be used in amongst others in the diagnosis of infectious diseases in humans and animals, in the identification of microorganisms in food and environment, and to track and trace microbial agents in all arenas globally. This will require...

  8. Factors affecting attendance to cervical cancer screening among women in the Paracentral Region of El Salvador: a nested study within the CAPE HPV screening program.

    Science.gov (United States)

    Alfaro, Karla M; Gage, Julia C; Rosenbaum, Alan J; Ditzian, Lauren R; Maza, Mauricio; Scarinci, Isabel C; Miranda, Esmeralda; Villalta, Sofia; Felix, Juan C; Castle, Philip E; Cremer, Miriam L

    2015-10-16

    Cervical cancer is the third most commonly occurring cancer among women and the fourth leading cause of cancer-related deaths in women worldwide, with more than 85 % of these cases occurring in developing countries. These global disparities reflect the differences in cervical cancer screening rates between high-income and medium- and low-income countries. At 19 %, El Salvador has the lowest reported screening coverage of all Latin American countries. The purpose of this study is to identify factors affecting public sector HPV DNA-based cervical cancer screening participation in El Salvador. This study was nested within a public sector screening program where health promoters used door-to-door outreach to recruit women aged 30-49 years to attend educational sessions about HPV screening. A subgroup of these participants was chosen randomly and questioned about demographic factors, healthcare utilization, previous cervical cancer screening, and HPV knowledge. Women then scheduled screening appointments at their public health clinics. Screening participants were adherent if they attended their scheduled appointment or rescheduled and were screened within 6 months. The association between non-adherence and demographic variables, medical history, history of cancer, sexual history, birth control methods, and screening barriers was assessed using Chi-square tests of significance and logistic regression. All women (n = 409) enrolled in the study scheduled HPV screening appointments, and 88 % attended. Non-adherence was associated with a higher number of lifetime partners and being under-screened-defined as not having participated in cervical cancer screening within the previous 3 years (p = 0.03 and p = 0.04, respectively); 22.8 % of participants in this study were under-screened. Adherence to cervical cancer screening after educational sessions was higher than expected, in part due to interactions with the community-based health promoters as well as the educational session

  9. Versatile Molecular Silver Ink Platform for Printed Flexible Electronics.

    Science.gov (United States)

    Kell, Arnold J; Paquet, Chantal; Mozenson, Olga; Djavani-Tabrizi, Iden; Deore, Bhavana; Liu, Xiangyang; Lopinski, Gregory P; James, Robert; Hettak, Khelifa; Shaker, Jafar; Momciu, Adrian; Ferrigno, Julie; Ferrand, Olivier; Hu, Jian Xiong; Lafrenière, Sylvie; Malenfant, Patrick R L

    2017-05-24

    A silver molecular ink platform formulated for screen, inkjet, and aerosol jet printing is presented. A simple formulation comprising silver neodecanoate, ethyl cellulose, and solvent provides improved performance versus that of established inks, yet with improved economics. Thin, screen-printed traces with exceptional electrical (molecular ink platform enables an aerosol jet-compatible ink that yields conductive features on glass with 2× bulk resistivity and strong adhesion to various plastic substrates. An inkjet formulation is also used to print top source/drain contacts and demonstrate printed high-mobility thin film transistors (TFTs) based on semiconducting single-walled carbon nanotubes. TFTs with mobility values of ∼25 cm 2 V -1 s -1 and current on/off ratios >10 4 were obtained, performance similar to that of evaporated metal contacts in analogous devices.

  10. Observed Screen (Air) and GCM Surface/Screen Temperatures: Implications for Outgoing Longwave Fluxes at the Surface.

    Science.gov (United States)

    Garratt, J. R.

    1995-05-01

    There is direct evidence that excess net radiation calculated in general circulation models at continental surfaces [of about 11-17 W m2 (20%-27%) on an annual ~1 is not only due to overestimates in annual incoming shortwave fluxes [of 9-18 W m2 (6%-9%)], but also to underestimates in outgoing longwave fluxes. The bias in the outgoing longwave flux is deduced from a comparison of screen-air temperature observations, available as a global climatology of mean monthly values, and model-calculated surface and screen-air temperatures. An underestimate in the screen temperature computed in general circulation models over continents, of about 3 K on an annual basis, implies an underestimate in the outgoing longwave flux, averaged in six models under study, of 11-15 W m2 (3%-4%). For a set of 22 inland stations studied previously, the residual bias on an annual basis (the residual is the net radiation minus incoming shortwave plus outgoing longwave) varies between 18 and 23 W m2 for the models considered. Additional biases in one or both of the reflected shortwave and incoming longwave components cannot be ruled out.

  11. Systematic review of model-based cervical screening evaluations.

    Science.gov (United States)

    Mendes, Diana; Bains, Iren; Vanni, Tazio; Jit, Mark

    2015-05-01

    Optimising population-based cervical screening policies is becoming more complex due to the expanding range of screening technologies available and the interplay with vaccine-induced changes in epidemiology. Mathematical models are increasingly being applied to assess the impact of cervical cancer screening strategies. We systematically reviewed MEDLINE®, Embase, Web of Science®, EconLit, Health Economic Evaluation Database, and The Cochrane Library databases in order to identify the mathematical models of human papillomavirus (HPV) infection and cervical cancer progression used to assess the effectiveness and/or cost-effectiveness of cervical cancer screening strategies. Key model features and conclusions relevant to decision-making were extracted. We found 153 articles meeting our eligibility criteria published up to May 2013. Most studies (72/153) evaluated the introduction of a new screening technology, with particular focus on the comparison of HPV DNA testing and cytology (n = 58). Twenty-eight in forty of these analyses supported HPV DNA primary screening implementation. A few studies analysed more recent technologies - rapid HPV DNA testing (n = 3), HPV DNA self-sampling (n = 4), and genotyping (n = 1) - and were also supportive of their introduction. However, no study was found on emerging molecular markers and their potential utility in future screening programmes. Most evaluations (113/153) were based on models simulating aggregate groups of women at risk of cervical cancer over time without accounting for HPV infection transmission. Calibration to country-specific outcome data is becoming more common, but has not yet become standard practice. Models of cervical screening are increasingly used, and allow extrapolation of trial data to project the population-level health and economic impact of different screening policy. However, post-vaccination analyses have rarely incorporated transmission dynamics. Model calibration to country

  12. The first three years of screening for medium chain acyl-CoA dehydrogenase deficiency (MCADD by newborn screening ontario

    Directory of Open Access Journals (Sweden)

    Fisher Lawrence

    2010-11-01

    Full Text Available Abstract Background Medium chain acyl-CoA dehydrogenase deficiency (MCADD is a disorder of mitochondrial fatty acid oxidation and is one of the most common inborn errors of metabolism. Identification of MCADD via newborn screening permits the introduction of interventions that can significantly reduce associated morbidity and mortality. This study reports on the first three years of newborn screening for MCADD in Ontario, Canada. Methods Newborn Screening Ontario began screening for MCADD in April 2006, by quantification of acylcarnitines (primarily octanoylcarnitine, C8 in dried blood spots using tandem mass spectrometry. Babies with positive screening results were referred to physicians at one of five regional Newborn Screening Treatment Centres, who were responsible for diagnostic evaluation and follow-up care. Results From April 2006 through March 2009, approximately 439 000 infants were screened for MCADD in Ontario. Seventy-four infants screened positive, with a median C8 level of 0.68 uM (range 0.33-30.41 uM. Thirty-one of the screen positive infants have been confirmed to have MCADD, while 36 have been confirmed to be unaffected. Screening C8 levels were higher among infants with MCADD (median 8.93 uM compared to those with false positive results (median 0.47 uM. Molecular testing was available for 29 confirmed cases of MCADD, 15 of whom were homozygous for the common c.985A > G mutation. Infants homozygous for the common mutation tended to have higher C8 levels (median 12.13 uM relative to compound heterozygotes for c.985A > G and a second detectable mutation (median 2.01 uM. Eight confirmed mutation carriers were identified among infants in the false positive group. The positive predictive value of a screen positive for MCADD was 46%. The estimated birth prevalence of MCADD in Ontario is approximately 1 in 14 000. Conclusions The birth prevalence of MCADD and positive predictive value of the screening test were similar to those

  13. Lynch Syndrome: Female Genital Tract Cancer Diagnosis and Screening.

    Science.gov (United States)

    Mills, Anne M; Longacre, Teri A

    2016-06-01

    Lynch syndrome is responsible for approximately 5% of endometrial cancers and 1% of ovarian cancers. The molecular basis for Lynch syndrome is a heritable functional deficiency in the DNA mismatch repair system, typically due to a germline mutation. This review discusses the rationales and relative merits of current Lynch syndrome screening tests for endometrial and ovarian cancers and provides pathologists with an informed algorithmic approach to Lynch syndrome testing in gynecologic cancers. Pitfalls in test interpretation and strategies to resolve discordant test results are presented. The potential role for next-generation sequencing panels in future screening efforts is discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Molecular biodiversity of Red Sea demosponges.

    Science.gov (United States)

    Erpenbeck, Dirk; Voigt, Oliver; Al-Aidaroos, Ali M; Berumen, Michael L; Büttner, Gabriele; Catania, Daniela; Guirguis, Adel Naguib; Paulay, Gustav; Schätzle, Simone; Wörheide, Gert

    2016-04-30

    Sponges are important constituents of coral reef ecosystems, including those around the Arabian Peninsula. Despite their importance, our knowledge on demosponge diversity in this area is insufficient to recognize, for example, faunal changes caused by anthropogenic disturbances. We here report the first assessment of demosponge molecular biodiversity from Arabia, with focus on the Saudi Arabian Red Sea, based on mitochondrial and nuclear ribosomal molecular markers gathered in the framework of the Sponge Barcoding Project. We use a rapid molecular screening approach on Arabian demosponge collections and analyze results in comparison against published material in terms of biodiversity. We use a variable region of 28S rDNA, applied for the first time in the assessment of demosponge molecular diversity. Our data constitutes a solid foundation for a future more comprehensive understanding of sponge biodiversity of the Red Sea and adjacent waters. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Molecular characterization of Cymbidium kanran cultivars based on ...

    African Journals Online (AJOL)

    Fifty-four Cymbidium kanran cultivars from China, Japan and Korea were examined and analyzed by using the successive screening of 3'-end extended random primer amplified polymorphic DNA (ERAPD) markers to determine their molecular diversity and relationships. In ERAPD analyses, the strandspecific DNA ...

  16. Chronic kidney disease screening: Results of the 2013 World ...

    African Journals Online (AJOL)

    Background: Chronic kidney disease (CKD) is on the rise globally due to the increase in prevalence of common risk factors. Screening for CKD risk factors is important for early detection and institution of measures to retard its progression. This study aimed to determine the markers of CKD and its risk factors in a selected ...

  17. Screening and rapid molecular diagnosis of tuberculosis in prisons in Russia and Eastern Europe: a cost-effectiveness analysis.

    Directory of Open Access Journals (Sweden)

    Daniel E Winetsky

    Full Text Available Prisons of the former Soviet Union (FSU have high rates of multidrug-resistant tuberculosis (MDR-TB and are thought to drive general population tuberculosis (TB epidemics. Effective prison case detection, though employing more expensive technologies, may reduce long-term treatment costs and slow MDR-TB transmission.We developed a dynamic transmission model of TB and drug resistance matched to the epidemiology and costs in FSU prisons. We evaluated eight strategies for TB screening and diagnosis involving, alone or in combination, self-referral, symptom screening, mass miniature radiography (MMR, and sputum PCR with probes for rifampin resistance (Xpert MTB/RIF. Over a 10-y horizon, we projected costs, quality-adjusted life years (QALYs, and TB and MDR-TB prevalence. Using sputum PCR as an annual primary screening tool among the general prison population most effectively reduced overall TB prevalence (from 2.78% to 2.31% and MDR-TB prevalence (from 0.74% to 0.63%, and cost US$543/QALY for additional QALYs gained compared to MMR screening with sputum PCR reserved for rapid detection of MDR-TB. Adding sputum PCR to the currently used strategy of annual MMR screening was cost-saving over 10 y compared to MMR screening alone, but produced only a modest reduction in MDR-TB prevalence (from 0.74% to 0.69% and had minimal effect on overall TB prevalence (from 2.78% to 2.74%. Strategies based on symptom screening alone were less effective and more expensive than MMR-based strategies. Study limitations included scarce primary TB time-series data in FSU prisons and uncertainties regarding screening test characteristics.In prisons of the FSU, annual screening of the general inmate population with sputum PCR most effectively reduces TB and MDR-TB prevalence, doing so cost-effectively. If this approach is not feasible, the current strategy of annual MMR is both more effective and less expensive than strategies using self-referral or symptom screening alone

  18. Screened Coulomb balls-structural properties and melting behaviour

    International Nuclear Information System (INIS)

    Golubnychiy, V; Baumgartner, H; Bonitz, M; Filinov, A; Fehske, H

    2006-01-01

    Classical molecular dynamics and Monte Carlo simulations are used to investigate three-dimensional spherical charged particle clusters which were experimentally observed in dusty plasmas (Arp et al 2004 Phys. Rev. Lett. 93 165005). The shell configuration and geometry of the ground state is found to change with the screening parameter. The melting temperature of small clusters exhibits a non-monotonic dependence on the total number of particles

  19. Screening of metal-organic frameworks for carbon dioxide capture from flue gas using a combined experimental and modeling approach.

    Science.gov (United States)

    Yazaydin, A Ozgür; Snurr, Randall Q; Park, Tae-Hong; Koh, Kyoungmoo; Liu, Jian; Levan, M Douglas; Benin, Annabelle I; Jakubczak, Paulina; Lanuza, Mary; Galloway, Douglas B; Low, John J; Willis, Richard R

    2009-12-30

    A diverse collection of 14 metal-organic frameworks (MOFs) was screened for CO(2) capture from flue gas using a combined experimental and modeling approach. Adsorption measurements are reported for the screened MOFs at room temperature up to 1 bar. These data are used to validate a generalized strategy for molecular modeling of CO(2) and other small molecules in MOFs. MOFs possessing a high density of open metal sites are found to adsorb significant amounts of CO(2) even at low pressure. An excellent correlation is found between the heat of adsorption and the amount of CO(2) adsorbed below 1 bar. Molecular modeling can aid in selection of adsorbents for CO(2) capture from flue gas by screening a large number of MOFs.

  20. Breast Cancer Challenges and Screening in China: Lessons From Current Registry Data and Population Screening Studies.

    Science.gov (United States)

    Song, Qing-Kun; Wang, Xiao-Li; Zhou, Xin-Na; Yang, Hua-Bing; Li, Yu-Chen; Wu, Jiang-Ping; Ren, Jun; Lyerly, Herbert Kim

    2015-07-01

    As one of its responses to the increasing global burden of breast cancer (BC), China has deployed a national registration and BC screening campaign. The present report describes these programs and the initial results of these national BC control strategies, highlighting the challenges to be considered. The primary BC incidence and prevalence data were obtained from the Chinese National Central Cancer Registry. MapInfo software was used to map the geographic distribution and variation. The time trends were estimated by the annual percentage of change from 2003 to 2009. The description of the screening plans and preliminary results were provided by the Ministry of Health. Chinese cancer registries were primarily developed and activated in the East and Coastal regions of China, with only 12.5% of the registries located in West China. Geographic variation was noted, with the incidence of BC higher in North China than in South China and in urban areas compared with rural areas. Of great interest, these registries reported that the overall BC incidence has been increasing in China, with an earlier age of onset compared with Western countries and a peak incidence rate at age 50. In response to this increasing incidence and early age of onset, BC screening programs assessed 1.46 million women aged 35-59 years, using clinical breast examinations and ultrasound as primary screening tools between 2009 and 2011. The diagnostic rate for this screening program was only 48.0/10(5) with 440 cases of early stage BC. Early stage BC was detected in nearly 70% of screened patients. Subsequently, a second-generation screening program was conducted that included older women aged 35-64 years and an additional 6 million women were screened. The cancer registration system in China has been uneven, with a greater focus on East rather than West China. The data from these registries demonstrate regional variation, an increasing BC incidence, and an early age of onset. The 2009 to 2011 BC

  1. Role of Open Source Tools and Resources in Virtual Screening for Drug Discovery.

    Science.gov (United States)

    Karthikeyan, Muthukumarasamy; Vyas, Renu

    2015-01-01

    Advancement in chemoinformatics research in parallel with availability of high performance computing platform has made handling of large scale multi-dimensional scientific data for high throughput drug discovery easier. In this study we have explored publicly available molecular databases with the help of open-source based integrated in-house molecular informatics tools for virtual screening. The virtual screening literature for past decade has been extensively investigated and thoroughly analyzed to reveal interesting patterns with respect to the drug, target, scaffold and disease space. The review also focuses on the integrated chemoinformatics tools that are capable of harvesting chemical data from textual literature information and transform them into truly computable chemical structures, identification of unique fragments and scaffolds from a class of compounds, automatic generation of focused virtual libraries, computation of molecular descriptors for structure-activity relationship studies, application of conventional filters used in lead discovery along with in-house developed exhaustive PTC (Pharmacophore, Toxicophores and Chemophores) filters and machine learning tools for the design of potential disease specific inhibitors. A case study on kinase inhibitors is provided as an example.

  2. Global distribution of novel rhinovirus genotype

    DEFF Research Database (Denmark)

    Briese, Thomas; Renwick, Neil; Venter, Marietjie

    2008-01-01

    Global surveillance for a novel rhinovirus genotype indicated its association with community outbreaks and pediatric respiratory disease in Africa, Asia, Australia, Europe, and North America. Molecular dating indicates that these viruses have been circulating for at least 250 years Udgivelsesdato...

  3. Newborn Screening for Primary Immunodeficiency Diseases: The Past, the Present and the Future

    Directory of Open Access Journals (Sweden)

    Jovanka King

    2017-08-01

    Full Text Available Primary immunodeficiency diseases (PID are a heterogeneous group of disorders caused by inborn errors of immunity, with affected children presenting with severe, recurrent or unusual infections. Over 300 distinct genetic molecular abnormalities resulting in PID have been identified, and this number continues to rise. Newborn screening for PID has been established in many countries, with the majority of centers using a PCR-based T cell receptor excision circle (TREC assay to screen for severe combined immunodeficiency (SCID and other forms of T cell lymphopenia. Multiplexed screening including quantitation of kappa-recombining exclusion circles (KREC has also been described, offering advantages over TREC screening alone. Screening technologies are also expanding to include protein-based assays to identify complement deficiencies and granulocyte disorders. Given the rapid advances in genomic medicine, a potential future direction is the application of next-generation sequencing (NGS technologies to screen infants for a panel of genetic mutations, which would enable identification of a wide range of diseases. However, several ethical and economic issues must be considered before moving towards this screening strategy.

  4. Innovative approaches to cervical cancer screening for sex trade workers: an international scoping review.

    Science.gov (United States)

    Thulien, Naomi S

    2014-03-01

    Female sex trade workers are among those at highest risk for developing and dying of cervical cancer, and yet many-particularly the most marginalized-are less likely than other women to be screened. This review summarizes global findings on innovative approaches to cervical cancer screening for female sex trade workers, highlights current gaps in the delivery of cervical cancer screening for female sex trade workers globally, and suggests areas for future research and policy development. A scoping review of peer-reviewed publications and grey literature was conducted. Medline (OVID), PubMed, EMBASE, and SCOPUS were searched for relevant studies written in English. There were no limitations placed on dates. Grey literature was identified by hand searching and through discussion with health care providers and community outreach workers currently working with sex trade workers. Twenty-five articles were deemed suitable for review. Articles detailing innovative ways for female sex trade workers to access cervical cancer screening were included. Articles about screening for sexually transmitted infections were also included if the findings could be generalized to screening for cervical cancer. Articles limited to exploring risk factors, knowledge, awareness, education, prevalence, and incidence of cervical cancer among sex trade workers were excluded from the review. Successful screening initiatives identified in the studies reviewed had unconventional hours of operation, understood the difference between street-based and venue-based sex trade workers, and/or used peers for outreach. Two significant gaps in health care service delivery were highlighted in this review: the limited use of unorthodox hours and the nearly exclusive practice of providing sexually transmitted infection screening for female sex trade workers without cervical cancer screening. In addition, although street-based (as opposed to venue-based) sex trade workers are likely at higher risk for

  5. Recent patents in plant biotechnology: impact on global health.

    Science.gov (United States)

    Hefferon, Kathleen L

    2012-08-01

    Agricultural biotechnology offers a robust series of tools by which to address global concerns such as food security, crop protection, and fuel/energy requirements. A number of advances made recently in plant molecular biology also have resulted in applications which largely focus on improving global human health. This review describes some of the recent innovations in plant biotechnology that have come to the forefront over the past year. Included are novel techniques by which plants can be improved as platforms for biopharmaceutical protein production, a growing field also referred to as 'molecular pharming'. The metabolic engineering of plants to produce compounds which have additional nutritional benefits is also outlined. The review concludes with a discussion of the future impact that these innovations may have both on global health and on the development of our future intellectual property landscape.

  6. Precision Medicine for Advanced Pancreas Cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) Trial.

    Science.gov (United States)

    Chantrill, Lorraine A; Nagrial, Adnan M; Watson, Clare; Johns, Amber L; Martyn-Smith, Mona; Simpson, Skye; Mead, Scott; Jones, Marc D; Samra, Jaswinder S; Gill, Anthony J; Watson, Nicole; Chin, Venessa T; Humphris, Jeremy L; Chou, Angela; Brown, Belinda; Morey, Adrienne; Pajic, Marina; Grimmond, Sean M; Chang, David K; Thomas, David; Sebastian, Lucille; Sjoquist, Katrin; Yip, Sonia; Pavlakis, Nick; Asghari, Ray; Harvey, Sandra; Grimison, Peter; Simes, John; Biankin, Andrew V

    2015-05-01

    Personalized medicine strategies using genomic profiling are particularly pertinent for pancreas cancer. The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial was initially designed to exploit results from genome sequencing of pancreatic cancer under the auspices of the International Cancer Genome Consortium (ICGC) in Australia. Sequencing revealed small subsets of patients with aberrations in their tumor genome that could be targeted with currently available therapies. The pilot stage of the IMPaCT trial assessed the feasibility of acquiring suitable tumor specimens for molecular analysis and returning high-quality actionable genomic data within a clinically acceptable timeframe. We screened for three molecular targets: HER2 amplification; KRAS wild-type; and mutations in DNA damage repair pathways (BRCA1, BRCA2, PALB2, ATM). Tumor biopsy and archived tumor samples were collected from 93 patients and 76 were screened. To date 22 candidate cases have been identified: 14 KRAS wild-type, 5 cases of HER2 amplification, 2 mutations in BRCA2, and 1 ATM mutation. Median time from consent to the return of validated results was 21.5 days. An inability to obtain a biopsy or insufficient tumor content in the available specimen were common reasons for patient exclusion from molecular analysis while deteriorating performance status prohibited a number of patients from proceeding in the study. Documenting the feasibility of acquiring and screening biospecimens for actionable molecular targets in real time will aid other groups embarking on similar trials. Key elements include the need to better prescreen patients, screen more patients, and offer more attractive clinical trial options. ©2015 American Association for Cancer Research.

  7. Nurses' roles in screening for intimate partner violence: a phenomenological study.

    Science.gov (United States)

    Al-Natour, A; Qandil, A; Gillespie, G L

    2016-09-01

    To describe Jordanian nurses' roles and practices in screening for intimate partner violence. Intimate partner violence is a recognized global health problem with a prevalence of 37% for the Eastern Mediterranean region. Jordanian nurses screening for intimate partner violence is as low as 10.8%. Nurses have encountered institutional and personal barriers hindering their screening practice. A descriptive phenomenological design was used for this study. A purposive sample of 12 male and female Jordanian nurses working at a university hospital in Jordan participated. Participants were interviewed in 2014 using a semi-structured, face-to-face interview. Steps of Colaizzi's phenomenological method were used to analyse the qualitative data. Four themes were derived from the data: (1) screening practices and roles for suspected IPV cases, (2) advantages for screening and disadvantages for not screening for intimate partner violence, (3) factors hindering screening practice and (4) feelings towards screening and not screening for intimate partner violence. Increasing Jordanian nurses' awareness of the need for intimate partner violence screening in this sample was needed. Professional education and training may facilitate the adoption of intimate partner violence screening practices. A key barrier to intimate partner violence screening is Jordanian nurses' personal beliefs. Overcoming these personal beliefs will necessitate a multi-faceted approach starting with schools of nursing and bridging into healthcare settings. Healthcare professionals including nursing and policy makers at health institutions should enforce screening policies and protocols for all receipt of care at first contact. In addition, an emphasis on modelling culturally congruent approaches to develop the trusting nurse-patient relationships and process for screening patients for intimate partner violence. © 2016 International Council of Nurses.

  8. Barriers to colorectal cancer screening in Asia: A systematic review ...

    African Journals Online (AJOL)

    Purpose: Colorectal cancer (CRC) is among the top five cancers afflicting both men and women globally. Once predominantly a Western disease, it has begun to rise in Asian countries as well. This systematic review aims to compile and analyze the various barriers towards colorectal cancer screening in Asia, and to ...

  9. High-resolution minisatellite-based typing as a portable approach to global analysis of Mycobacterium tuberculosis molecular epidemiology

    Science.gov (United States)

    Mazars, Edith; Lesjean, Sarah; Banuls, Anne-Laure; Gilbert, Michèle; Vincent, Véronique; Gicquel, Brigitte; Tibayrenc, Michel; Locht, Camille; Supply, Philip

    2001-01-01

    The worldwide threat of tuberculosis to human health emphasizes the need to develop novel approaches to a global epidemiological surveillance. The current standard for Mycobacterium tuberculosis typing based on IS6110 restriction fragment length polymorphism (RFLP) suffers from the difficulty of comparing data between independent laboratories. Here, we propose a high-resolution typing method based on variable number tandem repeats (VNTRs) of genetic elements named mycobacterial interspersed repetitive units (MIRUs) in 12 human minisatellite-like regions of the M. tuberculosis genome. MIRU-VNTR profiles of 72 different M. tuberculosis isolates were established by PCR analysis of all 12 loci. From 2 to 8 MIRU-VNTR alleles were identified in the 12 regions in these strains, which corresponds to a potential of over 16 million different combinations, yielding a resolution power close to that of IS6110-RFLP. All epidemiologically related isolates tested were perfectly clustered by MIRU-VNTR typing, indicating that the stability of these MIRU-VNTRs is adequate to track outbreak episodes. The correlation between genetic relationships inferred from MIRU-VNTR and IS6110-RFLP typing was highly significant. Compared with IS6110-RFLP, high-resolution MIRU-VNTR typing has the considerable advantages of being fast, appropriate for all M. tuberculosis isolates, including strains that have a few IS6110 copies, and permitting easy and rapid comparison of results from independent laboratories. This typing method opens the way to the construction of digital global databases for molecular epidemiology studies of M. tuberculosis. PMID:11172048

  10. The role of laboratory confirmations and molecular epidemiology in ...

    African Journals Online (AJOL)

    This review reports on the role of laboratory confirmation and molecular epidemiology in global eradication of measles. The role of laboratory confirmation and molecular epidemiology in defining the origins of measles outbreaks cannot be overemphasized. New serological tests based on recombinant proteins detect only a ...

  11. Retrofit Strategies for Incorporating Xenobiotic Metabolism into High Throughput Screening Assays (EMGS)

    Science.gov (United States)

    The US EPA’s ToxCast program is designed to assess chemical perturbations of molecular and cellular endpoints using a variety of high-throughput screening (HTS) assays. However, existing HTS assays have limited or no xenobiotic metabolism which could lead to a mischaracterization...

  12. Fluorescence-based high-throughput screening of dicer cleavage activity

    Czech Academy of Sciences Publication Activity Database

    Podolská, Kateřina; Sedlák, David; Bartůněk, Petr; Svoboda, Petr

    2014-01-01

    Roč. 19, č. 3 (2014), s. 417-426 ISSN 1087-0571 R&D Projects: GA ČR GA13-29531S; GA MŠk(CZ) LC06077; GA MŠk LM2011022 Grant - others:EMBO(DE) 1483 Institutional support: RVO:68378050 Keywords : Dicer * siRNA * high-throughput screening Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.423, year: 2014

  13. Overview of the status and global strategy for neonicotinoids.

    Science.gov (United States)

    Jeschke, Peter; Nauen, Ralf; Schindler, Michael; Elbert, Alfred

    2011-04-13

    In recent years, neonicotinoid insecticides have been the fastest growing class of insecticides in modern crop protection, with widespread use against a broad spectrum of sucking and certain chewing pests. As potent agonists, they act selectively on insect nicotinic acetylcholine receptors (nAChRs), their molecular target site. The discovery of neonicotinoids can be considered as a milestone in insecticide research and greatly facilitates the understanding of functional properties of the insect nAChRs. In this context, the crystal structure of the acetylcholine-binding proteins provides the theoretical foundation for designing homology models of the corresponding receptor ligand binding domains within the nAChRs, a useful basis for virtual screening of chemical libraries and rational design of novel insecticides acting on these practically relevant channels. Because of the relatively low risk for nontarget organisms and the environment, the high target specificity of neonicotinoid insecticides, and their versatility in application methods, this important class has to be maintained globally for integrated pest management strategies and insect resistance management programs. Innovative concepts for life-cycle management, jointly with the introduction of generic products, have made neonicotinoids the most important chemical class for the insecticide market.

  14. Interaction between molecular complexes in dispersive media

    International Nuclear Information System (INIS)

    Banagas, E.A.; Manykin, E.A.

    1987-01-01

    The interaction between molecular complexes in different dispersive media with local and nonlocal screening is investigated theoretically. On the basis of results of numerical analysis on a computer, the dependence of the coupled-system spectrum and the interaction energy of the polarized modes on the characteristic parameters of the dispersive media is considered

  15. Impact of cardiovascular counseling and screening in Hodgkin lymphoma survivors.

    Science.gov (United States)

    Daniëls, Laurien A; Krol, Stijn D G; de Graaf, Michiel A; Scholte, Arthur J H A; van 't Veer, Mars B; Putter, Hein; de Roos, Albert; Schalij, Martin J; van de Poll-Franse, Lonneke V; Creutzberg, Carien L

    2014-09-01

    Cardiovascular disease (CVD) is the most common nonmalignant cause of death in Hodgkin lymphoma (HL) survivors, especially after mediastinal irradiation. The role of screening for CVD in HL survivors is unclear, but confrontation with risks of CVD may have a negative influence on health-related quality of life (HRQL). As part of a phase 2 screening study using computed tomography angiography (CTA) among HL survivors, an HRQL analysis was done to evaluate the emotional and practical burden and perceived benefits of screening and the effect of CVD-specific counseling on patient satisfaction. Patients who participated in the screening study also took part in the HRQL study. The impact of undergoing screening was evaluated with a 9-item questionnaire, and impact on HRQL with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire C30, version 3.0. The effect of counseling of CVD on perceived provision of information was evaluated with EORTC INFO-25. All questionnaires were completed at baseline and after screening. Baseline questionnaires were received from 48 participants, and 43 completed questionnaires after screening. Mean age was 47 years, and mean time since diagnosis was 21 years. Of the total, 93% of subjects were content with participating, and 80% did not find the emphasis placed on late effects burdensome, although screening did have a small impact on social functioning and global quality of life. Perceived information on disease, medical tests, and treatment increased significantly after screening (Pinformation between patients with and without screen-detected CVD. Screening was evaluated favorably, whether CTA showed abnormalities or not. Extensive counseling resulted in substantially increased provision of information and improved information satisfaction. Screening by means of CTA and subsequent cardiac intervention was highly valued, and the benefits were felt to outweigh the emotional and practical

  16. Molecular characterization of Cymbidium kanran cultivars based on ...

    African Journals Online (AJOL)

    TUOYO

    2010-08-09

    Aug 9, 2010 ... Fifty-four Cymbidium kanran cultivars from China, Japan and Korea were examined and analyzed by using the successive screening of 3′-end extended random primer amplified polymorphic DNA (ERAPD) markers to determine their molecular diversity and relationships. In ERAPD analyses, the strand-.

  17. molecular identification of rotavirus strains associated with diarrhea

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. The study was carried out to determine the molecular characteristics of the rotavirus strains associated with diarrhea among children in Kwara state, Nigeria. A total of 150 stool samples were collected from diarrheic children. The stool samples were screened for rotavirus,using Enzyme linked Immunosorbent ...

  18. Molecular identification of rotavirus strains associated with diarrhea ...

    African Journals Online (AJOL)

    The study was carried out to determine the molecular characteristics of the rotavirus strains associated with diarrhea among children in Kwara state, Nigeria. A total of 150 stool samples were collected from diarrheic children. The stool samples were screened for rotavirus,using Enzyme linked Immunosorbent assay (ELISA).

  19. Screens

    OpenAIRE

    2016-01-01

    This Sixth volume in the series The Key Debates. Mutations and Appropriations in European Film Studies investigates the question of screens in the context both of the dematerialization due to digitalization and the multiplication of media screens. Scholars offer various infomations and theories of topics such as the archeology of screen, film and media theories, contemporary art, pragmatics of new ways of screening (from home video to street screening).

  20. The Diabetic Retinopathy Screening Workflow: Potential for Smartphone Imaging.

    Science.gov (United States)

    Bolster, Nigel M; Giardini, Mario E; Bastawrous, Andrew

    2015-11-23

    Complications of diabetes mellitus, namely diabetic retinopathy and diabetic maculopathy, are the leading cause of blindness in working aged people. Sufferers can avoid blindness if identified early via retinal imaging. Systematic screening of the diabetic population has been shown to greatly reduce the prevalence and incidence of blindness within the population. Many national screening programs have digital fundus photography as their basis. In the past 5 years several techniques and adapters have been developed that allow digital fundus photography to be performed using smartphones. We review recent progress in smartphone-based fundus imaging and discuss its potential for integration into national systematic diabetic retinopathy screening programs. Some systems have produced promising initial results with respect to their agreement with reference standards. However further multisite trialling of such systems' use within implementable screening workflows is required if an evidence base strong enough to affect policy change is to be established. If this were to occur national diabetic retinopathy screening would, for the first time, become possible in low- and middle-income settings where cost and availability of trained eye care personnel are currently key barriers to implementation. As diabetes prevalence and incidence is increasing sharply in these settings, the impact on global blindness could be profound. © 2015 Diabetes Technology Society.

  1. Noninvasive molecular screening for oral precancer in Fanconi anemia patients.

    Science.gov (United States)

    Smetsers, Stephanie E; Velleuer, Eunike; Dietrich, Ralf; Wu, Thijs; Brink, Arjen; Buijze, Marijke; Deeg, Dorly J H; Soulier, Jean; Leemans, C René; Braakhuis, Boudewijn J M; Brakenhoff, Ruud H

    2015-11-01

    LOH at chromosome arms 3p, 9p, 11q, and 17p are well-established oncogenetic aberrations in oral precancerous lesions and promising biomarkers to monitor the development of oral cancer. Noninvasive LOH screening of brushed oral cells is a preferable method for precancer detection in patients at increased risk for head and neck squamous cell carcinoma (HNSCC), such as patients with Fanconi anemia. We determined the prevalence of LOH in brushed samples of the oral epithelium of 141 patients with Fanconi anemia and 144 aged subjects, and studied the association between LOH and HNSCC. LOH was present in 14 (9.9%) nontransplanted patients with Fanconi anemia, whereas LOH was not detected in a low-risk group (n = 50, >58 years, nonsmoking/nonalcohol history) and a group with somewhat increased HNSCC risk (n = 94, >58 years, heavy smoking/excessive alcohol use); Fisher exact test, P = 0.023 and P = 0.001, respectively. Most frequent genetic alteration was LOH at 9p. Age was a significant predictor of LOH (OR, 1.13, P = 0.001). Five patients with Fanconi anemia developed HNSCC during the study at a median age of 39.6 years (range, 24.8-53.7). LOH was significantly associated with HNSCC (Fisher exact test, P = 0.000). Unexpectedly, the LOH assay could not be used for transplanted patients with Fanconi anemia because donor DNA in brushed oral epithelium, most likely from donor leukocytes present in the oral cavity, disturbed the analysis. Noninvasive screening using a LOH assay on brushed samples of the oral epithelium has a promising outlook in patients with Fanconi anemia. However, assays need to be adapted in case of stem cell transplantation, because of contaminating donor DNA. ©2015 American Association for Cancer Research.

  2. Dual Binding Site and Selective Acetylcholinesterase Inhibitors Derived from Integrated Pharmacophore Models and Sequential Virtual Screening

    Directory of Open Access Journals (Sweden)

    Shikhar Gupta

    2014-01-01

    Full Text Available In this study, we have employed in silico methodology combining double pharmacophore based screening, molecular docking, and ADME/T filtering to identify dual binding site acetylcholinesterase inhibitors that can preferentially inhibit acetylcholinesterase and simultaneously inhibit the butyrylcholinesterase also but in the lesser extent than acetylcholinesterase. 3D-pharmacophore models of AChE and BuChE enzyme inhibitors have been developed from xanthostigmine derivatives through HypoGen and validated using test set, Fischer’s randomization technique. The best acetylcholinesterase and butyrylcholinesterase inhibitors pharmacophore hypotheses Hypo1_A and Hypo1_B, with high correlation coefficient of 0.96 and 0.94, respectively, were used as 3D query for screening the Zinc database. The screened hits were then subjected to the ADME/T and molecular docking study to prioritise the compounds. Finally, 18 compounds were identified as potential leads against AChE enzyme, showing good predicted activities and promising ADME/T properties.

  3. Molecular models of zinc phthalocyanines: semi-empirical molecular orbital computations and physicochemical properties studied by molecular mechanics simulations

    International Nuclear Information System (INIS)

    Gantchev, Tsvetan G.; van Lier, Johan E.; Hunting, Darel J.

    2005-01-01

    To build 3D-molecular models of Zinc-phthalocyanines (ZnPc) and to study their diverse chemical and photosensitization properties, we performed quantum mechanical molecular orbital (MO) semi-empirical (AM1) computations of the ground, excited singlet and triplet states as well as free radical (ionic) species. RHF and UHF (open shell) geometry optimizations led to near-perfect symmetrical ZnPc. Predicted ionization potentials (IP), electron affinities (EA) and lowest electronic transitions of ZnPc are in good agreement with the published experimental and theoretical data. The computation-derived D 4h /D 2h -symmetry 3D-structures of ground and excited states and free radicals of ZnPc, together with the frontier orbital energies and Mulliken electron population analysis enabled us to build robust molecular models. These models were used to predict important chemical-reactivity entities such as global electronegativity (χ), hardness (η) and local softness based on Fukui-functions analysis. Examples of molecular mechanics (MM) applications of the 3D-molecular models are presented as approaches to evaluate solvation free energy (ΔG 0 ) solv and to estimate ground- and excited- state oxidation/reduction potentials as well as intermolecular interactions and stability of ground and excited state dimers (exciplexes) and radical ion-pairs

  4. Global Sensitivity Analysis of Environmental Models: Convergence, Robustness and Validation

    Science.gov (United States)

    Sarrazin, Fanny; Pianosi, Francesca; Khorashadi Zadeh, Farkhondeh; Van Griensven, Ann; Wagener, Thorsten

    2015-04-01

    Global Sensitivity Analysis aims to characterize the impact that variations in model input factors (e.g. the parameters) have on the model output (e.g. simulated streamflow). In sampling-based Global Sensitivity Analysis, the sample size has to be chosen carefully in order to obtain reliable sensitivity estimates while spending computational resources efficiently. Furthermore, insensitive parameters are typically identified through the definition of a screening threshold: the theoretical value of their sensitivity index is zero but in a sampling-base framework they regularly take non-zero values. There is little guidance available for these two steps in environmental modelling though. The objective of the present study is to support modellers in making appropriate choices, regarding both sample size and screening threshold, so that a robust sensitivity analysis can be implemented. We performed sensitivity analysis for the parameters of three hydrological models with increasing level of complexity (Hymod, HBV and SWAT), and tested three widely used sensitivity analysis methods (Elementary Effect Test or method of Morris, Regional Sensitivity Analysis, and Variance-Based Sensitivity Analysis). We defined criteria based on a bootstrap approach to assess three different types of convergence: the convergence of the value of the sensitivity indices, of the ranking (the ordering among the parameters) and of the screening (the identification of the insensitive parameters). We investigated the screening threshold through the definition of a validation procedure. The results showed that full convergence of the value of the sensitivity indices is not necessarily needed to rank or to screen the model input factors. Furthermore, typical values of the sample sizes that are reported in the literature can be well below the sample sizes that actually ensure convergence of ranking and screening.

  5. Screening of cellular proteins that interact with the classical swine ...

    Indian Academy of Sciences (India)

    In the current study, aiming to find more clues in understanding the molecular mechanisms of CSFV NS5A's function, the yeast two-hybrid (Y2H) system was adopted to screen for CSFV NS5A interactive proteins in the cDNA library of the swine umbilical vein endothelial cell (SUVEC). Alignment with the NCBI database ...

  6. Molecular dynamics of the structure and thermodynamics of dusty ...

    African Journals Online (AJOL)

    The static structure and thermodynamic properties of two-dimensional dusty plasma are analyzed for some typical values of coupling and screening parameters using classical molecular dynamics. Radial distribution function and static structure factor are computed. The radial distribution functions display the typical ...

  7. Molecular epidemiology and population structure of bovine Streptococcus uberis

    DEFF Research Database (Denmark)

    Rato, M G; Bexiga, R; Nunes, S F

    2008-01-01

    The molecular epidemiology and population structure of 30 bovine subclinical mastitis field isolates of Streptococcus uberis, collected from 6 Portuguese herds (among 12 farms screened) during 2002 and 2003, were examined by using pulsed-field gel electrophoresis (PFGE) for clustering of the isol...

  8. Quality control methodology for high-throughput protein-protein interaction screening.

    Science.gov (United States)

    Vazquez, Alexei; Rual, Jean-François; Venkatesan, Kavitha

    2011-01-01

    Protein-protein interactions are key to many aspects of the cell, including its cytoskeletal structure, the signaling processes in which it is involved, or its metabolism. Failure to form protein complexes or signaling cascades may sometimes translate into pathologic conditions such as cancer or neurodegenerative diseases. The set of all protein interactions between the proteins encoded by an organism constitutes its protein interaction network, representing a scaffold for biological function. Knowing the protein interaction network of an organism, combined with other sources of biological information, can unravel fundamental biological circuits and may help better understand the molecular basics of human diseases. The protein interaction network of an organism can be mapped by combining data obtained from both low-throughput screens, i.e., "one gene at a time" experiments and high-throughput screens, i.e., screens designed to interrogate large sets of proteins at once. In either case, quality controls are required to deal with the inherent imperfect nature of experimental assays. In this chapter, we discuss experimental and statistical methodologies to quantify error rates in high-throughput protein-protein interactions screens.

  9. Big pharma screening collections: more of the same or unique libraries? The AstraZeneca-Bayer Pharma AG case.

    Science.gov (United States)

    Kogej, Thierry; Blomberg, Niklas; Greasley, Peter J; Mundt, Stefan; Vainio, Mikko J; Schamberger, Jens; Schmidt, Georg; Hüser, Jörg

    2013-10-01

    In this study, the screening collections of two major pharmaceutical companies (AstraZeneca and Bayer Pharma AG) have been compared using a 2D molecular fingerprint by a nearest neighborhood approach. Results revealed a low overlap between both collections in terms of compound identity and similarity. This emphasizes the value of screening multiple compound collections to expand the chemical space that can be accessed by high-throughput screening (HTS). Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Screening for chronic kidney disease and its risk factors in Oghara ...

    African Journals Online (AJOL)

    Background: The risk factors associated with CKD such as hypertension, diabetes and obesity remain prevalent globally, resulting in a high prevalence of CKD especially in developing countries. Screening for CKD and its' risk factors is recommended for high-risk population. This study aimed to determine the prevalence ...

  11. Exploring the Molecular Basis for Selective Binding of Homoserine Dehydrogenase from Mycobacterium leprae TN toward Inhibitors: A Virtual Screening Study

    Directory of Open Access Journals (Sweden)

    Dongling Zhan

    2014-01-01

    Full Text Available Homoserine dehydrogenase (HSD from Mycobacterium leprae TN is an antifungal target for antifungal properties including efficacy against the human pathogen. The 3D structure of HSD has been firmly established by homology modeling methods. Using the template, homoserine dehydrogenase from Thiobacillus denitrificans (PDB Id 3MTJ, a sequence identity of 40% was found and molecular dynamics simulation was used to optimize a reliable structure. The substrate and co-factor-binding regions in HSD were identified. In order to determine the important residues of the substrate (l-aspartate semialdehyde (l-ASA binding, the ASA was docked to the protein; Thr163, Asp198, and Glu192 may be important because they form a hydrogen bond with HSD through AutoDock 4.2 software. neuraminidaseAfter use of a virtual screening technique of HSD, the four top-scoring docking hits all seemed to cation–π ion pair with the key recognition residue Lys107, and Lys207. These ligands therefore seemed to be new chemotypes for HSD. Our results may be helpful for further experimental investigations.

  12. Relativity Screens for Misvalued Medical Services: Impact on Noninvasive Diagnostic Radiology.

    Science.gov (United States)

    Rosenkrantz, Andrew B; Silva, Ezequiel; Hawkins, C Matthew

    2017-11-01

    In 2006, the AMA/Specialty Society Relative Value Scale Update Committee (RUC) introduced ongoing relativity screens to identify potentially misvalued medical services for payment adjustments. We assess the impact of these screens upon the valuation of noninvasive diagnostic radiology services. Data regarding relativity screens and relative value unit (RVU) changes were obtained from the 2016 AMA Relativity Assessment Status Report. All global codes in the 2016 Medicare Physician Fee Schedule with associated work RVUs were classified as noninvasive diagnostic radiology services versus remaining services. The frequency of having ever undergone a screen was compared between the two groups. Screened radiology codes were further evaluated regarding the RVU impact of subsequent revaluation. Of noninvasive diagnostic radiology codes, 46.0% (201 of 437) were screened versus 22.2% (1,460 of 6,575) of remaining codes (P < .001). Most common screens for which radiology codes were identified as potentially misvalued were (1) high expenditures (27.5%) and (2) high utilization (25.6%). The modality and body region most likely to be identified in a screen were CT (82.1%) and breast (90.9%), respectively. Among screened radiology codes, work RVUs, practice expense RVUs, and nonfacility total RVUs decreased in 20.3%, 65.9%, and 75.3%, respectively. All screened CT, MRI, brain, and spine codes exhibited decreased total RVUs. Policymakers' ongoing search for potentially misvalued medical services has disproportionately impacted noninvasive diagnostic radiology services, risking the introduction of unintended or artificial shifts in physician practice. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  13. PHIBSS: MOLECULAR GAS, EXTINCTION, STAR FORMATION, AND KINEMATICS IN THE z = 1.5 STAR-FORMING GALAXY EGS13011166

    Energy Technology Data Exchange (ETDEWEB)

    Genzel, R.; Tacconi, L. J.; Kurk, J.; Wuyts, S.; Foerster Schreiber, N. M.; Gracia-Carpio, J. [Max-Planck-Institut fuer extraterrestrische Physik (MPE), Giessenbachstr., D-85748 Garching (Germany); Combes, F.; Freundlich, J. [Observatoire de Paris, LERMA, CNRS, 61 Av. de l' Observatoire, F-75014 Paris (France); Bolatto, A. [Department of Astronomy, University of Maryland, College Park, MD 20742-2421 (United States); Cooper, M. C. [Department of Physics and Astronomy, Frederick Reines Hall, University of California, Irvine, CA 92697 (United States); Neri, R. [IRAM, 300 Rue de la Piscine, F-38406 St. Martin d' Heres, Grenoble (France); Nordon, R. [Sackler School of Physics and Astronomy, Tel Aviv University, Tel Aviv 69978 (Israel); Bournaud, F. [Service d' Astrophysique, DAPNIA, CEA/Saclay, F-91191 Gif-sur-Yvette Cedex (France); Burkert, A. [Universitaetssternwarte der Ludwig-Maximiliansuniversitaet, Scheinerstr. 1, D-81679 Muenchen (Germany); Comerford, J. [Department of Astronomy and McDonald Observatory, 1 University Station, C1402 Austin, TX 78712-0259 (United States); Cox, P. [Department of Physics, Le Conte Hall, University of California, 94720 Berkeley, CA (United States); Davis, M. [Department of Astronomy, Campbell Hall, University of California, Berkeley, CA 94720 (United States); Garcia-Burillo, S. [Observatorio Astronomico Nacional-OAN, Observatorio de Madrid, Alfonso XII, 3, E-28014 Madrid (Spain); Naab, T. [Max-Planck Institut fuer Astrophysik, Karl Schwarzschildstrasse 1, D-85748 Garching (Germany); Lutz, D., E-mail: genzel@mpe.mpg.de, E-mail: linda@mpe.mpg.de; and others

    2013-08-10

    We report matched resolution imaging spectroscopy of the CO 3-2 line (with the IRAM Plateau de Bure millimeter interferometer) and of the H{alpha} line (with LUCI at the Large Binocular Telescope) in the massive z = 1.53 main-sequence galaxy EGS 13011166, as part of the ''Plateau de Bure high-z, blue-sequence survey'' (PHIBSS: Tacconi et al.). We combine these data with Hubble Space Telescope V-I-J-H-band maps to derive spatially resolved distributions of stellar surface density, star formation rate, molecular gas surface density, optical extinction, and gas kinematics. The spatial distribution and kinematics of the ionized and molecular gas are remarkably similar and are well modeled by a turbulent, globally Toomre unstable, rotating disk. The stellar surface density distribution is smoother than the clumpy rest-frame UV/optical light distribution and peaks in an obscured, star-forming massive bulge near the dynamical center. The molecular gas surface density and the effective optical screen extinction track each other and are well modeled by a ''mixed'' extinction model. The inferred slope of the spatially resolved molecular gas to star formation rate relation, N = dlog{Sigma}{sub starform}/dlog{Sigma}{sub molgas}, depends strongly on the adopted extinction model, and can vary from 0.8 to 1.7. For the preferred mixed dust-gas model, we find N = 1.14 {+-} 0.1.

  14. Synthesis, biological evaluation and molecular docking studies of ...

    African Journals Online (AJOL)

    Synthesis, biological evaluation and molecular docking studies of Mannich bases derived from 1, 3, 4-oxadiazole- 2-thiones as potential urease inhibitors. ... Mannich bases (5-17) were subjected to in silico screening as urease inhibitors, using crystal structure of urease (Protein Data Bank ID: 5FSE) as a model enzyme.

  15. Recommendations for accreditation of laboratories in molecular biology of hematologic malignancies.

    Science.gov (United States)

    Flandrin-Gresta, Pascale; Cornillet, Pascale; Hayette, Sandrine; Gachard, Nathalie; Tondeur, Sylvie; Mauté, Carole; Cayuela, Jean-Michel

    2015-01-01

    Over recent years, the development of molecular biology techniques has improved the hematological diseases diagnostic and follow-up. Consequently, these techniques are largely used in the biological screening of these diseases; therefore the Hemato-oncology molecular diagnostics laboratories must be actively involved in the accreditation process according the ISO 15189 standard. The French group of molecular biologists (GBMHM) provides requirements for the implementation of quality assurance for the medical molecular laboratories. This guideline states the recommendations for the pre-analytical, analytical (methods validation procedures, quality controls, reagents), and post-analytical conditions. In addition, herein we state a strategy for the internal quality control management. These recommendations will be regularly updated.

  16. Rapid screening for nuclear genes mutations in isolated respiratory chain complex I defects.

    Science.gov (United States)

    Pagniez-Mammeri, Hélène; Lombes, Anne; Brivet, Michèle; Ogier-de Baulny, Hélène; Landrieu, Pierre; Legrand, Alain; Slama, Abdelhamid

    2009-04-01

    Complex I or reduced nicotinamide adenine dinucleotide (NADH): ubiquinone oxydoreductase deficiency is the most common cause of respiratory chain defects. Molecular bases of complex I deficiencies are rarely identified because of the dual genetic origin of this multi-enzymatic complex (nuclear DNA and mitochondrial DNA) and the lack of phenotype-genotype correlation. We used a rapid method to screen patients with isolated complex I deficiencies for nuclear genes mutations by Surveyor nuclease digestion of cDNAs. Eight complex I nuclear genes, among the most frequently mutated (NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS7, NDUFS8, NDUFV1 and NDUFV2), were studied in 22 cDNA fragments spanning their coding sequences in 8 patients with a biochemically proved complex I deficiency. Single nucleotide polymorphisms and missense mutations were detected in 18.7% of the cDNA fragments by Surveyor nuclease treatment. Molecular defects were detected in 3 patients. Surveyor nuclease screening is a reliable method for genotyping nuclear complex I deficiencies, easy to interpret, and limits the number of sequence reactions. Its use will enhance the possibility of prenatal diagnosis and help us for a better understanding of complex I molecular defects.

  17. Environmental scan of anal cancer screening practices: worldwide survey results

    International Nuclear Information System (INIS)

    Patel, Jigisha; Salit, Irving E; Berry, Michael J; Pokomandy, Alexandra de; Nathan, Mayura; Fishman, Fred; Palefsky, Joel; Tinmouth, Jill

    2014-01-01

    Anal squamous cell carcinoma is rare in the general population but certain populations, such as persons with HIV, are at increased risk. High-risk populations can be screened for anal cancer using strategies similar to those used for cervical cancer. However, little is known about the use of such screening practices across jurisdictions. Data were collected using an online survey. Health care professionals currently providing anal cancer screening services were invited to complete the survey via email and/or fax. Information was collected on populations screened, services and treatments offered, and personnel. Over 300 invitations were sent; 82 providers from 80 clinics around the world completed the survey. Fourteen clinics have each examined more than 1000 patients. Over a third of clinics do not restrict access to screening; in the rest, eligibility is most commonly based on HIV status and abnormal anal cytology results. Fifty-three percent of clinics require abnormal anal cytology prior to performing high-resolution anoscopy (HRA) in asymptomatic patients. Almost all clinics offer both anal cytology and HRA. Internal high-grade anal intraepithelial neoplasia (AIN) is most often treated with infrared coagulation (61%), whereas external high-grade AIN is most commonly treated with imiquimod (49%). Most procedures are performed by physicians, followed by nurse practitioners. Our study is the first description of global anal cancer screening practices. Our findings may be used to inform practice and health policy in jurisdictions considering anal cancer screening

  18. Biochemical and molecular diagnosis of tyrosinemia type I with two novel FAH mutations in a Hong Kong chinese patient: recommendation for expanded newborn screening in Hong Kong.

    Science.gov (United States)

    Mak, Chloe Miu; Lam, Ching-Wan; Chim, Stella; Siu, Tak-Shing; Ng, King-Fai; Tam, Sidney

    2013-01-01

    Tyrosinemia type I is an autosomal recessive disorder in tyrosine metabolism. In areas without expanded newborn screening, patients present with acute hepatorenal failure in early infancy. Diagnosis can be elusive when clinical presentation is non-specific and biochemical abnormalities are masked by secondary changes. This is the first Hong Kong Chinese report. A two-month-old Chinese male infant with unremarkable antenatal and postnatal history presented with progressive abdominal distension for three days. He suffered from end-stage liver failure, hypoglycemia and hepatic encephalopathy. Diagnostic work-up was complicated starting from rule-out sepsis, intestinal obstruction, volvulus, peritonitis, septic ileus, poisoning to metabolic diseases. Clinical, biochemical and genetic data was described. The patient showed increases in multiple plasma amino acids including tyrosine, phenylalanine and methionine, and hyper-excretions of 4-hydroxyphenyl-acetate, -pyruvate, and -lactate, as well as N-acetyltyrosine which could be seen in liver failure due to both tyrosinemia type I and non-metabolic conditions. Because of the volatile nature, succinylacetone was almost undetectable. The diagnosis was confirmed by genetic analysis of FAH with two novel mutations, viz. NM_000137.2:c.1063-1G>A and NM_000137.2:c.1035_1037del. Living-related liver transplantation was done. However, the patient still suffered many complications after the severe metabolic insult with hypoxic ischemic encephalopathy, cerebral atrophy, global developmental delay and cortical visual impairment. Because of the lack of expanded newborn screening in Hong Kong, this child unfortunately presented in the most severe form of tyrosinemia type I. Expanded newborn screening can save life and reduce the burden of diagnostic complexity. This illustrates the need for expanded newborn screening in Hong Kong. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights

  19. A Tendon Cell Specific RNAi Screen Reveals Novel Candidates Essential for Muscle Tendon Interaction.

    Directory of Open Access Journals (Sweden)

    Prabhat Tiwari

    Full Text Available Tendons are fibrous connective tissue which connect muscles to the skeletal elements thus acting as passive transmitters of force during locomotion and provide appropriate body posture. Tendon-derived cues, albeit poorly understood, are necessary for proper muscle guidance and attachment during development. In the present study, we used dorsal longitudinal muscles of Drosophila and their tendon attachment sites to unravel the molecular nature of interactions between muscles and tendons. We performed a genetic screen using RNAi-mediated knockdown in tendon cells to find out molecular players involved in the formation and maintenance of myotendinous junction and found 21 candidates out of 2507 RNAi lines screened. Of these, 19 were novel molecules in context of myotendinous system. Integrin-βPS and Talin, picked as candidates in this screen, are known to play important role in the cell-cell interaction and myotendinous junction formation validating our screen. We have found candidates with enzymatic function, transcription activity, cell adhesion, protein folding and intracellular transport function. Tango1, an ER exit protein involved in collagen secretion was identified as a candidate molecule involved in the formation of myotendinous junction. Tango1 knockdown was found to affect development of muscle attachment sites and formation of myotendinous junction. Tango1 was also found to be involved in secretion of Viking (Collagen type IV and BM-40 from hemocytes and fat cells.

  20. Depression Screening

    Science.gov (United States)

    ... Depression Screening Substance Abuse Screening Alcohol Use Screening Depression Screening (PHQ-9) - Instructions The following questions are ... this tool, there is also text-only version . Depression Screening - Manual Instructions The following questions are a ...

  1. Molecular markers of neuropsychological functioning and Alzheimer's disease.

    Science.gov (United States)

    Edwards, Melissa; Balldin, Valerie Hobson; Hall, James; O'Bryant, Sid

    2015-03-01

    The current project sought to examine molecular markers of neuropsychological functioning among elders with and without Alzheimer's disease (AD) and determine the predictive ability of combined molecular markers and select neuropsychological tests in detecting disease presence. Data were analyzed from 300 participants (n = 150, AD and n = 150, controls) enrolled in the Texas Alzheimer's Research and Care Consortium. Linear regression models were created to examine the link between the top five molecular markers from our AD blood profile and neuropsychological test scores. Logistical regressions were used to predict AD presence using serum biomarkers in combination with select neuropsychological measures. Using the neuropsychological test with the least amount of variance overlap with the molecular markers, the combined neuropsychological test and molecular markers was highly accurate in detecting AD presence. This work provides the foundation for the generation of a point-of-care device that can be used to screen for AD.

  2. Global Breast Cancer: The Lessons to Bring Home

    International Nuclear Information System (INIS)

    Formenti, S.C.; Formenti, S.C.; Arslan, A.A.; Arslan, A.A.; Love, S.M.; Love, S.M.

    2012-01-01

    Breast cancer is the most common cancer affecting women globally. This paper discusses the current progress in breast cancer in Western countries and focuses on important differences of this disease in low- and middle-income countries (LMCs). It introduces several arguments for applying caution before globalizing some of the US-adopted practices in the screening and management of the disease. Finally, it suggests that studies of breast cancer in LMCs might offer important insights for a more effective management of the problem both in developing as well as developed countries.high-energy Japanese immigrants female higher proliferative

  3. The Power of Neuroimaging Biomarkers for Screening Frontotemporal Dementia

    OpenAIRE

    McMillan, Corey T.; Avants, Brian B.; Cook, Philip; Ungar, Lyle; Trojanowski, John Q.; Grossman, Murray

    2014-01-01

    Frontotemporal dementia (FTD) is a clinically and pathologically heterogeneous neurodegenerative disease that can result from either frontotemporal lobar degeneration (FTLD) or Alzheimer’s disease (AD) pathology. It is critical to establish statistically powerful biomarkers that can achieve substantial cost-savings and increase feasibility of clinical trials. We assessed three broad categories of neuroimaging methods to screen underlying FTLD and AD pathology in a clinical FTD series: global ...

  4. Knowledge and beliefs about cervical cancer screening among men in Kumasi, Ghana.

    Science.gov (United States)

    Williams, M S; Amoateng, P

    2012-09-01

    The age-standardized mortality rate for cervical cancer in Ghana, West Africa is more than three times the global cervical cancer mortality rate (27.6/100,000 vs. 7.8/100,000 respectively). The Pap test and visual inspection with acetic acid are available at public and private hospitals in Ghana. Approximately, 2.7% of Ghanaian women obtain cervical cancer screenings regularly. Men in middle-income countries play a key role in cervical cancer prevention. Increasing spousal support for cervical cancer screening may increase screening rates in Ghana. Five focus groups were conducted with Ghanaian men (N = 29) to assess their cervical cancer and cervical cancer screening knowledge and beliefs. The qualitative data was analyzed via indexed coding. Targets for education interventions were identified including inaccurate knowledge about cervical cancer and stigmatizing beliefs about cervical cancer risk factors. Cultural taboos regarding women's health care behaviours were also identified. Several participants indicated that they would be willing to provide spousal support for cervical cancer screening if they knew more about the disease and the screening methods. Men play a significant role in the health behaviours of some Ghanaian women. Cervical cancer education interventions targeting Ghanaian men are needed to correct misconceptions and increase spousal support for cervical cancer screening.

  5. The fabrication, characterisation and electrochemical investigation of screen-printed graphene electrodes.

    Science.gov (United States)

    Randviir, Edward P; Brownson, Dale A C; Metters, Jonathan P; Kadara, Rashid O; Banks, Craig E

    2014-03-14

    We report the fabrication, characterisation (SEM, Raman spectroscopy, XPS and ATR) and electrochemical implementation of novel screen-printed graphene electrodes. Electrochemical characterisation of the fabricated graphene electrodes is undertaken using an array of electroactive redox probes and biologically relevant analytes, namely: potassium ferrocyanide(II), hexaammine-ruthenium(III) chloride, N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), β-nicotinamide adenine dinucleotide (NADH), L-ascorbic acid (AA), uric acid (UA) and dopamine hydrochloride (DA). The electroanalytical capabilities of the fabricated electrodes are also considered towards the sensing of AA and DA. The electrochemical and (electro)analytical performances of the fabricated screen-printed graphene electrodes are considered with respect to the relative surface morphologies and material compositions (elucidated via SEM, Raman, XPS and ATR spectroscopy), the density of electronic states (% global coverage of edge-plane like sites/defects) and the specific fabrication conditions utilised. Comparisons are made between two screen-printed graphene electrodes and alternative graphite based screen-printed electrodes. The graphene electrodes are fabricated utilising two different commercially prepared 'graphene' inks, which have long screen ink lifetimes (>3 hours), thus this is the first report of a true mass-reproducible screen-printable graphene ink. Through employment of appropriate controls/comparisons we are able to report a critical assessment of these screen-printed graphene electrodes. This work is of high importance and demonstrates a proof-of-concept approach to screen-printed graphene electrodes that are highly reproducible, paving the way for mass-producible graphene sensing platforms in the future.

  6. Screening, Aharonov - Bohm effect, and linking number in spin systems

    International Nuclear Information System (INIS)

    Borisenko, O.; Petrov, K.; Faber, M.

    2000-01-01

    Screening mechanisms and related effects are studied in a variety of spin systems coupled to an external magnetic field. We use a special order parameter which can distinguish between screening due to the kinetic energy of spin excitations and screening due to the magnetic field. The action of this order parameter is based on an analog of the Aharonov - Bohm (AB) effect. The order parameter may test the realization of discrete symmetries embedded into the group symmetry of the theory via probing a nontrivial discrete charge. As simple examples, we study the Gaussian and Ising models. For the latter, we performed also Monte-Carlo simulations for a constant magnetic field. We then apply our results to spin systems with abelian and nonabelian global symmetries in two dimensions and argue that the order parameter proposed could serve as a tool to detect the Berezinskii - Kosterlitz - Thouless (BKT) phase transition

  7. Screening of Particle Fever film and Comedy Night

    CERN Multimedia

    Brice, Maximilien

    2014-01-01

    This documentary brings to life the start-up of the world’s most powerful particle accelerator, the LHC, and the two-year-long global effort that led to the discovery of the Higgs boson. The screening will be followed by a discussion with director Mark Levinson, editor Walter Munch and the scientists featured in the documentary. The second part of the evening will see scientists take to the stage as comedians for the Comedy Night.

  8. Cystic fibrosis, molecular genetics for all life

    Directory of Open Access Journals (Sweden)

    Ausilia Elce

    2015-10-01

    Full Text Available Cystic fibrosis (CF is the most frequent lethal autosomal recessive disorder among Caucasians (incidence: 1:2,500 newborn. In the last two decades CF prognosis considerably improved and many patients well survive into their adulthood. Furthermore, milder CF with a late onset was described. CF is a challenge for laboratory of molecular genetics that greatly contributes to the natural history of the disease since fetal age. Carrier screening and prenatal diagnosis, also by non-invasive analysis of maternal blood fetal DNA, are now available, and many labs offer preimplantation diagnosis. The major criticism in prenatal medicine is the lack of an effective multidisciplinary counseling that helps the couples to plan their reasoned reproductive choice. Most countries offer newborn screening that significantly reduce CF morbidity but different protocols based on blood trypsin, molecular analysis and sweat chloride cause a variable efficiency of the screening programs. Again, laboratory is crucial for CF diagnosis in symptomatic patients: sweat chloride is the diagnostic golden standard, but different methodologies and the lack of quality control in most labs reduce its effectiveness. Molecular analysis contributes to confirm diagnosis in symptomatic subjects; furthermore, it helps to predict the disease outcome on the basis of the mutation (genotype-phenotype correlation and mutations in a myriad of genes, inherited independently by CF transmembrane conductance regulator (CFTR, which may modulate the clinical expression of the disease in each single patient (modifier genes. More recently, the search of the CFTR mutations gained a role in selecting CF patients that may benefit from biological therapy based on correctors and potentiators that are effective in patients bearing specific mutations (personalized therapy. All such applications of molecular diagnostics confirm the “uniqueness” of each CF patient, offering to laboratory medicine the

  9. Clinical and molecular phenotype of Aicardi-Goutieres syndrome

    DEFF Research Database (Denmark)

    Rice, Gillian; Patrick, Teresa; Parmar, Rekha

    2007-01-01

    complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we...

  10. A global survey of low-molecular weight carbohydrates in lentils

    Science.gov (United States)

    Lentils contain a range of low-molecular weight carbohydrates (LMWC); however, those have not been well characterized. The objectives of this study were to (1) determine the concentrations of LMWC in lentils grown in six locations, and (2) identify any genetic and environmental effects on those LMWC...

  11. Self-assembled nanogaps for molecular electronics.

    Science.gov (United States)

    Tang, Qingxin; Tong, Yanhong; Jain, Titoo; Hassenkam, Tue; Wan, Qing; Moth-Poulsen, Kasper; Bjørnholm, Thomas

    2009-06-17

    A nanogap for molecular devices was realized using solution-based self-assembly. Gold nanorods were assembled to gold nanoparticle-coated conducting SnO2:Sb nanowires via thiol end-capped oligo(phenylenevinylene)s (OPVs). The molecular gap was easily created by the rigid molecule itself during self-assembly and the gap length was determined by the molecule length. The gold nanorods and gold nanoparticles, respectively covalently bonded at the two ends of the molecule, had very small dimensions, e.g. a width of approximately 20 nm, and hence were expected to minimize the screening effect. The ultra-long conducting SnO2:Sb nanowires provided the bridge to connect one of the electrodes of the molecular device (gold nanoparticle) to the external circuit. The tip of the atomic force microscope (AFM) was contacted onto the other electrode (gold nanorod) for the electrical measurement of the OPV device. The conductance measurement confirmed that the self-assembly of the molecules and the subsequent self-assembly of the gold nanorods was a feasible method for the fabrication of the nanogap of the molecular devices.

  12. Self-assembled nanogaps for molecular electronics

    International Nuclear Information System (INIS)

    Tang Qingxin; Tong Yanhong; Jain, Titoo; Hassenkam, Tue; Moth-Poulsen, Kasper; Bjoernholm, Thomas; Wan Qing

    2009-01-01

    A nanogap for molecular devices was realized using solution-based self-assembly. Gold nanorods were assembled to gold nanoparticle-coated conducting SnO 2 :Sb nanowires via thiol end-capped oligo(phenylenevinylene)s (OPVs). The molecular gap was easily created by the rigid molecule itself during self-assembly and the gap length was determined by the molecule length. The gold nanorods and gold nanoparticles, respectively covalently bonded at the two ends of the molecule, had very small dimensions, e.g. a width of ∼20 nm, and hence were expected to minimize the screening effect. The ultra-long conducting SnO 2 :Sb nanowires provided the bridge to connect one of the electrodes of the molecular device (gold nanoparticle) to the external circuit. The tip of the atomic force microscope (AFM) was contacted onto the other electrode (gold nanorod) for the electrical measurement of the OPV device. The conductance measurement confirmed that the self-assembly of the molecules and the subsequent self-assembly of the gold nanorods was a feasible method for the fabrication of the nanogap of the molecular devices.

  13. Approaches to virtual screening and screening library selection.

    Science.gov (United States)

    Wildman, Scott A

    2013-01-01

    The ease of access to virtual screening (VS) software in recent years has resulted in a large increase in literature reports. Over 300 publications in the last year report the use of virtual screening techniques to identify new chemical matter or present the development of new virtual screening techniques. The increased use is accompanied by a corresponding increase in misuse and misinterpretation of virtual screening results. This review aims to identify many of the common difficulties associated with virtual screening and allow researchers to better assess the reliability of their virtual screening effort.

  14. Isotopic and molecular fractionation in combustion; three routes to molecular marker validation, including direct molecular 'dating' (GC/AMS)

    Science.gov (United States)

    Currie, L. A.; Klouda, G. A.; Benner, B. A.; Garrity, K.; Eglinton, T. I.

    The identification of unique isotopic, elemental, and molecular markers for sources of combustion aerosol has growing practical importance because of the potential effects of fine particle aerosol on health, visibility and global climate. It is urgent, therefore, that substantial efforts be directed toward the validation of assumptions involving the use of such tracers for source apportionment. We describe here three independent routes toward carbonaceous aerosol molecular marker identification and validation: (1) tracer regression and multivariate statistical techniques applied to field measurements of mixed source, carbonaceous aerosols; (2) a new development in aerosol 14C metrology: direct, pure compound accelerator mass spectrometry (AMS) by off-line GC/AMS ('molecular dating'); and (3) direct observation of isotopic and molecular source emissions during controlled laboratory combustion of specific fuels. Findings from the combined studies include: independent support for benzo( ghi)perylene as a motor vehicle tracer from the first (statistical) and second (direct 'dating') studies; a new indication, from the third (controlled combustion) study, of a relation between 13C isotopic fractionation and PAH molecular fractionation, also linked with fuel and stage of combustion; and quantitative data showing the influence of both fuel type and combustion conditions on the yields of such species as elemental carbon and PAH, reinforcing the importance of exercising caution when applying presumed conservative elemental or organic tracers to fossil or biomass burning field data as in the first study.

  15. The Oseen-Frank Limit of Onsager's Molecular Theory for Liquid Crystals

    Science.gov (United States)

    Liu, Yuning; Wang, Wei

    2018-03-01

    We study the relationship between Onsager's molecular theory, which involves the effects of nonlocal molecular interactions and the Oseen-Frank theory for nematic liquid crystals. Under the molecular setting, we prove the existence of global minimizers for the generalized Onsager's free energy, subject to a nonlocal boundary condition which prescribes the second moment of the number density function near the boundary. Moreover, when the re-scaled interaction distance tends to zero, the global minimizers will converge to a uniaxial distribution predicted by a minimizing harmonic map. This is achieved through the investigations of the compactness property and the boundary behaviors of the corresponding second moments. A similar result is established for critical points of the free energy that fulfill a natural energy bound.

  16. Psychometric properties of the Vulnerability to Abuse Screening Scale for screening abuse of older adults

    Directory of Open Access Journals (Sweden)

    Raquel Batista Dantas

    Full Text Available ABSTRACT OBJECTIVE Adapt and evaluate the psychometric properties of the Vulnerability to Abuse Screening Scale to identify risk of domestic violence against older adults in Brazil. METHODS The instrument was adapted and validated in a sample of 151 older adults from a geriatric reference center in the municipality of Belo Horizonte, State of Minas Gerais, in 2014. We collected sociodemographic, clinical, and abuse-related information, and verified reliability by reproducibility in a sample of 55 older people, who underwent re-testing of the instrument seven days after the first application. Descriptive and comparative analyses were performed for all variables, with a significance level of 5%. The construct validity was analyzed by the principal components method with a tetrachoric correlation matrix, the reliability of the scale by the weighted Kappa (Kp statistic, and the internal consistency by the Kuder-Richardson estimator formula 20 (KR-20. RESULTS The average age of the participants was 72.1 years (DP = 6.96; 95%CI 70.94–73.17, with a maximum of 92 years, and they were predominantly female (76.2%; 95%CI 69.82–83.03. When analyzing the relationship between the scores of the Vulnerability to Abuse Screening Scale, categorized by presence (score > 3 or absence (score < 3 of vulnerability to abuse, with clinical and health conditions, we found statistically significant differences for self-perception of health (p = 0.002, depressive symptoms (p = 0.000, and presence of rheumatism (p = 0.003. There were no statistically significant differences between sexes. The Vulnerability to Abuse Screening Scale acceptably evaluated validity in the transcultural adaptation process, demonstrating dimensionality coherent with the original proposal (four factors. In the internal consistency analysis, the instrument presented good results (KR-20 = 0.69 and the reliability via reproducibility was considered excellent for the global scale (Kp = 0

  17. Impact of Cardiovascular Counseling and Screening in Hodgkin Lymphoma Survivors

    Energy Technology Data Exchange (ETDEWEB)

    Daniëls, Laurien A., E-mail: l.a.daniels@lumc.nl [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands); Krol, Stijn D.G. [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands); Graaf, Michiel A. de [Department of Cardiology, Leiden University Medical Center, Leiden (Netherlands); Interuniversity Cardiology Institute of the Netherlands, Utrecht (Netherlands); Scholte, Arthur J.H.A. [Department of Cardiology, Leiden University Medical Center, Leiden (Netherlands); Veer, Mars B. van ' t [Department of Hematology, Leiden University Medical Center, Leiden (Netherlands); Putter, Hein [Department of Medical Statistics and Bio-informatics, Leiden University Medical Center, Leiden (Netherlands); Roos, Albert de [Department of Radiology, Leiden University Medical Center, Leiden (Netherlands); Schalij, Martin J. [Department of Cardiology, Leiden University Medical Center, Leiden (Netherlands); Poll-Franse, Lonneke V. van de [Research Department Comprehensive Cancer Center South, Eindhoven (Netherlands); Center of Research on Psychology in Somatic Diseases, Tilburg University, Tilburg (Netherlands); Creutzberg, Carien L. [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands)

    2014-09-01

    Purpose: Cardiovascular disease (CVD) is the most common nonmalignant cause of death in Hodgkin lymphoma (HL) survivors, especially after mediastinal irradiation. The role of screening for CVD in HL survivors is unclear, but confrontation with risks of CVD may have a negative influence on health-related quality of life (HRQL). As part of a phase 2 screening study using computed tomography angiography (CTA) among HL survivors, an HRQL analysis was done to evaluate the emotional and practical burden and perceived benefits of screening and the effect of CVD-specific counseling on patient satisfaction. Methods and Materials: Patients who participated in the screening study also took part in the HRQL study. The impact of undergoing screening was evaluated with a 9-item questionnaire, and impact on HRQL with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire C30, version 3.0. The effect of counseling of CVD on perceived provision of information was evaluated with EORTC INFO-25. All questionnaires were completed at baseline and after screening. Results: Baseline questionnaires were received from 48 participants, and 43 completed questionnaires after screening. Mean age was 47 years, and mean time since diagnosis was 21 years. Of the total, 93% of subjects were content with participating, and 80% did not find the emphasis placed on late effects burdensome, although screening did have a small impact on social functioning and global quality of life. Perceived information on disease, medical tests, and treatment increased significantly after screening (P<.01). Differences were clinically relevant. There were no differences in perceived information between patients with and without screen-detected CVD. Conclusions: Screening was evaluated favorably, whether CTA showed abnormalities or not. Extensive counseling resulted in substantially increased provision of information and improved information satisfaction. Screening by

  18. Impact of Cardiovascular Counseling and Screening in Hodgkin Lymphoma Survivors

    International Nuclear Information System (INIS)

    Daniëls, Laurien A.; Krol, Stijn D.G.; Graaf, Michiel A. de; Scholte, Arthur J.H.A.; Veer, Mars B. van 't; Putter, Hein; Roos, Albert de; Schalij, Martin J.; Poll-Franse, Lonneke V. van de; Creutzberg, Carien L.

    2014-01-01

    Purpose: Cardiovascular disease (CVD) is the most common nonmalignant cause of death in Hodgkin lymphoma (HL) survivors, especially after mediastinal irradiation. The role of screening for CVD in HL survivors is unclear, but confrontation with risks of CVD may have a negative influence on health-related quality of life (HRQL). As part of a phase 2 screening study using computed tomography angiography (CTA) among HL survivors, an HRQL analysis was done to evaluate the emotional and practical burden and perceived benefits of screening and the effect of CVD-specific counseling on patient satisfaction. Methods and Materials: Patients who participated in the screening study also took part in the HRQL study. The impact of undergoing screening was evaluated with a 9-item questionnaire, and impact on HRQL with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire C30, version 3.0. The effect of counseling of CVD on perceived provision of information was evaluated with EORTC INFO-25. All questionnaires were completed at baseline and after screening. Results: Baseline questionnaires were received from 48 participants, and 43 completed questionnaires after screening. Mean age was 47 years, and mean time since diagnosis was 21 years. Of the total, 93% of subjects were content with participating, and 80% did not find the emphasis placed on late effects burdensome, although screening did have a small impact on social functioning and global quality of life. Perceived information on disease, medical tests, and treatment increased significantly after screening (P<.01). Differences were clinically relevant. There were no differences in perceived information between patients with and without screen-detected CVD. Conclusions: Screening was evaluated favorably, whether CTA showed abnormalities or not. Extensive counseling resulted in substantially increased provision of information and improved information satisfaction. Screening by

  19. SEA Screening of voluntary Climate Change Plans

    DEFF Research Database (Denmark)

    Kørnøv, Lone; Wejs, Anja

    2013-01-01

    that discretionary judgement takes place and will impact on the screening decision. This article examines the results of discretion involved in screening of climate change plans (CCPs) in a Danish context. These years voluntary CCPs are developed as a response to the global and local emergence of both mitigation...... rests upon a docu- mentary study of Danish CCPs, interviews with a lawyer and ministerial key person and informal discussions between researchers, practitioners and lawyers on whether climate change plans are covered by SEA legislation and underlying reasons for the present practice. Based on a critical...... and adap- tation, and the voluntary commitment by the local authorities is an indication of an emerging norm of climate change as an important issue. This article takes its point of departure in the observation that SEA is not undertaken for these voluntary CCPs. The critical analysis of this phenomenon...

  20. Screening disrupted molecular functions and pathways associated with clear cell renal cell carcinoma using Gibbs sampling.

    Science.gov (United States)

    Nan, Ning; Chen, Qi; Wang, Yu; Zhai, Xu; Yang, Chuan-Ce; Cao, Bin; Chong, Tie

    2017-10-01

    To explore the disturbed molecular functions and pathways in clear cell renal cell carcinoma (ccRCC) using Gibbs sampling. Gene expression data of ccRCC samples and adjacent non-tumor renal tissues were recruited from public available database. Then, molecular functions of expression changed genes in ccRCC were classed to Gene Ontology (GO) project, and these molecular functions were converted into Markov chains. Markov chain Monte Carlo (MCMC) algorithm was implemented to perform posterior inference and identify probability distributions of molecular functions in Gibbs sampling. Differentially expressed molecular functions were selected under posterior value more than 0.95, and genes with the appeared times in differentially expressed molecular functions ≥5 were defined as pivotal genes. Functional analysis was employed to explore the pathways of pivotal genes and their strongly co-regulated genes. In this work, we obtained 396 molecular functions, and 13 of them were differentially expressed. Oxidoreductase activity showed the highest posterior value. Gene composition analysis identified 79 pivotal genes, and survival analysis indicated that these pivotal genes could be used as a strong independent predictor of poor prognosis in patients with ccRCC. Pathway analysis identified one pivotal pathway - oxidative phosphorylation. We identified the differentially expressed molecular functions and pivotal pathway in ccRCC using Gibbs sampling. The results could be considered as potential signatures for early detection and therapy of ccRCC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Global Variation of Human Papillomavirus Genotypes and Selected Genes Involved in Cervical Malignancies.

    Science.gov (United States)

    Husain, R S Akram; Ramakrishnan, V

    2015-01-01

    Carcinoma of the cervix is ranked second among the top 5 cancers affecting women globally. Parallel to other cancers, it is also a complex disease involving numerous factors such as human papillomavirus (HPV) infection followed by the activity of oncogenes and environmental factors. The incidence rate of the disease remains high in developing countries due to lack of awareness, followed by mass screening programs, various socioeconomic issues, and low usage of preventive vaccines. Over the past 3 decades, extensive research has taken place in cervical malignancy to elucidate the role of host genes in the pathogenesis of the disease, yet it remains one of the most prevalent diseases. It is imperative that recent genome-wide techniques be used to determine whether carcinogenesis of oncogenes is associated with cervical cancer at the molecular level and to translate that knowledge into developing diagnostic and therapeutic tools. The aim of this study was to discuss HPV predominance with their genotype distribution worldwide, and in India, as well as to discuss the newly identified oncogenes related to cervical cancer in current scenario. Using data from various databases and robust technologies, oncogenes associated with cervical malignancies were identified and are explained in concise manner. Due to the advent of recent technologies, new candidate genes are explored and can be used as precise biomarkers for screening and developing drug targets. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Assessing the utility and limitations of high throughput virtual screening

    Directory of Open Access Journals (Sweden)

    Paul Daniel Phillips

    2016-05-01

    Full Text Available Due to low cost, speed, and unmatched ability to explore large numbers of compounds, high throughput virtual screening and molecular docking engines have become widely utilized by computational scientists. It is generally accepted that docking engines, such as AutoDock, produce reliable qualitative results for ligand-macromolecular receptor binding, and molecular docking results are commonly reported in literature in the absence of complementary wet lab experimental data. In this investigation, three variants of the sixteen amino acid peptide, α-conotoxin MII, were docked to a homology model of the a3β2-nicotinic acetylcholine receptor. DockoMatic version 2.0 was used to perform a virtual screen of each peptide ligand to the receptor for ten docking trials consisting of 100 AutoDock cycles per trial. The results were analyzed for both variation in the calculated binding energy obtained from AutoDock, and the orientation of bound peptide within the receptor. The results show that, while no clear correlation exists between consistent ligand binding pose and the calculated binding energy, AutoDock is able to determine a consistent positioning of bound peptide in the majority of trials when at least ten trials were evaluated.

  3. Systematic Review of the Methodology Quality in Lung Cancer Screening Guidelines

    Directory of Open Access Journals (Sweden)

    Jiang LI

    2016-10-01

    Full Text Available Background and objective Lung cancer is the most common malignancy and screening can decrease the mortality. High quality screening guideline is necessary and important for effective work. Our study is to review and evaluate the basic characteristics and methodology quality of the current global lung cancer screening guidelines so as to provide useful information for domestic study in the future. Methods Electronic searches were done in English and Chinese databases including PubMed, the Cochrane Library, Web of Science, Embase, CNKI, CBM, Wanfang, and some cancer official websites. Articles were screened according to the predefined inclusion and exclusion criteria by two researchers. The quality of guidelines was assessed by AGREE II. Results At last, a total of 11 guidelines with methodology were included. The guidelines were issued mainly by USA (81%. Canada and China developed one, respectively. As for quality, the average score in the “Scale and objective” of all guidelines was 80, the average score in the “Participants” was 52, the average score in the “rigorism” was 50, the average score in the “clarity” was 76, the average score in the “application” was 43 and the average score in the “independence” was 59. The highest average score was found in 2013 and 2015. Canada guideline had higher quality in six domains. 7 guidelines were evaluated as A level. Conclusion The number of clinical guidelines showed an increasing trend. Most guidelines were issued by developed countries with heavy burden. Multi-country contribution to one guideline was another trend. Evidence-based methodology was accepted globally in the guideline development.

  4. Systematic screening of child abuse in out-of-hours primary care

    NARCIS (Netherlands)

    Schouten, MCM

    2017-01-01

    Child abuse is a serious global health problem. This thesis focused on – improving – the detection of child abuse in the out-of-hours primary care (OOH-PC). The main aim was to assess the diagnostic value of the screening instrument SPUTOVAMO-R2 for child abuse. We found that the detection rate of

  5. Glucose Tolerance, MTHFR C677T and NOS3 G894T Polymorphisms, and Global DNA Methylation in Mixed Ancestry African Individuals

    Directory of Open Access Journals (Sweden)

    Tandi E. Matsha

    2016-01-01

    Full Text Available The aim of this study is to quantify global DNA methylation and investigate the relationship with diabetes status and polymorphisms in MTHFR C677T and NOS3 G894T genes in mixed ancestry subjects from South Africa. Global DNA methylation was measured, and MTHFR rs1801133 and NOS3 rs1799983 polymorphisms were genotyped using high throughput real-time polymerase chain reaction and direct DNA sequencing. Of the 564 participants, 158 (28% individuals had T2DM of which 97 (17.2% were screen-detected cases. Another 119 (21.1% had prediabetes, that is, impaired fasting glucose, impaired glucose tolerance, or the combination of both, and the remainder 287 (50.9% had normal glucose tolerance. Global DNA methylation was significantly higher in prediabetes and screen-detected diabetes than in normal glucose tolerance (both p≤0.033 and in screen-detected diabetes compared to known diabetes on treatment (p=0.019. There was no difference in global DNA methylation between known diabetes on treatment and normal glucose tolerance (p>0.999. In multivariable linear regression analysis, only NOS3 was associated with increasing global DNA methylation (β=0.943; 95% CI: 0.286 to 1.560. The association of global DNA methylation with screen-detected diabetes but not treated diabetes suggests that glucose control agents to some extent may be reversing DNA methylation. The association between NOS3 rs1799983 polymorphisms and DNA methylation suggests gene-epigenetic mechanisms through which vascular diabetes complications develop despite adequate metabolic control.

  6. Glucose Tolerance, MTHFR C677T and NOS3 G894T Polymorphisms, and Global DNA Methylation in Mixed Ancestry African Individuals

    Science.gov (United States)

    Mutize, Tinashe; Erasmus, Rajiv T.

    2016-01-01

    The aim of this study is to quantify global DNA methylation and investigate the relationship with diabetes status and polymorphisms in MTHFR C677T and NOS3 G894T genes in mixed ancestry subjects from South Africa. Global DNA methylation was measured, and MTHFR rs1801133 and NOS3 rs1799983 polymorphisms were genotyped using high throughput real-time polymerase chain reaction and direct DNA sequencing. Of the 564 participants, 158 (28%) individuals had T2DM of which 97 (17.2%) were screen-detected cases. Another 119 (21.1%) had prediabetes, that is, impaired fasting glucose, impaired glucose tolerance, or the combination of both, and the remainder 287 (50.9%) had normal glucose tolerance. Global DNA methylation was significantly higher in prediabetes and screen-detected diabetes than in normal glucose tolerance (both p ≤ 0.033) and in screen-detected diabetes compared to known diabetes on treatment (p = 0.019). There was no difference in global DNA methylation between known diabetes on treatment and normal glucose tolerance (p > 0.999). In multivariable linear regression analysis, only NOS3 was associated with increasing global DNA methylation (β = 0.943; 95% CI: 0.286 to 1.560). The association of global DNA methylation with screen-detected diabetes but not treated diabetes suggests that glucose control agents to some extent may be reversing DNA methylation. The association between NOS3 rs1799983 polymorphisms and DNA methylation suggests gene-epigenetic mechanisms through which vascular diabetes complications develop despite adequate metabolic control. PMID:27990443

  7. Dissecting molecular descriptors into atomic contributions in density functional reactivity theory

    International Nuclear Information System (INIS)

    Rong, Chunying; Lu, Tian; Liu, Shubin

    2014-01-01

    Density functional reactivity theory (DFRT) employs the electron density of a molecule and its related quantities such as gradient and Laplacian to describe its structure and reactivity properties. Proper descriptions at both molecular (global) and atomic (local) levels are equally important and illuminating. In this work, we make use of Bader's zero-flux partition scheme and consider atomic contributions for a few global reactivity descriptors in DFRT, including the density-based quantification of steric effect and related indices. Earlier, we proved that these quantities are intrinsically correlated for atomic and molecular systems [S. B. Liu, J. Chem. Phys. 126, 191107 (2007); ibid. 126, 244103 (2007)]. In this work, a new basin-based integration algorithm has been implemented, whose reliability and effectiveness have been extensively examined. We also investigated a list of simple hydrocarbon systems and different scenarios of bonding processes, including stretching, bending, and rotating. Interesting changing patterns for the atomic and molecular values of these quantities have been revealed for different systems. This work not only confirms the strong correlation between these global reactivity descriptors for molecular systems, as theoretically proven earlier by us, it also provides new and unexpected changing patterns for their atomic values, which can be employed to understand the origin and nature of chemical phenomena

  8. Dissecting molecular descriptors into atomic contributions in density functional reactivity theory

    Energy Technology Data Exchange (ETDEWEB)

    Rong, Chunying [Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China) and Key Laboratory of Resource Fine-Processing and Advanced Materials of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan 410081 (China); Lu, Tian [School of Chemical and Biological Engineering, University of Science and Technology Beijing, Beijing (China); Liu, Shubin, E-mail: shubin@email.unc.edu [Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China) and Key Laboratory of Resource Fine-Processing and Advanced Materials of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan 410081 (China); Research Computing Center, University of North Carolina, Chapel Hill, North Carolina 27599-3420 (United States)

    2014-01-14

    Density functional reactivity theory (DFRT) employs the electron density of a molecule and its related quantities such as gradient and Laplacian to describe its structure and reactivity properties. Proper descriptions at both molecular (global) and atomic (local) levels are equally important and illuminating. In this work, we make use of Bader's zero-flux partition scheme and consider atomic contributions for a few global reactivity descriptors in DFRT, including the density-based quantification of steric effect and related indices. Earlier, we proved that these quantities are intrinsically correlated for atomic and molecular systems [S. B. Liu, J. Chem. Phys. 126, 191107 (2007); ibid. 126, 244103 (2007)]. In this work, a new basin-based integration algorithm has been implemented, whose reliability and effectiveness have been extensively examined. We also investigated a list of simple hydrocarbon systems and different scenarios of bonding processes, including stretching, bending, and rotating. Interesting changing patterns for the atomic and molecular values of these quantities have been revealed for different systems. This work not only confirms the strong correlation between these global reactivity descriptors for molecular systems, as theoretically proven earlier by us, it also provides new and unexpected changing patterns for their atomic values, which can be employed to understand the origin and nature of chemical phenomena.

  9. Molecular simulation of receptors of physiologically active compounds for purposes of medical chemistry

    Science.gov (United States)

    Baskin, Igor I.; Palyulin, Vladimir A.; Zefirov, Nikolai S.

    2009-06-01

    The general strategy of the molecular simulation of biological receptors and their interaction with ligands is considered. The procedures for construction of 3D protein models, molecular docking, evaluation of model quality, determination of the free energy of protein binding with ligands are discussed. The methods of molecular design of new medicaments based on molecular models of biological targets: virtual screening and de novo design, are presented. Examples of the above-listed approaches for the simulation of a number of pharmacologically significant receptors, analysis of receptor-ligand interactions and design of new biologically active organic compounds are given.

  10. Molecular simulation of receptors of physiologically active compounds for purposes of medical chemistry

    International Nuclear Information System (INIS)

    Baskin, Igor I; Palyulin, Vladimir A; Zefirov, Nikolai S

    2009-01-01

    The general strategy of the molecular simulation of biological receptors and their interaction with ligands is considered. The procedures for construction of 3D protein models, molecular docking, evaluation of model quality, determination of the free energy of protein binding with ligands are discussed. The methods of molecular design of new medicaments based on molecular models of biological targets: virtual screening and de novo design, are presented. Examples of the above-listed approaches for the simulation of a number of pharmacologically significant receptors, analysis of receptor-ligand interactions and design of new biologically active organic compounds are given.

  11. Molecular simulation of receptors of physiologically active compounds for purposes of medical chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Baskin, Igor I; Palyulin, Vladimir A; Zefirov, Nikolai S [Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow (Russian Federation)

    2009-06-30

    The general strategy of the molecular simulation of biological receptors and their interaction with ligands is considered. The procedures for construction of 3D protein models, molecular docking, evaluation of model quality, determination of the free energy of protein binding with ligands are discussed. The methods of molecular design of new medicaments based on molecular models of biological targets: virtual screening and de novo design, are presented. Examples of the above-listed approaches for the simulation of a number of pharmacologically significant receptors, analysis of receptor-ligand interactions and design of new biologically active organic compounds are given.

  12. Chemical Screening for Bioactivated Electrophilic Metabolites Using Alginate Immobilization of Metabolic Enzymes (AIME) (SOT)

    Science.gov (United States)

    The US EPA's ToxCast program is designed to assess chemical perturbations of molecular and cellular endpoints using a variety of high-throughput screening (HTS) assays. However, existing HTS assays have limited or no xenobiotic metabolism which could lead to a mischaracterization...

  13. Evaluation of pro-c global for identification of defects in protein c/s anticoagulant pathway

    International Nuclear Information System (INIS)

    Hanif, T.B.; Anwar, J.; Idrees, M.

    2011-01-01

    Background: Detection of protein C and S deficiency forms a major investigation in the laboratory evaluation of thrombophilia screening. It has key role in the diagnosis of protein C and S deficiency. The objective of this study is to determine the utility of ProC Global as a screening test for identifying the defects of protein C and S anticoagulant pathways. Methods: Two Hundred patients with venous thromboembolism were studied at the Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi, from October 2004 to March 2006. ProC Global test (Dade Behring Diagnostics) was performed and was followed up by protein C and S assays. ProC Global is an activated partial thromboplastin time based assay in which Protac (snake venom from Aghistroden contortrix) is used for activation of the endogenous protein C of the plasma sample. The protein C activation time in the presence of the activator was set in relation to a parallel determination of PCAT/O with addition of a buffer instead of activator reagent. The ratio PCAT: PCAT/O was transformed in normalized ratio by relating them to a calibrator. Control plasma for normal range and ProC control plasma for pathological range (Dade Behring Diagnostics) were assayed in each run for quality control. Results: A total of 200 patients, 132 (66%) males and 68 (34%) females with age ranging from 1 to 68 years were studied. ProC Global was positive in 29/200 (14.5%) patients. ProC Global was found to be 86% sensitive, 94% specific and its overall efficiency turned out to be 94%. Conclusion: Pro-C Global can be used effectively as a screening test to detect abnormalities in protein C and S anticoagulant pathways. (author)

  14. NMR screening in fragment-based drug design: a practical guide.

    Science.gov (United States)

    Kim, Hai-Young; Wyss, Daniel F

    2015-01-01

    Fragment-based drug design (FBDD) comprises both fragment-based screening (FBS) to find hits and elaboration of these hits to lead compounds. Typical fragment hits have lower molecular weight (FBDD since it identifies and localizes the binding site of weakly interacting hits on the target protein. Here we describe ligand-based NMR methods for hit identification from fragment libraries and for functional cross-validation of primary hits.

  15. Mapping of Drug-like Chemical Universe with Reduced Complexity Molecular Frameworks.

    Science.gov (United States)

    Kontijevskis, Aleksejs

    2017-04-24

    The emergence of the DNA-encoded chemical libraries (DEL) field in the past decade has attracted the attention of the pharmaceutical industry as a powerful mechanism for the discovery of novel drug-like hits for various biological targets. Nuevolution Chemetics technology enables DNA-encoded synthesis of billions of chemically diverse drug-like small molecule compounds, and the efficient screening and optimization of these, facilitating effective identification of drug candidates at an unprecedented speed and scale. Although many approaches have been developed by the cheminformatics community for the analysis and visualization of drug-like chemical space, most of them are restricted to the analysis of a maximum of a few millions of compounds and cannot handle collections of 10 8 -10 12 compounds typical for DELs. To address this big chemical data challenge, we developed the Reduced Complexity Molecular Frameworks (RCMF) methodology as an abstract and very general way of representing chemical structures. By further introducing RCMF descriptors, we constructed a global framework map of drug-like chemical space and demonstrated how chemical space occupied by multi-million-member drug-like Chemetics DNA-encoded libraries and virtual combinatorial libraries with >10 12 members could be analyzed and mapped without a need for library enumeration. We further validate the approach by performing RCMF-based searches in a drug-like chemical universe and mapping Chemetics library selection outputs for LSD1 targets on a global framework chemical space map.

  16. Diagnostic yield of molecular autopsy in patients with sudden arrhythmic death syndrome using targeted exome sequencing

    DEFF Research Database (Denmark)

    Nunn, Laurence M; Lopes, Luis R; Syrris, Petros

    2016-01-01

    AIMS: The targeted genetic screening of Sudden Arrhythmic Death Syndrome (SADS) probands in a molecular autopsy has a diagnostic yield of up to 35%. Exome sequencing has the potential to improve this yield. The primary aim of this study is to examine the feasibility and diagnostic utility...... of targeted exome screening in SADS victims, utilizing familial clinical screening whenever possible. METHODS AND RESULTS: To determine the feasibility and diagnostic yield of targeted exome sequencing deoxyribonucleic acid (DNA) was isolated from 59 SADS victims (mean age 25 years, range 1-51 years...... previously published rare (0.02-0.5%) candidate mutations-a total yield of 29%. Co-segregation fully confirmed two private SCN5A Na channel mutations. Variants of unknown significance were detected in a further 34% of probands. CONCLUSION: Molecular autopsy using targeted exome sequencing has a relatively...

  17. Creation of a National, At-home Model for Ashkenazi Jewish Carrier Screening.

    Science.gov (United States)

    Grinzaid, Karen Arnovitz; Page, Patricia Zartman; Denton, Jessica Johnson; Ginsberg, Jessica

    2015-06-01

    Ethnicity-based carrier screening for the Ashkenazi Jewish population has been available and encouraged by advocacy and community groups since the early 1970's. Both the American College of Medical Genetics and the American Congress of Obstetricians and Gynecologists recommend carrier screening for this population (Obstetrics and Gynecology, 114(4), 950-953, 2009; Genetics in Medicine, 10(1), 55-56, 2008). While many physicians inquire about ethnic background and offer appropriate carrier screening, studies show that a gap remains in implementing recommendations (Genetic testing and molecular biomarkers, 2011). In addition, education and outreach efforts targeting Jewish communities have had limited success in reaching this at-risk population. Despite efforts by the medical and Jewish communities, many Jews of reproductive age are not aware of screening, and remain at risk for having children with preventable diseases. Reaching this population, preferably pre-conception, and facilitating access to screening is critically important. To address this need, genetic counselors at Emory University developed JScreen, a national Jewish genetic disease screening program. The program includes a national marketing and PR campaign, online education, at-home saliva-based screening, post-test genetic counseling via telephone or secure video conferencing, and referrals for face-to-face genetic counseling as needed. Our goals are to create a successful education and screening program for this population and to develop a model that could potentially be used for other at-risk populations.

  18. Primary care colorectal cancer screening correlates with breast cancer screening: implications for colorectal cancer screening improvement interventions.

    Science.gov (United States)

    Weiss, Jennifer M; Pandhi, Nancy; Kraft, Sally; Potvien, Aaron; Carayon, Pascale; Smith, Maureen A

    2018-04-25

    National colorectal cancer (CRC) screening rates have plateaued. To optimize interventions targeting those unscreened, a better understanding is needed of how this preventive service fits in with multiple preventive and chronic care needs managed by primary care providers (PCPs). This study examines whether PCP practices of other preventive and chronic care needs correlate with CRC screening. We performed a retrospective cohort study of 90 PCPs and 33,137 CRC screening-eligible patients. Five PCP quality metrics (breast cancer screening, cervical cancer screening, HgbA1c and LDL testing, and blood pressure control) were measured. A baseline correlation test was performed between these metrics and PCP CRC screening rates. Multivariable logistic regression with clustering at the clinic-level estimated odds ratios and 95% confidence intervals for these PCP quality metrics, patient and PCP characteristics, and their relationship to CRC screening. PCP CRC screening rates have a strong correlation with breast cancer screening rates (r = 0.7414, p < 0.001) and a weak correlation with the other quality metrics. In the final adjusted model, the only PCP quality metric that significantly predicted CRC screening was breast cancer screening (OR 1.25; 95% CI 1.11-1.42; p < 0.001). PCP CRC screening rates are highly concordant with breast cancer screening. CRC screening is weakly concordant with cervical cancer screening and chronic disease management metrics. Efforts targeting PCPs to increase CRC screening rates could be bundled with breast cancer screening improvement interventions to increase their impact and success.

  19. More comprehensive discussion of CRC screening associated with higher screening.

    Science.gov (United States)

    Mosen, David M; Feldstein, Adrianne C; Perrin, Nancy A; Rosales, A Gabriella; Smith, David H; Liles, Elizabeth G; Schneider, Jennifer L; Meyers, Ronald E; Elston-Lafata, Jennifer

    2013-04-01

    Examine association of comprehensiveness of colorectal cancer (CRC) screening discussion by primary care physicians (PCPs) with completion of CRC screening. Observational study in Kaiser Permanente Northwest, a group-model health maintenance organization. A total of 883 participants overdue for CRC screening received an automated telephone call (ATC) between April and June 2009 encouraging CRC screening. Between January and March 2010, participants completed a survey on PCPs' discussion of CRC screening and patient beliefs regarding screening. receipt of CRC screening (assessed by electronic medical record [EMR], 9 months after ATC). Primary independent variable: comprehensiveness of CRC screening discussion by PCPs (7-item scale). Secondary independent variables: perceived benefits of screening (4-item scale assessing respondents' agreement with benefits of timely screening) and primary care utilization (EMR; 9 months after ATC). The independent association of variables with CRC screening was assessed with logistic regression. Average scores for comprehensiveness of CRC discussion and perceived benefits were 0.4 (range 0-1) and 4.0 (range 1-5), respectively. A total of 28.2% (n = 249) completed screening, 84% of whom had survey assessments after their screening date. Of screeners, 95.2% completed the fecal immunochemical test. More comprehensive discussion of CRC screening was associated with increased screening (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.03-2.21). Higher perceived benefits (OR = 1.46, 95% CI = 1.13-1.90) and 1 or more PCP visits (OR = 5.82, 95% CI = 3.87-8.74) were also associated with increased screening. More comprehensive discussion of CRC screening was independently associated with increased CRC screening. Primary care utilization was even more strongly associated with CRC screening, irrespective of discussion of CRC screening.

  20. Structure-based virtual screening and characterization of a novel IL-6 antagonistic compound from synthetic compound database

    Directory of Open Access Journals (Sweden)

    Wang J

    2016-12-01

    Full Text Available Jing Wang,1,* Chunxia Qiao,1,* He Xiao,1 Zhou Lin,1 Yan Li,1 Jiyan Zhang,1 Beifen Shen,1 Tinghuan Fu,2 Jiannan Feng1 1Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences, 2First Affiliated Hospital of PLA General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: According to the three-dimensional (3D complex structure of (hIL-6·hIL-6R·gp 1302 and the binding orientation of hIL-6, three compounds with high affinity to hIL-6R and bioactivity to block hIL-6 in vitro were screened theoretically from the chemical databases, including 3D-Available Chemicals Directory (ACD and MDL Drug Data Report (MDDR, by means of the computer-guided virtual screening method. Using distance geometry, molecular modeling and molecular dynamics trajectory analysis methods, the binding mode and binding energy of the three compounds were evaluated theoretically. Enzyme-linked immunosorbent assay analysis demonstrated that all the three compounds could block IL-6 binding to IL-6R specifically. However, only compound 1 could effectively antagonize the function of hIL-6 and inhibit the proliferation of XG-7 cells in a dose-dependent manner, whereas it showed no cytotoxicity to SP2/0 or L929 cells. These data demonstrated that the compound 1 could be a promising candidate of hIL-6 antagonist. Keywords: virtual screening, structural optimization, human interlukin-6, small molecular antagonist, XG-7 cells, apoptosis

  1. Spectroscopic investigations of plasma nitriding processes: A comparative study using steel and carbon as active screen materials

    Science.gov (United States)

    Hamann, S.; Burlacov, I.; Spies, H.-J.; Biermann, H.; Röpcke, J.

    2017-04-01

    Low-pressure pulsed DC H2-N2 plasmas were investigated in the laboratory active screen plasma nitriding monitoring reactor, PLANIMOR, to compare the usage of two different active screen electrodes: (i) a steel screen with the additional usage of CH4 as carbon containing precursor in the feeding gas and (ii) a carbon screen without the usage of any additional gaseous carbon precursor. Applying the quantum cascade laser absorption spectroscopy, the evolution of the concentration of four stable molecular species, NH3, HCN, CH4, and C2H2, has been monitored. The concentrations were found to be in a range of 1012-1016 molecules cm-3. By analyzing the development of the molecular concentrations at variations of the screen plasma power, a similar behavior of the monitored reaction products has been found for both screen materials, with NH3 and HCN as the main reaction products. When using the carbon screen, the concentration of HCN and C2H2 was 30 and 70 times higher, respectively, compared to the usage of the steel screen with an admixture of 1% CH4. Considering the concentration of the three detected hydrocarbon reaction products, a combustion rate of the carbon screen of up to 69 mg h-1 has been found. The applied optical emission spectroscopy enabled the determination of the rotational temperature of the N2+ ion which has been in a range of 650-900 K increasing with the power in a similar way in the plasma of both screens. Also with power the ionic component of nitrogen molecules, represented by the N2+ (0-0) band of the first negative system, as well as the CN (0-0) band of the violet system increase strongly in relation to the intensity of the neutral nitrogen component, i.e., the N2 (0-0) band of the second positive system. In addition, steel samples have been treated with both the steel and the carbon screen resulting in a formation of a compound layer of up to 10 wt. % nitrogen and 10 wt. % carbon, respectively, depending on the screen material.

  2. Practical tools to implement massive parallel pyrosequencing of PCR products in next generation molecular diagnostics.

    Directory of Open Access Journals (Sweden)

    Kim De Leeneer

    Full Text Available Despite improvements in terms of sequence quality and price per basepair, Sanger sequencing remains restricted to screening of individual disease genes. The development of massively parallel sequencing (MPS technologies heralded an era in which molecular diagnostics for multigenic disorders becomes reality. Here, we outline different PCR amplification based strategies for the screening of a multitude of genes in a patient cohort. We performed a thorough evaluation in terms of set-up, coverage and sequencing variants on the data of 10 GS-FLX experiments (over 200 patients. Crucially, we determined the actual coverage that is required for reliable diagnostic results using MPS, and provide a tool to calculate the number of patients that can be screened in a single run. Finally, we provide an overview of factors contributing to false negative or false positive mutation calls and suggest ways to maximize sensitivity and specificity, both important in a routine setting. By describing practical strategies for screening of multigenic disorders in a multitude of samples and providing answers to questions about minimum required coverage, the number of patients that can be screened in a single run and the factors that may affect sensitivity and specificity we hope to facilitate the implementation of MPS technology in molecular diagnostics.

  3. Cervical Cancer Screening Among Adult Women in China, 2010

    Science.gov (United States)

    Wang, Baohua; He, Minfu; Chao, Ann; Engelgau, Michael M.; Saraiya, Mona; Wang, Limin

    2015-01-01

    Introduction. Cervical cancer is one of the most commonly diagnosed cancers among women in China. The World Health Organization (WHO) recommends routine screening for cervical cancer, and the WHO Global Monitoring Framework suggests that every nation monitors cervical cancer screening. However, little information is available on cervical cancer screening behavior among women in China. Methods. We used data from the 2010 China Chronic Disease and Risk Factor Surveillance System that included 51,989 women aged 18 years and older. We report the proportion of women who reported ever having had a Papanicolaou (Pap) test, stratified by sociodemographic characteristics and geographic region. Multivariable logistic regression modeling was performed to adjust for potential confounders. Results. Overall, 21% of 51,989 women reported having ever had a Pap test. The highest proportion was reported among women aged 30–39 years (30.1%, 95% confidence interval, 26.8%–33.4%). In all geographic regions, women in rural areas were consistently less likely than women in urban areas to report having had a Pap test. Among women who reported ever having a Pap test, 82% reported having the most recent test in the past 3 years. Factors associated with reporting ever having a test were being aged 30–49 years, higher education, being married, and having urban health insurance. Conclusion. Our results indicate that screening programs need to be strengthened along with a more intense focus on specific demographic groups. National cervical cancer screening guidelines and comprehensive implementation strategies are needed to make screening services available and accessible to all women. Implications for Practice: This study is the largest nationwide and population-based assessment of self-reported history of Pap test for cervical cancer screening in China. This article describes cervical cancer screening behavior among women and examines key demographic and geographic factors. Only one

  4. GENIUS In Silico Screening Technology for HCV Drug Discovery.

    Science.gov (United States)

    Patil, Vaishali M; Masand, Neeraj; Gupta, Satya P

    2016-01-01

    The various reported in silico screening protocols such as molecular docking are associated with various drawbacks as well as benefits. In molecular docking, on interaction with ligand, the protein or receptor molecule gets activated by adopting conformational changes. These conformational changes cannot be utilized to predict the 3D structure of a protein-ligand complex from unbound protein conformations rigid docking, which necessitates the demand for understanding protein flexibility. Therefore, efficiency and accuracy of docking should be achieved and various available/developed protocols may be adopted. One such protocol is GENIUS induced-fit docking and it is used effectively for the development of anti-HCV NS3-4A serine protease inhibitors. The present review elaborates the GENIUS docking protocol along with its benefits and drawbacks.

  5. Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials.

    Science.gov (United States)

    Le Tourneau, Christophe; Kamal, Maud; Tsimberidou, Apostolia-Maria; Bedard, Philippe; Pierron, Gaëlle; Callens, Céline; Rouleau, Etienne; Vincent-Salomon, Anne; Servant, Nicolas; Alt, Marie; Rouzier, Roman; Paoletti, Xavier; Delattre, Olivier; Bièche, Ivan

    2016-04-01

    With the advent of high-throughput molecular technologies, several precision medicine (PM) studies are currently ongoing that include molecular screening programs and PM clinical trials. Molecular profiling programs establish the molecular profile of patients' tumors with the aim to guide therapy based on identified molecular alterations. The aim of prospective PM clinical trials is to assess the clinical utility of tumor molecular profiling and to determine whether treatment selection based on molecular alterations produces superior outcomes compared with unselected treatment. These trials use treatment algorithms to assign patients to specific targeted therapies based on tumor molecular alterations. These algorithms should be governed by fixed rules to ensure standardization and reproducibility. Here, we summarize key molecular, biological, and technical criteria that, in our view, should be addressed when establishing treatment algorithms based on tumor molecular profiling for PM trials. © The Author 2015. Published by Oxford University Press.

  6. Global mental health and neuroscience: potential synergies.

    Science.gov (United States)

    Stein, Dan J; He, Yanling; Phillips, Anthony; Sahakian, Barbara J; Williams, John; Patel, Vikram

    2015-02-01

    Global mental health has emerged as an important specialty. It has drawn attention to the burden of mental illness and to the relative gap in mental health research and services around the world. Global mental health has raised the question of whether this gap is a developmental issue, a health issue, a human rights issue, or a combination of these issues-and it has raised awareness of the need to develop new approaches for building capacity, mobilising resources, and closing the research and treatment gap. Translational neuroscience has also advanced. It comprises an important conceptual approach to understanding the neurocircuitry and molecular basis of mental disorders, to rethinking how best to undertake research on the aetiology, assessment, and treatment of these disorders, with the ultimate aim to develop entirely new approaches to prevention and intervention. Some apparent contrasts exist between these fields; global mental health emphasises knowledge translation, moving away from the bedside to a focus on health systems, whereas translational neuroscience emphasises molecular neuroscience, focusing on transitions between the bench and bedside. Meanwhile, important opportunities exist for synergy between the two paradigms, to ensure that present opportunities in mental health research and services are maximised. Here, we review the approaches of global mental health and clinical neuroscience to diagnosis, pathogenesis, and intervention, and make recommendations for facilitating an integration of these two perspectives. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. A Novel Multiplayer Screen-Based Simulation Experience for African Learners Improved Confidence in Management of Postpartum Hemorrhage.

    Science.gov (United States)

    Taekman, Jeffrey M; Foureman, Megan F; Bulamba, Fred; Steele, Michael; Comstock, Emily; Kintu, Andrew; Mauritz, Amy; Olufolabi, Adeyemi

    2017-01-01

    Postpartum hemorrhage (PPH) remains a global challenge, affecting thirteen million women each year. In addition, PPH is a leading cause of maternal mortality in Asia and Africa. In the U.S.A., care of critically ill patients is often practiced using mannequin-based simulation. Mannequin-based simulation presents challenges in global health, particularly in low- or middle-income countries. We developed a novel multiplayer screen-based simulation in a virtual world enabling the practice of team coordination with PPH. We used this simulation with learners in Mulago, Uganda. We hypothesized that a multiplayer screen-based simulation experience would increase learner confidence in their ability to manage PPH. The study design was a simple pre- and a post-intervention survey. Forty-eight interprofessional subjects participated in one of nine 1-h simulation sessions using the PPH software. A fifteen-question self-assessment administered before and after the intervention was designed to probe the areas of learning as defined by Bloom and Krathwohl: affective, cognitive, and psychomotor. Combined confidence scores increased significantly overall following the simulation experience and individually in each of the three categories of Bloom's Taxonomy: affective, cognitive, and psychomotor. We provide preliminary evidence that multiplayer screen-based simulation represents a scalable, distributable form of learning that may be used effectively in global health education and training. Interestingly, despite our intervention being screen-based, our subjects showed improved confidence in their ability to perform psychomotor tasks. Although there is precedent for mental rehearsal improving performance, further research is needed to understand this finding.

  8. A Novel Multiplayer Screen-Based Simulation Experience for African Learners Improved Confidence in Management of Postpartum Hemorrhage

    Directory of Open Access Journals (Sweden)

    Jeffrey M. Taekman

    2017-09-01

    Full Text Available IntroductionPostpartum hemorrhage (PPH remains a global challenge, affecting thirteen million women each year. In addition, PPH is a leading cause of maternal mortality in Asia and Africa. In the U.S.A., care of critically ill patients is often practiced using mannequin-based simulation. Mannequin-based simulation presents challenges in global health, particularly in low- or middle-income countries. We developed a novel multiplayer screen-based simulation in a virtual world enabling the practice of team coordination with PPH. We used this simulation with learners in Mulago, Uganda. We hypothesized that a multiplayer screen-based simulation experience would increase learner confidence in their ability to manage PPH.MethodsThe study design was a simple pre- and a post-intervention survey. Forty-eight interprofessional subjects participated in one of nine 1-h simulation sessions using the PPH software. A fifteen-question self-assessment administered before and after the intervention was designed to probe the areas of learning as defined by Bloom and Krathwohl: affective, cognitive, and psychomotor.ResultsCombined confidence scores increased significantly overall following the simulation experience and individually in each of the three categories of Bloom’s Taxonomy: affective, cognitive, and psychomotor.ConclusionWe provide preliminary evidence that multiplayer screen-based simulation represents a scalable, distributable form of learning that may be used effectively in global health education and training. Interestingly, despite our intervention being screen-based, our subjects showed improved confidence in their ability to perform psychomotor tasks. Although there is precedent for mental rehearsal improving performance, further research is needed to understand this finding.

  9. Semi-High Throughput Screening for Potential Drought-tolerance in Lettuce (Lactuca sativa) Germplasm Collections.

    Science.gov (United States)

    Knepper, Caleb; Mou, Beiquan

    2015-04-17

    This protocol describes a method by which a large collection of the leafy green vegetable lettuce (Lactuca sativa L.) germplasm was screened for likely drought-tolerance traits. Fresh water availability for agricultural use is a growing concern across the United States as well as many regions of the world. Short-term drought events along with regulatory intervention in the regulation of water availability coupled with the looming threat of long-term climate shifts that may lead to reduced precipitation in many important agricultural regions has increased the need to hasten the development of crops adapted for improved water use efficiency in order to maintain or expand production in the coming years. This protocol is not meant as a step-by-step guide to identifying at either the physiological or molecular level drought-tolerance traits in lettuce, but rather is a method developed and refined through the screening of thousands of different lettuce varieties. The nature of this screen is based in part on the streamlined measurements focusing on only three water-stress indicators: leaf relative water content, wilt, and differential plant growth following drought-stress. The purpose of rapidly screening a large germplasm collection is to narrow the candidate pool to a point in which more intensive physiological, molecular, and genetic methods can be applied to identify specific drought-tolerant traits in either the lab or field. Candidates can also be directly incorporated into breeding programs as a source of drought-tolerance traits.

  10. Heuristic lipophilicity potential for computer-aided rational drug design: Optimizations of screening functions and parameters

    Science.gov (United States)

    Du, Qishi; Mezey, Paul G.

    1998-09-01

    In this research we test and compare three possible atom-basedscreening functions used in the heuristic molecular lipophilicity potential(HMLP). Screening function 1 is a power distance-dependent function, b_{{i}} /| {R_{{i}}- r} |^γ, screening function 2is an exponential distance-dependent function, biexp(-| {R_i- r} |/d_0 , and screening function 3 is aweighted distance-dependent function, {{sign}}( {b_i } ){{exp}}ξ ( {| {R_i- r} |/| {b_i } |} )For every screening function, the parameters (γ ,d0, and ξ are optimized using 41 common organic molecules of 4 types of compounds:aliphatic alcohols, aliphatic carboxylic acids, aliphatic amines, andaliphatic alkanes. The results of calculations show that screening function3 cannot give chemically reasonable results, however, both the powerscreening function and the exponential screening function give chemicallysatisfactory results. There are two notable differences between screeningfunctions 1 and 2. First, the exponential screening function has largervalues in the short distance than the power screening function, thereforemore influence from the nearest neighbors is involved using screeningfunction 2 than screening function 1. Second, the power screening functionhas larger values in the long distance than the exponential screeningfunction, therefore screening function 1 is effected by atoms at longdistance more than screening function 2. For screening function 1, thesuitable range of parameter d0 is 1.5 < d0 < 3.0, and d0 = 2.0 is recommended. HMLP developed in this researchprovides a potential tool for computer-aided three-dimensional drugdesign.

  11. Molecular diagnosis and immunotherapy.

    Science.gov (United States)

    Sastre, Joaquín; Sastre-Ibañez, Marina

    2016-12-01

    To describe recent insights into how molecular diagnosis can improve indication and selection of suitable allergens for specific immunotherapy and increase the safety of this therapy. As specific allergen immunotherapy targets specific allergens, identification of the disease-eliciting allergen is a prerequisite for accurate prescription of treatment. In areas of complex sensitization to aeroallergens or in cases of hymenoptera venom allergy, the use of molecular diagnosis has demonstrated that it may lead to a change in indication and selection of allergens for immunotherapy in a large proportion of patients when compared with diagnosis based on skin prick testing and/or specific IgE determination with commercial extracts. These changes in immunotherapy prescription aided by molecular diagnosis have been demonstrated to be cost-effective in some scenarios. Certain patterns of sensitization to grass or olive pollen and bee allergens may identify patients with higher risk of adverse reaction during immunotherapy. Molecular diagnosis, when used with other tools and patients' clinical records, can help clinicians better to select the most appropriate patients and allergens for specific immunotherapy and, in some cases, predict the risk of adverse reactions. The pattern of sensitization to allergens could potentially predict the efficacy of allergen immunotherapy provided that these immunotherapy products contain a sufficient amount of these allergens. Nevertheless, multiplex assay remains a third-level approach, not to be used as screening method in current practice.

  12. Universal newborn hearing screening: preliminary experience at the University Hospital of Cagliari

    Directory of Open Access Journals (Sweden)

    Giulia Pinna

    2012-10-01

    Full Text Available Bilateral congenital or acquired sensorineural hearing loss is a pathological condition affecting 1-2 children per 1,000 live births; it represents a major issue in public health because its late identification can negatively affect speech and language development. The aim of hearing screening is to obtain diagnosis and management of hearing loss as soon as possible; in fact early diagnosis and treatment allow children with congenital hearing impairment to acquire adequate linguistic competence. The present study reports our preliminary experience in newborn hearing screening at Neonatology services of University of Cagliari (Italy. During the first semester of surveillance, between January 2012 and June 2012, hearing screening was performed on a total of 901 babies using two different methods, TEOAEs in healthy neonates and automated ABR in high-risk babies. All infants were screened prior to hospital discharge; in some cases, especially for preterm infants of Neonatal Intensive Care Unit and Puericulture Institute, the screening was performed after discharge, to achieve a possible better global and acoustic maturation; 5 cases of hearing impairment were found. In the present study the Authors confirmed that it is possible to start a universal hearing screening in a relatively short time reaching the percentages suggested by Joint Committee on Infant Hearing.

  13. Planetary Biology and Microbial Ecology: Molecular Ecology and the Global Nitrogen cycle

    Science.gov (United States)

    Nealson, Molly Stone (Editor); Nealson, Kenneth H. (Editor)

    1993-01-01

    This report summarizes the results of the Planetary Biology and Molecular Ecology's summer 1991 program, which was held at the Marine Biological Laboratory in Woods Hole, Massachusetts. The purpose of the interdisciplinary PBME program is to integrate, via lectures and laboratory work, the contributions of university and NASA scientists and student interns. The goals of the 1991 program were to examine several aspects of the biogeochemistry of the nitrogen cycle and to teach the application of modern methods of molecular genetics to field studies of organisms. Descriptions of the laboratory projects and protocols and abstracts and references of the lectures are presented.

  14. Molecular genetics of intraductal papillary-mucinous neoplasms of the pancreas.

    Science.gov (United States)

    Furukawa, Toru

    2007-01-01

    Intraductal papillary-mucinous neoplasms of the pancreas show characteristic clinicopathological and molecular pathobiological features which are distinct from those of conventional ductal adenocarcinomas. Alterations of KRAS, AKT/PKB, CDKN2A, TP53, SMAD4, STK11/LKB1, and DUSP6, and other molecular alterations, including global expression studies as well as their clinical implications, are discussed.

  15. Ovarian cancer: Novel molecular aspects for clinical assessment.

    Science.gov (United States)

    Palmirotta, Raffaele; Silvestris, Erica; D'Oronzo, Stella; Cardascia, Angela; Silvestris, Franco

    2017-09-01

    Ovarian cancer is a very heterogeneous tumor which has been traditionally characterized according to the different histological subtypes and differentiation degree. In recent years, innovative molecular screening biotechnologies have allowed to identify further subtypes of this cancer based on gene expression profiles, mutational features, and epigenetic factors. These novel classification systems emphasizing the molecular signatures within the broad spectrum of ovarian cancer have not only allowed a more precise prognostic prediction, but also proper therapeutic strategies for specific subgroups of patients. The bulk of available scientific data and the high refinement of molecular classifications of ovarian cancers can today address the research towards innovative drugs with the adoption of targeted therapies tailored for single molecular profiles leading to a better prediction of therapeutic response. Here, we summarize the current state of knowledge on the molecular bases of ovarian cancer, from the description of its molecular subtypes derived from wide high-throughput analyses to the latest discoveries of the ovarian cancer stem cells. The latest personalized treatment options are also presented with recent advances in using PARP inhibitors, anti-angiogenic, anti-folate receptor and anti-cancer stem cells treatment approaches. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Characterization of some bread wheat genotypes using molecular markers for drought tolerance.

    Science.gov (United States)

    Ateş Sönmezoğlu, Özlem; Terzi, Begüm

    2018-02-01

    Because of its wide geographical adaptation and importance in human nutrition, wheat is one of the most important crops in the world. However, wheat yield has reduced due to drought stress posing threat to sustainability and world food security in agricultural production. The first stage of drought tolerant variety breeding occurs on the molecular and biochemical characterization and classification of wheat genotypes. The aim of the present study is characterization of widely grown bread wheat cultivars and breeding lines for drought tolerance so as to be adapted to different regions in Turkey. The genotypes were screened with molecular markers for the presence of QTLs mapped to different chromosomes. Results of the molecular studies identified and detected 15 polymorphic SSR markers which gave the clearest PCR bands among the control genotypes. At the end of the research, bread wheat genotypes which were classified for tolerance or sensitivity to drought and the genetic similarity within control varieties were determined by molecular markers. According to SSR based dendrogram, two main groups were obtained for drought tolerance. At end of the molecular screening with SSR primers, genetic similarity coefficients were obtained that ranged from 0.14 to 0.71. The ones numbered 8 and 11 were the closest genotypes to drought tolerant cultivar Gerek 79 and the furthest genotypes from this cultivar were number 16 and to drought sensitive cultivar Sultan 95. The genotypes as drought tolerance due to their SSR markers scores are expected to provide useful information for drought related molecular breeding studies.

  17. Sequential Analysis of Global Gene Expression Profiles in Immature and In vitro Matured Bovine Oocytes: Potential Molecular Markers of Oocyte Maturation

    LENUS (Irish Health Repository)

    Mamo, Solomon

    2011-03-16

    Abstract Background Without intensive selection, the majority of bovine oocytes submitted to in vitro embryo production (IVP) fail to develop to the blastocyst stage. This is attributed partly to their maturation status and competences. Using the Affymetrix GeneChip Bovine Genome Array, global mRNA expression analysis of immature (GV) and in vitro matured (IVM) bovine oocytes was carried out to characterize the transcriptome of bovine oocytes and then use a variety of approaches to determine whether the observed transcriptional changes during IVM was real or an artifact of the techniques used during analysis. Results 8489 transcripts were detected across the two oocyte groups, of which ~25.0% (2117 transcripts) were differentially expressed (p < 0.001); corresponding to 589 over-expressed and 1528 under-expressed transcripts in the IVM oocytes compared to their immature counterparts. Over expression of transcripts by IVM oocytes is particularly interesting, therefore, a variety of approaches were employed to determine whether the observed transcriptional changes during IVM were real or an artifact of the techniques used during analysis, including the analysis of transcript abundance in oocytes in vitro matured in the presence of α-amanitin. Subsets of the differentially expressed genes were also validated by quantitative real-time PCR (qPCR) and the gene expression data was classified according to gene ontology and pathway enrichment. Numerous cell cycle linked (CDC2, CDK5, CDK8, HSPA2, MAPK14, TXNL4B), molecular transport (STX5, STX17, SEC22A, SEC22B), and differentiation (NACA) related genes were found to be among the several over-expressed transcripts in GV oocytes compared to the matured counterparts, while ANXA1, PLAU, STC1and LUM were among the over-expressed genes after oocyte maturation. Conclusion Using sequential experiments, we have shown and confirmed transcriptional changes during oocyte maturation. This dataset provides a unique reference resource

  18. Colon cancer screening

    Science.gov (United States)

    Screening for colon cancer; Colonoscopy - screening; Sigmoidoscopy - screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test; Colorectal cancer - screening; Rectal ...

  19. A Systematic Genetic Screen to Dissect the MicroRNA Pathway in Drosophila.

    Science.gov (United States)

    Pressman, Sigal; Reinke, Catherine A; Wang, Xiaohong; Carthew, Richard W

    2012-04-01

    A central goal of microRNA biology is to elucidate the genetic program of miRNA function and regulation. However, relatively few of the effectors that execute miRNA repression have been identified. Because such genes may function in many developmental processes, mutations in them are expected to be pleiotropic and thus are discarded in most standard genetic screens. Here, we describe a systematic screen designed to identify all Drosophila genes in ∼40% of the genome that function in the miRNA pathway. To identify potentially pleiotropic genes, the screen analyzed clones of homozygous mutant cells in heterozygous animals. We identified 45 mutations representing 24 genes, and we molecularly characterized 9 genes. These include 4 previously known genes that encode core components of the miRNA pathway, including Drosha, Pasha, Dicer-1, and Ago1. The rest are new genes that function through chromatin remodeling, signaling, and mRNA decapping. The results suggest genetic screens that use clonal analysis can elucidate the miRNA program and that ∼100 genes are required to execute the miRNA program.

  20. Molecular imaging in cervical cancer

    International Nuclear Information System (INIS)

    KHAN, Sairah R.; ROCKALL, Andrea G.; BARWICK, Tara D.

    2016-01-01

    Despite the development of screening and of a vaccine, cervix cancer is a major cause of cancer death in young women worldwide. A third of women treated for the disease will recur, almost inevitably leading to death. Functional imaging has the potential to stratify patients at higher risk of poor response or relapse by improved delineation of disease extent and tumor characteristics. A number of molecular imaging biomarkers have been shown to predict outcome at baseline and/or early during therapy in cervical cancer. In future this could help tailor the treatment plan which could include selection of patients for close follow up, adjuvant therapy or trial entry for novel agents or adaptive clinical trials. The use of molecular imaging techniques, FDG PET/CT and functional MRI, in staging and response assessment of cervical cancer is reviewed.

  1. An experience of qualified preventive screening: shiraz smart screening software.

    Science.gov (United States)

    Islami Parkoohi, Parisa; Zare, Hashem; Abdollahifard, Gholamreza

    2015-01-01

    Computerized preventive screening software is a cost effective intervention tool to address non-communicable chronic diseases. Shiraz Smart Screening Software (SSSS) was developed as an innovative tool for qualified screening. It allows simultaneous smart screening of several high-burden chronic diseases and supports reminder notification functionality. The extent in which SSSS affects screening quality is also described. Following software development, preventive screening and annual health examinations of 261 school staff (Medical School of Shiraz, Iran) was carried out in a software-assisted manner. To evaluate the quality of the software-assisted screening, we used quasi-experimental study design and determined coverage, irregular attendance and inappropriateness proportions in relation with the manual and software-assisted screening as well as the corresponding number of requested tests. In manual screening method, 27% of employees were covered (with 94% irregular attendance) while by software-assisted screening, the coverage proportion was 79% (attendance status will clear after the specified time). The frequency of inappropriate screening test requests, before the software implementation, was 41.37% for fasting plasma glucose, 41.37% for lipid profile, 0.84% for occult blood, 0.19% for flexible sigmoidoscopy/colonoscopy, 35.29% for Pap smear, 19.20% for mammography and 11.2% for prostate specific antigen. All of the above were corrected by the software application. In total, 366 manual screening and 334 software-assisted screening tests were requested. SSSS is an innovative tool to improve the quality of preventive screening plans in terms of increased screening coverage, reduction in inappropriateness and the total number of requested tests.

  2. Imaging and Screening of Kidney Cancer.

    Science.gov (United States)

    Diaz de Leon, Alberto; Pedrosa, Ivan

    2017-11-01

    Renal cell carcinoma (RCC) exhibits a diverse and heterogeneous disease spectrum, but insight into its molecular biology has provided an improved understanding of potential risk factors, oncologic behavior, and imaging features. Computed tomography (CT) and MR imaging may allow the identification and preoperative subtyping of RCC and assessment of a response to various therapies. Active surveillance is a viable management option in some patients and has provided further insight into the natural history of RCC, including the favorable prognosis of cystic neoplasms. This article reviews CT and MR imaging in RCC and the role of screening in selected high-risk populations. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Values of molecular markers in the differential diagnosis of thyroid abnormalities.

    Science.gov (United States)

    Tennakoon, T M P B; Rushdhi, M; Ranasinghe, A D C U; Dassanayake, R S

    2017-06-01

    Thyroid cancer (TC), follicular adenoma (FA) and Hashimoto's thyroiditis (HT) are three of the most frequently reported abnormalities that affect the thyroid gland. A frequent co-occurrence along with similar histopathological features is observed between TC and FA as well as between TC and HT. The conventional diagnostic methods such as histochemical analysis present complications in differential diagnosis when these abnormalities occur simultaneously. Hence, the authors recognize novel methods based on screening genetic defects of thyroid abnormalities as viable diagnostic and prognostic methods that could complement the conventional methods. We have extensively reviewed the existing literature on TC, FA and HT and also on three genes, namely braf, nras and ret/ptc, that could be used to differentially diagnose the three abnormalities. Emphasis was also given to the screening methods available to detect the said molecular markers. It can be conferred from the analysis of the available data that the utilization of braf, nras and ret/ptc as markers for the therapeutic evaluation of FA and HT is debatable. However, molecular screening for braf, nras and ret/ptc mutations proves to be a conclusive method that could be employed to differentially diagnose TC from HT and FA in the instance of a suspected co-occurrence. Thyroid cancer patients can be highly benefited from the screening for the said genetic markers, especially the braf gene due to its diagnostic value as well as due to the availability of personalized medicine targeted specifically for braf mutants.

  4. Questionnaires that screen for multiple sleep disorders.

    Science.gov (United States)

    Klingman, Karen J; Jungquist, Carla R; Perlis, Michael L

    2017-04-01

    The goal of this review was to identify, describe, and evaluate the existing multiple sleep disorders screening questionnaires for their comprehensiveness, brevity, and psychometric quality. A systematic review was conducted using Medline/PubMed, cumulative index to nursing & allied health literature, health and psychosocial instruments and the "grey literature". Search terms were "sleep disorders, screening, questionnaires, and psychometrics". The scope of the search was limited to English language articles for adult age groups from 1989 through 2015. Of the n = 2812 articles identified, most were assessment or treatment guideline reviews, topical reviews, and/or empirical articles. Seven of the articles described multiple sleep disorders screening instruments. Of the identified instruments, two questionnaires (the Holland sleep Disorders questionnaire and sleep-50) were evaluated as comprehensive and one questionnaire (the global sleep assessment questionnaire [GSAQ]) was judged to be both comprehensive and efficient. The GSAQ was found to cover four of the six core intrinsic disorders, sleep insufficiency, and daytime sequela with 11 questions. Accordingly, the GSAQ is the most suitable for application as a general sleep disorders screener. Additional work is required to validate this instrument in the context of primary care. Finally, the future development of multiple sleep disorders screening questionnaires should not only cover all six intrinsic sleep disorders but also acquire some basic demographic information (age, sex, body mass index, presence/absence of bed partner, work status and shift) and some limited data regarding sleep sufficiency and the daytime consequences of sleep disturbance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Taking place, screening place

    DEFF Research Database (Denmark)

    Hansen, Kim Toft; Waade, Anne Marit

    2019-01-01

    We introduce location studies as a new empirical approach to screen studies. Location studies represent an interdisciplinary perspective, including media, aesthetics and geography, and reflect a growing interest in places in a global media and consumption culture. The chapter analyses two recent......) with one being traditional and the other being commercial; both dramas include discussions of localities and social heritage, and both use local sports as a common metaphor for social cohesion; and both series have been partly funded by a local film Danish commissioner. However, The Legacy is shot...... to a large extent in studios, while Norskov is shot entirely on location. The study is based on interviews with producers, broadcasters, location scouts, production designers and writers, as well as quantitative and qualitative textual analyses of television drama series, the geographical places, and related...

  6. Viral hepatitis screening in transgender patients undergoing gender identity hormonal therapy.

    Science.gov (United States)

    Mangla, Neeraj; Mamun, Rifat; Weisberg, Ilan S

    2017-11-01

    Viral hepatitis is a global health issue and can lead to cirrhosis, liver failure, and hepatocellular carcinoma. Guidelines for viral hepatitis screening in the transgender population do not exist. Transgender patients may be at higher risk for contracting viral hepatitis due to socioeconomic and behavioral factors. The aim of this study was to measure the quality of screening, prevalence, and susceptibility of viral hepatitis, and to identify barriers to screening in transgender patients undergoing gender identity hormonal therapy. LGBTQ-friendly clinic visits from transgender patients older than 18 years in New York City from 2012 to 2015 were reviewed. Approximately 13% of patients were screened for any viral hepatitis on initial consultation. Screening rates for hepatitis C virus (HCV), hepatitis B virus (HBV), and hepatitis A virus (HAV) at any point were 27, 22, and 20%. HAV screening was performed in 28% of the female to male (FtM) patients and 16% of male to female (MtF) (P0.05). Prevalence of HCV, HBV, and HIV in FtM was 0, 0, and 0.44% and that in MtF was 1.78, 0.89, and 1.78%, respectively. Percentage of patients immune to hepatitis A in FtM and MtF subgroups were 55 and 47% (P>0.05). Percentage of patients immune to HBV in FtM and MtF subgroups were 54 and 48% (P>0.05). This study indicates a significant lack of hepatitis screening in the transgender population and a concerning proportion of patients susceptible to disease.

  7. Virtual screening approach to identifying influenza virus neuraminidase inhibitors using molecular docking combined with machine-learning-based scoring function.

    Science.gov (United States)

    Zhang, Li; Ai, Hai-Xin; Li, Shi-Meng; Qi, Meng-Yuan; Zhao, Jian; Zhao, Qi; Liu, Hong-Sheng

    2017-10-10

    In recent years, an epidemic of the highly pathogenic avian influenza H7N9 virus has persisted in China, with a high mortality rate. To develop novel anti-influenza therapies, we have constructed a machine-learning-based scoring function (RF-NA-Score) for the effective virtual screening of lead compounds targeting the viral neuraminidase (NA) protein. RF-NA-Score is more accurate than RF-Score, with a root-mean-square error of 1.46, Pearson's correlation coefficient of 0.707, and Spearman's rank correlation coefficient of 0.707 in a 5-fold cross-validation study. The performance of RF-NA-Score in a docking-based virtual screening of NA inhibitors was evaluated with a dataset containing 281 NA inhibitors and 322 noninhibitors. Compared with other docking-rescoring virtual screening strategies, rescoring with RF-NA-Score significantly improved the efficiency of virtual screening, and a strategy that averaged the scores given by RF-NA-Score, based on the binding conformations predicted with AutoDock, AutoDock Vina, and LeDock, was shown to be the best strategy. This strategy was then applied to the virtual screening of NA inhibitors in the SPECS database. The 100 selected compounds were tested in an in vitro H7N9 NA inhibition assay, and two compounds with novel scaffolds showed moderate inhibitory activities. These results indicate that RF-NA-Score improves the efficiency of virtual screening for NA inhibitors, and can be used successfully to identify new NA inhibitor scaffolds. Scoring functions specific for other drug targets could also be established with the same method.

  8. Post-travel screening of asymptomatic long-term travelers to the tropics for intestinal parasites using molecular diagnostics.

    Science.gov (United States)

    Soonawala, Darius; van Lieshout, Lisette; den Boer, Marion A M; Claas, Eric C J; Verweij, Jaco J; Godkewitsch, André; Ratering, Marchel; Visser, Leo G

    2014-05-01

    The incidence of asymptomatic travel-related parasitic infection is uncertain. Previous studies did not distinguish new incident infections, from past infections. Regardless of symptoms, we performed multiplex real-time polymerase chain reaction on pre- and post-travel stool samples of Dutch long-term travelers to the (sub)tropics. Serological screening for Schistosoma spp. was only performed in travelers to sub-Saharan Africa. In total, 679 travelers were included in the study. The follow-up rate was 82% (556 of 679). Participants' median travel duration was 12 weeks. There was one incident infection with Strongyloides stercoralis; there were none with Entamoeba histolytica, 4 with Cryptosporidium spp. (1%), and 22 with Giardia lamblia (4%). Nine of 146 travelers (6%) seroconverted for Schistosoma spp. Routine screening of stool samples for parasitic infection is not indicated for asymptomatic people, who travel to the (sub)tropics for up to 3 months. Screening for Schistosoma spp. should be offered to travelers with fresh-water contact in endemic regions.

  9. The cumulative risk of false-positive screening results across screening centres in the Norwegian Breast Cancer Screening Program

    Energy Technology Data Exchange (ETDEWEB)

    Roman, M., E-mail: Marta.Roman@kreftregisteret.no [Cancer Registry of Norway, Oslo (Norway); Department of Women and Children’s Health, Oslo University Hospital, Oslo (Norway); Skaane, P., E-mail: PERSK@ous-hf.no [Department of Radiology, Oslo University Hospital Ullevaal, University of Oslo, Oslo (Norway); Hofvind, S., E-mail: Solveig.Hofvind@kreftregisteret.no [Cancer Registry of Norway, Oslo (Norway); Oslo and Akershus University College of Applied Sciences, Faculty of Health Science, Oslo (Norway)

    2014-09-15

    Highlights: • We found variation in early performance measures across screening centres. • Radiologists’ performance may play a key role in the variability. • Potential to improve the effectiveness of breast cancer screening programs. • Continuous surveillance of screening centres and radiologists is essential. - Abstract: Background: Recall for assessment in mammographic screening entails an inevitable number of false-positive screening results. This study aimed to investigate the variation in the cumulative risk of a false positive screening result and the positive predictive value across the screening centres in the Norwegian Breast Cancer Screening Program. Methods: We studied 618,636 women aged 50–69 years who underwent 2,090,575 screening exams (1996–2010. Recall rate, positive predictive value, rate of screen-detected cancer, and the cumulative risk of a false positive screening result, without and with invasive procedures across the screening centres were calculated. Generalized linear models were used to estimate the probability of a false positive screening result and to compute the cumulative false-positive risk for up to ten biennial screening examinations. Results: The cumulative risk of a false-positive screening exam varied from 10.7% (95% CI: 9.4–12.0%) to 41.5% (95% CI: 34.1–48.9%) across screening centres, with a highest to lowest ratio of 3.9 (95% CI: 3.7–4.0). The highest to lowest ratio for the cumulative risk of undergoing an invasive procedure with a benign outcome was 4.3 (95% CI: 4.0–4.6). The positive predictive value of recall varied between 12.0% (95% CI: 11.0–12.9%) and 19.9% (95% CI: 18.3–21.5%), with a highest to lowest ratio of 1.7 (95% CI: 1.5–1.9). Conclusions: A substantial variation in the performance measures across the screening centres in the Norwegian Breast Cancer Screening Program was identified, despite of similar administration, procedures, and quality assurance requirements. Differences in the

  10. The cumulative risk of false-positive screening results across screening centres in the Norwegian Breast Cancer Screening Program

    International Nuclear Information System (INIS)

    Roman, M.; Skaane, P.; Hofvind, S.

    2014-01-01

    Highlights: • We found variation in early performance measures across screening centres. • Radiologists’ performance may play a key role in the variability. • Potential to improve the effectiveness of breast cancer screening programs. • Continuous surveillance of screening centres and radiologists is essential. - Abstract: Background: Recall for assessment in mammographic screening entails an inevitable number of false-positive screening results. This study aimed to investigate the variation in the cumulative risk of a false positive screening result and the positive predictive value across the screening centres in the Norwegian Breast Cancer Screening Program. Methods: We studied 618,636 women aged 50–69 years who underwent 2,090,575 screening exams (1996–2010. Recall rate, positive predictive value, rate of screen-detected cancer, and the cumulative risk of a false positive screening result, without and with invasive procedures across the screening centres were calculated. Generalized linear models were used to estimate the probability of a false positive screening result and to compute the cumulative false-positive risk for up to ten biennial screening examinations. Results: The cumulative risk of a false-positive screening exam varied from 10.7% (95% CI: 9.4–12.0%) to 41.5% (95% CI: 34.1–48.9%) across screening centres, with a highest to lowest ratio of 3.9 (95% CI: 3.7–4.0). The highest to lowest ratio for the cumulative risk of undergoing an invasive procedure with a benign outcome was 4.3 (95% CI: 4.0–4.6). The positive predictive value of recall varied between 12.0% (95% CI: 11.0–12.9%) and 19.9% (95% CI: 18.3–21.5%), with a highest to lowest ratio of 1.7 (95% CI: 1.5–1.9). Conclusions: A substantial variation in the performance measures across the screening centres in the Norwegian Breast Cancer Screening Program was identified, despite of similar administration, procedures, and quality assurance requirements. Differences in the

  11. Alcohol Use Screening

    Science.gov (United States)

    ... Depression Screening Substance Abuse Screening Alcohol Use Screening Alcohol Use Screening (AUDIT-C) - Instructions The following questions ... this tool, there is also text-only version . Alcohol Use Screening (AUDIT-C) - Manual Instructions The following ...

  12. Estimation of diffuse from measured global solar radiation

    International Nuclear Information System (INIS)

    Moriarty, W.W.

    1991-01-01

    A data set of quality controlled radiation observations from stations scattered throughout Australia was formed and further screened to remove residual doubtful observations. It was then divided into groups by solar elevation, and used to find average relationships for each elevation group between relative global radiation (clearness index - the measured global radiation expressed as a proportion of the radiation on a horizontal surface at the top of the atmosphere) and relative diffuse radiation. Clear-cut relationships were found, which were then fitted by polynomial expressions giving the relative diffuse radiation as a function of relative global radiation and solar elevation. When these expressions were used to estimate the diffuse radiation from the global, the results had a slightly smaller spread of errors than those from an earlier technique given by Spencer. It was found that the errors were related to cloud amount, and further relationships were developed giving the errors as functions of global radiation, solar elevation, and the fraction of sky obscured by high cloud and by opaque (low and middle level) cloud. When these relationships were used to adjust the first estimates of diffuse radiation, there was a considerable reduction in the number of large errors

  13. Final screening round of the NELSON lung cancer screening trial: the effect of a 2.5-year screening interval

    NARCIS (Netherlands)

    Yousaf-Khan, U.; Aalst, C. van der; Jong, P.A. de; Heuvelmans, M.; Scholten, E.T.; Lammers, J.-W.J.; Ooijen, P. van; Nackaerts, K.; Weenink, C.; Groen, H.; Vliegenthart, R.; Haaf, K. Ten; Oudkerk, M.; Koning, H. de

    2016-01-01

    In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

  14. Final screening round of the NELSON lung cancer screening trial : the effect of a 2.5-year screening interval

    NARCIS (Netherlands)

    Yousaf-Khan, Uraujh; van der Aalst, Carlijn; de Jong, Pim A; Heuvelmans, Marjolein; Scholten, Ernst; Lammers, Jan-Willem; van Ooijen, Peter; Nackaerts, Kristiaan; Weenink, Carla; Groen, Harry; Vliegenthart, Rozemarijn; Ten Haaf, Kevin; Oudkerk, Matthijs; de Koning, Harry

    BACKGROUND: In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

  15. Final screening round of the NELSON lung cancer screening trial : the effect of a 2.5-year screening interval

    NARCIS (Netherlands)

    Yousaf-Khan, Uraujh; van der Aalst, Carlijn; de Jong, Pim A.; Heuvelmans, Marjolein; Scholten, Ernst; Lammers, Jan-Willem; van Ooijen, Peter; Nackaerts, Kristiaan; Weenink, Carla; Groen, Harry; Vliegenthart, Rozemarijn; Ten Haaf, Kevin; Oudkerk, Matthijs; de Koning, Harry

    Background In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

  16. Molecular genetic studies of bacteroides fragilis

    International Nuclear Information System (INIS)

    Southern, J.A.

    1986-03-01

    This study aimed at providing a means for probing the molecular genetic organization of B.fragilis, particularly those strains where the DNA repair mechanisms had been described. The following routes of investigation were followed: the bacteriocin of B.fragilis BF-1; the investigation of any plasmids which might be discovered, with the aim of constructing a hybrid plasmid which might replicate in both E.coli and B.fragilis; and the preparation of a genetic library which could be screened for Bacteroides genes which might function in E.coli. Should any genes be isolated by screening the library they were to be studied with regard to their expression and regulation in E.coli. The above assays make use of radioactive markers such as 14 C, 35 S, 32 P, and 3 H in the labelling of RNA, plasmids and probes

  17. Development and validation of a Haitian Creole screening instrument for depression

    Science.gov (United States)

    Rasmussen, Andrew; Eustache, Eddy; Raviola, Giuseppe; Kaiser, Bonnie; Grelotti, David; Belkin, Gary

    2014-01-01

    Developing mental health care capacity in post-earthquake Haiti is hampered by the lack of assessments that include culturally bound idioms Haitians use when discussing emotional distress. The current study describes a novel emic-etic approach to developing a depression screening for Partners In Health/Zanmi Lasante. In Study 1 Haitian key informants were asked to classify symptoms and describe categories within a pool of symptoms of common mental disorders. Study 2 tested the symptom set that best approximated depression in a sample of depressed and not depressed Haitians in order to select items for the screening tool. The resulting 13-item instrument produced scores with high internal reliability that were sensitive to culturally-informed diagnoses, and interpretations with construct and concurrent validity (vis-à-vis functional impairment). Discussion focuses on the appropriate use of this tool and integrating emic perspectives into developing psychological assessments globally. The screening tool is provided as an Appendix. PMID:25080426

  18. Nanoscale Affinity Chip Interface for Coupling Inhibition SPR Immunosensor Screening with Nano-LC TOF MS

    NARCIS (Netherlands)

    Marchesini, G.R.; Buijs, J.; Haasnoot, W.; Hooijerink, H.; Jansson, O.; Nielen, M.W.F.

    2008-01-01

    The on-line nanoscale coupling of a surface plasmon resonance (SPR)-based inhibition biosensor immunoassay (iBIA) for the screening of low molecular weight molecules with nano-liquid-chromatography electrospray ionization time-of-flight mass spectrometry (nano-LC ESI TOF MS) for identification is

  19. Screening of Anti-Obesity Agent from Herbal Mixtures

    OpenAIRE

    Sung-Kee Jo; Uhee Jung; Changhyun Roh

    2012-01-01

    Globally, one in three of the World’s adults are overweight and one in 10 is obese. By 2015, World Health Organization (WHO) estimates the number of chubby adults will balloon to 2.3 billion—Equal to the combined populations of China, Europe and the United States. The discovery of bioactive compounds from herbs is one possible way to control obesity and to prevent or reduce the risks of developing various obesity-related diseases. In this study, we screened anti-obesity agents such as methyl ...

  20. Localizing Global Medicine: Challenges and Opportunities in Cervical Screening in an Indigenous Community in Ecuador.

    Science.gov (United States)

    Nugus, Peter; Désalliers, Julie; Morales, Juana; Graves, Lisa; Evans, Andrea; Macaulay, Ann C

    2018-04-01

    This participatory research study examines the tensions and opportunities in accessing allopathic medicine, or biomedicine, in the context of a cervical cancer screening program in a rural indigenous community of Northern Ecuador. Focusing on the influence of social networks, the article extends research on "re-appropriation" of biomedicine. It does so by recognizing two competing tensions expressed through social interactions: suspicion of allopathic medicine and the desire to maximize one's health. Semistructured individual interviews and focus groups were conducted with 28 women who had previously participated in a government-sponsored cervical screening program. From inductive thematic analysis, the article traces these women's active agency in navigating coherent paths of health. Despite drawing on social networks to overcome formidable challenges, the participants faced enduring system obstacles-the organizational effects of the networks of allopathic medicine. Such obstacles need to be understood to reconcile competing knowledge systems and improve health care access in underresourced communities.

  1. The Dynamics of an HIV/AIDS Model with Screened Disease Carriers

    Directory of Open Access Journals (Sweden)

    S. D. Hove-Musekwa

    2009-01-01

    Full Text Available The presence of carriers usually complicates the dynamics and prevention of a disease. They are not recognized as disease cases themselves unless they are screened and they usually spread the infection without them being aware. We argue that this has been one of the major causes of the spread of human immunodeficiency virus (HIV. We propose, in this paper, a model for the heterogeneous transmission of HIV/acquired immunodeficiency syndrome in the presence of disease carriers. The model allows us to assess the role of screening, as an intervention program that can slow the epidemic. A threshold value ψ*, for the screening rate is obtained. It is shown numerically that if 80% or more of the carrier population is screened, the epidemic can be contained. The qualitative analysis is done in terms of the model reproduction number R. The model has two equilibria, the disease free equilibrium and a unique endemic equilibrium. The disease free equilibrium is globally stable of R  1. A detailed discussion of the model reproduction number is given and numerical simulations are done to show the role of some of the important model parameters.

  2. Bridging the gap between morphological species and molecular barcodes - Exemplified by loricate choanoflagellates

    DEFF Research Database (Denmark)

    Frank, Nitsche; Thomsen, Helge Abildhauge; Daniel J, Richter

    2017-01-01

    species match a previously unidentified barcode from Tara Oceans, providing access to the global distribution of species isolated from Danish waters. One species, Calliacantha natans, is the second most globally abundant choanoflagellate present in Tara Oceans. Our project translating new ribosomal DNA......Translating the vast amounts of molecular barcodes from global surveys of microbial eukaryotes into ecological insight depends critically on a well-curated reference database with adequate taxonomic coverage. In this respect, the choanoflagellates resemble other eukaryotic lineages: reasonable...... represent an opportunity to link morphological with molecular data within a lineage of eukaryotes. To match morphospecies to sequences, we sampled the Kattegat and the Isefjord in Denmark in September 2014 and February 2015. We identified 45 morphospecies and sequenced ribosomal DNA of nine previously...

  3. MEMBANGUN KARAKTER BANGSA DI TENGAH-TENGAH BUDAYA GLOBAL

    Directory of Open Access Journals (Sweden)

    - Tukidi

    2012-03-01

    Full Text Available Condition of Indonesian character today is quite apprehensive, therefore, the government has take initiatives to prioritize the nation’s character development, both formal education in schools and other social institutions like government institutions, politics, society, families, businesses, NGOs and mass media. The progress of transportation an communication has brought fundamental change in our society, such as from closed societies to open societies, space and social interaction becomes more opened and globalize. In other side, globalize of social interaction can increace the horizon of life and welfare society, while it can couse the entry of foreign ideology and culture that confict with cultural values and character of Indonesia. Therefore, in order to build the character of the nation and screening the entry of foreign culture needed synergistic cooperation between various social and educational institutions, both formal and non formal. Keywords: nation character, globalization, social interaction

  4. Towards a systematic nationwide screening strategy for MODY.

    Science.gov (United States)

    Shields, Beverley; Colclough, Kevin

    2017-04-01

    MODY is an early-onset monogenic form of diabetes. Correctly identifying MODY is of considerable importance as diagnosing the specific genetic subtype can inform the optimal treatment, with many patients being able to discontinue unnecessary insulin treatment. Diagnostic molecular genetic testing to confirm MODY is expensive, so screening strategies are required to identify the most appropriate patients for testing. In this issue of Diabetologia, Johansson and colleagues (DOI 10.1007/s00125-016-4167-1 ) describe a nationwide systematic screening approach to identify individuals with MODY in the paediatric age range. They focused testing on patients negative for both GAD and islet antigen 2 (IA-2) islet autoantibodies, thereby ruling out those with markers of type 1 diabetes, the most common form of diabetes in this age group. This commentary discusses the advantages and limitations of the approach, and the caution required when interpreting variants of uncertain pathogenicity identified from testing whole populations rather than targeting only patients with a strong MODY phenotype.

  5. iScreen: Image-Based High-Content RNAi Screening Analysis Tools.

    Science.gov (United States)

    Zhong, Rui; Dong, Xiaonan; Levine, Beth; Xie, Yang; Xiao, Guanghua

    2015-09-01

    High-throughput RNA interference (RNAi) screening has opened up a path to investigating functional genomics in a genome-wide pattern. However, such studies are often restricted to assays that have a single readout format. Recently, advanced image technologies have been coupled with high-throughput RNAi screening to develop high-content screening, in which one or more cell image(s), instead of a single readout, were generated from each well. This image-based high-content screening technology has led to genome-wide functional annotation in a wider spectrum of biological research studies, as well as in drug and target discovery, so that complex cellular phenotypes can be measured in a multiparametric format. Despite these advances, data analysis and visualization tools are still largely lacking for these types of experiments. Therefore, we developed iScreen (image-Based High-content RNAi Screening Analysis Tool), an R package for the statistical modeling and visualization of image-based high-content RNAi screening. Two case studies were used to demonstrate the capability and efficiency of the iScreen package. iScreen is available for download on CRAN (http://cran.cnr.berkeley.edu/web/packages/iScreen/index.html). The user manual is also available as a supplementary document. © 2014 Society for Laboratory Automation and Screening.

  6. Nickel-resistance determinants in Acidiphilium sp. PM identified by genome-wide functional screening.

    Directory of Open Access Journals (Sweden)

    Patxi San Martin-Uriz

    Full Text Available Acidiphilium spp. are conspicuous dwellers of acidic, metal-rich environments. Indeed, they are among the most metal-resistant organisms; yet little is known about the mechanisms behind the metal tolerance in this genus. Acidiphilium sp. PM is an environmental isolate from Rio Tinto, an acidic, metal-laden river located in southwestern Spain. The characterization of its metal resistance revealed a remarkable ability to tolerate high Ni concentrations. Here we report the screening of a genomic library of Acidiphilium sp. PM to identify genes involved in Ni resistance. This approach revealed seven different genes conferring Ni resistance to E. coli, two of which form an operon encoding the ATP-dependent protease HslVU (ClpQY. This protease was found to enhance resistance to both Ni and Co in E. coli, a function not previously reported. Other Ni-resistance determinants include genes involved in lipopolysaccharide biosynthesis and the synthesis of branched amino acids. The diversity of molecular functions of the genes recovered in the screening suggests that Ni resistance in Acidiphilium sp. PM probably relies on different molecular mechanisms.

  7. Prostate Cancer Screening in Jamaica: Results of the Largest National Screening Clinic Prostate Cancer Screening in Jamaica: Results of the Largest National Screening Clinic

    International Nuclear Information System (INIS)

    Morrison, B. F.; Aiken, W.; Mayhew, R.; Gordon, Y.; Reid, M.

    2016-01-01

    Prostate cancer is highly prevalent in Jamaica and is the leading cause of cancer-related deaths. Our aim was to evaluate the patterns of screening in the largest organized screening clinic in Jamaica at the Jamaica Cancer Society. A retrospective analysis of all men presenting for screening at the Jamaica Cancer Society from 1995 to 2005 was done. All patients had digital rectal examinations (DRE) and prostate specific antigen (PSA) tests done. Results of prostate biopsies were noted. 1117 men of mean age 59.9 ± 8.2 years presented for screening. The median documented PSA was 1.6 ng/mL (maximum of 5170 ng/mL). Most patients presented for only 1 screen. There was a gradual reduction in the mean age of presentation for screening over the period. Prostate biopsies were requested on 11% of screening visits; however, only 59% of these were done. 5.6% of all persons screened were found to have cancer. Of the cancers diagnosed, Gleason 6 adenocarcinoma was the commonest grade and median PSA was 8.9 ng/mL (range 1.5-1059 ng/mL). Older men tend to screen for prostate cancer in Jamaica. However, compliance with regular maintenance visits and requests for confirmatory biopsies are poor. Screening needs intervention in the Jamaican population.

  8. Patient-generated subjective global assessment : innovation from paper to digital app

    NARCIS (Netherlands)

    Ottery, Faith D.; Isenring, Elizabeth; Kasenic, Suzanne; DeBolt, Susan P.; Sealy, Martine; Jager-Wittenaar, Harriët

    2015-01-01

    Purpose: The Patient-Generated Subjective Global Assessment (PG-SGA), including the PG-SGA Short Form (SF, aka ‘abridged’), was originally developed in the mid 1990’s as a scored, patient self-report, paperbased instrument and has been widely validated. The PG-SGA (SF) has been used for screening,

  9. Patient-generated subjective global assessment : Innovation from paper to digital app

    NARCIS (Netherlands)

    Faith D. Ottery; Suzanne Kasenic; Martine J. Sealy; Susan P. DeBolt; Elizabeth Isenring; Dr. Harriët Jager-Wittenaar

    2015-01-01

    Purpose: The Patient-Generated Subjective Global Assessment (PG-SGA), including the PG-SGA Short Form (SF, aka ‘abridged’), was originally developed in the mid 1990’s as a scored, patient self-report, paperbased instrument and has been widely validated. The PG-SGA (SF) has been used for screening,

  10. Molecular Epidemiology for Vector Research on Leishmaniasis

    Science.gov (United States)

    Kato, Hirotomo; Gomez, Eduardo A; Cáceres, Abraham G; Uezato, Hiroshi; Mimori, Tatsuyuki; Hashiguchi, Yoshihisa

    2010-01-01

    Leishmaniasis is a protozoan disease caused by the genus Leishmania transmitted by female phlebotomine sand flies. Surveillance of the prevalence of Leishmania and responsive vector species in endemic and surrounding areas is important for predicting the risk and expansion of the disease. Molecular biological methods are now widely applied to epidemiological studies of infectious diseases including leishmaniasis. These techniques are used to detect natural infections of sand fly vectors with Leishmania protozoa and are becoming powerful tools due to their sensitivity and specificity. Recently, genetic analyses have been performed on sand fly species and genotyping using PCR-RFLP has been applied to the sand fly taxonomy. In addition, a molecular mass screening method has been established that enables both sand fly species and natural leishmanial infections to be identified simultaneously in hundreds of sand flies with limited effort. This paper reviews recent advances in the study of sand flies, vectors of leishmaniasis, using molecular biological approaches. PMID:20617005

  11. Molecular Epidemiology for Vector Research on Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Hirotomo Kato

    2010-03-01

    Full Text Available Leishmaniasis is a protozoan disease caused by the genus Leishmania transmitted by female phlebotomine sand flies. Surveillance of the prevalence of Leishmania and responsive vector species in endemic and surrounding areas is important for predicting the risk and expansion of the disease. Molecular biological methods are now widely applied to epidemiological studies of infectious diseases including leishmaniasis. These techniques are used to detect natural infections of sand fly vectors with Leishmania protozoa and are becoming powerful tools due to their sensitivity and specificity. Recently, genetic analyses have been performed on sand fly species and genotyping using PCR-RFLP has been applied to the sand fly taxonomy. In addition, a molecular mass screening method has been established that enables both sand fly species and natural leishmanial infections to be identified simultaneously in hundreds of sand flies with limited effort. This paper reviews recent advances in the study of sand flies, vectors of leishmaniasis, using molecular biological approaches.

  12. Molecular epidemiology for vector research on leishmaniasis.

    Science.gov (United States)

    Kato, Hirotomo; Gomez, Eduardo A; Cáceres, Abraham G; Uezato, Hiroshi; Mimori, Tatsuyuki; Hashiguchi, Yoshihisa

    2010-03-01

    Leishmaniasis is a protozoan disease caused by the genus Leishmania transmitted by female phlebotomine sand flies. Surveillance of the prevalence of Leishmania and responsive vector species in endemic and surrounding areas is important for predicting the risk and expansion of the disease. Molecular biological methods are now widely applied to epidemiological studies of infectious diseases including leishmaniasis. These techniques are used to detect natural infections of sand fly vectors with Leishmania protozoa and are becoming powerful tools due to their sensitivity and specificity. Recently, genetic analyses have been performed on sand fly species and genotyping using PCR-RFLP has been applied to the sand fly taxonomy. In addition, a molecular mass screening method has been established that enables both sand fly species and natural leishmanial infections to be identified simultaneously in hundreds of sand flies with limited effort. This paper reviews recent advances in the study of sand flies, vectors of leishmaniasis, using molecular biological approaches.

  13. Automated docking screens: a feasibility study.

    Science.gov (United States)

    Irwin, John J; Shoichet, Brian K; Mysinger, Michael M; Huang, Niu; Colizzi, Francesco; Wassam, Pascal; Cao, Yiqun

    2009-09-24

    Molecular docking is the most practical approach to leverage protein structure for ligand discovery, but the technique retains important liabilities that make it challenging to deploy on a large scale. We have therefore created an expert system, DOCK Blaster, to investigate the feasibility of full automation. The method requires a PDB code, sometimes with a ligand structure, and from that alone can launch a full screen of large libraries. A critical feature is self-assessment, which estimates the anticipated reliability of the automated screening results using pose fidelity and enrichment. Against common benchmarks, DOCK Blaster recapitulates the crystal ligand pose within 2 A rmsd 50-60% of the time; inferior to an expert, but respectrable. Half the time the ligand also ranked among the top 5% of 100 physically matched decoys chosen on the fly. Further tests were undertaken culminating in a study of 7755 eligible PDB structures. In 1398 cases, the redocked ligand ranked in the top 5% of 100 property-matched decoys while also posing within 2 A rmsd, suggesting that unsupervised prospective docking is viable. DOCK Blaster is available at http://blaster.docking.org .

  14. Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm.

    Science.gov (United States)

    Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig

    2015-05-01

    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

  15. Automated Groundwater Screening

    International Nuclear Information System (INIS)

    Taylor, Glenn A.; Collard, Leonard B.

    2005-01-01

    The Automated Intruder Analysis has been extended to include an Automated Ground Water Screening option. This option screens 825 radionuclides while rigorously applying the National Council on Radiation Protection (NCRP) methodology. An extension to that methodology is presented to give a more realistic screening factor for those radionuclides which have significant daughters. The extension has the promise of reducing the number of radionuclides which must be tracked by the customer. By combining the Automated Intruder Analysis with the Automated Groundwater Screening a consistent set of assumptions and databases is used. A method is proposed to eliminate trigger values by performing rigorous calculation of the screening factor thereby reducing the number of radionuclides sent to further analysis. Using the same problem definitions as in previous groundwater screenings, the automated groundwater screening found one additional nuclide, Ge-68, which failed the screening. It also found that 18 of the 57 radionuclides contained in NCRP Table 3.1 failed the screening. This report describes the automated groundwater screening computer application

  16. Molecular Characterization of Staphylococcus warneri Catalase

    OpenAIRE

    Fukuda, Daisuke; Mizuno, Kouhei; Kohno, Mamiko; Sonomoto, Kenji; Ishizaki, Ayaaki

    2000-01-01

    The catalase gene was cloned by screening a genomic DNA library of S. warneri ISK-1 strain with a strong catalase activity for complementation of the activity in catalase-deficient E. coli strain. Nucleotide sequence analysis of a 2.2-kb DNA fragment revealed an open reading frame, called katA, encoding a peptide of 504 amino acids with a calculated molecular mass of 58kDa. The predicted amino acid sequence showed high similarities with the monofunctional catalases. No similarities were found...

  17. Post-Traumatic Hypopituitarism—Who Should Be Screened, When, and How?

    Directory of Open Access Journals (Sweden)

    Mark Quinn

    2018-02-01

    Full Text Available Traumatic brain injury (TBI remains a major, global public health concern. Over the last 15 years, a significant body of evidence has emerged demonstrating that post-traumatic hypopituitarism (PTHP is a common and clinically significant consequence of TBI. Non-specific symptomology and the lack of an agreed approach to screening for PTHP has led to significant under-diagnosis of this debilitating disease. In this review, we will discuss the frequency and clinical significance of acute and chronic PTHP as described in the current literature highlighting the evidence base for screening and hormone replacement in these patients. We will also offer a pragmatic approach to identifying relevant anterior pituitary dysfunction after TBI and a follow-up strategy for those patients. Specific controversies and remaining unanswered questions will be addressed.

  18. Heterogeneity of O blood group in India: Peeping through the window of molecular biology

    Directory of Open Access Journals (Sweden)

    Harita Gogri

    2018-01-01

    Results And Discussion: Overall, ten different genotypes were identified. Three rare alleles, namely, O05, O11, and O26 were seen in the mixed group category. These results suggest that there is an internal heterogeneity in the mixed group while Dhodias and Parsis, the groups which were screened earlier, seem to be more homogenous groups. An important piece of information emerges out from this study, that is, O01O02 genotype is expressing some selective force in population groups screened in India as well as many other groups worldwide. Conclusion: In the future, molecular genotyping of the ABO blood group system among different ethnic and tribal Indian groups would help in generating data to fill up the gaps in the molecular ABO map of the world.

  19. Novel Data Mining Methods for Virtual Screening of Biological Active Chemical Compounds

    KAUST Repository

    Soufan, Othman M.

    2016-11-23

    Drug discovery is a process that takes many years and hundreds of millions of dollars to reveal a confident conclusion about a specific treatment. Part of this sophisticated process is based on preliminary investigations to suggest a set of chemical compounds as candidate drugs for the treatment. Computational resources have been playing a significant role in this part through a step known as virtual screening. From a data mining perspective, availability of rich data resources is key in training prediction models. Yet, the difficulties imposed by big expansion in data and its dimensionality are inevitable. In this thesis, I address the main challenges that come when data mining techniques are used for virtual screening. In order to achieve an efficient virtual screening using data mining, I start by addressing the problem of feature selection and provide analysis of best ways to describe a chemical compound for an enhanced screening performance. High-throughput screening (HTS) assays data used for virtual screening are characterized by a great class imbalance. To handle this problem of class imbalance, I suggest using a novel algorithm called DRAMOTE to narrow down promising candidate chemicals aimed at interaction with specific molecular targets before they are experimentally evaluated. Existing works are mostly proposed for small-scale virtual screening based on making use of few thousands of interactions. Thus, I propose enabling large-scale (or big) virtual screening through learning millions of interaction while exploiting any relevant dependency for a better accuracy. A novel solution called DRABAL that incorporates structure learning of a Bayesian Network as a step to model dependency between the HTS assays, is showed to achieve significant improvements over existing state-of-the-art approaches.

  20. Molecular analysis for diagnosis of Marfan syndrome and Marfan-associated disorders

    Institute of Scientific and Technical Information of China (English)

    GAO Ling-gen; YAO Xiu-ping; ZHANG Lin; HUI Ru-tai; ZHOU Xian-liang

    2011-01-01

    Marfan syndrome is a systemic disorder of connective tissue, caused by mutations in the FBN1, TGFBR1 or TGFBR2 genes. This syndrome is characterized by involvement of three major systems, skeletal, ocular, and cardiovascular. The continuing improvements in molecular biology and increasing availability of molecular diagnosis in clinical practice allow recognition of Marfan syndrome in patients with incomplete phenotypes. Additionally, molecular analyses could also be used for preimplantation genetic diagnosis. The identification of a mutation allows for early diagnosis, prognosis, genetic counseling, preventive management of carriers and reassurance for unaffected relatives. The importance of knowing in advance the location of the putative family mutation is highlighted by its straightforward application to prenatal and postnatal screening.

  1. [Neonatal screening of hemoglobinopathies and G6PD deficiency in Catalonia (Spain). Molecular study of sickle cell disease associated with alpha thalassemia and G6PD deficiency].

    Science.gov (United States)

    Mañú Pereira, María Del Mar; Cabot, Anna; Martínez González, Ana; Sitjà Navarro, Eulalia; Cararach, Vicent; Sabrià, Josep; Boixaderas, Jordi; Teixidor, Roser; Bosch, Albert; López Vílchez, M Angeles; Martín Ibáñez, Itziar; Carrión, Teresa; Plaja, Pere; Sánchez, Mario; Vives Corrons, José Luis

    2007-06-30

    The prevalence of hemoglobinopathies and glucose-6-phosphate dehidrogenase (G6PD) deficiency in the Catalan neonatal population is increasing due to immigration. Coinheritance of more than a single RBC genetic defect is becoming more frequent and diagnostic pitfalls are also increasing. We intended to demonstrate the need to perform an early diagnosis of sickle cell disease (SCD) by means of neonatal screening, to establish the prevalence of SCD associated with alpha thalassemia and G6PD deficiency and to identify genotypes associated with sickle cell disease and G6PD deficiency. 4,020 blood samples from newborns were screened. For the screening of hemoglobinopathies the high performance liquid chromatography method was used and for G6PD deficiency the fluorescent spot test was employed. We studied the association between betaS gene and alpha thalassaemia del-3.7 Kb. SCD and G6PD deficiency genotypes were established. Prevalence of SCD in population at risk was 1/475 newborns. Prevalence of G6PD deficiency in population at risk was 1/43, and in autochthonous population was 1/527 newborns. In all the cases, sickle hemoglobin was confirmed by ARMS (amplification refractory mutation system). Association between betaS gene and alpha thalassaemia del-3.7 Kb was found in 32.2% of the samples, and an association between betaS gene and G6PD deficiency was observed in 7% of the samples. This study confirms the high prevalence of SCD and G6PD deficiency in population at risk as well as their genetic and clinical heterogeneity. The study of genotype/phenotype relationships allows a better knowledge of molecular mechanism and is useful to establish suitable criteria of diagnosis.

  2. A fast, simple method for screening radiation susceptibility genes by RNA interference

    International Nuclear Information System (INIS)

    Tsuji, Atsushi B.; Sudo, Hitomi; Sugyo, Aya; Otsuki, Marika; Miyagishi, Makoto; Taira, Kazunari; Imai, Takashi; Harada, Yoshi-nobu

    2005-01-01

    Radiotherapy can cause unacceptable levels of damage to normal tissues in some cancer patients. To understand the molecular mechanisms underlying radiation-induced physiological responses, and to be able to predict the radiation susceptibility of normal tissues in individual patients, it is important to identify a comprehensive set of genes responsible for radiation susceptibility. We have developed a simple and rapid 96-well screening protocol using cell proliferation assays and RNA interference to identify genes associated with radiation susceptibility. We evaluated the performance of alamarBlue-, BrdU-, and sulforhodamine B-based cell proliferation assays using the 96-well format. Each proliferation assay detected the known radiation susceptibility gene, PRKDC. In a trial screen using 28 shRNA vectors, another known gene, CDKN1A, and one new radiation susceptibility gene, ATP5G3, were identified. Our results indicate that this method may be useful for large-scale screens designed to identify novel radiation susceptibility genes

  3. A cross docking pipeline for improving pose prediction and virtual screening performance

    Science.gov (United States)

    Kumar, Ashutosh; Zhang, Kam Y. J.

    2018-01-01

    Pose prediction and virtual screening performance of a molecular docking method depend on the choice of protein structures used for docking. Multiple structures for a target protein are often used to take into account the receptor flexibility and problems associated with a single receptor structure. However, the use of multiple receptor structures is computationally expensive when docking a large library of small molecules. Here, we propose a new cross-docking pipeline suitable to dock a large library of molecules while taking advantage of multiple target protein structures. Our method involves the selection of a suitable receptor for each ligand in a screening library utilizing ligand 3D shape similarity with crystallographic ligands. We have prospectively evaluated our method in D3R Grand Challenge 2 and demonstrated that our cross-docking pipeline can achieve similar or better performance than using either single or multiple-receptor structures. Moreover, our method displayed not only decent pose prediction performance but also better virtual screening performance over several other methods.

  4. Application of molecular imaging combined with genetic screening in diagnosing MELAS, diabetes and recurrent pancreatitis.

    Science.gov (United States)

    Zhiping, W; Quwen, L; Hai, Z; Jian, Z; Peiyi, G

    2016-01-01

    We report molecular imaging combined with gene diagnosis in a family with 7 members who carried an A3243G mutation in mitochondrial tRNA and p.Thr 137 Met in cationic trypsinogen (PRSS1) gene presented with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), diabetes, and recurrent pancreatitis. DNA sequencing was used to detect and validate mitochondrial DNA and PRSS1. We also verified that mitochondrial heterozygous mutations and c.410 C>T mutation causing p.Thr 137 Met could be detected in oral epithelial cells or in urine sediment cells. In addition, molecular imaging was carried out in the affected family members. In this pedigree, MELAS syndrome accompanied by pancreatitis was an important clinical feature, followed by diabetes. Heteroplasmy of the mtDNA A3243G and c.410 C>T mutation of PRSS1 was found in all tissue samples of these patients, but no mutations were found in 520 normal control and normal individuals of the family. However, based on molecular imaging observations, patients with relatively higher lactate/pyruvate levels had more typical and more severe symptoms, particularly those of pancreatic disease (diabetes or pancreatitis). MELAS syndrome may be associated with pancreatitis. For the diagnosis, it is more reasonable to perform molecular imaging combined with gene diagnosis.

  5. Coproscopy and molecular screening for detection of intestinal protozoa.

    Science.gov (United States)

    Abu-Madi, Marawan; Boughattas, Sonia; Behnke, Jerzy M; Sharma, Aarti; Ismail, Ahmed

    2017-09-06

    Intestinal parasitosis is one of several health concerns about immigrants who travel from endemic to non-endemic regions. Reliable rapid sensitive diagnostic tools, for use in non-endemic regions, are urgently required to enable frequent assessment of immigrant workers in jobs where risk of local transmission is a particular concern (e.g. food-handlers). We assessed the burden of intestinal protozoa in newly arrived immigrants and those applying for renewal of work permits in Qatar (n = 735), by both microscopic examination of stool samples and by Real Time PCR methodology. Prevalence was considerably higher using RT-PCR compared with coproscopy (Blastocystis hominis: 65.2 vs 7.6%; Giardia duodenalis: 14.3 vs 2.9%; Entamoeba histolytica: 1.6 vs 1.2%). Dientamoeba fragilis was sought only by RT-PCR (prevalence of 25.4%). Prevalence of G. duodenalis was significantly higher in male subjects, associated with blue collar workers and declined over time. Prevalence of B. hominis varied significantly with region of origin of subjects with highest values recorded among African immigrants. Prevalence of D. fragilis also varied with region of origin of subjects, and was lower in young female subjects and in renewal applicants compared with first-time applicants for work permits. We strongly recommend that, henceforth, intestinal protozoa should be screened by RT-PCR, with a particular focus on frequent assessment of immigrant food-handlers.

  6. Breast cancer screening

    Science.gov (United States)

    Mammogram - breast cancer screening; Breast exam - breast cancer screening; MRI - breast cancer screening ... is performed to screen women to detect early breast cancer when it is more likely to be cured. ...

  7. The use of molecular descriptors in the development of co-amorphous formulations

    DEFF Research Database (Denmark)

    Meng-Lund, Helena Marie Lindholm; Korgaard, Georgia Kasten; Jensen, Katrine Birgitte Tarp

    2018-01-01

    -amorphisation between amino acid and drug. The predictions are thought to be used in an early screening phase to identify potential drug-amino acid combinations for further studies. A large variety of molecular descriptors was calculated for six drugs (carvedilol, mebendazole, carbamazepine, furosemide, indomethacin...

  8. Molecular Diagnostics, Targeted Therapy, and the Indication for Allogeneic Stem Cell Transplantation in Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Anthony Oyekunle

    2011-01-01

    Full Text Available In recent years, the panel of known molecular mutations in acute lymphoblastic leukemia (ALL has been continuously increased. In Philadelphia-positive ALL, deletions of the IKZF1 gene were identified as prognostically adverse factors. These improved insights in the molecular background and the clinical heterogeneity of distinct cytogenetic subgroups may allow most differentiated therapeutic decisions, for example, with respect to the indication to allogeneic HSCT within genetically defined ALL subtypes. Quantitative real-time PCR allows highly sensitive monitoring of the minimal residual disease (MRD load, either based on reciprocal gene fusions or immune gene rearrangements. Molecular diagnostics provided the basis for targeted therapy concepts, for example, combining the tyrosine kinase inhibitor imatinib with chemotherapy in patients with Philadelphia-positive ALL. Screening for BCR-ABL1 mutations in Philadelphia-positive ALL allows to identify patients who may benefit from second-generation tyrosine kinase inhibitors or from novel compounds targeting the T315I mutation. Considering the central role of the molecular techniques for the management of patients with ALL, efforts should be made to facilitate and harmonize immunophenotyping, cytogenetics, and molecular mutation screening. Furthermore, the potential of high-throughput sequencing should be evaluated for diagnosis and follow-up of patients with B-lineage ALL.

  9. [When history meets molecular medicine: molecular history of human tuberculosis].

    Science.gov (United States)

    Ottini, Laura; Falchetti, Mario

    2010-01-01

    Tuberculosis represents one of the humankind's most socially devastating diseases. Despite a long history of medical research and the development of effective therapies, this disease remains a global health danger even in the 21st century. Tuberculosis may cause death but infected people with effective immunity may remain healthy for years, suggesting long-term host-pathogen co-existence. Because of its antiquity, a supposed association with human settlements and the tendency to leave typical lesions on skeletal and mummified remains, tuberculosis has been the object of intensive multidisciplinary studies, including paleo-pathological research. During the past 10 years molecular paleo-pathology developed as a new scientific discipline allowing the study of ancient pathogens by direct detection of their DNA. In this work, we reviewed evidences for tuberculosis in ancient human remains, current methods for identifying ancient mycobacterial DNA and explored current theories of Mycobacterium tuberculosis evolution and their implications in the global development of tuberculosis looking into the past and present at the same time.

  10. Dense breasts: a review of reporting legislation and available supplemental screening options.

    Science.gov (United States)

    Ho, Jessica M; Jafferjee, Nasima; Covarrubias, Gabriel M; Ghesani, Munir; Handler, Bradley

    2014-08-01

    The objectives of this article are to discuss the Mammography Quality Standards Act (MQSA) and what it means for patients, define breast density and explain how it is measured, review the new state-based legislation regarding the reporting of dense breast tissue directly to patients and the possibility of an adjunct screening examination, describe possible supplemental screening options and the advantages and disadvantages of each, and outline the current shortcomings and unanswered questions regarding new legislation. Breast density is now established as an independent risk factor for developing breast cancer irrespective of other known risk factors. Women with breast density in the upper quartile have an associated four to five times greater risk of developing breast cancer relative to women with breast density in the lower quartile. Many states have enacted or proposed legislation requiring mammographers to report to patients directly if they have dense breast tissue and recommend discussing the possibility of a supplemental screening examination with their physicians. However, there is currently no consensus as to whether a supplemental screening examination should be pursued or which modality to use. Possible supplemental screening modalities include ultrasound, MRI, digital breast tomosynthesis, and molecular breast imaging. The U.S. Food and Drug Administration recently approved an automated breast ultrasound system for screening whole-breast ultrasound in patients with dense breasts. However, many questions are still unanswered including the impact on morbidity and mortality, cost-effectiveness, and insurance coverage.

  11. RBC Antibody Screen

    Science.gov (United States)

    ... C Cystic Fibrosis (CF) Gene Mutations Testing Cytomegalovirus (CMV) Tests D-dimer Dengue Fever Testing Des-gamma- ... Index of Screening Recommendations Not Listed? Not Listed? Newborn Screening Screening Tests for Infants Screening Tests for ...

  12. Design strategies to minimize the radiative efficiency of global warming molecules

    Science.gov (United States)

    Bera, Partha P.; Francisco, Joseph S.; Lee, Timothy J.

    2010-01-01

    A strategy is devised to screen molecules based on their radiative efficiency. The methodology should be useful as one additional constraint when determining the best molecule to use for an industrial application. The strategy is based on the results of a recent study where we examined molecular properties of global warming molecules using ab initio electronic structure methods to determine which fundamental molecular properties are important in assessing the radiative efficiency of a molecule. Six classes of perfluorinated compounds are investigated. For similar numbers of fluorine atoms, their absorption of radiation in the IR window decreases according to perfluoroethers > perfluorothioethers ≈ sulfur/carbon compounds > perfluorocarbons > perfluoroolefins > carbon/nitrogen compounds. Perfluoroethers and hydrofluorethers are shown to possess a large absorption in the IR window due to (i) the C─O bonds are very polar, (ii) the C-O stretches fall within the IR window and have large IR intensity due to their polarity, and (iii) the IR intensity for C-F stretches in which the fluorine atom is bonded to the carbon that is bonded to the oxygen atom is enhanced due to a larger C─F bond polarity. Lengthening the carbon chain leads to a larger overall absorption in the IR window, though the IR intensity per bond is smaller. Finally, for a class of partially fluorinated compounds with a set number of electronegative atoms, the overall absorption in the IR window can vary significantly, as much as a factor of 2, depending on how the fluorine atoms are distributed within the molecule. PMID:20439762

  13. Molecular profiles to biology and pathways: a systems biology approach.

    Science.gov (United States)

    Van Laere, Steven; Dirix, Luc; Vermeulen, Peter

    2016-06-16

    Interpreting molecular profiles in a biological context requires specialized analysis strategies. Initially, lists of relevant genes were screened to identify enriched concepts associated with pathways or specific molecular processes. However, the shortcoming of interpreting gene lists by using predefined sets of genes has resulted in the development of novel methods that heavily rely on network-based concepts. These algorithms have the advantage that they allow a more holistic view of the signaling properties of the condition under study as well as that they are suitable for integrating different data types like gene expression, gene mutation, and even histological parameters.

  14. Molecular signatures of thyroid follicular neoplasia

    DEFF Research Database (Denmark)

    Borup, R.; Rossing, M.; Henao, Ricardo

    2010-01-01

    The molecular pathways leading to thyroid follicular neoplasia are incompletely understood, and the diagnosis of follicular tumors is a clinical challenge. To provide leads to the pathogenesis and diagnosis of the tumors, we examined the global transcriptome signatures of follicular thyroid...... a mechanism for cancer progression, which is why we exploited the results in order to generate a molecular classifier that could identify 95% of all carcinomas. Validation employing public domain and cross-platform data demonstrated that the signature was robust and could diagnose follicular nodules...... and robust genetic signature for the diagnosis of FA and FC. Endocrine-Related Cancer (2010) 17 691-708...

  15. Serological and molecular tools to diagnose visceral leishmaniasis: 2-years' experience of a single center in Northern Italy.

    Directory of Open Access Journals (Sweden)

    Stefania Varani

    Full Text Available The diagnosis of visceral leishmaniasis (VL remains challenging, due to the limited sensitivity of microscopy, the poor performance of serological methods in immunocompromised patients and the lack of standardization of molecular tests. The aim of this study was to implement a combined diagnostic workflow by integrating serological and molecular tests with standardized clinical criteria. Between July 2013 and June 2015, the proposed workflow was applied to specimens obtained from 94 in-patients with clinical suspicion of VL in the Emilia-Romagna region, Northern Italy. Serological tests and molecular techniques were employed. Twenty-one adult patients (22% had a confirmed diagnosis of VL by clinical criteria, serology and/or real-time polymerase chain reaction; 4 of these patients were HIV-positive. Molecular tests exhibited higher sensitivity than serological tests for the diagnosis of VL. In our experience, the rK39 immunochromatographic test was insufficiently sensitive for use as a screening test for the diagnosis of VL caused by L. infantum in Italy. However, as molecular tests are yet not standardized, further studies are required to identify an optimal screening test for Mediterranean VL.

  16. Serological and molecular tools to diagnose visceral leishmaniasis: 2-years’ experience of a single center in Northern Italy

    Science.gov (United States)

    Ortalli, Margherita; Attard, Luciano; Vanino, Elisa; Gaibani, Paolo; Vocale, Caterina; Rossini, Giada; Cagarelli, Roberto; Pierro, Anna; Billi, Patrizia; Mastroianni, Antonio; Di Cesare, Simona; Codeluppi, Mauro; Franceschini, Erica; Melchionda, Fraia; Gramiccia, Marina; Scalone, Aldo; Gentilomi, Giovanna A.; Landini, Maria P.

    2017-01-01

    The diagnosis of visceral leishmaniasis (VL) remains challenging, due to the limited sensitivity of microscopy, the poor performance of serological methods in immunocompromised patients and the lack of standardization of molecular tests. The aim of this study was to implement a combined diagnostic workflow by integrating serological and molecular tests with standardized clinical criteria. Between July 2013 and June 2015, the proposed workflow was applied to specimens obtained from 94 in-patients with clinical suspicion of VL in the Emilia-Romagna region, Northern Italy. Serological tests and molecular techniques were employed. Twenty-one adult patients (22%) had a confirmed diagnosis of VL by clinical criteria, serology and/or real-time polymerase chain reaction; 4 of these patients were HIV-positive. Molecular tests exhibited higher sensitivity than serological tests for the diagnosis of VL. In our experience, the rK39 immunochromatographic test was insufficiently sensitive for use as a screening test for the diagnosis of VL caused by L. infantum in Italy. However, as molecular tests are yet not standardized, further studies are required to identify an optimal screening test for Mediterranean VL. PMID:28832646

  17. Data from Tiered High-Throughput Screening Approach to Identify Thyroperoxidase Inhibitors within the ToxCast Phase I and II Chemical Libraries

    Data.gov (United States)

    U.S. Environmental Protection Agency — High-throughput screening for potential thyroid-disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge...

  18. Towards Global QSAR Model Building for Acute Toxicity: Munro Database Case Study

    Directory of Open Access Journals (Sweden)

    Swapnil Chavan

    2014-10-01

    Full Text Available A series of 436 Munro database chemicals were studied with respect to their corresponding experimental LD50 values to investigate the possibility of establishing a global QSAR model for acute toxicity. Dragon molecular descriptors were used for the QSAR model development and genetic algorithms were used to select descriptors better correlated with toxicity data. Toxic values were discretized in a qualitative class on the basis of the Globally Harmonized Scheme: the 436 chemicals were divided into 3 classes based on their experimental LD50 values: highly toxic, intermediate toxic and low to non-toxic. The k-nearest neighbor (k-NN classification method was calibrated on 25 molecular descriptors and gave a non-error rate (NER equal to 0.66 and 0.57 for internal and external prediction sets, respectively. Even if the classification performances are not optimal, the subsequent analysis of the selected descriptors and their relationship with toxicity levels constitute a step towards the development of a global QSAR model for acute toxicity.

  19. Docking-based Screening of Ficus religiosa Phytochemicals as Inhibitors of Human Histamine H2 Receptor.

    Science.gov (United States)

    Chaudhary, Amit; Yadav, Birendra Singh; Singh, Swati; Maurya, Pramod Kumar; Mishra, Alok; Srivastva, Shweta; Varadwaj, Pritish Kumar; Singh, Nand Kumar; Mani, Ashutosh

    2017-10-01

    Ficus religiosa L. is generally known as Peepal and belongs to family Moraceae . The tree is a source of many compounds having high medicinal value. In gastrointestinal tract, histamine H2 receptors have key role in histamine-stimulated gastric acid secretion. Their over stimulation causes its excessive production which is responsible for gastric ulcer. This study aims to screen the range of phytochemicals present in F. religiosa for binding with human histamine H2 and identify therapeutics for a gastric ulcer from the plant. In this work, a 3D-structure of human histamine H2 receptor was modeled by using homology modeling and the predicted model was validated using PROCHECK. Docking studies were also performed to assess binding affinities between modeled receptor and 34 compounds. Molecular dynamics simulations were done to identify most stable receptor-ligand complexes. Absorption, distribution, metabolism, excretion, and screening was done to evaluate pharmacokinetic properties of compounds. The results suggest that seven ligands, namely, germacrene, bergaptol, lanosterol, Ergost-5-en-3beta-ol, α-amyrin acetate, bergapten, and γ-cadinene showed better binding affinities. Among seven phytochemicals, lanosterol and α-amyrin acetate were found to have greater stability during simulation studies. These two compounds may be a suitable therapeutic agent against histamine H2 receptor. This study was performed to screen antiulcer compounds from F. religiosa . Molecular modeling, molecular docking and MD simulation studies were performed with selected phytochemicals from F. religiosa . The analysis suggests that Lanosterol and α-amyrin may be a suitable therapeutic agent against histamine H2 receptor. This study facilitates initiation of the herbal drug discovery process for the antiulcer activity. Abbreviations used: ADMET: Absorption, distribution, metabolism, excretion and toxicity, DOPE: Discrete Optimized Potential Energy, OPLS: Optimized potential for liquid

  20. Targeting acetylcholinesterase: identification of chemical leads by high throughput screening, structure determination and molecular modeling.

    Directory of Open Access Journals (Sweden)

    Lotta Berg

    Full Text Available Acetylcholinesterase (AChE is an essential enzyme that terminates cholinergic transmission by rapid hydrolysis of the neurotransmitter acetylcholine. Compounds inhibiting this enzyme can be used (inter alia to treat cholinergic deficiencies (e.g. in Alzheimer's disease, but may also act as dangerous toxins (e.g. nerve agents such as sarin. Treatment of nerve agent poisoning involves use of antidotes, small molecules capable of reactivating AChE. We have screened a collection of organic molecules to assess their ability to inhibit the enzymatic activity of AChE, aiming to find lead compounds for further optimization leading to drugs with increased efficacy and/or decreased side effects. 124 inhibitors were discovered, with considerable chemical diversity regarding size, polarity, flexibility and charge distribution. An extensive structure determination campaign resulted in a set of crystal structures of protein-ligand complexes. Overall, the ligands have substantial interactions with the peripheral anionic site of AChE, and the majority form additional interactions with the catalytic site (CAS. Reproduction of the bioactive conformation of six of the ligands using molecular docking simulations required modification of the default parameter settings of the docking software. The results show that docking-assisted structure-based design of AChE inhibitors is challenging and requires crystallographic support to obtain reliable results, at least with currently available software. The complex formed between C5685 and Mus musculus AChE (C5685•mAChE is a representative structure for the general binding mode of the determined structures. The CAS binding part of C5685 could not be structurally determined due to a disordered electron density map and the developed docking protocol was used to predict the binding modes of this part of the molecule. We believe that chemical modifications of our discovered inhibitors, biochemical and biophysical

  1. Soil fungal community responses to global changes

    DEFF Research Database (Denmark)

    Haugwitz, Merian Skouw

    Global change will affect the functioning and structure of terrestrial ecosystems and since soil fungi are key players in organic matter decomposition and nutrient turnover, shifts in fungal community composition might have a strong impact on soil functioning. The main focus of this thesis...... was therefore to investigate the impact of global environmental changes on soil fungal communities in a temperate and subartic heath ecosystem. The objective was further to determine global change effects on major functional groups of fungi and analyze the influence of fungal community changes on soil carbon...... and nutrient availability and storage. By combining molecular methods such as 454 pyrosequencing and quantitative PCR of fungal ITS amplicons with analyses of soil enzymes, nutrient pools of carbon, nitrogen and phosphorus we were able to characterize soil fungal communities as well as their impact on nutrient...

  2. A molecular survey of acute febrile illnesses reveals Plasmodium vivax infections in Kedougou, southeastern Senegal.

    Science.gov (United States)

    Niang, Makhtar; Thiam, Laty Gaye; Sow, Abdourahmane; Loucoubar, Cheikh; Bob, Ndeye Sakha; Diop, Fode; Diouf, Babacar; Niass, Oumy; Mansourou, Annick; Varela, Marie Louise; Perraut, Ronald; Sall, Amadou A; Toure-Balde, Aissatou

    2015-07-19

    Control efforts towards malaria due to Plasmodium falciparum significantly decreased the incidence of the disease in many endemic countries including Senegal. Surprisingly, in Kedougou (southeastern Senegal) P. falciparum malaria remains highly prevalent and the relative contribution of other Plasmodium species to the global malaria burden is very poorly documented, partly due to the low sensitivity of routine diagnostic tools. Molecular methods offer better estimate of circulating Plasmodium species in a given area. A molecular survey was carried out to document circulating malaria parasites in Kedougou region. A total of 263 long-term stored sera obtained from patients presenting with acute febrile illness in Kedougou between July 2009 and July 2013 were used for malaria parasite determination. Sera were withdrawn from a collection established as part of a surveillance programme of arboviruses infections in the region. Plasmodium species were characterized by a nested PCR-based approach targeting the 18S small sub-unit ribosomal RNA genes of Plasmodium spp. Of the 263 sera screened in this study, Plasmodium genomic DNA was amplifiable by nested PCR from 62.35% (164/263) of samples. P. falciparum accounted for the majority of infections either as single in 85.97% (141/164) of Plasmodium-positive samples or mixed with Plasmodium ovale (11.58%, 19/164) or Plasmodium vivax (1.21%, 2/164). All 19 (11.58%) P. ovale-infected patients were mixed with P. falciparum, while no Plasmodium malariae was detected in this survey. Four patients (2.43%) were found to be infected by P. vivax, two of whom were mixed with P. falciparum. P. vivax infections originated from Bandafassi and Ninefesha villages and concerned patients aged 4, 9, 10, and 15 years old, respectively. DNA sequences alignment and phylogenetic analysis demonstrated that sequences from Kedougou corresponded to P. vivax, therefore confirming the presence of P. vivax infections in Senegal. The results confirm the

  3. Fletcher-Reeves based Particle Swarm Optimization for prediction of molecular structure.

    Science.gov (United States)

    Agrawal, Shikha; Silakari, Sanjay

    2014-04-01

    The determination of the most stable conformers of a molecule can be formulated as a global optimization problem. Knowing the stable conformers of a molecule is important because it allows us to understand its properties and behavior based on its structure. The most stable conformation is that involving the global minimum of potential energy. The problem of finding this global minimum is highly complex, and is computationally difficult because of the number of local minima, which grows exponentially with molecular size. In this paper, we propose a hybrid approach combining Particle Swarm Optimization (PSO) and the Fletcher-Reeves algorithm to minimize the potential energy function. The proposed hybrid algorithm is applied to a simplified molecular potential energy function in problems with up to 100 degrees of freedom and also to a realistic potential energy function modeling a pseudoethane molecule. The computational results for both the cases show that the proposed method performs significantly better than the other algorithms. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. The frequency of Tay-Sachs disease causing mutations in the Brazilian Jewish population justifies a carrier screening program.

    Science.gov (United States)

    Rozenberg, R; Pereira, L da V

    2001-07-05

    Tay-Sachs disease is an autosomal recessive disease characterized by progressive neurologic degeneration, fatal in early childhood. In the Ashkenazi Jewish population the disease incidence is about 1 in every 3,500 newborns and the carrier frequency is 1 in every 29 individuals. Carrier screening programs for Tay-Sachs disease have reduced disease incidence by 90% in high-risk populations in several countries. The Brazilian Jewish population is estimated at 90,000 individuals. Currently, there is no screening program for Tay-Sachs disease in this population. To evaluate the importance of a Tay-Sachs disease carrier screening program in the Brazilian Jewish population by determining the frequency of heterozygotes and the acceptance of the program by the community. Laboratory of Molecular Genetics--Institute of Biosciences--Universidade de São Paulo. 581 senior students from selected Jewish high schools. Molecular analysis of Tay-Sachs disease causing mutations by PCR amplification of genomic DNA, followed by restriction enzyme digestion. Among 581 students that attended educational classes, 404 (70%) elected to be tested for Tay-Sachs disease mutations. Of these, approximately 65% were of Ashkenazi Jewish origin. Eight carriers were detected corresponding to a carrier frequency of 1 in every 33 individuals in the Ashkenazi Jewish fraction of the sample. The frequency of Tay-Sachs disease carriers among the Ashkenazi Jewish population of Brazil is similar to that of other countries where carrier screening programs have led to a significant decrease in disease incidence. Therefore, it is justifiable to implement a Tay-Sachs disease carrier screening program for the Brazilian Jewish population.

  5. Biophysical Screening of a Focused Library for the Discovery of CYP121 Inhibitors as Novel Antimycobacterials.

    Science.gov (United States)

    Brengel, Christian; Thomann, Andreas; Schifrin, Alexander; Allegretta, Giuseppe; Kamal, Ahmed A M; Haupenthal, Jörg; Schnorr, Isabell; Cho, Sang Hyun; Franzblau, Scott G; Empting, Martin; Eberhard, Jens; Hartmann, Rolf W

    2017-10-09

    The development of novel antimycobacterial agents against Mycobacterium tuberculosis (Mtb) is urgently required due to the appearance of multidrug resistance (MDR) combined with complicated long-term treatment. CYP121 was shown to be a promising novel target for inhibition of mycobacterial growth. In this study, we describe the rational discovery of new CYP121 inhibitors by a systematic screening based on biophysical and microbiological methods. The best hits originating from only one structural class gave initial information about molecular motifs required for binding and activity. The initial screening procedure was followed by mode-of-action studies and further biological characterizations. The results demonstrate superior antimycobacterial efficacy and a decreased toxicity profile of our frontrunner compound relative to the reference compound econazole. Due to its low molecular weight, promising biological profile, and physicochemical properties, this compound is an excellent starting point for further rational optimization. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Degrees of Doubt: Legitimate, Real and Fake Qualifications in a Global Market

    Science.gov (United States)

    Brown, George M.

    2006-01-01

    This paper provides an analysis into the global phenomenon known as credential/qualification fraud, a $US 1 billion dollar "cottage" industry which has tainted higher education in Australia, and does not appear to be abating. The study is developed through a conceptual framework of credentialism, degree creep and screening theory, which…

  7. What is Molecular is not invisible to the eyes

    Directory of Open Access Journals (Sweden)

    Frank Lizaraso Caparó

    2017-01-01

    Full Text Available A molecular failure (in principle invisible will determine symptoms, diseases and conditions of Health pretty visible. Molecular studies have been developed mostly in populations in Europe, USA (Descendants of Europeans and African Americans Africa and Asia. The Peruvians are represented in the Latin / Hispanic who is genetically too heterogeneous (eg, Mexican Latino is different from Argentinian or Puerto Rican (11. Peru globally has about 70% of South American native ancestors, which has been scarcely represented In molecular studies there is a pending task to characterize its population, as well as being Watchers of our endemic pathogens and those adapted to our territory.

  8. Lead Screening for HIV-1 Integrase (IN Inhibited by Traditional Chinese Medicine

    Directory of Open Access Journals (Sweden)

    Tzu-Chieh Hung

    2014-01-01

    Full Text Available Human immunodeficiency virus causes the acquired immunodeficiency syndrome (AIDS and becomes a serious world-wide problem because of this disease's rapid propagation and incurability. Integrase strand transfer inhibitors (INSTIs supports HIV have rapid drug resistance for antitreatment. Screening the traditional Chinese medicine (TCM database by simulating molecular docking and molecular dynamics may select molecular compounds to inhibit INSTIs against HIV drug resistance. (S-cathinone and (1S,2S-norpseudoephedrine are selected based on structure and ligand-based drugs are designed and then get higher bioactivity predicted score from SVM than Raltegravir and other TCM compounds. The molecular dynamics are helpful in the analysis and detection of protein-ligand interactions. According to the docking poses, hydrophobic interactions and hydrogen bond variations define the main regions of important amino acids in integrase. In addition to the detection of TCM compound efficacy, we suggest (1S,2S-norpseudoephedrine is better than the others based on the analysis of interaction and the effect on the structural variation.

  9. Mini-review: Molecular mechanisms of antifouling compounds

    KAUST Repository

    Qian, Pei-Yuan

    2013-04-01

    Various antifouling (AF) coatings have been developed to protect submerged surfaces by deterring the settlement of the colonizing stages of fouling organisms. A review of the literature shows that effective AF compounds with specific targets are ones often considered non-toxic. Such compounds act variously on ion channels, quorum sensing systems, neurotransmitters, production/release of adhesive, and specific enzymes that regulate energy production or primary metabolism. In contrast, AF compounds with general targets may or may not act through toxic mechanisms. These compounds affect a variety of biological activities including algal photosynthesis, energy production, stress responses, genotoxic damage, immunosuppressed protein expression, oxidation, neurotransmission, surface chemistry, the formation of biofilms, and adhesive production/release. Among all the targets, adhesive production/release is the most common, possibly due to a more extensive research effort in this area. Overall, the specific molecular targets and the molecular mechanisms of most AF compounds have not been identified. Thus, the information available is insufficient to draw firm conclusions about the types of molecular targets to be used as sensitive biomarkers for future design and screening of compounds with AF potential. In this review, the relevant advantages and disadvantages of the molecular tools available for studying the molecular targets of AF compounds are highlighted briefly and the molecular mechanisms of the AF compounds, which are largely a source of speculation in the literature, are discussed. © 2013 Copyright Taylor and Francis Group, LLC.

  10. Urinary tract infection as a preventable cause of pregnancy complications: opportunities, challenges, and a global call to action.

    Science.gov (United States)

    Gilbert, Nicole M; O'Brien, Valerie P; Hultgren, Scott; Macones, George; Lewis, Warren G; Lewis, Amanda L

    2013-09-01

    The urinary tract is a common site of infection in humans. During pregnancy, urinary tract infection (UTI) is associated with increased risks of maternal and neonatal morbidity and mortality, even when the infection is asymptomatic. By mapping available rates of UTI in pregnancy across different populations, we emphasize this as a problem of global significance. Many countries with high rates of preterm birth and neonatal mortality also have rates of UTI in pregnancy that exceed rates seen in more developed countries. A global analysis of the etiologies of UTI revealed familiar culprits as well as emerging threats. Screening and treatment of UTI have improved birth outcomes in several more developed countries and would likely improve maternal and neonatal health worldwide. However, challenges of implementation in resource-poor settings must be overcome. We review the nature of the barriers occurring at each step of the screening and treatment pipeline and highlight steps necessary to overcome these obstacles. It is our hope that the information compiled here will increase awareness of the global significance of UTI in maternal and neonatal health and embolden governments, nongovernmental organizations, and researchers to do their part to make urine screening and UTI treatment a reality for all pregnant women.

  11. Prenatal screening and genetics

    DEFF Research Database (Denmark)

    Alderson, P; Aro, A R; Dragonas, T

    2001-01-01

    Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we...... examine definitions of the relevant concepts in order to illustrate this point. The concepts are i) prenatal, ii) genetic screening, iii) screening, scanning and testing, iv) maternal and foetal tests, v) test techniques and vi) genetic conditions. So far, prenatal screening has little connection...... with precisely defined genetics. There are benefits but also disadvantages in overstating current links between them in the term genetic screening. Policy making and professional and public understandings about screening could be clarified if the distinct meanings of prenatal screening and genetic screening were...

  12. Multi-level molecular modelling for plasma medicine

    International Nuclear Information System (INIS)

    Bogaerts, Annemie; Khosravian, Narjes; Van der Paal, Jonas; Verlackt, Christof C W; Yusupov, Maksudbek; Kamaraj, Balu; Neyts, Erik C

    2016-01-01

    Modelling at the molecular or atomic scale can be very useful for obtaining a better insight in plasma medicine. This paper gives an overview of different atomic/molecular scale modelling approaches that can be used to study the direct interaction of plasma species with biomolecules or the consequences of these interactions for the biomolecules on a somewhat longer time-scale. These approaches include density functional theory (DFT), density functional based tight binding (DFTB), classical reactive and non-reactive molecular dynamics (MD) and united-atom or coarse-grained MD, as well as hybrid quantum mechanics/molecular mechanics (QM/MM) methods. Specific examples will be given for three important types of biomolecules, present in human cells, i.e. proteins, DNA and phospholipids found in the cell membrane. The results show that each of these modelling approaches has its specific strengths and limitations, and is particularly useful for certain applications. A multi-level approach is therefore most suitable for obtaining a global picture of the plasma–biomolecule interactions. (paper)

  13. Genomic epidemiology of global VIM-producing Enterobacteriaceae.

    Science.gov (United States)

    Matsumura, Yasufumi; Peirano, Gisele; Devinney, Rebekah; Bradford, Patricia A; Motyl, Mary R; Adams, Mark D; Chen, Liang; Kreiswirth, Barry; Pitout, Johann D D

    2017-08-01

    International data on the molecular epidemiology of Enterobacteriaceae with VIM carbapenemases are limited. We performed short read (Illumina) WGS on a global collection of 89 VIM-producing clinical Enterobacteriaceae (2008-14). VIM-producing (11 varieties within 21 different integrons) isolates were mostly obtained from Europe. Certain integrons with bla VIM were specific to a country in different species and clonal complexes (CCs) (In 87 , In 624 , In 916 and In 1323 ), while others had spread globally among various Enterobacteriaceae species (In 110 and In 1209 ). Klebsiella pneumoniae was the most common species ( n  = 45); CC147 from Greece was the most prevalent clone and contained In 590 -like integrons with four different bla VIM s. Enterobacter cloacae complex was the second most common species and mainly consisted of Enterobacter hormaechei ( Enterobacter xiangfangensis , subsp. steigerwaltii and Hoffmann cluster III). CC200 (from Croatia and Turkey), CC114 (Croatia, Greece, Italy and the USA) and CC78 (from Greece, Italy and Spain) containing bla VIM-1 were the most common clones among the E. cloacae complex. This study highlights the importance of surveillance programmes using the latest molecular techniques in providing insight into the characteristics and global distribution of Enterobacteriaceae with bla VIM s. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Drug and bioactive molecule screening based on a bioelectrical impedance cell culture platform

    Directory of Open Access Journals (Sweden)

    Ramasamy S

    2014-12-01

    Full Text Available Sakthivel Ramasamy,1 Devasier Bennet,1 Sanghyo Kim1,2 1Department of Bionanotechnology, Gachon University, Gyeonggi-Do, Republic of Korea; 2Graduate Gachon Medical Research Institute, Gil Medical Center, Incheon, Republic of Korea Abstract: This review will present a brief discussion on the recent advancements of bioelectrical impedance cell-based biosensors, especially the electric cell-substrate impedance sensing (ECIS system for screening of various bioactive molecules. The different technical integrations of various chip types, working principles, measurement systems, and applications for drug targeting of molecules in cells are highlighted in this paper. Screening of bioactive molecules based on electric cell-substrate impedance sensing is a trial-and-error process toward the development of therapeutically active agents for drug discovery and therapeutics. In general, bioactive molecule screening can be used to identify active molecular targets for various diseases and toxicity at the cellular level with nanoscale resolution. In the innovation and screening of new drugs or bioactive molecules, the activeness, the efficacy of the compound, and safety in biological systems are the main concerns on which determination of drug candidates is based. Further, drug discovery and screening of compounds are often performed in cell-based test systems in order to reduce costs and save time. Moreover, this system can provide more relevant results in in vivo studies, as well as high-throughput drug screening for various diseases during the early stages of drug discovery. Recently, MEMS technologies and integration with image detection techniques have been employed successfully. These new technologies and their possible ongoing transformations are addressed. Select reports are outlined, and not all the work that has been performed in the field of drug screening and development is covered. Keywords: screening of bioactive agents, impedance-based cell

  15. Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives

    Directory of Open Access Journals (Sweden)

    Yoon Young Choi

    2016-01-01

    Full Text Available Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus–positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.

  16. Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives.

    Science.gov (United States)

    Choi, Yoon Young; Noh, Sung Hoon; Cheong, Jae-Ho

    2016-01-01

    Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA) project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus-positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.

  17. The University of New Mexico Center for Molecular Discovery

    Science.gov (United States)

    Edwards, Bruce S.; Gouveia, Kristine; Oprea, Tudor I.; Sklar, Larry A.

    2015-01-01

    The University of New Mexico Center for Molecular Discovery (UNMCMD) is an academic research center that specializes in discovery using high throughput flow cytometry (HTFC) integrated with virtual screening, as well as knowledge mining and drug informatics. With a primary focus on identifying small molecules that can be used as chemical probes and as leads for drug discovery, it is a central core resource for research and translational activities at UNM that supports implementation and management of funded screening projects as well as “up-front” services such as consulting for project design and implementation, assistance in assay development and generation of preliminary data for pilot projects in support of competitive grant applications. The HTFC platform in current use represents advanced, proprietary technology developed at UNM that is now routinely capable of processing bioassays arrayed in 96-, 384- and 1536-well formats at throughputs of 60,000 or more wells per day. Key programs at UNMCMD include screening of research targets submitted by the international community through NIH’s Molecular Libraries Program; a multi-year effort involving translational partnerships at UNM directed towards drug repurposing - identifying new uses for clinically approved drugs; and a recently established personalized medicine initiative for advancing cancer therapy by the application of “smart” oncology drugs in selected patients based on response patterns of their cancer cells in vitro. UNMCMD discoveries, innovation, and translation have contributed to a wealth of inventions, patents, licenses and publications, as well as startup companies, clinical trials and a multiplicity of domestic and international collaborative partnerships to further the research enterprise. PMID:24409953

  18. 3D mosquito screens to create window double screen traps for mosquito control.

    Science.gov (United States)

    Khattab, Ayman; Jylhä, Kaisa; Hakala, Tomi; Aalto, Mikko; Malima, Robert; Kisinza, William; Honkala, Markku; Nousiainen, Pertti; Meri, Seppo

    2017-08-29

    Mosquitoes are vectors for many diseases such as malaria. Insecticide-treated bed nets and indoor residual spraying of insecticides are the principal malaria vector control tools used to prevent malaria in the tropics. Other interventions aim at reducing man-vector contact. For example, house screening provides additive or synergistic effects to other implemented measures. We used commercial screen materials made of polyester, polyethylene or polypropylene to design novel mosquito screens that provide remarkable additional benefits to those commonly used in house screening. The novel design is based on a double screen setup made of a screen with 3D geometric structures parallel to a commercial mosquito screen creating a trap between the two screens. Owing to the design of the 3D screen, mosquitoes can penetrate the 3D screen from one side but cannot return through the other side, making it a unidirectional mosquito screen. Therefore, the mosquitoes are trapped inside the double screen system. The permissiveness of both sides of the 3D screens for mosquitoes to pass through was tested in a wind tunnel using the insectary strain of Anopheles stephensi. Among twenty-five tested 3D screen designs, three designs from the cone, prism, or cylinder design groups were the most efficient in acting as unidirectional mosquito screens. The three cone-, prism-, and cylinder-based screens allowed, on average, 92, 75 and 64% of Anopheles stephensi mosquitoes released into the wind tunnel to penetrate the permissive side and 0, 0 and 6% of mosquitoes to escape through the non-permissive side, respectively. A cone-based 3D screen fulfilled the study objective. It allowed capturing 92% of mosquitoes within the double screen setup inside the wind tunnel and blocked 100% from escaping. Thus, the cone-based screen effectively acted as a unidirectional mosquito screen. This 3D screen-based trap design could therefore be used in house screening as a means of avoiding infective bites and

  19. [Utilization of self-sampling kits for HPV testing in cervical cancer screening - pilot study].

    Science.gov (United States)

    Ondryášová, H; Koudeláková, V; Drábek, J; Vaněk, P; Slavkovský, R; Hajdúch, M

    2015-12-01

    To get initial experience with alternative sampling (self-sampling) for HPV testing as the means of cervical cancer screening program. Original work. Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc. Based on expression of interest, 215 self-sampling kits were posted to women. Evalyn(®) Brush Vaginal swabs obtained by self-sampling were analyzed for the presence of HPV infection by Cobas 4800 HPV (Roche) followed by genotyping using PapilloCheck(®) HPV-Screening (Greiner Bio-One). Sixty women randomly chosen from our sample were sent a questionnaire focused on their experience with self-sampling. One hundred seventy-four of 215 (81%) distributed self-sampling devices have been delivered to analysis. All cervicovaginal swabs were sampled correctly and it was possible to analyze them by Cobas 4800 HPV test. Similarly, 98% (171/174) samples were analyzable by PapilloCheck(®) HPV-Screening.One hundred twenty-five (72%) of 174 tested samples were HPV negative. Low risk HPV infection was detected only in 7 samples (4%), and high risk HPV (hrHPV) infection was present in 42 samples (24%). The most frequently detected hrHPV genotypes were HPV16 (11/42; 26%) and HPV53 (6/42; 14%). HrHPV co-infection was detected in 10 cases, in 5 of them lrHPV infection was find also.Of the 60 questionnaires, 48 (80%) were returned. From this group, 47 (98%) women rated their experience with self-sampling device as good to excellent. User manual of self-sampling device was considered good to excellent by all women (100%). All women also rated the convenience of self-sampling device using as good to excellent. As expected, most of the women (n = 42 [88%]) preferred self-sampling to physician sampling. Cervicovaginal self-sampling leads to valid results of HPV screening using two molecular genetics methods and was accepted by Czech women very well. The self-sampling as an opportunity to participate in cervical cancer

  20. Variations in screening outcome among pairs of screening radiologists at non-blinded double reading of screening mammograms: a population-based study

    NARCIS (Netherlands)

    Klompenhouwer, E. G.; Duijm, L. E. M.; Voogd, A. C.; den Heeten, G. J.; Nederend, J.; Jansen, F. H.; Broeders, M. J. M.

    2014-01-01

    Substantial inter-observer variability in screening mammography interpretation has been reported at single reading. However, screening results of pairs of screening radiologists have not yet been published. We determined variations in screening performances among pairs of screening radiologists at

  1. Incentives in Diabetic Eye Assessment by Screening (IDEAS): study protocol of a three-arm randomized controlled trial using financial incentives to increase screening uptake in London.

    Science.gov (United States)

    Judah, Gaby; Vlaev, Ivo; Gunn, Laura; King, Dominic; King, Derek; Valabhji, Jonathan; Darzi, Ara; Bicknell, Colin

    2016-03-18

    Diabetes is an increasing public health problem in the UK and globally. Diabetic retinopathy is a microvascular complication of diabetes, and is one of the leading causes of blindness in the UK working age population. The diabetic eye screening programme in England aims to invite all people with diabetes aged 12 or over for retinal photography to screen for the presence of diabetic retinopathy. However, attendance rates are only 81 %, leaving many people at risk of preventable sight loss. This is a three arm randomized controlled trial to investigate the impact of different types of financial incentives (based on principles from behavioral economics) on increasing attendance at diabetic eye screening appointments in London. Eligible participants will be aged 16 or over, and are those who have been invited to screening appointments annually, but who have not attended, or telephoned to rearrange an appointment, within the last 24 months. Eligible participants will be randomized to one of three conditions: 1. Control condition (usual invitation letter) 2. Fixed incentive condition (usual invitation letter, including a voucher for £10 if they attend their appointment) 3. Probabilistic incentive condition (invitation letter, including a voucher for a 1 in 100 chance of winning £1000 if they attend their appointment). Participants will be sent invitation letters, and the primary outcome will be whether or not they attend their appointment. One thousand participants will be included in total, randomized with a ratio of 1.4:1:1. In order to test whether the incentive scheme has a differential impact on patients from different demographic or socio-economic groups, information will be recorded on age, gender, distance from screening center, socio-economic status and length of time since they were last screened. A cost-effectiveness analysis will also be performed. This study will be the first trial of financial incentives for improving uptake of diabetic eye screening. If

  2. Evaluation of globally available precipitation data products as input for water balance models

    Science.gov (United States)

    Lebrenz, H.; Bárdossy, A.

    2009-04-01

    Subject of this study is the evaluation of globally available precipitation data products, which are intended to be used as input variables for water balance models in ungauged basins. The selected data sources are a) the Global Precipitation Climatology Centre (GPCC), b) the Global Precipitation Climatology Project (GPCP) and c) the Climate Research Unit (CRU), resulting into twelve globally available data products. The data products imply different data bases, different derivation routines and varying resolutions in time and space. For validation purposes, the ground data from South Africa were screened on homogeneity and consistency by various tests and an outlier detection using multi-linear regression was performed. External Drift Kriging was subsequently applied on the ground data and the resulting precipitation arrays were compared to the different products with respect to quantity and variance.

  3. Conformation guides molecular efficacy in docking screens of activated β-2 adrenergic G protein coupled receptor.

    Science.gov (United States)

    Weiss, Dahlia R; Ahn, SeungKirl; Sassano, Maria F; Kleist, Andrew; Zhu, Xiao; Strachan, Ryan; Roth, Bryan L; Lefkowitz, Robert J; Shoichet, Brian K

    2013-05-17

    A prospective, large library virtual screen against an activated β2-adrenergic receptor (β2AR) structure returned potent agonists to the exclusion of inverse-agonists, providing the first complement to the previous virtual screening campaigns against inverse-agonist-bound G protein coupled receptor (GPCR) structures, which predicted only inverse-agonists. In addition, two hits recapitulated the signaling profile of the co-crystal ligand with respect to the G protein and arrestin mediated signaling. This functional fidelity has important implications in drug design, as the ability to predict ligands with predefined signaling properties is highly desirable. However, the agonist-bound state provides an uncertain template for modeling the activated conformation of other GPCRs, as a dopamine D2 receptor (DRD2) activated model templated on the activated β2AR structure returned few hits of only marginal potency.

  4. Development of gel-filter method for high enrichment of low-molecular weight proteins from serum.

    Directory of Open Access Journals (Sweden)

    Lingsheng Chen

    Full Text Available The human serum proteome has been extensively screened for biomarkers. However, the large dynamic range of protein concentrations in serum and the presence of highly abundant and large molecular weight proteins, make identification and detection changes in the amount of low-molecular weight proteins (LMW, molecular weight ≤ 30kDa difficult. Here, we developed a gel-filter method including four layers of different concentration of tricine SDS-PAGE-based gels to block high-molecular weight proteins and enrich LMW proteins. By utilizing this method, we identified 1,576 proteins (n = 2 from 10 μL serum. Among them, 559 (n = 2 proteins belonged to LMW proteins. Furthermore, this gel-filter method could identify 67.4% and 39.8% more LMW proteins than that in representative methods of glycine SDS-PAGE and optimized-DS, respectively. By utilizing SILAC-AQUA approach with labeled recombinant protein as internal standard, the recovery rate for GST spiked in serum during the treatment of gel-filter, optimized-DS, and ProteoMiner was 33.1 ± 0.01%, 18.7 ± 0.01% and 9.6 ± 0.03%, respectively. These results demonstrate that the gel-filter method offers a rapid, highly reproducible and efficient approach for screening biomarkers from serum through proteomic analyses.

  5. Effect of cervical cancer education and provider recommendation for screening on screening rates: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jonah Musa

    Full Text Available Although cervical cancer is largely preventable through screening, detection and treatment of precancerous abnormalities, it remains one of the top causes of cancer-related morbidity and mortality globally.The objective of this systematic review is to understand the evidence of the effect of cervical cancer education compared to control conditions on cervical cancer screening rates in eligible women population at risk of cervical cancer. We also sought to understand the effect of provider recommendations for screening to eligible women on cervical cancer screening (CCS rates compared to control conditions in eligible women population at risk of cervical cancer.We used the PICO (Problem or Population, Interventions, Comparison and Outcome framework as described in the Cochrane Collaboration Handbook to develop our search strategy. The details of our search strategy has been described in our systematic review protocol published in the International Prospective Register of systematic reviews (PROSPERO. The protocol registration number is CRD42016045605 available at: http://www.crd.york.ac.uk/prospero/display_record.asp?src=trip&ID=CRD42016045605. The search string was used in Pubmed, Embase, Cochrane Systematic Reviews and Cochrane CENTRAL register of controlled trials to retrieve study reports that were screened for inclusion in this review. Our data synthesis and reporting was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA. We did a qualitative synthesis of evidence and, where appropriate, individual study effects were pooled in meta-analyses using RevMan 5.3 Review Manager. The Higgins I2 was used to assess for heterogeneity in studies pooled together for overall summary effects. We did assessment of risk of bias of individual studies included and assessed risk of publication bias across studies pooled together in meta-analysis by Funnel plot.Out of 3072 study reports screened, 28 articles were found to

  6. Prostate cancer - epidemiology, etiology, diagnostics, clinical symptoms, screening

    International Nuclear Information System (INIS)

    Ondrus, D.

    2006-01-01

    Prostate cancer presents a real important medical and social problem at present. It is one of the most common malignancy in males. In global point of view it means permanent incidence increase of this disease. Despite improvement of prostate cancer diagnosis and complex treatment mortality does not decreased significantly. Knowledge of etiological factors are relatively limited. Important factors are: genetic disposition, age, life style, race, positive familial history, circulated androgens. Diagnostics is well known, based on routine clinical methods: digital rectal examination, measurement of PSA a transrectal ultrasound. Benefit of prostate cancer screening is until now unclear, controversial. (author)

  7. Comparison between the diagnostic accuracy of clinico-pathological and molecular tests for feline infectious peritonitis (FIP

    Directory of Open Access Journals (Sweden)

    Angelica Stranieri

    2015-07-01

    Full Text Available The aim of this study was to compare the diagnostic accuracy for feline infectious peritonitis (FIP of conventional clinic-pathological tests with that of molecular tests such as routine PCR and PCR followed by the sequencing of the Spike (S gene. Blood, effusion and tissues specimens were collected from 21 FIP suspected cats. In vivo examination consisted of CBC, serum protein electrophoresis, AGP measurement, cytological and biochemical examination and the evaluation of the ΔTNC on effusions, and of molecular tests such the screening PCR (target: 3’UTR region and the PCR directed towards the S gene followed by the amplification products sequencing in order to detect the aminoacidic substitution recently considered diagnostic for FIP1. These molecular techniques were applied to tissues collected during necropsy, which also allowed forming an FIP group (13 cats and a non-FIP group (5 cats based on histology and immunohistochemistry. The best test on tissues was immunohistochemistry (sens: 92.3%; spec: 100%, while the screening PCR suffered of low specificity (spec: 33.3% and the S gene sequencing showed low sensitivity (sens: 69.2%.On effusions, the best tests resulted screening PCR and cytology (sens and spec: 100% in comparison with the ΔTNC measurement (sens: 85.7 %; spec: 100% and the S gene sequencing (sens: 42.8%; spec: 100%.On blood, the best test resulted AGP measurement (sens: 81.8%; spec: 100%, while serum protein electrophoresis showed a surprisingly low sensitivity (sens: 41.7%. Screening PCR (sens: 55.6%; spec: 100% and S gene sequencing (sens: 33.3%; spec: 100% proved again low accuracy.

  8. Comprehensive screening for immunodeficiency-associated vaccine-derived poliovirus: an essential oral poliovirus vaccine cessation risk management strategy.

    Science.gov (United States)

    Duintjer Tebbens, R J; Thompson, K M

    2017-01-01

    If the world can successfully control all outbreaks of circulating vaccine-derived poliovirus that may occur soon after global oral poliovirus vaccine (OPV) cessation, then immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) from rare and mostly asymptomatic long-term excretors (defined as ⩾6 months of excretion) will become the main source of potential poliovirus outbreaks for as long as iVDPV excretion continues. Using existing models of global iVDPV prevalence and global long-term poliovirus risk management, we explore the implications of uncertainties related to iVDPV risks, including the ability to identify asymptomatic iVDPV excretors to treat with polio antiviral drugs (PAVDs) and the transmissibility of iVDPVs. The expected benefits of expanded screening to identify and treat long-term iVDPV excretors with PAVDs range from US$0.7 to 1.5 billion with the identification of 25-90% of asymptomatic long-term iVDPV excretors, respectively. However, these estimates depend strongly on assumptions about the transmissibility of iVDPVs and model inputs affecting the global iVDPV prevalence. For example, the expected benefits may decrease to as low as US$260 million with the identification of 90% of asymptomatic iVDPV excretors if iVDPVs behave and transmit like partially reverted viruses instead of fully reverted viruses. Comprehensive screening for iVDPVs will reduce uncertainties and maximize the expected benefits of PAVD use.

  9. Cervical cancer: A global health crisis.

    Science.gov (United States)

    Small, William; Bacon, Monica A; Bajaj, Amishi; Chuang, Linus T; Fisher, Brandon J; Harkenrider, Matthew M; Jhingran, Anuja; Kitchener, Henry C; Mileshkin, Linda R; Viswanathan, Akila N; Gaffney, David K

    2017-07-01

    Cervical cancer is the fourth most common malignancy diagnosed in women worldwide. Nearly all cases of cervical cancer result from infection with the human papillomavirus, and the prevention of cervical cancer includes screening and vaccination. Primary treatment options for patients with cervical cancer may include surgery or a concurrent chemoradiotherapy regimen consisting of cisplatin-based chemotherapy with external beam radiotherapy and brachytherapy. Cervical cancer causes more than one quarter of a million deaths per year as a result of grossly deficient treatments in many developing countries. This warrants a concerted global effort to counter the shocking loss of life and suffering that largely goes unreported. This article provides a review of the biology, prevention, and treatment of cervical cancer, and discusses the global cervical cancer crisis and efforts to improve the prevention and treatment of the disease in underdeveloped countries. Cancer 2017;123:2404-12. © 2017 American Cancer Society. © 2017 American Cancer Society.

  10. Conductometric Sensor for PAH Detection with Molecularly Imprinted Polymer as Recognition Layer

    Directory of Open Access Journals (Sweden)

    Usman Latif

    2018-03-01

    Full Text Available A conductometric sensor based on screen-printed interdigital gold electrodes on glass substrate coated with molecularly imprinted polyurethane layers was fabricated to detect polycyclic aromatic hydrocarbons (PAHs in water. The results prove that screen-printed interdigital electrodes are very suitable transducers to fabricate low-cost sensor systems for measuring change in resistance of PAH-imprinted layers while exposing to different PAHs. The sensor showed good selectivity to its templated molecules and high sensitivity with a detection limit of 1.3 nmol/L e.g., for anthracene in water which is lower than WHO’s permissible limit.

  11. Molecular characterization of Streptococcus agalactiae and Streptococcus uberis isolates from bovine milk.

    Science.gov (United States)

    Shome, Bibek Ranjan; Bhuvana, Mani; Mitra, Susweta Das; Krithiga, Natesan; Shome, Rajeswari; Velu, Dhanikachalam; Banerjee, Apala; Barbuddhe, Sukhadeo B; Prabhudas, Krishnamshetty; Rahman, Habibar

    2012-12-01

    Streptococci are one among the major mastitis pathogens which have a considerable impact on cow health, milk quality, and productivity. The aim of the present study was to investigate the occurrence and virulence characteristics of streptococci from bovine milk and to assess the molecular epidemiology and population structure of the Indian isolates using multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Out of a total of 209 bovine composite milk samples screened from four herds (A-D), 30 Streptococcus spp. were isolated from 29 milk samples. Among the 30 isolates, species-specific PCR and partial 16S rRNA gene sequence analysis identified 17 Streptococcus agalactiae arising from herd A and 13 Streptococcus uberis comprising of 5, 7, and 1 isolates from herds B, C, and D respectively. PCR based screening for virulence genes revealed the presence of the cfb and the pavA genes in 17 and 1 S. agalactiae isolates, respectively. Similarly, in S. uberis isolates, cfu gene was present in six isolates from herd C, the pau A/skc gene in all the isolates from herds B, C, and D, whereas the sua gene was present in four isolates from herd B and the only isolate from herd D. On MLST analysis, all the S. agalactiae isolates were found to be of a novel sequence type (ST), ST-483, reported for the first time and is a single locus variant of the predicted subgroup founder ST-310, while the S. uberis isolates were found to be of three novel sequence types, namely ST-439, ST-474, and ST-475, all reported for the first time. ST-474 was a double locus variant of three different STs of global clonal complex ST-143 considered to be associated with clinical and subclinical mastitis, but ST-439 and ST-475 were singletons. Unique sequence types identified for both S. agalactiae and S. uberis were found to be herd specific. On PFGE analysis, identical or closely related restriction patterns for S. agalactiae ST-483 and S. uberis ST-439 in herds A and B

  12. Cancer screening guidelines.

    Science.gov (United States)

    Zoorob, R; Anderson, R; Cefalu, C; Sidani, M

    2001-03-15

    Numerous medical organizations have developed cancer screening guidelines. Faced with the broad, and sometimes conflicting, range of recommendations for cancer screening, family physicians must determine the most reasonable and up-to-date method of screening. Major medical organizations have generally achieved consensus on screening guidelines for breast, cervical and colorectal cancer. For breast cancer screening in women ages 50 to 70, clinical breast examination and mammography are generally recommended every one or two years, depending on the medical organization. For cervical cancer screening, most organizations recommend a Papanicolaou test and pelvic examination at least every three years in patients between 20 and 65 years of age. Annual fecal occult blood testing along with flexible sigmoidoscopy at five-year to 10-year intervals is the standard recommendation for colorectal cancer screening in patients older than 50 years. Screening for prostate cancer remains a matter of debate. Some organizations recommend digital rectal examination and a serum prostate-specific antigen test for men older than 50 years, while others do not. In the absence of compelling evidence to indicate a high risk of endometrial cancer, lung cancer, oral cancer and ovarian cancer, almost no medical organizations have developed cancer screening guidelines for these types of cancer.

  13. Star formation in evolving molecular clouds

    Science.gov (United States)

    Völschow, M.; Banerjee, R.; Körtgen, B.

    2017-09-01

    Molecular clouds are the principle stellar nurseries of our universe; they thus remain a focus of both observational and theoretical studies. From observations, some of the key properties of molecular clouds are well known but many questions regarding their evolution and star formation activity remain open. While numerical simulations feature a large number and complexity of involved physical processes, this plethora of effects may hide the fundamentals that determine the evolution of molecular clouds and enable the formation of stars. Purely analytical models, on the other hand, tend to suffer from rough approximations or a lack of completeness, limiting their predictive power. In this paper, we present a model that incorporates central concepts of astrophysics as well as reliable results from recent simulations of molecular clouds and their evolutionary paths. Based on that, we construct a self-consistent semi-analytical framework that describes the formation, evolution, and star formation activity of molecular clouds, including a number of feedback effects to account for the complex processes inside those objects. The final equation system is solved numerically but at much lower computational expense than, for example, hydrodynamical descriptions of comparable systems. The model presented in this paper agrees well with a broad range of observational results, showing that molecular cloud evolution can be understood as an interplay between accretion, global collapse, star formation, and stellar feedback.

  14. Development of a high risk pancreatic screening clinic using 3.0 T MRI.

    Science.gov (United States)

    Barnes, Chad A; Krzywda, Elizabeth; Lahiff, Shannon; McDowell, Dena; Christians, Kathleen K; Knechtges, Paul; Tolat, Parag; Hohenwalter, Mark; Dua, Kulwinder; Khan, Abdul H; Evans, Douglas B; Geurts, Jennifer; Tsai, Susan

    2018-01-01

    Selective screening for pancreatic cancer (PC) has been proposed. We describe the establishment of a comprehensive multidisciplinary screening program using 3.0 T MRI. Criteria for screening included the presence of PC in: ≥ 2 first degree relatives (FDR), 1 FDR and 1 s degree relative (SDR), ≥ 3 any degree relatives (ADR), or any known hereditary cancer syndrome with increased PC risk. Imaging with 3.0 T MRI was performed routinely and endoscopic ultrasound was used selectively. Screening was completed in 75 patients (pts). Hereditary cancer syndromes were present in 42 (56%) of the 75 pts: BRCA2 (18), ATM (8), BRCA1 (6), CDKN2A (4), PALB2 (3), Lynch (2), and Peutz-Jeghers (1). A family history of PC was present in ≥ 2 FDR in 12 (16%) pts, 1 FDR and 1 SDR in 5 (7) pts, and ≥ 3 ADR in 16 (21%) pts. Of the 65 pts who received screening MRI, 28 (43%) pts had pancreatic cystic lesions identified, including 1 (1%) patient in whom a cholangiocarcinoma was diagnosed as well. No patient underwent surgical resection. Using a 3.0 T MRI to screen patients at high risk for developing PC identified radiographic abnormalities in 43% of patients, which were stable on subsequent surveillance. Specific guidelines for the frequency of surveillance and indications for surgery remain areas of active investigation as the global experience with high risk screening continues to mature.

  15. Molecular signatures of biogeochemical transformations in dissolved organic matter from ten World Rivers

    Directory of Open Access Journals (Sweden)

    Thomas Riedel

    2016-09-01

    Full Text Available Rivers carry large amounts of dissolved organic matter (DOM to the oceans thereby connecting terrestrial and marine element cycles. Photo-degradation in conjunction with microbial turnover is considered a major pathway by which terrigenous DOM is decomposed. To reveal globally relevant patterns behind this process, we performed photo-degradation experiments and year-long bio-assays on DOM from ten of the largest world rivers that collectively account for more than one-third of the fresh water discharge to the global ocean. We furthermore tested the hypothesis that the terrigenous component in deep ocean DOM may be far higher than biomarker studies suggest, because of the selective photochemical destruction of characteristic biomolecules from vascular plants. DOM was molecularly characterized by a combination of non-targeted ultrahigh-resolution mass spectrometry and quantitative molecular tracer analyses. We show that the reactivity of DOM is globally related to broad catchment properties. Basins that are dominated by forest and grassland export more photo-degradable DOM than other rivers. Chromophoric compounds are mainly vascular plant-derived polyphenols, and partially carry a pyrogenic signature from vegetation fires. These forest and grassland dominated rivers lost up to 50% of dissolved organic carbon (DOC during irradiation, and up to 85% of DOC was lost in total if subsequently bio-incubated for one year. Basins covered by cropland, on the other hand, export DOM with a higher proportion of photo-resistant and bio-available DOM which is enriched in nitrogen. In these rivers, 30% or less of DOC was photodegraded. Consistent with previous studies, we found that riverine DOM resembled marine DOM in its broad molecular composition after extensive degradation, mainly due to almost complete removal of aromatics. More detailed molecular fingerprinting analysis (based on the relative abundance of >4000 DOM molecular formulae, however, revealed

  16. Screening effects on 12C+12C fusion reaction

    Science.gov (United States)

    Koyuncu, F.; Soylu, A.

    2018-05-01

    One of the important reactions for nucleosynthesis in the carbon burning phase in high-mass stars is the 12C+12C fusion reaction. In this study, we investigate the influences of the nuclear potentials and screening effect on astrophysically interesting 12C+12C fusion reaction observables at sub-barrier energies by using the microscopic α–α double folding cluster (DFC) potential and the proximity potential. In order to model the screening effects on the experimental data, a more general exponential cosine screened Coulomb (MGECSC) potential including Debye and quantum plasma cases has been considered in the calculations for the 12C+12C fusion reaction. In the calculations of the reaction observables, the semi-classical Wentzel-Kramers-Brillouin (WKB) approach and coupled channel (CC) formalism have been used. Moreover, in order to investigate how the potentials between 12C nuclei produce molecular cluster states of 24Mg, the normalized resonant energy states of 24Mg cluster bands have been calculated for the DFC potential. By analyzing the results produced from the fusion of 12C+12C, it is found that taking into account the screening effects in terms of MGECSC is important for explaining the 12C+12C fusion data, and the microscopic DFC potential is better than the proximity potential in explaining the experimental data, also considering that clustering is dominant for the structure of the 24Mg nucleus. Supported by the Turkish Science and Research Council (TÜBİTAK) with (117R015)

  17. Evaluating the mutagenic potential of aerosol organic compounds using informatics-based screening

    Science.gov (United States)

    Decesari, Stefano; Kovarich, Simona; Pavan, Manuela; Bassan, Arianna; Ciacci, Andrea; Topping, David

    2018-02-01

    Whilst general policy objectives to reduce airborne particulate matter (PM) health effects are to reduce exposure to PM as a whole, emerging evidence suggests that more detailed metrics associating impacts with different aerosol components might be needed. Since it is impossible to conduct toxicological screening on all possible molecular species expected to occur in aerosol, in this study we perform a proof-of-concept evaluation on the information retrieved from in silico toxicological predictions, in which a subset (N = 104) of secondary organic aerosol (SOA) compounds were screened for their mutagenicity potential. An extensive database search showed that experimental data are available for 13 % of the compounds, while reliable predictions were obtained for 82 %. A multivariate statistical analysis of the compounds based on their physico-chemical, structural, and mechanistic properties showed that 80 % of the compounds predicted as mutagenic were grouped into six clusters, three of which (five-membered lactones from monoterpene oxidation, oxygenated multifunctional compounds from substituted benzene oxidation, and hydroperoxides from several precursors) represent new candidate groups of compounds for future toxicological screenings. These results demonstrate that coupling model-generated compositions to in silico toxicological screening might enable more comprehensive exploration of the mutagenic potential of specific SOA components.

  18. Reverse screening methods to search for the protein targets of chemopreventive compounds

    Science.gov (United States)

    Huang, Hongbin; Zhang, Guigui; Zhou, Yuquan; Lin, Chenru; Chen, Suling; Lin, Yutong; Mai, Shangkang; Huang, Zunnan

    2018-05-01

    This article is a systematic review of reverse screening methods used to search for the protein targets of chemopreventive compounds or drugs. Typical chemopreventive compounds include components of traditional Chinese medicine, natural compounds and Food and Drug Administration (FDA)-approved drugs. Such compounds are somewhat selective but are predisposed to bind multiple protein targets distributed throughout diverse signaling pathways in human cells. In contrast to conventional virtual screening, which identifies the ligands of a targeted protein from a compound database, reverse screening is used to identify the potential targets or unintended targets of a given compound from a large number of receptors by examining their known ligands or crystal structures. This method, also known as in silico or computational target fishing, is highly valuable for discovering the target receptors of query molecules from terrestrial or marine natural products, exploring the molecular mechanisms of chemopreventive compounds, finding alternative indications of existing drugs by drug repositioning, and detecting adverse drug reactions and drug toxicity. Reverse screening can be divided into three major groups: shape screening, pharmacophore screening and reverse docking. Several large software packages, such as Schrödinger and Discovery Studio; typical software/network services such as ChemMapper, PharmMapper, idTarget and INVDOCK; and practical databases of known target ligands and receptor crystal structures, such as ChEMBL, BindingDB and the Protein Data Bank (PDB), are available for use in these computational methods. Different programs, online services and databases have different applications and constraints. Here, we conducted a systematic analysis and multilevel classification of the computational programs, online services and compound libraries available for shape screening, pharmacophore screening and reverse docking to enable non-specialist users to quickly learn and

  19. Ruling in or ruling out thyroid malignancy by molecular diagnostics of thyroid nodules

    DEFF Research Database (Denmark)

    Eszlinger, Markus; Hegedüs, László; Paschke, Ralf

    2014-01-01

    Routine morphologic cytology is the basis for any kind of (integrated) molecular FNA diagnostics. The rule out (gene expression classifier) approach requires confirmation by independent studies, whereas the rule in approach (detection of BRAF, NRAS, HRAS, and KRAS and PAX8/PPARG- and RET....../PTC rearrangements) has been investigated by several groups with overall reproducible results. Moreover, molecular screening for point mutations and rearrangements is feasible in routine air-dried FNA smears, offering several advantages over obtaining additional fresh FNA material. The current panel of somatic...

  20. Clustering Molecular Dynamics Trajectories for Optimizing Docking Experiments

    Directory of Open Access Journals (Sweden)

    Renata De Paris

    2015-01-01

    Full Text Available Molecular dynamics simulations of protein receptors have become an attractive tool for rational drug discovery. However, the high computational cost of employing molecular dynamics trajectories in virtual screening of large repositories threats the feasibility of this task. Computational intelligence techniques have been applied in this context, with the ultimate goal of reducing the overall computational cost so the task can become feasible. Particularly, clustering algorithms have been widely used as a means to reduce the dimensionality of molecular dynamics trajectories. In this paper, we develop a novel methodology for clustering entire trajectories using structural features from the substrate-binding cavity of the receptor in order to optimize docking experiments on a cloud-based environment. The resulting partition was selected based on three clustering validity criteria, and it was further validated by analyzing the interactions between 20 ligands and a fully flexible receptor (FFR model containing a 20 ns molecular dynamics simulation trajectory. Our proposed methodology shows that taking into account features of the substrate-binding cavity as input for the k-means algorithm is a promising technique for accurately selecting ensembles of representative structures tailored to a specific ligand.

  1. Ecosystem screening approach for pathogen-associated microorganisms affecting host disease.

    Science.gov (United States)

    Galiana, Eric; Marais, Antoine; Mura, Catherine; Industri, Benoît; Arbiol, Gilles; Ponchet, Michel

    2011-09-01

    The microbial community in which a pathogen evolves is fundamental to disease outcome. Species interacting with a pathogen on the host surface shape the distribution, density, and genetic diversity of the inoculum, but the role of these species is rarely determined. The screening method developed here can be used to characterize pathogen-associated species affecting disease. This strategy involves three steps: (i) constitution of the microbial community, using the pathogen as a trap; (ii) community selection, using extracts from the pathogen as the sole nutrient source; and (iii) molecular identification and the screening of isolates focusing on their effects on the growth of the pathogen in vitro and host disease. This approach was applied to a soilborne plant pathogen, Phytophthora parasitica, structured in a biofilm, for screening the microbial community from the rhizosphere of Nicotiana tabacum (the host). Two of the characterized eukaryotes interfered with the oomycete cycle and may affect the host disease. A Vorticella species acted through a mutualistic interaction with P. parasitica, disseminating pathogenic material by leaving the biofilm. A Phoma species established an amensal interaction with P. parasitica, strongly suppressing disease by inhibiting P. parasitica germination. This screening method is appropriate for all nonobligate pathogens. It allows the definition of microbial species as promoters or suppressors of a disease for a given biotope. It should also help to identify important microbial relationships for ecology and evolution of pathogens.

  2. Modification of -Adenosyl--Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation

    Directory of Open Access Journals (Sweden)

    Usman Sumo Friend Tambunan

    2017-04-01

    Full Text Available Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world’s population in tropical and subtropical countries. Nonstructural protein 5 (NS5 methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S -adenosyl- l -methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2′OH, resulting in S -adenosyl- l -homocysteine (SAH. The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity test. The 2 simulations were performed using Molecular Operating Environment (MOE 2008.10 software, whereas the ADME-Tox test was performed using various software. The modification of SAH compound was done using several functional groups that possess different polarities and properties, resulting in 3460 ligands to be docked. After conducting docking simulation, we earned 3 best ligands (SAH-M331, SAH-M2696, and SAH-M1356 based on ΔG binding and molecular interactions, which show better results than the standard ligands. Moreover, the results of molecular dynamics simulation show that the best ligands are still able to maintain the active site residue interaction with the binding site until the end of the simulation. After a series of molecular docking and molecular dynamics simulation were performed, we concluded that SAH-M1356 ligand is the most potential SAH-based compound to inhibit NS5 methyltransferase enzyme for treating dengue fever.

  3. The spectral distribution of intermediate L-K molecular-orbital radiation in symmetric heavy-ion collisions

    International Nuclear Information System (INIS)

    Heinig, K.-H.; Jager, H.-U.; Richter, H.; Woittennek, H.; Frank, W.; Gippener, P.; Kaun, K.-H.; Manfrass, P.

    1977-01-01

    Two distinct x-ray continua C1 and C2 above the characteristic lines are observed in high-energy collisions between atoms with atomic numbers of 28 to 57. This structure is explained by a superposition of K molecular-orbital (KMO) radiation and of an intermediate L-K molecular-orbital (ILKMO) radiation of high intensity which is due to 2psigma vacancies. In the framework of the dynamical theory of intermediate molecular phenomena and using a scaling of the H 2 + correlation diagram with screened state-dependent charges good agreement between the shapes of the measured and calculated spectra is obtained. (author)

  4. The frequency of Tay-Sachs disease causing mutations in the Brazilian Jewish population justifies a carrier screening program

    Directory of Open Access Journals (Sweden)

    Roberto Rozenberg

    Full Text Available CONTEXT: Tay-Sachs disease is an autosomal recessive disease characterized by progressive neurologic degeneration, fatal in early childhood. In the Ashkenazi Jewish population the disease incidence is about 1 in every 3,500 newborns and the carrier frequency is 1 in every 29 individuals. Carrier screening programs for Tay-Sachs disease have reduced disease incidence by 90% in high-risk populations in several countries. The Brazilian Jewish population is estimated at 90,000 individuals. Currently, there is no screening program for Tay-Sachs disease in this population. OBJECTIVE: To evaluate the importance of a Tay-Sachs disease carrier screening program in the Brazilian Jewish population by determining the frequency of heterozygotes and the acceptance of the program by the community. SETTING: Laboratory of Molecular Genetics - Institute of Biosciences - Universidade de São Paulo. PARTICIPANTS: 581 senior students from selected Jewish high schools. PROCEDURE: Molecular analysis of Tay-Sachs disease causing mutations by PCR amplification of genomic DNA, followed by restriction enzyme digestion. RESULTS: Among 581 students that attended educational classes, 404 (70% elected to be tested for Tay-Sachs disease mutations. Of these, approximately 65% were of Ashkenazi Jewish origin. Eight carriers were detected corresponding to a carrier frequency of 1 in every 33 individuals in the Ashkenazi Jewish fraction of the sample. CONCLUSION: The frequency of Tay-Sachs disease carriers among the Ashkenazi Jewish population of Brazil is similar to that of other countries where carrier screening programs have led to a significant decrease in disease incidence. Therefore, it is justifiable to implement a Tay-Sachs disease carrier screening program for the Brazilian Jewish population.

  5. Neonatal Screening: Some Ethical Issues of Expanding Spectrum for Genetically Determined Diseases

    Directory of Open Access Journals (Sweden)

    S. S. Deryabina

    2015-01-01

    Full Text Available The article considers philosophical questions of neonatal screening technology. The main focus is on ethical and methodological issues that inevitably arise when expanding the number of scanned nosologies and applying genetic research methods. Questions concerning the existing discrepancy between technical capacity and the practical level of healthcare delivery and the probabilistic nature of results obtained by molecular testing are analyzed in terms of methodology. Access to information about the DNA-testing of newborns and the linkage between neonatal screening and prenatal diagnostics are among the most topical ethical problems raised within this article. One of the purposes of this article is to draw the attention of the public — especially it concerns current and prospective parents and volunteer organizations — to these contemporary problems.

  6. Molecular profiling of cancer--the future of personalized cancer medicine: a primer on cancer biology and the tools necessary to bring molecular testing to the clinic.

    Science.gov (United States)

    Stricker, Thomas; Catenacci, Daniel V T; Seiwert, Tanguy Y

    2011-04-01

    Cancers arise as a result of an accumulation of genetic aberrations that are either acquired or inborn. Virtually every cancer has its unique set of molecular changes. Technologies have been developed to study cancers and derive molecular characteristics that increasingly have implications for clinical care. Indeed, the identification of key genetic aberrations (molecular drivers) may ultimately translate into dramatic benefit for patients through the development of highly targeted therapies. With the increasing availability of newer, more powerful, and cheaper technologies such as multiplex mutational screening, next generation sequencing, array-based approaches that can determine gene copy numbers, methylation, expression, and others, as well as more sophisticated interpretation of high-throughput molecular information using bioinformatics tools like signatures and predictive algorithms, cancers will routinely be characterized in the near future. This review examines the background information and technologies that clinicians and physician-scientists will need to interpret in order to develop better, personalized treatment strategies. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Discovery of novel inhibitors of Mycobacterium tuberculosis MurG: homology modelling, structure based pharmacophore, molecular docking, and molecular dynamics simulations.

    Science.gov (United States)

    Saxena, Shalini; Abdullah, Maaged; Sriram, Dharmarajan; Guruprasad, Lalitha

    2017-10-17

    MurG (Rv2153c) is a key player in the biosynthesis of the peptidoglycan layer in Mycobacterium tuberculosis (Mtb). This work is an attempt to highlight the structural and functional relationship of Mtb MurG, the three-dimensional (3D) structure of protein was constructed by homology modelling using Discovery Studio 3.5 software. The quality and consistency of generated model was assessed by PROCHECK, ProSA and ERRAT. Later, the model was optimized by molecular dynamics (MD) simulations and the optimized model complex with substrate Uridine-diphosphate-N-acetylglucosamine (UD1) facilitated us to employ structure-based virtual screening approach to obtain new hits from Asinex database using energy-optimized pharmacophore modelling (e-pharmacophore). The pharmacophore model was validated using enrichment calculations, and finally, validated model was employed for high-throughput virtual screening and molecular docking to identify novel Mtb MurG inhibitors. This study led to the identification of 10 potential compounds with good fitness, docking score, which make important interactions with the protein active site. The 25 ns MD simulations of three potential lead compounds with protein confirmed that the structure was stable and make several non-bonding interactions with amino acids, such as Leu290, Met310 and Asn167. Hence, we concluded that the identified compounds may act as new leads for the design of Mtb MurG inhibitors.

  8. pGLO Mutagenesis: A Laboratory Procedure in Molecular Biology for Biology Students

    Science.gov (United States)

    Bassiri, Eby A.

    2011-01-01

    A five-session laboratory project was designed to familiarize or increase the laboratory proficiency of biology students and others with techniques and instruments commonly used in molecular biology research laboratories and industries. In this project, the EZ-Tn5 transposon is used to generate and screen a large number of cells transformed with…

  9. Applications of self-organizing neural networks in virtual screening and diversity selection.

    Science.gov (United States)

    Selzer, Paul; Ertl, Peter

    2006-01-01

    Artificial neural networks provide a powerful technique for the analysis and modeling of nonlinear relationships between molecular structures and pharmacological activity. Many network types, including Kohonen and counterpropagation, also provide an intuitive method for the visual assessment of correspondence between the input and output data. This work shows how a combination of neural networks and radial distribution function molecular descriptors can be applied in various areas of industrial pharmaceutical research. These applications include the prediction of biological activity, the selection of screening candidates (cherry picking), and the extraction of representative subsets from large compound collections such as combinatorial libraries. The methods described have also been implemented as an easy-to-use Web tool, allowing chemists to perform interactive neural network experiments on the Novartis intranet.

  10. [The global medical record + (DMG+), tool for prevention in first line care].

    Science.gov (United States)

    Schetgen, M

    2012-09-01

    The "global medical record +" can be offered to all 45 to 75 year-old patients in the form of a prevention module within the global medical record and which the general practitioner and the patient will regularly update. It will include in particular an assessment of cardiovascular risk, cervical, breast and colon cancer screening, a check of main adult vaccinations, as well as a primary prevention section focused on smoking, alcohol consumption and various hygiene and dietary measures. The inclusion of this module in a computerized medical record will make it more efficient and will lighten the practitioner's workload.

  11. A plant-based chemical genomics screen for the identification of flowering inducers.

    Science.gov (United States)

    Fiers, Martijn; Hoogenboom, Jorin; Brunazzi, Alice; Wennekes, Tom; Angenent, Gerco C; Immink, Richard G H

    2017-01-01

    Floral timing is a carefully regulated process, in which the plant determines the optimal moment to switch from the vegetative to reproductive phase. While there are numerous genes known that control flowering time, little information is available on chemical compounds that are able to influence this process. We aimed to discover novel compounds that are able to induce flowering in the model plant Arabidopsis. For this purpose we developed a plant-based screening platform that can be used in a chemical genomics study. Here we describe the set-up of the screening platform and various issues and pitfalls that need to be addressed in order to perform a chemical genomics screening on Arabidopsis plantlets. We describe the choice for a molecular marker, in combination with a sensitive reporter that's active in plants and is sufficiently sensitive for detection. In this particular screen, the firefly Luciferase marker was used, fused to the regulatory sequences of the floral meristem identity gene APETALA1 (AP1) , which is an early marker for flowering. Using this screening platform almost 9000 compounds were screened, in triplicate, in 96-well plates at a concentration of 25 µM. One of the identified potential flowering inducing compounds was studied in more detail and named Flowering1 (F1). F1 turned out to be an analogue of the plant hormone Salicylic acid (SA) and appeared to be more potent than SA in the induction of flowering. The effect could be confirmed by watering Arabidopsis plants with SA or F1, in which F1 gave a significant reduction in time to flowering in comparison to SA treatment or the control. In this study a chemical genomics screening platform was developed to discover compounds that can induce flowering in Arabidopsis. This platform was used successfully, to identify a compound that can speed-up flowering in Arabidopsis.

  12. Screening for colorectal cancer.

    Science.gov (United States)

    He, Jin; Efron, Jonathan E

    2011-01-01

    March is national colorectal cancer awareness month. It is estimated that as many as 60% of colorectal cancer deaths could be prevented if all men and women aged 50 years or older were screened routinely. In 2000, Katie Couric's televised colonoscopy led to a 20% increase in screening colonoscopies across America, a stunning rise called the "Katie Couric Effect". This event demonstrated how celebrity endorsement affects health behavior. Currently, discussion is ongoing about the optimal strategy for CRC screening, particularly the costs of screening colonoscopy. The current CRC screening guidelines are summarized in Table 2. Debates over the optimum CRC screening test continue in the face of evidence that 22 million Americans aged 50 to 75 years are not screened for CRC by any modality and 25,000 of those lives may have been saved if they had been screened for CRC. It is clear that improving screening rates and reducing disparities in underscreened communities and population subgroups could further reduce colorectal cancer morbidity and mortality. National Institutes of Health consensus identified the following priority areas to enhance the use and quality of colorectal cancer screening: Eliminate financial barriers to colorectal cancer screening and appropriate follow-up of positive results of colorectal cancer screening. Develop systems to ensure the high quality of colorectal cancer screening programs. Conduct studies to determine the comparative effectiveness of the various colorectal cancer screening methods in usual practice settings. Encouraging population adherence to screening tests and allowing patients to select the tests they prefer may do more good (as long as they choose something) than whatever procedure is chosen by the medical profession as the preferred test.

  13. Skin Cancer Screening

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Skin Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Skin Cancer Key Points Skin cancer is a disease ...

  14. Health risks and changes in self-efficacy following community health screening of adults with serious mental illnesses.

    Directory of Open Access Journals (Sweden)

    Judith A Cook

    Full Text Available Physical health screenings were conducted by researchers and peer wellness specialists for adults attending publicly-funded community mental health programs. A total of 457 adults with serious mental illnesses attended health fairs in 4 U.S. states and were screened for 8 common medical co-morbidities and health risk factors. Also assessed were self-reported health competencies, medical conditions, and health service utilization. Compared to non-institutionalized U.S. adults, markedly higher proportions screened positive for obesity (60%, hypertension (32%, diabetes (14%, smoking (44%, nicotine dependence (62%, alcohol abuse (17%, drug abuse (11%, and coronary heart disease (10%. A lower proportion screened positive for hyperlipidemia (7%. Multivariable random regression analysis found significant pre- to post-screening increases in participants' self-rated abilities for health practices, competence for health maintenance, and health locus of control. Screening identified 82 instances of undiagnosed diabetes, hypertension or hyperlipidemia, and 76 instances where these disorders were treated but uncontrolled. These results are discussed in the context of how this global public health approach holds promise for furthering the goal of integrating health and mental health care.

  15. Screening for Cancer

    Science.gov (United States)

    Cancer screening is checking for cancer in people who don't have symptoms. Screening tests can help doctors find and treat several types of cancer early, but cancer screening can have harms as well as benefits.

  16. Domestic violence screening in a military setting: provider screening and attitudes.

    Science.gov (United States)

    Lutgendorf, Monica; Busch, Jeanne; Magann, Everett F; Morrison, John C

    2010-06-01

    Domestic violence is an important healthcare problem, and it appears more prevalent in military patient populations although no one has demonstrated the cause behind this phenomenon. The purpose of this observational study was to assess data regarding domestic violence screening from practitioners at one military training center. This study used an anonymous questionnaire for physicians, nurses and nurse midwives, which surveyed current methods, attitudes toward screening, and barriers for such assessment. Fifty-seven surveys were distributed, and 26 were returned for a response rate of 45.6%. Only about a third (38.5%) of the practitioners screened all obstetric patients while the remainder screened selected patients for domestic violence. Even less (19%) screened gynecology patients routinely, whereas 69% reported they screened selected women with chronic or somatic complaints. A history of prior abuse in the respondents led practitioners to try to identify such patients within their practice. Lack of education or training was the most common barrier to universal screening followed by time constraints and frustration about not being able to address adequately the problem when noted. These results emphasized the importance of an educational program to increase domestic violence awareness and routine screening.

  17. Colorectal Cancer Screening

    Science.gov (United States)

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

  18. Screening_mgmt: a Python module for managing screening data.

    Science.gov (United States)

    Helfenstein, Andreas; Tammela, Päivi

    2015-02-01

    High-throughput screening is an established technique in drug discovery and, as such, has also found its way into academia. High-throughput screening generates a considerable amount of data, which is why specific software is used for its analysis and management. The commercially available software packages are often beyond the financial limits of small-scale academic laboratories and, furthermore, lack the flexibility to fulfill certain user-specific requirements. We have developed a Python module, screening_mgmt, which is a lightweight tool for flexible data retrieval, analysis, and storage for different screening assays in one central database. The module reads custom-made analysis scripts and plotting instructions, and it offers a graphical user interface to import, modify, and display the data in a uniform manner. During the test phase, we used this module for the management of 10,000 data points of various origins. It has provided a practical, user-friendly tool for sharing and exchanging information between researchers. © 2014 Society for Laboratory Automation and Screening.

  19. Cytogenetic and molecular markers for detecting Aegilops uniaristata chromosomes in a wheat background.

    Science.gov (United States)

    Gong, Wenping; Li, Guangrong; Zhou, Jianping; Li, Genying; Liu, Cheng; Huang, Chengyan; Zhao, Zhendong; Yang, Zujun

    2014-09-01

    Aegilops uniaristata has many agronomically useful traits that can be used for wheat breeding. So far, a Triticum turgidum - Ae. uniaristata amphiploid and one set of Chinese Spring (CS) - Ae. uniaristata addition lines have been produced. To guide Ae. uniaristata chromatin transformation from these lines into cultivated wheat through chromosome engineering, reliable cytogenetic and molecular markers specific for Ae. uniaristata chromosomes need to be developed. Standard C-banding shows that C-bands mainly exist in the centromeric regions of Ae. uniaristata but rarely at the distal ends. Fluorescence in situ hybridization (FISH) using (GAA)8 as a probe showed that the hybridization signal of chromosomes 1N-7N are different, thus (GAA)8 can be used to identify all Ae. uniaristata chromosomes in wheat background simultaneously. Moreover, a total of 42 molecular markers specific for Ae. uniaristata chromosomes were developed by screening expressed sequence tag - sequence tagged site (EST-STS), expressed sequence tag - simple sequence repeat (EST-SSR), and PCR-based landmark unique gene (PLUG) primers. The markers were subsequently localized using the CS - Ae. uniaristata addition lines and different wheat cultivars as controls. The cytogenetic and molecular markers developed herein will be helpful for screening and identifying wheat - Ae. uniaristata progeny.

  20. AFFINITY BIOSENSOR BASED ON SCREEN-PRINTED ELECTRODE MODIFIED WITH DNA FOR GENOTOXIC COMPOUNDS DETECTION

    Directory of Open Access Journals (Sweden)

    Bambang Kuswandi

    2010-06-01

    Full Text Available An electrochemical method for the detection of the genotoxic compounds using a DNA-modified electrode was developed. This electrode was successfully used for the electrochemical detection of genotoxic compounds in water samples. The electrochemical results clearly demonstrated that, the development is related to the molecular interaction between the surface-linked DNA obtained from calf thymus and the target compounds, such as pollutants, in order to develop a simple device for rapid screening of genotoxic compounds in environmental samples. The detection of such compounds was measured by their effect on the oxidation signal of the guanine peak of the DNA immobilised on the surface of carbon based Screen-Printed Electrode (SPE in disposable mode, and monitored by square-wave voltametric analysis. The DNA biosensor is able to detect known intercalating and groove-binding genotoxic compounds such as Dioxin, Bisphenol A, PCBs, and Phtalates. Application to real water samples is discussed and reported.   Keywords: electrochemical, screen-printed electrode, DNA biosensor, genotoxic compounds

  1. Screening the Medicines for Malaria Venture "Malaria Box" against the Plasmodium falciparum aminopeptidases, M1, M17 and M18.

    Directory of Open Access Journals (Sweden)

    Alessandro Paiardini

    Full Text Available Malaria is a parasitic disease that remains a global health burden. The ability of the parasite to rapidly develop resistance to therapeutics drives an urgent need for the delivery of new drugs. The Medicines for Malaria Venture have compounds known for their antimalarial activity, but not necessarily the molecular targets. In this study, we assess the ability of the "MMV 400" compounds to inhibit the activity of three metalloaminopeptidases from Plasmodium falciparum, PfA-M1, PfA-M17 and PfM18 AAP. We have developed a multiplex assay system to allow rapid primary screening of compounds against all three metalloaminopeptidases, followed by detailed analysis of promising compounds. Our results show that there were no PfM18AAP inhibitors, whereas two moderate inhibitors of the neutral aminopeptidases PfA-M1 and PfA-M17 were identified. Further investigation through structure-activity relationship studies and molecular docking suggest that these compounds are competitive inhibitors with novel binding mechanisms, acting through either non-classical zinc coordination or independently of zinc binding altogether. Although it is unlikely that inhibition of PfA-M1 and/or PfA-M17 is the primary mechanism responsible for the antiplasmodial activity reported for these compounds, their detailed characterization, as presented in this work, pave the way for their further optimization as a novel class of dual PfA-M1/PfA-M17 inhibitors utilising non-classical zinc binding groups.

  2. Screening of molecular cell targets for carcinogenic heterocyclic aromatic amines by using CALUX® reporter gene assays.

    Science.gov (United States)

    Steinberg, Pablo; Behnisch, Peter A; Besselink, Harrie; Brouwer, Abraham A

    2017-06-01

    Heterocyclic aromatic amines (HCAs) are compounds formed when meat or fish are cooked at high temperatures for a long time or over an open fire. To determine which pathways of toxicity are activated by HCAs, nine out of the ten HCAs known to be carcinogenic in rodents (2-amino-9H-pyrido[2,3-b]indole (AαC), 2-aminodipyrido[1,2-a:3',2-d]imidazole (Glu-P-2), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAαC), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2)) were tested in the estrogen receptor α (ERα), androgen receptor (AR), glucocorticoid receptor (GR), peroxisome proliferator-activated receptor γ2 (PPARγ2), polycyclic aromatic hydrocarbons (PAH), Nrf2, and p53 CALUX® reporter gene assays. Trp-P-1 was the only HCA that led to a positive response in the ERα, PPARγ2, and Nrf2 CALUX® assays. In the PAH CALUX® assay, Trp-P-2, MeAαC, and AαC induced luciferase activity to a greater extent than MeIQ and PhIP. In the p53 CALUX® assay without a coupled metabolic activation, only Trp-P-1 and Trp-P-2 enhanced luciferase expression; when a metabolic activation step was coupled to the p53 CALUX® assay, Trp-P-1, Glu-P-2, MeIQ, MeIQx, and PhIP induced a positive response. No HCA was positive in the AR and GR CALUX® assays. Taken together, the results obtained show that the battery of CALUX® assays performed in the present study can successfully be used to screen for molecular cell targets of carcinogenic compounds such as HCAs.

  3. Screen-film mammography

    International Nuclear Information System (INIS)

    Logan, W.W.; Janus, J.A.

    1987-01-01

    The development of screen-film mammography has resulted in the re-emergence of confidence, rather than fear, in mammography. When screen-film mammography is performed with state-of-the-art dedicated equipment utilizing vigorous breast compression and a ''soft'' x-ray beam for improved contrast, screen-film images are equivalent or superior to those of reduced-dose xeromammography and superior to those of nonscreen film mammography. Technological aids for conversion from xeromammographic or nonscreen film mammographic techniques to screen-film techniques have been described. Screen-film mammography should not be attempted until dedicated equipment has been obtained and the importance of vigorous compression has been understood

  4. Measurement and Monte Carlo modeling of the spatial response of scintillation screens

    Energy Technology Data Exchange (ETDEWEB)

    Pistrui-Maximean, S.A. [CNDRI (NDT using Ionizing Radiation) Laboratory, INSA-Lyon, 69621 Villeurbanne (France)], E-mail: spistrui@gmail.com; Letang, J.M. [CNDRI (NDT using Ionizing Radiation) Laboratory, INSA-Lyon, 69621 Villeurbanne (France)], E-mail: jean-michel.letang@insa-lyon.fr; Freud, N. [CNDRI (NDT using Ionizing Radiation) Laboratory, INSA-Lyon, 69621 Villeurbanne (France); Koch, A. [Thales Electron Devices, 38430 Moirans (France); Walenta, A.H. [Detectors and Electronics Department, FB Physik, Siegen University, 57068 Siegen (Germany); Montarou, G. [Corpuscular Physics Laboratory, Blaise Pascal University, 63177 Aubiere (France); Babot, D. [CNDRI (NDT using Ionizing Radiation) Laboratory, INSA-Lyon, 69621 Villeurbanne (France)

    2007-11-01

    In this article, we propose a detailed protocol to carry out measurements of the spatial response of scintillation screens and to assess the agreement with simulated results. The experimental measurements have been carried out using a practical implementation of the slit method. A Monte Carlo simulation model of scintillator screens, implemented with the toolkit Geant4, has been used to study the influence of the acquisition setup parameters and to compare with the experimental results. An algorithm of global stochastic optimization based on a localized random search method has been implemented to adjust the optical parameters (optical scattering and absorption coefficients). The algorithm has been tested for different X-ray tube voltages (40, 70 and 100 kV). A satisfactory convergence between the results simulated with the optimized model and the experimental measurements is obtained.

  5. Molecular Classification and Correlates in Colorectal Cancer

    OpenAIRE

    Ogino, Shuji; Goel, Ajay

    2008-01-01

    Molecular classification of colorectal cancer is evolving. As our understanding of colorectal carcinogenesis improves, we are incorporating new knowledge into the classification system. In particular, global genomic status [microsatellite instability (MSI) status and chromosomal instability (CIN) status] and epigenomic status [CpG island methylator phenotype (CIMP) status] play a significant role in determining clinical, pathological and biological characteristics of colorectal cancer. In thi...

  6. Integration of Family Planning Counselling to Mass Screening Campaign for Cervical Cancer: Experience from Guinea

    Directory of Open Access Journals (Sweden)

    D. W. A. Leno

    2018-01-01

    Full Text Available Aim. To assess feasibility of integrating family planning counselling into mass screening for cervical cancer in Guinea. Methodology. This was a descriptive cross-sectional study conducted over a month in Guinea regional capital cities. The targeted population comprised women aged 15 to 49 years. Nearly 4000 women were expected for the screening campaigns that utilized VIA and VIL methods with confirmation of positive tests through biopsy. A local treatment was immediately performed when the patient was eligible. Results. Overall 5673 women aged 15 to 60 years were received, a surplus of 42% of the expected population. 92.3% of women were aged 15–49 years and 90.1% were 25–49 years. Long-acting methods were the most utilized (89.2% of family planning users. 154 precancerous and cancerous lesions were screened, a global positivity rate of 2.7%. Conclusion. Integration of counselling and family planning services provision during cervical cancer mass screening is a feasible strategy. A cost-effective analysis of this approach would help a better planning of future campaigns and its replication in other contexts.

  7. Implementation of the first worldwide quality assurance program for cystic fibrosis multiple mutation detection in population-based screening.

    Science.gov (United States)

    Earley, Marie C; Laxova, Anita; Farrell, Philip M; Driscoll-Dunn, Rena; Cordovado, Suzanne; Mogayzel, Peter J; Konstan, Michael W; Hannon, W Harry

    2011-07-15

    CDC's Newborn Screening Quality Assurance Program collaborated with several U.S. Cystic Fibrosis Care Centers to collect specimens for development of a molecular CFTR proficiency testing program using dried-blood spots for newborn screening laboratories. Adult and adolescent patients or carriers donated whole blood that was aliquoted onto filter paper cards. Five blind-coded specimens were sent to participating newborn screening laboratories quarterly. Proficiency testing results were evaluated based on presumptive clinical assessment. Individual evaluations and summary reports were sent to each participating laboratory and technical consultations were offered if incorrect assessments were reported. The current CDC repository contains specimens with 39 different CFTR mutations. Up to 45 laboratories have participated in the program. Three years of data showed that correct assessments were reported 97.7% of the time overall when both mutations could be determined. Incorrect assessments that could have lead to a missed case occurred 0.9% of the time, and no information was reported 1.1% of the time due to sample failure. Results show that laboratories using molecular assays to detect CFTR mutations are performing satisfactorily. The programmatic results presented demonstrate the importance and complexity of providing proficiency testing for DNA-based assays. Published by Elsevier B.V.

  8. Molecular clock on a neutral network.

    Science.gov (United States)

    Raval, Alpan

    2007-09-28

    The number of fixed mutations accumulated in an evolving population often displays a variance that is significantly larger than the mean (the overdispersed molecular clock). By examining a generic evolutionary process on a neutral network of high-fitness genotypes, we establish a formalism for computing all cumulants of the full probability distribution of accumulated mutations in terms of graph properties of the neutral network, and use the formalism to prove overdispersion of the molecular clock. We further show that significant overdispersion arises naturally in evolution when the neutral network is highly sparse, exhibits large global fluctuations in neutrality, and small local fluctuations in neutrality. The results are also relevant for elucidating aspects of neutral network topology from empirical measurements of the substitution process.

  9. Molecular outflows in the L1641 region of Orion

    International Nuclear Information System (INIS)

    Morgan, J.A.

    1990-01-01

    Little is known about the interaction between molecular outflows associated with young stellar objects and the parent molecular cloud that produced them. This is because molecular outflows are a recently discovered phenomenon and, so, have not had their global properties studied in great detail and molecular clouds were not mapped to sufficiently high spatial resolution to resolve the interaction. The interaction between molecular outflows and the L1641 molecular cloud is addressed by both identifying and mapping all the molecular outflows as well as the detailed structure of the cloud. Candidate molecular outflows were found from single point 12-CO observations of young stellar objects identified from the IRAS survey data. The candidate sources were then mapped to confirm their molecular outflow nature. From these maps, molecular outflow characteristics such as their morphology, orientation, and energetics were determined. In addition, the Orion molecular cloud was mapped to compare directly with the molecular outflows. The molecular outflows identified were found to have rising infrared spectra, radio continuum emission that suggests a stellar wind or optically thick H II region, and molecular line strengths that indicate that they are embedded within a very dense environment. The lack of an optical counterpart for many molecular outflows suggests that they occur at the earliest stages of stellar evolution. The lack of an optical counterpart for many molecular outflows suggest that they occur at the earliest stages of stellar evolution. The orientations of the molecular outflows appear to lie in no preferred direction and they have shapes that indicate that the molecular cloud is responsible for determining their direction and collimation

  10. Engineering aspects of Passavant screening

    International Nuclear Information System (INIS)

    Siddle, K.R.; Sharma, R.K.

    1978-01-01

    The Passavant screen was developed in Europe almost 30 years ago. The Passavant screen is a vertical traveling screen; however, the basic difference between the conventional vertical traveling screen and the Passavant screen is that in the conventional screen water passes through the front screen belt and then the back screen belt, whereas in the Passavant screen the water enters in between the two belts and passes laterally through either of the belts. Thus, theoretically, the screening surface of the Passavant screen is doubled as compared to the same size conventional vertical traveling screen. Various design and operational modifications of the Passavant screen are possible to yield optimum design and performance characteristics which make it amenable to installation at power plants for safe removal of not only fish but also smaller organisms such as fish eggs and larvae. In this paper, details of the screen design and operational characteristics are discussed with notes on how these features can be modified to suit site- and organism-specific requirements

  11. Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski’s Rule of Five and ZINC Databank

    Directory of Open Access Journals (Sweden)

    Pablo Andrei Nogara

    2015-01-01

    Full Text Available Alzheimer’s disease (AD is a progressive and neurodegenerative pathology that can affect people over 65 years of age. It causes several complications, such as behavioral changes, language deficits, depression, and memory impairments. One of the methods used to treat AD is the increase of acetylcholine (ACh in the brain by using acetylcholinesterase inhibitors (AChEIs. In this study, we used the ZINC databank and the Lipinski’s rule of five to perform a virtual screening and a molecular docking (using Auto Dock Vina 1.1.1 aiming to select possible compounds that have quaternary ammonium atom able to inhibit acetylcholinesterase (AChE activity. The molecules were obtained by screening and further in vitro assays were performed to analyze the most potent inhibitors through the IC50 value and also to describe the interaction models between inhibitors and enzyme by molecular docking. The results showed that compound D inhibited AChE activity from different vertebrate sources and butyrylcholinesterase (BChE from Equus ferus (EfBChE, with IC50 ranging from 1.69 ± 0.46 to 5.64 ± 2.47 µM. Compound D interacted with the peripheral anionic subsite in both enzymes, blocking substrate entrance to the active site. In contrast, compound C had higher specificity as inhibitor of EfBChE. In conclusion, the screening was effective in finding inhibitors of AChE and BuChE from different organisms.

  12. An NRG Oncology/GOG study of molecular classification for risk prediction in endometrioid endometrial cancer.

    Science.gov (United States)

    Cosgrove, Casey M; Tritchler, David L; Cohn, David E; Mutch, David G; Rush, Craig M; Lankes, Heather A; Creasman, William T; Miller, David S; Ramirez, Nilsa C; Geller, Melissa A; Powell, Matthew A; Backes, Floor J; Landrum, Lisa M; Timmers, Cynthia; Suarez, Adrian A; Zaino, Richard J; Pearl, Michael L; DiSilvestro, Paul A; Lele, Shashikant B; Goodfellow, Paul J

    2018-01-01

    The purpose of this study was to assess the prognostic significance of a simplified, clinically accessible classification system for endometrioid endometrial cancers combining Lynch syndrome screening and molecular risk stratification. Tumors from NRG/GOG GOG210 were evaluated for mismatch repair defects (MSI, MMR IHC, and MLH1 methylation), POLE mutations, and loss of heterozygosity. TP53 was evaluated in a subset of cases. Tumors were assigned to four molecular classes. Relationships between molecular classes and clinicopathologic variables were assessed using contingency tests and Cox proportional methods. Molecular classification was successful for 982 tumors. Based on the NCI consensus MSI panel assessing MSI and loss of heterozygosity combined with POLE testing, 49% of tumors were classified copy number stable (CNS), 39% MMR deficient, 8% copy number altered (CNA) and 4% POLE mutant. Cancer-specific mortality occurred in 5% of patients with CNS tumors; 2.6% with POLE tumors; 7.6% with MMR deficient tumors and 19% with CNA tumors. The CNA group had worse progression-free (HR 2.31, 95%CI 1.53-3.49) and cancer-specific survival (HR 3.95; 95%CI 2.10-7.44). The POLE group had improved outcomes, but the differences were not statistically significant. CNA class remained significant for cancer-specific survival (HR 2.11; 95%CI 1.04-4.26) in multivariable analysis. The CNA molecular class was associated with TP53 mutation and expression status. A simple molecular classification for endometrioid endometrial cancers that can be easily combined with Lynch syndrome screening provides important prognostic information. These findings support prospective clinical validation and further studies on the predictive value of a simplified molecular classification system. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Validation and global uncertainty of a liquid chromatographic with diode array detection method for the screening of azoxystrobin, kresoxim-methyl, trifloxystrobin, famoxadone, pyraclostrobin and fenamidone in grapes and wine.

    Science.gov (United States)

    de Melo Abreu, Susana; Caboni, Pierluigi; Cabras, Paolo; Garau, Vincenzo Luigi; Alves, Arminda

    2006-07-28

    Azoxystrobin, kresoxim-methyl, trifloxystrobin, pyraclostrobin, famoxadone and fenamidone are permitted Q(o) Inhibitor (Q(o)I) fungicides applied to vine in some European countries for the treatment of downy and powdery mildews. In this work, a method is validated for the analysis of these fungicides in grapes and wine. This screening method consists in a simple one step liquid-liquid extraction followed by liquid chromatography (LC) fitted with a diode array detector (DAD). Limits of detection for grapes and wine were below 0.2 mg kg(-1) or mg l(-1), precision was not above 13%, and recoveries were, on average, 95+/-5% for grapes and 104+/-6% for wine. Global uncertainties evaluated in the concentration range from 0.25 to 2.50 mg l(-1) were below 20%. A confirmatory method by gas chromatography (GC) with mass spectrometry (MS) detection was used.

  14. Airport exit and entry screening for Ebola--August-November 10, 2014.

    Science.gov (United States)

    Brown, Clive M; Aranas, Aaron E; Benenson, Gabrielle A; Brunette, Gary; Cetron, Marty; Chen, Tai-Ho; Cohen, Nicole J; Diaz, Pam; Haber, Yonat; Hale, Christa R; Holton, Kelly; Kohl, Katrin; Le, Amanda W; Palumbo, Gabriel J; Pearson, Kate; Phares, Christina R; Alvarado-Ramy, Francisco; Roohi, Shah; Rotz, Lisa D; Tappero, Jordan; Washburn, Faith M; Watkins, James; Pesik, Nicki

    2014-12-12

    In response to the largest recognized Ebola virus disease epidemic now occurring in West Africa, the governments of affected countries, CDC, the World Health Organization (WHO), and other international organizations have collaborated to implement strategies to control spread of the virus. One strategy recommended by WHO calls for countries with Ebola transmission to screen all persons exiting the country for "unexplained febrile illness consistent with potential Ebola infection." Exit screening at points of departure is intended to reduce the likelihood of international spread of the virus. To initiate this strategy, CDC, WHO, and other global partners were invited by the ministries of health of Guinea, Liberia, and Sierra Leone to assist them in developing and implementing exit screening procedures. Since the program began in August 2014, an estimated 80,000 travelers, of whom approximately 12,000 were en route to the United States, have departed by air from the three countries with Ebola transmission. Procedures were implemented to deny boarding to ill travelers and persons who reported a high risk for exposure to Ebola; no international air traveler from these countries has been reported as symptomatic with Ebola during travel since these procedures were implemented.

  15. Evaluation of the efficacy of six nutritional screening tools to predict malnutrition in the elderly.

    Science.gov (United States)

    Poulia, Kalliopi-Anna; Yannakoulia, Mary; Karageorgou, Dimitra; Gamaletsou, Maria; Panagiotakos, Demosthenes B; Sipsas, Nikolaos V; Zampelas, Antonis

    2012-06-01

    Malnutrition in the elderly is a multifactorial problem, more prevalent in hospitals and care homes. The absence of a gold standard in evaluating nutritional risk led us to evaluate the efficacy of six nutritional screening tools used in the elderly. Two hundred forty eight elderly patients (129 men, 119 female women, aged 75.2 ± 8.5 years) were examined. Nutritional screening was performed on admission using the following tools: Nutritional Risk Index (NRI), Geriatric Nutritional Risk Index (GNRI), Subjective Global Assessment (SGA), Mini Nutritional Assessment - Screening Form (MNA-SF), Malnutrition Universal Screening Tool (MUST) and Nutritional Risk Screening 2002 (NRS 2002). A combined index for malnutrition was also calculated. Nutritional risk and/or malnutrition varied greatly, ranging from 47.2 to 97.6%, depending on the nutritional screening tool used. MUST was the most valid screening tool (validity coefficient = 0.766, CI 95%: 0.690-0.841), while SGA was in better agreement with the combined index (κ = 0.707, p = 0.000). NRS 2002 although was the highest in sensitivity (99.4%), it was the lowest in specificity (6.1%) and positive predictive value (68.2%). MUST seem to be the most valid in the evaluation of the risk for malnutrition in the elderly upon admission to the hospital. NRS 2002 was found to overestimate nutritional risk in the elderly. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  16. Toxicology screen

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003578.htm Toxicology screen To use the sharing features on this page, please enable JavaScript. A toxicology screen refers to various tests that determine the ...

  17. Mental Health Screening Center

    Science.gov (United States)

    ... Releases & Announcements Public Service Announcements Partnering with DBSA Mental Health Screening Center These online screening tools are not ... you have any concerns, see your doctor or mental health professional. Depression Screening for Adult Depression Screening for ...

  18. Plasma nitriding monitoring reactor: A model reactor for studying plasma nitriding processes using an active screen

    Science.gov (United States)

    Hamann, S.; Börner, K.; Burlacov, I.; Spies, H.-J.; Strämke, M.; Strämke, S.; Röpcke, J.

    2015-12-01

    A laboratory scale plasma nitriding monitoring reactor (PLANIMOR) has been designed to study the basics of active screen plasma nitriding (ASPN) processes. PLANIMOR consists of a tube reactor vessel, made of borosilicate glass, enabling optical emission spectroscopy (OES) and infrared absorption spectroscopy. The linear setup of the electrode system of the reactor has the advantages to apply the diagnostic approaches on each part of the plasma process, separately. Furthermore, possible changes of the electrical field and of the heat generation, as they could appear in down-scaled cylindrical ASPN reactors, are avoided. PLANIMOR has been used for the nitriding of steel samples, achieving similar results as in an industrial scale ASPN reactor. A compact spectrometer using an external cavity quantum cascade laser combined with an optical multi-pass cell has been applied for the detection of molecular reaction products. This allowed the determination of the concentrations of four stable molecular species (CH4, C2H2, HCN, and NH3). With the help of OES, the rotational temperature of the screen plasma could be determined.

  19. Plasma nitriding monitoring reactor: A model reactor for studying plasma nitriding processes using an active screen

    International Nuclear Information System (INIS)

    Hamann, S.; Röpcke, J.; Börner, K.; Burlacov, I.; Spies, H.-J.; Strämke, M.; Strämke, S.

    2015-01-01

    A laboratory scale plasma nitriding monitoring reactor (PLANIMOR) has been designed to study the basics of active screen plasma nitriding (ASPN) processes. PLANIMOR consists of a tube reactor vessel, made of borosilicate glass, enabling optical emission spectroscopy (OES) and infrared absorption spectroscopy. The linear setup of the electrode system of the reactor has the advantages to apply the diagnostic approaches on each part of the plasma process, separately. Furthermore, possible changes of the electrical field and of the heat generation, as they could appear in down-scaled cylindrical ASPN reactors, are avoided. PLANIMOR has been used for the nitriding of steel samples, achieving similar results as in an industrial scale ASPN reactor. A compact spectrometer using an external cavity quantum cascade laser combined with an optical multi-pass cell has been applied for the detection of molecular reaction products. This allowed the determination of the concentrations of four stable molecular species (CH 4 , C 2 H 2 , HCN, and NH 3 ). With the help of OES, the rotational temperature of the screen plasma could be determined

  20. Plasma nitriding monitoring reactor: A model reactor for studying plasma nitriding processes using an active screen

    Energy Technology Data Exchange (ETDEWEB)

    Hamann, S., E-mail: hamann@inp-greifswald.de; Röpcke, J. [INP-Greifswald, Felix-Hausdorff-Str. 2, 17489 Greifswald (Germany); Börner, K.; Burlacov, I.; Spies, H.-J. [TU Bergakademie Freiberg, Institute of Materials Engineering, Gustav-Zeuner-Str. 5, 09599 Freiberg (Germany); Strämke, M.; Strämke, S. [ELTRO GmbH, Arnold-Sommerfeld-Ring 3, 52499 Baesweiler (Germany)

    2015-12-15

    A laboratory scale plasma nitriding monitoring reactor (PLANIMOR) has been designed to study the basics of active screen plasma nitriding (ASPN) processes. PLANIMOR consists of a tube reactor vessel, made of borosilicate glass, enabling optical emission spectroscopy (OES) and infrared absorption spectroscopy. The linear setup of the electrode system of the reactor has the advantages to apply the diagnostic approaches on each part of the plasma process, separately. Furthermore, possible changes of the electrical field and of the heat generation, as they could appear in down-scaled cylindrical ASPN reactors, are avoided. PLANIMOR has been used for the nitriding of steel samples, achieving similar results as in an industrial scale ASPN reactor. A compact spectrometer using an external cavity quantum cascade laser combined with an optical multi-pass cell has been applied for the detection of molecular reaction products. This allowed the determination of the concentrations of four stable molecular species (CH{sub 4}, C{sub 2}H{sub 2}, HCN, and NH{sub 3}). With the help of OES, the rotational temperature of the screen plasma could be determined.